Prevalence of Vitreoretinal Disorders in a Rural Population of SouthernIndia:  The Aravind Comprehensive Eye Study FREE

Nearly 80% of the considerable burden of blindness in India is attributedto curable causes, such as cataracts and refractive errors.¹ Arecent study² found that retinal disordersare an important cause of blindness in India. It is estimated that there willbe 244 million people (14.9% of the population) 65 years and older by 2050compared with 42 million (4.5% of the population) in 1995.³ Thisshift in demographics is likely to be accompanied by a shift in the prevalenceof retinal diseases as major causes of blindness in India. Several studies^4- 7 reporton the prevalence of diabetic retinopathy (DR) in urban populations of India;however, there is a lack of information on the prevalence of DR in rural India.Although age-related macular degeneration (AMD) is a major cause of blindnessin European-derived populations and has been previously reported^8- 13 ata lower prevalence in pigmented populations, there is no information on theprevalence of AMD in India. Such information is essential to understand themagnitude of the problem and the need for services, including rehabilitation.This article reports on the prevalence of vitreoretinal disorders in a ruralpopulation of southern India.

The Aravind Comprehensive Eye Study is a population-based prevalencestudy of vision and other eye diseases in a rural population 40 years andolder in 3 districts—Madurai, Tirunelveli, and V.O Chidambaranar—inthe state of Tamil Nadu in southern India. The study design and methods aredescribed in detail elsewhere.¹⁴ In brief,50 representative clusters were selected from these 3 districts by using stratified,multistage cluster sampling. Demographic details were collected from all enumeratedindividuals after completion of a door-to-door survey by trained interviewers.All individuals 40 years and older were invited to the base hospital (AravindEye Hospital, Madurai, India) for comprehensive eye examinations, which includedinitial and best-corrected distance and near visual acuity using illiterateE LogMAR charts, slitlamp biomicroscopy for the external eye and anteriorsegment, applanation tonometry for intraocular pressures, gonioscopy usinga Goldmann single-mirror contact lens (Ocular Instruments Inc, Bellevue, Wash),and slitlamp lens grading using the Lens Opacities Classification System III.¹⁵ All participants with open anterior chamber anglesdetermined by gonioscopy using the Schaffer classification had their pupilsdilated with either 1% tropicamide or 10% phenylephrine hydrochloride. Participantswho had dilation deferred because of occludable or narrow angles underwentdilated examinations after laser iridotomy on the same day or on a subsequentday. Fundus examinations after dilation were performed using a 78-diopter(D) lens at the slitlamp and indirect ophthalmoscopy with a 20-D lens. Determinationof retinal disorders was primarily based on clinical evidence, and supportivelaboratory investigations were not always performed for logistical reasons.Retinal photography was not attempted because of cost and logistics. All findingswere confirmed by a fellowship-trained retinal specialist.

Three levels of informed consent were used in this study—community,household, and individual. Meetings were held with community leaders and allhealth-related personnel in the area to explain the purpose of the study.Once approval was obtained at these meetings, the study was fully explainedto all adults in the household to address any concerns and to secure consentfor the household to participate. Before screening and definitive examinations,the study was explained in detail to all potential participants, the consentstatement was read to each individual, and their voluntary consent was solicited.All informed consent was verbally obtained, as a substantial proportion ofthis population is illiterate. We did not obtain thumbprints as this was consideredproblematic because many villagers have been conned into giving away propertyby providing thumbprints to documents that they could not read. The studywas approved, and annually reapproved, by the Committee on Human Researchat the Johns Hopkins Bloomberg School of Public Health and by the EthicalReview Committee of the Aravind Eye and Children's Hospitals. This investigationadhered to the tenets of the Declaration of Helsinki.

The assessment of diabetes mellitus was based on either the use of diabeticmedications or a postprandial blood sugar level of 180 mg/dL or greater (≥10.0mmol/L). We did not measure glycosylated hemoglobin levels as this measurementwas not available at the time of the study in southern India. Based on fundusfindings, regardless of a history of diabetes mellitus or glucose levels,we used the modified classification of DR based on the retinopathy levelsused by Klein et al¹⁶ to categorize personswith DR. Briefly, DR was classified as nonproliferative (levels 1-3), preproliferative(levels 4 and 5), or proliferative (levels 6 and 7).¹⁶ Thepresence of clinically significant macular edema was assessed using a 90-Dlens at the slitlamp. The presence of retinal photocoagulation scars was assessedusing indirect ophthalmoscopy.

We classified epiretinal membranes based on the method used by Kleinet al¹⁷ and the more recent Blue MountainsEye Study.¹⁸ We identified 2 types of epiretinalmembranes: an early "cellophane macular reflex," described as a "glintingwater silk, shifting light reflex" due to a thin layer of preretinal cells,initially causing little distortion of the retinal surface, and a later stageof premacular fibrosis, occurring as the membrane thickens and contracts,with the appearance of superficial retinal folds or traction lines, becomingopaque or gray.¹⁹

Age-related macular degeneration was assessed independent of visualacuity measurements using a slitlamp with a 78-D lens after adequate pupillarydilation was achieved. Age-related macular degeneration was defined accordingto the international classification²⁰ developedby the International ARM Epidemiological Study Group. Briefly, drusen weredefined as discrete whitish-yellow spots external to the neuroretinal pigmentepithelium or retinal pigment epithelium (RPE). The largest drusen determinedthe grade for maximum drusen size and predominant drusen type. Type was basedon the size of drusen, uniformity of appearance across the breadth, and thesharpness of edges. Soft distinct drusen have uniform density and sharp edges,and soft indistinct drusen have decreasing density from the center outwardand fuzzy edges. Pigmentary abnormalities included either increased pigmentationassociated with drusen or depigmentation or hypopigmentation of the RPE, moresharply demarcated than drusen, without any visibility of choroidal vesselsassociated with drusen. Geographic atrophy was defined as any sharply delineatedapproximately round or oval area of hypopigmentation or depigmentation orapparent absence of the RPE in which choroidal vessels are more visible thanin surrounding areas, at least 175 µm. Exudative AMD was defined asthe presence of any of the following: (1) RPE detachments or serous detachmentof the sensory retina, (2) subretinal or sub-RPE neovascular membranes, (3)subretinal hemorrhages, and (4) epiretinal, subretinal, intraretinal, or sub–pigmentepithelial scar or glial tissue or fibrinlike deposits. Early AMD was definedas the presence of soft large drusen (>125 µm) with pigment epithelialabnormalities, as described previously herein. Late AMD was defined as thepresence of signs of exudative AMD or geographic atrophy.

We defined systemic hypertension as either a measured systolic bloodpressure of 140 mm Hg or greater or a diastolic blood pressure of 90 mm Hgor greater or current use of systemic antihypertensive medications. We analyzedserum cholesterol level as a categorical variable; values greater than 200mg/dL (>5.17 mmol/L) were considered high. We used height and weight measurementsof individual participants to calculate body mass index (BMI) (calculatedas weight in kilograms divided by height [meters squared]). We classifiedindividuals as lean if the BMI was less than 20 for men and less than 19 forwomen, as normal if the BMI was 20 to 25 for men and 19 to 24 for women, asoverweight if the BMI was 25 to 30 for men and 24 to 29 for women, and asobese if the BMI was greater than 30 for men and greater than 29 for women.²¹ We elicited a history of smoking; the duration ofsmoking was estimated for current smokers from the age at which participantsstarted smoking and the current age and for past smokers from the age at whichparticipants started smoking and the age at which they stopped smoking. Dataregarding the number of cigarettes or beedis (a beedi is tobacco rolled indried leaves) smoked per day was elicited for current and past smokers andwas used to estimate smoking-years. We classified smoking-years as zero years,low (below the 25th percentile), medium (25th-75th percentile), and high (abovethe 75th percentile).

Statistical analysis was performed using a software package (Stata version7.0; Stata Corp, College Station, Tex). The 95% confidence intervals (CIs)of the prevalence estimates were calculated using a Poisson approximationof the binomial distribution. Bivariate and multivariate analyses were usedto look for associations between risk factors and early and late AMD.

We performed comprehensive clinical examinations on 5150 (93%) of the5339 enumerated individuals 40 years and older. Of the 5150 individuals examined,complete retinal data were available for 4917 (95.5%). Media opacities, particularlyage-related cataracts, were the major reason for not having adequate retinaldata. The median age of these 4917 persons was 50.0 years (range, 40-90 years;mean, 52.5 years), and 55.0% were women. Participants without retinal dataavailable were more likely to be older (aged ≥60 years; P <.001). There were no differences in sex between those who hadretinal data available and those who did not.

Increasing age was associated with vitreoretinal disorders (P <.001) (Table 1).There were no significant differences in the age-adjusted prevalence of vitreoretinaldisorders between sexes. The prevalence of various vitreoretinal disordersin this population, by eyes, is given in Table 2. The prevalence of any vitreoretinal disorder, includingAMD, was 10.8% (95% CI, 9.9%-11.8%); after excluding AMD, the prevalence was8.2% (95% CI, 7.4%-9.0%).

Diabetes mellitus was present in 142 persons (4.0%) younger than 60years, 59 (4.9%) aged 60 to 69 years, and 27 (6.5%) aged 70 years and older(overall population prevalence, 4.4%; 95% CI, 3.8%-5.0%). Diabetic retinopathywas present in 14 persons (0.4%) younger than 60 years, 6 (0.6%) aged 60 to69 years, and 4 (1.2%) aged 70 years or older (overall population prevalence,0.5%; 95% CI, 0.3%-0.7%). The population prevalence was 0.4% (95% CI, 0.3%-0.7%)for nonproliferative DR, 0.04% (95% CI, 0.005%-0.15%) for preproliferativeDR, 0.06% (95% CI, 0.01%-0.18%) for proliferative DR, and 0.06% (95% CI, 0.01%-0.18%)for clinically significant macular edema. Among people with diabetes mellitus,the prevalence of nonproliferative DR was 9.2% (95% CI, 5.7%-14.1%), of preproliferativeDR was 0.9% (95% CI, 0.1%-3.2%), and of proliferative DR was 1.3% (95% CI,0.2%-3.8%). Among those who were aware of their diabetic status, 58.3% hadclinical evidence of DR. Only 12.5% of those with DR in this study had a previousophthalmic examination, including 6.7% who were aware of their diabetic status.

An epiretinal membrane was present in 14 persons (population prevalence,0.3%; 95% CI, 0.2%-0.5%). We did not find Eales disease in any eye.

The prevalence of early and late AMD increased significantly with increasingage (P <.001) (Table 3). There was no evidence that sex was associated with eitherearly or late AMD after adjusting for age (P = .70)(Table 3). The median age of individualswith any AMD was 58 years (range, 40-82 years), and 52.9% were women. Theage-specific prevalence of AMD was 1.3% (95% CI, 0.1%-1.9%) for those aged40 to 49 years, 3.9% (95% CI, 2.9%-5.0%) for those aged 50 to 59 years, 5.0%(95% CI, 3.8%-6.5%) for those aged 60 to 69 years, and 6.9% (95% CI, 4.4%-10.3%)for those 70 years and older. The prevalence of early AMD was 2.7% (95% CI,2.2%-3.2%), and that of late AMD was 0.6% (95% CI, 0.4%-0.8%). The age-adjusted(adjusted to the population estimates for 2000 for India [from the US CensusBureau, International Data Base, October 2002 version]) prevalence of AMDwas 3.1% (95% CI, 2.7%-3.6%).

Soft large drusen greater than 125 µm were present in 95 persons(population prevalence, 1.9%; 95% CI, 1.6%-2.4%), pigmentary changes werepresent in 40 persons (0.8%; 95% CI, 0.6%-1.1%), exudative changes were presentin 6 persons (0.1%; 95% CI, 0.0%-0.3%), and geographic atrophy was presentin 23 persons (0.5%; 95% CI, 0.3%-0.7%). Exudative changes were not foundin individuals younger than 60 years.

Systemic hypertension (odds ratio [OR], 1.19; 95% CI, 0.8-1.7), diabetesmellitus (OR, 1.12; 95% CI, 0.5-2.3), history of smoking (OR, 0.90; 95% CI,0.6-1.3), and smoking-years (OR, 0.92; 95% CI, 0.6-1.3) were not significantlyassociated with AMD. Serum cholesterol levels greater than 200 mg/dL (>5.17mmol/L) were protective on univariate analysis for early AMD (OR, 0.44; 95%CI, 0.3-0.8). Adjustment for multiple risk factors did not change the observedassociations to any appreciable degree (Table 4).

Of the 1834 eyes with initial visual acuity worse than 6/60 in botheyes, 56 (3.1%) had any retinal disorder present. After best correction, 127persons with AMD (78.9%) had visual acuity of 6/18 or better, 4 (2.5%) hadvisual acuity between 6/60 and 3/60, and 1 (0.6%) had visual acuity worsethan 3/60. After best correction, 1 person with DR (4.4%) had visual acuityworse than 6/60. Overall, 19 persons (3.5%) with any vitreoretinal disorderhad visual acuity worse than 6/60 after best correction. However, the prevalenceof bilateral blindness attributable to vitreoretinal diseases was 0.3% (95%CI, 0.1%-0.5%).

Population-based data on the magnitude of disease is essential to planfor required services. Previous studies^2,4- 7 fromIndia have merely mentioned that retinal disorders cause blindness or havefocused on DR.

The lack of fundus photographs is a limitation of this study. However,all participants were subject to a dilated fundus examination using slitlampbiomicroscopy with a 78-D lens and indirect ophthalmoscopy with a 20-D lens,and all findings were confirmed by a fellowship-trained retinal specialist.It is possible that we may have underestimated the prevalence of vitreoretinaldisorders in the absence of fundus photographs. Five percent of individualswho had comprehensive eye examinations did not have complete retinal dataavailable. These persons were statistically significantly older than participantsand were more likely to have retinal disorder. Therefore, the total prevalencereported may be an underestimate, although there is no indication of selectionbias in the age-sex analyses.

A population prevalence of bilateral blindness of 0.3% after best correctionamong persons with vitreoretinal disorders suggests that vitreoretinal disordersmay not currently be a major public health problem in India. This prevalenceis similar to the 0.2% (95% CI, 0.1%-0.3%) reported by another study² in a different state in India. However, the relativelyhigher prevalence of any vitreoretinal disorder, including AMD (10.8%; 95%CI, 9.9%-11.8%), in older age groups is indicative of the potential for vitreoretinaldisorders to contribute to the burden of blindness in India as the populationdemographics shift toward aging. The population older than 65 years is expectedto be 137 million by 2021 (compared with 42 million in 1995).²² Itis also estimated that there will be a rapid increase in the number of personswith diabetes mellitus—approximately 57 million patients with diabetesmellitus in India by 2025 compared with 19 million in 1995.²³ Thechallenge the ophthalmic health care system in India may face is evident whenwe consider that if even as low as 5% to 10% of the estimated 57 million individualswith diabetes mellitus (by 2025) develop severe retinopathy, approximately3 to 6 million persons may require laser or surgical intervention for severeDR within the next 2 decades. Getting these people into the eye care deliverysystem at an appropriate time to preserve vision could be a major challenge,especially considering that only 6.7% of those who were aware of their diabeticstatus had visited an ophthalmologist (and none of the visits occurred inthe year immediately preceding this study). This suggests the need for increasedawareness in the community regarding vitreoretinal diseases and their potentialfor causing blindness and the need for improved networking between internistsand ophthalmologists to ensure that all those with systemic diseases thathave a potential for affecting the eye receive an ophthalmic examination,including dilated fundus examinations.

The association of AMD with increasing age in this study is similarto other studies in different populations.^24- 27 Wedid not find statistically significant sex differences in the prevalence ofAMD, and neither did we find an association between cigarette smoking or systemichypertension and AMD. There have been conflicting findings on the associationof smoking with AMD.^28- 32

Serum cholesterol levels greater than 200 mg/dL (>5.17 mmol/L) werefound to be protective for early AMD in our study. However, this study waslimited in that we did not measure individual lipid components other thancholesterol. The Beaver Dam Eye Study³³ didnot show any association between AMD and serum cholesterol levels. Body massindex was not statistically significantly associated with AMD in our studypopulation after adjusting for other factors, in contrast to the POLA (PathologiesOculaires Liées à l'Age) study,²⁷ whichreported ORs of 2.3 (95% CI, 1.0-2.5) for late AMD and 1.5 (95% CI, 1.1-2.3)for pigmentary changes among obese individuals (BMI >30). Other population-basedstudies^34- 35 have shown increasedrisk as BMI increases, but these results were not statistically significant.The differences in association of risk factors such as serum cholesterol level,diabetes mellitus, and BMI in the study population compared with other populationsmay be related to a lower prevalence of these risk factors in this rural southernIndian population. Less than 25% of our population had a serum cholesterollevel greater than 200 mg/dL (>5.17 mmol/L), less than 5% had diabetes mellitus,and less than 8% were obese.

Currently available therapies for AMD are not curative and are pricedmuch higher than services for other easily treatable conditions, such as cataractsor refractive errors, in India. The relatively low affordability of therapeuticservices for AMD and the low potential of current treatment modalities topreserve vision will mean that a sizable number of patients with AMD may remainvisually impaired or blind. Therefore, greater emphasis should be placed onrehabilitative and low-vision services, an underdeveloped specialty area inIndia.

We did not find any cases of Eales disease in the study sample, suggestingthat the population prevalence of this disease may actually be much lowerthan previously believed. There could be several reasons for this. First,Eales disease is more common at a younger age, usually in the early to middle30s, and our study population was 40 years and older. In addition, more diagnosticlaboratory tests are available now and have led to the identification of specificentities that were likely to be classified as Eales disease in the past.

Strategies to address the issue of vitreoretinal disorders in India,besides focusing on infrastructure development, including trained personneland low-vision and rehabilitative services, should also look at current ophthalmicpractices in India. Residency programs need to be more comprehensive in natureto include training for certain levels of interventions for vitreoretinaldiseases, including lasers. Dilated fundus examinations, at least at baseline,have to be made mandatory for all patients unless otherwise contraindicated.Such examinations should use slitlamp biomicroscopy and indirect ophthalmoscopy.Eye care programs and practitioners need to develop wider networks with internistsand physicians to ensure that ophthalmic examinations are performed in patientswith systemic illness associated with ocular complications, most notably diabetesmellitus. Further studies are required to understand the changing trends invitreoretinal diseases in India and their risk factors so that effective preventivestrategies can be formulated.

Corresponding author: Alan L. Robin, MD, Lake Falls ProfessionalBuilding, 6115 Falls Rd, Suite 333, Baltimore, MD 21209-2226 (e-mail: glaucomaexpert@cs.com).

Submitted for publication June 16, 2003; final revision received November24, 2003; accepted December 8, 2003.