Contents „„ EDITORIAL

ƒƒ Biomedical Journalism in SAARC Countries Prof. M. Yasin Khan Durrani------173

„„ ORIGINAL ARTICLES

ƒƒ Prevalence of Pseudo-exfoliative Glaucoma & its Preponderance of Age, Sex and Laerality in Patients of Pseudo-exfoliation Syndrome Sardar Bahadur Khan et al ------174

ƒƒ Correlation between Axial Length & Retinal Nerve Fiber Layer thickness in Myopic Eyes Khurram Nafees et al ------177

ƒƒ Success of Probing in Congenital Nasolacrimal Duct Obstruction (CNLDO) Muhammad Junaid Sethi ------181

ƒƒ Ocular Features of Joubert syndrome Shabana Chaudhry et al ------183

ƒƒ Frequency of Convergence Insufficiency in Orthoptic Clinic Imran Khalid et al ------188

ƒƒ Difference in Central Corneal Thickness between Male & Female in Adults Danish Zafar et al ------191

ƒƒ Prevalence of Refractive Error in School going Children in Southern Punjab (Pakistan) Mazhar Zaman Soomro et al ------194

ƒƒ Trabeculectomy with & without Peripheral Iridectomy in Open Angle Glaucoma Muhammad Nazim et al ------197

ƒƒ Frequency of Retinal Detachment in Ocular Trauma Bilal Khan et al ------200

ƒƒ Safety of Intra-Cameral Moxifloxacin and its use in Prophylaxis of Post-Operative Endophthalmitis Imran Ahmad et al ------204

ƒƒ Co-relation between Serum HbA1c with Sorbitol Concentration in the Lens of a Diabetic Patient Prof. Tariq Arain et al ------208

ƒƒ Orbicularis Bi-pedicle Flap for Eye Lid Reconstruction: SAM’S Technique Sameera Irfan ------212

„„ GENERAL SECTION

ƒƒ Age Related Structural changes in the Vermiform Appendix Sikander Hayat Niazi et al ------217

ii Ophthalmology Update Vol. 11. No. 4, October-December 2013 „„ CURRENT RESEARCH

ƒƒ Possible New Strategy in AMD Prevention Prof. Rajendra Apte et al ------222

ƒƒ Human Corneal Anatomy Redefined Prof. Harminder Singh Dua ------224

ƒƒ Are Nerve Fibers being Atrophied or Severed in Glaucoma? Syed S. Hasnain et al ------226

„„ SHORT COMMUNICATION

ƒƒ Promising Results of Eye Therapy in Post - Traumatic Stress Disorder (PTSD) Patients Abbas Hasnain ------229

ƒƒ Where the mystery of Glaucoma lies? Syed S. Hasnain ------231

„„ REVIEW ARTICLE

ƒƒ Ideal Glaucoma Drug: How close we are? Prof. Marianne L. Shahsuvaryan ------233

ƒƒ History of Ophthalmic Surgery & Contribution of Muslim Scholars Madiha Durrani et al ------237

„„ POSTGRADUATE DIARY

ƒƒ How to Give Intravitreal Injections, Indications & Risk Management Michelle E. Wilson et al ------241

„„ PROFILE

ƒƒ Sameera Irfan ------244

ƒƒ Prof. Harminder Singh Dua ------245

„„ OPHTHALMOLOGY NOTEBOOK ------250

Ophthalmology Update Vol. 11. No. 4, October-December 2013 iii



Editorial Biomedical Journalism in SAARC Countries Scientific publications of a country reflects the true encourage the young ophthalmolo- scientific progress and development of a country and gists to undertake research and fos- it plays an important role for dissemination and ex- ter new ideas in the skill of writing. change of knowledge. Holding such conferences is an The journal publishes peer-reviewed important milestone in the right direction. Such meet- articles, case reports, review articles, ings provide recognition and encourage the full poten- commentaries, articles on medi- tial for promoting research in a particular field which is cal education, new technology and the main objective of establishing a common platform of editorials covering core biomedical the SAARC countries. We need to make such ventures health subjects, emerging commu- more practical and viable in order to develop a common nity problems like environmental health and popula- lingua franca in every field of life especially in Medicine. tion. The editorial board of the journal is headed by In the best interest of the welfare of our people we the highly experienced and high profile academicians must improve the quality of life by accelerating the at international level. In fact “Ophthalmology Update” economic growth and social progress, which will fur- concentrates on quality of articles, its production with ther help in bringing the peace in the region. In fact, utmost regularity and in time publication. You will not in the current scenario, active collaboration and mutual be very surprised to find the journal on your office table assistance is the need of the hour. exact on the due date. In this context the SAARC Youth Award was a sig- With the Grace of God, the journal is becoming nificant scheme instituted in 1996 to provide recognition popular after each passing day and it has the largest cir- to extraordinary young talents and to encourage overall culation amongst the biomedical journals. It is duly ap- potential in our youth in the age group of 20-35 years. proved and indexed by the Pakistan Medical & Dental The award consisted of a Gold Medal and a cash prize Council, Higher Education Commission and Pakistan of 1500 US dollars; currently the scheme seems to be Medical Research Council. At the Govt. level it is reg- hanging in doldrums now. We need to rejuvenate and istered with the Government of Pakistan under Press & formulate more such schemes in the field of community Publication Ordinance and is ABC certified by the Press services like development of biomedical journalism, do- Information Department. It has its own website and we nation of human organs especially the eyes to meet the are vigorously pursuing the facility of on-line submis- challenge of growing blindness in South Asian coun- sion, reviewing and editing. tries. We know Sri Lanka is a torch bearer in this direc- As such the journal needs your active support and tion. The name of late Dr. Hudson Sylva will ever be we assure you that it will serve the best interest of our remembered who established an International Eye Bank scientists, health professional, ophthalmologists of the in his country and freely supplied donation of eyes to 77 South Asian region especially the member states of the countries of the world. He has motivated his own people SAARC countries. The Editorial Board and the man- to donate eyes after death, giving light to the millions agement of Ophthalmology Update cordially welcome and bringing them into the main stream of normal life the participating delegates of this conference and hope and making them economically a viable member of the their stay is comfortable, enjoyable and very fruitful. society. In this context, we have established a scientific jour- Prof. M. Yasin Khan Durrani nal ”Ophthalmology Update” internationally indexed MBBS., DO., MD., FRCOphth(London) and recognized, being published quarterly from Islama- Editor in Chief bad, Pakistan for the last 12 years. The main idea is to Phones: 009251 2299113, 0092 333 5158885 improve medical research especially in Ophthalmic E-mail: [email protected] sciences by approaching a wider spectrum of reader- Website: www.ophthalmologyupadte.com ship for the mutual benefit of our people, essentially to Address: 267-A, St: 53, F-10/4, Islamabad, Pakistan

Ophthalmology Update Vol. 11. No. 4, October-December 2013 173 ORIGINAL ARTICLE Prevalence of Pseudo-exfoliative Glaucoma & its Preponderance of Age, Sex and Laterality in Patients of Pseudo- Bahadur Khan exfoliation Syndrome

Sardar Bahadur Khan FCPS1, Muhammad Alam FCPS2, Tariq Muhammad Saeed MBBS3 Muhammad Ayub Khan MBBS4, Prof Muhammad Saleem FCPS5.

ABSTRACT: Objective: To study the prevalence of Pseudoexfoliative glaucoma and it’s preponderance of age, sex and laterality in Pseudo exfoliation syndrome patients. Materials and Methods: This descriptive study was conducted at the Department of Ophthalmology Gomal Medical College, District Headquarter Teaching Hospital D. I. Khan from January 2009 to December 2012 with the objective to know the prevalence of pseudoexfoliative glaucoma and it’s preponderance of age, sex and laterality in pseudo exfoliation syndrome patients. Proper proforma was designed for documentation of patients. Informed consent was taken from each patient. In these 4 years, total 625 patients suffering from this disease were included in the study. Out of these 625 patients, 335(53.6%) were male and 290(46.4%) were female with age range from 50 years and above. They were divided into three groups, Group A, B and C with age range from 50 to 60 years, 61-70 years and more than 70 years respectively. The ocular examination included visual acuity testing , biomicroscopy of the anterior segment, applanation tonometry, gonioscopy, fundus examination and visual fields. Pupil was dilated with tropicamide 1% eye drops for detailed slit lamp examination. On Slit lamp, the lens was examined for the most commonly recognized feature of 3-ring Sign on the anterior lens capsule. The dilated fundus examination was performed with direct, Indirect ophthalmoscope using 20 D lens, and with slit lamp using 78 D lens. Results. Total 51 (8.16%) patients were found to be glaucomatous. Out of male 335 patients 32 (9.55%) had glaucoma while in female out of 290 patients 19(6.55%) had glaucoma. The prevalence of glaucoma increased with age. In 92.15% it was bilateral while in 7.85% patients it was unilateral. Conclusion: Pseudoexfoliative glaucoma is more common. Its prevalence increases with increase of age. It is more common in male. Mostly it is bilateral. Abbreviation: Pseudoexfoliation Syndrome(PXS).Pseudoexfoliative, Glaucoma(PXG). Intra Ocular Pressure(IOP). Key words: Pseudoexfoliation syndrome. Pseudoexfoliative glaucoma.

INTRODUCTION tissue metabolism6. Pseudo exfoliation is thought to be Pseudo exfoliation syndrome is an age related the common identifiable cause of open angle glaucoma condition being characterized by deposition of Pol- worldwide7. There is considerable variation in different ymorphic fibrillar material in the anterior segment of countries of PXS attributable to glaucoma 8,9. eye. This condition was first described by Lindberg a The exfoliation material gets deposited into the Finish Ophthalmologist in 1917, followed by Vogt, trabecular meshwork passively and also seems to be and initially termed “glaucoma capsulare”. The clas- produced actively in the juxtacanalicular portion of sic white flaky dandruff like material was initially the trabecular meshwork particularly endothelium of thought to originate from the lens capsule1. PXS has schlemm’s canal. All these lead to disorganization of been shown to increase with age and to be associated the canal architecture with a collapse of inner and outer with Glaucoma2,3. PXS has also geographical variation walls narrowing of the lumen of canal. All these mech- of prevalence 4,5. In PXS fibrillar material in addition to anism lead to resistance of out flow10. Pseudo exfolia- ocular deposition, has been found to be deposited in tion syndrome causes open angle glaucoma as well many organs of the body including heart, lung, liver, as angle closure glaucoma. Some studies have demon- kidneys and meninges suggesting abnormal connective strated closed angle mechanism in pseudo- exfoliation 11,12 1 Associate Professor Ophthalmology, Gomal Medical College, syndrome . D.I.Khan. 2Senior Registrar, Ophthalmology Department, LRH Prevalence of PXG in PXS has variation according Peshawar. 3Medical Officer, Ophthalmology Department, LRH Peshawar. 4Muhammad Ayub Khan, Postgraduate Resident to race, gender, geographical distribution. A popula- Ophthalmology, Services Hospital, Lahore. 5 Prof. of Ophthalmology tion based study in Iran by MN. Kouran ,N Nautraran Department, Gomal Medical College, D.I.Khan. has shown 13% prevalence of PXG in PXS13. Study of Correspondence: Dr Sardar Bahadur Khan, Sardar Flour Mills, Jae Hee Kara. Stephane Loois has revealed that PXG Daraban Road, Dera Ismail Khan. KPK. increases with increase in age in PXS patients14. There Email: [email protected] Cell .03005792251 is greater geographical variation of PXG prevalence in Received: July’2013 Accepted: Sep’2013 PXS. S. Shakya, S Dural has reported 33.3% patients of

174 Ophthalmology Update Vol. 11. No. 4, October-December 2013 Prevalence of Pseudo-exfoliative Glaucoma & its Preponderance of Age

PXS to be suffering from PXG15. This descriptive study RESULTS: was conducted to know the prevalence of PXG and it’s Out of 625 patients only 51 (8.16%) patients had preponderance of age, sex and laterality in PXS Pa- PXG. Out of 51 patients according to sex distribution in tients. male 335 patients PXG was present in 32 (9.55%) while MATERIALS AND METHOD in female 290 patients 19 (6.55%) had PXG. Table - III. This descriptive study was conducted at Depart- Regarding laterality in out of 51 patients 47 (92.15%) ment of Ophthalmology, Gomal Medical College, DHQ were bilateral while 4 (7.85%) were unilateral. Table- Teaching Hospital, D.I. Khan from January 2009 to IV. According to age distribution out of 51 patients 11 December 2012 with the objective to know the prev- (21.55%) were in group A, 19 (37.25%) were in group B alence of PXG and its preponderance of age, sex while 21 (41.18%) patients were in group C. Table- V. and laterality in patients suffering from PXS. Proper proforma was designed for documentation of patients TABLE IV. Laterality No 51 .Informed consent was taken from each patient. Laterality No Percentage The ocular examination included visual acuity Unilateral 4 7.85 % testing, biomicroscopy of the anterior segment, appla- Bilateral 47 92.15 % nation tonometry, gonioscopy, fundus examination and visual fields. Pupil was dilated with tropicamide 1% eye drops for detailed slit lamp examination. On TABLE V. Affected patients Slit lamp, the lens was examined for the most com- according to age group.no 51 monly recognized feature of 3-ring Sign on the an- Group No Percentage terior lens capsule. The dilated fundus examination A 11 21.56 % was performed with direct, Indirect ophthalmoscope B 19 37.25 % using 20 D lens, and with slit lamp using 78 D lens. C 21 41.18 % Inclusive Criteria: 1. All PXS patients. 2. IOP more than 21 mmHg. DISCUSSION: 3. Abnormal C.D ratio. Pseudoexfoliative Glaucoma is the most frequent 4. Visual field defect. open angle glaucoma in PXS. Our study demonstrates Total 625 patients from age 50 years and above the prevalence of PXG to be more common in males comprising of 335 (53.6%) males and 290 (46.4%) fe- and its prevalence increases with age. Mostly it is bilat- males who had PXS were examined. Table - I. These eral. Our study is comparable in various parameters patients were divided into three groups according to with national and international studies. Although there age group A, B,C, with age from 50 – 60, 61 – 70 and are variations which could be explained and justified more than 70 years respectively. Table - II. on substantial grounds.The prevalence of PXG varies considerably across the world. Tens has reported that IOP at diagnosis is higher in patients with PXG16. Da- TABLE I. Gender Distribution No -625 vid C March, Takayuki Shamuzu et al. have reported Gender No Percentage PXG in older patients and more bilateral being similar Male 335 53.6 % to our study results but they have reported it more in Female 290 46.4 % female which is contradictory to our study17. This dif- ference may be due to geographical or sample size ef- fect. Rehman F, Rashid H, have reported prevalence of TABLE II. Age Distribution No-625 PXG in 9.3% patients suffering from PXS, more bilateral

Group Age No Percentage and in older age group. This study is comparable to our study18. Our study revealed that in 92.15 patients PXG A 50 – 60 years 180 28.8 % was bilateral and in 7.85% patients it was unilateral. B 61 – 70 years 270 43.2 % Various reports speak of different figures of laterality. C > 70 years 175 28% Some national studies report the unilateral cases in 20 – 25% patients19,20. The low prevalence of unilateral cases in our study TABLE III. Affected patients according to sex. may be due to advanced nature of disease or record- Group Total No Affected Percentage ing the approximate age in most of the patients. Rao. Male 335 32 9.55% RQ, Aaim TM, Ahmed MA have reported in their stud- Female 290 19 6.55% ies 100% cases to be bilateral21. Study by Xu Y, Comos

Ophthalmology Update Vol. 11. No. 4, October-December 2013 175 Prevalence of Pseudo-exfoliative Glaucoma & its Preponderance of Age

N. Gantagains S reported more bilateral cases as in our 10. Schlotzer Schrehardt U, naumann, GO. Trabecular meshwork in study. But the prevalence of PXG was 22% in PXS pa- pseudoexfoliation syndrome with and without open angle glau- 22 coma. A morphometric, ultra structural study. Invest Ophthal- tients which were more than our study . Shazky TA, mol Vis Sci 1995;36:1750-64. Farraq AN,Kamal A have reported bilateral PXS in 82.2 11. Ritch R. Exfoliation syndrome and occludable angles. Trans Am of cases and PXG in 30.3% of PXS patients23. Which Ophthalmol Soc 1994;92:845-944. have variation from our study. Mitchll A, Wang JJ have 12. Bartholonew RS. Pseudoexfoliation and angle closure glaucoma. J Glaucoma 1981;3:213-6. reported that in PXS patients there is 2 to 3 fold more 13. N M Kouros, N nastaran, S Ramin et al. Pseudoexfoliation syn- risk of PXG in their Blue Mountain Study24. Krishnadas. drome in central Iran: A Population based survey. Acta Ophthal- R, Praveen K, have reported that PXS was more com- mol scand. 1999;77:581-584. mon is old age, male and 7.5% of patients had PXG of 14. H. K Jae Loomis S, L. Janey et al. demographic and Geographic 25 Features of exfoliation glaucoma in 2 United States Based Pro- PXS patients. The results are comparable to our study . spective Cohorts. Ophthalmology 2012;119:27-35. CONCLUSION: 15. Shakya S, Dulal S, Maharjan IM. Pseudoexfoliation syndrome Although the prevalence of PXG is more in PXS in various ethnic population of Nepal. Nepal Med Coll J patients but it is not necessary that every PXS patient 2008;10(3):147-150. 16. Teus MA, Castejon MA, Calvo MA, et al. intraocular pressure will have glaucoma. The prevalence increases pro- as a risk factor for visual field loss in pseudoexfoliative and in portionately with increase in age. It is more common primary open angle glaucoma. Ophthalmology. 1998;105:2225-9. in male and it is mostly bilateral. Every PXS patient 17. Musch DC, Shimizu T, Leslie M et al. Clinical Characteristics should be carefully examined for glaucoma. of Newly Diagnosed Primary, Pigmentary, and Pseudoexfolia- tive open angle Glaucoma in the collaborative initial glaucoma REFERENCES: Treatment Study. Br J Ophthalmol. 2012 September; 96(9): 1180- 1. Tarkkanen A, Kivela T, John G. Lindbergh and the discovery of 1184. exfoliation syndrome. Acta Ophthalmol Scand 2002; 80:151-154. 18. Rahman F, Rashid H. Pseudoexfoliation syndrome and its ef- 2. Dickson DH, Ramsey MS. Review of the nature and origin of fects on intraocular Pressure. Pak J Med Res Vol. 45, No. 4, 2006. pseudoexfoliative deposits. Trans Ophthal Soc U K 1979;99:284- 19. Khanzada AM. Exfoliation syndrome in Pakistan. Pak J Oph- 292. thalmol 1986;2:7-9. 3. Brusini P, Tosoni C, Miani P. increased prevalence of occludable 20. Mohammad S, Kazmi N. Subluxation of the lens and ocular hy- angles and angle closure glaucoma in patients with pseudoexfo- pertension in exfoliation syndrome. Pak J Ophthalmol 1986;2:77- liation. Am Ophthalmol 1994;118:540. 8. 4. Taylor HR. Pseudoexfoliation –an environmental disease? Trans 21. Rao RQ, Arain TM, Ahad MA. The prevalence of pseudoexfolia- Ophthalmol Soc U K 1979;99:302-307. tion syndrome in Pakistan. Hospital based study. BMC Ophthal- 5. McCarty CA, Taylor HR. Pseudoexfoliation syndrome in Aus- mology 2006; 6: 27. tralian Adults. Am J Ophtamol 2000;129:629-633. 22. Xu Y, Cosmas N, Gartaganis S. statistical analysis of pseudo- 6. Naumann GO, Schlotzer Schrehardt U, Kuchle M. Pseudo- exfoliation syndrome prevalence, Glaucoma and coronary ar- exfoliation syndrome for the comprehensive ophthalmolo- tery disease of the patients with . Int J Biomed Sci. 2011 gist: intraocular and systemic manifestations. Ophthalmology March; 7 (1): 35-43. 1998;105:951-968. 23. Shazly TA, Farrag AN, Kamel A, Al-Husaini AK. Prevalence of 7. Ritch R. Exfoliation syndrome: the most common identifiable pseudoexfoliation syndrome and pseudoexfoliation glaucoma cause of open angle glaucoma. J Glaucoma 1994;3:176-177. Upper Egypt. BMC Ophthalmology 2011; 11:18. 8. Topouzis F, Wilson R, Harris A, et al. prevalence of open angle 24. Mitchell P, Wang JJ, Hourihan F: the relationship between glau- glaucoma in Greece: the Thessaloniki Eye study. Am J Opthal- coma and pseudoexfoliation: The Blue Mountains eye Study. mol 2007;144:511-519. Arch ophthalmol 1999; 117:1319-1324. 9. Mitchell P, Wang JJ, Hourihan F. The relationship between glau- 25. Krishnadas R, Praveen K, Ramakrishnan R, et al. pseudoexfolia- coma and pseudoexfoliation. The blue Mountains Eye study. tion in a rural population of southern India: The Aravind Com- Arch Ophthalmol 1999;117:1319-1324. prehensive Eye survey. AM J Ophthalmol 2003; 135:830-837.

Cataract & Refractive Symposium

The Ophthalmological Society of Pakistan, Lahore branch held one day Cataract & Refractive Symposium in collaboration with the Association of Cataract & Refractive Surgeons on 31st August;2013 at a local hotel in Lahore. Dr. Zaheer uddin Aqil Kazi, Dr. Sharif Hashmani, Dr. Qasim Lateef, Prof. Jamshed Nasir and Dr. Maqsood Ahmed Burq read the papers.

176 Ophthalmology Update Vol. 11. No. 4, October-December 2013 ORIGINAL ARTICLE

Correlation between Axial Length & Retinal Nerve Fiber Layer thickness in Myopic Eyes Khurram Nafees M. Naeem Azhar

Khurram Nafees MBBS1, Muhammad Naeem Azhar FCPS2, Waqas Ahmad MBBS3 LRBT Free Eye Hospital, Lahore

ABSTRACT Purpose: To determine the correlation between the axial length and mean RNFL thickness in myopic eyes Material and Methods: 150 patients with spherical equivalent <-0.50 D having visual acuity at least 6/12 with or without glasses of aged 15 to 50 years were included in this cross sectional study for a period of six months from 08-09-2009 to 07-03-2010 and taken from the out-door patient department of Layton Rahmatulla Benevolent Trust Free Eye and Cancer Hospital, Lahore. Axial length was measured with A-scan and RNFL thickness in four quadrants was measured with optical coherence tomography (OCT) around the centre of the optic disc and taken mean RNFL thickness. Results: Significant correlation was found between the axial length and mean RNFL thickness (r=-0.815, P < 0.05). Conclusion: There is a negative correlation between the axial length and RNFL thickness.

INTRODUCTION sociated with myopia is glaucoma which is character- Myopia is a refractive condition in which the im- ized by progressive degeneration of retinal ganglion age of a distant object is formed anterior to the retina of cells. Numerous studies have confirmed that retinal the relaxed eye. It occurs when the refractive power of nerve fiber layer thickness measurement is sensitive for the eye is too great compared to the length of the eye- detection of glaucoma and the extent of retinal nerve ball and this may occurs because the eye has a greater fiber layer damage correlates with the sensitivity of the refractive power, a longer axial length or a combina- functional deficit in the visual field5. tion of both. In fact, the axial length is nearly always too Although retinal nerve fiber layer thinning is in- long compared to the refractive power and the myopic dicative of glaucomatous damage, it remains uncer- eye is importantly a long eye1. tain whether retinal nerve fiber layer thickness would Myopia is the most common ocular abnormal- vary with the refractive status of the eye 6. It is there- ity worldwide. Its prevalence in Pakistan is 8.9% de- fore important to investigate whether any correlation termined in a study held in Karachi2. The prevalence exists between retinal nerve fiber layer thickness and rates of myopia in the multicenter refractive study in axial length in myopia with regard to the observation children aged 5 to 15 years were 7.4% in India, 4.0% in that the risk of development of glaucoma is increased South Africa and < 3% in Nepal3. In some of the Asia with an increasing degree of myopia. In a study held Pacific countries, the increase in prevalence has reached at Hong Kong Eye Hospital, Pearson coefficient of cor- an epidemic scale. In Singapore, it has been estimated relation (r) between axial length and retinal nerve fiber that 38.7% of adult Chinese are myopic and 9.1% are layer thickness was calculated to be -0.314 in myopic high myopic. High myopia is potentially a blinding eyes 6. For every 1mm greater axial length, mean reti- condition and may lead to ocular morbidity such as nal nerve fiber layer thickness decreases by approxi- glaucoma, cataract, retinal detachment and myopic mately 2.2 µm7. neovascular macular degeneration. Retinal changes in The optical coherence tomography is a modern persons with high myopia include peripapillary atro- imaging device designed to measure the retinal nerve phy, peripheral lattice degeneration, tilting of the optic fiber layer thickness in a non-contact and non-inva- disc, posterior staphyloma and breaks in Bruch’s mem- sive manner. With the high axial scanning resolution brane 4. (< 10µm) provided with the latest model of optical co- One of the potentially blinding ocular diseases as- herence tomography, retinal nerve fiber layer measure- ments have been reliable and reproducible8. 1 Resident Medical Officer, 2 Ophthalmologist, 3 RMO MATERIALS AND METHODS Corrspondence: Dr. Khurram Nafees MBBS LRBT Free Eye Hospital Lahore. Mobile +923009417115, E.mail address: [email protected] 150 patients with spherical equivalent <-0.50 D Received: July’ 2013 Accepted: August’ 2013 having visual acuity at least 6/12 with or without

Ophthalmology Update Vol. 11. No. 4, October-December 2013 177 Correlation between Axial Length & Retinal Nerve Fiber Layer thickness in Myopic Eyes glasses of aged 15 to 50 years were included in this cross and the axial length (r = -0.899, p < 0.05). Analysis at sectional study for a period of six months from 08-09- individual quadrants of retinal nerve fiber layer thick- 2009 to 07-03-2010 and taken form the out-door patient ness showed that each quadrant had significant corre- department of Layton Rahmatulla Benevolent Trust lation with the axial length i.e. correlation between the Free Eye and Cancer Hospital, Lahore. Patients with axial length and temporal RNFL thickness was – 0.384 Spherical equivalent less than–0.50 D as diagnosed by (p < 0.05), correlation between the axial length and su- auto-refractometer, best corrected visual acuity(BCVA) perior RNFL thickness was – 0.529 (p < 0.05), correla- of at least 6/12 as assessed by recording visual acuity tion between the axial length and nasal RNFL thickness with Snellen’s chart Both genders, age 15 to 50 years was – 0.561 (p < 0.05), and the correlation between the and patients having clinical evidence of cataract, glau- axial length and inferior RNFL thickness was – 0.610 coma, macular degeneration, peripapillary atrophy ex- (p < 0.05). Significant correlation between the spheri- tending> 1.7 mm from the center of the disc, staphylo- cal equivalent and RNFL thickness were found at each ma and retinal detachment (assessed by using slit lamp quadrant of retinal nerve fiber layer thickness i.e. cor- bimicroscope and indirect ophthalmoscope), Intraocu- relation between spherical equivalent and temporal lar pressure > 21mm (assessed by using Goldmann ap- RNFL thickness was 0.305 (p < 0.05), correlation be- planation tonometer), visual field defects (diagnosed tween spherical equivalent and superior RNFL thick- by Humphrey perimetery), history of intraocular and ness was 0.525 (p < 0.05), correlation between spherical refractive surgery, history of neurological diseases e.g. equivalent and nasal RNFL thickness was 0.531 (p < multiple sclerosis and optic atrophy, history of trauma 0.05) and the correlation between spherical equivalent to the eye were excluded. Axial length was measured and inferior RNFL thickness was 0.597 (p < 0.05). with A-scan and RNFL thickness in four quadrants was measured with optical coherence tomography (OCT) Table 1: Correlation between Axal around the center of the optic disc and taken mean Length and Mean NFL Thickness RNFL thickness. Variable Correlation with Axial Length P Value DATA ANALYSIS: Mean RNFL - 0.815 <0.05 Data analysis was done with SPSS 10. The quan- Thickness titative variables under study were age, axial length, Spherical equivalent and retinal nerve fiber layer thick- ness. These variables were presented as mean ± stand- Table 2: Descriptive statistics for ard deviation. The qualitative variable like gender was Quantitative Variables presented as frequency and percentage. Correlation Standard Variables Mean between axial length and retinal nerve fiber layer thick- Deviation ness was examined by the Pearson Coefficient of corre- Age (years) 24.22 ±7.65 lation. P ≤ 0.05 was considered statistically significant. Spherical Equivalent (D) -4.99 ±3.86 RESULTS: One hundred and fifty (150) myopic eyes of 150 Axial Length(mm) 25.53 ±1.86 subjects were analyzed. Significant correlation was Mean RNFL Thickness (µm) 94.76 ±10.22 found between the axial length and mean retinal nerve fiber layer thickness (r = -0.815, p < 0.05). The mean age, spherical equivalent, axial length and mean reti- Table 3: Correlation between the Axial Length nal nerve fiber layer thickness were 24.22 ± 7.65 years and other quantitative Variables (range, 15 to 44), -4.99 ± 3.86 D (range, -14.50 to -0.75), Correlation with Variables P Value 25.73 ± 1.86 mm (range, 22.12 to 29.92), and 94.76 ± Axial Length (r) 10.22 µm (range, 76.5 to 121), respectively. Frequencies Mean RNFL Thickness -0.815 <0.05 of male, female, right and left eyes were 71 (47.3%), 79 (52.7%), 79 (52.7%) and 71 (47.3%), respectively. Spherical Equivalent -0.899 <0.05

Significant correlation was found between the Temporal RNFL Thickness -0.384 <0.05 axial length and mean retinal nerve fiber layer thick- ness (r = -0.815, p < 0.05). The spherical equivalent cor- Superior RNFL Thickness -0.529 <0.05 <0.05 related significantly with mean retinal nerve fiber layer Nasal RNFL Thickness -0.561 thickness (r = 0.773, p < 0.05). There is also a significant Inferior RNFL Thickness -0.610 <0.05 correlation was found between spherical equivalent

178 Ophthalmology Update Vol. 11. No. 4, October-December 2013 Correlation between Axial Length & Retinal Nerve Fiber Layer thickness in Myopic Eyes

In a recent study, Hoh et al. 10 also reported no correlation between axial length/spherical equivalent and the mean peripapillary RNFL measured by OCT1. Bozkurt et al. showed that the average RNFL thickness measured by GDx in myopic eyes (n = 41; age range, 7-60 years; mean spherical refractive error = -12.5 ± 3.5 D; range, -7.50 to 22.00 D) was significantly higher than the age matched healthy control eyes (mean spherical refractive error = -0.25 ± 0.50 D). The discrepancy was attributed to the high scleral reflectivity as a result of peripapillary chorioretinal atrophy associated with high myopia which led to an apparent increase in retar- dation values. The collection of large number of myopic eyes (150) with spherical equivalent range, -0.75 to -14.25 D in this study allowed a better characterization. My find- ings demonstrated a clear association between RNFL Scatter Plot of Mean RNFL Thickness (µm) thickness and axial length / negative spherical equiva- against Axial Length (mm) of the Eye lent. The reduction of RNFL thickness with increasing axial length could be explained by the observation that DISCUSSION: there is increased scleral and retinal thinning in myopic In this study, we found that RNFL thickness de- eyes. In myopic eyes, the elongation of the globe leads creased with the increase in axial length / negative to mechanical stretching and thinning of the retina. spherical equivalent in myopic eyes and there was a Therefore, it is conceivable that the extent of the elonga- linear correlation between RNFL thickness and axial tion would be related to the degree of retinal thinning, length. Previous investigations on the relation between although it is yet to be ascertained whether the RNFL RNFL and refractive error have been essentially based thickness is decreased at the histologic level. on scanning laser polarimetry without customized Population based studies indicate that the risk of corneal birefringence compensation and the findings glaucoma increases with the increasing degree of myo- 9 have been equivocal . Ozdek et al. studied 85 subjects pia. The Blue Mountains Eye Study found a strong re- with myopia (age range, 7-83 years) with mean spheri- lationship between open angle glaucoma and myopia cal equivalent of -4.56 ±2.72 D using first generation of with an odds ratio of 2.3 in eyes with low myopia (be- scanning laser polarimetry (NFA-1, NFA version 2.1.17, tween -1.0 and -3.0 D) and 3.3 in eyes with moderate Diagnostic Technologies, San Diego, CA). They showed to high myopia ( more than -3.0 D). A large popula- that there was a gradual decrease in the superior and tion-based study in Sweden with >32,000 subjects, also inferior RNFL with increasing myopia. For each diop- identified myopia as an important risk factor for glau- ter decrease in spherical equivalent, there were 0.122 coma. Although the mechanisms responsible for the µm and 0.092 µm reductions in superior and infe- link between glaucoma and myopia are poorly under- rior RNFL thickness, respectively. With the use of the stood, it has been postulated that the optic nerve head Nerve Fiber Analyzer (GDx, Carl Zeiss Meditec, Inc.), in myopic eyes may be structurally more susceptible to 9 Kremmer et al. also reported a linear correlation be- glaucomatous damage because of the changes in con- tween average RNFL thickness and spherical equiva- nective tissue structure and its arrangements. As the lent (average RNFL thickness = -2.848 × SE + 76.529) in integrity of RNFL is a recognized surrogate for glauco- 75 myopic eyes of healthy volunteers (age range, 21-40 matous change, the finding of decreasing RNFL thick- years, mean spherical equivalent = -4.6D; range -0.75 ness with increasing myopic supports the conclusions to -8.5 D). However, no correlation was found between of these population-based studies. On the one hand, the axial length and any of the GDx parameters. In the im- increased risk of development of glaucomatous change aging study by Bowd et al. in a group of 155 subjects may be related to the already reduced RNFL thickness (age range 23-80.8 years; refractive error -5.0 to +5.0 D), in myopic eyes. On the other hand, the reduced RNFL it was concluded that refraction is not associated with thickness in myopia may itself represent a risk factor any of the RNFL parameters measured by GDx or OCT for the development of glaucoma. The lower RNFL (OCT1; Carl zeiss Meditec, Inc.). measurement in highly myopic eyes would therefore

Ophthalmology Update Vol. 11. No. 4, October-December 2013 179 Correlation between Axial Length & Retinal Nerve Fiber Layer thickness in Myopic Eyes translate to a higher risk. Further studies with longitu- RNFL is being measured farther from the disc margin. dinal follow-up would be useful to address this ques- It is because the optic disc size may also increase with tion fully. myopia 12. An age matched normative database consisting In summary, RNFL thickness decreases with of normal subjects of different ethnicity is available the axial length and negative spherical equivalent of in the analysis package in Topcon 3D OCT-1000 and the eye. As corrections for refractive error and axial provides information on the normal limits of RNFL length in the measurement of RNFL have not been thickness 11. This normative database was designed incorporated in OCT, RNFL measurements should be to provide a useful diagnostic aid in the detection of interpreted carefully in myopic subjects and should not ocular disease involving RNFL. Jeoung et al. have just rely on the normative database. shown that the localized nerve fiber defect identified by CONCLUSION: this normative database had good agreement with that There is a negative correlation between the axial by red-free photographs in Asian eyes. However, the length and RNFL thickness. validity of applying this database to healthy subjects REFERENCES: with myopia has not been verified. Therefore, the 1. MH Edwards, CSY Lam. The epidemiology of myopia in Hong Kong. Ann Acad Med Singapore. 2004; 33:34-8. normative database may not be reliable when analyzing 2. Alam H, Siddiqui I, Jafri SI, Khan AS, Ahmed SI, Jafar M. RNFL in myopic subjects and refractive error should Prevalence of refractive error in school children of Karachi. J always be considered in the interpretation of RNFL Pak Med Assoc. 2008; 58(6):322-5. measurements. More data on RNFL measurements in 3. Saw SM, Tong L, Chua WH, Chia KS, Koh D, Tan DT, et al. Incidence and progression of myopia in Singaporean school myopia should be collected to refine the confidence children. Invest Ophthalmol Vis Sci. 2005; 46(1):51-7. limits in the current OCT normative database. It would 4. Panozzo G, Mercanti A. Optical coherence tomography also be of interest to examine whether there is any findings in myopic traction maculopathy. Arch Ophthalmol. 2004; 122:1455-60. difference in RNFL measurements between Asian and 5. Hoffmann EM, Medeiros FA, Sample PA. Relationship between Non-Asian myopic eyes. patterns of visual field loss and retinal nerve fiber layer The default of axial length in Topcon 3D OCT-1000 thickness measurements. Am J Ophthalmol. 2006; 141:463-71. 6. Leung CK, Mohammad S, Leung KS, Cheung CY, Chan SL, scan is 24.39 mm and the scanning radius for the fast/ Cheng DK, et al. Retinal nerve fiber layer measurements in standard RNFL scanning protocol is fixed at 1.7 mm. myopia: An optical coherence tomography study. Invest although one can input the patient’s axial length and Ophthalmol Vis Sci. 2006; 47(12):5171-6. refractive correction in OCT, it has no impact on the 7. Budenz DL, Anderson DR, Varma R, Schuman J, Cantor L, Savell J, et al. Determinants of normal retinal nerve fiber layer magnification during scanning. Therefore, the actual thickness measured by stratus OCT. Ophthalmology. 2007; scanning radius in a myopic eye could be longer than 114(6):1046-52. 1.7 mm due to magnification effect. The relationship 8. Budenz DL, Chang RT, Huang X. Reproducibility of retinal nerve fiber layer measurements using the startusOCT in between the measurement of OCT image and the size normal and glaucomatous eyes. Invest Ophthalmol Vis Sci. of the actual fundus dimension can be expressed as 2005; 46:2440-4. t = p.q.s, where t is the actual fundus dimension, s is 9. Kremmer S, Zadow T, Steuhl KP, Selbach JM. Scanning laser polarimtery in myopic and hyperopic subjects. Graefes Arch the measurement on OCT, p is a magnification factor Clin Exp Ophthalmol. 2004; 242:489-94. related to the camera of the OCT imaging system and q 10. Hoh ST, Lim MC, Seah SK, Lim AT, Chew SJ, Foster PJ, et al. is magnification factor related to the eye. The correction Peripapillary retinal nerve fiber layer thickness variations with factor q (in mm per degree) can be determined with the myopia. Ophthalmology. 2006; 113: 773-7. 11. Jeoung JW, Park KH, Kim TW, Khwarg SI, Kim DM. Diagnostic formula q = 0.01306(x – 1.82), where x is the axial length. ability of optical coherence tomography with normative Therefore, the actual scanning radius in an eye of axial database to detect localized retinal nerve fiber layer defects. length 29.92 mm (the longest axial length in our study) Ophthalmology. 2005;112: 2157-63. 12. Wang Y, Xu L, Zhang L, Yang H, Ma Y, Jonas JB. Optic disc size would be 1.7 × [0.01306(29.92 – 1.82)] / [0.01306(24.39 in a population based study in northern China: the Beijing Eye – 1.82)] = 2.1 mm. Although the actual scanning radius Study. Br J Ophthalmol. 2006;90(3):353-6. is longer than 1.7 mm, it may not suggest that the

180 Ophthalmology Update Vol. 11. No. 4, October-December 2013 ORIGINAL ARTICLE

Success of Probing in Congenital Nasolacrimal Duct Obstruction (CNLDO) M. Junaid Sethi Muhammad Junaid Sethi FCPS, FRCS, Fellow Oculoplasty (Germany)1 Madiha Durrani FRCS 2

Abstract Objective: Objective of this study was to find out success rate of probing in congential nasolacrimal duct obstruction in relation to age. Material and method: This is a prospective and comparative study. It was conducted for 2 years between January 2011 to December 2012. A total of 93 eyes of 81 patients were treated. Patients were divided in two groups. In Group-1, 39 children aged 6-12 months were enrolled. In Group-2, 42 children age 12 months to 2 years were enrolled. Results: Success rate was 96% in Group-1 and 88% in Group-2. Key words: Epiphora, Congenital Nasolacrimal duct obstruction, CNLDO

Introduction drops. Children with lower lid entropion and punctual Nasolacrimal duct is the anatomical passage for agenesis or malposition were excluded for the pur- drainage of tears from eye to nose. Epiphora in infancy pose of study. Children were divided into two groups. is most commonly the result of a failure of canalization Group-1 there were 39 children. Six of them had bilat- of the distal end of the nasolacrimal duct1. However eral NLD block. In Group-2 there were 42 children. 6 of 20-30% of newborn have obstruction of nasolacrimal them had bilateral involvement. duct2. This results in watering and sticky eyes3 which Probing was done under short General Anaesthe- can be distressing to both child and parents. sia. Probing was done first by upper punctum and then The standard management is to commence with lower punctum. Each obstructed NLD system was se- conservative management which means that parents quentially probed with larger diameter NLD probes. are taught to massage the lacrimal sac area along with After recovery from general anaesthesia patients topical antibiotic to treat infection if spontaneous canal- were advised moxifloxacin eye drops QID for 10 days. ization4,5 of the NLD does not occur probing should be Follow up was done at 2 weeks, 1 month and 2 months. done. Probing was considered successful in children who The timing of probing is controversial some au- were free from discharge, stickiness, Epiphora and thors consider that probing of NLD beyond one year is negative sac regurgitation test. highly successful and postponement of the procedure until that time did not result in increased rate of failure Results or complication6. However from reviewed literature we Table I have found that spontaneous opening of NLD mostly Gender Group Unilateral Bilateral Success take place in the first 6 months of infant’s life, so we Male Female rate have studied the possibility of probing after that age. I 19 20 33 6 96% Material and methods II 18 24 36 6 88% This is a prospective observational and compara- tive study conducted in Azan Eye Hospital from Janu- Discussion ary 2011 – December 2012. A total of 93 eyes of 81 pa- This prospective study compared the results of tients were treated. All these children enrolled in the early probing before 1 year of age to probing done be- study were having congenital NLD block and were tween 1 year to 2 years of age. It was found that success initially treated with local massage and antibiotic eye rate was much higher (96%) in children probed before 1 year of age as compared to 88% in children more the 1.Senior Registrar Eye Department, Lady Reading Hospital, 1 year7 T. Baarah also found in their study that probing Peshawar. 2. Ophthalmologist, Dubai. UAE carried out on infant with CNLDO between 6 and 12 Correspondence: Dr. Muhammad Junaid Sethi, Senior Registrar Eye Department, Lady Reading Hospital, Peshawar. 33-Defence Officers’ months significantly reduce Epiphora compared with Colony, St: 4, Khyber Road, Peshawar. Cell: 0333 9182595. probing undertaken on older age group8. E.Mail> [email protected] Kong Won study show probing result of 100% Received: July’2013 Accepted: August’2013 in patients under six months and 60% success in pa-

Ophthalmology Update Vol. 11. No. 4, October-December 2013 181 Success of Probing in Congenital Nasolacrimal Duct Obstruction (CNLDO) tients beyond 6 months of age. So success rate decrease 4. Mac Ewans CJ, Young JDH, Barras CW, Ram B, White PS. significantly9 with increasing age. H Sarfaraz, Arif M, Value of nasal endoscopy and probing in the diagnosis and management of children with congenital Epiphora. Br. J Oph- 10 SM Muhammad show success rate of 93% . Rajat Ma- thalmol 2000; 85:314-8. heshwari study reveal 99% result in patients of age be- 5. Rob RM. Success rates of nasolacrimal duct probing at time in- tween 1-2 year and success rate decreaed to 80.9% after tervals after 1 year of age. Ophthalmology 1998;105:1307-1309. 6. Yap EY, Yip CC. Outcome of late probing for congenital nasol- 11 two years of age . AD Syed Khan, Zada MA, Jotoi SM acrimal duct obstruction in Singapore children. Int Ophthalmol study shows 93.3% success rate under 1 year and 84.4% 1997-98;21:331-4. success rate beyond one year age12. Postponement of 7. Zwaan J. Treatment of congenital nasolacrimal duct obstruc- tion before and after the age of 1 year. Ophthalmic Surg Lasers procedure result in decreased success rate because of 1997;28:932-6. chronic inflammation and secondary fibrosis13. 8. Baarah BT, Laban WA. Management of congenital nasolacri- Conclusion mal duct obstruction: comparison of probing Vs conservative medical approach. Bahrain Medical Bulletin 2000; 22 (1). We advise parents of infants with CNLDO to treat 9. Kim YS, Moon SC. Congenital nasolacrimal duct obstruction obstruction conservatively until the age of 6 months and irrigation or probing. Korean J Ophthalmol 2000; 14:90-96. to perform probing between ages of 6 and 12 months. 10. Syed SH, Arif M, Mahmood MS. Syringing and probing results for congenital nasolacrimal duct obstruction. A.P.M.L 2003; 3 (1). References 11. Maheshwari R. Results of probing for congenital nasolacrimal 1. Lavrich JB, Nelson LB. Disorders of the lacrimal system appa- duct obstruction in children older than 13 month of age. Indian ratus. Pediatr Clin North Am 1993;40:767-76. J Ophthalmol 2005;53:49-51. 2. Pollack K, Sommer E. Analysis of congenital dacryostenosis 12. Dabir SA, Gul S, Jatoi MS. Efficacy of probing CNLDO in chil- in consideration of mucoceles. Jahrestagung der DOG, 2002; dren uptill twenty four months of age. Medical Channel 2009;4 10:10-12. Oct-Dec. 3. Nucci P, Capoferri C, Alfarano R, Brancato R. Conservative 13. Richard S. Snell. Clinical anatomy by regions. 8th edition. Wash- management of congenital Nasolacrimal duct obstruction. J ington DC, USA 2007. Paeditar Strabismus 1989;26:39-43.

Lenticular changes in electrical injury

A patient presented lenticular changes after severe electrical shock and admitted at Sussex Eye Hospital, Brighton and Sussex University Hospitals, Brighton, BN2 5BE, UK

Courtesy: CEH Journal UK

182 Ophthalmology Update Vol. 11. No. 4, October-December 2013 ORIGINAL ARTICLE

Ocular Features of Joubert syndrome Shabana Shabana Chaudhry FCPS, FRCS1, Intizar Hussain FCPS, FRCS2, Amna Adil FCPS3, Kamila Iftikhar MD4

ABSTRACT Purpose of Study: To enlist the ocular phenotype in patients with Joubert syndrome in Pakistani pediatric population. Patients & Methods: This Prospective case series of seven children diagnosed as Joubert syndrome clinically with radio- logic confirmation was carried out at Department of Pediatric Ophthalmology, Children Hospital & Institute of Child Health Lahore.All patients underwent complete ophthalmic, psychiatric/ neurological and radiological examination after informed consent from the families. The ophthalmic and oculomotor examination also included cycloplegic refraction and dilated fundus examination. MRI brain, Electromyography (EMG) and Forced duction test (FDT) were done in all patients. 42.8% also had Tensilon test. Results: Age ranged from 5-months to 10 years. Three males and four females were included in the study. One boy of 10-years and two pair of siblings presented with progressive bilateral ptosis and ocular deviation while one pair of siblings had the history of oculomotor aparaxia and nystagmus respectively. All affected patients showed a partial loss of ocular movement. A variable degree of ptosis was present in 71% patients. The horizontal movement varied from complete loss of motility (external Ophthalmoplegia) to partial restriction of adduction and abduction only. The ptosis caused chin elevation and bilateral amblyopia in 71% children. One patient had internal ophthalmoplegia in addition to external ophthalmoplegia. The neurologic–psychiatric examination showed mild to moderate abnormalities in 71% patients. All had classical “Molar Tooth Sign” on MRI except one who had mild hypoplasia of vermis. Conclusion: Joubert syndrome can present with a wide range of limitation of extraocular movements and ptosis. Key Words: Joubert syndrome, Molar tooth sign, external ophthalmoplegia, ptosis

INTRODUCTION nopathy, renal and hepatic abnormalities can also be Joubert syndrome (JS) is a rare autosomal reces- found4,16,17 . sive congenital malformation of the brainstem and Neuroimaging of the brain in the axial plane cerebellar vermis1,2 Diagnostic criteria is based on demonstrate the molar tooth sign, a term that refers hypotonia, ataxia, developmental delay, molar tooth to the deep interpeduncular fossa, hypoplasia of the sign1,2,3,4,5,6,7,8,9,10 ,abnormal breathing or abnormal eye cerebellar vermis, and horizontally oriented and thick movements. In 1969 Marie Joubert described four superior cerebellar peduncles, is highly suggestive siblings with episodic tachypnoea, developmental of JS diagnosis­ 7,8,18,19,20,21.This study was carried out to delay, ataxia, abnormal eye movements and absence evaluate the ocular features in patients with JS. of the cerebellum for the first time1. Ocular and ocu- PATIENTS & METHOD lomotor involvement is common in JS8,10,11,12,13,14.How- This prospective case series of seven children di- ever, findings differ considerably because of a wide agnosed as Joubert syndrome clinically with radiolog- range of phenotypic variability among patients with ic confirmation was carried out at department of pedi- JS.Abnormal eye movements include nystagmus, stra- atric ophthalmology, Children’s Hospital and Institute bismus, oculomotor apraxia and vertical gaze palsy. of Child Health Lahore. After obtaining informed con- Because of the syndrome’s rarity the diagnoses of Jou- cent from the families all patients underwent complete bert Syndrome can easily be overlooked4,15. In some ophthalmic, psychiatric/neurological and radiologi- cases, Leber congenital amaurosis, pigmentary reti- cal examination. MRI brain, Electromyography (EMG) and forced duction test (FDT) was done in all patients. 1.Senior registrar, Department of Ophthalmology, Children Hospital, Lahore 2.Assistant Professor, Department of Ophthalmology, Tensilon test was done in 42.8%. Abdominal ultra- Services Institute of Medical Sciences & Services Hospital sound and biochemical analysis to evaluate kidney Lahore.3.Ophthalologist, Department of Ophthalmology, Services and liver function were also performed. The ophthal- Institute of Medical Sciences & Services Hospital Lahore. mic and oculomotor examination included assessment 4.Developmental Paediatrics Fellow, Department of Developmental Paediatrics, Children Hospital Lahore of visual acuity, pupil examination, extraocular move- Correspondence: Dr. Shabana Chaudhry FCPS FRCS, 254-A New ments and slit-lamp or penlight examination for the Muslim Town, Lahore, 54600.E.Mail:

Ophthalmology Update Vol. 11. No. 4, October-December 2013 183 Ocular Features of Joubert syndrome was performed and dilated fundus examination with was present in 5/7 patients. Brow elevation/arched eye indirect ophthalmoscopy was done for each patient. brow seen in 3/7 patients to overcome ptosis. The hori- Vestibulo-ocular reflex was measured by having the zontal movement varied from complete loss of motility subject fixate a target while the head was rotated hori- (external Ophthalmoplegia) to partial restriction of ad- zontally or vertically. duction and abduction only. The ptosis and ocular re- striction caused chin elevation/face turn and bilateral Fig 1 (A) Bilateral Ptosis and Exotropia amblyopia in five (5/7) children (Fig 1 A). Normal ves- tibule-ocular reflex was present in only one pair of sib- lings. Saccades dysfunction was present in all patients. Abnormalities were seen in persuit and convergence (6/7). Pupil examination showed sluggish reaction in one patient. A mid-dilated fixed pupil along with ptosis and external ophthalmoplegia was also found in anoth- er patient (3rd nerve palsy). Cycloplegic refraction and fundus examination was normal in all cases (Table 1).

Table 1: Ophthalmic features of Joubert Syndrome

No.of patient Ophthalmic features Findings / %age Bilateral amblyopia Present 3/7(42.85%)

Fig 1(B) Molar Tooth Sign Ptosis Present 5/7(71.42%)

Anterior segment Normal 7/7 (100%)

Sluggish (1/7) & Pupil 2/7 (28.57%) fixed,mid dilated (1/7)

Strabismus Exotropia (XT) 3/7 (42.85%)

Nystagmus Present 1/7 (14.28%)

VOR Normal 2/7 (28.57%)

Saccades dysfunction Present 7/7(100%)

Smooth persuit Abnormal 6/7 (85.7%) Head thurst Present 1/7 (14.28%) (oculomotor aparaxia) Convergence deficit Present 3/7 (42.85%) RESULTS Normal fundus Seven consecutive patients diagnosed with JS Normal 7/7 (100%) examination underwent ocular and oculomotor examination with ages ranged from 5-months to 10 years. Developmen- Standard clinical MRIs were reviewed by a paedi- tal delay sometimes limited ophthalmic examination atric neuro-radiologist and a developmental paediatri- that was present in all patients. Parents of two pairs of cian. The neurologic–psychiatric examination showed siblings were first cousin; consanguinity was denied in mild to moderate abnormalities in 5/7 patients. Im- the remaining families. Three males and 4 females were aging uniformly revealed a small or absent cerebellar included in this study. One boy of 10-years and two vermis, horizontally orientated long, thick superior cer- pair of siblings presented with progressive bilateral ebellar peduncles and an abnormally deep inter-pedun- ptosis and ocular deviation while one pair of siblings cular fossa, classical “Molar Tooth Sign” on MRI (6/7) (5-months old sister and 3 years old brother) had the (Fig 1 B) except one of the sibling with ptosis,external history of oculomotor aparaxia and nystagmus respec- and internal ophthalmoplegia with no “molar tooth tively. Vision could be assessed on the Snellen chart in sign” but mild hypolasia of vermis. Electromyography only 3 patients (BVA: ranges 6/7.5-CF). All affected pa- (EMG) and Forced duction test (FDT) were normal in tients showed a partial loss of ocular movement. Only 5/7 children. Tensilon test was done in 3/7 of patients 3 patients had exotropia. A variable degree of ptosis because of progressive worsening of ptosis to rule out

184 Ophthalmology Update Vol. 11. No. 4, October-December 2013 Ocular Features of Joubert syndrome

Table 2: MRI and general features of Joubert Syndrome

Age at Parental Visual acuity Independent Developmental delay/ Electromyography H/o squint Patient Gender diagnosis Facial Features Speech MRI consanguinity R.E & LE walk autism (EMG) surgery (years)

1 Male 10 N 6/7.5 & 6/12 Large forehead, arched brow Dysarthria Ataxic gait Aggression MTS Normal +

Depressive, mood 2 Female 8 Y 6/18 & CF - Normal Normal MTS Normal + swings

3 Female 6 Y - - Normal Normal Learning disability MTS - Normal

Learning disability, Vermis 4 Female 9 N CF & 6/36 Large forehead, arched brow Normal Normal Normal _ Depressive hypoplasia

H/o frequent 5 Male 7 N F &F - Normal Autistic MTS Normal - falls

0.5 Severe global Hypotonia/consistant low set ears, depressed nasal 6 Female (5- Y - - - developmental delay, MTS with congental - bridge, polydactyly months) failure to thrive myopathy Flat occiput, low set ears, Hypotonia/consistant Moderate global 7 Male 3 Y F &F depressed nasal bridge, Dysarthria Cannot walk MTS with congental - developmental delay polydactyly, myopathy myasthenia gravis, it was normal in all 3 cases (Table 2). may vary in each family and even between affected In all patients abdominal ultrasound reported nor- siblings. Respiratory abnormalities, as hyperapnea and mal renal echogenicity as well as normal renal and liver apnea, one of the primary diagnostic criteria4,7 were function tests. Moderate behaviour disturbance, with seen in 2/7 patients of our series. 4/10 patient with mild autistic features, was seen in two individuals. Pigmentry fundus changes, retinal dystrophy and se- Facial distinctive features as prominent forehead vere visual loss are described by Sturm et al recently and thick eyebrow were seen in three patients. All associated with JS26. That has been also described in patients showed facial features of muscle wasting other studies.11,12,13,14.In our cases pigmentry fundus (temporal hollowness as in progressive external changes and retinal dystrophy were not found clinically ophthalmolplegia). however, variable degree of amblyopia was present in DISCUSSION (6/7) patients and in one patient there was occulomotor JS was uniformly associated with a spectrum of aparaxia.(1/7). ocular motor deficits consistent with malformation of Manifest deviations were observed in 3/7 of pa- midline structures and crossed neural pathways of the tients in our study. Ocular misalignment is common cerebellum and brain stem. Brain MRI provided gross in JS10,13,14. In 6/7 of the patients, performance during anatomic evidence for hypoplasia of the cerebellar ver- smooth persuit and saccades was poor. Our findings of mis, nodulus, flocculus, deep cerebellar nuclei, and oculomotor defects are in agreement with the findings pons. Within the cerebellum and brain stem, neural of earliest studies8,10,13,14.The association of JS with con- structures are interconnected by neural pathways that genital ocular fibrosis was reported previously for the cross the midline25. Weiss et al described quantitative first time by Appleton et al in a 16-month old child27and eye movements that provided indirect evidence for de- then by Jacobson et al.28Demer et al & Wu et al also cussation abnormalities of neural pathways that were described Congenital fibrosis of the extraocular mus- not visualized by MRI. Therefore, eye movement stud- cles in their case series.29,30.Congenital fibrosis of the ies complement the MRI findings by providing indirect extraocular muscles is referred to complex strabismus functional evidence of neuro-anatomic abnormalities syndromes characterized by congenital non-progres- within the brain stem and cerebellum that occur in JS25. sive ophthalmoplegia with or without ptosis affecting Recognition of molar tooth sign at brain MRI is part or all of the oculomotor nucleus and nerve and its an essential cue for the diagnosis of JS. Early signs, as innervated muscles and/or the trochlear nucleus and abnormal eye movements and respiratory abnormali- nerve and its innervated muscle.29,30. ties might suggest this possibility, but in most of cases, We found similar ptosis in 5/7 of our patients clinical features are non-specific. Once diagnosis of JS but in contrast to Demer et al & Wu et al ptosis and is made, it is recommended to perform a comprehen- limitation of EOM was progressive and became appar- sive functional and morphological evaluation of liver, ent around the age of 3-4 years. One (1/7) of our series kidney and visual function. Clinical variability in JS had progressive cerebellar ataxia that is also reported is explained not only by its genetic heterogeneity but previously. Again our patient had progressive ocular also by the remarkable phenotype diversity seen with motility disorder and ptosis along with progressive different mutations in the same gene. Clinical features ataxic gait.31,32. Periodic clinical re-evaluation is highly

Ophthalmology Update Vol. 11. No. 4, October-December 2013 185 Ocular Features of Joubert syndrome recommended; for instance, abnormal liver tests in one related disorders) .Eur J Hum Genet 2007;15:511-521. study were detected only after the first decade of life. JS 5. Kumandas S, Akeakus M, Coskun A, Gumus H. Joubert syndrome: review and report of seven new cases.Eur J Neurol 2004; 11:505-10. 33 prognosis at an early age is difficult to be determined . 6. Alorainy IA, Sabir S, Seidahmed MZ, et al. Brain stem and In earlier reports, JS was considered to be a dis- cerebellar findings in joubert syndrome. J Comput Assist Tomogr tinct clinical entity. More recently, this disorder has 2006;30:116-21. 7. Maria BL, Boltshauser E, Palmer SC, Tran TX. Clinical features and been found to be genetically heterogeneous with muta- revised diagnostic criteria in Joubert syndrome. J Child Neurol tions in NPHP1, AHI1, CEP290, RPGRIPIL,MKS3 and 1999;14:583-590 CCD2A identified in approximately 40% of patients34-40. 8. Maria BL, Hoang KB, Tusa RJ, et al. “Joubert syndrome” revisited: key ocular motor signs with magnetic resonance imaging Each genotypic variant of JS may be associated with correlation. J Child Neurol. 1997;12:423–430. distinctive developmental and functional abnormali- 9. King MD, Dudgeon J, Stephenson JB. Joubert’s syndrome with ties of the cerebellum and brain stem. Although these retinal dysplasia: neonatal tachypnoea as the clue to a genetic genetic disorders are heterogeneous they share a func- brain-eye malformation.Arch Dis Child. 1984;59:709–718. 10. Lambert SR, Kriss A, Gresty M, Benton S, Taylor D. Joubert tional abnormality of the primary cilium/basal body syndrome.Arch Ophthalmol. 1989;107:709–713. organelle. To describe these genetic disorders which 11. Moore AT, Taylor DS. A syndrome of congenital retinal dystrohy share overlapping features the term Joubert syndrome and saccade palsy-A subset of Leber’samaurosis. Br J Ophthalmol 34 - 40 1984;68:421-431 and related disorders (JSRD) is used. 12. Steinlin M, Schmid M, Landau K, Boltshauser E, Follow-up in In conclusion, patients were affected by multi- children with Joubert syndrome.Neuropediatrics 1997;28:204-11. complex neuropathological findings of the cerebellar 13. Tusa RJ, Hove MT, Ocular and oculomotor signs in Joubert syndrome. J Child Neurol 1999;14:621-7. vermis and of several pontine and medullary structures. 14. Hodgkins PR, Harris CM, Shawkat FS,Thompson DA,Chong Furthermore, it may arise from the wide genetic hetero- K,Timms C et al: Joubert Syndrome: long-term follow-up.Dev Med geneity of JS and related disorders, as only about 25% of Child Neurol 2004; 46:694-699 causative genes and loci have been detected today. For 15. Merritt L. Recognition of the clinical signs and symptoms of Joubert syndrome.Adv Neonatal Care 2003;3: 178-86. further analysis of the ocular motor phenotype, a larger 16. Valente EM, Brancati F, Dallapiccola B. Genotypes and phenotypes cohort of affected patients and higher resolution MRI of Joubert syndrome and related disorders.Eur J Med Genet to help and characterize the neuroanatomical and func- 2008;51:1-23. 17. Zaki MS, Abdel-Aleem A, Abdel-Salam G, et al. The molar tooth tional abnormalities associated with specific genotypes sign. A new Joubert syndrome and related cerebellar disorders of JS is suggested. classification system tested in Egyptian families. Neurology CONCLUSION 2008;70:556-565. 18. Maria BL, Quisling RG, Rosainz LC,Yachnis AT,Gitten Jc,Dede DE Joubert Syndrome can present with a wide range et al. Molar tooth sign in Joubert syndrome: clinical, radiologic, and of limitation of extraocular movements and ptosis. In pathologic significance. J Child Neurol. 1999;14:368–376. addition to abnormalities of the eye movements, there is 19. Quisling RG, Barkovich AJ, Maria BL. Magnetic resonance imaging variable clinical presentation of the disease mentioned features and classification of central nervous system malformations in Joubert syndrome. J Child Neurol. 1999;14:628–635 in literature. Joubert syndrome is both a clinical and 20. Maria BL, Bozorgmanesh A, Kimmel KN, Theriaque D, Quisling radiological diagnosis. Although the neuro-imaging is RG. Quantitative assessment of brainstem development in typical, the diagnosis should be supported by clinical Joubert syndrome and Dandy-Walker syndrome. J Child Neurol. 2001;16:751–758. evidence. 21. Gleeson JG, Keeler LC, Parisi MA,Marsh SE,Chance PF,Glass Increased awareness of the possibility of this syn- IA et al. Molar tooth sign of the midbrain-hindbrain junction: drome occurring in patients who exhibit developmen- Occurrence in multiple distinct syndromes. Am J Med Genet A. 2004;125:125–134 tal delay, extraocular muscle movement abnormalities, 22. Braddock SR, Henley KM, Maria BL. The face of Joubert nystagmus and hypotonia in early childhood will lead syndrome:a study of dysmorphology and anthropometry. Am J to early diagnosis, appropriate counselling, and proper Med Genet A 2007;143:3235-42 rehabilitation. 23. Ferland RJ, Eyaid W,Collura RV,Tully LD,Hill RS,Al-Rumayyan A et al. Abnormal cerebellar development and axonal decussation REFERENCES due to mutations in AHI1 in Joubert syndrome. Nat Genet 1. Joubert M, Eisenring JJ, Robb JP, Andermann F. Familial agenesis 2004;36:1008-13. of the cerebellar vermis. A syndrome of episodic hyperpnea, 24. Poretti A, Boltshauser E, Loenneker T,Valente EM,Brancati abnormal eye movements, ataxia, and retardation.Neurology. F,Yosov II et al. Diffusion tensor imaging I Joubert syndrome.Am 1969;19:813–825. J Neuroradiol 2007;28:1929-33. 2. Boltshauser E, Isler W. Joubert syndrome: episodic hyperpnea, 25. Weiss AH, Doherty D, Parisi M, Shaw D, Glass I, Phillips JO.Eye abnormal eye movements, retardation and ataxia, associated with movement abnormalities in Joubert syndrome.Invest Ophthalmol dysplasia of the cerebellar vermis.Neuropadiatrics. 1977;8:57–66. Vis Sci. 2009;50:4669-77. 3. Dekaban AS. Hereditary syndrome of congenital retinal blindness 26. Sturm V, Leiba H, Menke MN,Valente EM, Poretti A, Landau (Leber), polycystic kidneys and maldevelopment of the brain. Am J K,,Boltshauser E.Ophthalmological findings in Joubert syndrome. Ophthalmol 1969;68:1029-37. Eye 2010;24:222–225. 4. Parisi MA, Doherty D, Chance PF, Glass IA. Joubert syndrome (and 27. Appleton RE, Chitayat D, Jan JE, Kennedy R, Hall JG. Joubert’s

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syndrome associated with congenital ocular fibrosis and jouberin, cause Joubert syndrome with cortical polymicrogyria. histidinemia. Arch Neurol. 1989;46:579-82. Am J Hum Genet. 2004;75:979-87. 28. Jacobson DM, Johnson R, Frens DB Joubert’s syndrome, ocular 35. Parisi MA, Doherty D, Eckert ML,Shaw DW,Ozyurek H,Aysun fibrosis, and normal histidine levels. Am J Ophthalmol1992; S et al. AHI1 mutations cause both retinal dystrophy and renal 113:714-716. cystic disease in Joubert syndrome. J Med Genet. 2006; 43:334-9. 29. Demer JL, Clark RA, Engle EC. Magnetic resonance imaging 36. Sayer JA, Otto EA, O’Toole JF,Nurnberg G,Kennedy MA,Becker evidence for widespread orbital dysinnervation in congenital C et al. The centrosomal protein nephrocystin-6 is mutated in fibrosis of extraocular muscles due to mutations in KIF21A. Joubert syndrome and activates transcription factor ATF4.Nat Invest Ophthalmol Vis Sci. 2005;46:530–9. Genet. 2006;38:674-81. 30. Wu L, Zhou LH, Liu CS, Cha YF, Wang J, Xing YQ. Magnetic 37. Baala L, Romano S, Khaddour R,Saunier S,Smith UM,Audollent resonance imaging features in two Chinese family with congenital S et al. The Meckel-Gruber syndrome gene, MKS3, is mutated in fibrosis of extraocular muscles.Zhonghua Yan KeZaZhi. Joubert syndrome.Am J Hum Genet. 2007; 80:186-94. 2009;45:971–6. 38. Delous M, Baala L, Salomon R, Laclef C,Vierkotten J,Tory K et al. 31. Yoshida K, Okano T, Hoshi K, Yahikozawa H, Suzuki K, The ciliary gene RPGRIP1L is mutated in cerebello-oculo-renal Banno H, Tamura T, Sobue G, Ikeda S. Congenital fibrosis of syndrome (Joubert syndrome type B) and Meckel syndrome. Nat the extraocular muscles (CFEOM) syndrome associated with Genet. 2007; 39:875-81. progressive cerebellar ataxia. Am J Med Genet 2007;143:1494-501. 39. Arts HH, Doherty D, van Beersum SE,Perisi MA,Letteboer 32. Gunzler SA, Stoessl AJ, Egan RA, Weleber RG, Wang P, Nutt SJ,Gorden NT et al. Mutations in the gene encoding the basal JG. Joubert syndrome surviving to adulthood associated with a body protein RPGRIP1L, a nephrocystin-4 interactor, cause progressive movement disorder.MovDisord. 2007;22:262-5. Joubert syndrome. Nat Genet. 2007; 39:882-8. 33. Leão EK, Lima MM, Maia OO Jr, Parizotto J, Kok F.Joubert 40. Gorden NT, Arts HH, Parisi MA,Coene Kl,Letteboer SJ, Van syndrome: large clinical variability and a unique neuroimaging Beersum SE etal. CC2D2A Is Mutated in Joubert Syndrome and aspect.Arq Neuropsiquiatr. 2010;68:273-6. Interacts with the Ciliopathy-Associated Basal Body Protein 34. Dixon-Salazar T, Silhavy JL, Marsh SE, Louie CM, Scott CEP290.Am J Hum Genet. 2008;83:559-57 LC,Gururaj A et al. Mutations in the AHI1 gene, encoding

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Ophthalmology Update Vol. 11. No. 4, October-December 2013 187 ORIGINAL ARTICLE

Frequency of Convergence Insufficiency in Orthoptic Clinic Imran Khalid Imran Khalid B.Sc (Hons) Vision Sciences1, Amtul Mussawar Sami FCPS2, Prof. Muhammad Tayyib FRCS, FRCOphth3 Services Institute of Medical Sciences, Services Hospital, Lahore

ABSTRACT: Objectives: To assess the frequency of convergence insufficiency with reference to age, sex, near point of convergence, exophoria, fusional vergence and refractive error. Study Design: Community based descriptive type /cross sectional study. Material and Methods: This study had been carried out at the Orthoptic clinic of SIMS/ Services Hospital Lahore from September 2010 to March 2013. Patients without higher refractive error and manifest squint presented with a complaint of asthenopia and headache were referred to the orthoptic clinic after anterior segment examination. Near point of convergence was measured, alternate cover test was done at distance and near to examine the heterophoria, exophoria and fusional vergence was measured with prism bar at near. Retinoscopy and fundoscopy done to evaluate refractive error and posterior segment anomalies respectively. Results: Convergence insufficiency (75%), 38/51 found to be more in the age of 11 to 30 years. Female affected 61% (n= 31) more as compared to male 39% (n= 20). 65% (n=33) had exophoria and 35% (n= 18) had orthophoria. 63% had NPC between 16 to 20 cm. 72% reported diplopia between 16 to 20 prism diopter base out. 51% had no refractive error, 18% had low myopia, 25% simple myopic astigmatism and 6% had presbyopia. Conclusion: Three fourth of CI (75%) patients were in the age of 11 to 30 years and it affects more commonly in females (61%). One third population of CI had orthophoria at near. The professional readers, students and workers who engaged in near distance activities for extended hours daily, presented with a complaint of asthenopia and headache without high refractive error and manifest squint prone to have a definitive convergence insufficiency, required orthoptic consultation and orthoptic exercises along with the required refractive correction. Key words: Convergence insufficiency, near point of convergence, exophoria, fusional reserve Abbreviations used in this study: Convergence insufficiency= CI, Near point of convergence= NPC, Positive fusional vergence= PFV, Prism diopter= PD

INTRODUCTION tive error, accommodative insufficiency and defective In 1855, Von Graefe first time described the symp- fusion.2 Functional disorder to rule out pseudo conver- toms of convergence Insufficiency (CI) and thought it gence insufficiency, basic exophoria, divergence excess to be myogenic in origin.1It is a common binocular vi- (greater exophoria at distance). Convergence paralysis sion disorder that is often associated with a variety of due to ischemic infraction, demyelination, flu or viral symptoms including eye strain, headache, blurred and infection, Parkinson’s disease, perinaud syndrome. double vision in near distance activities, difficulty in Medial rectus weakness due to multiple sclerosis, my- concentration during reading. To reduce the symptoms asthenia gravis and previous squint surgery.3 Patients patient have to squint, rubbed or closed one eye and have visual acuity 6/6 at distance and N6 at near yet have to change their posture just to refresh the eyes and they have symptoms of CI in majority of cases. Conver- used different tools like pencil, mouse and ruler for gence insufficiency may occur in presence of exophoria, better tracking of the lines. At the end of the day, they orthophoria or esophoria. However, the symptoms are felt frequent headache and asthenopia. However, not exacerbated in patients with exophoria because the ba- all patient presents with same symptoms and it vary sic exodeviation must be overcome by fusion before the in individuals depending upon the severity of CI, pro- eyes can begin to converge.4 Lack of sleep, illness, anxi- fessional needs, proper usage of refractive prescription ety, general health weakness, prolonged near work are and orthoptic exercises. Predisposing causes are the the factors that aggravates the symptoms of CI. wide inter-pupillary distance, occupation using mainly MATERIAL & METHODS uni-ocular vision, poor lightening, uncorrected refrac- In Pakistan no reliable statistical data is available 1.Orthoptist,2. Assistant Professor of Ophthalmology3. Professor of up till now that discussed the frequency of convergence Ophthalmology insufficiency regarding to age, gender, near point of Correspondence: Imran Khalid, Orthoptist, Eye unit 1, Services convergence, exophoria and positive fusional reserve Hospital, Lahore. Cell: 03334548183, at the near. Therefore, it was considered to be studied E.Mail>[email protected] this disorder of convergence in the orthoptic clinic of Received: July 2013 Accepted: August’ 2013 Services Hospital Lahore. This study considered three

188 Ophthalmology Update Vol. 11. No. 4, October-December 2013 Frequency of Convergence Insufficiency in Orthoptic Clinic clinical signs of CI receded NPC, exophoria at near, in- DISCUSSION: sufficient positive fusional vergence at near. The most Before diagnosing definitive convergence insuffi- frequent signs found in this study are the receded NPC, ciency, history and other investigation must be carried positive fusional vergence and the exophoria was pre- out because in diseases like multiple sclerosis, myas- sent 65%. The frequency of convergence insufficiency thenia gravis and Parkinsonism presented in the or- can vary tremendously (50.4% to 6.0%) in a clinical set- thoptic clinic with reduced near point of convergence. ting depending upon which characteristics are selected It’s better to treat the underlying cause rather than to to define this condition, sampling size and the number give orthoptic exercises until the underlying condition of population under studied.5 will be stabled. Some patients with convergence insuf- Inclusion Criteria: ficiency will initially show a fairly good near point of Patient’s age between seven to forty years. convergence, fusional reserve at near and by giving proper instruction about the awareness of diplopia, the Patient has asthenopia and headache without high patient subjective response will certainly be increased; refractive error and manifest strabismus. No pathology however on repeating the test at least two times, they in the anterior and posterior segment. get fatigued and show almost actual amount of NPC. Exclusion Criteria: While measuring the NPC objectively, it’s necessary to Patient’s age below seven and above forty years. consider the short inter-pupillary distance and epican- Basic exophoria, accommodative insufficiency, myas- thi folding because these factors can mask the objective thenia gravis measurement of NPC. One hundred patients who had RESULTS: no anterior and posterior segment pathology, no high Table -1: Distribution of patients according to age: refractive error and manifest squint with a complaint of Age Frequency Percentage asthenopia and headache were referred to the orthoptic <10 5/51 10% clinic. Fifty one patients was diagnosed with CI (51%), 11-20 18/51 35% others had Pseudo convergence insufficiency, accom- modative insufficiency, ocular surface disorder, myas- 21-30 20/51 39% thenia gravis, parkison’s isease, progressive supranu- >31 8/51 16% clear palsy and low refractory problems. Three fourth Table -2: Distribution of patients according to gender: (75%) of CI patients were in the age of 11 to 30 years. All were professional readers and have to work at a close distance in daily life. So, the reason of increasing Gender percentage of convergence insufficiency is due to age, in which doctors, engineers, and students enrolled in higher education have to read and write at the near more frequently in a day. CI affected more to female (61%) as compared to male (39%) might be due to fact that in Pakistan, the enrolment of female in higher education is more as compared to male but almost similar finding exist in a ratio 67 female and 33 male,6 (Archana Gupta et al) in contrast to Rouse et al5 study where no gender predilection was described. A remote near point of convergence is the most consistent finding in convergence insufficiency and it remained single Table -3: Distribution of patients according to NPC: clinical characteristics in the diagnosis of CI in Norn7, Letourneau et al8 studies. Convergence insufficiency NPC treatments trial (CITT) used inclusion criteria are greater than or equal to 6cm9. 63% had near point of convergence between 16 to 20 cm and 10% even had NPC 25 cm. So, whenever a patient come with a complain of ocular asthenopia, should measure near point of convergence and near point of accommodation, who professionally adhered to see the fine details of targets at near for sufficient hours daily. 65% had an exophoria at near while 35% were orthophoric.

Ophthalmology Update Vol. 11. No. 4, October-December 2013 189 Frequency of Convergence Insufficiency in Orthoptic Clinic

Cushman and Burri reported that 63% of CI patients (51%) in defined population of this study in which the exhibited an exophoria on alternate cover test at female affected (61%) as compared to male and (75%) CI near. However, most of the patients with CI had an was in age group between 11 to 30 years indicated that exophoria. The presence of abnormal exophoria at near further studies should be conducted institutional wise is not necessary for the diagnosis of common CI10 as at national level to find out its prevalence in students, one third of population exhibit orthophoria at the near. teachers and workers who are professionally engaged The possibility of 35% were being orthophoric during in near and distance activities for extended hours of CI evaluation may due to the patient using more fusion work daily. at that time and exophoric component or its magnitude REFERENCES: merely masked at that moment. Exophoric association 1. Von Graefes A. Uber myopia in distans nebst Betrachtungen with CI, if left untreated and patient do daily routine uber sehen jenseits der grenzen unserer accomodataion. Graefes Arch ophthalomol 1855; 2: 158-66. work, it produce serious discomfort in professional 2. Rowe, F. Clinical Orthoptics. 2nd Edition; Blackwell; 2004. life and there is a greater risk of exophoric conversion 3. Schieman, M. Wick, B. Clinical Management of Binocular Vision. to intermittent exotropia. Normal positive fusional Philadelphia, 3rd Edition; Lippincott Williams&Wilkins, 2008. 4. Von noorden GK, Helveston EM. Strabismus a Decision Making vergence amplitude for near is 30 to 35 PD but patient Approach. First edition, Mosby, London, 1994. with convergence insufficiency usually break with less 5. Rouse MW, Hyman L, Hussein M, Solan H. Frequency than 20 PD base out.11 In this study 72% (n=37) patient of convergence insufficiency in optometry clinic settings. presented with poor fusional reserve between 16 to 20 Optometry and vision science, vol. 75, no. 2, February1998. 6. Gupta A, SK Kailwoo, Vijayawali. Convergence insufficiency in PD and this finding is much closer to Matti Westman patients visiting eye OPD with headach. JK Science vol 10, no 3, et al12 study where the PFV was 71.1%. Refraction has July-September 2008. much significant position in the prognosis of CI. It is 7. Norn MS. Convergence insufficiency. Incidence in ophthalmic practice. Results of orthoptic treatment. Acta Ophthalmol (Kbh) desirable to evaluate myopic astigmatic association to 1966; 44: 132-8. provide clear, comfort view and to enhance the visual 8. Letourneau JE, Lapierre N, Lamont A. The relationship between span of the desired contents. Necessary counseling the convergence insufficiency and school achievement. Am J required for the presbyopic patients having CI to Optom Physiol Opt 1979; 56: 18-22. 9. Scheiman M, Mitchell GL, Cotter S. A randomized clinical use best possible minimum plus prescription and do trial treatment for convergence insufficiency in children. Arch regular exercises with an accommodative target. In Ophthalmol 2005; 123: 14-24. vision therapy room/ orthoptic clinic can give sufficient 10. Cooper J, Jamal N. Convergence insufficiency -- a Major review. Optometry.2012 Apr 30; 83(4):137-58. time to train the patient for orthoptic exercises. Pencil 11. Wright KW, Spiegel PH, Thompson LS. Hand Book of Pediatric push-up-therapy (PPT) was the most common first Strabismus and Amblyopia. 2nd edition, Springer science, 2003, line of treatment (78.8% ophthalmologist). Failure of USA. PPT 86.7% considered a lack of compliance as major 12. Westman M, Liinamaa MJ. Relief of asthenopic symptoms with 13 orthoptic exercises in Convergence insufficiency is achieved in reason perceived by ophthalmologist. An intensive both adults and children. Journal of optometry (2012) 5, 62- 67. orthoptic program appears to be the treatment of choice 13. Patwardhan SD, Sharma P, Sexena R, Khanduja SK. Preferred for reducing the signs and symptoms of convergence clinical practice in Convergence insufficiency in India: A Survey. insufficiency.14 Indian journal of ophthalmology vol 56, issue 4, 2008 page 303- 306. CONCLUSION: 14. Lavrich JB. Convergence insufficiency and its current treatment. The high frequency of convergence insufficiency Current opinion in ophthalmology 2010; 21(5): 356-60.

190 Ophthalmology Update Vol. 11. No. 4, October-December 2013 ORIGINAL ARTICLE

Difference in Central Corneal Thickness between Male & Female in Adults. Danish Zafar Danish Zafar FCPS1, Zulfiquar Ali FCPS2, Prof. S. Ashfaq Ali Shah FCPS3 Prof. Hassan Sajid Kazmi FCPS 4

ABSTRACT Background: Corneal thickness measurements are important in refractive surgery, for interpretation of IOP and in corneal diseases. The study was designed to know the difference in CCT between male and female in our setup in adult population. Material and Method: It was a case series study of 300 patients examined in the out patient department of Ophthalmology, Ayub Medical College, Abbotabad from April 2011 to November 2011. Results: 300 patients were examined, 158 (52.7 %) were male 142 (47.3 %) were female. The mean CCT was 548.7 for males and mean CCT was 547.8 for female. There was no difference of mean CCT between right and left eye, so CCT has no significance statistical difference between male and female and p value is > 0.05. Conclusion: - CCT is not affected by gender and age. Keywords: - CCT (Central Corneal Thickness).

INTRODUCTION: previous data gave no difference in CCT between male Glaucoma remains one of the leading causes of and female. the acquired blindness. According to national survey To our knowledge no study has been done in our of blindness in Pakistan, glaucoma is the second most setup in this regard. The purpose of the study is to find leading cause after cataract1. The applanation tonome- out difference in CCT between male and female of our try is the gold standard for measuring IOP. It estimates setup to make ground for further research. the IOP by pressure required flattening the central cor- MATERIAL AND METHOD: nea, so thinner can lead to under estimation of Patients attending eye out-patient department of IOP and thicker cornea can lead to over estimation of Ayub Medical College Abbottabad during the study true IOP2-4. In addition thinner central corneal measure- period, were divided into seven groups according to ments are associated with the development of glau- age < 25, 25 - 34, 35 – 44, 45 – 54, 55 – 64, and 65 – 75, coma5, and more advanced damages due to glaucoma6. above 80. All of them were examined through informed Therefore CCT is important in glaucoma assessment. In consent. Information was collected on structured Per- a same way corneal thicknesses measurements are im- forma. No patient with previous history of any intra oc- portant in refractive surgeries which are the need of the ular or extra ocular surgery was included in the study. day. The surgeries are done for the treatment of myo- Central corneal thickness was measured by ultrasonic pia, hypermetropia and astigmatism. But before plan- pachymetery. SPSS version 16 was used for data analy- ning the surgeries we need details of corneal thickness. sis. Mean were calculated for variable right and left eye CCT will tell us about our plan of management and CCT and age. Age was co related to mean corneal thick- prognosis of treatment. In a same way CCT is helpful ness in male and female. in other corneal diseases. RESULTS: Corneal thickness is known to be influenced by 300 patients were examined, age ranging from 20 – the body size, body height, gender, age and refractive 80 years, among which 158 were male 142 were female. state7-24. Some previous studies have shown the differ- Mean age was 42.23 + 15.43 years. Mean CCT for male ence in the central corneal thickness during a months’ is 548.7 and mean CCT for female is 547.8 there was time in females25 some studies showed thicker cornea no difference between mean CCT of right and left eye in male as compared to female26 and some results from which are 549.48 and 548.33 respectively. 1.Assistant Prof. of Ophthalmology, Northern Institute of Medical 2. Sciences, Abbottabad Assistant Professor, Ayub Medical College, TABLE : 1 Mean sex related corneal thickness Abbottabad 3.Prof. of Ophthalmology, Ayub Medical College, corneal thickness Abbottabad 4.Prof. of Ophthalmology, Gender corneal thickness Correspondence: Dr. Danish Zafar, House No 13 St: 2, Police Housing Colony. Mirpur Abbottabad. Mean 548.7785 e-mail; [email protected] Cell: 0315 9110555 male N 158 Received: May’2013 Accepted: July’2013 Std. Deviation 23.36927

Ophthalmology Update Vol. 11. No. 4, October-December 2013 191 Difference in Central Corneal Thickness between Male & Female in Adults

Mean 547.8380 547.8 Studies have been done in western and Chinese female N 142 population to show correlation between gender and Std. Deviation 25.86589 CCT. Some studies showed thicker cornea in male then Mean 548.3333 female25. Study done in Chinese adult has shown sig- Total N 300 nificant association of CCT with urban region and male Std. Deviation 24.54555 gender. But it also showed no association with body (Table No.2) Age was correlated with the CCT (Table weight, body height and age. No:3) showing no difference in CCT between male and Study done by Soni PS, showed that corneal thick- female with age. P value for CCT with gender is > 0.05. ness is affected by cyclic changes in hormones during menstrual cycle in female24. CCT is thinnest before ovu- TABLE .2 Sex related mean difference in corneal lation and thicker before and after menstruation. No thickness between two eyes such change has been found in males. Dong – Hee Lee has shown in his study that there was no statistical corneal thickness * sex Gender Rt. corneal thickness Lt. corneal thickness difference in mean central corneal thickness between 26 Male 549.93 548.77 male and female . Age, refractive errors and BMI can Female 548.97 547.83 also affect the CCT. In this study no changes with age Total 549.48 548.33 in CCT has been observed in both genders. However some previous studies show that young age is positive- TABLE .3 Age related mean difference in corneal thickness ly co-related with CCT. But in our study no remark- able differences has been noticed. The central corneal corneal thickness * Age in years Rt. corneal Lt. corneal thickness is maximum in second to third decade in Age in years thickness thickness both genders. Namil study has shown decrease in CCT < 25 years Mean 548.38 548.07 with increasing age. Decrease in CCT with each decade 25-35 years Mean 552.63 550.06 (2.6 micrometer decrease in CCT with every decade)26. 36-45 years Mean 553.27 551.27 Dong - Hee Lee study has also shown no changes in 46-55 years Mean 543.87 543.70 central corneal thickness with age. However a change 56-65 years Mean 544.71 544.73 has been observed in peripheral corneal thickness with 27 65 -74 years Mean 559.14 559.43 age . > 74 years Mean 545.00 531.00 The mean CCT in our study is 548.33 which almost 27 Mean 549.48 548.33 the same as in Korean population . Total N 300 300 CONCLUSION: Central corneal thickness is not sig- Std. Deviation 25.913 24.546 nificantly affected by gender and age. So same mecha- nism of IOP checking and refractive surgery can be ap- Graph No 1 plied to both male and female. REFRENCES: 1. Dineen B, Bourne RRA, Jadoon Z , Shah S ,Khan MA , et al . Causes of blindness and visual impairment in Pakistan. Br J Ophthalmol 2007; 91: 1005 – 10. 2. Hansen FK,Ehlers N.Elevated tonometer readings caused by a thick cornea. Acta Ophthalmol (Copenh). 1971;49:775–778. 3. Ehlers N, Bramsen T, Sperling S.Applanation tonometry and central corneal thickness. Acta Ophthalmol (Copenh). 1975;53:34–43. 4. Doughty MJ, Zaman ML.Human corneal thickness and its impact on intraocular pressure measures: a review and meta- analysis approach. Surv Ophthalmol. 2000;44:367–408. 5. Gordon MO, Beiser JA, Brandt JD, et al.The Ocular Hypertension Treatment Study: baseline factors that predict the onset of primary open-angle glaucoma. Arch Ophthalmol. 2002;120:714–720; discussion 829–830. 6. De Moraes CG, Juthani VJ, Liebmann JM, et al.Risk factors for DISCUSSION: visual field progression in treated glaucoma. Arch Ophthalmol. 2011;129:562–568. This study has shown no significant difference 7. Eeva-Liisa Martola, Md; Jules L Baum, MD. Central and in central corneal thickness between male and female. peripheral thickness. Arch Ophthalmol; 1968: 79: 28 – 30. The mean CCT for male was 548.7 and for female was 8. Herndon LW, Weizer JS, Stinnett SS.Central corneal thickness

192 Ophthalmology Update Vol. 11. No. 4, October-December 2013 Difference in Central Corneal Thickness between Male & Female in Adults

as a risk factor for advanced glaucoma damage. Arch Kailu county, inner Mongolia. Ophthalmology. 2011;118:1982–1988. Ophthalmol. 2004;122:17–21. 18. Tomidokoro A, Araie M, Iwase A, Tajimi Study Group.Corneal 9. Foster PJ, Baasanhu J, Alsbirk PH, Munkhbayar D, Uranchimeg thickness and relating factors in a population-based study in D, Johnson GJ.Central corneal thickness and intraocular Japan: the Tajimi study. Am J Ophthalmol. 2007;144:152–154. pressure in a Mongolian population. Ophthalmology. 19. Tomoyose E, Higa A, Sakai H, et al.Intraocular pressure and 1998;15:969–973. related systemic and ocular biometric factors in a population- 10. Thapa SS, Paudyal I, Khanal S, Paudel N, Mansberger SL, van based study in Japan: the Kumejima study. Am J Ophthalmol. Rens GH.Central corneal thickness and intraocular pressure 2010;150:279–286. in a Nepalese population: the Bhaktapur glaucoma study. J 20. Vijaya L, George R, Arvind H, et al.Central corneal thickness Glaucoma. 2011;21:481–485. in adult South Indians: the Chennai Glaucoma Study. 11. Casson RJ, Abraham LM, Newland HS, et al.Corneal thickness Ophthalmology. 2010;117:700–704. and intraocular pressure in a nonglaucomatous Burmese 21. Ang M, Chong W, Tay WT, et al.Anterior segment optical population: the Meiktila Eye Study. Arch Ophthalmol. coherence tomography study of the cornea and anterior 2008;126:981–985. segment in adult ethnic South Asian Indian eyes. Invest 12. Day AC, Machin D, Aung T, et al.Central corneal thickness Ophthalmol Vis Sci. 2012;53:120–125. and glaucoma in East Asian people. Invest Ophthalmol Vis Sci. 22. Nangia V, Jonas JB, Sinha A, Matin A, Kulkarni M.Central 2011;52:8407–8412. corneal thickness and its association with ocular and general 13. Su DH, Wong TY, Foster PJ, Tay WT, Saw SM, Aung T.Central parameters in Indians: the Central India Eye and Medical corneal thickness and its associations with ocular and systemic Study. Ophthalmology. 2010;117:705–710. factors: the Singapore Malay Eye Study. Am J Ophthalmol. 23. Nishitsuka K, Kawasaki R, Kanno M, et al.Determinants and 2009;147:709–716. risk factors for central corneal thickness in Japanese persons: 14. Wong TT, Wong TY, Foster PJ, et al.The relationship of the Funagata Study. Ophthalmic Epidemiol. 2011;18:244–249. intraocular pressure with age, systolic blood pressure, and 24. Soni PS. Effect of oral contraceptive steroid thickness of human central corneal thickness in an Asian population. Invest cornea .Am J Optom Physiol Opt 1980; 57: 825 - 34. Ophthalmol Vis Sci. 2009;50:4097–4102. 25. Haitho Zhang, Liang Xu, Changxi Chen and Josat b.Jonas. 15. Zhang H, Xu L, Chen C, Jonas JB.Central corneal thickness in Central corneal thickness in adult Chinese. Association with adult Chinese. Association with ocular and general parameters. ocular and general parameters. The Beijing Eye Study. Graefes Arch Clin Exp Ophthalmol. 26. H w a n g K i K i m , Y o n g H o S o h n a n d Y o u n g H o o n H w a n g 2008;246:587–592. The central corneal thickness in Korean population. Namil 16. Wang D, Huang W, Li Y, et al.Intraocular pressure, central study invest.opthalmo;Oct 2012:53,116851. corneal thickness, and glaucoma in chinese adults: the Liwan 27. Dong – Hee Lee, Douk – Hoon Kim, and Seung – Hwan Park. eye study. Am J Ophthalmol. 2011;152:454–462. Age and sex related changes in cornel thickness and anterior 17. Song W, Shan L, Cheng F, et al.Prevalence of glaucoma in a rural corneal curvature in Korean population. J. Opt .Soc. Korea; Northern China adult population: a population-based survey in 2011:15, 68 -73.

Ophthalmology Update Vol. 11. No. 4, October-December 2013 193 ORIGINAL ARTICLE Prevalence of Refractive Error in School going Children in Southern Punjab (Pakistan) Mazhar Zaman Soomro Mazhar Zaman Soomro1, Sidra Riaz2, Muhammad Arshad3 Mohamad Ramazan Halili4

ABSTRACT Purpose: The objective of the study was to estimate the prevalence of refractive error in union council Nawan Kot, Tehsil Khanpur. Material and Methods: This was a population based cross sectional study conducted from 1st July 2012 to 31st Decem- ber 2012. 5000 school going children of union council Nawankot were inducted in the study. All students were examined thoroughly. Examination consisted of Visual acuity testing using Snellens Chart, Pupillary reaction, Ocular motility , direct ophthalmoscopy and anterior segment examination with Biomag (Bio-magnification). Ocular motility was checked by cover and uncover test for distance and near vision. Students with decreased vision (<6/9 or less by Snellens’ chart) underwent auto-refraction. Results: Out of 5000 students of the Governments schools of union council Nawan Kot Tehsil Khanpur, 862(17.24%) students were ammetropic. Mean age of students was 6 years. 2213 (44.26%) were below 8years, 1714(34.28%) were be- tween 8 to 12 years and 1073(21.46%) were between 12 to 16 years. There were 1852 (37.04%) males and 3148(62.96%) females .Total students with ametropia were 862, among them female 508(58.93%) and 354(41.06%) male. Among female 508 ametrope were 299(58.85%) were myopic, 81 (15.94%) hpermetropia and 12825.19%) astigmatic. While on the male side of 354 ametrope were 2 02 (57.06%) myopic, 60 (16.95%) hpermetropia and 92 (25.99% astigmatic). Conclusion: This study has shown that refractive errors are a major problem in school going children which go undetected especially in rural area. This may lead to visual impairment in school going children affecting their future life, and eventually leading to social stigmatization. Keywords: refractive error, schoolchildren, vision screening INTRODUCTION pur from 1st July 2012 to 31st December 2012. Area of Blindness at any stage of life is a concern to public epidemiological study was union council Nawankot, health; however its health burden is significantly aggra- Tehsil Khanpur of Southern Punjab Pakistan. 5000 vated when it occurs at an early stage in life. Childhood School going children of Government school of either blindness limits the child‘s development, affects qual- sex from age of 6 to 16 years were included in this study. ity of life, education and socioeconomic development An informed consent was taken from parents/teachers of the child.1 According to many studies on refractive of the children under study after explaining the pro- error, uncorrected refractive error is one of main cause cedures and outcomes of the study. Students of age of visual impairment in children because refractive er- above 16 and below 4years, from private schools and ror may affect their learning abilities and their physical who had previous ocular surgery were excluded from and mental development. Failure of treatment of refrac- the study. All the government schools boys and girls tive errors in children may lead to amblyopia which were included in the study. There were 18 boys and 18 turns into decreased vision of the child throughout his girls school in the union council. The ocular examina- life span. As far as refractive error is concerned, it is one tion included visual acuity measurement with Snellens’ of the top priorities of Vision-2020 initiative.2 Manage- chart in day light and at distance of 6 meters, Ocular mo- ment of the refractive errors is relatively easy, effective tility, Pupillary reaction, anterior segment examination and beneficial just by giving correct glasses to the chil- and fundus examination. All examination steps were dren. performed either by an experienced ophthalmologists MATERIAL AND METHODS: and ophthalmic technicians. Children having uncor- The study was conducted by Eye Infirmary Khan- rected visual acuity(UCVA) less than 6/9 underwent objective refraction using an auto-refectometer. Ocular 1Ophthalmic Surgeon, Eye Infirmary, Khanpur. 2Assistant Professor, Akhter Saeed Medical College, Lahore 3Registrar, Ophthalmology motility including cover test was performed in order Department, Bahawal Victoria Hospital, Bahawalpur, 4Ophthalmic to detect heterophorias and to rule out any comitant/ Technician, Eye Infirmary, Khanpur incomitant strabismus as a cause of decreased vision. Correspondence: Dr. Mazhar Zaman Soomro, Ophthalmic Surgeon, Cycloplegic refraction using cylcopentolate 1% drops Eye Infirmary, Khanpur was only performed in children of less than 8 years age. E. Mail> [email protected] cell # 0300 6702740 Children with spherical equivalent of -.50 D or worse Received: July 2013 Accepted: September 2013 were labeled myopic, and +2.0 D, hyperopic. Astigmat-

194 Ophthalmology Update Vol. 11. No. 4, October-December 2013 Prevalence of Refractive Error in School going Children in Southern Punjab (Pakistan) ic students were those with a cylinder refraction of 0.75 DISCUSSION D or more in at least one eye. According to the bulletin of the World Health Or- Children whose vision did not improve with re- ganization (WHO)in 2004, more than 161 million peo- fractive correction were referred to tertiary eye care ple were visually impaired worldwide, among them centre for complete checkup in order to determine the 124 million people had low vision and 37 million were cause of decreased vision. Glasses were prescribed to blind .3 This figure does not include children with de- the children. The data forms were checked for accuracy creased vision due to refractive error. The inclusion of and complete data entry. this would have raised these figures to 314 million peo- RESULTS ple to be visually impaired. Cataract is the main cause 5000 students of the Governments school of union of adult blindness and uncorrected refractive error council NawanKot Tehsil Khanpur were examined. ranks second .4 One of the five priorities of ―VISION 862(17.24%)students were ammetropic. Mean age 2020-The Right to Sight is to eliminate unnecessary of students was 6 years. There were 1852 (37.04%) blindness and to provide good vision among children males and 3148(62.96%) females as shown in Table 1. including treatment of refractive error and to pay more 2213 (44.26%) were below 8years, 1714(34.28%) were attention.5 between 8 to 12 years and 1073(21.46%) between 12 to For children, refractive error is another priority in 16 years as in Table 2. Students with ametropia were terms of visual disability that needs treatment. At the 508(58.93%) female and 354 (41.06%) male as in Table-3. same time focus on refractive services as part of pri- Prevalence of myopia was 502(58.23%), Hypermetropia mary health care and school services, and low-cost pro- 140(16.24%) and astigmatism was 220(25.52%) as in duction of spectacles are highly desirable.6 One of the Table-4. Among female 299(58.85%) myopic 81(15.94%) leading causes of blindness is due to visual impairment hypermetropic and 128 (25.19%) astigmatic as in caused by refractive error in children, accounting for Table 5. While on the male side 202 (57.06%) were 3% of blindness in southern Indian school children and myopic, 60(16.95%) were hyperopic and astigmatic much higher (prevalence of myopia 21.6% and hypem- were 92 (25.99%) as in Table : 6. etropia 2.7%) in China. Refractive error can have a sig- nificant impact on a child‘s life affecting their future life, Gender distribution Table : 1 and eventually leading to social stigmatization.7VISION Gender Male Female 2020- the Right to Sight is a WHO and IAPB global ini- 5000.00 (100%) 1852 (37.04%) 3148 (62.96%) tiative launched in 1999 to eliminate the main causes of avoidable blindness by the year 2020 by giving priori- Age wise distribution Table :2 ties on cataract, refractive errors, trachoma, oncocercia- sis and certain causes of childhood blindness.8 Age Between 4 Between 8 Between 12 to 8 yrs to 12 Yrs to 16yrs According to UNICEF, a child is defined as young- Total 2213 1714 1073 er than 16 years old. The World Health Organization 5000 (100%) (44.26%) (34.28%) (21.46%) (WHO) defines blindness as visual acuity in the better eye of less than 3/60, and severe visual impairment as Ametropic distribution gender wise Table: 3 a corrected acuity in the better eye of less than 6/60. Gender of refractive error Male Female For this study, visual impairment is defined as visual Total 862 (100%) 354 (41.06%) 508 (58.93%) acuity worse than of 6/12 in either eye for the school children aged 6 to 16 years. To maintain comparability Distribution Ametropia wise Table: 4 of our results with those of studies conducted in other Type of Myopia Hypermetropia Astigmatism parts of the world, the same definitions for refractive Ametropia errors were used: a spherical equivalent of -.50 D or Total 862 (100%) 502(58.23%) 140(16.24%) (25.52%) worse for myopia, and +2.0 D or more for hyperopia. Students with myopia in one or both eyes were classi- Type of Ametropia on female side Table: 5 fied as myopic, and those with hyperopic in one or both Type of Refractive errors Myopia Hypermetropia Astigmatism eyes. Astigmatic students were those with a cylindrical 9 Total 508 (100) 299 (58.85%) 81 (15.94%) 128 (25.19%) refraction of 0.75 D or more in at least one eye. To best of our knowledge this was first time in un- Type of Ametropia on male side Table: 6 ion council Nawankot such type of study was conduct- Type of refractive Myopia Hypermetropia Astigmatism ed. The union council is underprivileged as far from the errors center of country and more than 8o % people live on Total 354(100%) 202 (57.06%) 60 (16.95%) 92 (25.99%) agriculture sector with below than poverty line.

Ophthalmology Update Vol. 11. No. 4, October-December 2013 195 Prevalence of Refractive Error in School going Children in Southern Punjab (Pakistan)

First multi-county epidemiological study on re- like Union Council Nawan Kot Tehsil Khanpur Paki- fractive error in children was done in China10 Chili11& stan, and these refractive problems often lead to visual Nepal.12The data reveals that there are significant geo- impairment in school going children of our area. graphical differences in prevalence of refractive error. REFERENCES The prevalence of refractive error in our study was 1. Negrel AD, Maul E, Pakharel GP. Refractive error study higher than percentage of refractive error in China in children: sampling and measurement methods for amulticountysurvey. Am J Ophthalmol.2000;129:421-6. 13 11.3%,In Chilli 9.8%, in southern Ethopia ,11.8%, in 2. Gilbert C, Foster A. Childhood blindness in context of vision Tanzania146.1%& in Turkey 1511%. In our study refrac- 2020 – the right to sight. Bull World Health Organization. 2001; tive errors are more common in female than male. 79:227-32. 3. Resnikoff S.Global data on visual impairment in the year 2002. We are working on prevalence of refractive error in Bull World Health Organization 2004; 82: 844-851. the school going children and we did not record best 4. Resnikoff S, Pascolini D, Mariotti SP, Pokharel GP. Global visual acuity after refraction and uncorrected refractive magnitude of visual impairment caused by uncorrected refractive error in 2004. Bull World Health Organ. 2008 Jan; error. 86(1):63-70. In our study prevalence of myopia was 58.23%, Hy- 5. Gilbert C, Foster A. Blindness in children: control priorities and permetropia was16.24% and astigmatism was 25.52%. research opportunities. Br J Ophthalmol 2001; 85: 1025-1027. 6. Thylefors B. A global initiative for the elimination of avoidable Also our study reveals myopia is more common than blindness.Community Eye health Journal, 1998. 11(25) 1-3. hypermetropia and astigmatism is more common than 7. World Health Organization, Geneva. Preventing blindness hypermetropia. In one study in Iran reveals overall my- in Children: Report of a WHO/IAPB Scientific meeting, Hyderabad, India; 13-17 April, 1999; 13-14 (WHO_PBL_00.77). opia was 3.4%, Hypermetropia 16.6% and astigmatism 8. World Health Organization, The State of the World‘s Sight, 2005. 16 18.7%. In a study done by Afghani et al in school chil- VISION 2020: The Right to Sight .1995-2005. dren found that myopia was three times more common 9. Negrel AD, Maul E, Pokharel GP, et al. Refractive error study (3.26%) than hypermetropia (0.99%).17 Our study also in children: sampling and measurement methods for a multi- country survey. Am J Ophthalmol 2000;129:421–6. revealed that there was a negative correlation between 10. Dandona R, Dandona L. Refractive error blindness. Bull World spherical equivalent and the age of the children. This Health Organization.2001;79:237-43 is consistent with other studies18 where there was a de- 11. Zhao J. Pan X, Sui R, Munoz SR, Sperduto RD, Ellwein LB, et al. Refractive error study in children: results from shunyi district, crease in the proportion of hypemetropia with age and China. Am J Ophthalmol.2000;129:427-35. an increase in myopia. This trend may be attributed to 12. Maul E, Barroso S, Munoz SR, Sperduto RD, Ellwein LB. the theory of emmetropization in which there is a shift Refractive error study in children: results from La Florida, Chile. Am J Ophthalmol.2000; 129:445-54. from hypermetropia in early childhood to emmetropia 13. Worku Y, Bayu S. Screening for ocular abnormalities and as the child grows. Myopia has been reported to be as- subnormal vision in school children for Batayira Town, Southern sociated with female gender, older children, parental Ethopia. Ethop J of Health and Develop. 2002; 16:165-171. 14. Wedner SH, Rose DA. Myopia in School students in Manza educational attainment, ethnicity, urban dwellers and city, Tanzania; The need for national screening programme.Br J parental and sibling myopia.19, 20, 21 Ophthalmol. 2002;86:1200-6. There is also a low uptake of refractive error ser- 15. Lewellen S, Lowdon R, Countright P, Mehl GL. Population based survey of prevalence of refractive error in Malawi; Ophthalmic vices among this group. This may in part account for Epidemiol. 1995; 3: 145-9. the high prevalence of refractive error. Refractive errors 16. Fotouchi A, Hashemi H, Khiabazkhoob M, Mohammad K. The are significant cause of visual disability in school chil- prevalence of refractive errors among school children in Dezful, dren. While vision screening by teachers tremendously Iran.Br J Ophthalmol.2007; 91:287-92. 17. Afghani T, Vine HA, Bhatti A, Qadir MS, Akhtar J, Tehzib M, decreases the workload of ophthalmic staff. Teachers et al. Al-Shifa – Al-Noor (ASAN) refractive error study of one should be trained for the use of Snellen’s chart for visual million school children. Pak J Ophthalmol. 2003; 19:101-7. acuity measurement as we did it in our study. Teachers 18. Maul E, Barroso S, Munoz SR, Sperduto RD, Ellwein LB. Refractive error study in children: results from La Florida, Chile. can effectively identify children with poor vision, just Am J Ophthalmol. 2000;129(4):445–454. by doing refraction by ophthalmic staff and by giving 19. Dandona R, Dandona L, Srinivas M, et al. Refractive error a pair glasses to the concerned; children may improve inchildren in a rural population in India. Invest Ophthamol Vis Sci.2002;43(3):615–622. themselves socially, academically and may become ben- 20. Goh PP, Abqariyah Y, Pokharel GP, Ellwein LB. Refractive eficial to the community as well as for themselves. error and visual impairment in school-age children in Gombak CONCLUSION District, Malaysia.Ophthamol. 2005;112(4):678–685. 21. Mabaso RG, Oduntan AO, MpolokengMBL.Refractive Status of This study shows that the refractive errors are Primary School Children in Mopani District, Limpopo Province, highly prevalent in school going children of rural areas South Africa.S AfrOptom. 2006;65(4):125–133.

196 Ophthalmology Update Vol. 11. No. 4, October-December 2013 ORIGINAL ARTICLE

Trabeculectomy with & without Peripheral Iridectomy in Open Angle Glaucoma Muhammad Nazim Muhammad Nazim FCPS1, Yousaf Jamal Mahsood MBBS2, Muhammad Naeem MBBS3 Lal Muhammad FCPS4, Mushtaq Ahmad FCPS5 ABSTRACT Objective: To compare the outcome of trabeculectomy with and without peripheral iridectomy in eyes with open angle glaucoma. Design: Randomized control trial. Setting: Department of Khyber Institute of Ophthalmic Medical Sciences, Hayatabad Medical Complex, Peshawar, from 1st Jan 2012 to1st Jan 2013. Subjects: Forty eight eyes of 42 patients. Methodology: Forty eight eyes were randomized into peripheral iridectomy (PI) group and no peripheral iridectomy (no-PI) group. Primary trabeculectomy with MMC augmentation was performed by a single surgeon, on eyes in both the groups diagnosed as having POAG or PXG. MMC was used in a dose of 0.2 mg/dl for 2 minutes. Preoperative and postoperative IOP were noted together with any adverse events during surgery and during study follow up. SPSS version 17 was used for data analysis. Follow up were done on day 1, 7, 30 and after 3 months and 6 months. Results: Mean presenting IOP was 24mmHg in PI group and 27mmHg in no-PI group. At final follow up of 6 month success rate (IOP of ≤ 20mmHg without medication) was 92% for both the groups. Two cases (8%) of hyphema were found in PI group. The inflammatory reactions were on the higher side in PI group but difference between two groups was not statisti- cally significant. Complications like pupil block and incarceration were not noted in our study. Conclusion: There is no statistically significant difference between the two groups in terms of IOP control. No severe ad- verse effects were noted in both the groups. Key words: trabeculectomy, PI: peripheral iridectomy, MMC: mitomycin-C. INTRODUCTION of cataract formation.4 Peripheral iridectomy (PI) is a frequently per- The mechanical benefits of PI e.g. avoidance of formed step in trabeculectomy surgery. The logic com- pupil block is potentially more in narrow angle eyes monly given for PI is that it prevents an attack of angle and in pseudo-phakic eyes but it is also routinely per- closure glaucoma due to pupil block and also prevents formed in open angle glaucoma. In this study we aim the blockage of sclerotomy by iris incarceration.1 The to determine whether avoiding a PI affects the outcome risk of pupil block is potentially more in eyes with nar- and safety of the procedure in open angle glaucoma i.e. row angles and pseudo-phakia compared to that with primary open angle and pseudo-exfoliation glaucoma. open angles.2 Apart from the above mentioned benefits MATERIALS AND METHODS PI also has some unwanted effects e.g. increased inflam- Forty eight eyes of 42 patients of both genders aged mation because of blood aqueous barrier disruption more than 35years, having either POAG or PXG were which can cause enhanced wound healing response randomly divided into PI and no PI groups. Eyes which and thus increased risk of bleb failure.3 PI also increases were excluded, had trabeculectomy or cataract surgery the risk of bleeding into the anterior chamber. Moreo- or glaucoma laser procedure like laser iridotomy, argon ver there is added risk of ciliary processes damage and laser trabeculoplasty etc., in the past, eyes with history anterior capsule disruption which might increase risk of conjunctival manipulation either surgical or trau- 1. Senior Medical Officer, Khyber Institute of Ophthalmic Medical matic between 9 to 3 o`clock position around the limbus Sciences (KIOMS), Hayatabad Medical Complex (HMC) Peshawar.2.3. like peritomy for retinal reattachment surgeries, eyes Post graduate Trainee, Ophthalmology Department Hayatabad Medical Complex, Peshawar.4. Associate Professor & Head with preoperative co-morbidities which can affect IOP Ophthalmology Department Khyber Medical University Institute of level like uveitis, retinal detachment were excluded. Medical Sciences, Kohat KPK. Patients underwent thorough ophthalmological 5.Senior Registrar Ophthalmology Department Hayatabad Medical Complex Peshawar. examination including visual acuity (VA) with Snel- len’s chart, intraocular pressure (IOP) check up with Correspondence: Dr Mushtaq Ahmad, House No 31B, street no 2, Goldman tonometer (3 times with 6 hours interval a sector N4, Phase 4, Hayatabad, Peshawar E. Mail> [email protected] Cell: 03339119605 day before the surgery without antiglaucoma medica- tions), anterior chamber angle examination with Gold- Received: July’2013 Accepted: September’2013 man mirror. Anterior segment slit lamp examination

Ophthalmology Update Vol. 11. No. 4, October-December 2013 197 Trabeculectomy with & without Peripheral Iridectomy in Open Angle Glaucoma after dilatation of pupil. Posterior segment examina- in each group at 1st post-operative day. One case of PI tion by slit lamp biomicroscopy with 78D Lens with group had hypotony at 30th day which needed revised special emphasis for cup/disc ratio (both vertical and surgery. horizontal) and asymmetry between the eyes. Humph- ery visual field was done to record any glaucomatous Table I: Preoperative patient characteristics. PI group Non-PI group damage. characteristics p-value n(SD) n(SD) Surgical Technique: Primary trabeculectomy was Mean age 56.75±10.79 55.25±11.59 0.605 done by a single experienced ophthalmologist using Mean IOP 24.12±7.81 27.75±7.81 0.091 peribulbar anaesthesia. Conjunctiva was incised from Mean LogMAR VA 0.417±.868 0.408±.827 0.205 11-O-clock to 1-O-clock at limbus and then dissection PI- peripheral iridectomy, n-number, SD- standard deviation, VA- was done towards the fornix. After gentle wet cautery visual acuity, IOP-intraocular pressure. 4 mm2 half thickness sclera flap was raised. MMC was applied in a concentration of 0.2mg/dl for 1minute be- Table II: Mean IOP: PI versus no PI trabeculectomy PI group(n=24) IOP No-PI group IOP fore sclerotomy, paracentesis incision was made with Follow up P-value mmHg (mean±SD) mmHg (mean±SD) 15° knife after thorough wash of surgical area. Scler- st otomy was made with 15° knife. Based on randomiza- 1 day 9.75±7.74 10.67±7.64 0.205 th tion PI was made using vannas scissors without using 7 day 8.7±14.96 9.38±5.27 0.656 miotics. Sclera flap was sutured with two 7/0 vicryl 30th day 9.89±2.62 9.83±3.96 1.000 stiches. Tenon capsule and conjunctiva were sutured 3 months 10.25±2.46 12.13±4.68 0.091 separately with same 7/0 vicryl. Paracentesis was done 6th months 12.31±3.41 13.39±6.11 0.205 to form anterior chamber and to prevent plugging of PI: peripheral iridectomy, SD: standard deviation, VA: visual acuity, sclerotomy by iris tissue. IOP: intraocular pressure, Patients were followed on day 1, 7, 30 and after 3 months and 6 months. Success was defined as IOP of 7- Table III: Post -operative complications: PI versus no PI trabeculectomy. 20mmHg without IOP lowering medications. An IOP of Characteristics PI group (n=24) no PI group (n=24) equal to or less than 6mmHg was declared as hypotony Post op inflammation: while an IOP of less than 8 mmHg with a formed bleb Moderate 3 1 and with or without shallow AC was defined over-fil- Severe 2 0 Hyphema 2 0 teration. Inflammation was graded on 1st and 7th day as Overfilteration 6 5 mild (<25 cells) moderate (25-50 cells) and severe (>50 Hypotony 4 4 cells) using 1×2mm beam with maximum illumination Hypotony maculopathy 0 0 Wound leak 1 1 and magnification. Data was analyzed using version 17 Blebitis/endophthalmitis 0 0 of SPSS software. Student t- test was applied for data Iris incarceration 0 0 involving means. P-value of less than 0.05 was consid- Pupil block 0 0 ered statistically significant. PI: peripheral iridotomy, n: number. RESULTS Total of 48 eyes of 42 patients were included in the DISCUSSION study, 24 eyes were grouped into peripheral iridectomy Peripheral iridectomy is presumed to be essential in group (PI) and 24 eyes into no peripheral iridectomy trabeculectomy. Rationally it seems to be more benefi- group (N-PI) trabeculectomy. Eleven eyes (22.9%) had cial for angle closure glaucoma, eyes that had shorter pseudo-exfoliation glaucoma while 37(77%) cases had axial length and in cases of phaco-trabeculectomy with POAG. There were 18(75%) male and 6 (25%) female in intra operative iris prolapse. The logic commonly given PI group while 17(71%) male and 7(29%) female in non- for PI is that it prevents an attack of angle closure glau- PI group. coma due to pupil block and that it prevents the block- Patient characteristics are summarized in Table I. age of sclerotomy by iris tissue incarceration.1 These Table II summarizes mean IOP of the two groups at dif- possibilities are more in cases of narrow angle eyes but ferent follow up visits. Two patients in each group had iridectomy is also commonly done in open angle glau- IOP above 20mmHg at final follow up. Post-operative coma cases.5 Our study was to compare the peripheral complications are given in Table 3. Six eyes (25%) in iridectomy (PI) with no peripheral iridectomy (no-PI) PI group 5 (20%) in non PI showed over-filteration on in eyes with open angle glaucoma. It was a prospec- 1st post- operative day which was reduced to 1 eyes in tive randomized control trial with a sample size of 48 each group at 30th day. There were 4 cases of hypotony eyes and minimum follow up of 6 months. All surger-

198 Ophthalmology Update Vol. 11. No. 4, October-December 2013 Trabeculectomy with & without Peripheral Iridectomy in Open Angle Glaucoma ies were carried out by single experienced surgeon on tis didn’t occur in any group. eyes with open angle glaucoma (primary open angle, CONCLUSION pseudo-exfoliation, steroid induced glaucoma). We conclude that surgical iridectomy may be There was no difference between the two groups omitted in trabeculectomy for open angle glaucoma in terms of IOP control at all the follow up visits. Same as mechanical problems in the form of bupil block and effect regarding efficacy has been mentioned in other iris incarceration are much less an issue in open angle studies.5-8 Although the inflammation was more in PI trabeculectomies at the same time in doing so we may group in the 1st month post- operative period compared avoid potential risks in the form of hyphema, increased to non-PI group and we assumed more vigorous heal- inflammation, ciliary process damage and possible in- ing response and thus early bleb failure in PI group but creased risk of cataract formation. it didn’t actually happen.3,6 It was probably due to the REFERENCES use of MMC in the first place which effectively com- 1. Khaw PT, Chiang M, Shah P. Glaucoma filtration surgery; in- dications, techniques, and complications. In: Albert D, Mill- bated any exaggerated healing response and secondly er J, Azar D, Blodi B, editors. 3rdedition.Canada: Elseviers; due to selection of cases, which had no risk factors for 2008.p.2821-40. bleb failure. 2. Van Bushkirt EM. Papillary block after intraocular lens implan- More importantly no case of pupil block and iris tation. Am J Ophthalmol 1983; 95: 55-9. 3. Siriwadena D, Kotecha A, Miinasian D, Dart JK, Khaw PT. An- incarceration was noted in non PI group. This is in ac- terior chamber flare after trabeculectomy and after phacoemul- cordance with many previous studies.5,6 It shows that sification. Br J Ophthalmol 2000; 84: 1056-7. the step of PI may be omitted in open angle glaucoma 4. Lim LS, Hussain R, Gazzard G, Seah SK, Aung T. Cataract progression after prophylactic laser peripheral iridotomy: po- trabeculectomies although larger studies are required tential implications for the prevention of glaucoma blindness. to further elucidate this finding. There were 2 case of Ophthalmology 2005; 112: 1355-9. hyphema, one layered of less than 1/3rd anterior cham- 5. Messas AK, Cohen Y, Blumenthal EZ, Avni I. Trabeculectomy and phacotrabeculectomy with and without peripheral iridec- ber depth and microscopic in PI group. This complica- tomy. Euro J Ophthalmol 2009; 19: 231-4. tion of PI is relatively common as iris being very vascu- 6. De Barros DS, Da Silva RS, Siam GA, Gheith ME, Nunes CM, lar structure bleeds easily. Lankaranian D, et al. should trabeculectomy be performed as Overfilteration and hypotony occurred in both groups part of trabeculectomy? Two surgeons clinical experience. Eye 2009; 23: 362-7. and resolved with conservative management except 7. Shingleton BJ, Chaudry IM, O΄Donoghue MW. Phacotrabecu- in one non PI group which needed surgical revision. lectomy: Peripheral iridectomy or no peripheral iridectomy? J Hypotony didn’t lead to hypotony maculopathy in any Cataract Refractive Surg 2002; 28: 998-1002/ 8. Manners TD, Mireskandari K. phacotrabeculectomy without case. Serious complications like blebitis, endophthalmi- peripheral iridectomy. Ophthalmic Surg Laser 1999; 30: 631-5.

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Ophthalmology Update Vol. 11. No. 4, October-December 2013 199 ORIGINAL ARTICLE

Frequency of Retinal Detachment in Bilal Khan Ocular Trauma Nuzhat Rahil Co-Author Bilal Khan FCPS1, Nuzhat Rahil FCPS2, Rahil Malik FCPS3 ABSTRACT Objective: To determine the frequency of Retinal detachment in ocular trauma. Materials & Methods: It was a cross sectional descriptive study done in Eye Department, Lady Reading Hospital, Peshawar from 5th July 2010 to 5th April 2011. A total of 91 patients of ocular trauma were included in the study. Diagnostic criteria was made on the basis of history, best corrected visual acuity on Snellen’s chart, Indirect ophthalmoscopy with 20D lens and B scan where fundus view was hazy. Indirect ophthalmoscopy and B-scan were performed by the same senior ophthalmologist in order to control bias in the study. Results: A total of 91 patients of ocular trauma were included in the study. There were 62 (68.13%) male and 29 (31.87%) females. Average age of the patients was 42.07 years +/-10.07 SD with range of 13-64 years. The most common age group for ocular trauma was 21-35 years (51.6%). Retinal detachment in ocular trauma was observed in 19 (20.88%) patients while 72 (79.12%) patients had no retinal detachment. Discussion: Retinal detachment was observed in 33.3% of patient of age less than 20 years. Among the patients in the age group 21-35 years, 17.0% had retinal detachment while in the age group of 36-50 years, 26.1% of patients had retinal de- tachment. Gender-wise retinal detachment in ocular trauma showed that gender had no specific role over retinal detachment. CONCLUSION The study showed that Retinal Detachment following ocular trauma is quite a common encounter in the eye centers and further prevalence studies are needed in the general population or at multiple centers in the country, where there are retinal clinics . Key Words: Retinal detachment, Ocular trauma, Ophthalmoscopy, Visual acuity.

INTRODUCTION: south west England. Ophthalmic trauma is a major public health prob- The most common worldwide etiologic factors as- lem. Majority of the involved are male and under 30 sociated with retinal detachment are myopia, aphakia, years of age. Open globe injuries are more frequent. pseudophakia and trauma (10-20%). Many risk factors Violence and occupational injuries are the major causes may result in retinal detachment including blunt ocular of ocular trauma. Ophthalmic trauma comprised 6.78% trauma and other causes. In most cases, frequency of of the hospital admissions.1 The incidence of ocular retinal detachment after blunt ocular trauma is 61.60%.4 injuries was first reported by Zander and Geissler, who Trauma is very common in our setup and has many in 1864, reported it to be between 1.8 % to 9 %. Stud- serious ocular complications most of which are vision ies from India and Pakistan showed incidence of 20.3 threatening. Retinal detachment is one of the serious % and 12.9% respectively.1 Bilateral ocular trauma oc- complications. Based on the results of the study, we curs in 2.9%. Ocular injury is significant (5.1%) in the shall create awareness among ophthalmologists that community and causes monocular visual impairment fundus examination should be done in detail to avoid in about one third (34.6%) of cases.2,3 missing any retinal detachment because missing of Retinal detachment is a potentially blinding oph- retinal detachment will ultimately result in prolifera- thalmic pathology caused by a separation of the neu- tive vitreo retinopathy which will result in poor visual rosensory retina from the underlying retinal pigment prognosis. Early diagnosis and proper management epithelium and the accumulation of fluid within this has good visual prognosis. potential space. It is responsible for up to 2% of blind MATERIAL AND METHODS: and partial sight registrations in Ireland, Scotland and It was a cross sectional descriptive study done in 1.Consultant Ophthalmologist, KEF Hospital Peshawar 2.Junior Eye Department, Lady Reading Hospital, Peshawar Registrar, Lady Reading Hospital, Peshawar 3. Senior Registrar, Lady from 5th July 2010 to 5th April 2011. A total of 91 patients Reading Hospital, Peshawar of ocular trauma were included in the study. Inclusion Correspondence: Dr. Rahil Malik, Senior Registrar, Lady Criteria included all patients with ocular trauma, both Reading Hospital, Peshawar, KPK. [email protected] Cell. 0333 9106959 male and female patients of any age. Exclusion criteria included Diabetes Mellitus because tractional retinal Received: July’2013 Accepted: Sep’2013 detachment may have occurred before trauma , high

200 Ophthalmology Update Vol. 11. No. 4, October-December 2013 Frequency of Retinal Detachment in Ocular Trauma myopia of more than 5D, detected by history of using retinal detachment. high power minus glasses. Retinal degenerations, de- tected by indirect ophthalmoscope with 20D lens Before Fig :1 Retinal detachment in ocular trauma starting the study, permission from the hospital ethical committee was obtained and the study was conducted in the Department of Ophthalmology Lady Reading Hospi- tal, Peshawar. Diagnostic criteria were made on the basis of history of ocular trauma. An informed written consent was obtained from the patients. A special data collection proforma was filled hav- ing a detailed record of patient including name, age, gender, and address. Visual acuity was tested using standard Snellen’s visual acuity chart along with best corrected visual acuity using pin hole. Indirect oph- thalmoscopy with 20D lens was performed to look for retinal degenerations, presence or absence of retinal detachment, and if fundus view is hazy, B-scan was Fig 2 Age wise distribution of retinal detachment performed to look for presence or absence of retinal showed that retinal detachment in old age was little detachment. Indirect ophthalmoscopy and B-scan were bit low as that of younger age. The patients having age performed by same senior ophthalmologist to control less than or equal to 20 years of age have retinal detach- bias in the study. Exclusion criteria were followed ment 33.3% while no retinal detachment was 66.7%, age strictly to control confounders and bias in the study re- group 21-35 years had 17.0% retinal detachment and sults. All the analysis were done in SPSS version 10.0. 83% showed no retinal detachment, 36-50 years age Frequencies and percentages were calculated for cate- groups gave results of 26.1% retinal detachment with gorical variables like gender and presence of retinal de- 73.9% had no retinal detachment and patients having tachment. Mean ± Standard Deviation were computed more than 50 years of age had 22.2% retinal detachment for numeric variables like age and duration of ocular while 77.8% had no retinal detachment due to ocular trauma. All the results were presented in the form of trauma. Table: 2. tables and graphs RESULTS Table: 2 Age wise distribution of retinal detachment A total of 91 patients of ocular trauma were in- cluded in the study. There were 62 (68.13%) male and Retinal Detachment Total 29 (31.87%) were female. Male to female ratio was 2.3:1. Yes No Average age of the patients was 42.07 years+/- 10.07SD < 20yrs 1 2 3 with a range of 13-64 years. Patient’s age was divided in Percentage 33.3% 66.7% 100.0% four groups, out of which most common age group for 21 – 35 yrs 8 39 47 ocular trauma was 21-35 years. There were 3(3.3%) pa- age percentage 17.0% 83.0% 100.0% tients in the age less than 20 years. Forty seven (51.6%) (in years) 36 – 50 yrs 6 17 23 patients were in the age range of 21-35 years, 23 (25.3%) percentage 26.1% 73.9% 100.0% were in the age range of 36-50 years, while 18 (19.8%) 51+ yrs 4 14 18 percentage presented at age more than 50 years of age. Table 1 22.2% 77.8% 100.0% 19 72 91 Total Table 1: Age wise distribution 20.9% 79.1% 100.0% Cumulative AGE groups No. Patients Percent Percent Gender wise retinal detachment in ocular trauma < 20 years 3 3.3 3.3 showed that gender had no specific role over retinal de- 21 – 35years 47 51.6 54.9 tachment. There were 21% retinal detachment in male 36 – 50 years 23 25.3 80.2 and 79% had no retinal detachment. On the other hand, 51+ years 18 19.8 100.0 20.7% of female patients suffered from retinal detach- ment while 79.3% had no retinal detachment. Table: 3. Total 91 100.0 DISCUSSION The retinal detachment in ocular trauma was observed Retinal diseases are the major causes of visual im- in 19 (20.88%) while in 72 (79.12%) patients show no pairment in the western countries but may be less im-

Ophthalmology Update Vol. 11. No. 4, October-December 2013 201 Frequency of Retinal Detachment in Ocular Trauma portant in the developing world where vision loss from tion for this difference at least in our setup could be that preventable causes like cataract and corneal scarring males (for various reasons) have the custom to show up predominate. However, a population-based survey in at health (eye) care services more often than females do. India indicated that retinal diseases were the primary In all age groups, there were also no significant causes of blindness in a significant percentage 12.7% differences in involvement of either the right or the left of the studied population6. In the United States7, 8 and eye with RD (p-value=0.51). Out of male patients with Europe9,10, an annual incidence of retinal diseases or RD involving one eye, (58.8%) of them had RD in the retinal detachment (RD) between 6 to 12 per 100,000 right eye and (41.2%) in the left eye. Similarly out of population per year have been reported. the female patients with RD in one eye, (42.8%) of them Trauma is a well-recognized cause of retinal de- had RD in the right eye and (57.2%) in the left eye. tachment, which was reported by Eagling11 to affect Ocular trauma is a leading cause of RD in chil- 4-6% of such injuries. The characteristics of post contu- dren and adolescents18 and it is an important cause sion retinal detachments were described by Cox et al12 of RD in Africa15. Retinal breaks resulting from blunt and the mechanism of break formation was elucidated traumas are usually due to compression of the globe by Delori et al13 who studied the effect of high speed along its antero-posterior diameter with compensato- projectiles on enucleated pig eyes. Experimental evi- ry expansion at the equatorial plane. In our study, RD dence indicates that retinal breaks form at the time of was the cause of ocular trauma in (20.7%) patients. In ocular impact. However, clinical reports show consid- other studies, trauma contributed to RD in 30% of eyes erable delay in the diagnosis of post-traumatic retinal in South Africa, 23% in Zaire, and 8% in Kenya19. Our detachment. For example, Cox et al12 reported that only finding is comparable to that of the study done in Zaire. 30% of post-traumatic retinal detachments were diag- Our experience emphasizes the great importance of fre- nosed within one month of injury, and Ross14 found quent and early examination of the retinal periphery 40% in a similar period. after ocular trauma if vision is to be preserved. When Ocular trauma was the most common etiology vitreous hemorrhage or hyphaema obscures the view, for pediatric RD in the initial research for this series, the patient should be frequently re-examined until a accounting for 25 (42%) of the surgical cases for pedi- complete view of the ora serrata is obtained. atric RD at Emory University between 1991 and 1997. CONCLUSION Winslow and Tasman noted a similar incidence of RD The study showed that RD is quite a common en- attributed to trauma (44%) in their review of juvenile counter in the eye centre and further prevalence study RD in 1978. When considered across all age groups, in the general population or at multiple centers in the RD occurs following trauma in approximately 11% of country, Significant proportions of patients in our study cases.8,10 were coming from the all our province as Lady Reading In our study the mean age at presentation was 42 Hospital and Hayatabad Medical Complex are the only years with 70% of the patients being between 21 and governmental centres in the province where standard 50 years of age, and the median age was 40 years. This vitreoretinal surgeries are performed. It is therefore is comparable to other studies done by Rosman et al recommended to establish vitreoretinal setups in other in Singapore and Yorston et al15 in East Africa where eye care centres as well and train additional vitreoreti- they found mean ages of 46.1 and 47 years respectively. nal surgeons in order to expand the service. But in another study done in Croatia by Ivanisevic et REFERENCES al16, the mean age was 58.3 years, which is higher than 1. Babar TF, Khan MT, Marwat MZ, Shah SA, Murad Y, Khan that of the other studies. The higher mean age in the MD. Patterns of ocular trauma.J Coll Physicians Surg Pak 2007;17:148-53. Croatian study could be justified by the fact that this 2. Babar TF, Khan MN, Jan s, Shah sa, Zaman m, Khan MD. Fre- study (unlike the others three) excluded all traumatic quency and causes of bilateral ocular trauma. J Coll Physicians RD cases which actually tend to occur in young adults. Surg Pak 2007;17:679-82. 3. Tesfaye A, Bejiga A East Ocular injuries in a rural Ethiopian It has been thought that there might be a sex difference community. Afr Med J. 2008; 85:593-6. among patients with RD with a preponderance of males 4. Mitry D, Charteris DG, Yorston D, Fleck BW, Wright A, Camp- even when cases with traumatic RD are excluded9. bell H, Singh J. Rhegmatogenous retinal detachment in Scot- land: research design and methodology. BMC Ophthalmol Our study also showed that RD was significantly 2009; 24:9:2. more common in males 68% than in females 32%. This 5. Liu RJ, Xia WT, Fan LH. Forensic medical assessment in post-trau- finding is also comparable to studies done in East Af- ma retinal detachment. Fa Yi Xue Za Zhi. 2007 Aug; 23(4):261-8. 6. Dandona L, Dandona R, Srinivas M, Dandona L, Dandona 15 17 rica and Singapore where 62.2% and 70% of RD, re- R, Srinivas M, et al. Blindness in the Indian State of Andhra spectively, manifested in men. One possible explana- Pradesh. Invest Ophthalmol Vis Sci 2001;42:908-916.

202 Ophthalmology Update Vol. 11. No. 4, October-December 2013 Frequency of Retinal Detachment in Ocular Trauma

7. Rowe JA, Erie JC, Baratz KH, Hodge DO, Gray DT, Butterfield 15. Yorston DB, Wood ML, Gilbert C. Retinal detachments in East L, et al. Retinal detachment in Olmsted County, Minnesota, Africa. Ophthalmol 2002;109:2279-83. 2002;24:101-6. 1976 through 1995. Ophthalmol 1999;106:154-9. 16. Ivanisevic M, Bojic L, Eterovic D. Epidemiological Study of 8. Haimann MH, Burton TC, Brown CK. Epidemiology of retinal Non traumatic Phakic Rhegmatogenous Retinal Detachment. detachment. Arch Ophthalmol 1982;100:289 –292. Journal for research in experimental and clinical ophthalmol 9. Tornquist R, Stenkula S, Tornquist P. Retinal detachment: A 2000;32:5. study of a population-based patient material in Sweden 1971- 17. Rosman M, Tien YW, Sze GO, Chong LA. Retinal detachment 1981. Acta Ophthalmologica 1987;65:213-222. in Chinese, Malaysian and Indian residents in Singapore: A 10. Laatikainen L, Tolppanen EM. Characteristics of rhegmatog- comparative study on risk factors, clinical presentation and enous retinal detachment. Acta Ophthalmol 1985;63:146 –54. surgical outcomes. Intl Ophthalmol Brian PC and Carl DR. 11. Eagling EM. Ocular damage after blunt trauma to the eye. Br J Rhegmatogenous Retinal Detachment. In: Tasman W, Jae- Ophthalmol 1974;58:126-40. ger EA (Eds). Duane’s Clinical Ophthalmology. Lippincott’s,; 12. Cox MS, Schepens CL, Freeman HM. Retinal detachment due 1999.p.5. to ocular contusion. Arch Ophthalmol 1966;76:678-85. 18. Sullivan PM, Luff AJ, Aylward GW. Results of primary retinal 13. Delori F, Pomerantzeff 0, Cox MS. Deformation of the globe un- reattachment surgery: a prospective audit. Eye 1997;11:869-71. der high speed impact: its relation to contusion injuries.Invest 19. Kaimbo K, Maertens K, Kayembe L, Kabuni M, Kikudi H, Mis- Ophthalmol Vis Sci 1969;3:290-301. sotten L. Retinal Detachment in Patients from Zaire: Etiologi- 14. Ross WH. Traumatic retinal dialyses. Arch Ophthalmol cal, clinical aspects, surgical treatment. Bull Soc Belge Ophthal- 1981;99:1371-4. mol 1986;218:83-93.

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This light microscope image by Spike Walker is of blood capillaries in the ciliary body of an ox’s eye: the tiny holes that secrete aqueous humour are shown providing most of the nutrients for the lens and cornea. This image was created from a stack of 27 images taken at different depths and combined to give a three- dimensional appearance. The capillaries have been made visible by injecting an insoluble dye into the artery.

(Image: M. I. Walker) Courtesy: Welcome Trust-2009

Ophthalmology Update Vol. 11. No. 4, October-December 2013 203 ORIGINAL ARTICLE Safety of Intra-Cameral Moxifloxacin and its use in Prophylaxis of Post-Operative Endophthalmitis Imran Ahmad Imran Ahmad FCPS1, Muhammad Rafiq FCPS2, Junaid Faisal Wazir DO3 Mubashir Rehman MBBS4, Zeeshan Tahir MBBS5, Akbar Khan MBBS6

ABSTRACT Objectives: To determine the safety and role of intra-cameral moxifloxacin in phacoemulcification for the prophylaxis of post-operative endophthalmitis. Study Design: Interventional study Material and methods: The study was conducted from January 2012 to January 2013. A total of 80 patients with age related fulfilling the inclusion criteria were included in the study. Intra-operatively 0.5 ml of undiluted moxifloxacin ophthalmic solution was injected intracamerally at the completion of phacoemulcification. Patients were followed on 1st post- operative day, after 1 week and after 4 weeks and checked for visual acuity, anterior chamber cells and flare, pachymetery and intra ocular pressure. Results: Total of 80 patients completed the study. The mean age was 58 + 8.25 years. All patients were having best corrected visual acuity of better than 6/12. There was no statistically significant difference between the pre-operative and post-operative corneal thickness (p=0.31) and intraocular pressure (p=0.23). There were minimal anterior chamber reaction (up to +2 cells and flare) on 1st post-operative day which completely resolved after 4 weeks of follow-up. Conclusion: Moxifloxacin 0.5% ophthalmic solution is safe for intra-cameral use for the prevention of post-operative endophthalmitis.

INTRODUCTION commonly used6. Retrospective analysis showed that Postoperative endophthalmitis remains one of the vancomycin reduced the risk of post-operative en- most devastating complications of cataract surgery1. It dophthalmitis but is suspected to be associated with poses a significant public health issue considering mil- increased risk of clinically significant cystoid macular lions of people who have cataract surgery each year2. edema (CME) seen on fluorescein angiography7. Issues Despite of aggressive treatment, only about half of pa- have also been raised regarding the emergence of van- tients with endophthalmitis achieve 6/12 or better vi- comycin resistant enterococci and methicillin resistant sion and many are left without light perception3. The staphylococcus aureus. Because of these facts the rou- Endophthalmitis Vitrectomy Study showed that 70% of tine prophylactic use of vancomycin in cataract surgery infections are caused by coagulase-negative Staphylo- is now discouraged worldwide8. In contrast cefuroxime coccus, followed by 9.9% Staphylococcus aureus, 2.2% is available in systemic preparation like vancomycin. Enterococcus, and another 5.9% Gram-negative bacte- Reconstituted drug can cause toxic anterior segment ria, fungi are estimated to cause 3% of cases4. The use syndrome if there is incorrect concentration, incorrect of prophylactic antibiotics in cataract surgery remains pH and incorrect osmolality9. Endothelial toxicity lead- controversial. Despite the lack of evidence that these ing to corneal decompensation is another severe com- agents prevent postoperative infection, many cataract plication of cataract surgery due to mechanical and surgeons routinely administer intracameral antibiot- chemical insult to the endothelium related to chemical ics to avert the potentially devastating outcome of en- composition, concentration, pH and osmolality of the dophthalmitis5. Amongst the antibiotics given intra- substance that come in contact with the endothelium camerally, cefuroxime and vancomycin are the most and may lead to irreversible corneal edema.

1.3.Medical Officer, Khyber Teaching Hospital, Peshawar. Considering the possible complications with van- 2.Senior Registrar Ophthalmology unit, RMI, Peshawar 4.5.Medical comycin and cefuroxime, moxifloxacin seems to be the Officer, Lady Reading Hospital, Peshawar 6.Trainee Medical Officer, better choice of antibiotic for endophthalmitis prophy- Ophthalmology Unit, KTH, Peshawar laxis because of its broad-spectrum coverage and mode Correspondence: Dr. Imran Ahmad, House No 40, Street No 2, Sector of action. Moxifloxacin is a fourth-generation fluoro- H1,Phase 2, Hayatabad Peshawar. quinolone antibacterial agent that is active against a E.mail>[email protected] Cell: 0333-9255244 broad spectrum of gram-positive and gram-negative ocular pathogens, atypical micro-organisms, and an- Received: August’2013 Accepted September’2013 aerobes10,11. The ophthalmic solution is isotonic and for-

204 Ophthalmology Update Vol. 11. No. 4, October-December 2013 Safety of Intra-Cameral Moxifloxacin and its use in Prophylaxis of Post-Operative Endophthalmiti mulated at pH 6.8 with an osmolality of approximately The mean age was 58.4 + 8.25 years including 46 males 290 mOsm/kg (product description, moxifloxacin hy- and 34 female. 4 weeks later all eyes were having best drochloride ophthalmic solution 0.5% (Vigamox), Al- corrected visual acuity better than 6/12. 68.75% were con Laboratories, reference: AAA083–0604); both val- having visual acuity of 6/6. No corneal edema was re- ues are within the compatible range for humans (pH corded in any patient after post-operatively. There were 6.5 to 8.5 and osmolality 200 to 400 mOsm/kg)12,13. It grade 1 corneal striations in 12 patients and grade 2 in 7 is a self-preserved with no added preservatives, com- patients on 1st post-operative day, which resolved after mercial ophthalmic formulation that require no special 4 weeks of follow up. On 1st post-operative day there preparation for intracameral delivery, reducing the risk were traces to +2 cells and flare in all patients which of toxic anterior segment syndrome. Early studies of also completely resolved after 1 weeks of follow up. rabbit eyes did not show intraocular toxicity after injec- The mean pachymetery reading were 543.32 + 25.46 mi- tion of intravitreal or intra-cameral moxifloxacin14. crometer pre-operatively and 558.73 + 22.73 microme- MATERIAL AND METHODS ter post-operatively, which is very minimal change and The study was conducted from October 2011 to is not significant (p=0.31). The mean intra-ocular pres- April 2013 in Khyber Teaching Hospital and Rehman sure pre-operatively and post-operatively was 16.5 + 2 Medical Institute Peshawar. Patients were included mm of Hg and 16.0 + 2 mm of Hg respectively showing with mean age of 58.4 + 8.25 years with age related no statistical significant difference ( p=0.23). cataracts. Pre-operative examination included best cor- rected visual acuity, slit lamp examination, tonometery, Anterior Chamber Cells/Flare fundoscopy and pachymetery. Patients with glaucoma, maculopathy, diabetic or other retinopathy, , vitreous opacities, visual pathway lesions, uveitis, corneal endothelial disease and pseudoexfolia- tion were excluded from the study. Patients who devel- op intra-operative complication or difficulties were also excluded from the study. Surgical Technique Pupils were dilated with a solution of tropicamide 1% and Phenylephrine 10%. All surgeries were per- formed using peri-bulbar anesthesia. The eyelid skin and peri-ocular area were cleaned with iodine povi- done. Iodine povidone 5% solution were instilled into the conjunctival sac in all patients. All surgeries were performed through phacoemulcification and hydro- phobic lens implanted, using hyaluronic acid as viscoe- lastic. At the end of surgery more than 0.1ml solution of a newly opened bottle of Moxifloxacin (Vigamox) was aspirated in 1cc sterile syringe in scrub conditions. The volume excess of 0.1ml used to be discarded leaving only 0.1ml in the syringe. This volume contains 0.5mg of non-preserved moxifloxacin. This solution then used to be injected into the anterior chamber through 25 gauge cannula. Post operatively the patients were giv- en topical Vigamox 2 hourly for 3 days and then 4 times a day for 2 weeks along with dexamethasone eye drops. Follow up DISCUSSION The patients were followed post-operatively on 1st Endophthalmitis cases after cataract surgery in- day, 1st week and after 4 weeks. Visual acuity, anterior creased since last two decades, with a reported inci- chamber cells and flare, intra-ocular pressure and pa- dence of 2.15 per 1000 cases15. Thus, there is a need for chymetery readings were recorded in all visits. protective antibiotics to combat the rise in endophthal- RESULTS mitis and to better treat patients, especially in the light A total of eighty 80 patients completed the study. of increasing antibacterial resistance among causative

Ophthalmology Update Vol. 11. No. 4, October-December 2013 205 Safety of Intra-Cameral Moxifloxacin and its use in Prophylaxis of Post-Operative Endophthalmiti organisms. Povidone-iodine 5% is topical prophylactic The capacity of anterior chamber after intra-ocular agent which reduces the risk of endophthalmitis in a lens implantation is approximately 0.525ml23, so after prospective manner.16 Intracameral antibiotic adminis- injection of 0.1 ml of moxifloxacin its concentration tration also has been widely accepted and used17. Due would have been 500 microgram in 0.525ml. The me- to resistance development to some previously used an- dian MIC of even moxifloxacin resistant endophthalmi- tibiotics, new drugs are offered like fourth generation tis isolates has been established to be no higher than 3 fluoroquinolones, for the prophylaxis against endoph- microgram/ml17. Therefore the moxifloxacin level after thalmitis18. Fluoroquinolones were introduced for treat- injection in anterior chamber in our cases was atleast ment of corneal and conjunctival infections; however, 300 times the median MIC of endophthalmitis causing these antibiotics found a greater role in prophylaxis organisms. Espiritu CR in his study used the same con- before surgery to prevent endophthalmitis.19 Kowalski centration and calculated the concentration of moxi- et al reported in 2001 that none of the staphylococcus floxacin in anterior chamber to be 300 times of MIC5. isolates found in endophthalmitis were sensitive to Moxifloxacin did not increase intra-ocular pres- second generation of fluoroquinolones14. The fourth- sure and there was no significant statistical difference generation Fluoroquinolones offer several advantages between the pre-operative and post-operative intra- over other antibiotics that would theoretically favor ocular pressure (16.5 + 2 and 16.0 + 2 respectively). their use in endophthalmitis prophylaxis. The benefits Similar observation was also made in a study done by include a broader spectrum of antibacterial activity and Koktekir BE and Aslan BS.24 Sleve Arshinoff has also greater potency against gram-positive pathogens, supe- recommended the routine use of intra-cameral moxi- rior ocular penetration characteristics for moxifloxacin, floxacin which is the safest and simplest broad spec- and reduced susceptibility to resistance development.20 trum antibiotic for the prevention of post-operative en- Moxifloxacin is fourth generation antibiotic is the most dophthalmitis1. potent and having the minimum inhibitory concentra- The unavailability of observation of the corneal tion (MIC) for most bacterial endophthalmitis isolates.21 endothelium changes with confocal microscopy is the Thus, it seems to be a better choice for prophylactic limitation of our study, but the pachymetric changes antibiotic. The moxifloxacin injection we used was a also give some information about the corneal thickness commercially available ophthalmic solution labeled for and thus might give an idea about the impact of the topical use with the brand name Vigamox (Alcon). Vig- drug on corneal endothelium. amox does not contain preservatives, which in addition CONCLUSION to its broad-spectrum activity led us to investigate its Moxifloxacin given intracamerally appeared to intraocular use. It has a pH of 6.8 and an osmolality of be the best choice in prevention of post-operative en- 290 mOsm/kg; both values are within the compatible dophthalmitis after cataract surgery in terms of visual range for humans as demonstrated in study done by results, anterior chamber reaction and pachymetery. Trinkhaus-Randall V and collegeus.22 In this study con- REFERENCES: cerns about biocompatibility of the antibiotic was ad- 1. O’Brien TP, Arshinoff SA, Mah FS. Perspective on antibiotics for dressed by observing its effects on the corneal thickness post-operative endophthalmitis prophylaxis: Potential role of moxifloxacin. J Cataract Refract Surg 2007;33:1790-1800. and blood–aqueous barrier (BAB) (aqueous flare) and 2. Javitt JC, Kendix M, Tielsch JM. Geographic variation in utiliza- whether it causes inflammation in the anterior cham- tion of cataract surgery. Med Care 1995;33-90-105. ber (aqueous cells) and affect intraocular pressure. 3. Kernt M, Kampik A. Endophthalmitis: pathogenesis, clinical Confounding factors were controlled by excluding pa- presentation, management and perspectives. Clin Ophthalmol 2010;4:121-35. tients with corneal problems and other ocular patholo- 4. Results of the Endophthalmitis Vitrectomy Study. A random- gies. Like study done by Lane SS et al, our study also ized trial of immediate vitrectomy and of intravenous antibiot- showed no significant statistical difference between pre ics for the treatment of post-operative bacterial endophthalmitis. Endophthalmitis Vitrectomy Study Group. Arch Ophthalmol and post-operative corneal thickness and corneal clar- 1995;113:1479-96. ity after 4 weeks of follow-up. In addition, there was 5. Espiritu RG, Caparas VL, Bolinao JG. Safety of prophylactic intra- no evidence that moxifloxacin causes increased Blood cameral moxifloxacin 0.5% ophthalmic solution in cataract- sur gery patients. J Cataract refract Surg 2007;33:63-8. Aqueous Barrier (BAB) disturbance or secondary in- 6. Masket S. Preventing, diagnosing and treating endophthalmitis. J flammation, which would have caused raise aqueous Cataract Refract Surg 1998;24:725-6. flare and cells level, respectively, similar to observation 7. Axer-Siegel R, Stiebel-Kalish H, Rosenblatt I. Cystoid macular made by Espiritu CR and his colleagues5. All eyes had 0 edema after cataract surgery with intraocular vancomycin. Oph- thalmology 1999;106:1660-4. cells and flare at the 1-week postoperative visit. No eye 8. Centers of disease control. Staphylococcus aureus resistance to lost a line of BCVA from the preoperative acuity. vancomycin – United States,2002. MMWR Morb Mortel Wkly

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Rep.2002;51:565-7. study; the ESCRS Endophthalmitis Study Group. J. Cataract Re- 9. Mamalis R, Edelhauser HF, Dawson DG. Toxic anterior segment fract. Surg. 2006;32:407–410. syndrome. J Catarct Refract Surg 2006;32:324-33. 18. Moshirfar, M., Feiz, V., Vitale, A.T., et al. Endophthalmitis after 10. Mather R, Karenchak LM, Romanowski EG, Kowalski RP. Fourth uncomplicated cataract surgery with the use of fourth-generation generation fluoroquinolones: a new weapons in the arsenal of fluoroquinolones; a retrospective observational case series. Oph- ophthalmic antibiotics. Am J Ophthalmol 2002;133:463-6. thalmology 2007;114:686–691. 11. Stroman DW, Dajcs JJ, Cupp GA, Schlech BA. In vitro and in vivo 19. Mather R, Karenchak LM, Romanowski EG, Kowalski RP. Fourth potency of moxifloxacin and moxifloxacin ophthalmic solution generation Fluoroquinolones: new weapons in the arsenal of oph- 0.5%; a new topical fluoroquinolone. SurvOphthalmol 2005;50:16- thalmic antibiotics. Am J Ophthalmol 2002;133:463-6. 31. 20. Mah FS. Fourth-generation fluoroquinolones: new topical agents 12. Gonnering R, Edelhauser HF, Van Horn DL, Durant W. The pH in the war on ocular bacterial infections. Curr Opin Ophthalmol. tolerance of rabbit and human corneal endothelium. Invest Oph- 2004;15:316–20. thalmol Vis Sci 1979;18:373-90. 21. Stroman DW, Dajcs JJ, Cupp GA, Schlech BA. In vitro and in 13. Edelhauser HF, Hanneken AM, Pederson HJ, Van Horn DL. Os- vivo potency of moxifloxacin and moxifloxacin ophthalmic- so motic tolerance of rabbit and human corneal endothelium. Arch lution 0.5%; a new topical fluoroquinolone. Surv Ophthalmol Ophthalmol 1981;99:1281-7. 2005;50(suppl):16-31. 14. Kawalski RP, Romanowski EG, Mah FS. Intracameral Vigamox 22. Trinkhaus-Randall V, Edelhauser HF, Leibowitz HM, Freddo TF. (moxifloxacin 0.5%) is non-toxic and effective in preventing endo- Corneal structure and function. In: Leibowitz HM, WaringIII GO, phthalmitis in a rabbit model. Am J Ophthalmol 2005;140:497-504. eds, Corneal Disorders; Clinical Diagnosis and Management, 2nd 15. West ES, Behrens A, McDonnell PJ. The incidence of endophthal- ed. Philadelphia, PA, WB Saunders, 1998;21–7. mitis after cataract surgery among the U.S. Medicare population 23. Mindel JS. Pharmacokinetics. In: Tasman W, Jaeger EA, eds. between 1994 and 2001. Ophthalmology 2005;112:1388-94. Duane’s Foundations of Clinical Ophthalmology on CD-ROM. 16. Speaker MG, Menikoff JA. Prophylaxis of endophthalmitis with Philadelphia PA, Lippincott Williams and Wilkins, 2006;vol.3 topical povidone–iodine. Ophthalmology 1991; 98:1769–1775. Chap 23. 17. Barry, P., Seal, D.V., Gettinby, G., et al. ESCRS study of prophy- 24. Koktekir BE, Aslan BS. Safety of prophylactic intracameral moxi- laxis of postoperative endophthalmitis after cataract surgery; pre- floxacin use in cataract surgery 2005;140(3):497-504. liminary report of principal results from a European multicenter

Chronology of Winners of SAARC Youth Award: • 1997: Outstanding Social Service in Community Welfare - Sukur Salek (Bangladesh) • 1998: New Inventions and Shanu - Dr. Najmul Hasnain Shah (Pakistan) • 2001: Creative Photography: South Asian Diversity - Mushfiqul Alam (Bangladesh) • 2002: Outstanding contribution to protect the Environment - Dr. Masil Khan (Pakistan) • 2003: Invention in the Field of Traditional Medicine - Hassan Sher (Pakistan) • 2004: Outstanding contribution to raising awareness for TB, HIV/AIDS –Ajij Prasad Poudyal (Nepal) • 2006: Promotion of Tourism in South Asia - Syed Zafar Abbas Naqvi (Pakistan) • 2008: Protecting the Environment in South Asia - Uswatta Liyanage Deepani Jayantha (Sri Lanka) • 2009: Outstanding contribution to humanitarian works after Natural Disasters – Dr. Ravikant Singh (India) • 2010: Outstanding contribution for the Protection of Environment and mitigation of Climate Change - Anoka Primrose Abeyrathne (Sri Lanka)

Ophthalmology Update Vol. 11. No. 4, October-December 2013 207 ORIGINAL ARTICLE

Co-relation between Serum HbA1c with Sorbitol Tariq Arain Concentration in the Lens of a Diabetic Patient. Rizwan Khan Prof. Tariq Mahmood Arain FCPS (Ophthalmology)1, M. Rizwan Khan FCPS 2 Saira SaleemMBBS3, Prof. Asma Shaukat FCPS (Pathology), 4 Quaid-e-Azam Medical College & Victoria Hospital Bahawalpur ABSTRACT Objectives: To find out relation between HbA1c with sorbitol concentration in the lens of a diabetic patient. Study Design: cross-sectional study Setting: Conducted in the Pathology Department of Quaid-e-Azam Medical College in collaboration with Department of Ophthalmology , Bahawal Victoria Hospital Bahawalpur. Material & Method: 32 diagnosed patients of type-2 diabetes mellitus for more than 5yrs who were admitted in eye ward for cataract Surgery included in this study. Patients fulfilling the inclusion and exclusion criteria explained and informed about the purpose of this research and a proper documented consent was taken from them. Patients of DM admitted in eye ward for cataract surgery included in the study. Blood sample of the patients for HbA1c assay and their crystalline intraocular lens samples for sorbitol obtained after extra ocular cataract extraction surgery collected The serum Hb1c and sorbitol level measurement in the obtained lens was done in pathology department by researcher herself. The data was collected on a pre-designed proforma form the eye department by the researcher herself along with patients bio data . Results: Our results are 21 males suffering from DM last mean 7yrs had serum HbA1c 8.2% and lens sorbitol 8.2 μg/100mg. wet wt and 11 femeles having DM mean 5.5 had serum HbA1c 7.5% and lense sorbitol 27.5 μg/100mg.wet wt. value of Pearson co-efficient between serum HbA1c with lense sorbitol level was 0.85 with P-value 0.04 which is significant. Conclusion: Serum Hemoglobin A1c correlated positively with the concentrations of sorbitol in the lens of diabetic patients. Key words: HbA1c,lens sorbitol levels, diabetes, cataract

INTRODUCTION: metabolises into fructose3 . Accumulation of these two Diabetic mellitus is the one of the most common sugars in the lens in hyperglycemic state, increases the health problems of the modern world1 and opacifica- osmotic pressure within the lens, drawing in the water. tion of intraocular lens is a complication of diabetes The result is swelling of lens fibers, disruption of nor- mellitus. In human lens, energy production depends mal cytoskeletal architecture and lens opacification1,3. largely on glucose metabolism1,2. The goal of lens me- Less than 4% of lens glucose is normally converted tabolism is the maintenance of transparency3. Three to sorbitol . Cataractuous lens of diabetic subjects con- metabolic pathways for glucose metabolism occur in tains greater amount of sorbitol , fructose and glucose the lens. These are anaerobic glycolysis, HMP shunt than do those of non-diabetics1,3. The diabetes control and sorbitol pathway1,3. The most active of these path- and complications trial showed that, maintaining the ways is anaerobic glycolysis1,3. near normal glucose levels in blood had a large and In hyperglycemic state, when glucose increases in beneficial effect on delaying the development and de- the lens, the sorbitol pathway is activatetd relatively creasing the progression of long term complications more than glycolysis and sorbitol accumulates in the of diabetes mellitus4. The most important advance- lens3. Aldose reductase is the key enzyme in sorbitol ment in glycemic control is self monitoring of blood pathway. This enzyme plays a key role in the develop- glucose .In recent decades, the ability to measure the ment of sugar cataract1,3. In lens sorbitol also partially glycosylated hemoglobin levels has significant im- proved the long term glucose control surveillance. All 1. 2 Associate Professor, Head of Department Eye Unit-2, Ophthalmologist the blood proteins are exposed to glucose and they 3Postgraduate Resident, Chemical Pathology. 4Professor of Chemical 3 Pathology. Quaid-e-Azam medical college BWP. can become glycosylated . High concentration of glu- Correspondence: Dr.Saira Saleem PGR Pathology Department, cose and long periods of exposure result in a high con- Bahawal Victoria Hospital, Bahawalpur. Room 27 lady doctor lodge centration of glycosylated proteins. As the half life of Bahawal Victoria Hospital, Bahawalpur. [email protected] blood hemoglobin is 60 days , thus the glycosylated Hb Cell: 03356092739 levels reflect the glycemic control of proceeding two Received: August’13 Accepted: September’13 months3.Hemoglobin A1C, the most abundant of the

208 Ophthalmology Update Vol. 11. No. 4, October-December 2013 Co-relation between Serum HbA1c with Sorbitol Concentration in the Lens of a Diabetic Patient glycosylated hemoglobin, is expressed as a percentage stratification. Correlation between HbA1c and sorbitol of total hemoglobin3. in lens was examined by Pearson’s coefficient of corre- The purpose of our study is to find the correla- lation. The P value <0.05 was taken as significant. tion of blood HbA1c concentration with concentration RESULTS: of sorbitol in the lens of a diabetic patient, so that a A total 32 patients were included in study which were causal relation can be established between chronic hy- undergone extracapsular extraction after development perglycemic states and development of cataract in dia- of cataract and blood sample was taken 2weeks before betic individuals. surgery for HbA1c level. MATERIAL AND METHOD: Among 32 patients included in the study , 21 were It was a cross-sectional study which was con- male and 11 patients were female. The age varied from ducted in the pathology department of Quaid-e-Azam 50-70 years. Mean age of the male patients was 62 years Medical College in collaboration with Department of and female patients was 57years.Mean of duration of Ophthalmology , Bahawal Victoria Hospital, Bahawal- disease in males was 7yrs and in females was 5.5 years. pur. It was non-probability consecutive sampling. All the 32 patients completed the study. Inclusion Criteria: Our results are 21 males suffering from DM last mean Age: 50 to 70 years 7yrs had serum HbA1c 8.2% and lens sorbitol 8.2 Both genders. μg/100mg.wet wt and 11 femeles having DM mean Diagnosed patients of DM who are admitted in eye 5.5 had serum HbA1c 7.5% and lense sorbitol 27.5 ward for cataract Surgery. DM was diagnosed in these μg/100mg.wet wt. value of patients on the basis of serum sugar level of more than Our results showed that value of Pearson co-efficient 110mg/dl fasting. between serum HbA1c with lens sorbitol level was 0.85 Diabetes mellitus for > 5 years with P-value 0.04 which is significant. Value of Pearson Exclusion criteria: co-efficient established that serum HbA1c and lens Un cooperative patients sorbitol level in diabetes has direct relation and both Ocular hypertension has causal relationship behind development of cataract. Suspected cases of DM Patients also suffering from other ocular disease. Table.1 Distribution of Study Population according to Age and gender Data collection procedure: Age Males Females A documented permission was taken from the hos- Years n(%) n(%) pital ethics committee before conducting this research. 50-55 10 5 First 30 patients fulfilling the inclusion and exclusion 56-60 4 3 criteria explained and informed about the purpose of 61-65 5 2 this research and a proper documented consent was 66-70 2 1 taken from them. The study was conducted in collabo- Table.2 Mean concentration of serum HbA1c and sorbitol ration with ophthalmology department, QAMC/BVH, among females and males. Bahawalpur. Patients of DM admitted in eye ward for cataract surgery was included in the study. Blood Gender Male Female sample of the patients for HbA1c assay and their crys- No of cases. 21 11 talline intraocular lens samples for sorbitol obtained Mean age.(years) 62yrs 57yrs after extra ocular cataract extraction surgery was col- Duration of disease.(years) 7yrs 5.5yrs lected form the eye department by the researcher her- Sorbitol level (mean)±SD 28.40 27.5 self along with patients bio data .The serum Hb1c and μg/100mg.wet wt sorbitol level measurement in the obtained lens was HbA1c(mean). % 8.2 7.5 done in pathology department by researcher herself. The data was collected on a pre-designed proforma. Table.3 Correlation between serum % hemoglobin A Data analysis procedure: (c and sorbitol in cataractuous lens from diabetic patients. The collected data was entered and analyzed by Linear regression equation Pearson co-efficient ( r ) P-value using the computer software SPSS version 13. The qual- 0.04x+9.40 0.70 0.04 itative data like sex was presented as frequency distri- bution. The quantitative data like age, duration of DM, DISCUSSION: conc. of serum Hb1c and sorbitol in lens was presented Diabetic mellitus is the one of the most common as mean and standard deviation .Effect modifiers like health problems of the modern world1 and opacifica- age, gender and duration of diabetes was controlled by tion of intraocular lens is a complication of diabetes

Ophthalmology Update Vol. 11. No. 4, October-December 2013 209 Co-relation between Serum HbA1c with Sorbitol Concentration in the Lens of a Diabetic Patient mellitus. Cataract is considered a major cause of visual free glucose. According to Varma et al10. The concentra- impairment in diabetic patients as the incidence and tions of sorbitol, fructose, and myo-inositol in lens in- progression of cataract is elevated in patients with dia- crease as the concentration of blood glucose increases. betes mellitus5,6. The association between diabetes and Pirie and Heyningen11 reported that the concentra- cataract formation has been shown in clinical epidemi- tion of glucose in cataractous lens of diabetic patients ological and basic research studies. Due to increasing was higher than in non-diabetics. We could not confirm numbers of type 1 and type 2 diabetics worldwide, the this. This disparity may be due to the better glycemic incidence of diabetic cataracts steadily rises. The in- control of our patients before the extraction of their creased accumulation of sorbitol creates a hyperosmot- lens. More lens should be analyzed to confirm the find- ic effect that results in an infusion of fluid to countervail ings of Pirie and Heyningen. the osmotic gradient that leading to cataract develop- The same study12was repeated on the cataractous ment. lens of subjects with NIDDM, the concentration of free The enzyme aldose reductase (AR) catalyzes the glucose showed significant positive correlations with reduction of glucose to sorbitol through the polyol the concentrations of adonitol, fructose, and sorbitol. In pathway, a process linked to the development of dia- NIDDM, the proportion of hemoglobin A1, measured betic cataract. Extensive research has focused on the several days before the extraction of a lens, correlated central role of the AR pathway as the initiating factor in positively with the concentrations of adonitol and sorb- diabetic cataract formation. It has been shown that the itol and inversely with the concentration of lenticular intracellular accumulation of sorbitol leads to osmotic myo-inositol. These findings suggest that glycemic con- changes resulting in hydropic lens fibers that degener- trol, whether assessed with glyco-hemoglobin or with ate and form sugar cataracts6,7. In the lens, sorbitol is blood glucose as clinical markers, may be useful for produced faster than it is converted to fructose by the decreasing the concentrations of sorbitol, fructose, and enzyme sorbitol dehydrogenase. adonitol in lens to normal values. HbA1c reflects average plasma glucose over the Our study proved that that patient having higher previous eight to 12 weeks5. It can be performed at any serum HbA1c had more concentration of sorbitol in time of the day and does not require any special prepa- their lenses and short duration of development of cata- ration such as fasting. These properties have made it the ract. Another studies have shown that osmotic stress preferred test for assessing glycaemic control in people in the lens caused by sorbitol accumulation13 induces with diabetes. In our study we used it to see glycemic apoptosis in lens epithelial cells (LEC)14 leading to the control and compared it with lens sorbitol. development of cataract. In our study we compared serum HbA1c with lens From our study we can say that by reducing the sorbitol level after cataract extraction of 32 patients. level of lens sorbitol level, we can prevent the develop- This study showed that Serum Hemoglobin A1c cor- ment of cataract. As same Varma et al9 reported that related positively with the concentrations of sorbitol in an aldose reductase inhibitor inhibited the function of the lens of diabetic patients. So by controlling hyper- the sorbitol pathway in lens and suppressed the syn- glycemia we can delay or prevent the cataract develop- thesis of sorbitol and fructose in lens but did not affect ment in diabetic patients. the concentration of lenticular myo-inositol. However, Like our study, Heyningen’s report8 that, polyols they did not mention the concentrations of other poly- of ocular lens have been evaluated by many scientists9,10, ols. It is of great interest to us to examine the findings who used paper chromatography, electrophoresis, and of Varma et al. in-vitro studies, i.e., the effect of aldose GLC. They found that sorbitol, fructose and glucose reductase inhibitors on the polyol pattern of lens in a accumulated in cataractous lens of diabetic animals as high-glucose medium. Such studies, together with our well as in human diabetics. The accumulation of pol- present data, should help us clarify the role of lenticular yols in a lens presumably raises the osmotic pressure polyols in cataractogenesis and may provide a better and increases the water volume in the lens enough to understanding of the prevention, initial stages, and de- cause swelling of the lens and rupturing of the lens fib- velopment of lens opacification in diabetes. ers. This phenomena, together with the malfunctioning In one study14, we found that the serum polyol of lens fiber’s cation pump a result of osmotic changes pattern in diabetics is characterized by increased con- in the lens are thought to cause lens opacification. centrations of glucose, mannose, and myo-inositol; a Pine and Heyningen8 reported that the cataractu- decreased concentration of 1-deoxyglucose; and occa- ous lens of diabetics contains more glucose than that of sional detections of peaks from mannitol and sorbitol. non-diabetics, we failed to find an increase of lenticular However, the lenticular polyol pattern in diabetics re-

210 Ophthalmology Update Vol. 11. No. 4, October-December 2013 Co-relation between Serum HbA1c with Sorbitol Concentration in the Lens of a Diabetic Patient flected the accumulation of sorbitol, fructose, and glu- REFERENCES: cose; the decrease of 1-deoxyglucose; and the relatively 1. Purdy EP, Bolling JP, Kaldawy R, Varma R, Walker J, Shaw HE low concentration of myo-inositol. et al. American Academy of ophthalmology , Basic and clinical science course 2007-08(P)201-20. 15 Another study conducted in 1991 has shown that 2. Kanski JJ. Clinical ophthalmology – a systematic, approach. 6th effect of diabetes on the free polyol pattern in catarac- ed. London Butterworth Heinemann Elsevier; 2007,340-1. tuous lens and proved that in diabetics, hemoglobin 3. Kumar V, Abbas AK, Fausto N, Mitchell RN. Robbins basic th A, (%) correlated positively with the concentration of pathology. 8 ed. India Elsevier Saunders; 2007;(20):775-87. 4. ColledgeNR , Walker BR, Ralston SH. Davidson’s principles adonitol in the lens and inversely with the concentra- and practice of medicine , Churchill Livingstone Elsevier tion of lens myo-inositol; however, it did not correlate 2010;(22)829-31. with the concentration of glucose in lens. Regulation of 5. J. J. Harding, M. Egerton, R. van Heyningen, and R. S. Harding, both the metabolism of lenticular polyols and the pat- “Diabetes, glaucoma, sex, and cataract: analysis of combined tern of polyols in serum may be necessary for normal- data from two case control studies,” British Journal of Ophthalmology, vol. 77, no. 1, pp. 2–6, 1993. izing lenticular polyol content. Results of this study are 6. P. E. Stanga, S. R. Boyd, and A. M. P. Hamilton, “Ocular similar to our study to establish the cause of cataract. manifestations of diabetes mellitus,” Current Opinion in Our results showed that Pearson co-efficient be- Ophthalmology, vol. 10, no. 6, pp. 483–489, 1999. tween serum HbA1c with lens sorbitol level was 0.85 7. G. Tabin, M. Chen, and L. Espandar, “Cataract surgery for the developing world,” Current Opinion in Ophthalmology, vol. 19, with P-value 0.04 which significant. Value of Pearson no. 1, pp. 55–59, 2008. co-efficient established that serum HbA1c and lens 8. Pine A, Heyningen R. The effect of diabetes on the content sorbitol level in diabetes has direct relation and both ofsorbitol, glucose, fructose and inositol in the human lens. Exp has causal relationship behind development of cataract. Eye Res 1964;3:124-31. A study15 that was done by Shigetake Yoshioka shown 9. Varma SD, Schocket SS, Richard RD. Implications of aldosereductase in cataracts in human diabetes. Invest that serum HbA1c and lens sorbitol level in diabetes Ophthalmol Visual Sci 1979;18:237-41. had correlation by measuring serum HbA1c and lens 10. S.K. Srivastava, K. V. Ramana, and A. Bhatnagar, “Role of aldose sorbitol level in diabetic patients. reductase and oxidative damage in diabetes and the consequent This is the 1st cross sectional study done in Paki- potential for therapeutic options,” Endocrine Reviews, vol. 26, stan to see correlation between serum HbA1C and lens no. 3, pp. 380–392, 2005 11. Wiwanitkit V. Energy consumption for the formation of sorbitol level in diabetic patients. Results of our study hemoglobin A1c: a reappraisal and implication on the poor- shows we can prevent development of cataract in dia- controldiabetes mellitus patients. J Diabetes Compl 2006; 20:384- betic patients by glycemic control. So in future by gly- 6. cemic control or by using aldose reductase inhibitor to 12. Heyningen R. Formation of polyols by the lens of the rat inhibit sorbitol concentration we can prevent or delay with“sugar” cataract. Nature (London) 1959;184:194-5. 13. Y.Takamura, Y. Sugimoto, E. Kubo, Y. Takahashi, and Y. Akagi, the development of cataract in diabetic patients. “Immunohistochemical study of apoptosis of lens epithelial CONCLUSION: cells in human and diabetic rat cataracts,” Japanese Journal of Serum Hemoglobin A1c correlated positively with the Ophthalmology, vol. 45, no. 6, pp. 559–563, 2001. concentrations of sorbitol in the lens of diabetic pa- 14. Yoshioka S, Tainura K, Kagimoto S, et al. Variations of tients. Glycemic control, whether assessed with glyco- freenon-glucose polyols content in serum from patients with diabetesmellitus and their correlation with hemoglobin A1. J hemoglobin or with blood glucose as clinical mark- NatlDefMed Coll 1990;15:217-23. ers, may be useful for decreasing the concentrations 15. Yoshioka S, Kameyama K, Sanaka M, Sekine I, Kagimoto S, of sorbitol, which is the main cause behind cataract Fujitsuka S, et al. Effect of Diabetes on the Free Polyol Pattern in in diabetic patients. Cataractous Lenses. Clinchem . 1991;37(5):686-89.

Ophthalmology Update Vol. 11. No. 4, October-December 2013 211 ORIGINAL ARTICLE

Orbicularis Bi-pedicle Flap for Eye Lid Reconstruction: SAM’S Technique Sameera Irfan Sameera Irfan FRCS Consultant Oculoplastic Surgeon & Strabismologist Moghul Eye Trust Hospital, Lahore

ABSTRACT: Objective: To describe a technique for eyelid reconstruction with loss of more than two thirds of the lid tissue and to assess the visual and functional outcome. Materials & Methods: This is a prospective interventional case series at a tertiary referral center, from Jan 2010 - June 2012.11 consecutive cases requiring unilateral reconstruction of either the upper or the lower lid following tumor excision and loss of more than two-thirds of the lid tissue were included; 7 cases had BCC (Basal cell carcinoma), 3 had squamous cell carcinoma and one had a sebaceous gland carcinoma. The median age of patients was 62 years (range 45 - 71 years), with 6 female and 5 male patients. After an informed consent was obtained verbally, all cases had tumor excision including 5mm of surrounding healthy lid tissue and a primary repair by a single surgeon (SI). The surgical technique involved reconstruction of the posterior lamella by mobilizing the forniceal conjunctiva and a donor scleral graft. This was covered by an orbicularis bi-pedicle flap (from the orbital part of the orbicularis oculi) and a free skin graft. Post-operative follow-up was after 1, 2 weeks and then after 1, 3, 6 months and 1 year. At each visit, visual acuity, status of the cornea and of the reconstructed lid was observed regarding complications like lagophthalmos, ptosis, lid-retraction, entropion, ectropion, epiphora, corneal exposure and tumor recurrence. Patient satisfaction was also noted. Results: All patients were satisfied with the final cosmetic appearance. Punctate corneal staining was noted in 3 cases of upper lid reconstruction at 2nd week follow-up which was due to lagophthalmos. This was managed by downwards lid massage, lubricating eye ointment and taping the lids at night. A 2 mm lid retraction was noted in 2 cases after 3 months of the upper lid reconstruction which was managed with levator recession. None of the cases of lower lid reconstruction had any complication. Conclusion: This is a single-staged technique particularly useful for reconstruction of shallow, full-thickness lid defects, involving loss of 2/3 of the lid lengths or more. Since the lids are not sutured together, it is particularly useful in patients with an only seeing eye. If done properly, it is associated with lower rate of complications as compared to other techniques. Key Words: Lid reconstruction, lid tumor excision, lid margin defects, orbicularis bi-pedicle flap.

INTRODUCTION: correct the deformity/defect or remove the tumor, but Procedures for repairing eyelid defects, incurred to improve function and restore normalcy to the eyelid following trauma or tumor excision, have been around as aesthetically as possible. For proper management for a very long time. Eyelid reconstruction continues of any lid defect, a thorough knowledge of the to encompass a wide range of reconstructive options.1,2 surgical anatomy of eyelids is mandatory.3 It must be Since the beginning of sub-specialties of plastic and re- remembered that the eyelids comprise of two lamellae, constructive surgery, new techniques have continually anterior and posterior: the anterior lamella includes being introduced which keep on undergoing further skin and orbicularis muscle and the posterior lamella is refinements and modifications to make them as simple made up of the tarsal plate and the conjunctiva. These and complication-free as possible; the method of choice four structures must be included in any reconstructive will ultimately depend on a combination of factors, procedure to ensure the structural and functional including the size, the site of the defect, availability of integrity of the lids. tissues and a surgeon’s experience with the available Options for reconstruction are generally classified modes of reconstruction. using the “reconstructive ladder,” proceeding from Reconstruction is indicated for all defects that may the least invasive to the most invasive in terms of lead to secondary complications if not repaired. These morbidity. At the bottom of the ladder is secondary complications may include lid notching, epiphora, intention healing4 in which defects granulate over a corneal exposure, lid retraction and lagophthalmos. period of weeks in a moist, semi-occlusive environment. The goal of reconstructive eyelid surgery is not only to Other options for lid reconstruction1,2 include grafts, local flaps, and free tissue transfer. When planned Corresponding address: Dr.Sameera Irfan FRCS, No. 301, H1 Block, Johar Town, Lahore. E-Mail: [email protected] and executed properly, local skin flaps allow for rapid Cell: 0336 4500901 reconstruction with a reliable and adequate blood Received: August 2013 Accepted: September 2013 supply and a good skin color/texture match.

212 Ophthalmology Update Vol. 11. No. 4, October-December 2013 Orbicularis Bi-pedicle Flap for Eye Lid Reconstruction: SAM’S Technique

Factors that should be cosidered regarding the best MATERIALS & METHODS: surgical option preoperatively5 are: This is a prospective interventional case series 1) A patient’s age: In younger age group, the skin performed at Mughal Eye Trust Hospital, Lahore, a and muscles are tight; the tissues relax with tertiary referral center, from Jan’ 2010 to June 2012. 11 increasing age. Hence, for young patients, a small consecutive cases requiring unilateral reconstruction defect is considered to be involving 25-35% of the of either the upper (7 cases) or the lower lid (4 cases) lid length, a medium defect involves 35-45%, and following tumor excision and loss of more than two- a large defect involves greater than 55% of the thirds of the lid tissue were included. There were 6 lid length. For older patients with lax lids, a small female and 5 male patients (Table 1), with a median age defect is 35-45%, a medium is 45-55% and a large of 62 years (range 45 - 71 years). 7 cases had Basal cell defect involves more than 65% of the lid length. carcinoma, 3 had squamous cell carcinoma and one had a sebaceous gland carcinoma, proven by an incision 2) The size and orientation of the defect: A typical biopsy pre-operatively (Table 2). After an informed defect may involve 50% of the central portion of consent was obtained verbally, all cases had tumor the upper eyelid or a combination of the eyelid excision including 5mm of surrounding healthy lid and canthi. If the eyelid margin is spared, closure tissue and a primary repair by a single surgeon (SI). by local flap or skin graft may suffice. Once the The surgical technique: Firstly the extent of tumor margin is involved, surgical repair must restore was marked under the microscope by a marking pen the integrity of the eyelid margin to avoid lid and then a 5mm area around it was marked. The lid notching. was infilterated with a local anesthetic mixture of 3cc 3) Vascular supply to the surrounding tissues: this bupivacaine + 2 cc Xylocaine and 0.1 ccc of adrenaline determines the site from where flaps or free grafts 1:1000. The tumor was excised along with 5 mm of can be taken. The arterial anatomy of the eyelids the sorrounding healthy lid tissue. A 4/0 silk traction and the importance to eyelid reconstruction has suture was passed through the lateral and medial 6 been described by Erdogmus and Gosva. wound edges to bring them closer and the exact 4) Previous treatment recieved e.g. surgical repair or extent of lid defect was measured. To reconstruct the irradiation. posterior lamella first, after securing hemostasis by a 5) Age of the wound: in a recent injury, there is more cautery, conjunctiva was mobilized from the lower tissue edema and swelling. Hence after trauma, a fornix in case of a lower lid defect and from the upper primary repair should be done within 24 hours; in fornix in case of an upper lid defect (Fig 1a). Then a older defects, more tissue scarring has already set piece of donor sclera, soaked in an antibiotic solution in because of which the tissues lose their elasticity. for 2 hours and trimmed according to the size of defect The options available for reconstruction of small was sutured to the remaining tarsus at the lateral and to medium lid defects are a direct closure which medial wound margins by a non-absorbable suture can be combined with lateral cantholysis,7 Tenzel (ethibond 5/0) (Fig1b). In 3 cases where the wound Rotational Flap,8 Mustarde9 (rotational cheek) extended to the lateral canthal angle, the donor sclera Flap. For reconstruction of large lid defects (greater was sutured to the periosteum of the orbital rim while than 2/3 of the horizontal width of the lid), the in one case where it involved the medial canthus, the choice is limited to two-staged procedures: for donor sclera was attached to the medial canthal tendon lower lid reconstruction is the Hughes Procedure10 (MCT). Next, the mobilized conjunctiva was sutured to and its modification;11 for the upper lid is a Cutler- the upper border of donor sclera with a running 6/0 vicryl suture. Any tension in the conjunctival layer was Beard Flap.12 In both of these techniques, at the relieved by a short, horizontal relaxing incision deep in first stage, tissues are borrowed partially from one the fornix. Then the lower lid retractors were identified lid to recostruct the other and that eye is occluded and attached to the lower border of the scleral graft for at least 6 weeks. At a second stage, once tissue with a 6/0 vicryl suture. This step is very important to healing has occured, the lids are opened. prevent subsequent inward-bending of the posterior This new technique described here allows the lamella, hence preventing entropion. In case of the reconstruction of both upper and lower eyelid defects upper lid reconstruction, the levator aponeurosis was greater than 2/3rd of the lid width without the identified and sutured to the donor sclera. occluding the eye for 6 weeks. This is a single-staged To reconstruct the anterior lid lamella, the orbital procedure and is very useful in people with an only or the preseptal portion of the orbicularis oculi muscle, eye. which had retracted backwards into the orbit, was

Ophthalmology Update Vol. 11. No. 4, October-December 2013 213 Orbicularis Bi-pedicle Flap for Eye Lid Reconstruction: SAM’S Technique freed from the overlying skin, a 4-5 mm strip was Table 3: Post-operative complications split (Fig.1c) from the remaining muscle while it was Complications No of cases still attached by a medial and a lateral pedicle to the Entropion 0 remaining muscle at the canthal angles. This bi-pedicle Ectropion 0 flap was mobilized and sutured to the upper border of Lag-ophthalmos and punctate corneal staining 3 (27%) the scleral graft with a 6/0 vicryl, continuous suture, taking bites of the mobilized conjunctiva as well (Fig Lid notching 0 1d). A free graft of skin was taken either from the upper Lid sagging 0 lid or the retro-auricular skin and sutured to all four Lid retraction which needed levator recession 2 (18%) margins of the wound with a 7/0 vicryl suture (Fig.1e). Total no of complications 5 (45%) The lid was placed under traction for 5 days with a 4/0 silk traction suture. An antibiotic onitment was applied on the lid, covered by a pressure dressing for 72 hours, after which the wound was inspected and the dressing replaced for another 2 days. All cases were given oral antibiotic for 5 days, steroid/antibiotic skin cream for the reconstructed eyelid twice a day and lubricating eye ointment at night. Post-operative follow-up was after 1st and 2nd week and then after 1, 3, 6 months and 1 year. At each visit, visual acuity, status of the cornea and of the reconstructed lid was observed regarding complications Fig. 1-a: Tumor excised and conjunctiva like lagophthalmos, ptosis, lid-retraction, entropion, in lower fornix mobilized. ectropion, epiphora, corneal exposure and tumor recurrence. Patient satisfaction was also noted. RESULTS: All patients were satisfied with the final cosmetic appearance. Complications (Table 3) like punctate corneal staining was noted in 3 cases (27%) of upper lid reconstruction at 2nd week follow-up which was due to lagophthalmos (27%). This was managed by downwards lid massage, lubricating eye ointment and taping the lids at night. A 2 mm lid retraction was noted in 2 cases (18%) after 3 months of the upper lid reconstruction which was managed with levator recession. None of the cases of lower lid reconstruction had any complication like sagging of the lower lid, Fig.1-b: A free graft of donor sclera sutured to the two ends of remaining tarsus. entropion or ectropion.

Table 1: Patient Demographics Gender No Males 5 Females 6 Total 11

Table 2: Pathological type of excised tumors: Type of tumor No of cases Basal cell carcinoma 7 Squamous cell carcinoma 3

Sebaceous gland carcinoma 1 Fig.1-c: A bi-pedicle flap from orbital part of Total 11 orbicularis muscle split and mobilized.

214 Ophthalmology Update Vol. 11. No. 4, October-December 2013 Orbicularis Bi-pedicle Flap for Eye Lid Reconstruction: SAM’S Technique

tise of the surgeon and the patient’s needs. However, achieving a good functional and aesthetic result always remains a challenging task. Lower eyelid defects involving the entire lower eyelid may be reconstructed using a Mustarde cheek rotation flap.9 Since this flap only comprises of skin and subcutaneous tissue without the support provided by the tarsal plate, postoperatively lower lid ectropion can result from anterior lamella shortening or lower lid lax- ity, which is worsened by the affect of gravity result- ing in an altered lid mobility. This complication can be Fig.1-d: Mobilized orbicularis bi-pedicle flap sutured avoided by anchoring the newly constructed lid using to upper border of conjunctiva and scleral graft. a non-absorbable suture fixed to the periosteum inside the lateral orbital rim above the mid-pupillary line. Lower eyelid defect involving more than two thirds of the horizontal eyelid length may be repaired by Hughe’s Technique first described in 1937. This tech- nique is best used for reconstructing full-thickness de- fects involving the central portion of the lower eyelid, in which the posterior lamella is recreated with a tarso- conjunctival bridge flap from the upper eyelid includ- ing the lid margin.10 This method has undergone vari- ous modifications; in modified Hughe’s procedure11, a tarso-conjunctival flap is mobilized 4mm proximal to the lid margin thus preserving the structural integrity Fig. 1-e: Free skin graft from opposite lid or retro- of the upper lid. This is covered by a free skin graft. The auricular area sutured to the margins of the defect. flap must be left in place from 4-6 weeks before it can be divided and lids separated as a second-stage proce- dure. Hence, it is not suitable for patients sighted only in the involved eye or in children at risk of developing occlusion amblyopia. Similarly, for the large defects of the upper lid, (more than 2/3 of the horizontal lid length), Cutler Beard Technique12 is mostly preferred which again uti- lizes a musculo-cutaneous bridge flap from the lower lid to fill in the upper lid defect. This flap is later di- Fig. 2: A BCC excised and reconstructed by Sam’s Technique. vided after 6 weeks as a second staged procedure. Both Hughe’s and Cutler Beard Techniques in- volve lid-sharing and may result in some structural damage to the donor eyelid. However, the technique described here is a single-staged procedure and does not damage the other lid. Moreover, the same tech- nique can be used for reconstruction of large defects of both the upper and lower lids. Demir et al13 described the reconstruction of a large upper lid defect by a V shaped orbicularis oculi myocutaneous flap advanced Fig. 3: A squamous cell carcinoma excised and lid reconstructed by Sam’s Technique. from the depth of the defect following tumor excision to reconstruct the anterior lamella while the posterior DISCUSSION: lamella was reconstructed with a mucoperiosteal graft Depending on the size, location, and extent of de- harvested from the hard palate. fects, a myriad of surgical approaches have been uti- Similarly, a mid-lateral lid margin defect was lized to repair the eyelids, depending upon the exper- reconstructed by an orbicularis oculi musculocutaneous

Ophthalmology Update Vol. 11. No. 4, October-December 2013 215 Orbicularis Bi-pedicle Flap for Eye Lid Reconstruction: SAM’S Technique advancement flap and a free conchal cartilage graft together at night for a month post-operatively. None of by Matsuo et al14. A “Sandwich Block” technique was the cases of lower lid reconstruction (4 cases) had any described by Fatima et al15 in which a full-thickness complication (Fig. 2 & 3). pentagonal graft from the opposite lid was sutured into CONCLUSION: the full-thickness defect after removal of the orbicularis This is a simple, single-stage procedure which is oculi muscle from the graft. The orbicularis muscle flap easy to learn. It does not damage the other lid and is from the recipient eyelid was mobilized and brought associated with minimal number of complications, in for vascular supply between tarsus and skin of the particularly in the upper lid, which are easy to graft. manage. It is less invasive than other techniques, and A rigid support to the reconstructed lid is at the same time allows a good functional and aesthetic mandatory to avoid complications like lid bending reconstruction. It is particularly useful in monocular resulting in an entropion or ectropion. This was patients and in children predisposed to occlusion provided in our study by donor sclera which was readily amblyopia available in our tertiary care facility from donor eyes REFERENCES for corneal grafts. However, hard palate or nasal septal 1. Codner MA, Weinfeld AB. Pr47 comprehensive eyelid reconstruction. ANZ J Surg. May 2007;77 Suppl 1:A71. chondromucosa can be used as an alternative which [Medline]. provides sufficient tissue for both eyelids, whereas 2. Mathijssen IM, van der Meulen JC. Guidelines for reconstruction a free tarsoconjunctival graft can be used for only 1 of the eyelids and canthal regions. J Plast Reconstr Aesthet eyelid reconstruction. Since the lower lid retractors Surg. Jun 24 2009;[Medline]. 3. Bhupendra Patel, Arlen D Meyers. Eyelid anatomy. 17 June were attached to the lower border of the donor sclera, 2013;(emedicine.medscape.com) outward movement of the reconstructed lower lid 4. Lowry JC, Bartley GB, Garrity JA. The role of second-intention margin and inward bending of the upper lid margin healing in periocular reconstruction. Ophthal Plast Reconstr Surg. Sep 1997;13(3):174-88. [Medline]. was prevented hence avoiding entropion. Both medial 5. Mounir Bashour, Lars M Vistnes.Lower Eyelid Reconstruction. and lateral margins of the scleral graft were firmly April 9, 2013 (emedicine.medscape.com) attached by non-absorbable suture (5/0 ethibond) to 6. Erdogmus S, Govsa F. The arterial anatomy of the eyelid: importance for reconstructive and aesthetic surgery. J Plast the remaining tarsus or the periosteum of orbital rim Reconstr Aesthet Surg. 2007;60(3):241-5. [Medline] hence avoiding an ectropion. In the upper lid, levator 7. Holds JB, Anderson RL. Medial canthotomy and cantholysis aponeurosis was approximated to the scleral graft thus in eyelid reconstruction. Am J Ophthalmol. Aug 15 avoiding ptosis but too much tightening of the levator 1993;116(2):218-23. [Medline]. 8. Boynton JR. Semicircle flap reconstruction “plus”. Ophthalmic aponeurosis or a narrow scleral graft can predispose Surg. Dec 1993;24(12):826-30. [Medline]. to lagophthalmos or lid retraction. The presence of a 9. Ambrozová J, Mesták J, Smutková J. Reconstruction of the free tissue graft in the posterior lamella (free tarsus, lower eyelid after excision of major tumours. Acta Chir Plast. 1993;35(3-4):131-45. [Medline]. donor sclera, nasal septal chondromucosa or hard 10. Custer PL. Tarsal kinking after Hughes flap. Ophthal Plast palate) demands an overlying vascular flap for the Reconstr Surg. Sep 1998;14(5):349-51. [Medline]. anterior lamella which was provided by the mobilized 11. Rohrich RJ, Zbar RI. The evolution of the Hughes tarsoconjunctival flap for the lower eyelid reconstruction. Plast orbicularis bi-pedicle flap covered over by a free skin Reconstr Surg. Aug 1999;104(2):518-22; quiz 523; discussion graft either from the opposite lid or the retro-auricular 524-6. [Medline]. region. 12. Cutler NL, Beard C. A method for partial and total upper lid Complications like lid retraction up to the level reconstruction. Am J Ophthalmol. Jan 1955;39(1):1-7. [Medline]. 13. Demir Z, Yuce S, Karamursel S, Celebioglu S. Orbicularis of limbus was noted in 2 cases (18%) following upper oculi myocutaneous advancement flap for upper eyelid lid reconstruction which was managed initially by reconstruction. Plast Reconstr Surg. Feb 2008;121(2):443-50. downwards lid massage for 2 weeks; when it failed [Medline]. 14. Matsuo K, Sakaguchi Y, Kiyono M, Hataya Y, Hirose to improve then levator recession was performed. T. Lid margin reconstruction with an orbicularis oculi Punctate corneal staining was noted in another 3 cases musculocutaneous advancement flap and a conchal cartilage (27%) following upper lid reconstruction which was graft. Plast Reconstr Surg. Jan 1991;87(1):142-5. [Medline] 15. Fatma Akdag, MD, Willem van den Bosch, MD, PhD, Elizabeth due to lagophthalmos. This was managed by lubricant Ganteris, “Sandwich Block” for Eyelid Reconstruction. April eye drops during the day two hourly and lubricating 2010, Vol. 29, No. 2 , Pages 110-113(http://informahealthcare. eye ointment at night along with taping the two lids com/doi/abs/10.1080/10717540600987513)

216 Ophthalmology Update Vol. 11. No. 4, October-December 2013 GENERAL SECTION ORIGINAL ARTICLE

Age Related Structural changes in the Vermiform Appendix

Sikander Hayat Sikander Hayat Niazi FCPS (Surgery)1, Sabiha M. Haq FCPS (Surgery)2, Dr. Shafqat Ali M. Phil. (Anatomy)3

ABSTRACT Objective. To know the microanatomy of the organ at different age groups for better understanding of histopathology of acute appendicitis. Study type, settings and duration: Comparative study done at Railway Hospital Rawalpindi from August 2011 to July 2013. Material and Methods. Four age groups (each containing 10 normal looking histological sections of surgically amputated vermiform appendix) spacing 15 years between each group, except last group which had no limit because of less availability of the specimens, were made. The various parameters i.e. lumen size, wall thickness (mucosa to serosa) and number of lymphoid nodules were measured in micrometers under the microscope, after staining. Results. It was observed that there was some inverse relationship between the lumen size and wall thickness. The mean number of lymphoid nodules decreased with advancing age but good number of lymphoid nodules were observed even at the age of sixties. A case of obliteration of the lumen was observed at middle age group beside old age group. Conclusion. The lumen size decreased as age advanced but not obliterated even at the age of 65 years. The lymphoid nodules decreased with advancing age and were replaced by connective tissue but these are present even at age of 65 years. Key words. Vermiform appendix, Lymphoid nodule, Micro-anatomy.

INTRODUCTION contains the lymphoid nodules which appear in the ap- The clinical presentations associated with this pendix about two weeks after birth10. tube (vermiform appendix) so much so that many lives The general anatomical morphology of vermiform have lost in the past as a result of either misdiagnosed appendix as described in standard anatomy, text books, or mismanagement of conditions associated with it. journals and other studies is not analyzed and dis- Acute appendicitis does not occur or arise de novo ex- cussed. It is the histomorpho-meteric profile and varia- cept as a consequence of the interplay of various factors tions of observed parameters that are being considered (diet, bacterial infection, parasitic infestations etc1) that at different age groups. For better understanding of involve its wall, length, diameter, position in abdomen histopathology of acute appendicitis, the knowledge of 2 normal microanatomy of the appendix at different age or pelvis or its blood supply . The vermiform (worm like) appendix is a blind ended tubular part of gut. The groups is the main objective of this study. appendix length varies from 2 to 20 cm with an average In Pakistan no such type of study has been con- 3 ducted as per literature review. In other countries, the of 9 cm . The longest appendix ever removed measured 26 cm from a patient in Zagreb; Croatia4. Its opening various studies have been conducted but as a single pa- into the caecum is guarded by a semicircular fold of rameters i.e. either lumen size or wall thickness etc. of mucous membrane known as valve of Gerlack5. The the postmortem appendices and appendectomy speci- appendices freely mobile on their mesentery attach- mens. ment encountered in 72% of fetal and 62.5% of adults6 . MATERIAL AND METHODS Zahid A. suggested that the vermiform appendix is no This study was conducted at Railway Hospital, 7 Rawalpindi from August 2011 to July 2013. The vari- more a vestigial organ . Appendix is a part of gut as- sociated tissue (GALT) which consists of both isolated ous parts of preserved specimen were embedded in im- and aggregated lymphoid follicles8.The mucosal folds pregnated paraffin and blocks were made. The section- and irregularity of the lumen of vermiform appendix ing of tissue blocks with microtome, of 4-5 micrometer are due to lymphoid follicles9. The vermiform appendix thickness was made. Haemotoxylin and Eosin staining used. Only the results of middle part of the vermiform 1,2Associate Professors of Anatomy, Islamic International Medical appendix are included in this study. The histologi- College, Rawalpindi 3.Professors of Anatomy, Pak International Medical College, Peshawar cal slides were examined under the light microscope after calibration of ocular micrometer. The total of 40 Correspondence: Lt. Col. (r). Dr. Sikander Niazi, House No. 428 surgically removed appendicectomy specimens (micro- Street No. 16 Chaklala Scheme-3 Rawalpindi. Ph: 051-5153528 Mob. 0333-5328643 scopically near to the normal histology of the appen- dix) were included and divided into four equal groups Received: August2013, Accepted: September’2013 (each group containing 10 specimens) according to age.

Ophthalmology Update Vol. 11. No. 4, October-December 2013 217 Age Related Structural changes in the Vermiform Appendix

The groups are, group A (0-15 years), group B (16-30 was between 6-74 year (mean age 32 years). The age years), group C (31-45 years) and group D (46-74 years). range, in group A was 6-14 years (mean age 10 years), The last group had large range because of less availabil- in group B 16-26 years (mean age 20 years), in group C ity of the specimens. 31-45 years (mean age 38 years) and in group D 46-74 RESULTS. years (mean age 60.5 years). The male to female ratio In this study, four groups A, B, C, & D were made was, in group A 6:4, in group B 9:1, in group C 7:3, in according to the age and microscopic study was done group D 9:1 and among all groups was 29:11. The re- after calibration of ocular micrometer. The age range sults are shown in Table 1,2,3,4, and 5.

Table 1 Group A (0-15 years)

Serial Age Lumen Wall Lumen + wall No. of No. (Years) + Sex Size (µm) Thickness (µm) Thickness (µm) Lymphoid Nodules

1 06 Male 305 158 463 11

2 06 Male 131 157 288 09

3 08 Male 130 225 356 11

4 10Female 350 170 520 10

5 10 Male 223 150 373 10

6 11Female 188 205 393 12

7 11Female 205 133 338 10

8 12Female 180 173 353 07

9 13Female 325 144 469 10

10 14Female 248 218 466 09

Mean 10 years 229 173 402 9.9 Value 4Male 6Female (197Male 249 Female) (167 Male,174 Female) (370 Male 423 Female) (9.7 Female,10.1 Male

Table 2 Group B (16-30 years)

Age Lumen Wall Lumen + wall No. of Serial No. (Years) Sex Size (µm) Thickness (µm) Thickness (µm) Lymphoid Nodules

1 16 Male 55 305 360 08

2 16 Male 127 240 367 16

3 18 Male 82 308 390 15

4 20 Male 205 178 383 08

5 20 Male 43 370 413 07

6 20 Male 173 223 396 10

7 21 Male 195 270 465 08

8 23 Male 108 225 333 10

9 24 Female 115 228 343 10

10 26 Male 193 235 428 11

20 years Mean 130 258 388 10.3 (M 9,F 1)

218 Ophthalmology Update Vol. 11. No. 4, October-December 2013 Age Related Structural changes in the Vermiform Appendix

Table: 3 Group C (31-45 years)

Serial Age Lumen Wall Lumen + Wall No. of No. (Years) +Sex Size (µm) Thickness (µm) Thickness (µm) Lymphoid Nodules

1 31 Female 53 358 411 06

2 31 Male 111 235 346 06

3 34 Male 168 335 503 10

4 35 Male 155 218 373 08

5 38 Female 105 253 358 08

6 40 Male 90 260 350 05

7 40 Male 80 245 325 nil

8 42 Male 105 353 458 05

9 43 Female 123 294 417 10

10 45 Male 138 208 346 08

38 Years 113 (93 276 (302 Female, 389 (395 Female, 6.6 Mean (Female 3, Male 7) Female, 121 Male) 251 Male) 372 Male) (8 Female,6 Male)

Table: 4 Group D (46-74years)

Lumen + wall No. of Lymphoid Serial No. Age (Years) Lumen Size (µm) Wall Thickness (µm) Thickness (µm) Nodules

1 46 Female 105 235 340 04

2 53 Male 101 275 376 03

3 56 Male 95 195 290 03

4 58 Male 45 200 245 03

5 60 Male 18 393 411 06

6 63 Male 83 203 286 07

7 65 Male 38 380 418 02

8 65 Male 128 278 406 07

9 65 Male 63 343 406 03 No Crypts

10 74 Male 63 212 275 nil No crypts

Mean 60.5 yrs (9 M, 1 F) 77 271 348 3.8

Table 5 Comparison of all groups means values

Groups Age Mean lumen Mean wall thickness Mean lumen Size + wall Mean number of range + Mean age) size (µm) (µm) Thickness (µm) lymphoid nodules

A (0-15 years) (10 years) 229 173 402 9.9

B (16-30 years) (20 years) 130 258 388 10.3

C (31-45 years) (38 years ) 113 276 389 6.6

D (46-74 years) (65.5 years) 77 271 348 3.8

Ophthalmology Update Vol. 11. No. 4, October-December 2013 219 Age Related Structural changes in the Vermiform Appendix

12 The mean luminal size (229µm) is greatest in group A. studv , although the luminal diameter is greater in The minimum mean luminal size (77 µm) is in group group A (0-20 years) and females but the groups are D. The maximum luminal size (350µm) is observed in not standardized according to the age. In a study of 13 group A. The mean wall thickness (mucosa to serosa) Shgabu, Umar and Singh , the lumen size is variable at is minimum in group A (173µm). The mean wall thick- different parts of one specimen. ness in group C and D has negligible difference i.e. In our study, there is some inverse relationship be- 276µm and 271µm. In group B the mean wall thickness tween wall thickness and luminal size. In a recent Nige- (258µm) is slightly less than group C and group D. rian study, the luminal size decreases when either the The maximum numbers of lymphoid nodules thickness or more importantly the lymphoid diameter 13 (10.3) are in Group B and minimum numbers of lym- increases in size . phoid nodules (3.8) are in group D. Although the mean In this study, the highest number of lymphoid numbers of lymphoid nodules are less in group D but nodules (10.3) is in the group B (16-30 years) and the number of lymphoid nodules even at the ages of 60 lowest number of lymphoid nodules (3.8) is in the years, 63 years and 65 years are six, seven and seven group D (46-74years). In another Bangladesh study14, respectively. It was also observed that in a male of 74 the highest number of lymphoid follicles were in age years the lymphatic tissue is scattered but no lymphoid group up to 20 years and lowest in age group between nodule and no crypts of Lieberkuhn are seen. 56-70 years and similarly the diameter of lymphoid fol- As the male and female specimens of vermiform licles is highest in age group up to 20 years and lowest appendix were not adequate, so gender comparison is in age group of 56-70 years but the age grouping was not made except in group A, where the females have somewhat different from our study. In another study, greater mean luminal size (249µm) than male (197µm). the highest average diameter of lymphoid follicles was It was also observed that mean luminal size gradually found in group 0-20 years and lowest average diam- 15 decreases from group A to group D. eter was found above 50 years age . The above referred In our study, the sum of the mean luminal size and study agreed with Borley9 and Arey 16. In another Bang- mean wall thickness in group B and group C has no ladesh study17 the mean numbers of lymphoid nodules difference but only small differences with group A and are less than half of our study. group D. In a book of surgery18, it is observed that after 15 The striking results are that, the specimens of all years, there is progressive atrophy of lymphoid tissue the groups which have minimum luminal size have proceed concomitantly with fibrosis of wall and partial maximum thickness of wall. Another striking feature or complete obliterations of the lumen. It is observed in is observed that there are no lymphoid nodules in the our study, that although the mean number of lymphoid male of 40 years. follicles is lowest (3.8) in group D (45-74Years) but even DISCUSSION at the ages of 60 years, 63 years, and 65 years, the num- The microanatomy of appendix is variable at dif- ber of lymphoid nodules are equivalent to some speci- ferent age groups. The lumen size and wall thickness mens of group A, B, and C. mainly depends on number and diameter of lymphoid In one specimen of our study, it is striking feature nodules. The most conspicuous feature of the appendix that a male of 40 years have no lymphoid nodule and is the large number of lymphoid nodules and its prima- no crypts, even the lumen size and wall thickness is ry function is an organ of lymphatic system. The nor- within normal limits of that age group. According to mal function of appendix probably helps to suppress the book of histology, in many adults the normal struc- potentially destructive humeral antibody responses ture of the appendix is lost and appendage is filled with while promoting local immunity11. Zahid A7, suggested fibrous scar tissue19 . that it play a role in both manufacturing hormones in In two cases (21years male & 44 years female) fetal development as well as functioning to train the which were excluded from our study, there is oblitera- immune system exposing the body to antigens so that tion of lumen and the whole wall is replaced by fibrous it can produce antibodies. The research performed at tissue (including the crypts and lymphoid tissue). It is Winthrop University Hospital showed that individu- concluded in one study that high incidence of fibrosis als without an appendix were four time more likely to in autopsy group suggests that this is an age related have a recurrence of Clostridium difficile. change20. In another very old study the author is firmly In our study, the mean luminal size of group A convinced that obliteration of lumen of human appen- (0-15 years) is greatest of all groups and mean luminal dix was a pathological process21. It is also observed in size is greater in females than males. In a Bangladesh our study that mean luminal size gradually decreases

220 Ophthalmology Update Vol. 11. No. 4, October-December 2013 Age Related Structural changes in the Vermiform Appendix from group A (229µm) to group D (77 µm) but even at fetal and adult age groups. The Anatomical Record, March the age of 65 years, the lumen size is 128µm. 1960; 136(3): 385-91. First published on line 2 Feb 2005. 11: Bockman DE. Functional Histology of appendix. Arch Histol CONCLUSION Jpn, 1983; 46(3):271-90. The lumen size decreased as age advanced but not 12: Rehman MM, Khalil M, Sultan SZ, Jahan MK, Shafiquzzaman obliterated even at the age of 65 years. The lymphoid M, Parvin B, Islam MT, Histomorphometric study of lumen nodules decreased with advancing age and were re- of human vermiform appendix. Mymensingh Med J Jan 2012; 21(1): 39-43. placed by connective tissue but these are present even 13: Shugaba AI, Umar MBT, Sing SP. Histomorphometric Profile at age of 65 years. of the Human Vermiform Appendix. J Med Sci, May-June 2006; REFERENCES 6(3): 445-51. 1: Moren B, Farquharsan M. Farquharsan text book of Operative 14. Rehman MM, Begum J, Khalid M, Latif SA, Nessa A, Jahan General Surgery. 9th ed. Holder Arnold; London:2005. MK, Shafiquzzaman M, Parvin B, Akhunda AK. Histomor- 2: William GR. A history of appendicitis. Ann Surg, 1983; 197: phological study of lymphoid follicle of vermiform appendix. 495-506. 2: Snell RS Clinical Anatomy. 7th ed. Baltimore: Lip- Mymensingh Med J, 2008 July; 17(2): 134-40. poncot William and Willkin 2004. 15. Paul UK, Noshaba H, Md Alam J, BegumT, Md Hussain M, Md 3: Snell RS. Clinical Anatomy. 7th ed. Baltimore: Lipponcot Wil- Rehman A. Histological study on the diameter of the lymphoid liam and Willkin 2004. follicle of vermiform appendix in Bangladesh people. Bangla- 4: Guinness world record for longest appendix removed. Guin- desh Journal of Anatomy, 2010; 8(1): 5-9. nessworldrecords.com. Retrieved 03 Oct 2o11. 16. Arey LB. Human Histology. 4th ed. Philadelphia: W B Sanders 5: Neeta V Kulkurni. Clinical Anatomy of students: Problem solv- Company; 1974. ing approach. 1st ed. Japee Brothers; New Dehli: 2006. 17. Rehman MM, Khalil M, Jahan KM, Shafquzzaman M, Parvia B. 6: Maisel H. The position of the human vermiform appendix in Mass of vermiform appendixin Bangladeshi people. J, Bangla- fetal and adult age groups. The Anatomical Record, March desh soc. Physiol.Dec 2008; 3: 8-12. 1960; 136(3): 385-91. First published on line 2 Feb 2005. 18. Lawrence WW, Doherty GM. Current Surgical diagnosis and 7: Zahid A. The Vermiform appendix: not a useless organ. J Coll treatment. 11th ed. London: McGraw- Hill 2003. Physician and Surgeons, April 2004; 14(4): 256-8. 19. Michael H Ross, Wojciech P. Histology; A Text and Atlas. 5th 8: Neutra MR, Mantis N J, Kraehenbuhl J P. Collaboration of epi- ed. Baltimore: lipponcot,Willium&Wilkins; 2006. thelial cells with organized mucosal lymphoid tissue. Nature 20. Andreous P, Blain S, Duboulay CEH. A histopathological Immunology, 2001; 2(11): 1004-9. study of the appendix at autopsy and after surgical resection 9: Borley NR. Vermiform appendix. Gray,s anatomy: Ellis H, Histopathology, Nov 1990 (On line Apr 2007); 17(5): 427-3. Healy JC, Johnson D, William A, Collins P, et al. Delhi: 2006. 21: Berry JA. The vermiform appendix of man and structural Anatomical basis of clinical practice. 39th ed. Edinburg: changes therein coincident with age. J Anat Physiol, April Elsevier,Churchill Livingstone; 2005. 1906; 40(part 3): 247-56. 10: Maisel H. The position of the human vermiform appendix in

Corrigendum:

The readers may please note the following correction: ‘In the article Frequency of Cataract in Eye Malformations’ published in the July-September issue (Vol.II No:3, page.197) of Ophthalmology update, the address of the 2nd author may please be read as : Dr. Shafqat Ali, Associate Prof of Anatomy, Pak International Medical College, Peshawar instead of Islamic International Medical College, Rawalpindi. The omission is very much regretted……….Editor

Ophthalmology Update Vol. 11. No. 4, October-December 2013 221 CURRENT RESEARCH

Possible New Strategy in AMD Prevention Prof. Rajendra Apte, M.D., Ph.D Professor of Ophthalmology & Vision Sciences Washington University in St. Louis. USA

Dr. Grace Shen, Ph.D Program Director, National Eye Institute National Institute of Health

Edited by: Dr. Madiha Durrani, FRCS Dubai, UAE

Targeting cholesterol metabolism in the eye might help prevent a severe form of age-related macular degeneration (AMD), one of the most common causes of blindness in aged population, as indicated in a study in mice.

INTRODUCTION: tors. They scavenge for debris, engulf it, and process it. Macrophages appear to play a key role in clear- In previous studies, Dr. Apte found that macrophages ing cholesterol from the eye, and that with aging mac- normally help limit the growth of new blood vessels rophages become less efficient at processing cholesterol in the eye, but with the advancing age, the cells lose due to a decrease in the level of ABCA1 protein. How- this ability. The new study suggests that prior to these ever, restoration of cholesterol efflux using Liver-X re- changes, old macrophages become less efficient at pro- ceptor (LXR) agonists or miR-33 inhibitors reverses it. cessing cholesterol. “Ideally, macrophages should take Additionally, a similar drop in ABCA1 levels in blood up cholesterol, process it, and spit it out into the blood- cells donated by older people (ages 67 to 87) compared stream. In AMD, the cells are ingesting cholesterol but with younger people (ages 25 to34) has been found. not able to spit it out and these inflamed macrophages The ABCA1 gene has been identified as a risk factor for promote blood vessel growth. AMD. Prof. Rajendra Apte theorizes that targeting cho- The disorder causes damage to the macula, a re- lesterol buildup in the eye may slow age-related vision gion of the retina responsible for central, high-reso- loss as revealed in a study in mice, supported by the lution vision. The macula is dense with light-sensing National Eye Institute. cells called photoreceptors responsible for sharp vision, Genetic Studies: such as reading, driving, and recognizing faces. This Cholesterol build-up in arteries and veins, or ath- sharp vision deteriorates in AMD, which can take two erosclerosis, occurs as a natural consequence of aging. forms. In one, sometimes referred to as Dry AMD, vi- An eye care professional can detect AMD prior to vi- sion loss is due to a gradual loss of photoreceptors in sion loss by looking for drusen, which are yellow de- the macula. In the other Wet or Neovascular AMD, ab- posits under the retina that contain cholesterol and normal blood vessels grow under the macula, leaking other debris Although small drusen are a normal part blood and causing rapid damage to the photoreceptors. of aging, larger drusen typically indicate AMD. What The protein ABCA1 is needed for macrophages triggers AMD is unclear. Drusen and the cholesterol to release cholesterol into the bloodstream. In these within them, have been the prime suspects and based experiments on mice, Dr. Apte Ph.D., and Dr. Grace on genetic studies, including a recent genome-wide as- Shen, Ph.D., a program director at NIH’s National Eye sociation analysis, the immune system appears to play Institute and his team found that in old macrophages, a role, too. But researchers have had few details to con- there is a decrease in the level of ABCA1 protein. The nect these two pathways. researchers found a similar drop in ABCA1 levels in Dr. Apte thinks that macrophages, a type of im- blood cells — the source of macrophages — in samples mune cell, may provide a crucial link. Macrophages, donated by older people (ages 67-87) vs. younger ones (literally “big eaters” in Greek), act like garbage collec- (ages 25-34). The ABCA1 gene has been identified as a

222 Ophthalmology Update Vol. 11. No. 4, October-December 2013 Possible New Strategy in AMD Prevention risk factor for AMD. To investigate the link between away cholesterol might help. these changes and blood vessel growth, the researchers Having high blood cholesterol is not strongly re- first performed tests in cell culture. When grown in a lated to AMD, and it remains to be determined whether dish with blood vessel cells, young macrophages effi- statins and other cholesterol-modifying drugs on the ciently stopped the cells from multiplying, but old mac- market can reduce the risk of AMD. LXR agonists and rophages did not. Deleting the ABCA1 gene in young other agents that modify cellular release of cholesterol macrophages caused them to behave like old mac- are at various stages of investigation for many disor- rophages. Next, the researchers tried treating old mac- ders. Some studies have found that when the drugs are rophages with an LXR agonist; these drugs are known given orally to mice, they appear to reduce atheroscle- to enhance cholesterol transport from macrophages by rosis, but there have been concerns about potential tox- turning on the ABCA1 gene. Exposure to the drug re- ic effects on the liver. Dr. Apte theorizes that therapy juvenated the old macrophages and enabled them to limited to the eye would not raise the same safety is- inhibit blood vessel cell growth. sues. The National Eye Institute, part of the National The researchers also tested the LXR agonist in mice Institutes of Health, leads the Federal Government’s with an eye injury that produces abnormal blood ves- research on the visual system and eye diseases. sel growth, similar to that seen in neovascular AMD. CONCLUSION Eye drops of the drug significantly reduced the blood This study points to a novel strategy for early vessel growth when given several days before the in- intervention to prevent the progression of AMD to jury. Although there is no cure for AMD, a number of the severe neovascular form of the disease. The study treatments are available. A combination of antioxidants published in Cell Metabolism in April’2013, shows and zinc known as the AREDS formulation can help that large cells called macrophages appear to play a slow vision loss in people with intermediate (but not key role in clearing cholesterol from the eye, and that early) stages of AMD. There are several treatments for with aging, these cells become less efficient at this task. advanced neovascular AMD; the most common choice Eye drops containing a type of drug known to promote involves injecting the eye with drugs that block the ef- cholesterol release from macrophages, called a liver fects of a secreted protein involved in new blood vessel X receptor (LXR) agonist, helped restore macrophage formation. However, such anti VEGF drugs must be function and prevent AMD progression in a mouse given frequently up to once a month. If we could pre- model. vent the blood vessels from growing, it would be better REFERENCE: than trying to eliminate them, and using additionally Sene A, and Khan A. et al. “Impaired cholesterol efflux in senescent macrophages promotes age-related macular degeneration. LXR agonists or other drugs to help macrophages clear

Ptosis Crutches: Patient with CPEO using Ptosis crutches

A patient with CPEO along with the Ptosis crutches fitted into the spectacles. We had them made in Karachi. Basically two shops in Karachi help us with these patients. 1. Eyeland, Shaheed -e - Millat Road, Karachi 2. Central Optics, Saddar, Karachi. Contact: Mr. Asim This is a common problem for oculoplastic surgeons dealing with inoperable cases of ptosis . These crutches are used for short periods and patients are guided on using lubricants. This particular patient did very well.

Dr. Alyscia M. Cheema FCPS, FRCS.(Edin) Associate Prof. Ophthalmology Jinnah Postgraduate Medical Centre, Karachi

Ophthalmology Update Vol. 11. No. 4, October-December 2013 223 CURRENT RESEARCH

Human Corneal Anatomy Redefined Harminder Prof. Harminder Singh Dua MS, FRCS, FRCOphth., MD, PhD. Chairperson, Prof. of Ophthalmology, Visual Sciences University of Nottingham. UK President, Royal College of Ophthalmologists, United Kingdom

British Ophthalmologists have discovered new layer in the cornea – the Dua’s Layer (previously undetected), which may improve the corneal surgeries more safer and simpler with better understanding of both biomedics and corneal pathologies like , acute hydrops, descemetocele and pre-descetmet’s dystrophies. The whole SIKH nation feels proud of an outstanding scholar Professor Harminder Singh Dua when a Pooran Gur Sikh has contributed to the scientific world and for humanity at large.

INTRODUCTION strong enough to be able to withstand one and a half to Scientists previously believed the cornea to be two bars of pressure. comprised of five layers, from front to back, the corneal The scientists now believe that corneal hydrops, a epithelium, Bowman’s layer, the corneal stroma, De- bulging of the cornea is caused by fluid build-up that scemet’s membrane and the corneal endothelium. The occurs in patients with keratoconus, is caused by a tear new Dua’s Layer after the name of Prof. Harminder in the Dua’s layer, resulting in waterlogging. The dis- Dua lies between the corneal stroma and the descet- covery will have an impact on advancing and under- met’ membrane. standing of a number of diseases of the cornea. This is a major discovery that will mean ophthalmology text books, literally need to be re- written. Having identified this new and distinct layer deep in the cornea, we can now exploit its presence to make operations much safer and simpler for patients. From a clinical perspective, there are many diseases that affect this layer and which clinicians across the

Left: schematic diagram of the human eye showing the, vertical section of the cornea

MATERIAL & METHODS: Investigators have identified a novel, acellular, strong layer in the pre-Descemet’s cornea. Harminder S. Dua, and colleagues from the University of Notting- ham in the United Kingdom have discovered the layer by examining the separation that often occurs along the world are already beginning to relate to the presence, last row of keratocytes during the big bubble (BB) tech- absence or tear in this layer. Although the layer is, nique. Surgeons have long used the BB technique to ef- just 15 microns thick, the entire cornea is around 550 fectively peel off the Descemet’s membrane (DM) for microns thick or 0.5mm. It is incredibly tough and is use in the deep anterior lamellar keratoplasty (DALK) Correspondence: Prof. Harminder Singh Dua, 0115 849 3354, 0115 procedure. In 2002, investigators found that there was 970 9963 Queens Medical Centre, Derby Road, Nottingham, NG7 a layer attached to the deep stroma that was also re- 2UH, UK E.Mail>[email protected] moved by mechanical dissection. The Management of Opthalmology Update is highly gratified to Professor Harminder Sing Dua for permitting to publish his current The current study expands on this previous work research work in journal and identifies a distinct layer that is 10.15 ± 3.6 microns

224 Ophthalmology Update Vol. 11. No. 4, October-December 2013 Human Corneal Anatomy Redefined thick at the posterior surface of the corneal stromal. The corneal stroma via the ‘Big Bubble technique’ authors emphasized that this layer is not “residual stro- • If the bubble bursts it causes damage to the eye. ma.” • But if the air bubble is injected under Dua’s layer The analysis was performed on 31 human donor instead of above it, the layer’s strength reduces the sclera-corneal discs (including 6 controls). The study risk of tearing was performed on the eyes with a mean age of 77.7 • Diseases of the cornea including acute hydrops, years. Having performed all types of corneal trans- Descematocele and pre-Descemet’s dystrophies plants, we had certain doubts about the plane at which may be affected by the discovery of Dua’s layer the air injected into the cornea separated the ‘DM.’ Problems with the layer could also explain many There were clues that it was not the DM while separat- eye diseases that until now were elusive in origin. Hav- ing and doing DALK. So we decided to investigate this ing identified this new and distinct layer deep inthe by simulating the operation in human eyes (not suit- tissue of the cornea, we can now exploit its presence to able for transplant for various reasons) obtained from make operations much safer and simpler for patients. the UK eye banks. Dr. Dua and colleagues identified From a clinical perspective, there are many diseases two types of BB: type 1 was well-circumscribed with that affect the back of the cornea which clinicians across an elevation of up to 8.5 mm (n = 14), and type 2 was the world are already beginning to relate to the pres- thin-walled with a maximum diameter of 10.5 mm (n = ence, absence or tear in this layer. Researchers proved 5). The researchers also found eyes with a mixed type of the layer existed by simulating human corneal trans- BB (n = 3). plants and grafts on eyes donated for research. During We were able to induce separation of the layer these experiments, tiny bubbles of air were injected into by injecting air and prove by electron microscopy and the cornea to separate the different layers. The scientists other means that there was a new layer and that the then subjected the separated layers to electron micros- cleavage was not between DM and stroma, as every- copy, allowing them to study them at many thousand one thought. The simple and clinical evidence is in the times their actual size and revealing Dua’s layer.The videos linked to the paper which they can be accessed authors say that the discovery will have an impact on advancing understanding of a number of other diseases only online at the Ophthalmology journal’s Web site,” If of the cornea. it is, indeed, an actual layer of the cornea, it should be present in children as well, and that work still needs to CONCLUSION The discovery as it explains a few things that were be done happening during lamellar corneal surgery and we did The authors suggest that recognition of this novel not previously understand. It will make the operation layer will affect posterior corneal surgery. Specifically, safer and may also improve our understanding of some it may be possible to use the plane between the Dua’s corneal diorders layer and stroma to generate tissue for endothelial : transplant. The authors also propose that “the discov- REFERENCES ery will aid in the understanding of corneal biome- 1. Harminder S. Dua, Harminder S. Dua & Kadaba N. Rajku- mar, Clinical Diagnosis: Ophthalmology (anterior Segment & Glau- chanics and pathology in patients with acute hydrops, coma)(Rila Publications Ltd, 1998) Descematocoele, and pre-Descemet’s dystrophies are 2. BMJ: Harminder Singh Dua biography Bibliographic informa- most likely to benefit from the discovery. tion: Harminder S. Dua et al. 2013. Human Corneal Anatomy Redefined: A Novel Pre-Descemet’s Layer (Dua’s Layer).Oph- DISCUSSION thalmology, in press; doi: 10.1016/j.ophtha.2013.01.018 what does the discovery of Dua’s layer mean? 3. Kristin Butler (June 12, 2013). “Scientists discover new layer of • Knowledge of Dua’s Layer could improve out- human cornea”. UPI. Retrieved June 12, 2013.[unreliable medical source?] 4. Dua, H. S.; Faraj, L. A.; Said, D. G.; Gray, T.; Lowe, J. (2013). comes for patients undergoing corneal grafts and “Human Corneal Anatomy Redefined: A Novel Pre-Descem- transplants et’s Layer (Dua’s Layer)”. Ophthalmology. doi:10.1016/j.oph- • During surgery, tiny air bubble are injected into tha.2013.01.018. edit

Ophthalmology Update Vol. 11. No. 4, October-December 2013 225 CURRENT RESEARCH

Are Nerve Fibers being Atrophied or Severed in Glaucoma? Syed S. Hasnain Sikandra Hasnain Syed S. Hasnain, MD1. Sikandra Hasnain, BA2

INTRODUCTION: are being destroyed in chronic glaucoma. Atrophy of an organ or tissue is defined as shrink- About one million nerve fibers originating from age in size, not disappearance, of a developed organ, the RGC’s leave the eyeball through meshwork of the whereas the severance of an organ would result in its Lamina Cribrosa (LC) and form the optic disc. There total disappearance. Keeping this distinction in mind are two main aspects in which the nerve fibers are ar- would be of paramount importance in elucidating ranged in the retina and optic disc. First, the nerve whether the nerve fibers are being atrophied or severed fibers in the retina are arranged in layers superficial to in glaucoma. Glaucoma is defined as an optic disc neu- deep. The fibers originating closest to the disc lie most ropathy implying that nerve fibers are being atrophied superficial (closest to vitreous) and exit from the most just as in other conditions in which nerve fibers are tru- central part of the disc whereas nerve fibers originat- ly being atrophied, such as in multiple sclerosis. Optic ing from most peripheral retina lie deepest (closest to atrophy is the end result of any disease that damages sclera) and exit closest to the edge of the scleral open- nerve cells anywhere between the retinal ganglion cells ing. Second, the nerve fibers originating from the nasal (RGC) and the lateral geniculate nucleus (LGN). retina proceed directly to the nasal part of the disc and Although glaucoma is also considered an optic much of the of the macular fibers proceed horizontally atrophy, there are many distinctive features between to the temporal part of disc. However, the fibers origi- the glaucomatous disc (GD) and non-glaucomatous nating from the temporal macular area and temporal atrophic discs (NGAD). In glaucoma there is develop- peripheral retina arch above and below the macular fib- ment of excavation or empty spaces in GD whereas ers to reach the disc, hence known as arcuate fibers. there’s no excavation occurring in NGAD. Moreover, Nerve fibers are always being destroyed in a spe- in glaucoma the nerve fibers are being destroyed in a cific sequence, never haphazardly in glaucoma. The specific orderly sequence whereas in NGAD the nerve most peripheral temporal fibers, due to inherent tem- fiber loss is non-specific and haphazard. poral tilt of the disc are destroyed first, resulting in the In light of glaucoma having an orderly destruction loss of most peripheral nasal field. However, the early of the nerve fibers, arcuate field defects and excavation, nasal loss is easily undiagnosed due to normal varia- it is hypothesized that the nerve fibers are being sev- tion in the extent of peripheral fields. When the damage ered, not atrophied in glaucoma. reaches the paracentral area and begins to destroy the arcuate fibers, then pathognomonic arcuate field de- DISCUSSION: fects are produced. Central fields are retained until the Before we begin our discussion, it is important to end-stage of glaucoma. Similarly orderly destruction of mention the arrangement of the nerve fibers in the ret- the nerve fibers occurs in both high-tension and nor- ina/optic disc and the sequence in which nerve fibers mal-tension glaucoma, suggesting there is a common 1General Ophthalmologist, 2Sikandra Hasnain is a third year medical student who Plans to pursue ophthalmology. Ms. Hasnain’s personal ground somewhere in the course of their pathogenesis. interests include pediatric Ophthalmology. Currently her research We would discuss whether the nerve fibers were project is hypothesis of the cause of Glaucoma. Sikandra Hasnain being destroyed in an orderly fashion from peripheral has also volunteered at the Shaukat Khanum Cancer Hospital during her summer vacations while studying at University of California, Los to central either due to cupping or due to direct role of Angeles. raised IOP. Can ‘cupping’ explain the production of glaucomatous Correspondence: Dr. Syed S. Hasnain, MD1,General Ophthalmologist, 560 W. Putnam Ave. Suite #6 Porterville, CA 93257 Tel: 559.781.7482 field defects? Fax: 559.781.8446 Email: [email protected] Currently, the LC is the presumed site of injury in Web: www.hasnaineye.com glaucoma. Posterior bowing of the LC (cupping) due

226 Ophthalmology Update Vol. 11. No. 4, October-December 2013 Are Nerve Fibers being Atrophied or Severed in Glaucoma to high IOP pinches the axons, thus impeding the axo- on the nerve fibers/RGC’s appears invalid. plasmic flow and leading to apoptosis of the RGC’s and Can the nerve fibers be destroyed in an orderly fashion atrophy of the nerve fibers. The term cupping implies if glaucoma a neuro-degenerative disease? that pathology starts from the central part and extends Glaucoma is also being considered as a neuro-de- peripherally to disc margin. If cupping was indeed oc- generative disease akin to Parkinsons and Alzheimers. curring then, the nerve fibers originating closest to the However, the random degeneration of the neurons is disc should be destroyed first as they occupy the most the hallmark of a neuro-degenerative disease and thus central position in the disc and result in continuous con- the course of a neuro-degenerative disease varies in centric enlargement of the blind spot involving first the each individual. In glaucoma, on the other hand, the central vision and finally the peripheral in glaucoma. nerve fibers are being destroyed in a specific sequence But according to glaucomatous field defects, the nerve and never at random. How is it possible that neuro-de- fibers are being destroyed in a reverse order starting generation of the RGC’s in glaucoma will always start with the peripheral and ending with the central fibers. with those which serve the peripheral vision and never It appears that some mechanism other than cupping randomly as occurring in other neuro-degenerative seems to be involved which is causing the peripheral diseases? If glaucoma is a neuro-degenerative disease, fibers to be destroyed first and central at the end-stage then our genes must first have predicted the impend- in an orderly fashion in glaucoma. In view of the afore- ing glaucoma so to initiate apoptosis only with those mentioned the cupping of the disc may not be occur- RGC’s which serve the peripheral vision and ending ring in glaucoma. with central vision in a systematic approach, an unlike- It is published extensively that nerve fibers are ly scenario. In view of aforementioned, glaucoma being present only in the rim of the optic disc whereas the a neuro-degenerative disease appears unlikely 2 central cupped area is devoid of neural tissue. Unfor- In fact, it is unlikely that raised IOP or in fact any tunately I have been unable to find even a single histol- other pathology, acting directly would cause the de- ogy of any normal or diseased disc having such dough- struction of nerve fibers or their RGC’s in an orderly nut arrangement of the nerve fibers. Histology of the fashion. If the nerve fibers are being destroyed in an normal optic disc reveals that the entire LC is packed orderly fashion in glaucoma, then the mechanism caus- with nerve fibers and there is no empty space at all. ing their destruction should be orderly as well. If doughnut arrangement is true: it will imply that Then, why are the nerve fibers being destroyed in an or- someone born with 0.7 cup would become totally blind derly sequence in glaucoma? sooner because of his/her small rim or would it take For answer to the above question, I hypothesize longer because the force of raised IOP will be quickly that the optic disc may be sinking in glaucoma, a para- dissipated in the larger central hole and thus the neural digm shift.1 As a result of sinking disc, the pre-laminar rim would escape injury. The term cupping was origi- peripheral nerve fibers being closest to the scleral edge nally given by Heinrich Muller in 1856 (Duke-Elder) are involved first.FIG 2 and since then it has become synonymous with glau- As a result of sinking disc the nerve fibers would coma. The concept of cupping is a conundrum and ap- be stretched since one end is attached to the soma of pears mistakenly given 150 years ago. RGC and other end fastened in the sinking LC and ul- Can the Nerve fibers be destroyed in an orderly se- timately get broken. As the peripheral fibers are be- quence due to direct effect of raised IOP? ing severed and depleted, the next in line central fibers It has been postulated that nerve fibers are dam- would move towards the scleral edge to occupy the va- aged either due to direct effect or due to ischemia in- cant space and thus also get stretched and broken. In duced by direct compression of the blood vessels by addition to the circular border tissue the optic disc is raised IOP. anchored in the scleral opening by 360 degrees of the Arguments against the direct role of IOP: it would be retinal fibers as roots anchor the tree. The anchorage an unlikely scenario that raised IOP acting directly will of the disc would become weak due to severing of the always destroy the peripheral nerve fibers first, then nerve fibers and thus the disc would sink further result- the paracentral and finally the central among the mil- ing in severing of additional nerve fibers. Sinking of the lion or so densely packed nerve fibers in a 1.5mm disc disc and severing of the nerve fibers will become self- in an orderly sequence and not destroy haphazardly. propagated and will continue until all the nerve fibers Similarly ischemia resulting from raised IOP could not are severed beginning with the peripheral and end- destroy the nerve fibers in an orderly fashion. In view ing with central fibers in an orderly fashion and this is of aforementioned the role of raised IOP acting directly what’s revealed by glaucomatous field defects

Ophthalmology Update Vol. 11. No. 4, October-December 2013 227 Are Nerve Fibers being Atrophied or Severed in Glaucoma

Is there any evidence of sinking disc and severing of the CRV are pulled nasally. nerve fibers in glaucoma? Analogy: if the roots were cut from one side, the tree 1. It has been published that there is posterior migra- would shift to the opposite. Since the nerve fibers are tion of the LC from early stages of glaucoma, 3 sub- not being severed there is no nasal shifting of CRV in stantiating the disc may be sinking. NGAD. 2. Sloping/kinking of the blood vessels at the disc 10. Progressive thinning of the RNFL in the glauco- margin prior to any change in the contour of the matous disc as revealed on OCT is due to continu- physiological cup suggests that optic disc may be ous severing of the nerve fibers as it is not occur- sinking in glaucoma. ring in the NGAD. 3. Arcuate field defects appear to be produced as a 11. Excavation occurring in the glaucomatous disc result of severance of the nerve fibers. As the disc (GD) is due to severing of the nerve fibers, a unique sinks, entire temporal fibers (macular, superior and feature of glaucoma. Histology of the end-stage inferior arcuate) are being severed.FIG3 However, glaucomatous disc (ESGD) is distinctively differ- the superior and inferior arcuate fibers being fewer ent from NGAD, such as due to Multiple Sclerosis. in number compared to the macular fibers, will be In ESGD there is total disappearance of the nerve depleted earlier giving rise to arcuate field defect/ fibers, FIG 5 whereas in Multiple Sclerosis the nerve ring scotoma. FIG 4 Arcuate fibers can’t be selectively fibers are still present though shrunken.FIG 6 Total atrophied, out of million or so densely packed fibers disappearance of the nerve fibers in the ESGD can in a 1.5 mm disc, due to any pathology. only be explained by severance, not due to their 4. Decrease in thickness of the macular ganglion cell atrophy. ESGD may not be a 100% cupped, atro- complex observed in the early stages of glaucoma phied disc but an empty crater leftover after the substantiates the fact that the macular fibers are also severance of the nerve fibers. severed along with the arcuate fibers from the very CONCLUSION: beginning. The sloping/kinking of the blood vessels at disc 5. Severing of the nerve fibers would explain the si- margin, prior to any change in the contour of the physi- multaneous death of the RGC’s due to retrograde ological cup, suggests that the optic disc may be sink- degeneration and of the neurons in the LGN due to ing in glaucoma. The development of excavation, ar- Wallerian degeneration. RGC’s may not be dying cuate field defects, progressive thinning of the RNFL primarily due to apoptosis but secondary to sever- suggests that the nerve fibers are being severed in glau- ing of the nerve fibers. coma. Hemorrhages at the disc margin may be due to 6. Splinter hemorrhages, disappearance of smaller severance of the smaller vessels. Histology of ESGD – a vessels around the disc and characteristic whitish totally empty crater/bean-pot, supports the fact that pallor appears to be due to severance of smaller vas- the nerve fibers are being severed in glaucoma. If nerve culature meeting the same fate as of nerve fibers. fibers were indeed being severed then glaucoma would 7. Superior and inferior notching resulting in vertical be a mechanical failure- in fact a herniation of the disc enlargement of the physiological cup appear to be in the scleral canal. Glaucoma may not be an optic disc due to severance and depletion of arcuate fibers at neuropathy but an axotomy. the point of their entry at the respective poles of the REFERENCES disc. 1. Hasnain SS. Scleral edge, not optic disc or retina is the primary site of injury in chronic glaucoma. Medical Hypothesis 2006; 8. Wedge-shaped defects in the retina pertaining to 67(6); 1320-1325. the area of the arcuate fibers location are due to the 2. Hasnain SS. Can Glaucoma be a Neurodegenerative Disease? severance of nerve fibers, not due to their atrophy. Highlights of Ophthalmology. 2012;(40)3. Such retinal defects do not occur in NGAD. 3. Yang H et al. Optic nerve head . Lamina Cribrosa Insertion mi- gration and pialization in early Non-Human primate Experi- 9. Nasal shifting of the central retinal vessels (CRV) mental Glaucoma. Poster Presentation ARVO meeting May 03, can be explained by loss of anchorage due severance 2010. of the nerve fibers. Due to temporal tilt, the tempo- 4. Hasnain SS. Pathogenesis of Arcuate Field Defect in Glaucoma. Highlights of Ophthalmology 2012;(40)6. ral fibers are severed earlier than the nasal’s so the

228 Ophthalmology Update Vol. 11. No. 4, October-December 2013 SHORT COMMUNICATION

Promising Results of Eye Therapy in Post-Traumatic Stress Disorder (PTSD) Patients Abbas Hasnain Abbas Hasnain MD, JD. ABSTRACT There are various treatment options available for patients suffering from Post Traumatic Stress Disorder (PTSD). Although there is no ‘clear drug treatment’ for PTSD, many drugs can alleviate the symptoms of illness including nightmares, - backs, depression, and sleep disturbances. One of the unique and controversial methods of non-pharmacologic treatment includes eye movement desensitization and reprocessing psychotherapy (EMDR).

INTRODUCTION receiving daily SSRIs. (Selective Serotonin Reuptake in- This extraordinary form of psychotherapy has be- hibitors (SSRIs), are a category of drugs, such as Prozac come quite promising since its discovery over 15 years (fluoxetine), that works by inhibiting the re-uptake of ago. What happens is that a therapist asks the patient to serotonin by neurons in the CNS, thus allowing more hold their memories of the PTSD event in their minds serotonin to be available. Low serotonin levels are im- and at the same time the therapist will ask the patient plicated in those with depression to follow his/her finger back and forth.1 This process This study was conducted by Dr. Asad Ullah Jan at is repeated until the patient no longer feels anxiety or the Armed Forces Institute of Mental Health in Rawal- fear while thinking of these thoughts. After the patient pindi, Pakistan. The study involved following 60 males no longer feels distressed, he/she will think of a posi- survivors in war trauma. Half of the subjects were start- tive thought that both the patient and therapist have ed on weekly EMDR therapy while the other half were agreed upon beforehand.2 It is different from hypnotic started on 20mg doses of Paroxetine. The study con- methods as instead of the patient being relaxed, these ducted a checklist of PTSD at baseline and compared it PTSD patients are asked to bring about their disturbing to the checklist completed after 6 weeks. thoughts. The researchers found that amongst the patients There have been many proposed theories as to who received EMDR, 90% of the subjects had a treat- how the eye movement therapy is effective in decreas- ment response (in being 20 points decreased on the ing the symptoms of PTSD images and thoughts that PTSD scale.)3 Of the other half the subjects receiving accompany the memory. A popular theory posits that paroxetine, 36% had a treatment response according to since our thoughts are refiled in a different way every the checklist.3 time we recall them, the eye movements cause a sort The other study conducted investigated the recov- of distraction with the thoughts as they are refiled in ery rate of PTSD between both EMDR and eclectic psy- the brain. The eye movement distraction makes the chotherapy. Eclectic psychotherapy is an approach that imagery and richness of the images less disturbing as utilizes techniques and therapies from various schools they are returned to the brain. Thus, the patient is left of thought. This study was similar as the study con- with much less traumatic images when remembering ducted in Pakistan as an assessment was conducted at the distressing memory. baseline and after 6 weeks measuring the PTSD symp- Two randomized controlled studies have recently toms. The trial was also longer as the total duration of emerged regarding EMDR. One study conducted in Pa- the study was 17 weeks. The study was distinguished kistan and recently presented at the International Con- from the first study as this study had a much larger gress of Royal College of Psychiatrist this year investi- number of subjects – 140 PTSD patients. gated whether EMDR was more efficacious than those The results found that although there negligible differences in the assessment scores at the end of the 17 Mr. Abbas has done his MD and wants to go into Forensic Psychiatry, weeks, there was a marked decline in PTSD symptoms an emerging field of Medicine, where he can help the medical profession in lawsuits. (such as general anxiety and depressive symptoms) af- ter 6 weeks amongst the EMDR group.4 Correspondence: 560 W. Putnam Ave. Suite #6, Porterville, CA 93257 Tel: 559.781.7482 Fax: 559.781.8446 Although these two studies would benefit larger Email: [email protected] scale studies to strengthen their conclusions, the insight

Ophthalmology Update Vol. 11. No. 4, October-December 2013 229 Promising Results of Eye Therapy in Post-Traumatic Stress Disorder (PTSD) Patients provided could potentially change the way we treat this REFERENCES: difficult disorder. SSRIs can produce many distress- 1. EMDR: Taking a Closer Look. Scott O. Lilienfeld. Scientific American. ing side effects (sexual dysfunction, cardiovascular is- 2. Treating Post-Trauma Stress Disorder. Christoph Rothmayr. sues, effects on sleep, and weight gain) whereas EMDR Department of Psychology, Vanderbilt University. therapy has no known side effects. Also, EMDR may be 3. Eye Therapy Has It Over Antidepressant for PTSD. Deborah Brauser. Medscape Medical News particularly ideal in cases where the patient needs to 4. Eye Movement Therapy Offers Faster Recovery From PTSD. reduce the PTSD symptoms as soon as possible.4 Deborah Brauser. Medscape Medical News

(Note: The review article describes the recent studies regarding EMDR therapy, a Pakistani study conducted at the Armed Forces Institute in Rawalpindi. I am also conducting my own study in view of this particular therapy to be published soon.)

Acute corneal hydrops with infantile glaucoma Anil K. Mandal, M.D., Vijaya K. Gothwal, Ph.D. L V Prasad Eye Institute, Hyderabad, Andhra Pradesh, India

A healthy 3-month-old boy was brought to the emergency department because of the acute onset of corneal edema of the left eye (Panel A). One hour before presentation, his parents noticed that the left cornea was cloudy and the right eye was normal after he had been crying. While the patient was under anesthesia, evaluation revealed severe corneal edema of the left eye. The horizontal corneal diameter was 12 mm in the right eye and 13.5 mm in the left eye (reference range, 10 to 12). Intraocular pressure was 12 mm Hg in the right eye and 32 mm Hg in the left eye. Acute corneal hydrops with infantile glaucoma was diagnosed in the left eye. The boy underwent primary combined trabeculotomy and trabeculectomy in the left eye. Two weeks postoperatively, the left cornea showed dramatic improvement (Panel B). Six months postoperatively, an evaluation showed a clear cornea with Haab’s striae (Panel C, arrows), which may affect vision if located centrally, and normal intraocular pressure (10 mm Hg in both eyes). At the last follow-up (2 years postoperatively), there was no corneal edema, the intraocular pressure was 12 mm Hg, and the visual acuity was 20/40 in both eyes.

(Courtesy: Anil K. Mandal, M.D., Vijaya K. Gothwal, Ph.D.) L V Prasad Eye Institute, Hyderabad, Andhra Pradesh, India [email protected]

230 Ophthalmology Update Vol. 11. No. 4, October-December 2013 SHORT COMMUNICATION

AMERICAN ACADEMY OF OPHTHALMOLOGY Syed S. Hasnain Where the mystery of Glaucoma lies?

Community Connection : fibers originating closest to the optic disc lie most Dr. S. S. Hasnain has posted following three superficial (closest to the vitreous) and exit from the questions on the Academy forum. The moderator of this most central part of the disc. The nerve fibers are always forum, in his response, has put forward these questions being destroyed in a specific sequence from peripheral to in the academy communications to its members. central and never haphazardly in glaucoma. If cupping 1. Are the nerve fibers being atrophied or severed in was indeed occurring then, the nerve fibers originating chronic glaucoma? closest to the disc should be destroyed first as they 2. Is the optic disc really cupping in glaucoma? occupy the most central position in the disc and result 3. Are nerve fibers present solely in rim area whereas in continuous concentric enlargement of the blind spot central cupped area of optic disc is empty? involving first the central vision and finally the peripheral The mystery of glaucoma lies in the answers to in glaucoma. However, according to glaucomatous field these questions. defects, the nerve fibers are being destroyed in a reverse “Are the nerve fibers being atrophied or severed in order starting with the peripheral and ending with the chronic glaucoma? “ central fibers. It appears that some mechanism other Subspecialty Connection: than cupping seems to be involved which is causing the It has recently come under community discussion peripheral fibers to be destroyed first and central at the in view of “Proposed Increasing Physician Quality end-stage in an orderly fashion in glaucoma. In view of Reporting System” by American Academy of the afore-mentioned the cupping of the disc may not be Ophthalmology. occurring in glaucoma. Looking forward for comments. Accordingly the Academy’s Discussion Forum. 3. Are nerve fibers present solely in rim area whereas “Histology of the end-stage glaucomatous disc resembles central cupped area of optic disc is empty? an empty bean-pot- no nerve fibers at all. Where did the Subspecialty Connection nerve fibers go? In contrast the histology of the non- It is published extensively that nerve fibers are glaucomatous disc such as due to multiple sclerosis if present only in the rim of the optic disc whereas full of nerve fibers though shrunken. It is hypothesized the central cupped area is devoid of neural tissue. that the end-stage glaucomatous disc being empty, was Unfortunately I have been unable to find even a single due to severance of the nerve fibers in glaucoma.” Do histology of any normal or diseased disc having this you agree? doughnut arrangement of the nerve fibers. Is the optic disc really cupping in glaucoma? If true: will it imply that someone born with 0.7 Subspecialty Connection cup would become totally blind sooner because of his/ The term cupping implies that nerve fibers are being her small rim or would take longer because the force of destroyed from central to the peripheral part of the disc raised IOP will be quickly dissipated due to larger central resulting in concentric enlargement of the physiological hole and thus the neural rim would escape injury? What cup in glaucoma. The term cupping was originally given happens to the discs in glaucoma born with no cup? by Heinrich Muller in 1856 (Duke-Elder) and since Dr. Syed Hasnain, MD, is seeking input on whether then it has become synonymous with glaucoma.We nerve fibers are really only present in the rim area of the would discuss the issue of cupping in the context of optic disc and the central cup is devoid of neural tissue. the arrangement of the nerve fibers in the retina/optic Dr. Hasnain has been unable to find histology having a disc and the sequence in which nerve fibers are being “doughnut” arrangement of nerve fibers. destroyed in glaucoma. Nerve fibers arising from the most peripheral retina lie deepest (closest to the sclera) (Ref: AAO, Community Connections, July 8, 2013 issue, and exit closest to the scleral edge, whereas the nerve with courtsey of AAO, through Dr. Syed Hasnain, MD)

Ophthalmology Update Vol. 11. No. 4, October-December 2013 231 Where the mystery of Glaucoma lies

Copy: Shields MB: Textbook of Glaucoma: Wlliams & Wilkins; 1992

Fig 1. Nerve fibers originating nearest the disc lie closer to vitreous and exit most central part of disc and those originating farthest lie deepest and exit closer to the scleral edge.

Figure 4. Right eye: Double arcuate/ring scotoma after arcuate fibers have been severed. Arcuate fibers being fewer in number compared to macular fibers, will be depleted earlier resulting in arcuate field defects.

Figure 2. Note the sinking of the disc resuting in stretching and severing of the peripheral fibers. Most Peripheral fiber (5) has been severed and disappeared and this procerss will continue until central most fiber (1) has been severed. There will be Figure 5. End-stage glaucomatous disc. Empty bean-pot/ movement of the central fibers to the periphery to occupy the crater resulting from the severance of entire nerve fibers. space created by severance of the peripheral fibers. Disc copy from Kolker AE, Hetherington Jr J. Becker-Shaffer’s diagnosis and therapy of the glaucoma, Mosby, 1976, 9146..

Figure 6. Flat disc atrophy due to multiple sclerosis. Note the Figure 3. Due to temporal sinking all the temporal fibers nerve fibers though atrophied and shrunken are still present (macular, superior and inferior arcuate) are being axotomized. in contrast to glaucomatous disc. There is no excavation of Howerver, the arcuate fibers being fewer in number will be the disc since there is no sinking and thus no severance of depleted earlier resulting in arcuate field defects as shown nerve fibers is occurring in flat disc atrophy. Disc copy from in fig.4 Yanoff, Ocular Pathology, Harper and Row 1975

232 Ophthalmology Update Vol. 11. No. 4, October-December 2013 REVIEW ARTICLE

Ideal Glaucoma Drug: How close we are?

Prof. Marianne Prof. Marianne L. Shahsuvaryan, MD, PhD, DSc (in medicine) Professor of Ophthalmology, Yerevan State Medical University Republic of Armenia

ABSTRACT Back Ground: Glaucoma is a leading cause of blindness worldwide. About 66.8 million people worldwide are afflicted with glaucoma The expected increase in longevity will mean an inevitable increase in the prevalence of glaucoma, by one-third worldwide over next decade . As a major health problem with a continuous demand for treatment the management of glaucoma has considerable economic consequences . Objective: The objective of this review is to evaluate the current ideal glaucoma drug candidates. Based on our current knowledge about glaucoma, the ideal glaucoma drug will fulfill following criteria: to be a substance that not only reduces intraocular pressure (IOP), but also possesses neuroprotective and vasoprotective characteristics, and at the same time have to have a fairly neutral effect on a patient’s quality of life. Key words: glaucoma, pressure-independent mechanisms, pressure-dependent mechanisms, neuroprotection, neurorescue.

INTRODUCTION blockers, carbonic anhydrase inhibitors8. Glaucoma is a leading cause of blindness Biologically and physically, glaucoma is character- worldwide1. About 66.8 million people worldwide ized by changes in the optic disc, optic nerve, and brain are afflicted with glaucoma2. Bilateral blindness will and by ganglion cell death9. Glaucoma is currently be present in 5.9 million people with open-angle recognized to be a multifactorial, progressive, neuro- glaucoma and 5.3 million people with angle-closure degenerative disease10, 11, causing optic neuropathy fre- glaucoma in 20201. The expected increase in longevity quently associated with elevated intraocular pressure, will mean an inevitable increase in the prevalence of ocular vascular changes and extracellular matrix re- glaucoma, by one-third worldwide over next decade[3]. modeling at the optic nerve head and in the trabecular As a major health problem with a continuous demand meshwork12. for treatment that may be medical and surgical, the The medical treatment of glaucoma has management of glaucoma has considerable economic undergone significant development in recent years. consequences4. Better knowledge of the pathogenesis of the disease For the past century glaucoma has been has opened up new therapeutical approaches. The considered a disease for which diagnosis and treatment neuroprotection and possibly neuroregeneration and was focused mainly on intraocular pressure. Because neuro enhancement is the future treatment modality11 elevated intraocular pressure (IOP) was associated look up. Based on the latest etiologic concepts , any with the development of glaucoma, and reducing IOP, therapy for glaucoma protecting retinal ganglion cells reduced the risk of visual field progression, IOP was (RGCs) from death, preventing or delaying this process considered a good surrogate for glaucoma treatment5. It and drugs which save already compromised neurons or is well established that an IOP reduction improves, on which induce regrowth of axonal/dendritic connections average, the prognosis of all types of glaucoma. It is also and restore function may be termed neuroprotective13. known, however, that even an ideal IOP does not stop Therefore, neuroprotection in glaucoma is aimed at progression in all patients6. Pathogenesis of open-angle protecting those neurons that are damaged or likely to glaucoma involves both pressure-dependent damaging be damaged in glaucomatous optic neuropathy which factors and pressure-independent damaging factors7. consists of neurons along the entire visual pathway, One of the pressure-independent factor is a primary chiefly the RGC axons. This strategy is an addition to vascular dysregulation (PVD) frequently observed in that achieved by IOP lowering alone14. normal tension glaucoma patients. An unstable blood Elevated glutamate leads to an increased inflow flow leads to recurrent mild reperfusion injury (chronic of Ca2+ into ganglion cells, which in excess can lead oxidative stress) affecting particularly the mitochondria to neuron damage. Crish and Calkins[15] investigating of the optic nerve head8. Ocular blood flow regulation neurochemical cascades in glaucoma have found can be improved by magnesium, calcium channel evidence on the pathological progression of neuro- degeneration in glaucoma and some of the Ca2+- Received: July’013 Accepted: September’2013 dependent mechanisms that could underlie these

Ophthalmology Update Vol. 11. No. 4, October-December 2013 233 Ideal Glaucoma Drug: How close we are changes. The recent findings revealed that blood flow in visual field and ocular circulation in glaucoma with the optic nerve head (ONH) is of primary importance in low-normal pressure. No topical ocular hypotensive the pathogenesis of glaucoma. The potential to modify drugs were prescribed. the blood flow in the ONH and its related structures The authors concluded that nilvadipine (2 mg has been reported in various agents, including topical twice daily) slightly slowed the visual field progression antiglaucoma drugs and systemic drugs such as calcium and maintained the optic disc rim, and the posterior channel antagonists16. It is logical then to investigate choroidal circulation increased over 3 years in calcium channel blockers in the management of patients with open-angle glaucoma with low –normal glaucoma. At the same time, topical administration intraocular pressure. In the latest clinical trial Araie 25 of calcium channel blockers has been found to have evidenced that a low dose of oral nilvadipine (4mg/ a moderate ocular hypotensive effect, with a more day) significantly decreased the rate of mean deviation consistent reduction of intraocular pressure than has deterioration in NTG patients as compared to placebo. been observed following systemic administration17. The results of these studies add to the growing Based on our current knowledge about glaucoma, the body of evidence that nilvadipine may be useful for ideal glaucoma drug will fulfill following criteria: to be a neuroprotection in glaucoma. substance that not only reduces IOP, but also possesses Lomerizine: Lomerizine dihydrochloride is a calcium neuroprotective and vasoprotective characteristics, and channel blocker with relatively selective CNS effects. at the same time have to have a fairly neutral effect on a Lomerizine was developed as a potential agent for the patient’s quality of life. The objective of this review is selective improvement of the ocular or cerebrovascular to evaluate the current ideal glaucoma drug candidates. circulation with minimal adverse cardiovascular effects. IDEAL GLAUCOMA DRUG CANDIDATES PROFILES Lomerizine have been evaluated in many experimental Nilvadipine: Nilvadipine, a calcium antagonist of and clinical studies26-29. Tamaki et al.26 investigated the the dihydropyridine class, selectively blocks calcium effects of lomerizine on the ocular tissue circulation in channels. Ogata et al18 have evaluated the effects rabbits and on the circulation in the optic nerve head of nilvadipine on retinal blood flow and concluded and choroid in healthy volunteers and have found that that this agent may directly and selectively increase lomerizine increases blood velocity, and probably blood retinal tissue blood flow, while having only minimal flow, in the optic nerve head and retina in rabbits, and effect on systemic circulation including arterial blood it also increases blood velocity in the optic nerve head pressure. Another experimental study conducted by in healthy humans, without significantly altering blood Uemura and Mizota19 have also advocated the use of pressure or heart rate. Evidences from study conducted nilvadipine for the treatment of glaucoma or other by Hara et al27 also suggested that in healthy humans, retinal diseases that have some relation to apoptosis, lomerizine increased blood velocity in the optic nerve based on claims that nilvadipine has high permeability head, without significantly altering blood pressure to retina and neuroprotective effect to retinal cells. Otori or heart rate. Moreover, lomerizine reduced retinal et al20 in the experimental study of different calcium damage in rats both in vitro and in vivo, presumably channel blockers protective effect against glutamate through a Ca(2+) channel blocking effect via an action neurotoxicity in purified retinal ganglion cells has that may involve a direct protection of retinal neurons found that nilvadipine significantly reduce glutamate- as well as an improvement in the ocular circulation. induced apoptosis. These results indicate that lomerizine may be useful as a In addition to direct effects of calcium channel therapeutic drug against ischemic retinal diseases (such blockers on intracellular concentrations of calcium ion as glaucoma and retinal vascular occlusive diseases) in ganglion cells, other indirect effect is expected such that involve a disturbance of the ocular circulation. The as increased choroidal blood flow21. Several clinical general consensus is that lomerizine do not seem to trials have shown the effectiveness of nilvadipine in affect systemic hypotension26-28. glaucoma. Yamamoto et al22, Tomita et al.23, Niwa et al.24 In the experimental study Karim et al.30 have found that nilvadipine reduces vascular resistance have found that lomerizine alleviates secondary in distal retrobulbar arteries and significantly increases degeneration of retinal ganglion cells induced by an velocity in the central retinal artery in patients with optic nerve crush injury in the rat, presumably by normal tension glaucoma. Tomita et al.24 also stated improving the impaired axoplasmic flow. The latest that reduced orbital vascular resistance after a 4-week experimental study [31] evaluated protective properties treatment with 2 mg oral nilvadipine consequently against neuronal degeneration within the dorsal lateral increases the optic disc blood flow. Koseki et.[21] al geniculate nucleus and superior colliculus in mice eyes conducted a randomized, placebo-controlled, double- evidenced that lomerizine reduces the retinal damage masked, single-center 3-year study of nilvadipine on and affords some protection against trans-synaptic

234 Ophthalmology Update Vol. 11. No. 4, October-December 2013 Ideal Glaucoma Drug: How close we are neuronal degeneration within the visual center of the evidenced that the new topical 0.05% flunarizine has a mouse brain. At present Santen Pharmaceutical has good ocular bioavailability, reaches the target tissues at lomerizine in Phase II trials to inhibit the progression effective concentrations and therefore may be used in of visual field defects32. In Conclusion, Nilvadipine and the treatment of glaucoma. Lomerizine have an interesting profile as a potential Flunarizine is also improves blood flow to the optic ideal glaucoma drug. nerve head ,due to vasodilatory properties, in patients Iganidipine: Iganidipine hydrochloride is a with low-tension glaucoma43. The latest randomized, new dihydropyridine-derivative Ca2+ antagonist33. At placebo-controlled, double blind pilot study evaluated present, due to its relative water solubility it is the only the efficacy and tolerability of topical flunarizine calcium channel blocker available as an ophthalmic on intraocular pressure in patients with open-angle solution. Evaluating the effect of topical iganidipine glaucoma (OAG) or ocular hypertension (OH) was on the impaired visual evoked potential of rabbits Oku conducted by Kaweh et al.44. The authors concluded et al.34 evidenced its usefulness for the treatment of that a single dose of 0.05% flunarizine significantly ischemic retinal and optic nerve disorders. Ishii et al.33 reduced IOP when compared with baseline values. The also in pharmacokinetic evaluation in pigmented rabbits results of this study supports usefulness of flunarizine concluded that in a 0.03% iganidipine solution reaches as a potentially useful calcium channel blocker for the ipsilateral posterior retina or retrobulbar periocular glaucoma treatment due to its neuroprotective and space by local penetration at concentrations sufficient hypotensive properties with good ocular bioavailability to act as a Ca2+ antagonist. Extrapolating to the human reaching the target tissues at effective concentrations eye, the presented results suggest the possibility that a after topical application. Ca2+ antagonist can be locally delivered to the posterior CONCLUSION parts of the eye or to the retrobulbar periocular tissues Currently, Flunarizine fulfills the ideal glaucoma at pharmacologically active concentrations by topical drug criteria, due to its neuroprotective and hypotensive instillation in humans34. The impact of iganidipine on properties with good ocular bioavailability reaching circulation of optic nerve head have been evaluated in the target tissues at effective concentrations after other experimental studies35,36. Waki et al.35 evidenced topical application, and will be a valuable weapon in that in rabbit eyes with normal and impaired ocular the fight against glaucoma. Recently study by Lorber et circulation after the instillation of 0.1% iganidipine al.45 showed that damaged retinal ganglion cells from ONH blood flow is increased. In rabbits and monkey glaucomatous rat eyes can have a regenerative capacity, eyes36 0.03% iganidipine significantly increased ONH mediated in part, by activated retinal glia. Based on blood velocity. these findings, future ideal glaucoma drug also will Neuroprotective effect of 0.03% iganidipine have to have a neuro-regenerative properties. While solution was confirmed by Ohashi et al.37. glaucoma remains a mysterious disease, there is a huge In conclusion, iganidipine may have following amount of effort being made to help us understand properties: ameliorates ocular blood flow, decreases it and new drugs are bringing us ever closer to the IOP and stabilises visual field. This drug is under management of glaucoma. continued research. REFERENCES: Flunarizine: The diphenyl-alkylamine flunarizine is 1. Quigley HA, Broman AT. The number of people with glaucoma worldwide in 2010 and 2020. Br J Ophthalmol. 2006;90(3):262-7. classified as a nonselective calcium channel antagonist. 2. Vyas P, Naik U, Gangaiah JB. Efficacy of bimatoprost 0.03% Flunarizine promotes retinal ganglion cells (RGC) in reducing intraocular pressure in patients with 360 degrees survival after optic nerve transection in mice[38]. The synechial angle-closure glaucoma: a preliminary study. Indian J neuroprotective action of flunarizine may occur partly Ophthalmol. 2011;59(1):13–16. 3. Hitchings R. Ageing population. Eurotimes, 2012;17(11),27. due to increased blood supply to the affected tissues. 4. Rahman MQ, Beard SM, Discombe R, Sharma R, Montgomery In the experimental study on the rat and rabbit retina DMI. Direct healthcare costs of glaucoma treatment. Br J Osborne et al.39 revealed topical hypotensive effect of Ophthalmol 2013;97:720-724 doi:10.1136/bjophthalmol-2012-302525 flunarizine and also neuroprotective effect on ganglion 5. Mozaffarieh M, Fraenkl S, Konieczka K, Flammer J. Targeted preventive measures and advanced approaches in personalised cells through reduced influx of calcium and sodium treatment of glaucoma neuropathy. EPMA J. 2010; 1(2): 229–235. 39 into stressed neurons . Flunarizine itself lowers IOP 6. Cybulska-Heinrich A, Mozaffarieh M, Flammer J. Value of non- when applied topically in the monkey eye40 and dogs IOP lowering therapy for glaucoma.Klin Monbl Augenheilkd. eye41. In a dose-dependent manner flunarizine reduces 2013;230(2):114-9. doi: 10.1055/s-0032-1327825. Epub 2013 Feb 21. 7. Araie M. Basic and clinical studies of pressure-independent IOP due to increase in tonographic outflow when damaging factors of open angle glaucoma. Nihon Ganka Gakkai administered to glaucomatous monkey eyes, but also Zasshi. 2011;115(3):213-36; discussion 237. has an ocular hypotensive effect on the contralateral 8. Mozaffarieh M, Flammer J.New insights in the pathogenesis and untreated eyes40. Study by Maltese and Bucolo42 has treatment of normal tension glaucoma. Curr Opin Pharmacol.

Ophthalmology Update Vol. 11. No. 4, October-December 2013 235 Ideal Glaucoma Drug: How close we are

2013;13(1):43-9. doi: 10.1016/j.coph.2012.10.001. Epub 2012 Oct 22. 27. Muñoz-Negrete FJ, Pérez-López M, Won Kim HR, Rebolleda G. 9. Chader GJ. Advances in glaucoma treatment and management: [New developments in glaucoma medical treatment]. Arch Soc neurotrophic agents. Invest Ophthalmol Vis Sci. 2012;53(5):2501-5. Esp Oftalmol. 2009;84(10):491-500. doi: 10.1167/iovs.12-9483n. 28. Ito Y., Nakamura, S., Tanaka, H., Tsuruma, K., Shimazawa, M., 10. Igras E, Loughman J,Ratzlaff M, O’Caoimh R, O’Brien C.Evidence Araie, M. ,Hara, H. Lomerizine, a Ca2+ Channel Blocker, Protects of lower macular pigment optical density in chronic open angle against Neuronal Degeneration within the Visual Center of glaucoma. Br J Ophthalmol doi:10.1136/bjophthalmol-2013-303153 the Brain after Retinal Damage in Mice. CNS Neuroscience & 11. Mowatt L, Mc Intosh M. Strategies for Neuroprotection in Therapeutics.2010; 16: 103–114. Glaucoma.Ch. from Glaucoma - Basic and Clinical Aspects, Ed. by 29. Karim Z, Sawada A, Kawakami H, et al. A new calcium channel Rumelt S. ISBN 978-953-51-1064-4, Published: April 17, 2013 antagonist, lomerizine, alleviates secondary retinal ganglion 12. Prendes MA, Harris A, Wirostko BM, Gerber AL, Siesky cell death after optic nerve injury in the rat. Curr Eye Res.2006; B.The role of transforming growth factor β in glaucoma and 31(3):273-283. the therapeutic implications. Br J Ophthalmol 2013;97:680-686 30. Kaushik S, Pandav SS, Ram J. Neuroprotection in glaucoma. J doi:10.1136/bjophthalmol-2011-301132 Postgrad Med. 2003;49(1):90-5. Review. PMID: 12865582. 13. Schmidt K-G, Bergert H, Funk R.H.W.Neurodegenerative 31. Dutton G.Ocular Therapeutics Target the Retina. Wall Street Diseases of the Retina and Potential for Protection and BioBeat , 2012 ; 32( 15) Recovery. Curr Neuropharmacol. 2008; 6(2): 164–178. doi: 32. Ishii K, Matsuo H, Fukaya Y, Tanaka S, Sakaki H, Waki M, Araie 10.2174/157015908784533851PMCID: PMC2647152 M.Iganidipine, a new water-soluble Ca2+ antagonist: ocular and 14. Vasudevan SK, Gupta V, Crowston JG.Neuroprotection in periocular penetration after instillation. glaucoma. Indian J Ophthalmol. 2011; 59(Suppl1): S102–S113. doi: 33. Invest Ophthalmol Vis Sci. 2003;44(3):1169-77. 10.4103/0301-4738.73700 PMCID: PMC3038513 34. Oku H, Sugiyama T, Kojima S, Watanabe T, Ikeda T . Improving 15. Crish SD, Calkins DJ. Neurodegeneration in Glaucoma: Progression effects of topical administration of iganidipine, a new calcium and Calcium-Dependent Intracellular Mechanisms. Neuroscience. channel blocker, on the impaired visual evoked potential after 2011; 176: 1–11. doi: 10.1016/j.neuroscience.2010.12.036 endothelin-1 injection into the vitreous body of rabbits. Curr Eye 16. Mayama C, Araie M. Effects of antiglaucoma drugs on blood flow Res.2000; 20(2):101-108. of optic nerve heads and related structures. Jpn J Ophthalmol. 35. Waki M, Sugiyama T, Watanabe N, Ogawa T, Shirahase H, Azuma 2013;57(2):133-49. doi: 10.1007/s10384-012-0220-x. Epub 2013 Jan I. Effect of topically applied iganidipine dihydrochloride, a novel 16. calcium antagonist, on optic nerve head circulation in rabbits. Jpn 17. Netland PA, Erickson KA. Calcium channel blockers in glaucoma J Ophthalmol. 2001;45(1):76-83. management. Ophthalmol Clin North Am 1995; 8:327-34. 36. Ishii K, Fukaya Y, Araie M, Tomita G. Topical administration 18. Ogata Y, Kaneko T, Kayama N, et al. Effects of nilvadipine on of iganidipine, a new water-soluble Ca2+ antagonist, increases retinal microcirculation and systemic circulation. Nippon Ganka ipsilateral optic nerve head circulation in rabbits and cynomolgus Gakkai Zasshi. 2000.;104(10):699-705. Japanese. monkeys.Curr Eye Res. 2004;29(1):67-73. 19. Uemura A, Mizota A . Retinal concentration and protective 37. Ohashi M, Saito S, Fukaya Y, Tomidokoro A, Araie M, Kashwagi effect against retinal ischemia of nilvadipine in rats. Eur J K, Suzuki Y. Ocular distribution after topical instillation and Ophthalmol.2008; 18(1):87-93. potential neuroprotective effect after intravitreal injection of the 20. Otori Y, Kusaka S, Kawasaki A, et al. Protective effect of nilvadipine calcium channel blocker iganipidine Curr Eye Res. 2005;30(4):309- against glutamate 17. 21. neurotoxicity in purified retinal ganglion cells. Brain Res.2003; 38. Eschweiler GW, Bahr M. Flunarizine enhances rat retinal ganglion 31;961(2):213-219. cell survival after axotomy. J Neurol Sci 1993; 6:34-40. 22. Koseki N, Araie M, Tomidokoro A . A placebo-controlled 3-year 39. Osborne NN, Wood JP, Cupido A, Melena J, Chidlow G.Topical study of a calcium blocker on visual field and ocular circulation flunarizine reduces IOP and protects the retina against ischemia- in glaucoma with low-normal pressure. Ophthalmology.2008; excitotoxicity. Invest Ophthalmol Vis Sci. 2002;43(5):1456-64. 115(11):2049-2057. 40. 40. Wang RF, Gagliuso DJ, Podos SM.Effect of flunarizine, a 23. Yamamoto T, Niwa Y, Kawakami H, et al. The effect of nilvadipine, calcium channel blocker, on intraocular pressure and aqueous a calcium-channel blocker, on the hemodynamics of retrobulbar humor dynamics in monkeys. J Glaucoma. 2008;17(1):73-8. doi: vessels in normal-tension glaucoma. J Glaucoma.1998; 7(5):301-305. 10.1097/IJG.0b013e318133a845 Tomita G, Niwa Y, Shinohara H, et al. Changes in optic 41. Greller AL, Hoffman AR, Liu C, Ying G , Vudathala DK, Acland nerve head blood flow and retrobular hemodynamics GM, Komromy AM. Effects of the topically applied calcium- following calcium-channel blocker treatment of normal- channelblocker flunarizine on intraocular pressurein clinically tension glaucoma. Int Ophthalmol.1999; 23(1):3-10. normal dogs.Am J Vet Res 2008;69:273–278) 24. Niwa Y, Yamamoto T, Harris A, et al. Relationship between the 42. Maltese A, Bucolo C.Pharmacokinetic profile of topical flunarizine effect of carbon dioxide inhalation or nilvadipine on orbital blood in rabbit eye and plasma. J Ocul Pharmacol Ther. 2003;19(2):171-9. flow in normal-tension glaucoma. J Glaucoma. 2000; 9(3):262-267. 43. Cellini M, Possati GL, Caramazza N, Profazio V, Caramazza R. The 24. Araie M. Neuroprotective therapy of the visual pathway in use of flunarizine in the management of low-tension glaucoma: glaucoma. European Association of Vision and Eye Research, a color Doppler study. Acta Ophthalmol Suppl. 1997.;224:57–58. Oct.2012 44. Kaweh M, Sergio Estrela S, Tarek S.Efficacy and Tolerability of 25. Tamaki Y, Araie M, Fukaya Y, et al. Effects of lomerizine, a calcium Topical 0.05% Flunarizine in Patients With Open-angle Glaucoma channel antagonist, on retinal and optic nerve head circulation in or Ocular Hypertension—A Pilot Study. J Glaucoma 2011; 20(8): rabbits and humans. Invest Ophthalmol Vis Sci. 2003; 44(11):4864- 519-522 doi: 10.1097/IJG.0b013e3181f3eb34 71. 45. Lorber B, Guidi A, Fawcett JW, Martin KR. Activated retinal glia 26. Hara H, Toriu N, Shimazawa M. Clinical potential of lomerizine, a mediated axon regeneration in experimental glaucoma. Neurobiol Ca2+ channel blocker as an anti-glaucoma drug: effects on ocular Dis. 2012;45(1):243-52. doi: 10.1016/j.nbd.2011.08.008. Epub 2011 circulation and retinal neuronal damage. Cardiovasc Drug Rev. Aug 10. 2004 Fall;22(3):199-214.

236 Ophthalmology Update Vol. 11. No. 4, October-December 2013 REVIEW ARTICLE

History of Ophthalmic Surgery & Contribution of Muslim Scholars Madiha Durrani

Ahsanzeb Durrani1, Inam ul Haq Khan FCPS2 Misbah Durrani FCPS3, Zohra Akhter. M.A.4, Zainab Inam5 Edited by: Dr. Madiha Durrani, FRCS. Ophthalmologist, Dubai UAE

ABSTRACT History: Ophthalmological diseases, mainly cataract has its own history. Hippocrates, the father of Medicine himself treated cataract by depressed or couched method. The same methodology was adopted by other Greek scholars. When Tib reached into the land of Arabia, the system derived other techniques and instruments for the management of cataract. Surgeons i.e. the Arab scholars such as Galen, Albucasis (Zahravi), Isa Bin Kahhal, Ibn Al Haithum, Avenzoar(Ibn Zohr), were known as the renowned Ophthalmologists of their time. Later on their pioneer works was translated by French scholars and other European scientists. They modernized the work of those Arab & Unani scientists, we are the followers in todays’ scenario.

INTRODUCTION Hippocrates. The knowledge of surgery is as old as is the pre- (460–377 BC), was a Greek historic man, who used to check bleeding from the physician, traditionally considered wounds in those days by pressing the two edges with as one of the most outstanding the finger or by suctioning the wound. The Edwin figures in the history as the father Smith Papyrus (1600 B.C.) was considered the earliest of medicine surgical papyrus.

Claudius Galenus (AD 129–c. 200/c. 216), known as Galen of Pergamon (modern Tur- key.) A prominent Roman physi- cian, surgeon and philosopher, ar- guably the most accomplished of all medical researchers of antiquity, Galen contributed greatly to the un- derstanding of numerous scientific disciplines, includ- ing anatomy, pathology, pharmacology and neurology including ophthalmology. He eviscerated the eye of an ape and was given the position of personal physician to several emperors. The earliest known medical document known to man. Edwin Smith was an Egyptologist who bought fragments of the document in London in 1862. In the 20th century Ibn Zuhr (Avenzoar) ‘Abū-Marwān this vastly important work was rediscovered. Dating ʻAbd al-Malik ibn Abī al-ʻAlāʼ back to 1600 BC it is our first known medical writing. Ibn Zuhr (1094–1162 CE), was an Arab-Muslim physician, surgeon. 1Computer Engineer 2Ophthalmologist 3Radiologist 4Socialologist Ibn Zuhr was known for his em- 5Student. phasis on a more rational, empiric Acknowledgement: Chief Editor and the management feel highly basis of medicine. Ibn Zuhr per- gratified to Hamdard Foundation and to M.Y. Siddiqui, Mohammad formed the first experimental tra- Mohsin and Muhammad Shoaib, Department of Moalejat, Ajmal cheostomy on a goat. He presented an accurate descrip- Khan Tibbiya College, Aligarh Muslim University, Aligarh-202001, UP, India for permitting us to take some excerpts from the original tion of the esophageal and stomach cancers. Ibn Zuhr article………… Chief Editor. introduced animal testing as an experimental method

Ophthalmology Update Vol. 11. No. 4, October-December 2013 237 History of Ophthalmic Surgery of testing surgical procedures in ophthalmology, before Antyllus, Galen, Albucasis, Isa bin Kahhal, applying them to human patients. Hunain bin-Ishaq and several other surgeons, as well Ophthalmology was one of the most important as traditional practitioners of those days, adopted area in Islamic medicine,1 and Arabs have special credit the method as well as added a lot in ophthalmologic as they performed almost all eye operations. Avicenna surgeries including lens extraction methods. The historical sketch of the treatment of cataract as was the first person to treat lachrymal fistula by probing mentioned were: and he knew the cataract was due to lens opacity.2 1. Simply depressed method or couched. This operation though followed abundantly is of great Abū Alī al-Husayn ibn Abd antiquity, having been known to the Egyptians and Allāh ibn Sīnā Indians and was probably the only one practiced Ibn Sina (Avicenna) (980-1037) up to the Christian era. was a Persian polymath, father 2. First mentioned by Galen apparently as a recent of modern medicine, who wrote invention, it may be extracted entirely. almost 450 treatises on a wide 3. The lens may be broken up and left to be absorbed. range, was one of the foremost Galen clearly described the operation, which philosophers of the golden age rightly confines to soft cataracts. of Islamic tradition that also 4. The lens may be broken up and at once removed included al-Farabi and Ibn by suction; this operation recently introduced in Rushd. He was also known as al-Sheikh al-Rais (Leader modern medicine was long practiced in Persia. among the wise men) a title that was given to him According to Al-Zahrawi it was invented there in by his students. In the west he is also known as the “Prince of Physicians” for his famous medical text al- his time (11th century). Qanun “Canon”. Muhammad ibn Zakariya The most original and significant contribution al-Razi to the anatomy of eye came from a physicist Ibn Al- (Abu Bakr Mohammad Bin Yahia Haitham (Al-Hazen); his well-known contribution Bin Zakaria Al-Razi).(865-925) was to establish a relation of optics to the anatomy of eye and his pioneer work was to create the science of Muhammad ibn Zakariya physiological optics. He gives the theory of vision in his al-Razi who was himself a treatise Kitab-ul-Manazir, and also gives the functional Persian Muslim and had special anatomy of the eye on the basis of close textual analysis inducements to study the and its detailed comparison with Galen together with treatment of cataract, attributes to such representative of Galenic tradition in Arabic as earliest mention both of extraction Hunain bin-Ishaq and Isa bin Kahhal. It will be shown and suction as indicated by Antyllus who was a Greek that Ibn Al-Haitham’s description is comprehensive. surgeon, lived in the 2nd century AD in Rome. He was

Ibn Al-Haitham: (Al-Hazen), father of optics and describer of vision theory Ibn Al-Haitham’s anatomy, in fact, represents the first effort to quantitatively define the biconvexity and the forward position of lens as well as the optical axis in strictly anatomical terms i.e. the structure of the eye. Moreover he investigated functional significance of the various parts of eye as an optical system. The contribution of Unani scholars in the field of Ophthalmology is a pioneer work dates back with the history of medicine, Hippocrates, the Father of Medicine himself was treating cataract by couching most notable for his method of treatment for aneurysms. method. In this methodology the lens is depressed in Antyllus is also said to have developed a procedure vitreous humor with the help of a couch (fine probe to extract cataracts from the eye via suction, later needle) and the same methodology was adopted by improved by Muhammad ibn Zakariya al-Razi in the several other Greeks. 10th century who was a prominent figure in Islamic

238 Ophthalmology Update Vol. 11. No. 4, October-December 2013 History of Ophthalmic Surgery

Golden Age. He was also a pioneer of ophthalmology. landmark textbook on ophthalmology in medieval Razi was the first physician to distinguish small pox Islam, for which he was known in Europe as Jesu and measles through his clinical characterization of the Occulist. two diseases. He became chief physician of Rey and Ibn ‘Isa is considered one of the most famous Baghdad Hospitals. The modern-day Razi Institute physicians of the tenth century. His famous Notebook in Tehran and Razi University in Kermanshah were of the Oculists combined information obtained from named after him both Greco-Roman and Arab sources. The book encom- Antyllus said: “some have also made an opening under passed information on treatment and classification of the pupil and have extracted the cataract, this can be over one hundred different eye diseases. In the book, done when the cataract is small, but if large it cannot eye diseases were sorted by their anatomical location. be extracted, for the aqueous humour comes out with The Notebook of the Oculists was widely used by Eu- it, and some have used a glass instrument (Concilum ropean physicians for hundreds of years. Ibn Isa’s book vitruim), have sucked out the cataract with it”3. was one of the first, along with Hunayn ibn Ishaq’s Ten Treatises on the Eye, to illustrate anatomy of the eye. Specifically, Ibn Isa illustrated the optic chiasm Abu al-Qasim 2 Khalaf ibn al-Abbas and brain. Ibn Isa was the first to describe and suggest Al-Zahrawi, Albucasis treatment for an array of diseases. For example, he was (936-1013) the first to discover the symptoms of Vogt-Koyanagi- Abu al-Qasim Khalaf ibn al- Harada Syndrome (VKH)-ocular inflammation associ- Abbas Al-Zahrawi was born near ated with a distinct whitening of the hair, eyebrows, and 3 Cordoba, Spain, when it was part eyelashes. Ibn Isa was also the first to classify epiphora of the Islamic Empire. He was a as being a result of overzealous cautery of pterygium. physician, surgeon and a chemist. In addition to this pioneering description, Ibn Isa also He is best remembered for his encyclopedia of medicine, suggested treatments for epiphora based on the stage of the Al-Tasrif li man ajaz an-il-talif (An Aid for Those the disease–namely treatment in the early stages with who lack the capacity to read big books), known as astringent materials, for example ammonia salt, burnt the al-Tasrif. This became a standard reference in copper, or lid paste and a hook dissection with a feath- 4 Islamic and European medicine for over 500 years. In ered quill for chronic stages of epiphora. Ibn Isa is also Europe, Al-Zahrawi was known as Albucasis, and was thought to be the first to describe temporal arteritis, al- particularly famous for his surgical knowledge. Al- though Sir Jonathan Hutchinson (1828–1913) was er- Zahrawi’s encyclopedia included sections on surgery, roneously credited with this. medicine, orthopedics, ophthalmology, pharmacology and nutrition. In it he described over 300 diseases and His title name Kahhal is their treatments. He also included detailed descriptions enough for his introduction as of numerous surgical procedures, and the use of over 200 ophthalmologist (kohal=Surma). surgical instruments, many of which he developed. The He was committed to ophthal- most famous section of the encyclopedia, on surgery, mology and related surgeries; he was translated into Latin by Gerard of Cremona in the performed the operation of cata- 1100s. From this time it also became a standard text in ract, lachrymal sac disorder as Europe, and was still being reprinted in 1770s. While well as pterygium and pinguec- ula etc.4. famed for his writing, Al-Zahrawi was also a prominent practitioner and teacher. In recognition of his skills, he was appointed as the court physician to King Al- Hakam II of Spain. His manuscript on surgery, divides surgery into three parts in his book viz. 1. Cauterization and vascular surgery 2. General and ophthalmic surgery 3. Treatment of fracture and dislocation Alī ibn Īsā al-Kahhal ( 1010 AD), surnamed “the oculist” (al-kahhal) was one of Islam’s most famous ophthalmologists. He was known in medieval Europe as Jesu Occulist. He was the author of the Hunain bin-Ishaq had his own independent work influential Memorandum of the Oculists He wrote the on ophthalmology; his book Kitab al-Ashr-Maqalat-

Ophthalmology Update Vol. 11. No. 4, October-December 2013 239 History of Ophthalmic Surgery fil-‘Ain includes twenty chapters on anatomy and book is the first known systematic treatment of this field physiology of the eye with proper illustrations5. and was most likely used in medical schools at the time. These men of medicine placed the practice of Throughout the book, Hunayn explains the eye and its ophthalmology to the dignified level of a profession by anatomy in minute detail; its diseases, their symptoms succeeding centuries. The knowledge of ophthalmology and their treatments. He discusses the nature of cysts thus gathered, transmitted and translated by scholars and tumors, and the swelling they cause. He discusses of France and other Europeans. They modernized the how to treat various corneal ulcers through surgery, works and finally transmitted to the modern world, and the therapy involved in treating cataracts. “Ten despite having rich experiences and works done by Treatises on Ophthalmology” demonstrates the skills Unani and Arab scholars. Hunayn ibn Ishaq was not just a translator and a physi- Moreover, Unani institutions find no separate cian, but also as a surgeon. He was a famous and in- recognition and establishment, which is more fluential Assyrian of the Islamic Abbasid Caliphate unfortunate and needs measures aimed at the revival heyday. He mastered four languages: Arabic, Syriac, of this art in the light of our grand historical record of Greek and Persian. achievements in the field of ophthalmology. (Source: Cathedra for Family Medicine, Faculty of Medicine of Sarajevo University, B&H. [email protected]) REFERENCES 1. Russell, G.A., (March-April 1402/1982). The anatomy of the eye; Ibn al-Haitham and the Galenic Tradition, Bulletin of Is- lamic Medicine, Vol. III, K.F.A.S., State of Kuwait, p. 176. 2. Shobhana Mathur and Sakait Rama Rao, G., (March-April 1402/1982). Contribution of Muslim scientists toward surgery, Bulletin of Islamic Medicine, Vol. III, K.F.A.S., State of Kuwait, p. 227. 3. Adward Theodore Withington, (1894). Medical History from the Earliest Time, The Scientific Press Ltd., 428, Strand W.C. London, pp. 92-94. 4. Hassan Grami Mohammad Hakim, (1999). Tareekh-e-Tib, 3rd Edn, Qaumi Council Baraye Faroghe Urdu Zuban, New Delhi, ’Abū Zayd Ḥunayn ibn ’Isḥāq al-‘Ibādī(809–873) p. 334. 5. Campbell, Donald, (1926). Historiography of Islam, Vol. I, p. 43. 6. Anis Ismail, Khan, A.B., (1964). Surgery in the medieval world, Indian Journal of History of Science, 19(1), pp. 64-70.

The eye according to Hunain ibn Ishaq. From a manuscript dated 1200.

’Abū Zayd Ḥunayn ibn ’Isḥāq al-‘Ibādī enriched the field of ophthalmology. His developments in the study of the human eye can be traced through his innovative book, “Ten Treatises on Ophthalmology.” This text-

240 Ophthalmology Update Vol. 11. No. 4, October-December 2013 POSTGRADUATE DIARY

How to Give Intravitreal Injections, Indications & Risk Management Adrienne W. Scott Michelle E. Wilson, BS,1 Adrienne W. Scott, MD2 Edited by :Ingrid U. Scott, MD, MPH, and Sharon Fekrat, MD Wilmer Eye Institute, The Johns Hopkins School of Medicine

INTRODUCTION be as low as 0.05 percent per injection.2 Intravitreal injection enables highly targeted drug Contraindications. Active external eye infection therapy, maximizing therapeutic drug delivery to the (including conjunctivitis, meibomianitis, and significant posterior pole while minimizing systemic toxicity. With blepharitis) is a contraindication to intravitreal injection the increasing use of intravitreal anti-VEGF agents and should be treated prior to injection. 3 Glaucoma is in the treatment of neovascular age-related macular common among patients requiring intravitreal injection degeneration (AMD), diabetic macular edema, retinal and is not a contra-indication to therapy despite the vein occlusion, and various other retinal vascular transient rise in intraocular pressure (IOP) that may disorders, intravitreal injection has become the most occur following injection. Despite the theoretical common ophthalmic procedure performed in the United increased risk of intraocular hemorrhage in patients States. This review offers practical guidance for the on long-term anticoagulation who receive intravitreal delivery of intravitreal injections based on published, injection, that risk has not been substantiated in studies. peer-reviewed literature, and expert consensus where evidence is lacking. OVERVIEW Background and indications. Intravitreal injection was first described in 1911 with the use of an air bubble to tamponade a retinal detachment. Triamcinolone acetonide (Kenalog) became the first intravitreal agent with widespread application, used as a treatment for macular edema associated with a variety of etiologies, such as diabetic retinopathy and retinal vein occlusion. It also was used as an adjunct to photodynamic therapy in the treatment of choroidal neovascularization (CNV) related to AMD. Potential complications. These include intraocular inflammation, retinal detachment or perforation, traumatic lens damage, intraocular hemorrhage, Fig 1: PATIENT PREP. The patient should 1 be instructed to direct his gaze away from sustained ocular hypertension, and hypotony. Of all the site of needle entry. postinjection complications, endophthalmitis has the greatest potential to be visually devastating. According PRE-INJECTION RISK MANAGEMENT: to studies assessing the safety profile of intravitreal We recommend the following steps: injection, the rate of endophthalmitis has been found to 1) Apply a topical anesthetic; 2) apply 5 percent or 10 percent povidone-iodine 1.Ms. Wilson is a medical student and research assistant, 2. Assistant Professor of Ophthalmology; drops and/or periocular povidone-iodine eyelid Correspondence: Dr. Adrienne W. Scott, MD, Medical Director, preparation; Wilmer at Parris-Castoro, Assistant Professor of Ophthalmology 3) insert a sterile speculum to separate the lids; and Retina Division, The Wilmer Eye Institute, The Johns Hopkins School reapply povidone-iodine immediately over the of Medicine, Johns Hopkins Hospital, 600 N. Wolfe St., Baltimore, MD 21287 > [email protected] injection site prior to injection. Local anesthetic. Nearly all injections are performed Acknowledgement: The management of Ophthalmology Update is highly gratified for permission to reprint the excerpts of the article in with local anesthesia, with topical anesthetic drops order to give a wider readership of the subjec……………Chief Editor employed most commonly. Studies show no significant

Ophthalmology Update Vol. 11. No. 4, October-December 2013 241 How to Give Intravitreal Injections, Indications & Risk Management difference in injection-related pain with the use of Needle selection. Needle size varies according topical drops, subconjunctival anesthesia, or topical to the substance injected, with 27-gauge needles often anesthetic gel. There is some concern that viscous used for crystalline substances such as triamcinolone anesthetic gel may prevent adequate sterilization of the acetonide and 30-gauge needles commonly used for ocular surface. the anti-VEGF agents ranibizumab, bevacizumab, Povidone-iodine. Povidone-iodine is the only and aflibercept. Studies suggest that smaller, sharper agent shown to decrease bacterial colonization as well needles require less force for penetration and result in as the risk of endophthalmitis. Application of povidone- less drug reflux. Some physicians have begun using iodine to the conjunctival surface, eyelids, and lashes is 31-gauge needles (the size commonly used by diabetic recommended prior to introducing the sterile speculum. patients to test blood sugar and inject insulin), as (The speculum prevents the needle tip from touching smaller needle size may decrease patient discomfort. the lids or lashes prior to needle insertion.) Studies Needle length between 0.5 and 0.62 inches (12.7 to 15.75 have found that a 5 percent povidone-iodine solution mm) is recommended, as longer needles may increase is as effective as 10 percent and is less irritating to the risk of retinal injury if the patient accidentally moves eye. There is controversy as to whether using drops or forward during the procedure. a flush is more effective. We recommend reapplication Injection site. The patient should be instructed to of povidone-iodine immediately over the injection site direct his or her gaze away from the site of needle entry prior to injection. (Fig. 1). The injection is placed 3 to 3.5 mm posterior Antibiotics. The use of pre-injection antibiotics to the limbus for an aphakic or pseudophakic eye, and is controversial. There is evidence showing decreased 3.5 to 4 mm posterior to the limbus for a phakic eye. colonization of the ocular surface with the use of pre- Injection in the inferotemporal quadrant is common, injection antibiotics, particularly in conjunction with although any quadrant may be used. Sterile ophthalmic povidone-iodine; however, there is no evidence to calipers or the hub of a sterile tuberculin syringe may suggest that the use of pre-injection antibiotics actually be used to mark the injection site and to verify that decreases the risk of endophthalmitis. Moreover, repeat adequate anesthesia has been achieved. injections are associated with more resistant flora. Injection technique. Some guidelines suggest Using a face mask. The use of a face mask for pulling the conjunctiva over the injection site with the injecting physician, injection assistants, and the forceps or a sterile cotton swab to create a steplike patient is not currently considered standard of care.4 entry path. While this approach may, in theory, However, recovery of common respiratory flora from decrease reflux and risk of infection, a straight injection vitreous culture aspirates in patients diagnosed with path is most commonly employed.6 After the sclera is endophthalmitis after intravitreal injection strongly penetrated, the needle is advanced toward the center supports efforts to minimize talking, coughing, or of the globe and the solution is gently injected into the sneezing during the injection procedure.5 midvitreous cavity. The needle is removed, and a sterile Bilateral injections. For bilateral injections, we cotton swab is immediately placed over the injection recommend separate preparation of each eye. Separate site to prevent reflux. instruments and medication vials should be used for POST-INJECTION RISK MANAGEMENT each eye to decrease the risk of potential bilateral Antibiotics. These are used by many physicians contamination. post-injection and often consist of a fourth-generation IOP rise. A transient, volume-related rise in IOP fluoroquinolone. However, as with pre-injection is common following injection. There is no evidence antibiotics, there is no evidence showing clinical benefit to suggest that prophylactic IOP-lowering agents of its use. Experimental evidence suggests insufficient are effective in preventing the post-injection volume- penetration into the vitreous to prevent infection. There mediated IOP spike, and their use is not recommended. is also an increase in resistant bacterial strains with PERI-INJECTION RISK MANAGEMENT repeated use. Injection volume. An injection volume of 0.05 mL IOP measurement. Post-injection IOP may be is most commonly used. The maximum safe volume measured, especially for patients who have glaucoma, to inject without pre-injection paracentesis is believed who are receiving large injection volumes, or who to be 0.1 mL to 0.2 mL. Larger injection volumes are complain of pain or reduced vision. Some guidelines uncommon, with two exceptions: the injection of gas recommend a funduscopic examination after each for pneumatic retinopexy and the injection of multiple injection to assess central retinal artery perfusion intravitreal agents in one session. and identify injection-related hemorrhage or retinal

242 Ophthalmology Update Vol. 11. No. 4, October-December 2013 How to Give Intravitreal Injections, Indications & Risk Management detachment. Instead, many physicians employ (vancomycin 1 mg/0.1 mL and ceftazidime 2.25 mg/0.1 functional tests such as a determination of at least mL). Urgent vitrectomy may be considered. Pseudo- counting fingers vision or assessment of absence of endophthalmitis is a sterile inflammatory reaction light perception. that does not involve true microbial infection. This Central retinal artery occlusion is indicated by the has been reported most commonly following injection absence of light perception. In this case, paracentesis is of triamcinolone acetonide and bevacizumab. Unlike indicated in an attempt to restore central retinal artery true endophthalmitis, pseudoendophthalmitis occurs perfusion immediately. Vision is typically recovered earlier, typically within one day of injection, and often quickly after decreasing IOP with rapid paracentesis. subsides without specific treatment. Routine pre- or post-injection paracentesis is not CONCLUSION: recommended for standard 0.05 mL intravitreal Follow up: After the injection, all patients should injections. be provided with information regarding the signs Complications. Transient, mild elevations of and symptoms of complications, such as eye pain or IOP are common, although IOP usually drops below discomfort, redness, photophobia, and diminished 30 mmHg 15 to 20 minutes postinjection and returns vision. Patients should be instructed to contact the to within 4 to 5 mmHg of baseline after 30 minutes. physician’s office mmediatelyi if symptoms develop. IOP normalization may take slightly longer in patients REFERENCES: with glaucoma. As noted above, endophthalmitis is 1. Jager RD et al. Retina. 2004;24(5):676-698. the most feared complication of intravitreal injection, 2. Bhavsar AR et al. Am J Ophthalmol. 2007;144(3):454-456. because of the potential for severe vision loss. If post- 3. Aiello LP et al. Retina. 2004;24(5 suppl):S3-S19. 4. Schimel AM et al. Arch Ophthalmol. 2011;129(12):1607-1609. injection endophthalmitis is suspected, recommended 5. McCannel CA. Retina. 2011;31(4):654-661. management includes immediate vitreous tap (for 6. Knecht PB et al. Retina. 2009;29(3):1175–1181. culture) and injection of intravitreal antibiotics

Eyelid Swelling and Primary Sjögren’s Syndrome Jian-Wei Zhu, M.D., and Jian-You Wang, M.D.

A 43-year-old woman with a 3-year history of frequent sleep disturbances, dry mouth, and dry eyes presented with swelling of the upper eyelids that had progressed during the previous several months. Physical examination revealed a non-tender enlargement of the lacrimal glands and submandibular salivary glands. The Schirmer’s test for tear production was positive. A salivary-gland biopsy specimen revealed lymphocytic sialadenitis. Computed tomography revealed enlarged lacrimal and salivary glands. Serologic analysis was positive for anti–extractable nuclear antigen and anti-Ro (SS-A) autoantibodies. These findings support the diagnosis of primary Sjögren’s syndrome. After the patient had been treated with prednisolone for approximately 5 months, exocrine-gland enlargement subsided and xerostomia and xerophthalmia improved. She remained free of symptoms for the next 10 months, with no recurrence of glandular enlargement. Since Sjögren’s syndrome is a systemic disorder, patients may present with variable combinations of systemic manifestations. (Courtesy: N Engl J Med 2013; 368:2501June 27, 2013)

Ophthalmology Update Vol. 11. No. 4, October-December 2013 243 PROFILE

Dr. Sameera Irfan FRCS

Being a highly devoted professional, Dr. Sameera is an ophthalmic doyenne and the pride of our country. She is currently serving as an ophthalmologist with additional expertise in oculoplastic and strabismus at Moghul Eye Trust Hospital, Lahore since 2009.

Dr. Sameera acquired her early education at in her practical life. Endowed with scholarly aptitude, Lahore and qualified MBBS from Fatima Jinnah she is deeply committed to clinical research and has Medical College, Lahore in 1987. She was adjudged published 22 original research papers in the national the 2nd best graduate with honors in Ophthalmology. and 5 clinical research papers in international journals. She started her career in Ophthalmology at Sir Ganga She has presented scientific papers, given lectures Ram Hospital Lahore as House Officer and completed and run courses not only in Pakistan but also in India, her postgraduate training in UK in 1992 and qualified UK and Germany. Moreover, she has authored 3 text FRCS., (Edin) in 1993. It is highly books on the subject of Oculoplastic, creditable of her to have cleared all Strabismus and Amblyopia. As a the examinations in her life in the first noted Ophthalmologist, she is also attempt. a member of many Ophthalmic After her post-graduation Dr. societies both locally as well as Sameera has received her specialized internationally. Currently, she has training on Oculoplastic, Paediatric started her own website offering hope Ophthalmology/Strabismus, to millions of Amblyopic patients of Glaucoma and Neuro-ophthalmology all ages around the world. at Leeds’ General Infirmary and Dr. Sameera has a singular worked as a junior Ophthalmologist credit of introducing new drug at various hospitals in UK i.e. Queen therapies i.e. cyclosporine eye drops, Mary’s Hospital, Yorkshire, North Acetyl cysteine eye drops and the Staffordshire Infirmary, Scunthorpe art of corneal tattooing. She has District Hospital and Bradford Royal ultimately returned to the homeland Informary. She has also served as Senior Registrar in after spending 18 years of her fruitful professional Sir Ganga Ram Hospital, Lahore as well as at Al-Shifa life. If you ever meet her you will find her a perfect Trust Eye Hospital, Rawalpindi. embodiment of simplicity filled with complacency Before returning to Pakistan she served as consultant and great love for the sick. She is married with two Ophthalmologist at Al-Mana Hospital, Saudi Arabia children and happily settled in Lahore. Dr. Sameera for a period of 5 years till 2005. Dr. Sameera has a great is a highly delightful lady who keeps her busy in oil predilection for post graduate teaching and is deeply painting, photography and cooking very tasty dishes involved for every minute of her life encompassing post in her leisure. The management of Ophthalmology Fellowship training program in her hospital. Gifted Update wishes her a successful career and a happy with a life of scholarship, she has achieved professional future life……………. Chief Editor eminence by dint of sheer hard work and devotion

244 Ophthalmology Update Vol. 11. No. 4, October-December 2013 PROFILE

Prof. Harminder Singh Dua, FRCS

Prof. Harminder Singh Dua, FRCS, FRCOphth., including the Oxford Ophthalmological Congress FEBO, MD, PhD., is the Chairperson and Professor of Founders’ Cup, the Ian Fraser prize, the Julia Duane Ophthalmology & Visual Sciences, University of Not- Scholarship, Spencer Walker Prize, and 18 eponymous tingham. Formerly, he was associate professor at the lectures including the Duke Elder Lecture at the Royal Thomas Jefferson University, Philadelphia, USA. Pro- College of Ophthalmologists Annual Congress in 2005. fessor Dua’s clinical subspecialty interest is in ocular He was on three international panels convened to draw surface/cornea and refractive surgery, and his research up guidelines for the diagnosis and management of oc- interests are in ocular immunology and ocular surface ular surface problems like Blepharitis and Conjunctivi- diseases. He holds membership to various national and tis (International Ocular Inflammation Society) and Dry international councils, board of governors and adviso- Eye (Delphi panel, Baltimore). He has been endowed ry panels including the Royal College of Ophthalmolo- with honorary life membership of two international gists as one of the Vice Presidents academic societies. and chairman of education, Oxford His recent awards include Ophthalmological Congress, the the achievement award for distin- Iris Fund, Fight for Sight, Medi- guished services, by the American cal Research Council (UK), Sight Academy of Ophthalmology (Octo- Savers International, International ber 2010); the His Royal Highness Ocular Surface Society, and the Eye Prince Abdulaziz Al Saud Preven- Research Institute (Philadelphia). tion of Blindness Shield and Gold He is currently Editor-in-Chief medal lecture by the Ophthalmo- of the British Journal of Ophthal- logical society of South Africa. On mology and President of EuCornea, 13 November 2010, the Times news- (the European society of Cornea paper, UK, published a roll of Brit- and Ocular surface diseases) He is ain’s top doctors and Prof. Dua also the President of the European was one of five ophthalmologists Association for Vision and Eye Re- named in this list. search (EVER) Foundation (EVERF) The cornea and external eye and past President of EVER. He was disease service at Nottingham was recently elected to the distinguished chair of Academia established under his auspices in 1994 and is now a Ophthalmologica Internationalis and has been invited leading British national centre, especially for ocular to join as member of the American Ophthalmological surface diseases, attracting tertiary referrals from all Society by thesis. He was elected to the prestigious over the country and abroad. To complement and aug- post of President of the Royal College of Ophthalmolo- ment this service to patients, he established the first gists, United Kingdom with effect from 25th May 2011. national ocular surface tissue laboratory, sponsored He has over 200 research publications and 14 by Nottingham West Lions Club, at the Queens Medi- book chapters to his credit. He has been invited to sev- cal Centre, Nottingham. This has now been upgraded eral international conferences and meetings worldwide into a trust based clinical tissue laboratory to provide as a speaker or chairman of scientific sessions, both processed stem cells and tissue constructs for patient clinical and basic sciences, related to the sub-speciality management. The facility was commissioned in 2008 of cornea and ocular surface. and is accredited by the Human Tissue Authority, UK. He has received several awards for his research ………………...... Chief Editor

Ophthalmology Update Vol. 11. No. 4, October-December 2013 245 Some National Birds of SAARC Countries

Chakor (Pakistan) Peafowl Peacock (India)

Magpie Robin (Bangladesh) Raven or Doel (Bhutan)

Himalayan Monal (Nepal) Srilankan Junglefowl (Srilanka)

246 Ophthalmology Update Vol. 11. No. 4, October-December 2013 Some National Flowers of SAARC Countries

Tulip (Afghanistan) Jasmine (Pakistan)

Lotus (Bangladesh) White Water Lily (Bangladesh)

Lali Gurans’ in the Nepalilanguage (Nepal) Bhutan (Blue Poppy)

Maldives (Pink Rose) Blue water Lily (Sri Lanka)

Ophthalmology Update Vol. 11. No. 4, October-December 2013 247 Tourism in Islamabad

Tourist form SAARC Countries: from L to R: Rageshwari, Shruti Seth, Dolly Thakur, Manju Lodha and Sangeeta Jindal Participating artists. Women Art Foundation, art lovers,

248 Ophthalmology Update Vol. 11. No. 4, October-December 2013 Various Varieties of Roses in Pakistan

Ophthalmology Update Vol. 11. No. 4, October-December 2013 249 Ophthalmology Notebook News, views, letters and events

Medicinal Value of Fruits Healthier Eating for Sight MANGO Prevention of AMD & Cataract A SEASONAL DELIGHT WITH HEAVENLY TASTE According to the Academy of Nutrition & Dietic’s, Zainab Inam. Nowshera following foods can help promote healthier eyes: 1. Kale: (A kind of cabbage - (band ghobi) protects There is something for which the summer is against cataract in cases of ultra violet exposure loved and anxiously awaited and that is Mango, the and Macular Degeneration. king of all fruits. You can hear the bird koel singing coo 2. Sweet Potatoes: Rich in beta carotene and may coo, only when the mango tree blossoms on the arrival help in thwarting Macular Degeneration. of spring. Who can resist the sweet and delicious taste 3. Strawberries: Rich in Vit. C helps in protecting of mango, its fragrance that fills the air and the very against cataract. thought of it waters our mouth. 4. Salmon Fish: Rich in Omega 3, loaded with The name Mango has been derived from the antioxidants may help in protecting both against Tamil word (Indian origin) Mangkay. It is the national Cataract and Macular Degeneration. fruit of Pakistan, India and Philippine and it is the 2nd major fruit crop in our country, is reckoned fourth in the world in terms of production. Most popular varieties of mango in Pakistan are sindhri, chaunsa, anwar Ratole, langra, summer Congratulation bahisht (paradise), Dusehri, neelam, fagli, salem and almas etc etc., Mangoes are full of nutrients and is excellent source of Vit. A, B, & C, proteins, sugar, fats, fiber, rich source of iron, potassium and anti-oxidants. Prof. Khalid Iqbal Talpur elevated as Chairman Sindh Institute of Ophthalmology and Visual Sciences. A normal size mango contains 60 calories of energy Hyderabad with no cholesterol. Total fats are 0.6 gm. Mangoes Government of Sindh has recently elevated Prof. are commonly used in ice creams, milk shakes and is Khalid Iqbal Talpur to the coveted position of chair- processed into jams, juices, chatney and murraba. The man of newly established Sindh Institute of Ophthal- latter is popularly used by patients for instant energy. mology and Visual Sciences by upgrading Liaquat Uni- The raw mangoes are also used for making pickles and versity Eye Hospital, Hyderabad. It speaks volumes of dried mango powder known as amchur, commonly his dedication and devotion to achieve professional ex- used as a recipe in preparing our meals. The mango cellence as an experienced academician. We hope that tree plays has a sacred role in a neighboring country the general public will get high quality of ophthalmic and is termed as a symbol of love for the newly wedded care and above all our budding ophthalmologists will couple. Its fresh leaves are hanged out at the front door get a conducive environment to high quality training as a sign of blessing to the inmates. and research as well. There is a popular myth that the mangoes are The management and the editorial board of fattening therefore the weight-conscious people avoid Ophthalmology Update congratulates him and wishes taking mangoes. Since it is acidic in nature, people him a successful career. May Allah bless him enough prefer to take them it with liquified milk -kachi lassi. strength and vigor to continue serving the nation and The fruit is presented to friendly head of states as a ameliorating the sufferings of humanity to his best. gesture of love and good wishes. Amin!...... Chief Editor

250 Ophthalmology Update Vol. 11. No. 4, October-December 2013 Dear Prof. Durrani Thanks a lot for your kind and encouraging reply. From my little experience around the world I found that we Pakistanis are very hardworking but lack in documentation and publishing their work. The teachers like you are the inspiration to us who are doing great work by encouraging the new comers like me into the field. Kind Regards

Dr Shabana Chaudhry, FRCS, FCPS Fellowship in Paediatic Ophthalmology & Strabismus Lahore

Dear Prof. Durrani I have just read the new issue (July-Sep’2013) of Ophthalmology Update with great interest and I am again impressed by whole content of your journal starting from your editorial. I admire your brilliant Editorship! I also express my deep gratitude to you for publication of my paper. I have just finished my new paper, for the special edition at SAARC countries meeting in Oct’2013. With many thanks for your continued kind cooperation. Wishing you further successful editorship and prosperity, Warmest regards

Prof. Marianne L. Shahsuvaryan MD, PhD, DSc.(Medicine) Professor of Ophthalmology Yerevan State Medical University Republic of Armenia Letters to the Editor Dear Prof. Durrani Dear Prof. Durrani I hope you and your family are in best of health. I Thanks for July-Sep 2013 issue of Ophthalmology wanted to share good news with you. American update. Actually I would like to add that Ophtec phakic Academy has mailed my hypothesis to all its about IOLs in spherical as well as toric powers are available 30000 members couple of days ago. I had put my with Al-Ain International Specialist Eye Hospital, question on Academy’s forum “ Are the nerve fibers G-10/3, Islamabad. As a refractive surgeon using these being atrophied or severed in chronic glaucoma” which on a regular basis with superb results. Besides that I am this time Academy considered it and has mailed to all implanting INTACs in clinically significant Keratoconus its members. I am attaching the copy of their letter. I patients, as well as using Fugo Plasma Technology for am very thankful to Allah that Academy is now paying Microtrack Glaucoma Filtration, Scleroplasty or RSFO attention to my hypothesis. As you know that the nerve (retro-sclero-filling operation) in order to halt myopia fibers being severed, not atrophied is the nutshell of my in young high myopes as well as to improve choroidal/ theory. Now ophthalmologists have the choice between retinal circulation in such patients. Regards sinking disc or 150 -years old cupping theory. Dr Irfan ullah Kundi, MRCOphth., FRCS Dr. Syed S. Hasnain M.D. Al-Ain International Specialist Eye Hospital General Ophthalmology, Porterville, CA 93257 G-10/3, Islamabad. Phone: 0092 512298715 Email: [email protected] Irfan Kundi> [email protected]

Ophthalmology Update Vol. 11. No. 4, October-December 2013 251 Instructions to the authors

Instructions to the Authors

All materials submitted for publication should be Abstract: Abstract of original article should be in sent to the journal ‘Ophthalmology Update’. Articles/ structured format with the following sub-headings: research papers which have already been published Objective, Design, Place and duration of Study, Patients or accepted elsewhere for publication should not be & Methods, Result and Conclusion. submitted. A paper that has been presented at a scientific Introduction: This should include the purpose of meeting, if not published in full in proceeding or similar the article. The rationale for the study or observation publication may be submitted. Press reports of meetings should be summarized. will not be considered as breach of this rule. Methods: Study design and sampling methods Ethical Aspects: If articles, tables, illustrations or should be mentioned. The selection of the observational photographs, which have already been published, are or experimental subjects (patients or experimental included, a letter of permission for republication (or animals, including controls) should be described clearly. its excerpts) should be obtained from the author(s) as The methods and the apparatus used should be identified well as the editor of the journal where it was previously and procedures described in sufficient details to allow published. other workers to reproduce the results and references Material for Publication: The material submitted to established methods. All drugs and chemicals used for publication may be in the form of original research, a should be identified precisely, including generic names, review article, short communications, a case report, recent doses, routes of administration. advances, new techniques, review on clinical/medical/ Results: These should be presented in a logical ophthalmic education, a letter to the editor, medical quiz, sequence in the text, tables and illustrations. Only Ophthalmic highlights/update, news and views related important observations should be emphasized or to the field of medical sciences. Editorials are written by summarized. invitation. Report on Ophthalmic obituaries should be Discussion: The author’s comments on the result, concise. Author should keep one copy of the manuscript supported with contemporary references, including for reference, and send three copies (laser or inkjet) to arguments and analysis of identical work done by others. the Managing Editor, Ophthalmology Update through Brief acknowledgement may be made at the end. E-mail/CD or by post in MS word. Photocopies are not Conclusion: Conclusion should be provided under accepted. Any illustrations or photographs should also separate heading and highlighting new aspects arising be sent in duplicate. Authors from outside Pakistan can from the study. It should be in accordance with the also e-mail their manuscript. It should include a title study. page, E-mail address, fax and phone numbers of the Copyright: Material printed in this journal is the corresponding author. There should be no more than 40 copyright of the publisher of Ophthalmic Newsnet/ references in an original/review article. If prepared on Ophthalmology Update and may not be reproduced computer, a CD should be sent with the manuscript. without the permission of the editor/publisher. Dissertation/Thesis Based Article: An article based The publisher only accepts the original material for on dissertation submitted as part of the requirement publication with the understanding that except for for a Fellowship can be sent for publication after it has abstracts, no part of the data has yet been published been approved by the relevant institution. Dissertation or will be submitted for publication elsewhere before based article should be re-written in accordance with the appearing in the journal. The Editorial Board makes instructions to authors. every effort to ensure the accuracy and authenticity of References: References should be numbered in the material printed in the journal. However, conclusions the order in which they are called in the text. At the and statements expressed are the views of the authors end of the article, the full list of references should give and do not necessarily reflect the opinions of the the names and initials of all authors in Vancouver style Editorial Board. Publishing of advertising material does based on the format used by the NLM in Index Medicus. not imply an endorsement by the Ophthlmic Newsnet / It verify the references against the original documents Ophthalmology Update. before submitting the article. Address for Correspondence: The Chief Editor, Peer Review: Every paper will be read by at least Ophthalmology Update, 267-A, St: 53, F-10/4, Islamabad, two staff editors of the editorial board. The paper selected Pakistan. E-mail: [email protected] will then be sent to one or more external viewers.