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Orbit and Oculoplasty - I Comparative Study of Probing Vs Probing with Intubation for Naso Lacrimal Obstruction in Children------713 Dr. Shreya Shah, Dr. Prerana Shah, Dr. Nirav Patel, Dr. Amisha Jain Should We Perform Levator Resection in Congenital Ptosis Patients with Poor Levator Function------718 Dr. Adit Gupta, Dr. Tarjani Dave, Dr. Milind Naik Lamellar Icthyosis: A Chronic Struggle------723 Dr. Pratheeba Devi J, Dr. Nirmala Subramanian, Dr. Nivean M Adult Onset Xanthogranulomatosis with Massive Involvement of all Four Eyelids------728 Dr. Ravindra Mohan E, Dr. Arthi Dwarakanath Corneal Topography and Higher order Aberrations in Blepharoptosis-731 Dr. Rath Suryasnata, Dr. Sujata Das, Dr. Kapil Arunkumar Bhatia Correction of Lagophthalmos with Modified Full-Thickness Upper Lid Blepharotomy and Lower Lid Lift------742 Dr. Roshmi Gupta Intravenous Methylprednisolone in Moderate to Severe Thyroid Associated Orbitopathy (TAO) in Indians------746 Dr. Shweta Gupta, Dr. Usha Singh, Dr. Manpreet Singh, Dr. Zoramthara Are Frozen Section Margin Control and Conjunctival Map Biopsy Mandated in Sebaceous Gland Carcinoma of the Eyelid?------755 Dr. Fairooz PM, Dr. Santosh G Honavar, Dr. Vemuganti Geeta Kashyap Neoadjuvant Systemic Chemotherapy in the Management of Eyelid Sebaceous Gland Carcinoma------766 Dr. Swathi Kaliki, Dr. Anuradha Ayyar, Dr. Tarjani Dave, Dr. Milind Naik Orbit and Oculoplasty Free Papers

Orbit and Oculoplasty - I Chairman: Dr. Gupta V P l Co-Chairman: Dr. Sujatha Y Convenor: Prof. Dr. Ravindra Mohan E l Moderator: Dr. Poonam Jain

Comparative Study of Probing Vs Probing with Intubation for Naso Lacrimal Obstruction in Children Dr. Shreya Shah, Dr. Prerana Shah, Dr. Nirav Patel, Dr. Amisha Jain ongenital NLD obstruction is the most common cause of epiphora in Cchildren. The most common location is at the opening of NLD system because of imperforate valve of Hasner.1 Other causes of obstruction may be atypical in the NLD to end, within the bony nasal lacrimal canal, in the wall of maxillary sinus or below the inferior turbinate. Chronic epiphora must be carefully evaluated to rule out other causes of lacrimation such as conjunctivitis, punctual occlusion, canalicular stenosis, amniotocele, dacryoocystocele, epiblepharon, entropion, or ectropion. Congenital glaucoma is usually associated with photophobia and excess 713 lacrimation. Embryologically, the lacrimal system proceeds from proximal to distal and 30% of full term newborns present with an imperforate valve of Hasner2 Most infants undergo spontaneous valve opening by age 6 weeks, but the remaining 10% may require probing of the nasolacrimal system. Probing is known modality of treatment as far as NLD obstruction in children are concernedrecurrence of NLD obstruction is also very common, particularly if the age is above one year. If conservative treatment does not relieve symptoms of tearing due to nasolacrimal obstruction, probing may be indicated between 6 and 13 months of age. Intubation can give result in failure cases

Materials and methods A prospective interventional study was conducted at Drashti Netralaya, Dahod. All pediatric patients with congenital NLD obstructions are included in the study. All patients with reason of excess lacrimation other than NLD obstruction., acquired NLD block, trauma to lacrimal passages and high risk for general anesthesia were excluded from the study. 73rd AIOC 2015, New Delhi

Instruments used during the procedure are lacrimal probing instruments include a punctual dilator, Bowman probes, Lacrimal irrigation cannula, Irrigation tip, BSS-filled syringe, Lacrimal intubation system (Crawford silicone stent set 28-0185, jedmed Instrument Company, St. Louis, Mo.) Retrieval hook to Silastic intubation tube (supplied with the lacrimal intubation set). We recommend general endotracheal anesthesia for children during nasolacrimal probing. Mask anesthesia can be used when the silastic tube is removed. After induction of general anesthesia, neurosurgical cottonoids moistened with oxymetazoline hydrochloride 0.05% (Afrin spray) are placed medial and lateral to the inferior turbinate. The cottonoids are removed after 5–10 min. We perform the probing first through the upper canaliculus and then through the lower canaliculus. Surgical procedure The length of the Bowman probe is measured prior to using the dilator in order to assess length of passage through the nasolacrimal canal or nose, repectively. The upper canaliculus is dilated carefully with a blunt punctual dilator 714 for a distance of 2 mm. The punctal dilator is withdrawn and a no. 0 or 1 Bowman probe is passed immediately after withdrawal of the punctual dilator vertically for 2 mm and then reoriented horizontally. Little resistance is felt when passing the probe into the nose. You may feel a rubbery resistance or “pop” when passing through the valve of Hasner. The probe is passed 18–20 mm in children before entering the nose through the obstructed site typically at the valve of Hasner. The probe may be identified into the nares either by direct or endoscopic visualization or palpated with a periosteal elevator. Medial infracture or displacement of the inferior turbinate may be necessary if the turbinate prevents visualization of the inferior meatus and the probe within it. Prior to passing the Crawford probe and tube, the Bowman probe is passed through the nasolacrimal duct before passing the stent in order to define the anatomy of the passage and direction of the probe. This will define the length of the tube required to the probe through the ostium of the duct and into the nares. The Crawford metal probes are thinner and more difficult to pass than the firm Bowman probe. The olive tips are placed first through the upper canalicular and nasolacrimal duct, and then the lower canaliculus. They may be received with the Crawford hook or small haemostat. Orbit and Oculoplasty Free Papers

Figure 1: age wise distribution of all Figure 2: age wise distribution of patients patients participating in study who underwent probing with and without stent

Once both stents have been passed into the nose, proper positioning of the loop of silastic tubing within the eye should be evaluated in the eye. The metallic probes are pulled off or cut off. The loose tubing is pulled anteriorly using needle holders and, four more knots are completed preferably tying the knots over a no. 1 Bowman probe. The tied tubes are then allowed to retract into the nose. Observe for intranasal bleeding at this time. Prior to extubation, if bleeding is noted, gently pack the nose with a narrow merocel dampened with xylocaine and epinephrine (Figure). Post-op care 715 Topical Antibiotics combined with steroid if no infection,systemic antibiotics,nasal decongestants Tube removal Generally, the tube is left in place for at least 6 months after intubation and once symptoms are stable.4 If there is unroofing or stretching of the canaliculus, earlier removal may be considered. After 3–6 months, the tube can be removed .It can sometimes be done in the office but in most instances requires mask anesthesia in the operating room. An antibiotic/steroid eye drop four times daily is recommended for 10 days after removal of the tube. All data were filled up in pretested online format during first visit and follow up visits, all data from the system exported in to excel sheet and data analyzed with SPSS-15 software. Analyses done with cross tabulation and for Pearson’s x2 test used for significance as well as Anova used for comparative study.

Results Out of 117 enrolled patients, 82 underwent probing only and 35 underwent probing along with monocanalicular or bicanalicular intubation. 73rd AIOC 2015, New Delhi

Table 1: Age and Sex Distribution Sex Total F M F AGE 0 TO 0.5 28 23 51 0.6 TO 1 9 10 19 1.1 TO 3 12 17 29 >3 6 12 18 Total 55 62 117

Table 2: Distribution of Procedures Number (n) Percentage (%) Probing+intubation 35 29.9 Probing only 82 70.1

Table 3: Type of Intubation Intubation Number(n) Percentage (%) Silicone bicanalicular 29 82.85 Silicone monocanalicular 6 17.15 Total 35 100

716 Table 4: Comparative study with and without Intubation Variable Intubation No Intubation P Watering Yes 08 02 0.000 No 27 41 No Follow Up 00 39 Total 35 82 Discharge Yes 00 20 0.000 No 35 23 No Follow Up 00 39 Total 35 82 Swelling Yes 00 09 0.000 No 35 34 No Follow Up 00 39 Total 35 82 Age Category 0 To 0.5 03 48 0.000 0.6 To 1 03 16 1.1 To 3 14 15 >3 15 03 Follow Up 0 To 50 02 00 0.000 Duration 51 To 100 07 82 (Days) 101 To 300 26 00 35 82 Orbit and Oculoplasty Free Papers

There was significant difference in outcome in patients undergoing probing with and without intubation and it is not dependent on age of presentation and duration of follow up.

Discussion Out of 117 enrolled patients, 82 underwent probing only and 35 underwent probing along with monocanalicular or bicanalicular intubation. When we have compared our results with other studies Frick et. al. reported. The relative cost-effectiveness of these strategies for treatment of nasolacrimal duct obstruction depends on the spontaneous resolution rate after diagnosis. Our studies did not include cases of spontaneous resolution. Repka et. al. reported Both balloon catheter dilation and nasolacrimal duct intubation alleviate the clinical signs of persistent nasolacrimal duct obstruction in a similar percentage of patients. Our studies reported success of all cases. Miller et. al. reported Performing nasolacrimal duct probing in the office successfully treats NLDO in the majority of cases in children aged 6 to <15 months. Our study has included patients upto age of 5 years, The success rate is lower with bilateral disease or when more than one clinical sign of NLDO is present. 717

Conclusion Probing with intubation is very successful treatment particularly in children above one year where the probing often fails. In our data the success rate for intubation is 100%.

References 1. Crawford JS: Intubation in the lacrimalsystem. Can J Ophthalmol 1977;12:289-92. 2. Bedrossian EJ Jr: The lacrimal system. In: Tasman W, Jaeger E (eds). Duane’s foundation of clinical ophthalmology, 1996;1:179-87. 3. Katowitz JA, Welsh MG: Timing of initial probing and irrigation in congenital nasolacrimal duct obstruction. Ophthalmology 1987;94:698–704. 4. Welsh MG, Katowitz JA: Timing of silastic tubing removal after intubation for congenital nasolacrimal duct obstruction. Ophthalmol Plast Reconstr Surg. 1989; 5:43-8. 5. Frick KD, Hariharan L, Repka MX, Chandler D, Melia BM, Beck RW; Pediatric Eye Disease Investigator Group (PEDIG). Cost-effectiveness of 2 approaches to managing nasolacrimal duct obstruction in infants: the importance of the spontaneous resolution rate. Arch Ophthalmol. 2011;129:603-9. doi: 10.1001/ archophthalmol.2011.80. 73rd AIOC 2015, New Delhi

6. Repka MX, Chandler DL, Holmes JM, Hoover DL, Morse CL, Schloff S, Silbert DI, Tien DR; Pediatric Eye Disease Investigator Group.Balloon catheter dilation and nasolacrimal duct intubation for treatment of nasolacrimal duct obstruction after failed probing. Arch Ophthalmol. 2009;127:633-9. do10.1001/ archophthalmol.2009.66. 7 Miller AM, Chandler DL, Repka MX, Hoover DL, Lee KA, Melia M et. al. Office probing for treatment of nasolacrimal duct obstruction in infants. J AAPOS. 2014;18:26-30. doi: 10.1016/j.jaapos.2013.10.016.

Should We Perform Levator Resection in Congenital Ptosis Patients with Poor Levator Function Dr. Adit Gupta, Dr. Tarjani Dave, Dr. Milind Naik ongenital ptosis results from abnormal development of the levator Cmuscle, which is usually fibrosed or replaced by fat or areolar tissue.1 Primary congenital ptosis is usually non-progressive, and if severe, can be associated with amblyopia.2 The excursion of the upper lid depends on the 718 action of the levator muscle and hence the severity of the ptosis is inversely proportional to the levator function. Levator function is traditionally defined as ‘poor’ when it measures 4 mm or less, and is commensurate with severe congenital ptosis. Severe congenital ptosis has been traditionally managed with frontalis sling surgery.3 There are only few studies describing levator resection surgery for the correction of severe congenital ptosis. The purpose of this study is to report the outcomes of levator resection in cases of severe congenital ptosis with poor levator function.

Materials and Methods This retrospective, interventional study was performed at LV Prasad Eye Institute, Hyderabad, India. All patients with unilateral primary congenital ptosis and poor levator function (<5 mm) who underwent LPSR surgery were enrolled. Exclusion criteria included poor Bells phenomenon, LPS function 5 or greater, neurogenic or myogenic ptosis. All patients were managed from January 2009 to December 2013. The patient medical record was evaluated for medical history and detailed ocular examination. Data pertinent to ptosis included ocular movements, pupillary reaction, corneal sensation, lagophthalmos, Bell’s phenomenon, and synkinesis such as the presence of Marcus Gunn Jaw-winking ptosis. Ocular parameters measured during the preoperative and postoperative evaluations were: a) Vertical Orbit and Oculoplasty Free Papers

palpebral fissure width (distance in mm between the central upper and lower lid margin with the eyes in the primary position of gaze), b) MRD- 1 (distance in mm between a light reflex on the cornea and the upper lid margin in primary gaze), (3) Levator function (lid excursion from downgaze to upgaze while immobilizing the frontalis muscle), and (4) Lagophthalmos- (distance in mm between the centre of the upper lid to the lower lid when the patient was asked to close the lids). Each patient underwent routine postoperative follow-up evaluations until stabilization of eyelid height was observed. During the postoperative evaluation, ocular parameters were examined and recorded. Exposure keratopathy was graded according to involvement of the cornea by fluorescein staining. Each complication was recorded and evaluated at each clinic visit. All the patients had detailed systemic evaluation to rule out secondary cause of the ptosis. Surgical Technique All the patients were operated by a single surgeon (MN) under general/local anesthesia depending on the age of the patient. Eyelid crease was marked to match the other eye with a fine tipped surgical marker. Skin incision was placed, and orbicularis was incised using the radio frequency monopolar cautery to expose the anterior surface of the tarsus. Dissection was carried out superiorly to isolate the levator aponeurosis by releasing the septum, and dissecting in the sub-levator plane. The superior dissection was carried 719 out till the Whitnall’s ligament. The cardinal sutures were placed with 6-0 prolene suture. The central cardinal suture was placed first, extending from the mid-tarsal partial thickness bite towards the levator aponeurosis. The pass on the levator was adjusted to achieve the desired lid height as per Berke’s rule. In most cases, the eyelid was left at the superior limbus. The lateral and medial cardinal sutures were then passed to adjust the contour of the lid comparing with the other eye. Lid crease forming sutures were passed via the aponeurosis to the sub-dermis with 6-0 polyglactin suture. Skin was closed with 6-0 prolene suture. The lateral and medial levator horns were not severed. Face photographs of all patients were taken at pre-operative and each post- operative visit. Images were taken in a standardized manner with a Nikon D2X Digital SLR Camera with indirect lighting from a distance of 45 cms. All the images were uniformly cropped to include Trichion to Menton vertically and tragus to tragus horizontally. Image size was 6 inches (height) by 4.5 inches (width), stored at 300 dpi in TIFF format. Patient’s pre-operative and final postoperative photograph was aligned side-by-side in a collage. A code number (Between 1-26) was randomly assigned to the face photographs. Two physicians were asked to evaluate the surgical outcome using the following visual grading scale: 73rd AIOC 2015, New Delhi

Perfect symmetry: Operated eyelid exactly matches the height and contour of other eye. Mild under correction: Less than 2 mm difference between the operated eyelid and normal eye. Moderate under correction: More than 2 mm difference between the operated eyelid and normal eye No benefit: Operated eyelid looks similar to the preoperative picture Assessed clinical parameters, and the cosmetic outcome were analyzed.

Results The study included 26 patients with unilateral congenital ptosis of which 17 (64.38%) were males. Mean age at presentation was 16.07±9.05 years (range 4-33 yrs). Right eye was involved in 11 (42%) cases. The mean LPS action was 3.84%0.88 mm (range 2-5 mm). The clinical details of each case have been enlisted in Table 1. Functional success was noted in 23 eyes (88.4%) eyes. The mean follow-up duration was 7.84±7.95 months (3-36 months). At the final follow-up, objective grading of the cosmetic correction by two independent physicians reported 12 cases with perfect symmetry, 6 with mild under correction, 4 with moderate under correction, and 4 with no benefit. The 720 mean lagophthalmos was 2.07±1.62 mm at the 6 week postoperative visit which reduced to 1.15±1.07 mm at the last follow-up visit. Complications were noted in 5 cases (19.23%), which included exposure keratopathy in 4, microbial keratitis in 2, and contour abnormality in 1 case.

Discussion Many surgical procedures with modifications have been devised for the management of severe congenital ptosis. Although a lot of them are indeed successful in clearing the visual axes and providing functional success, but as we evolve surgically, we also need to take into account the aesthetic value associated with these procedures. Hence surgical management of severe congenital ptosis remains a point of debate. Frontalis sling suspension has been considered as the procedure of choice for people with severe congenital ptosis with a poor levator function.3 Various materials, such as silicon sticks, mersilene nets, nylon thread, lyophilized or autologous fascia lata have been tried in the past.3,6 Fascia lata has been shown to provide the best outcomes although the harvesting of well-tolerated autologous fascia lata is difficult and often yields insufficient material, especially in small children. Also a short lasting effect of these techniques combined with the complications associated like granuloma formation and suture extrusion don’t make it the most ideal technique for Orbit and Oculoplasty Free Papers

these cases.7 Further disadvantages are the asymmetry induced in facial appearance and the brow position in unilateral cases that we are dealing with in our study. Frontalis suspension flaps have also been described as an alternative to suspension material in severe congenital ptosis but they also have their own associated problems including extensive soft tissue dissection and the distortion of the normal anatomy making resurgery almost impossible.8,9 In contrast, transcutaneous levator resection provides a good alternative to sling if performed meticulously. There are a few studies in literature, which have supported this concept but it still has failed to gained popularity due to the fear of exposure keratopathy and the lagophthalmos induced. Beard was the first to recommend the maximal levator resection in 1976, with the restriction that it be performed from 3 years of age upwards, when an adequate examination of the child is possible.10 Epstein et. al., described the super-maximum levator resection as one surgical approach for the correction of severe blepharoptosis with poor levator function in 1984 wherein they demonstrated a cosmetically acceptable result in 75% of their cases.11 Later the same group modified their technique and added a superior tarsectomy in addition to levator resection in 18 cases to further propagate this technique and take care of the under correction associated with it.12 721 Anderson et. al., used the Whitnall’s sling for severe ptosis and concluded it to be a good alternative to frontalis suspension in patient with levator function between 3-5 mm. They reported an incidence of 30.7% of under correction over a 1-year follow-up in a series of 69 ptotic eyelids that were corrected with maximum levator aponeurosis resection (Whitnall’s sling) without tarsectomy.13 In our series where we did a photographic evaluation of the pre and the postoperative photos, we found a functional success in 23 eyes (88%). Good cosmesis was seen in 12 cases and acceptable cosmesis was noted in 10 cases. Acceptable cosmesis was defined as a good lid fold with the upper lid position within 2 mm of the contralateral lid position. The main advantage, which this procedure offers, is the lid fold, which can be adjusted according to the contralateral lid giving good symmetry and cosmesis to the face. The main concerns that are associated while using this technique are the risk of exposure keratopathy and the lagophthalmos induced due to tightening of the muscle. We had 8 cases with signs of exposure keratopathy ranging from few superficial punctate lesions to epithelial defect and microbial keratitis. 3 of these patients needed reversal of the procedure to prevent further damage to the cornea. Remaining 5 patients could be managed 73rd AIOC 2015, New Delhi

with copious lubrication and frost sutures. So, a word of caution before going ahead with this procedure is to ensure that the patient has a very good Bells phenomenon. Over a period of time we realized that children tolerated lagophthalmos and induced exposure much better than adults as none of the children developed exposure keratopathy in our study group. Also the use of a bandage contact lens at the end of surgery can alleviate the development of exposure keratopathy. Frequent follow-up visits in the first 2 weeks and copious lubrication also helped us in managing these cases appropriately to avoid undue harm to the cornea. We believe that the 3 patients needing reversal had a good Bells preoperatively but still developed this complication due to occurrence of orbicularis spasm and pain in the immediate postoperative period not allowing them to use their Bells to full effect. The lagophthalmos induced is maximum in the immediate postoperative period, which goes on decreasing and comes within acceptable levels as noted in our series by the end of 3 months which could be attributed to better use of orbicularis by these patients. We believe that the main advantage of the procedure is that it is the most anatomically normal procedure that can be performed minus complications like granuloma formation and implant extrusion. Also we did not need 722 tarsectomy in our series to augment the lid height, which also helps avoid lid instability and induced ectropion. So, in cases of severe congenital ptosis this may be considered as an option alongside a Whitnall’s sling depending on the comfort of the oculoplastic surgeon. Some authors hypothesize that excessive levator resection might result in the loss of orbital support for the lacrimal gland, because the procedure involves severing the horns of the levator.14 In our technique we did not severe the horns of the levator except in one case thus avoiding the occurrence of this complication. There are certain drawbacks of this study it being retrospective. Also, although the number of participants was fairly decent, a prospective randomized comparative study of similar patients undergoing sling surgery would present a clearer picture. Despite this, the study still provides a new perspective to manage unilateral ptosis cases with poor levator function with a cosmetically better outcome and a more physiological method. The procedure above all always leaves us a scope to consider frontalis suspension as the second option in cases of failure. Thus, we conclude that levator resection with a slightly modified approach should be considered as the first option for severe unilateral congenital ptosis patients with a poor levator function before frontalis suspension methods Orbit and Oculoplasty Free Papers

References 1. Baroody M, Holds J, Vick V. Advances in the diagnosis and treatment of ptosis. Curr Opin Ophthalmol. 2005;16:351–5. 2. Anderson R, Baumgarter S. Amblyopia in ptosis. Arch Ophthalmol. 1980;98:1068–9. 3. Treatment of unilateral congenital ptosis: putting the debate to rest. Bernardini F, Cetinkaya A, Zambelli A. Curr Opin Ophthalmol 2013;24:484 –7. 4. Downers R, Collins JR. The mersilene mesh ptosis sling. Eye. 1990;4:456–63. 5. Saunders RA. Early correction of severe congenital ptosis. J Pediatr Ophthalmol Strabismus. 1991;5:271–3. 6. Wilson ME, Johnson RW. Long-term results of treatment using lyophilized fascia lata for frontalis suspension. Ophthalmology. 1991;98:1234 –7. 7. Ben Simon GJ, Macedo AA, Schwarcz RM, Wang DY, McCann JD, Goldberg RA. Frontalis suspension for upper eyelid ptosis: Evaluation of different surgical designs and suture material. Am J Ophthalmol 2005;140:877-85. 8. Early results of frontalis muscle flap technique for treatment of congenital ptosis. Tong JT, Goldberg RA, Perry JD, McCann JD. J AAPOS 2000;4:186-7. 9. Han K, Kang J. Tripartite frontalis muscle flap transposition for blepharoptosis. Ann Plast Surg. 1993;30:224-32. 10. Beard C. Ptosis 2nd ed. St Louis, MO: Mosby; 1976:18-22. 11. Epstein GA, Putterman AM. Super-maximum levator resection for severe unilateral congenital blepharoptosis. Ophthalmic Surg. 1984;15:971–9. 723 12. Superior tarsectomy augments super-maximum levator resection in correction of severe blepharoptosis with poor levator function. Pak J, Shields M, Putterman AM. Ophthalmology 2006;113:1201–8. 13. Anderson RL, Jordan DR, Dutton JJ. Whitnall’s sling for poor function ptosis. Arch Ophthalmol 1990;108:1628–32. 14. Anderson RL, Dixon RS. The role of Whitnall’s ligament in ptosis surgery. Arch Ophthalmol 1979;97:705–7.

Lamellar Icthyosis: A Chronic Struggle Dr. Pratheeba Devi J, Dr. Nirmala Subramanian, Dr. Nivean M cthyosis is a condition characterized by extreme dryness of the skin Ithroughout the body.1 Icthyosis is a skin disorder characterized by increased formation of epidermal scales. Progressive subepithelial cicatrization and abnormal cornification of eyelid skin causes progressive ectropion in both eyelids, which leads to restrictive lagophthalmos and 73rd AIOC 2015, New Delhi

corneal complications. This condition should be managed at the right time otherwise it can cause blindness due to corneal scarring. We present three different case scenarios which were managed successfully.

Materials and methods We report 3 patients with icthyosis who presented with cicatricial ectropion to our institute. We analyzed the way they were managed. The donor skin should be processed well before doing the surgery or else there will be contracture of the graft. We advised the patients to copiously lubricate the whole body with moisturizers. Full thickness grafting or split thickness grafting can be done. Lid crease incision was made. Subcutaneous dissection was made. The raw area was measured. The area required was marked and the SSG was taken from the thigh usually. The graft was placed over the host and was anchored with interrupted mersilk sutures and a tie over bolster was placed. Usually we remove the bolsters after 8 days. The sutures are removed after 10 days. Case report Case 1 4 month old male with lamellar icthyosis came to us with complaints of inability to close both eyes since birth. On examination he was fixing and 724 following light with both eyes. He had cicatricial ectropion of both upper lids. Anterior segment was normal in both the eyes. Fundus evaluation was with in normal limits. His skin all over the body was dry. Dermatologist opinion was sought. He was advised to use liquid paraffin liberally. We planned to take graft from the thigh so he was told to use tretinoin ointment locally. After 2 weeks the patient was reviewed. Donor site was better than before. Even the lagophthalmos had reduced with use of liquid paraffin. We advised bilateral cicatrical ectropion release with split thickness skin grafting (SSG) in the upper lid under general anaesthesia. Patient underwent the procedure as advised. Post operatively lagophthalmos disappeared in both the eyes. Patient was advised to continue liquid paraffin to soften the skin. On review after 1 ½ years patient is doing well. Case 2 6 year old male with lamellar icthyosis came with complaints of inability to close the eyes and eversion of both upper and lower lids. On examination his whole body was covered by dry scaly skin. His best corrected vision in both the eyes were 6/6; n6. Anterior segment examination revealed nebulomacular corneal scar in both the eyes. His fundus examination was within normal limits. There was cicatricial ectropion of lower lids in both eyes causing lagophthalmos. The corneal scarring was due to exposure. We Orbit and Oculoplasty Free Papers

planned to do a full thickness skin graft in the lower lid of both eyes. We planned to take graft from the groin. We advised the patient to use copious lubricants and to frequently moisturize the whole body with liquid paraffin. We used tretinion ointment over the donor area. Lower lid reconstruction with full thickness graft was done in both eyes. Post operatively the ectropion was corrected well. There was minimal lagophthalmos in both the eyes. It was due to the anterior lamellar shortening. We planned to do lengthening of the anterior lamellae later. Patient was advised to use the lubricants regularly. Case 3 A 50 year old female came to us with complaints of defective vision in both the eyes. She had dry scaly skin all over the body. She came to us with complaints of defective vision in both the eyes since 6 months. Her best corrected visual acuity was 6/18 and counting fingers close to face in both the eyes respectively. On examination she had ectropion of both the lower lids. She had cataract in both the eyes left more than the right. We decided to treat the ectropion before cataract surgery. The patient was advised to use liquid paraffin all over the body and tretinoin ointment in the donor area. After 2 weeks the condition of skin improved. 725 She underwent ectropion release with split thickness grafting. Her intra and post operative periods were uneventful. The graft uptake was good. After 2 months she underwent cataract surgery in both her eyes. At her final follow up she had no ectropion in her lower lids in both the eyes.

Discussion Lamellar ichthyosis is a condition that mainly affects the skin. Infants with this condition are typically born with a tight, clear sheath covering their skin called a collodion membrane. This membrane is usually shed during the first few weeks of life, but remaining effects include scaly skin and outward turning eyelids and lips. Ichthyosis is an infrequent clinical entity worldwide (1:300,000 births). When diagnosed in a newborn, two forms can be identified: collodion baby and its most severe form, harlequin fetus or maligna keratoma.2 In both cases, clinical manifestations are thick and hard skin with deep splits. The splits are more prominent in the flexion areas. The youngest reported case is a 4 day old baby.3 The four main types of icthyosis are ichthyosis vulgaris, sex- linked recessive, bullous and non-bullous epidermolytic hyperkeratosis. It has autosomal recessive pattern of inheritance.4 Patients with icthyosis have extremely dry skin which makes it very unsuitable for grafting. 73rd AIOC 2015, New Delhi

Since 1834 when Sir Arnold described the first case of ectropion due to icthyosis there are several reports in literature.4 Ocular manifestations include exposure keratitis secondary to ectropion, unilateral megalocornea, enlarged corneal nerves, blepharitis, absence of the meibomian gland, trichiasis, madarosis, absence of lacrimal puncta and ectropion of both upper and lower lids.3 Our patients had only lid signs. Pinna et. al.5 have suggested that the interaction between eyelid malposition and corneal disease is complex and corneal damage depends on several other factors, including upper eyelid restriction, lack of Bell’s phenomenon and eyelash retraction. Autografts have been used successfully, provided an available donor site can be found. Grafts taken from the arm, eyelids, postauricular skin, and groin have been used with success. Prepucial skin can be used in males if it is healthy.6 In patients with icthyosis the skin should be processed well before grafting. Various lubrication measures have been tried. We generally prefer to moisten the skin with liquid paraffin. We encourage the use of liquid paraffin several times a day. This procedure of making the skin should be done for at least a month. We advise the patients to use tretinoin ointment in the area where we plan to take a graft. If we require more amount of graft then we can go for grafting from groin 726 or thighs. Care must be taken to oversize the graft and to put the lid on traction postoperatively since skin shrinkage occurs following surgery. Repeat skin grafting is sometimes necessary because of the recurrence of ectropion and surgical results are good.4 We also felt that repeated hydration of the entire body also gives a good moisturizing effect. We can suggest the patients to cover their body with wet cloth several times a day. It is better to wear thin cotton clothes always due to the nature of their skin condition. Patients with milder variant can lead a normal life as in our patient who had lived 50 years of life without any intervention. It is always better to correct it before cataract surgery to avoid any post-operative infection. Honavar et. al.7 have published an article on use of maternal allograft for a case of severe ectropion due to lamellar icthyosis in a 6 month old infant. They had a 10 month follow up at the time of publication with good results. They have not done HLA typing and they have said they have not given any immunosuppressants. However that technique may also be a good alternative in very severe cases of ectropion which is visually threatening where we cannot afford to wait till the skin quality becomes better. Sigurdson8 et. al. has published an Orbit and Oculoplasty Free Papers

article wherein they have tried inverting sutures with systemic retinoids and lubricants only. They have reported good improvement with a five years follow-up. Lamelllar ichthyosis can be a part of syndromic association like IFAP syndrome (ichthyosis follicularis, atrichia and photophobia) and KID syndrome (Keratitis ichthyosis deafness syndrome).9,10 Systemic complications like temperature instability, cutaneous infections, hypernatremic dehydration and septicemia can occur. Death can occur in as many as 25% due to septicemia or dehydration. Patients with ichthyosis should be monitored lifelong.

Conclusion The eyelid abnormalities in lamellar ichthyosis are lifelong so careful serial ophthalmic examination for corneal exposure is warranted. Proper processing of the skin before grafting is mandatory. The patients should be on life long lubricants for the eyes and moisturizers for the skin.

References 1. A. J. Singh, Atkinson. Ocular manifestations of congenital lamellar Ichthyosis. Eur J Ophthalmol 2005;15:118–22. 2. Bhardwaj, Phougat, Dey, Raut, Srivastav, Gupta. A rare case of collodion baby 727 with ophthalmic involvement. Nepal J Ophthalmol 2012;4:184-6. 3. Chandana chakraborti, Partha Tripathi and Dayal Bandhu Mazumder. Congenital bilateral ectropion in lamellar ichthyosis. Oman J Ophthalmol 2011;4: 35–6. 4. Jay B, Blach RK, Wells. Ocular manifestations of ichthyosis. Br J Ophthalmol. 1968;52:217–26. 5. Pinna A, Ena P, Carta F. Eye changes in a patient with lamellar ichthyosis and toe pseudoainhum. Eye 2004;18:445–6. 6. Uthoff D1, Gorney M, Teichmann C. Cicatricial ectropion in ichthyosis: a novel approach to treatment. Ophthal Plast Reconstr Surg. 1994;10:92-5. 7. Sima das et. al.. Maternal Skin Allograft for Cicatricial Ectropion in Congenital Icthyosis. Ophthal Plast Reconstr Surg. 2010;26:1. 8. Sigurdsson H1, Baldursson BT. Inverting Sutures With Systemic Retinoids and Lubrication Can Correct Ectropion in Ichthyosis. Ophthal Plast Reconstr Surg. 2014 Sep 11. [Epub ahead of print]. 9. Claus Cursiefen, Schlötzer-Schrehardt U, Holbach LM, Pfeiffer RA, Naumann. Ocular Findings in Ichthyosis Follicularis, Atrichia and Photophobia Syndrome. Arch Ophthalmol. 1999;117:681-4. 10. Messmer EM, Kenyon KR, Rittinger O, Janecke AR, Kampik A. Ocular manifestations of keratitis– ichthyosis–deafness (KID) syndrome. 2005;112:e 1-6. 73rd AIOC 2015, New Delhi

Adult Onset Xanthogranulomatosis with Massive Involvement of all Four Eyelids Dr. Ravindra Mohan E, Dr. Arthi Dwarakanath dult Xanthogranulomatous disease involving the ocular or orbital Atissue is rare and constitutes a group of entities with varying manifestations. These are non Langerhans histiocytic disorders that are diagnosed histopathologically by the infiltration of orbital soft tissues rather than bone (bone involvement is seen in Langerhans histiocytosis).1,2 The infiltration is composed of “Hallmark Cells” especially foamy histiocytes and Touton giant cells along with lymphocytes, accompanied by varying degree of fibrosis and, in some entities, necrosis. Based on systemic associations, there are four subtypes that comprise the disorder of Adult Xanthogranulomas.1,3 • Adult Onset Xanthogranuloma (AOX) – Solitary lesion (usually eyelid) with no systemic involvement. • Adult Onset Asthma and Periocular Xanthogranuloma (AAPOX) – Eyelid and anterior orbit lesion with adult onset Asthma. 728 • Necrobiotic Xanthogranuloma (NBX) – Eyelid and anterior orbit lesion ,skin lesions that tend to ulcerate and become fibrotic, paraproteinemia and multiple myeloma. • Erdheim Chester Disease (ECD) – lesion involves posterior orbit and internal organs, cardiomyopathy, severe lung disease, chronic renal failure, bone involvement. AOX is an isolated xanthogranulomatous lesion without immune dysfunction and systemic involvement. It is the least common among the four subtypes. Patients affected are in the ages ranging from 38 - 79 years, with no sex preference. Management involves surgical excision or intralesional corticosteroid injection. The significance of recognising this entity is that it is often self limited and does not require aggressive treatment unlike the other subtypes, which can sometimes cause significant morbidity3

Materials and Methods A 60 year old female presented with a painless, progressive swelling of upper and lower lids in both eyes of 2 years duration. The patient was a known diabetic and hypertensive with no previous history of asthma or allergies. Orbit and Oculoplasty Free Papers

Examination revealed bilateral yellowish, non tender, non ulcerated, firm, rubbery, infiltrative lid masses involving all four lids and producing mechanical ptosis (Figure 1). There was no restriction of ocular movements or proptosis. Anterior segment and fundus examination was unremarkable except for senile cataracts in both eyes. Systemic examination was essentially normal with no evidence of any other skin lesions elsewhere in the body and no preauricular and cervical lymphadenopathy. Figure 1: Preoperative picture Figure 2: CT Orbits showing She was evaluated showing infiltrative eyelid lesion hyperdense, preseptal causing mechanical ptosis infiltrative eyelid lesions. with complete more severe on the left side. hemogram, blood sugars, lipid profile, renal parameters and liver function tests, with normal results. Computed tomography showed homogenous, hyperdense preseptal infiltrative lesion of both upper and lower eyelids (Figure 2). In view of the extensive nature of the lesion involving all four lids and mechanical ptosis, patient was advised , and underwent a bilateral radiosurgical debulking with upper eyelid blepharoplasty under local 729 anaesthesia. The lesion involved all tissue anterior to the orbital septum. It was meticulously excised in along with overlying skin. It had a firm consistency and appeared greyish white to pale yellow and was sent for histopathological examination

Results Histopathological examination revealed a lesion beneath the surface epithelium displaying mixed inflammatory cell infiltrate composed of lymphocytes, neutrophils, touton giant cells and foamy macrophages, against a background of granulation tissue (Figure 3,4 and 5), suggestive of Xanthogranulomatous inflammation.

Figure 3: Photomicrograph Figure 4: Photomicrograph Figure 5: Photomicrograph showing subepithelial mixed showing foamy macro- showing Touton giant cells. cellular infiltrate. phages. 73rd AIOC 2015, New Delhi

Following upper eyelid surgery, patient had excellent correction of her mechanical ptosis (Figure 6).

Figure 6: Post upper eyelid Figure 7: Post lower eyelid Patient underwent debulking and blepharoplasty. debulking. bilateral radiosurgical debulking and lower eyelid blepharoplasty two years after the first procedure, with similar histopathological diagnosis. She tolerated the procedures well. She developed a mild right lower lid ectropion (Figure 7) within a year of the surgery, but no recurrence was seen nearly three years after the upper eyelid and one year after the lower eyelid surgeries.

Discussion Our patient had Adult Onset Xanthogranuloma which is the least common subtype among the Adult Xanthogranulomas, with characteristic bilateral, periocular involvement not extending into deep orbital and perioptic connective tissue, and with no systemic involvement. Hence visual acuity remained intact and ocular motility preserved despite massive involvement 730 of all the eyelids. Excellent function and cosmesis can be achieved,like in our patient with appropriate surgical debulking. Other than having to distinguish this specific entity from the other more morbid subtypes with systemic involvement , differential diagnosis may include seemingly innocuous conditions like dermatochalasis or xanthelesma to potentially fatal ones like lymphoma. Hence patients with eyelid thickening should undergo histopathological examination of the tissue removed at surgery followed by systemic evaluation as appropriate to enable definitive diagnosis and optimal management and to prevent misdiagnosis and delayed treatment.4

References 1. J A Sivak-Callcott et. al.,Adult xanthogranulomatous disease of the orbit and ocular adnexa: new immunohistochemical findings and clinical review. Br J Ophthalmol 2006;90:602–8. doi: 10.1136/bjo.2005.085894 et. al. 2. Adult orbital xanthogranuloma with periosteal infiltration. R Malhotra et. al., Br J Ophthalmol 2003;87:120-1 doi:10.1136/bjo.87.1.120-a. 3. Guo and Wang. Adult Orbital Xanthogranulomatous Disease. Arch Pathol Lab Med 2009;Vol 133. 4. F A Jakobiec. Periocular xanthogranulomas associated with severe adult-onset asthma. Trans Am Ophthalmol Soc. 1993;91:99–129. Orbit and Oculoplasty Free Papers

Corneal Topography and Higher order Aberrations in Blepharoptosis Dr. Rath Suryasnata, Dr. Sujata Das, Dr. Kapil Arunkumar Bhatia lepharoptosis denotes droopiness of the eyelid and can cause change Bin the shape of the cornea.1,2 Irregular astigmatism caused by irregular corneal shape cannot be corrected by spectacles, soft contact lens or conventional refractive surgeries. Of the 18 types of irregular astigmatism, 5 which are clinically relevant include spherical aberration, coma, trefoil, quadrafoil and secondary astigmatism.3 Wavefront aberration surfaces are simply graphs generated using Zernike polynomials.4,5 There are several techniques for measuring wavefront aberrations clinically, but the most popular is based on the Hartmann-Shack wavefront sensor. Few studies have determined the correlation between ptosis and corneal aberrations. The objective of this study was to evaluate the effect the blepharoptosis on corneal topography and ocular higher order aberrations and also evaluate if they change after correction.

Materials and Methods A prospective observational study was approved by the institutional ethics 731 committee and was in accordance with tenets of Declaration of Helsinki. All patients presenting with complaints of drooping of one or both upper eyelids between November 2012 to June 2013, and willing to participate in the study were included. In bilateral cases, patients willing to undergo surgery were included. Patients who had blepharoptosis which was neurogenic, myogenic in etiology were excluded. Patients with contraindications or unwilling for surgery and/or aberrometry and corneal topography were also excluded. All patients found eligible for the study underwent a comprehensive eye examination including standard ptosis evaluation. Corneal topography and aberrometry were done by Orbscan IIZ with Zywave Aberrometer from Baush and Lomb, based on Hartmann – Shack aberrometry principle. All measurements were taken between 10 am and 1 pm to nullify the effect of diurnal variation in aberrometry measurement. All patients were dilated with a combination of Tropicamide 0.8% and Phenylephrine 5%, to dilate the pupil and overcome the effect of pupil size as well as accommodation. Measurements were taken 30-45 minutes after instillation of drops. Patients were asked to blink 2-3 times before taking measurements and no lubricating drops were used. Ptotic eyelid was lifted with thumb without applying undue pressure over the globe 73rd AIOC 2015, New Delhi

during measurement. Corneal Topography was obtained in Zyoptic mode, taking average of 3 measurements. Ocular Higher order Aberrations were measured with Zywave. The machine takes 5 readings and automatically selects best 3 measurements, the final reading being the average of the selected 3. All patients underwent blepharoptosis correction based on the degree of ptosis, levator action and Bell’s phenomenon. Patients with Unilateral Ptosis who refused surgery were still a part of the study, with their fellow eye serving as control. Follow-up All patients who underwent surgery were followed up at 6 weeks, 3 and 6 months after surgery. Unilateral Ptosis patients not undergoing surgery were not followed up. In all other patients, Pre and Post-operative data were compared. All patients underwent the following on follow-up visits: Refraction, Corneal Topography and Aberrometry, any residual Ptosis noted. Corneal topography and aberrometry performed and the print outs preserved and compared: Before and after surgery in operated cases; Normal and Affected eye in cases of unilateral ptosis. 732 Following parameters were recorded for analysis All these parameters were compared between Ptotic and Fellow eye, and also Pre-operatively and Post-operatively. For analysis purpose 3 groups were formed Ptotic Group (all eyes with Ptosis), Congenital Group (Eyes with Congenital Ptosis), Acquired Group(Eyes with Acquired Ptosis). Unpaired t test with Welch correction (Welch t test) was used to compare between Ptotic and Fellow eyes. Paired t test was used to compare between eyes pre-operatively and post-operatively. Fisher’s exact test was used to compare BCVA and Astigmatism between Ptotic and Fellow eyes.

Results A total of 28 eyes of 25 patients with blepharoptosis were included in this study, 14 males and 11 females. 22 patients had unilateral ptosis (22 eyes) and 3 patients had bilateral ptosis (6 eyes). There were 17 patients with congenital ptosis (18 eyes) and 8 patients with acquired ptosis (10 eyes). Ptotic Group: Mean age was 23.8±13.19 years, with a mean MRD1 of -1±2.2 mm. The mean duration of ptosis was 15.8±10.1 years. Mean SEQ was -0.71±2.5D and mean CYL was -0.90±1.4D with mean BCVA of 0.14±0.3 Logmar. Orbit and Oculoplasty Free Papers (Z331+Z330+Z531+Z530) (Z311+Z310+Z511+Z510) (Z441+Z421+Z400+Z420+Z440) Total 5th orderTotal aberrations Total PentafoilTotal (Z551+Z550)

Total 4th order aberrations aberrations order 4th Total (Z421+Z420) Total Coma Coma Total Total SecondaryTotal Astigmatism (Z331+Z311+Z310+Z330)

Total Trefoil Trefoil Total QuadrafoilTotal (Z441+Z440) Total 3rd orderTotal aberrations (Z551+Z531+Z511+Z510+Z530+Z550) Calculated

733 Vertical Secondary Coma (Z511) Pupil plane refraction CYL (PPRCYL) Vertical Pentafoil (Z551) Vertical Secondary (Z531) Trefoil Horizontal (Z440) Quadrafoil AberrationsTotal 5mm) at 5mm (Tot and 6mm (Tot) Pupil plane refraction SEQ (PPRSEQ) (HO5mm) and 6mm (HO) Spherical Aberration (Z400) (Z420) SecondaryHorizontal Astigmatism Horizontal Coma (Z310) Coma Horizontal Horizontal Pentafoil (Z550) Higher order aberrations at 5mm Vertical Secondary Astigmatism (Z421) SecondaryVertical Astigmatism Vertical Coma (Z311) Vertical (Z331) Trefoil Horizontal Secondary (Z530) Trefoil Horizontal (Z330) Trefoil Vertical Quadrafoil (Z441) Secondary (Z510) Horizontal Coma Aberrometry

(AntBFS)

Anterior Best Fit Sphere 5mm Irregularity5mm (5mmirr) Pachymetry

3mm Irregularity (3mmirr) Simulated Keratometry Keratometry Simulated Kappa Astigmatism (SKAst) Astigmatism Maximum (SKMax) Simulated Keratometry (Post BFS) Simulated Keratometry Minimum (SKMin) Sphere Fit Best Posterior Topography

Table 1

Best Corrected Visual Acuity (BCVA) Cylinder of Refraction (CYL)

Duration of ptosis

of Refraction (SEQ)

Age Spherical equivalent Distance 1 (MRD1) Demography Margin Reflex 73rd AIOC 2015, New Delhi P- 0.76 0.52 0.57 0.65 0.05 0.68 0.86 0.196 0.724 0.327 0.493 0.562 0.698 0.458 0.008 0.986 value

0.303

Fellow Mean±sd Acquired 0.28±0.05 0.0016±0.1 0.0067±0.1 0.105±0.08 0.06±0.097 -0.017±0.04 -0.03±0.075 -0.084±0.09 0.183±0.026 0.026±0.025 -0.055±0.031 -0.023±0.048 0.0041±0.025 -0.0416±0.065 -0.0068±0.015 -0.0033±0.032 -0.0033±0.035

Ptosis 0.01±0.05 Acquired -0.09±0.18 0.063±0.11 0.015±0.03 0.081±0.28 0.521±0.23 0.015±0.09 0.288±0.06 0.0033±0.2 -0.068±0.27 0.0168±0.05 0.0033±0.06 -0.051±0.198 -0.028±0.183 -0.0133±0.04 -0.0216±0.05 -0.0016±0.05

0.2 0.55 0.35 0.44 0.34 0.142 0.192 0.199 0.743 0.755 0.231 0.658 0.938 0.289 0.222 0.266 0.0021 P-value

Fellow 0.36±0.11 Mean±sd Mean±sd 0.23±0.08 0.168±0.12 0.012±0.07 0.024±0.04 0.024±0.04 -0.005±0.11 Congenital -0.002±0.04 -0.097±0.117 -0.012±0.044 -0.0275±0.22 -0.0068±0.03 0.0055±0.021 0.0035±0.026 -0.0013±0.057 -0.0076±0.026

-0.00018±0.017

734 Ptosis 0.02±0.2 0.01±0.03 Mean±sd 0.423±0.2 0.033±0.10 0.285±0.14 0.007±0.03 0.012±0.05 0.075±0.25 0.003±0.06 0.0056±0.5 -0.015±0.17 -0.057±0.17 -0.056±0.13 -0.027±0.05 Congenital -0.002±0.08 -0.0028±0.05 0.0016±0.044

0.018 0.572 0.323 0.257 0.232 0.695 0.604 0.664 0.846 0.548 0.1335 0.0315 0.6335 0.0394 0.2584 0.2668 0.5484 P-value

±0.123 4 0.344±0.1 Mean±sd 0.008±0.2 0.1 -0.01±0.04 0.217±0.07 0.006±0.06 Fellow eye 0.0097±0.07 0.0162±0.04 0.003±0.025 -0.094±0.108 -0.012±0.033 -0.002±0.016 0.0037±0.025 0.0051±0.038 -0.0018±0.112 -0.0091±0.062 -0.0096±0.035

tatistically significantvalues are shown in bold

Ptosis 0.01±0.2 0.45±0.2 Mean±sd -0.04±0.17 0.007±0.05 0.036±0.25 0.041±0.103 -0.02±0.052 0.0073±0.19 0.285±0.122 0.008±0.062 0.009±0.034 0.0006±0.05 -0.026±0.121 -0.055±0.146 0.0019±0.038 0.0095±0.051 -0.0024±0.042

Table 2: Mean 2: Table and standard deviation of various aberrometry parameters are shown along with the corresponding p value. S Horizontal Sec. Trefoil Higher Order berrationsA 5mm Horizontal Pentafoil Vertical Coma Vertical Quadrafoil Higher Order Aberrations 6mm Spherical Aberration

Parameters Vertical Trefoil Horizontal Sec. Coma Horizontal Trefoil Vertical Sec.Vertical Astigmatism Horizontal Coma Vertical Pentafoil Vertical Sec. Trefoil Vertical Sec. Coma Horizontal Sec. Sec. Horizontal Astigmatism Horizontal Quadrafoil Orbit and Oculoplasty Free Papers 0.3 0.2 0.17 0.97 0.97 0.53 0.84 0.46 0.193 0.456

0.107±0.16 0.036±0.15 0.941±0.49 0.686±0.39 0.173±0.172 -0.038±0.06 -0.147±0.115 -0.058±0.096 -0.004±0.064 Figure 1: Congenital Ptosis: Pre-op(left) -0.0088±0.046

and 6-months post-op(right): Topography

of Ptotic and Fellow eye. Note the lack of mirror symmetry, Bow tie pattern and persistence of asymmetry post-operatively 0.07±0.1 1.23±0.41 0.03±0.45 -0.05±0.12 -0.01±0.06 -0.035±0.5 0.835±0.25 -0.011±0.26 -0.073±0.144 -0.0033±0.09

0.65 0.33 0.06 0.186 0.035 0.927 0.033 0.588 0.205 0.453

Figure 2: Acquired Ptosis: Pre-op(left) and 1.01±0.75 0.15±0.31 0.714±0.5 0.156±0.2 0.03±0.04 0.012±0.07 -0.08±0.125 -0.023±0.24 -0.004±0.08 0.0175±0.06 6-months post-op(right): Topography of

Ptotic and Fellow eye. Note the lack of mirror

symmetry initially but post-operatively maps tend to become symmetrical 735 2.2±2.5 0.03±0.11 3.16±3.65 0.01±0.08 -0.025±0.13 0.031±0.315 0.023±0.195 -0.011±0.275 0.0135±0.072 0.00075±0.133

0.07 0.99 0.06 0.114 0.137 0.748 0.635 0.503 0.0288 0.0295

Figure 3: Congenital Ptosis: Pre-op(left) and 6-months post-op(right): Total and Higher order 0.7±0.47 0.123±0.2 0.155±0.28 0.012±0.23 0.993±0.68 0.02±0.048

-0.004±0.07 Aberrations of Ptotic and Fellow eye. Note -0.101±0.123 -0.001±0.072 -0.003±0.077

the lack of mirror symmetry and persistence

of asymmetry post-operatively 1.82±2.21 2.63±3.21 0.042±0.11 0.007±0.07 0.013±0.363 -0.019±0.137 -0.032±0.127 0.0137±0.211 0.0065±0.084 0.00022±0.323

Figure 4: Acquired Ptosis: Pre-op(left) and 6-months post-op(right): Total and Higher order Aberrations of Ptotic and Fellow eye. Note the lack of mirror symmetry initially and Total Sec.Total Astigmatism PentafoilTotal Total Coma Total Total QuadrafoilTotal Total 3rd order Total Total 5th orderTotal Total 4th order Total Total AberrationsTotal 6mm Total Trefoil Total Total AberrationsTotal 5mm attainment of symmetry post-operatively 73rd AIOC 2015, New Delhi

Congenital Group: This group included 16 eyes of 16 patients. Mean age was 19.93±8.52 years, with a mean MRD1 of -0.87±2.217 mm. The mean duration of ptosis was 19.93±8.52 years. Mean SEQ was -0.86±2.7 and mean CYL was -1.17±1.5D with mean BCVA of 0.15±0.32 Logmar. Acquired This group included 6 eyes of 6 patients. Mean age was 34.34±18.22 years, with a mean MRD1 of -1.34±2.5 mm. The mean duration of ptosis was 4.84±3.3 years. Mean SEQ was -0.10±0.25D and mean CYL was -0.20±0.5D with mean BCVA of 0.1±0.22 Logmar. Post-operative 6 months Post-operatively9 eyes of 8 patients were analysed at 6 months. Of the total 9 eyes, 5 eyes had congenital ptosis and 4 eyes had acquired ptosis.

Discussion Effect of ptosis on corneal shape and astigmatism is well known.6-9 Gullstrand10 reasoned that corneal astigmatism was changed by the pressure of the eyelids in with-the-rule direction, attributing this to a flattening of the cornea by the eyelids. In addition, various upper and lower eyelid conditions, including hemangiomas, gold weight implants, chalazia, epibulbar dermoids,and 736 involutional ectropion, have been reported to affect corneal shape.11,15 Effects of ptosis on corneal topography have also been studied.16,19 Asymmetric/ symmetric bow tie pattern is more common in ptotic eyes than normal eyes. Bow tie patterns have a statistically significant and clinically meaningful astigmatism than other patterns. Topography of one eye is mirror symmetry of the fellow eye. There is lack of this symmetry in ptotic eyes, both in acquired and congenital ptosis. While this asymmetry persists even after surgery in congenital ptosis, this is reversible in cases of acquired ptosis, and tends to become as symmetric with the fellow eye as possible as illustrated in Figure-1 and Figure-2. In the ptotic group, there was significant difference in SimKAst, 3 mm and 5 mm zone irregularity, mostly contributed by the congenital group. These changes signify irregularity and astigmatism caused by change in the shape of cornea due to pressure exerted by the ptotic eyelid. No statistically significant difference was observed among the topography parameters in acquired ptosis when ptotic and fellow eyes were compared. But as observed in the illustration above, acquired ptosis affects corneal topography, however in a moderate and reversible way. While effects on topography were observed in the congenital group, changes after ptosis surgery were observed more frequently in the acquired group. Orbit and Oculoplasty Free Papers

At 6 months post- op, there was P- 0.8 0.12 0.21 0.69 0.85 0.413 0.015 value 0.867 0.436 no significant 0.954 0.4545 0.2388 difference <0.0001 between pre- op and post-op topography in 0 0 Fellow 1.7±0.38 7.9±0.32 0.25±0.6 Mean±sd Acquired 4.16±0.75 4.86±1.22 43.91±2.05 44.65±1.84 6.481±0.215 both congenital 529.6±33.76 -0.766±0.273 1.283±0.4262

and acquired groups. Recently there has Ptosis 0.1±0.2 -1±0.63 -1.7±2.0 -0.2±0.5 5.9±1.42 1.95±0.6 -0.1±0.25 Mean±sd Acquired 44.81±1.5 7.85±0.29 1.98±0.87 6.45±0.23 539.8±50.5 been a study on 43.85±1.925

effects of congenital ptosis on higher 0.47 0.81 0.69 0.09 0.04 0.28 0.88 0.44 0.078 order aberrations, 0.025 0.3404 0.0068 P-value <0.0001 where the authors have compared

the zernicke 0 0.373 Fellow 7.9±0.3 coefficients and 3.8±0.5 1.55±0.5 -0.17±0.3 Mean±sd 43.69±1.7 44.38±1.8 1.26±0.53 6.43±0.29 -0.18±0.66 found various Congenital coefficients signi- 737 ficantly different

between ptotic and Ptosis 2.01±0.7 7.98±0.3 -1.17±1.5 -1.1±2.19 -1.31±1.3 Mean±sd -0.86±2.7 6.47±0.28 43.15±2.2 44.48±1.8 1.53±0.85 513.5±29.3 493.9±31.5 4.85±2.709 4.67±1.44 fellow eyes.20 This Congenital study compares 0.07 0.83 0.26 0.06

the RMS values 0.125 0.784 0.024 0.632 0.492 0.0195 0.15±0.3 0.0014 0.4885 P-value of various higher <0.0001 order aberrations in both congenital and tatistically significantvalues are shown in bold acquired ptosis, as 0 3.9±0.5 7.90±0.3 1.6±0.46 1.26±0.5 Mean±sd 4.72±1.36 6.45±0.27 -0.70±0.34 43.75±1.75 Fellow eye 44.46±1.76 well as change in 503.6±35.3 -0.125±0.325 aberrations after -0.0625±0.66 ptosis surgery.

Total and higher -1±2.2 Ptosis -0.9±1.4 0.14±0.3 7.95±0.3 -0.71±2.5 Mean±sd 44.57±1.7 5.13±2.44 1.66±0.85 -1.22±1.18 43.34±2.11 520.7±36.9 6.47±0.262 order aberrations 1.995±0.65 were statistically different between ptotic and fellow eyes in the ptotic group, Table 3: Mean 3: andTable standard deviation of examined and various topography parameters are shown along being greater in with the corresponding p value. S Anterior BFS Posterior BFS

Parameters Refraction SEQ Sim K Ast 3mm Irregularity 5mm Irregularity Sim K Max Sim K Min Refraction CYL Pachymetry Kappa MRD1 BCVA 73rd AIOC 2015, New Delhi P- 0.38 0.96 0.147 0.143 0.743 0.749 0.782 0.441 0.763 0.624 0.633 0.653 0.494 0.498 0.689 0.364 value 0.0071 0.0083

Fellow 0.13±0.13 0.57±0.15 Mean±sd Acquired -0.02±0.12 -0.01±0.04 -0.03±0.03 0.015±0.08 0.025±0.02 0.222±0.04 0.005±0.06 -0.055±0.15 -0.05±0.049 0.3175±0.05 0.0325±0.04 -0.0775±0.07 -0.0525±0.06 0.01225±0.041 0.02275±0.045 0.00925±0.022

Ptosis 0.11±0.15 0.72±0.19 Mean±sd 0.06±0.13 Acquired 0.04±0.05 0.265±0.04 -0.107±0.16 -0.1175±0.2 -0.045±0.04 0.0025±0.19 0.0525±0.01 0.0275±0.26 0.5325±0.24 0.0575±0.34 -0.0125±0.05 -0.0225±0.05 0.0175±0.025 -0.005±0.066 0.0125±0.067

0.3 0.2 0.2 0.18 0.62 0.65 0.35 0.725 0.541 0.799 0.579 0.327 0.686 0.839 0.558 0.386 0.299 0.843 P-value

Fellow Mean±sd 0.02±0.04 -0.04±0.19 0.374±0.11 -0.01±0.06 1.09±1.003 0.074±0.08 0.066±0.14 0.012±0.05 0.024±0.07 0.022±0.04 0.236±0.06 Congenital -0.028±0.15 -0.092±0.17 -0.014±0.04 -0.016±0.04 -0.028±0.05 0.0034±0.03 -0.062±0.083

tatistically significantvalues are shown in bold 738 Ptosis 1.15±1.2 Mean±sd 0.27±0.08 -0.01±0.03 -0.01±0.02 -0.02±0.03 0.034±0.13 0.394±0.12 0.032±0.06 0.036±0.27 0.006±0.03 0.006±0.05 0.006±0.04 -0.126±0.19 -0.018±0.12 Congenital -0.02±0.123 -0.018±0.04 -0.002±0.01 -0.004±0.04

0.32 0.118 0.411 0.195 0.189 0.211 0.312 0.316 0.341 0.278 0.957 0.939 0.595 0.892 0.638 0.369 0.3599 0.0084 P-value

0.86±0.76 0.34±0.09 0.23±0.05 -0.06±0.15 0.017±0.04 0.042±0.15 0.043±0.12 0.027±0.05 0.021±0.04 Fellow eye Fellow 0.006±0.02 -0.046±0.16 -0.057±0.07 -0.012±0.95 -0.03±0.049 -0.006±0.05 0.0022±0.04 -0.0033±0.06

0.0066±0.11

Ptosis Mean±sd Mean±sd 0.96±0.89 0.037±0.14 -0.02±0.04 0.455±0.18 0.021±0.07 0.012±0.04 0.267±0.06 0.044±0.09 -0.011±0.04 -0.028±0.16 -0.048±0.14 -0.016±0.04 -0.044±0.26 0.0011±0.05 0.032±0.254 0.0066±0.02 -0.0088±0.14 -0.0055±0.05

Mean and standard deviation of various aberrometry parameters are shown along with the correspon- Table 4: 4: Table ding p-value, comparing the pre-op and post-op values. S Total AberrationsTotal 5mm Horizontal Pentafoil Higher Order Aberrations 6mm Higher Order Aberrations 5mm Horizontal Sec. Trefoil Horizontal Sec. Coma Vertical Sec. Coma Vertical Sec. Trefoil Vertical Quadrafoil Vertical Pentafoil Horizontal Trefoil

Horizontal Coma Horizontal Quadrafoil Horizontal Sec. Sec. Horizontal Astigmatism Spherical Aberration Vertical Sec. Astigmatism Vertical Trefoil Vertical Coma Parameters Orbit and Oculoplasty Free Papers P- 0.59 0.94

0.181 0.411 0.611 0.412 0.702 0.05 0.56 0.86 value 0.508 0.504 0.876 0.923 0.566 0.266 0.8295 0.6443

Fellow 2.1±0.63 1.55±0.5 7.79±0.11 Mean±sd 6.37±0.14 Acquired 5.33±2.08 0.07±0.13 509±21.49 45.15±0.67 -0.665±0.28 44.475±0.83 0.0127±0.09 0.0375±0.08 0.8425±0.22 0.065±0.099 -0.0675±0.08 -0.0525±0.09 -0.0457±0.043 -0.0535±0.043

Ptosis 2±1.03 7.79±0.13 Acquired -0.02±0.13 1.975±0.75 6.395±0.14 45.025±0.6 0.055±0.13 0.207±0.37 1.025±0.33 0.088±0.28 -0.117±0.48 -0.725±0.47 510.75±20.6 0.0025±0.11 44.325±0.87 0.00001±0.07 -0.0775±0.166

0.41 0.79 0.107 5.288±1.360.756 0.621 0.826 0.223 0.545 0.844 0.718 0.192 0.749 0.319 0.326 0.689 0.046 0.896 0.344 P-value

Fellow 7.94±0.1 1.54±1.4 1.4±0.66 0.01±0.11 Mean±sd Mean±sd 6.42±0.16 -1.18±1.14 5.58±1.02 1.62±0.37 0.014±0.12 0.058±0.09 0.006±0.05 44.38±0.63 43.48±0.84 Congenital -0.094±0.14 -0.106±0.21 0.021±0.092 0.0146±0.087

739 Ptosis 7.93±0.1 1.32±0.5 44.6±0.7 6.42±0.17 1.54±0.28 5.43±0.62 0.01±0.29 -1.32±1.07 514.4±58.8 516.8±54.1 1.618±1.78 43.28±1.02 0.016±0.08 Congenital 0.038±0.06 -0.076±0.14 -0.048±0.05 -0.004±0.06 tatistically significantvalues are shown in bold -0.104±0.105

-0.03±0.07

0.7 0.6 0.25 0.06 0.76 0.419 0.82 0.65 0.59 0.781 0.89 0.818 0.249 0.448 0.117 0.326 0.336 0.8916 P-value

0.02±0.1 1.23±1.08 0.04±0.09 -0.08±0.15 -0.024±0.1 0.0088±0.1 -0.021±0.15 -0.012±0.07 5.47±1.4 6.4±0.14 1.46±0.5 512±43.7 7.87±0.13 Mean±sd 1.83±0.53 -0.94±0.87 43.75±1.03 Fellow eye 44.72±0.73

0.009±0.07

Mean±sd 1.35±1.3 0.097±0.32 Ptosis 0.0009±0.1 0.045±0.09 -0.036±0.11 -0.016±0.07 -0.109±0.34 -0.025±0.08 5.37±0.9 -0.0031±0.22 1.62±0.8 7.87±0.13 6.41±0.15 Mean±sd 43.7±1.05 1.73±0.55

-1.05±0.87 44.79±0.66 514.11±40.4

Mean and standard deviation of various topography parameters are shown along with the corresponding Table 5: 5: Table p-value, comparing the pre-op and post-op values. S Anterior BFS 5mm Irregularity Posterior BFS Sim K Ast 3mm Irregularity 3mm Kappa Sim K Min Pachymetry

Parameters Sim K Max Total Pentafoil Total Total QuadrafoilTotal Sec. AstigmatismTotal Total AberrationsTotal 6mm Total Trefoil Total Total 5th order Total Total Coma Total 3rd order Total Total 4th order Total 73rd AIOC 2015, New Delhi

amplitude. Z331 was significantly different between ptotic and fellow eyes, being of lower amplitude in the ptotic eyes. In addition, PPRCyl and SimKAst was significantly higher in ptotic eyes. Total 3rd and 4th order aberrations were lower in ptotic eyes than fellow eyes. Difference was noted between the effects of congenital and acquired ptosis on ocular aberrations. In congenital group, Total aberrations at 5 mm and 6 mm were significantly higher along with PPRCyl. Z331 and Total Trefoil were significantly lower in ptotic eyes. In acquired group, however, higher order aberrations were more affected, being significantly higher in ptotic eyes. PPRSeq and PPRCyl were also statistically different between ptotic and fellow eyes. As with corneal topography, ocular aberrations, both total and higher order are mirror symmetric between eyes. This symmetry is lost in presence of ptosis. As with topography, higher order aberrations become symmetric after surgery in acquired ptosis, while in congenital ptosis no such change is observed, as illustrated in Figure-3 and Figure-4. At 6 months, Z310 and Total Coma were found to be statistically different between ptotic and fellow eyes. In the congenital group, at 6 months post-op, only Total Coma was found to be significantly different between ptotic and fellow eyes, being greater in ptotic eyes. Thus, 6 months after surgery total coma aberrations increase in ptotic eyes. 740 In the acquired group, at 6 months post-op, total aberrations at 5 mm and 6 mm along with Z310 were significantly reduced in ptotic eyes. Thus, at 6 months, in acquired ptosis, total aberrations decrease after surgery. The difference in the reversibility of aberration profile post-operatively between congenital and acquired ptosis may be due to ‘Corneal Hysteresis’- the viscoelastic property of cornea.21 Limitations of this study include • A small sample size and a still smaller sample for follow-up after surgery. • Short follow up time. • Inherent property of aberrations to get affected by the time of the day, size of pupil and state of accommodation. • Reliability and repeatability of Orbscan. In conclusion, ptosis affects the corneal shape as also corneal topography and ocular aberrations. There is difference in the effects of congenital and acquired ptosis, where congenital ptosis cause increase in total aberrations, acquired ptosis cause increase in higher order aberrations. Postoperatively, effects of congenital ptosis are irreversible, while that of acquired reverse after surgery. Orbit and Oculoplasty Free Papers

REFERENCEs 1. Bradley EA, Chapman KL, Bartley GB. Albert and Jakobiec’s principles and practice of ophthalmology. Philadelphia, USA. Saunders Elsevier; 2008;3rd ed:p. 3395. 2. Holck DE, Dutton J J, Wehrly SR. Changes in astigmatism after ptosis surgery measured by corneal topography. Ophthal Plast Reconstr Surg. 1998;14:151-8. 3. Basic and Clinical Science Course, Section 3- Clinical Optics, p.93-103,237-240, Section 13- Refractive Surgery, p.5-9, American Academy of Ophthalmology, 2011-2012 4. Thibos, L. N. Handbook of Visual Optics, Draft Chapter on Standards for Reporting Aberrations of the Eye. 1999; http://research.opt.indiana.edu/ Library/HVO/Handbook.html. 5. Thibos, L., Applegate, R.A., Schweigerling, J.T., Webb, R., VSIA Standards Taskforce Members (2000), “Standards for Reporting the Optical Aberrations of Eyes,” OSA Trends in Optics and Photonics Vol. 35, Vision Science and its Applications, Lakshminarayanan, V. (ed) (Optical Society of America, Washington, DC), pp: 232-244 6. Brown MS, Siegel IM, Lisman RD. Prospective analysis of changes in corneal topography after upper eyelid surgery. Ophthal Plast Reconstr Surg. 1999;15:378- 83. 7. Gingold MP, Ehlers WH, Rodgers RI, Hornblass A. Changes in refraction and keratometry after surgery for acquired ptosis. Ophthal Plast Reconstr Surg. 741 1994;10:241-6. 8. Cadera W, Orton RB, Hakim O. Changes in astigmatism after surgery for congenital ptosis. J Pediatr Ophthalmol Strabismus. 1992;29:85-8. 9. Wilson G, Bell C, Chotai S. The effect of lifting the lids on corneal astigmatism. Am J Optom Physiol Opt. 1982;59:670-4. 10. Gullstrand A. The cornea. In: Southall JPC, ed. Helmholtz’s Treatise on Physiological optics. New York, NY: Dover Publications Inc; 1962:320-1. 11. Robb RM. Refractive errors associated with hemangiomas or the eyelids and orbit in infancy. Am J Ophthalmol. 1977;83:52-8. 12. Mavrikakis I, Beckingsale P, Lee E, Riaz Y, Brittain P. Changes in corneal topography with upper eyelid gold weight implants. Ophthal Plast Reconstr Surg. 2006;22:331-4. 13. Nisted M, Hofstetter HW. Effect of chalazion on astigmatism. Am J Optom Physiol Opt. 1974;51:579-82. 14. Cuttone JM, Durso F, Miller M, Evans LS. The relationship between soft tissue anomalies around the orbit and globe and astigmatic refractive errors: a preliminary report. J Pediatr Ophthalmol Strabismus. 1980;17:29-36. 15. Detorakis ET, Ioannakis K, Kozobolis VP. Corneal topography in involutional ectropion of the lower eyelid: preoperative and postoperative evaluation. Cornea. 2005;24:431-4. 73rd AIOC 2015, New Delhi

16. Bogan S J, Waring GO, Ibrahim 0, Drews C, Curtis L.Classification of normal corneal topography based on computer-assisted videokeratography. Arch Ophthalmol 1990;108:945-9. 17. Wilson SE, Klyce SD. Quantitative descriptors of corneal topography: A clinical study. Arch Ophthalmol 1991;109:349-53. 18. Dingeldein SA, Klyce SD. The topography of normal corneas. Arch Ophthalmol 1989;107:512-8. 19. Ugurbas SH, Zilelioglu G. Corneal topography in patients with congenital ptosis. Eye (Lond). 1999;13:550-4. 20. Agarwal A, et. al., Unilateral Congenital Ptosis And Ocular Higher Order Aberrations In Children. Mehdi Ophthalmol 2013; Vol. 2, No 2. 21. Schroeder B, Hager A, Kutschan A et. al. Measurement of viscoelastic corneal parameters (corneal hysteresis) in patients with primary open angle glaucoma. Ophthalmology. 2008;105:916-20.

Correction of Lagophthalmos with Modified 742 Full-Thickness Upper Lid Blepharotomy and Lower Lid Lift Dr. Roshmi Gupta aralytic lagophthalmos is commonly seen after Bell’s palsy, Pmicrovascular facial nerve paresis, trauma, and post parotid surgery or intra-cranial surgery, particularly for acoustic neuroma. The first two conditions are self-limiting; temporising measures with lubrication, ocular surface protection and occasionally temporary tarsorrhaphy are adequate to prevent serious corneal effects. Long-standing paralytic lagophthalmos gives rise to exposure keratopathy, with watering, foreign body sensation, or even vision-threatening corneal ulcer. Patients with history of acoustic neuroma are at a greater risk still, due to lack of corneal sensation. Levator recession has also been suggested in order to reduce the palpebral fissure height and decrease lagophthalmos.1 There are multiple other suggested modalities of management for such patients. These include tarsorrhaphy, reanimation with temporalis muscle transfer, lid weighing with gold or platinum, and palpebral springs.2,4 Any management of paralytic lagophthalmos should address both the lower and the upper lid. When the orbicularis oculi is paralysed, both Orbit and Oculoplasty Free Papers

superior and inferior lid retractors act unopposed. Eventually, with loss of orbicularis tone, the lower lid begins to sag to the effect of gravity, and an ectropion results. Lower lid retractor release and re-suspension of the lower lid at a higher level can improve the lower lid position. This may or may not be in addition to lower lid spacer. Full thickness blepharotomy as described by is practiced widely for lowering the upper lid position for lid retraction in thyroid eye disease and in lid retraction not associated with thyroid orbitopathy.5,7 This study explores the utility of the same technique, along with the lower lid lift in patients with paralytic lagophthalmos. Aim of this study is to looks at the efficacy of combining upper lid full thickness blepharotomy with lower lid lift in correction of paralytic lagophthalmos.

Materials and Methods This is a retrospective non-comparative interventional case series of patients operated by a single surgeon between 2010 and 2013. Records of all surgeries performed by this technique were reviewed, and patients with follow up 6 months or longer were included in this study. 743 All patients were operated under local anesthesia. Upper lid crease incision was made, and dissection was carried out in the sub-orbicularis plane to expose 5-6 mm of the levator aponeurosis. With a corneal shield in place, using a monopolar probe of a radiofrequency surgical unit, incision was made full thickness of the levator-mullers-conjunctival layer. The incision was placed 3-4 mm above the upper border of the tarsus to avoid haemorrhaging from the superior vascular arcade. The incision was extended along the horizontal length of the lid, beginning at the lateral aspect. The patient is asked to look up and down , and the lagophthalmos was assessed on table. If further correction is desired, the horizontal extent of the incision is increased. A small bridge of tissue is left in the centre. This was in order to maintain a good lid contour, and not cause ‘flattening’. Through the same incision, tenotomy scissors are spread to dissect superiorly to the lateral third of the superior orbital rim. In the lower lid, a lateral canthotomy and cantholysis are performed. The lower lid is everted, and the monopolar probe is used to make an incision in the conjunctiva 2-3 mm inferior to the inferior edge of the lower lid tarsus. The conjunctival and lower lid retractors are dissected off their attachments to the lower lid tarsus. If placement of a lower lid spacer is planned, at 73rd AIOC 2015, New Delhi

this stage a donor scleral strip about 6 -8 mm in width and full length of the horizontal extent of the tarsus is used. It is secured inferiorly to the conjunctiva-lower lid retractor and superiorly to the inferior edge of the tarsal plate with 6-0 vicryl sutures. A 5-0 polypropylene suture on a half- circle cutting needle is taken. The suture is passed through the periosteum on the lateral aspect of the superior orbital margin. The suture is passed inferiorly through the lateral end of the upper lid incision to emerge in the lateral canthotomy incision. The suture is passes through the lateral end of the tarsal plate, and returned through the lateral canthotomy, and coming out of the upper lid incision. The 5-0 polypropylene is tied, thus lifting the lower lid and suspending it from the superior orbital rim. The upper lid incision is repaired with interrupted 6-0 polypropylene sutures, leaving the deeper layers separated. The lateral canthotomy is similarly repaired. The conjunctival incision in the lower lid is left unsutured. A marginal suture tarsorrhaphy is performed securing the upper and the lower lids together to keep them on stretch while the healing takes place. The eye is patched for a day, and put on systemic antibiotics and analgesics. 744 The patient is reviewed at 10-14 days, the skin sutures as well as the traction sutures are removed. In each patient, the preoperative lagophthalmos, and that at first post- operative review, at 6 weeks and at every subsequent visit is noted. The Bells phenomenon, any keratopathy are also noted.

Results Nine eyes of 9 patients were operated. Six patients were male and three were female. The age range of the patients was form 23 to 67 years. The duration of the lagophthalmos ranged from 6 months to 10 years. At presentation, eight of nine eyes had exposure keratopathy, seen with fluoresceine stain on slit lamp examination. The above described technique was performed in all patients. One patient had an additional donor sclera lower lid spacer used. At first post-operative follow up at 10th or 14th day, lagophthalmos was resolved in all eyes. The follow up duration was from 6 months to 3 years (mean 1.5 years). At final follow up no patient had exposure keratopathy, and lubricants had been discontinued. Residual lagophthalmos was 0 in 4 eyes, 1 mm in 2 and 2 mm in 3 eyes. One eye had a pyogenic granuloma in the lower lid conjunctival aspect, which was excised and did not recur. Orbit and Oculoplasty Free Papers

Discussion Management of paralytic lagophthalmos required both a dynamic and a static correction. The orbicularis oculi is unable to contract strongly to close the lid. The unopposed action of the lid retractors, levator palpebrae superioris in the upper lid and the lower lid retractors in the lower lid further exaggerate the lid retraction and increase the lagophthalmos. The lid positions should be such that the lagophthalmos is eliminated, but ptosis induced is minimal. Levator aponeurosis recession is used extensively to weaken the upper lid retractors. However, the outcome is not predictable.1 Lid loading with gold and platinum is practiced. This is a simple technique. It however incurs the additional expense of the implant.2,3 There is a very real risk of exposure of the metal implant.2 Palpebral springs are used in very few centers. They are technically challenging. Although they offer a dynamic lid correction, they are also prone to exposure and metal fatigue.4 Myotomy is an accepted technique of weakening the action of a muscle. Myotomies are used for squint correction. In the eyelid, the blepharotomy advised by Elner et. al. for thyroid lid retraction results in myotomy of the levator, and weakening of its effect. The technique described in this study uses the same principle to reduce the unopposed action of the upper lid 745 levator and correct lagophthalmos. In conclusion, this method corrects lid retractors antagonistic to orbicularis, and lower lid malposition. Expense of a metal implant and risk of extrusion is avoided. The technique is simple and effective, and helps to improve protection of the cornea in a patient with lagophthalmos.

References 1. Ueland HO(1), Uchermann A, Rødahl E. Levator recession with adjustable sutures for correction of upper eyelid retraction in thyroid eye disease. Acta Ophthalmol. 2014 Apr 3. [Epub ahead of print]. 2. Bladen JC(1), Norris JH, Malhotra R. Indications and outcomes for revision of gold weight implants in upper eyelid loading. Br J Ophthalmol. 2012;96:485-9. 3. Bladen JC(1), Norris JH, Malhotra R. Cosmetic comparison of gold weight and platinum chain insertion in primary upper eyelid loading for lagophthalmos. Ophthal Plast Reconstr Surg. 2012;28:171-5. 4. Demirci H(1), Frueh BR. Palpebral spring in the management of lagophthalmos and exposure keratopathy secondary to facial nerve palsy. Ophthal Plast Reconstr Surg. 2009;25:270-5. 5. Nimitwongsakul A(1), Zoumalan CI, Kazim M. Modified full-thickness blepharotomy for treatment of thyroid eye disease. Ophthal Plast Reconstr Surg. 2013;29:44-7. 73rd AIOC 2015, New Delhi

6. Demirci H(1), Hassan AS, Reck SD, Frueh BR, Elner VM. Graded full-thickness anterior blepharotomy for correction of upper eyelid retraction not associated with thyroid eye disease. Ophthal Plast Reconstr Surg. 2007;23:39-45. 7. Elner VM(1), Hassan AS, Frueh BR. Graded full-thickness anterior blepharotomy for upper eyelid retraction. Arch Ophthalmol. 2004;122:55-60. 8. De Ancos E, Strickler J, Klainguti G. Treatment of alphabetic “V” syndromes. Klin Monbl Augenheilkd. 1995;206:347-50. French. 9. De Faber JT, von Noorden GK. Medial rectus muscle marginal myotomies forpersistent esotropia. Am J Ophthalmol. 1991;112:702-5.

Intravenous Methylprednisolone in Moderate to Severe Thyroid Associated Orbitopathy (TAO) in Indians Dr. Shweta Gupta, Dr. Usha Singh, Dr. Manpreet Singh, Dr. Zoramthara 746 hyroid associated Orbitopathy (TAO) is an autoimmune disorder of the Tretrobulbar tissue2 that is often associated with Graves’ disease, but it also occurs in patients who are hypothyroid due to chronic autoimmune Hashimoto thyroiditis, as well as in patients with normal thyroid function (euthyroid orbitopathy).3 Approximately half of the patients with Graves’ disease have ocular involvement, but it is usually mild; clinically relevant moderate to severe disease occurs in 20-30% and is sight-threatening in 3-5% of patients.4 Steroids are the first-line treatment for moderate-to severe and active TAO.5 Several studies have documented the effectiveness of steroid by the oral, intravenous or intrabulbar route,4,6 but the optimal treatment involving no or minimal side effects is still undefined. Although the intravenous route is considered to be more effective and better tolerated than the oral route, severe adverse events, are more common in patients who receive intravenous steroids, usually exceeding 8g, though it may occur on low doses as well.6,7 The aim of the present study was to analyze the efficacy and safety of combined intravenous methylprednisolone (IVMP) therapy followed by oral steroids.

Materials and Methods The study included 18 patients from the oculoplastics clinic of Advanced Eye Centre of Post Graduate Institute of Medical Education and Research, Orbit and Oculoplasty Free Papers

Chandigarh, India, between June 2011 and April 2014. Inclusion criteria was previously untreated, active, moderate-to-severe TAO (lid retraction >2 mm, moderate/severe soft tissue involvement, exophthalmos >3 mm, diplopia) and sight threatening TAO (optic neuropathy and/ or corneal breakdown), whereas patient with mild disease were excluded. Complete blood biochemical( blood sugar levels, liver function tests) and thyroid profile along with clinical evaluation including blood pressure monitoring and endocrinology consultation were done before the start of the treatment and follow-up. Informed consent was obtained from all patients. Patients received IVMP in three different protocols, which were regular treatment of 1 gm IVMP for three days repeated after every 24 h (10 pts), pulse therapy of 500mg of methylprednisolone in 500ml of physiologic saline weekly for six weeks followed by 250 mg weekly for six weeks (5 patients) and combined treatment (3 patients). After completion of intravenous infusion, patients were started on oral prednisone according to the following schedule: 40 mg/day for the first week, 30 mg/day for the second week, 20 mg/day for the third week and 10 mg/day for the fourth week.8 This sequence of therapy was repeated each month for the next 2 months i.e. in each of the following protocols IVMP was then followed by tapering doses of oral prednisone for 6-8 weeks. The cumulative dose was 9g (not exceeding 10g). Ophthalmological assessment was performed before, at 1 week, 1 month, 3 month and 6 months after start of treatment. Side effects of steroid therapy 747 were evaluated and recorded each month. Ophthalmological evaluation Complete ophthalmological examination of patients was done at baseline, at 1 week, 1 month, 3 month and 6 months. VISA classification1 was used for the analysis of improvement in Vision, Inflammation, Strabismus and Appearance and included evaluation Visual acuity, Visual field, RAPD, disc status, soft tissue involvement and disease activity, diplopia, proptosis, intraocular pressure and schirmer test. Visual fields assessment was done using 76’2 SITA standard strategy, with Humphery VF Analyser. Soft tissue involvement was documented with reference to the Color Atlas given by EUGOGO.9 Proptosis was evaluated using the Hertel exophthalmometer. Assessment of disease activity was carried out using the clinical activity score (CAS) which consists of seven points: spontaneous retrobulbar pain, pain during eye movement, conjunctival redness, redness of the eyelids, chemosis, swelling of the caruncle and swelling of the eyelids; the final score was calculated as the sum (1 point for each) of all items.11 Eye muscle involvement was assessed using the Gorman diplopia score: no diplopia (absent), diplopia when patient is tired or awakening (intermittent), diplopia at extremes of gaze (inconstant) and continuous diplopia in the primary 73rd AIOC 2015, New Delhi

Table 1: Demographic and clinical data of Thyroid patients with moderate to Severe disease Age (years) 52.92±11.7 years (32-75 y) Female: male 7:11 (F-38.8%) UL:BL 9:9 Duration of thyroid disease (months) 56.5 m (1 m,30 year ) Duration of TAO (months) 3.6 m (2 d,2 yr) History of Smoking 1 (5.55%) Family h/o of thyroid disease 1 (5.55%) Thyroid Status Graves’ disease 8 (44.44%) Hashimoto thyroiditis 3 (16.66%) Euthyroidism 7 (38.8%) Associated systemic disease Diabetic 4 (22.22%) Hypertension 7 (38.8%) Associated dermopathy/ Autoimmune disease: None

Table 2: Change in CAS, proptosis and ocular pressure before and 748 after therapy Before After P value Proptosis(mm) 4.70±1.83 2.87±2.20 P< 0.05 Intraocular pressure (mmHg) 20.8±8.12 18.9±6.76 Not significant CAS 4.05±1.22 (6,1) 1.38±1.06 (5,0) P <0.05

and reading position (constant).10 The overall response to the therapy after 6 months was defined as a relevant improvement of at least the two major criteria (decrease in proptosis and lid width of 2 mm each, changes in degree of diplopia, changes in the CAS of 2 points or more and changes of 1/10 or more in visual acuity) and one minor criterion (soft tissue changes, self assessment evaluation).12 In addition, all adverse events and biochemistry analysis were recorded at monthly intervals. Patients were followed for the next 6 months. Evaluation of thyroid function Thyroid function was assessed by measuring serum total T3 (TT3;0.9-2.8 nmol/L, total T4 (TT4; normal range 55-160nmol/L), and TSH (normal range 0.15- 0.5mIU/L). Statistical analysis The normality assumption for continuous variables was evaluated by Orbit and Oculoplasty Free Papers

Table 3: Comparison of our study with reported western literature Our study[Indian Study] Belesin et. al. Hormones 2014 No. of patients(n) 18 50 Age(yrs) 52.92±11.7 48±10 Evaluation period (m) 3 6 IV methylpred regime 1g*3 days 250 mg wkly *6 wks 500 mg for 2 alternate days* 6m Combined Improvement in VA 61.1% 36% Decrease in mean CAS 4.0 to 1.38 4.5 to 2 Improvement 16(94.4%) 37(74%) No change Nil 13(26%) Deterioration 1(5.55%) Nil Diplopia improvement 4 (100%) 21(42%) Overall Response 17(94.4%) 33(66%) Side effects 2(11.1%) 35(70%) Relapse 1/17(5.55%) 2/33(6%) the Kolmogorov-Smirnov test. Continuous variables are presented as means and standard deviations for normally distributed variables. They 749 were compared using the one-way Student’s t test for paired samples, or its non-parametric equivalent, the Wilcoxon matched-pair signed rank test. Categorical variables are presented as counts and percentages and were compared with the chi-square test or McNemar’s test for repeated measurements. To test parameters independently associated with treatment response, variables (age, gender, smoking, duration of TAO ) multivariable regression was used. For all analyses, a two-sided p<0.05 was considered statistically significant.

RESULTS The demographic and clinical data of the study patients are presented in Table 1. The mean age group of patients was 52.92±11.7 years ranging from (32-75) out of which 11(61.11%) were male. At presentation, 8(44.44%) patients were hyperthyroid, 7(38.88%) patients were euthyroid while 3(16.66%) patients were hypothyroid. All patients became euthyroid after hormonal therapy and remained euthyroid during the treatment. Most common presenting symptoms were proptosis (9), followed by swelling of eyelids (7), watering (5), diplopia (4), redness (5), dimunition of vision (2), pain at rest (2), foreign body sensation (1), drooping of eyelid (1). Most common signs were conjunctival inflammation (18), eyelid signs (15), eyelid inflammation (15), 73rd AIOC 2015, New Delhi

eyelid retraction (14), caruncle inflammation (5) and ptosis (1). VISION of VISA classification [Figure 1]. Visual acuity of majority of patients was ranging from 20/40 to 20/200 both pre and post treatment. One patient who was denied light Figure 1: Response in Visual Acuity after treatment with IV intravenous Methylprednislone in thyroid perception improved to light disease with active disease. perceiving after treatment. Visual fields, relative afferent pupillary defect, disc edema which were present in 8 (44.4%), 5 (27.7%) and 3 (16.6%) patients respectively were completely resolved. Vision improved in 11/18(61.1%) of patients and deteriorated in 1(5.55%) of patients, while there was stable visual acuity in 6/18 (33.33%) of patients. Inflammation CAS9 (Clinical Activity Score) Mean CAS values decreased from 4.05±1.22 to 1.38±1.06 (p<0.01). 17 patients 750 (94.44%) demonstrated improvement, and one of the patients (5.55%) presented with deterioration of inflammatory status. Strabismus Diplopia Before treatment, inconstant and constant diplopia was present in 1(5.55%), and 3(16.66%) patients, respectively, whereas 14 patients (77.77%) did not have diplopia. Following treatment, no diplopia was present in any of the patients (p<0.001). Improvement is seen in all 4 patients i.e. disappeared completely (100%), while no deterioration was observed. Improvement is seen in all the patients with raised RETROBULBAR RESISTANCE AND EOM RESTRICTION which were present in 16 patients each respectively. Appearance Proptosis There was significant change in the mean values of proptosis from 4.70±1.83 to 2.87±2.20 (p<0.05) at the end of treatment. There was improvement in 14 (77.77%) of patients, deterioration in 3(16.66%) and no change in 1(5.55%) of patients (Figure 2). However, abnormal exophthalmometer readings Orbit and Oculoplasty Free Papers

(values of >19) persisted at the end of follow-up in most of the patients 13(72.22%) which were present in 17(94.44%) patients pretreatment. Intraocular pressure There was no significant difference in the mean values of intraocular pressure before and after treatment. Out of Figure 2: Response of thyroid patients with active 11 patients with raised IOP, disease to Intravenous IV methylprednisolone. ocular pressure improved in Comparison of pre and post treatment. 6/11 (54.54%) of patients and deteriorated in 2/11 (18.18%) of patients, while there was no change in 3/11 (27.27%) of patients. Corneal involvement was present in 4(22.2%) patients pretreatment, which was resolved in two patients. Improvement was also observed in Shirmer test, values <5 which were present in 7(38.8%) patients pretreatment were reduced to 2 patients post treatment. Overall clinical response 751 Treatment with IVMP resulted in rapid and clinically significant improvement. According to the defined criteria, 17 out of 18 patients (94.4%) demonstrated treatment response. Improvement in VISA classification after 6 month of follow up[figure 2]. A. Vision: Vision improved in 11/18 (61.1%) of patients while there was stable visual acuity in 6/18(33..33%) of patients.and deteriorated in 1/18(5.55%) of patients, B. Inflammation: 17 patients (94.44%) demonstrated improvement, and one of the patients (5.55%) presented with deterioration of inflammatory status. C. Strabismus: 100% improvement in Strabismus/ Extraocular movement restriction. D. Appearance: 14/18(77.77%) patients became better in appearance, 1(5.55%) patients was stable while 3(16.66%) patients deteriorated. Adverse effects of steroid therapy The overall rate of steroid-related side effects was 4/18 (22.22 %), but the majority of them were mild and only one patient developed serious major side effect. Out of the 4 patients , 3 developed raised intraocular pressure 73rd AIOC 2015, New Delhi

while one patient developed psychosis which were resolved completely with treatment. There was mild, but clinically non-significant, increase in blood pressure was observed. There was no significant weight gain (defined as increase of >3 kg), blood glucose, serum lipids, amino transferases in the study population over 6 months month follow-up. None of the patients developed hirsutism, myalgia, urinary infections, sleeplessness, palpitations, Gastrointestinal discomfort, Depression, Transient leukocytosis, Herpes Zoster infection or pulmonary tuberculosis. During the 6 months follow-up 1/18 patients (5.55%) had relapse.

DISCUSSION This was a retrospective analysis of efficacy and tolerability of a combined parenteral and oral steroid therapy in 18 patients with untreated and active Thyroid associated orbitopathy. The present study also evaluated the effects of different parameters such as smoking, CAS, duration of TAO, duration of hyperthyroidism, gender and age impact on the response to steroids. We have demonstrated that combined parenteral and oral steroid therapy is effective and safe in the treatment of TAO.

752 The response rate in our study group was 94.4 %. As expected, IV Steroids showed the greatest effectiveness on soft tissue changes (incorporated in the CAS), whereas proptosis was less responsive. Average decrease in CAS of 2.5 and 3.5 points and inactivation of Graves orbitopathy according to CAS of 59% and 89% was reported in randomized and nonrandomized trials, respectively.6 Our results demonstrating a significant decrease of 2.6 points are in concordance with previous reports. Proptosis did not change significantly in our study and improvement of at least 2 mm occurred in 9(50%) of patients, which is similar with several previous studies,13,14 while some other studies showed a better response.15,16 In the study by Belesin et. al. 19 patients with CAS >4 points had better treatment response (80%) compared with patients with CAS<4 who had treatment response of 23% (p<0.05). In our study, all the patients were having CAS>4. According to multivariable regression analysis, the only independent parameter associated with positive treatment response was CAS>4 (p<0.001). Steroids have anti-inflammatory and immunosuppressive actions and have favorable effects during the active phase of TAO. High CAS, high TSHRAb levels and shorter duration of orbitopathy are well known parameters of TAO activity and predictors of therapeutic efficacy. In our patients the response to IVMP therapy was influenced by long duration of thyroid disease, associated diabetes Orbit and Oculoplasty Free Papers

mellitus, high intraocular pressure, smoking behavior and pulse therapy, which were found to be associated with the patients, who responded sub optimally to the treatment. Smoking affects the immunological reactions in the pathogenesis of the disease, alters the structure of thyrotropin receptor making it more immunogenic that leads to the production of thyrotropin receptor stimulating antibodies that react strongly with retro-orbital tissue.17 In addition, smoking decreases the effectiveness of glucocorticoids in a dose-dependent manner during treatment.18 We did not find any impact of gender and age on the response to therapy, unlike a previous study where patients younger than 50 years of age and female subjects responded better to steroid therapy.16 Adverse events are a major concern of steroid therapy with morbidity and mortality rates of 6.5 and 0.6%, respectively.6 There are numerous case series and reports on the potential serious cardiovascular, cerebrovascular, hepatic risk and severe infections some even with fatal outcome.6 In our study, blood sugar levels, liver enzymes, BP evaluated every month, were in the normal range in all patients. One patient in our group developed psychosis which has been documented as serious side effects.7 All other side effects were non-severe and resolved with treatment. Belesin et. al. [Table 1] found that weight gain and hirsutism are the most common side 19 effects, whereas serious side effects depend on preexisting disease as well. 753 In our study all patients had significant improvement in the Quality of life related to vision, physical(symptoms) and psychological function after the treatment. In regard to treatment protocol, it is documented that the intravenous route is more effective and better tolerated than the oral route.15,16 However, deterioration of vision is very common problem after discontinuation of pulse therapy. A recent multicenter study7 described relapse in 33%, 21% and 40% corresponding to different cumulative doses of 2.25, 4.98 or 7.47g, respectively, in 12 weekly infusions. Relapse rate in our study was only 5.55%. It seems that intermittent pulse oral prednisone reduces recurrence rate and maintains improvement stability. Common protocol uses a 4.5g cumulative dose of methylprednisolone subdivided into 12 weekly infusions.16 Some patients, especially those who live far from a tertiary care centre and need several hours of travel, preferred regular high dose IVMP protocol to a weekly protocol and find it more convenient. Thus, the protocol including hospitalization of the patients for 3 days, including for IVMP and oral therapy at home afterwards, seems more clinically appropriate and feasible. Moreover, considering the possibility of development of side effects, it seems to be safer for the patients to have monthly biochemical and clinical evaluation. 73rd AIOC 2015, New Delhi

In comparison to other studies evaluating the effects and safety of different IV steroids protocols in TAO, the present study is the only study which is being reported in the Indian context. Since this study includes only limited number of patients with short follow up and retrospective analysis of data; a well controlled, large randomised prospective, study will give further insight in this scenario. In conclusion, Intravenous methylprednisolone is safe and efficacious in improving TAO in majority of acute cases along with control of co- morbid conditions. Thorough clinical evaluation, close monitoring while administering the drug and adequate management of co-morbid conditions make it a safe therapy. Appropriate selection of patients based on the severity of the disease and the potential for the development of side effects from the high doses of steroid therapy is warranted.

REFERENCES 1. Dolman PJ, Rootman J., VISA Classification for Graves orbitopathy. Ophthalmic Plastic Reconstructive Surgery 2006;22:319–24. 2. Bahn RS. Graves ophthalmopathy. N Engl J Med 2010;362:726-38. 3. Burch HB, Wartofsky L, Graves ophthalmopathy: Current concepts regarding pathogenesis and treatment. Endocr Rev 1993;14:747-93. 754 4. Bartalena L, Pinchera A, Marcocci C, Management of Graves ophthalmopathy: Reality and perspectives Endocr Rev 2000;21:168-99. 5. Bartalena L, Baldeschi L, Dickinson AJ, et. al., Consensus statement of the European group on Graves orbitopathy (EUGOGO) on management of Graves orbitopathy. Thyroid 2008;18:336-46. 6. Zang S, Ponto KA, Kahaly GJ. Intravenous glucocorticoids for Graves orbitopathy: Efficacy and morbidity. J Clin Endocrinol Metab 2011;96:320-32. 7. Bartalena L, Krassas GE, Wiersinga W, Efficiacy of three different cumulative doses of intravenous methylprednisolone for moderate to severe and active Graves’ orbitopathy. J Clin Endocrinol Metab 2012;97:4454-63. 8. Kendall-Taylor P, Crombie AL, Stephenson AM, et. al., Intravenous methylprednisolone in the treatment of Graves ophthalmopathy. Br Med J 1988;297:1574-8. 9. Dickinson AJ, Perros P. Controversies in the clinical evaluation of active thyroid associated orbitopathy: use of a detailed protocol with compartice photographs for objective assessment. Clin Endocrinol (Oxf) 2001;55:283-303. 10. Bahn RS, Gorman C. Choice of therapy and criteria for assessing treatment outcome in thyroid-associated ophthalmopathy. Endocrinol Metab Clin N Am 1987;16:391- 407. 11. Mourits MP, Prummel MF, Wiersinga WM, Koornneef L. Clinical activity score as a guide in the management of patients with Graves ophthalmopathy. Clin Endocrinol (Oxf) 1997;47:9-14. Orbit and Oculoplasty Free Papers

12. Bartalena L, Marcocci C, Bogazzi F, et. al., Relation between therapy for hyperhyroidism and the course of Graves ophthalmopathy. N Engl J Med 1998;338:73-8. 13. Kendall-Taylor P, Crombie AL, Stephenson AM, et. al. Intravenous methylprednisolone in the treatment of Graves’ Ophthalmopathy. Br Med J 1998;297:1574-8. 14. Kaupinen-Makelin R, Karma A, Leinomen E, et. al., High dose intravenous methylprednisolone pulse therapy versus oral prednisone for thyroid associated ophthalmopathy. Ophthalmol Scand 2002;80:316-21. 15. Marcocci C, Bartalena L, Tanda LM, et. al., 2001 Comparison of the effectiveness and tolerability of intravenous or oral glucocorticoids associated with orbital radiotherapy in the management of severe Graves’ ophthalmopathy: results of a prospective, single-blind, randomized study. J Clin Endocrinol Metab. 2001;86: 3562-7. 16. Kahaly GJ, Pitz S, Hommel G, Dittmar M. Randomized, single blind trial of intravenous versus oral steroid monotherapy in Graves’ orbitopathy. J Clin Endocrinol Metab 2005;90:5234-40. 17. Utiger RD. Effects of smoking on thyroid function. Eur J Enocrinol 1998;138: 368-9. 18. Hegedius L, Brix TH, Vestergaard P. Relationship between cigaretes smoking and Graves ophthalmopathy. J Endocrinol Invest 2004;27:265-71. 19. Beleslin BN, Ciric J, Zarkovic M, Stojkovic M. Efficacy and safety of combined parenteral and oral steroid therapy in Graves’ orbitopathy. Hormones 2014. 755

Are Frozen Section Margin Control and Conjunctival Map Biopsy Mandated in Sebaceous Gland Carcinoma of the Eyelid? Dr. Fairooz PM, Dr. Santosh G Honavar, Dr. Vemuganti Geeta Kashyap ebaceous gland carcinoma (SGC) is one of the most lethal malignant Seyelid tumors, with rate of systemic metastasis ranging from 8% to 28%, culminating in death in 6 to 8%.1,6 The reported rate of local tumor recurrence following excision ranges from 8 to 36%.1,4-1 As in any other malignant disease, early diagnosis and optimal treatment can reduce recurrence and improve patient survival. Rao et. al. identified the poor prognostic factors in SGC; these included infiltrative pattern and conjunctival intraepithelial spread, apart from other parameters.3 Failure to excise the tumor completely carries high chance of local recurrence and regional and systemic metastasis. Local tumor 73rd AIOC 2015, New Delhi

recurrence, regional lymph node metastasis and systemic metastasis can be minimized with optimal primary management.12,13 The standard of care is excision of the tumor with intraoperative margin control, followed by eyelid reconstruction as appropriate.1,8,11,15-16 Intraoperative frozen section technique is specifically used to rapidly confirm margin clearance in malignant eyelid tumors.17 However, the need and the validity of this technique is often questioned. Detection of intraepithelial spread by conjunctival map biopsy has come to be an essential part of the clinical management of SGC.18-21 However, it is not yet a standard practice in many centers. Thus, there seems to be a paucity of literature on the validity of the two basic principles of surgical management in eyelid SGC – intraoperative frozen section margin control and conjunctival map biopsy. This study was performed to evaluate the utility of frozen section margin control and, conjunctival map biopsy in eyelid SGC.

Materials and Methods We retrospectively analyzed the medical records of all the patients with eyelid SGC who underwent primary excision biopsy with or without frozen section margin control and with or without conjunctival map biopsy at a tertiary care ocular oncology center in Southern India from January 1998 to Dec 2011. These two subsets were analyzed individually. Institutional 756 review board approval was obtained. Of the 143 eyes with eyelid sebaceous gland carcinoma, we included 107 consecutive patients (107 eyes) who underwent primary surgical excision biopsy. Patients with orbital invasion, regional lymph node metastasis and systemic metastasis at the initial presentation and, those with follow up less than 12 months were excluded form the study. The retrospective data analyzed constituted demographic profile including age at diagnosis (in years), gender, ethnicity and laterality. Presenting symptoms and duration of symptom were recorded. The ocular examination data included the laterality, location (upper eyelid, lower eyelid, both, caruncle), color, surface vascularity, size of the tumor (greatest dimension in mm, type (nodular, diffuse), fixity to the overlying skin, loss of eyelashes, and morphological appearance of the eyelid margin. Associated conjunctival (tarsal, bulbar and forniceal) congestion and/or thickening was specifically evaluated. Staging was performed according to American Joint Committee on Cancer (AJCC) TNM staging, 7th edition. Surgical records were analyzed for the nature of the surgical procedure, and margin excised (in mm). The data was tabulated separately for the two subgroups – frozen section margin control and conjunctival map biopsy. In the subgroup of frozen Orbit and Oculoplasty Free Papers

section margin control, patients were divided into two groups, Group A, who underwent frozen section margin control and, Group B where only primary excision with 4 mm margin was performed. The specimen was oriented on sterile filter paper by the surgeon and the margins were inked indicating the exact orientation. The specimen were placed on a cryostat chuck with minimal amount of OCT media and immersed in liquid nitrogen (-1960C) for 10 to 15 seconds until the tissue was completely frozen. Thinner sections (15 to 200m) were then cut and placed on the cryostat (-200C). The sections were stained by rapid H&E technique and reviewed by an experienced pathologist for evidence of positive or negative margins. Those with positive margins were subjected to an additional 2 mm margin excision and resubmitted for frozen section margin control. The frozen section reports were corroborated with the fixed section histopathology report. Other histopathological features including growth pattern (lobular, comedo or papillary), differentiation (well-differentiated, moderately differentiated or poorly differentiated) and, perivascular and perineural invasion were noted. We also performed univariate and multivariate analysis of the various clinical and histopathological factors leading to recurrence and evaluated the importance of margin status to prevent recurrence. Conjunctival map biopsy performed to determine the extent of conjunctival involvement and included 17 sites – 3, 6, 9 and 12 O’clock perilimbal bulbar 757 conjunctiva; medial, central and lateral superior and inferior fornicial conjunctiva; medial, central and lateral upper and lower tarsal conjunctiva; and plica semilunaris-caruncle. The map biopsy specimens each measuring about 2x2 mm were laid down on a filter paper with appropriate marking and numbering. These were processed for permanent section and evaluated on histopathology for the intraepithetlial involvement. The results were correlated with clinical parameters. Statistical Analysis Descriptive statistics were tabulated and reported. Univariable analysis was carried out by using either Chi-square test or Fischer’s exact test as appropriate. Independent sampled t-test was used to compare the means between the groups. Factors that were associated with the outcome recurrence with a p-value of ≤0.10 in the univariable analysis were considered for the multivariable logistic regression model. The logistic regression model fitness was assessed using the Hosmer-Lemeshow test. The variables, duration of symptom (weeks) and tumor size were categorized into groups based on its median. Kappa statistics was calculated to find the agreement between frozen section results and paraffin fixed section report. Statistical analysis was performed using the SPSS ver 17.0 for Windows (Chicago, IL). A p-value of less than 0.05 was considered to be statistically significant. 73rd AIOC 2015, New Delhi

Results We evaluated 107 consecutive eligible patients undergoing primary excision for eyelid SGC. The median age was 55 years (range, 30 to 86 years), with 60% females (n=64) and 40% males (n=43) of Asian ethnicity. The mean follow up was 44±30 (median 36, range 12 to 146) months. Tumor characteristics were studied in detail. The mean diameter (largest dimension) was found to be 13±7 mm. The tumor involved the upper eyelid (n=71, 66%), lower eyelid (n=31, 29%), both the eyelids (n=3, 3%) and caruncle (n=2, 2%). Clinical signs of diffuse conjunctival intraepithelial involvement (loss of eyelashes, loss of meibomian gland orifices, intermarginal strip telangiectatsia, rounding of the posterior eyelid margin, congestion of the tarsal or bulbar conjunctiva, thickening of the palpebral or bulbar conjunctiva, greyish discoloration of the tarsal or bulbar conjunctiva – all in the area of the eyelid where there was no obvious eyelid tumor, and thick ropy discharge) was noted in 6% (n=6). Multifocal SGC was found in 9% (n=10). The most common gland of origin was meibomian (n=85, 79%), followed by Zeis (n=17, 16%). According to AJCC classification, patients were staged as IC-T2b N0 M0 (n=41, 38%), II- T3a N0 M0 (n=4, 4%), and IIIA-T3b N0 M0 (n=25,23%). Histopathologically, 103 tumors were graded as G1 (n=17, 17%), G2 (n=80,78%) and, G3 (n=6,6%). Of the 107 eyes that underwent primary excision with 4 mm clinically clear 758 margins, 83 (78%) eyes underwent intraoperative frozen section margin control (Group A) and 24 (22%) eyes did not (Group B). Of 83 who underwent intraoperative frozen section margin control, 67 (81%) were reported negative and 16 (19%) were reported positive with tumor present in one of the margins. These 16 patients underwent excision of an additional 2 mm of the involved margin. Of these, 14 were negative. Two, which were reported as indeterminate with focal atypical cells, underwent double-freeze-thaw cryotherapy to the excision edge. In all, at the end of surgery, 81 (98%) were margin clear and 2 (2%) were indeterminate. In Group A, final histopathology on fixed sections showed 81 (98%) with margin negative. Two (2 of 67, 3%) of those whose initial frozen section was negative showed positive margins on fixed sections while two (2 of 16, 12.5%) where initial frozen section was positive showed negative margins on fixed sections. The frozen section-fixed section discordance rate was 5% (4 of 83). Of those who underwent excision of the tumor with 4 mm clinically clear margins but without intraoperative frozen section margin control, 12 (50%) eyes showed positive margins on fixed sections. The association between frozen section and margin status on final histopathology fixed sections was statistically significant. The negative margin status was more commonly seen in those where frozen section was done, 97.5% Vs 50% (p=0.002) Orbit and Oculoplasty Free Papers

The local tumor recurrence rate in eyes that underwent primary excision without frozen section margin control was found to be 38%, compared to 13% in eyes undergoing frozen section margin control (p=0.011). Univariate analysis of clinical features showed that tumors with diffuse borders had significantly higher recurrence rate 53% (9/17) Vs 11% (10/88) (p<0.0001). There was borderline association between multicentricity and tarsal involvement with recurrence (p=0.089 and 0.087 respectively). Pathological factors were analyzed separately including margin clearance, pagetoid spread, perivascular and perineural invasion and tumor differentiation. It showed that margin involvement and local tumor recurrence had significant association accounting to 43% (6/14) in those with positive margins, as compared to 15% (14/93) with clear margin (p<0.023). Mutlivariate analysis of pathological factors showed that margin status and recurrence had significant association. The multivariable logistic regression model has a better fit according to Hosmer-Lemeshow Test (Chi-square, 3.53; p=0.619). After adjustment in the multivariable logistic regression model for clinical and pathological features separately. SGC with clinically diffuse margins had higher recurrence rate, OR=7.05 [95% CI, 2.07, 23.99 (p=0.002)]. On a similar account margin positivity and recurrence rate had statistical significance, OR=2.78 [(95% CI, 0.66, 11.62 (p=0.162)]. 759 Frozen section results were corroborated with the final fixed section histopathology evaluation. Of the 83 eyes undergoing frozen section, 4 eyes did not corroborate with the final histopathology. We found fair agreement (Kappa= 0.32; p< 0.0001) between frozen section evaluation and, parafiin wax fixed section in 83 eyes. Overall, regional lymph node metastasis was found in 6% (n=6) and, prompt local lymph node dissection and external beam radiotherapy was performed in all. Out of the 3(3%) patients who died, 2(2%) had systemic metastasis and died due to disease progression, and one patient was detected to have bladder carcinoma. The patient was not evaluated for Muir-Torre syndrome. However, there existed no statistical significance for metastasis and death between the two groups. Of the 69 eyes that underwent map biopsy, 7(10%) were positive. Out of which, there was clinical suspicion in 6. The features suggesting clinical suspicion of intraepithelial spread included 1) diffuse thickening of eyelid margin, 2) loss of eyelashes, 3) loss of meibomian gland architecture, 4) surface telangiectasia, 5) associated diffuse conjunctival congestion, 6) discharge. It was found that the probability of positive map biopsy was higher if there was clinical suspicion of pagetoid spread (p=0.004). 73rd AIOC 2015, New Delhi

Table 1: Demographic Features of 107 patients with Sebaceous Gland Carcinoma

Demographic features Number (%) Age (years) Median (mean; range) 55 (56±12; 30 to 86) Gender Female 64 (60) Male 43 (40) Race Asian 107 (100) Lateratily Unilateral 107 (100) Bilateral 0 (0) Symptom duration (months) Median (mean; range) 13 (22±27; 2 to 130) Follow up (months) Median (mean; range) 36 (44±30; 12 to 146)

Table 2: Tumor Characteristics in 107 eyes with Sebaceous Gland 760 Carcinoma Tumor features Number (%) Size (largest dimension in mm) Median (mean; range) 12 (13±7; 3 to 30) Location Upper eyelid 71 (66) Lower eyelid 31 (29) Both eyelids 3 (3) Caruncle 2 (2) Conjunctival intraepithelial 5 (5) Cornea 0(0) Gland of origin Meibomian 85 (79) Zeiss 17 (16) Ectopic 5 (5) Multicentric 10(9) Miscellaneous Skin fixity 23(21) Tarsal fixity 89(83) Loss of lashes 75(70) Orbit and Oculoplasty Free Papers

Table 3: American Joint Committee on Cancer (AJCC) Staging and Classification

TNM Staging (n=107) Number (%) 0- T1s N0 M0 0 (0) IA- T1 N0 M0 0 (0) IB- T2a N0 M0 0 (0) IC- T2b N0 M0 41 (38) II- T3a N0 M0 4 (4) IIIA- T3b N0 M0 25 (23) IIIB- Any T N1 M0 0 (0) IIIC- T4 anyN M0 0 (0) IV- Any T anyN M1 0 (0) Histopathological grading (n=103) GX- grade cannot be identified 0 (0) G1- well differentiated 17 (17) G2- moderately differentiated 80 (78) G3- poorly differentiated 6 (6) 761 G4- undifferentiated 0 (0)

Table 4: Surgical treatment outcome of Group A (with frozen section) and, Group B eyes (without frozen section) Frozen section No Recurrence no. Recurrence no. Total no. (%) (%) (%) Performed- Group A 72 (87) 11 (13) 83 (78) Not performed- Group B 15 (62.5) 9 (37.5) 24 (22) Total 87 (81) 20 (19) 107 (100)

Table 5: Margin Status Vs Recurrence in 107 Eyes undergoing Primary Surgical Excision Biopsy Margin clearance Group A- frozen section Group B- without frozen section Status Total no. No. of eyes Total no. No. of eyes with of eyes (%) recurrence (%) of eyes (%) recurrence (%) Negative 81 (97.5) 11 (13.5) 12 (50) 3 (2.5) Positive 2 (2.5) 0 (0) 12 (50) 6(50) Total 83 (100) 11(13) 24 (100) 9 (37.5) 73rd AIOC 2015, New Delhi

Table 6: Outcome in terms of recurrence in Group A and Group B eyes Group A + Recurrence no. No Recurrence no. Total no. Group B (%) (%) (%) Performed- Group A 72 (87) 11 (13) 83 (78) Not performed- Group B 15 (62.5) 9 (37.5) 24 (22) Total 87 (81) 20 (19) 107 (100)

Discussion Eyelid SGC carries high rate of local tumor recurrence and systemic metastasis.1,11 SGC commonly arises form the meibomian glands of the tarsus or from the glands of Zeis as a yellowish, vascular, nodular/ noduloulcerative growth of the eyelid.1,3,14,22 Various authors have reported the intraepithelial (bowenoid, pagetoid and papillary) pattern in 40 to 80%, clinically mimicking other inflammatory conditions, thus leading to misdiagnosis.8,14,19,20,23 Six (6%) patients had diffuse conjunctival involvement with eyelid thickening in our series. Shields et. al. have reported metastasis in 8% and death due to disease in 6%.1 Rao et. al. showed mortality as high as 60% in locally advanced SGC.3 762 The optimal management includes early diagnosis, complete excision with clear margins and identification of intraepithelial spread and multiple tumor foci. Often, major factor leading to recurrence and tumor progression is incomplete excision.15 The standard surgical procedure recommended by various authors is complete excision including 4 to 5 mm normal appearing margin and frozen section margin control in well-circumscribed tumors. Dogru et. al. reported 36% recurrence in eyes with 1-3 mm margin clearance compared to no recurrence in those with 5 mm clearance.10 Margin involvement is found to be major risk factor for recurrence in our series. It was found that recurrence was as high as 43% in those without margin clearance compared to 15% in those with clear margins (p<0.0001). In the multivariate analysis, tumor with diffuse border had significantly high recurrence rate. Other factors that are suggested to favor local tumor recurrence are multicentricity, mandating intraoperative margin control before proceeding with eyelid reconstruction. Intraoperative frozen section and Moh’s micrographic surgery techniques can ensure margin control.4,11,14,15,24,25 Various reports support the utility of frozen section margin control in SGC to reduce the recurrence rate and re-operation. In our series the recurrence rate was 3 times higher in eyes undergoing excision without margin control (38%) compared to those with margin control (13%). Of the 29 eyes that underwent primary excision by Zucher Orbit and Oculoplasty Free Papers

et. al., frozen section and Moh’s surgery was performed in 9 and one case respectively, in which none had recurrence. Despite 4 mm margin clearance in 19 eyes without frozen section, the recurrence rate was 36% (n=7), requiring exenteration (n=2) and radiotherapy (n=1).13 Yoon et. al. analyzed 24 cases and, reported lower recurrence rate of 5.9% after complete excision under frozen section control and, 71.4% in incomplete excision and post- operatively irradiated eyes.11 This clearly demonstrates that inappropriate primary surgical excision leads to failure of complete cure necessitating additional treatment. Re-operative rates are high in such situations with increased morbidity and financial burden. Some authors believe that freezing and cryostat cutting may have low quality specimen for accurate diagnosis.17,26 Preito et. al. reported the diagnostic accuracy of en-face frozen section in melanocytic lesions of skin by dermatopathologists and, showed accurate assessment of margins cannot be achieved with enface frozen section in melanocytic lesions. Diagnostic discrepancies were seen in 40% of 330 evaluations of 22 cases by 15 dermatopathologists.27 Similar, descriptive studies in eyelid tumors have not been reported. Controversies still exist among ocular pathologists as to whether frozen section should be performed, or to wait for permanent formalin fixed sections. Tenzel in the initial reports on SGC stated “the use of frozen section for assurance of the adequacy of the margins of surgical 763 excision in mandatory”.17 Diagnostic accuracy of frozen section in SGC has been questioned due to the presence of pagetoid spread and multifocal tumors. Recently, While et. al. reported 17 patients who underwent excision biopsy (3 mm margin clearance) and, delayed reconstruction with rapid paraffin section analysis. Seven eyes showed positive margin on fixed section and, 2 patients (12%) had recurrence, of which one eye was reported to have multicentric tumor.25 Overall, histopathological diagnostic inaccuracy has been reported in >50% cases of SGC, mostly in inexperienced hands.7 Yoon et. al. reported a frozen section diagnostic discrepancy in 8.3% (2/24), where results turned positive after permanent section evaluation.11 However several studies have used immunohistochemistry to differentiate SGC from squamous cell carcinoma (SCC) and basal cell carcinoma (BCC), but often applicable for paraffin wax permanent section.28,29 We evaluated frozen section- fixed section discrepancies in 83 eyes examined by a single pathologist, and found that 4 eyes (5%) did not corroborate with paraffin wax fixed section. Two eyes were reported as positive on frozen section, but proven to be negative in fixed section, and vice versa in the other two eyes. We found fair agreement between frozen section and final fixed section reports according to Kappa statistics with a p value <0.0001. 73rd AIOC 2015, New Delhi

One of the unique characteristics of SGC is intraepithelial spread that poses a major challenge for complete cure. Putterman advocated the technique of map biopsy to evaluate the extent of tumor spread, as SGC has the tendency for diffuse spread.18 Orbital invasion was found to be higher (36%) with intraepithelial involvement compared to those without (7%). 8 In contrast, Margo and Grossniklaus commented on the biologic behavior of intraepithelial SGC to be noninvasive and, incapable of causing distant metastasis as the lymphatics and blood vessels are absent in the epithelium.23 Chao et. al. did not find any tumor related risk of metastasis in patients with conjunctival intraepithelial spread when compared to those without.8 However, it is essential to delineate the extent of conjunctival involvement for appropriate management. Several other authors demonstrated the utility of map biopsy in diagnosis of intraepithelial SGC. In the presence of diffuse, ill-defined edges with or without a nodular component map biopsy is often performed.18-20,30 Multifocality in SGC also poses a greater risk for recurrence, because it can spawn new tumors in a different location. We found multicentricity in 10 (9%), of which 4 (40%) recurred. In the 69 eyes undergoing map biopsy 7 patients were found to be positive and of these, 6 eyes (86%) had clinical suspicion of intraepithelial spread. Since we 764 found that the probability of positive map biopsy is high in the presence of clinical suspicion, we recommend the procedure in such clinical scenarios and avoid in eyes with well-defined nodular type of SGC.

Conclusion SGC of the eyelid has increased tendency for local recurrence, metastasis and death if not appropriately managed unlike other malignant eyelid tumors. Optimal treatment includes complete surgical excision with clear margins with intraoperative frozen section control. To our knowledge, this is the first and largest series of SGC where primary excision biopsy with frozen section margin control was compared with excision alone. We found significantly high recurrence rate in eyes not subjected to frozen section margin control and, there was fair agreement between frozen section reports and final fixed section. Conjunctival map biopsy can be reserved for patients with clinical features suggestive of diffuse pagetoid invasion.

References 1. Shields JA, Demirci H, Marr BP, Eagle RC Jr, Shields CL. Sebaceous carcinoma of the eyelids: personal experience with 60 cases. Ophthalmology 2004;111:2151–7. 2. Boniuk M, Zimmerman LE: Sebaceous carcinoma of the eyelid, eyebrow, caruncle and orbit. Int Ophthalmol Clin 1972;12:225–57. Orbit and Oculoplasty Free Papers

3. Rao NA, Hidayat AA, McLean IW, Zimmerman LE. Sebaceous carcinomas of the ocular adnexa: a clinicopathologic study of 104 cases, with five-year follow- up data. HumPathol 1982;13:113–22. 4. Shields JA, Shields CL. Sebaceous adenocarcinoma of the eyelid. Int Ophthalmol Clin 2009;49:45-61. 5. Doxanas MT, Green WR. Sebaceous gland carcinoma. Review of 40 cases. Arch Ophthalmol 1984;102:245–9. 6. Searl SS, Kuo PK, et. al.: Sebaceous cell carcinomas of the ocular adnexa. Int Ophthalmol Clin 1982;22:23–61. 7. Khan JA, Doane JF, Grove AS Jr. Sebaceous and meibomian carcinomas of the eyelid: recognition, diagnosis, and management. Ophthal Plast Reconstr Surg 1991;7:61–6. 8. Chao AN, Shields CL, Krema H, Shields JA. Outcome of patients with periocular sebaceous gland carcinoma with and without conjunctival intra-epithelial invasion. Ophthalmology 2001;108:1877–83. 9. Nunery WR, Welsh MG, McCord CD: Recurrence of seba- ceous carcinoma of the eyelid after radiation therapy. Am J Ophthalmol 1983;96:10–5. 10. Dogru M, Matsuo H, Inoue M, et. al.: Management of eyelid sebaceous carcinomas. Ophthalmologica 1997;211:40–3. 11. Yoon JS, Kim SH, Lee CS, Lew H, Lee SY. Clinicopathological analysis of periocular sebaceous gland carcinoma. Ophthalmologica 2007;22:331-9.21. 12. Muqit MM, Roberts F, Lee WR, Kemp E. Improved survival rates in sebaceous 765 carcinoma of the eyelid. Eye (Lond) 2004;18:49-53. 13. Zu --rcher M, Hintschich CR, Garner A, et. al.: Sebaceous carcinoma of the eyelid: a clinicopathological study. Br J Ophthalmol 1998;82:1049–55. 14. Shields JA, Demirci H, Marr BP, Eagle RC Jr, Shields CL. Sebaceous carcinoma of the ocular region: a review. Surv Ophthalmol 2005;50:103-22. Review. 15. Tenzel RR, Stewart WB, Boynton JR, Zbar M. Sebaceous adenocarcinoma of the eyelid. Definition of surgical margins. Arch Ophthalmol 1977;95:2203-4. 16. Tan KC, Lee ST, Cheah ST. Surgical treatment of sebaceous carcinoma of eyelids with clinico-pathological correlation. Br J Plast Surg. 1991;44:117-21. 17. Chévez-Barrios P. Frozen section diagnosis and indications in ophthalmic patholog y. Arch Pathol Lab Med 2005;129:1626-34. Review. 18. Putterman AM. Conjunctival map biopsy to determine pagetoid spread. Am J Ophthalmol 1986;102:87–90. 19. Honavar SG, Shields CL, Maus M, et. al. Primary intraepithe- lial sebaceous gland carcinoma of the palpebral conjunctiva. Arch Ophthalmol 20 01;119:764 –7. 20. Shields JA, Demirci H, Marr BP, Eagle RC Jr, Stefanyszyn M, Shields CL. Conjunctival epithelial involvement by eyelid sebaceous carcinoma. The 2003 J. Howard Stokes lecture. Ophthal Plast Reconstr Surg. 2005;21:92-6. 21. Lisman RD, Jakobiec FA, Small P. Sebaceous carcinoma of the eyelids. The role of adjunctive cryotherapy in the management of conjunctival pagetoid spread. Ophthalmology 1989;96:1021–6. 73rd AIOC 2015, New Delhi

22. Shields JA, Shields CL. Sebaceous carcinoma of the glands of Zeis. Ophthal Plast Reconstr Surg. 1988;4:11–4. 23. Margo CE, Grossniklaus HE. Intraepithelial sebaceous neoplasia without underlying invasive carcinoma. Surv Ophthalmol 1995;39:293–301. 24. Kvannli L, Benger R, Gal A, Swamy B. The method of en face frozen section in clearing periocular basal cell carcinoma and squamous cell carcinoma. Orbit 2012;31:233 -7. 25. Spencer JM, Nossa R, Tse DT, Sequeira M. Sebaceous carcinoma of the eyelid treated with Mohs micrographic surgery. J Am Acad Dermatol 2001;44:1004-9. 26. While B, Salvi S, Currie Z, Mudhar HS, Tan JH. Excision and delayed reconstruction with paraffin section histopathological analysis for periocular sebaceous carcinoma. Ophthal Plast Reconstr Surg. 2014;30:105-9. 27. Prieto VG, Argenyi ZB, Barnhill RL et. al. Are en face frozen sections accurate for diagnosing margin status in melanocytic lesions? Am J Clin Pathol 2003;120:203-8. 28. Muthusamy K, Halbert G, Roberts F. Immunohistochemical staining for adipophilin, perilipin and TIP 47. J Clin Pathol 2006;59:1166-70. 29. Jakobiec FA, Mendoza PR. Eyelid sebaceous carcinoma: clinicopathologic and multiparametric immunohistochemical analysis that includes adipophilin. Am J Ophthalmol 2014;157:186-208. 30. Margo CE, Lessner A, Stern GA. Intraepithelial sebaceous carcinoma of the conjunctiva and skin of the eyelid. Ophthalmology 1992;99:227-31. 766

Neoadjuvant Systemic Chemotherapy in the Management of Eyelid Sebaceous Gland Carcinoma Dr. Swathi Kaliki, Dr. Anuradha Ayyar, Dr. Tarjani Dave, Dr. Milind Naik yelid is the most common site of SGC owing to the high density of Esebaceous glands.1 Sebaceous gland carcinoma is the most common eyelid malignancy in the Asian Indian population accounting for 28 to 60% cases,2,4 while it is relatively uncommon in the western population accounting for only 4 to 5% of eyelid malignancies.2 The standard treatment for eyelid SGC is wide excision biopsy under frozen section or Mohs microsurgery control and subsequent eyelid reconstruction. The use of systemic chemotherapy for eyelid SGC is sparsely described in the literature as isolated case reports.5,8 Hereby, we describe our experience with the use of systemic intravenous chemotherapy in the management of eyelid SGC in 10 patients. Orbit and Oculoplasty Free Papers

Materials and Methods This is a retrospective interventional case series. All patients with “eyelid sebaceous gland carcinoma (SGC)” treated with neoadjuvant systemic chemotherapy from January 1st 2000 to April 30th 2014 at the Ocular Oncology Service, L V Prasad Eye Institute, Hyderabad, India were included in this study. Institutional Review Board approval was obtained. The patients who were lost to follow-up during the course of neoadjuvant chemotherapy were excluded. The demographic data and details of past history retrieved from the medical records. Best-corrected visual acuity was recorded. Tumor details were noted. Photographic documentation was done in all cases, which were reviewed. In those cases with no visualization of posterior extent of tumor, computed tomography of the orbit was performed. Locoregional lymph node examination was done and in those cases with palpable lymph nodes, fine needle aspiration cytology was performed. Systemic metastatic workup was done with chest x-ray, ultrasound abdomen, and liver function tests. All tumors were retrospectively classified by TNM staging (Tx, 0, is, 1, 2, 3 or 4; N0 or 1; M0 or 1) based on 7th edition of American Joint Cancer Committee Classification.9 Prior to systemic intravenous chemotherapy, incision biopsy from the tumor 767 was done to confirm the diagnosis of SGC by histopathology. Treatment details regarding systemic intravenous chemotherapy were recorded. Based on the response to treatment, the tumor response was classified as good response (>75% reduction in tumor size and 100% reduction in orbital component), moderate response (50% to 75% reduction in eyelid tumor size and <100% reduction in orbital component), or poor response (<50% reduction in eyelid tumor size and <100% reduction in orbital component) to treatment. Details of surgical and adjuvant treatment were noted. Histopathology features were noted. The final outcome at last follow-up was recorded.

Results Of the 191 cases with eyelid SGC, 16 patients were advised neoadjuvant systemic chemotherapy. Of these 16 cases, only 10 cases were included in this study based on our inclusion criteria. The mean age at presentation of eyelid SGC was 58 years (median, 55 years; range, 45 to 72 years). There were 6 females and 4 males. The most common presenting complaint was appearance of an eyelid mass (n=10). The mean duration of symptoms was 18 months (median, 17 months; range, 5 to 26 months). There was a previous history of excision biopsy in 6 cases. In 73rd AIOC 2015, New Delhi

these 6 cases, the time interval between prior excision biopsy and tumor recurrence was 11 months (median, 13 months; range, 1 to 26 months). All cases had massive eyelid lesion (largest tumor basal diameter > 20 mm) on presentation with a mean tumor basal diameter of 36 mm (median, 31 mm, range, 20 to 65 mm). Tumor epicenter was located in upper (n=6) or lower (n=4) eyelid. Orbital tumor extension was evident in 9 cases. There were associated features of loss of eyelashes (n=8), overlying skin fixity (n=5), and underlying conjunctival involvement (n=8). Based on TNM Classification, the tumors were classified as T3 (n=10), N1 (n=6), and M1 (n=2). All patients received a combination of cisplatin/carboplatin and 5-fluorouracil as neoadjuvant systemic chemotherapy every 3 weeks. Three cycles of neoadjuvant chemotherapy was planned in all cases, but the number of cycles was modified based on tumor response. The mean number of cycles of neoadjuvant systemic chemotherapy per patient was 3 (median, 3; range, 3 to 4). The mean percentage reduction of tumor basal diameter after neoadjuvant chemotherapy was 74% (median, 80%; range, 30% to 90%). Post-chemotherapy, surgical treatment for residual tumor was performed in 7 cases, while 3 cases were lost to follow-up after neoadjuvant chemotherapy. Five cases had good response to treatment and underwent eyelid excision biopsy with wide margins under frozen section control, 768 and 2 cases with moderate response to treatment with residual orbital component underwent eyelid-sparing orbital exenteration. Histopathology revealed residual tumor in 5 cases with tumor-free margins and 2 cases had no evidence of residual tumor. External beam radiotherapy to the orbit and/ or regional lymph nodes was performed in 7 cases as adjuvant treatment. No tumor recurrence was noted in any patient at a mean follow-up period of 18 months (median, 14 months; range, 3 to 63 months). Of the 3 cases with no surgical intervention, one case had good response and 2 had moderate response to treatment. In this series, one patient died due to systemic metastasis 19 months after completion of neoadjuvant chemotherapy.

Discussion Systemic chemotherapy either as neoadjuvant, concomitant or adjuvant chemotherapy is beneficial in the management of locally advanced head and neck cancers. Neoadjuvant systemic chemotherapy downstages the disease and provides significant benefits of organ preservation, locoregional tumor control, lower risk of distant metastasis, and prolonged overall survival period.10,12 The standard chemotherapy agents used in the management of head and neck cancers are platinum-based agents (cisplatin/carboplatin) and 5-fluorouracil.10,12 With the encouraging results of the use of neoadjuvant Orbit and Oculoplasty Free Papers

systemic chemotherapy in the management of head and neck squamous cell carcinoma, similar treatment has been used for locally advanced eyelid SGC.5,8 In our study, a combination of platinum-based agents (cisplatin/ carboplatin) and 5-fluorouracil was used in all cases. The overall response rate following neoadjuvant chemotherapy in our series ranged from 30% to 100% with a complete response (with no evidence of tumor on histopathology) in 2 cases. Neoadjuvant chemotherapy for eyelid SGC could facilitate eyelid and globe preservation by significant tumor volume reduction, spare the patient from radical neck dissection in those with regional lymph node metastasis, lower the risk of systemic metastasis, and prolong the disease-free survival period. In this series, there was no evidence of tumor recurrence in any case, and disease-related mortality occurred in only 1 case. However, the follow- up duration is short with a mean follow-up period of 18 months, and four patients had a follow-up duration of less than a year. Long-term results in a larger group of patients are warranted.

References 1. Thomas WW, Fritsch VA, Lentsch EJ. Population-based analysis of prognostic indicators in sebaceous carcinoma of the head and neck. Laryngoscope 769 2013;123:2165-9. 2. Shields JA, Demirci H, Marr BP, Eagle RC Jr, Shields CL. Sebaceous carcinoma of the ocular region: A Review. Surv Ophthalmol 2005;50:103-22. 3. Abdi U, Tyagi N, Maheshwari V, Gogi R, Tyagi SP. Tumours of eyelid: a clinicopathologic study. J Indian Med Assoc 1996;94:405-9, 416, 418. 4. Sihota R, Tandon K, Betharia SM, Arora R. Malignant eyelid tumors in an Indian population. Arch Ophthalmol 1996;114:108-9. 5. Paschal BR, Bagley CS. Sebaceous gland carcinoma of the eyelid: complete response to sequential combination chemotherapy. N C Med J 1985;46:473-4. 6. Murthy R, Honavar SG, Burman S, Vemuganti GK, Naik MN, Reddy VA. Neoadjuvant chemotherapy in the management of sebaceous gland carcinoma of the eyelid with regional lymph node metastasis. Ophthal Plast Reconstr Surg. 2005;21:307-9. 7. Priyadarshini O, Biswas G, Biswas S, Padhi R, Rath S. Neoadjuvant chemotherapy in recurrent sebaceous carcinoma of eyelid with orbital invasion and regional lymphandenopathy. Ophthal Plast Reconstr Surg. 2010;26:366-8. 8. Gogia A, Pushker N, Sen S, Bakhshi S. Avoidance of exenteration in orbital sebaceous gland carcinoma with neoadjuvant chemotherapy. Graefes Arch Clin Exp Ophthalmol. 2013;251:2479-80. 9. Edge SB, Byrd DR, Compton CC, et. al., eds. Carcinoma of the Eyelid. In: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer; 2010;523-30. 73rd AIOC 2015, New Delhi

10. Blanchard P, Baujat B, Holostenco V, et. al.; MACH-CH Collaborative group. Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): A comprehensive analysis by tumour site. Radiother Oncol 2011;100:33-40. 11. Pignon JP, le Maître A, Maillard E, Bourhis J; MACH-NC Collaborative Group. Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): An update on 93 randomised trials and 17,346 patients. Radiother Oncol 2009;92:4-14. 12. Posner MR. Paradigm shift in the treatment of head and neck cancer: The role of neoadjuvant chemotherapy. Oncologist 2005;10:11-9.

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