Systemic Hypertension and Primary Open Angle Glaucoma

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES

PROTOCOL FOR DISSERTATION

EVALUATION OF SYSTEMIC HYPERTENSION AS A RISK FACTOR FOR PRIMARY OPEN ANGLE GLAUCOMA

1. DR. SHARON D’SOUZA DEPARTMENT OF OPHTHALMOLOGY ST. JOHN’S MEDICAL COLLEGE JOHNNAGAR BANGALORE-560034

2. NAME OF THE INSTITUTION : St. John’s Medical College Hospital

3. COURSE: M.S. Ophthalmology

4. DATE OF ADMISSION TO THE COURSE : 14/04/2008

5. TITLE OF THE TOPIC : EVALUATION OF SYSTEMIC HYPERTENSION AS A RISK FACTOR FOR PRIMARY OPEN ANGLE GLAUCOMA

6. BRIEF RESUME OF THE INTENDED WORK

INTRODUCTION Glaucoma is a potentially blinding disease that affects 66 million persons worldwide. It is the second leading cause of visual loss in the world. With an expected increase in population and longevity, primary open angle glaucoma (POAG) is likely to become a major cause of ocular morbidity in the developing world. It is a multifactorial optic neuropathy in which there is characteristic atrophy of the optic nerve. (1) The disease is characterized by typical changes in the optic nerve with associated visual field defects. The etiology of POAG remains unclear despite a number of epidemiological studies that have investigated various potential risk factors for the disease (2). Various risk factors are known to be associated with the occurrence of glaucoma such as age, gender, race, diabetes mellitus, myopia and family history. Some of these factors have been proven to be significant risk factors for the development of POAG, while the relations between factors such as systemic hypertension or perfusion pressures and open angle glaucoma remain controversial and need further evaluation.

6.1 NEED FOR THE STUDY Recognition of all risk factors for POAG is important for early diagnosis and intervention. POAG is often diagnosed on routine ocular examination and in many instances in the late stage. It manifests mainly as peripheral visual field loss with central vision being preserved almost till the end stage. By the time the patient is symptomatic the visual loss is irreversible (3) .Therefore, early diagnosis is essential so that treatment to halt progression can be instituted. Systemic hypertension has not yet been established as a risk factor for POAG. Hypertension is a disease which is becoming increasingly more common in the developing countries.(4) Recent data suggest common mechanisms related to altered epithelial sodium transport in the distal nephron and ciliary epithelium. Excessive renal sodium retention leads to systemic hypertension, and increased ciliary epithelial sodium transport leads to extrusion of sodium into the aqueous humour. If increased sodium reabsorption underpinned the occurrence of hypertension and glaucoma then an epidemiological link between the two should be demonstrable (5) This relationship has been demonstrated in some studies, while some others have refuted it.

6.2 REVIEW OF LITERATURE : Systemic hypertension has been implicated as a risk factor for developing glaucoma in some studies. The Baltimore Eye Study (2) showed a positive association between POAG and higher systemic blood pressures. The relationship was not linear and there was a threshold effect seen at systolic blood pressure 130mmHg. Patients with systolic blood pressure above 130mmHg were found to have increased risk of developing POAG. It was also hypothesized in the study that hypertension in younger age groups could have a protective effect against glaucoma and becomes detrimental only in the later stages once the damage to small vessels has occurred . Another important finding in this study was the strong association between diastolic perfusion pressures < 50mmHg with the development of POAG. The Beaver Dam Eye study (6) was a population based study which evaluated the association between high blood pressure and risk of developing POAG. Raised systemic blood pressure was found to be significantly associated with change in IOP in The Beaver Dam study (5). They reported a 0.21 mm Hg increase in IOP for every 10 mmHg increase in systolic pressure and 0.43 mmHg increase in IOP for every 10 mmHg increase in diastolic blood pressure. Adjustment for diabetes mellitus and medication use did not alter the associations found in this study. This finding should be evaluated in detail especially with respect to the possibility of decreasing the risk of open angle glaucoma.

Mitchel P et al in the Blue Mountain Eye Study (7) concluded that hypertension was significantly associated with Open angle glaucoma. This association was strongest in subjects with poorly controlled hypertension compared with normotensive subjects, independent of the effect of BP on IOP and other glaucoma risk factors. In this study it was found that the population attributable risk for hypertension was higher than for the other identified open angle glaucoma risk factors. However they could not exclude nocturnal hypotensive episodes in treated patients.

A study was carried out by Hulsman et al to study the cross-sectional associations between blood pressures, arterial stiffness and open angle glaucoma(OAG). Participants were included from the population based Rotterdam study(8).Cases of OAG were classified into high tension OAG and normal tension OAG, based on an IOP of greater than or less than 21mmHg respectively. No significant association was found between systolic and diastolic blood pressure and high tension glaucoma. An inverted association was found between low diastolic perfusion pressure and open angle glaucoma.

Vijaya L et al (9) conducted a study in rural south India on the prevalence of OAG. It was the first study from India to diagnose glaucoma according to International Society of Geographical and Epidemiologic Ophthalmology(ISGEO) criteria and is therefore comparable to other studies all over the world which use the same criteria .They also studied some of the associated risk factors for POAG such as age, gender, IOP, myopia and hypertension . No association was found between systemic hypertension and POAG in this study.

In another study done by Vijaya L et al known as the Chennai glaucoma study (10) age and gender adjusted prevalence of POAG among subjects 40 or older were compared among urban and rural south Indian population. The prevalence of POAG in the urban population was more than double that in the rural population. As in the previous study no statistically significant association was found between POAG and systemic hypertension even though the prevalence of hypertension was more in urban India than rural areas. 6.3 OBJECTIVES OF THE STUDY: 1. To determine if systemic hypertension is a risk factor for developing Primary open angle glaucoma 2. To study the importance of Diastolic perfusion pressure in predicting POAG

7. MATERIALS AND METHODS 7.1 Study design – The study will be a cross-sectional case control study Sample size – 100 patients and 100 age and sex matched controls Inclusion criteria –  Patients with hypertension  Age > 40 years of age  Age and sex matched controls, in the ratio of 1:1

Exclusion Criteria –  Recent ocular surgery done for causes other than glaucoma and cataract within last 6 months  Hypertensives <40 years of age  Secondary glaucoma  Uveitis  Corneal scarring or opacity  Other causes of optic atrophy

7.2 Method of collection of data: Patients with systemic hypertension presenting to the department of Ophthalmology will be included in the study. A detailed history including information regarding past medical illness including hypertension, diabetes mellitus, ocular disease including myopia and family history of glaucoma will be taken. History of any medications that the patient is on will also be included. A detailed physical examination will be done including height, weight, pulse and blood pressure which will be recorded with the patient in sitting position after resting for five minutes. Ophthalmological examination will include best corrected visual acuity, slit lamp examination and gonioscopy, fundus examination along with fundus photographs following mydriasis, applanation tonometry using Perkins hand held Tonometer Mk2, visual field testing with Humphrey field analyzer, Zeiss model 720, pachymetry using pachymeter SP 3000 (Tomey Corporation ) and nerve fibre analysis using GDx VCC 3635 Analyzer from Zeiss. Intraocular pressure (IOP) will be measured three times in each eye, with the median value chosen as the pressure in that eye. IOP for a person will be defined as the highest of the pressures of the two eyes (3). Statistical analysis Univariate analysis using Chi-square test to test correlation of categorical variables and student t test for quantitative variables will be done first. Then multiple logistic regression will be used for multivariate analysis.

7.3 Does the study require any investigations or interventions to be conducted on patients or other humans or animals? If so, please describe briefly: The various tests which have been enumerated as part of the study are routinely done as a part of workup for patients suspected to have glaucoma or found to be at increased risk of developing glaucoma.

7.4 Was ethical clearance obtained from your institution in case of 7.3 Yes 8. LIST OF REFERENCES 1. Rand AR, Damji KF, Bruce Shields M. Shield’s textbook of glaucoma,5th ed. Lippincott:2005;9:197

2. Tielsch JM, Katz J, Sommer A, Quigley HA, Javitt JC. Hypertension,Perfusion pressure and primary open angle glaucoma. Arch Ophthalmol 1995 Feb;113:216- 22

3. Palimkar A, Khandekar R, Venkataraman V. Prevalence and distribution of glaucoma in central India. (Glaucoma Survey -2001). Indian J Ophthalmol 2008;56:57-62

4. Gupta R . Trends in hypertension epidemiology in India . J Hum Hypertens, 2004 Feb ;18(2):73-8.

5. Langman MJS, Lancashire RJ, Cheng KK, Stewart PM. Systemic hypertension and glaucoma: mechanisms in common and occurrence. Br J Ophthalmol 2005;89:960-963

6. Klein BK, Klein R, Knudtson MD . Intraocular pressure and systemic blood pressure : longitudinal perspective : The Beaver Dam Eye Study. Br J Ophthalmol 2005;89:284-287.

7. Mitchell P, Lee AJ , Rochtchina E, Wang JJ. Open angle glaucoma and systemic hypertension : The Blue Mountains Eye Study. J Glaucoma. 2004 Aug;13(4):19- 26.

8. Hulsman CA, Vingerling JR, Hofman A, Witteman JC, Jong PT. Blood Pressure, Arterial Stiffness, and Open-Angle Glaucoma. Arch Ophthalmol 2007;125(6):805-812.

9. Vijaya L, George R, Paul PG, Baskaran M, Aravind H, Raju P, et al . Prevalence of open angle glaucoma in a rural south Indian population. Invest Ophthalmol vis sci. 2005;46(12):4461-4467.

10. Vijaya L, George R, Baskaran M, Arvind H, Raju P, Ramesh SV, et al. Prevalence of Primary open angle glaucoma in urban south Indian population and comparison with a rural population, The Chennai Glaucoma Study. Ophthalmology 2008 Apr;115(4):648-654. 9. SIGNATURE OF THE CANDIDATE

10.REMARKS OF THE GUIDE

Open angle glaucoma is the second commonest cause for blindness in the developed world and the incidence in India is comparable to western literature. Systemic Hypertension is also a common disease affecting the elderly. Establishing a correlation between these two common conditions will help in identifying patients with glaucoma earlier so that early treatment can be instituted, preventing irreversible visual loss.

11. NAME AND DESIGNATION OF ( In block letters )

11.1 GUIDE DR.SUNEETHA N. PROFESSOR DEPARTMENT OF OPHTHALMOLOGY

11.2 SIGNATURE

11.3 CO-GUIDE : DR. MARY JOSEPH ASSOCIATE PROFESSOR DEPARTMENT OF OPHTHALMOLOGY

11.4 SIGNATURE

11.5 HEAD OF DEPARTMENT : DR. COLIN NAZARETH PROFESSOR DEPARTMENT OF OPHTHALMOLOGY

11.6 SIGNATURE

12. 12.1 REMARKS OF THE CHAIRMAN AND PRINCIPAL

12.2 SIGNATURE