Methods

The study adhered to the tenets of the Declaration of Helsinki and was approved by the Institutional Review Board of the Hyderabad Eye Research Foundation; L V Prasad Eye Institute (LVPEI), Hyderabad, India; and the London School of Hygiene & Tropical Medicine (LSHTM), London. Written informed consent was obtained from all participants. The first phase of the APEDS (APEDS I) was conducted from 1996 to 2000 and included 10,293 participants of all ages. The sample was selected using a multistage cluster sampling procedure from 1 urban and 3 rural areas of the then undivided Andhra Pradesh state in southern India. The urban area was Hyderabad, and the rural areas were located in the West Godavari District (affluent rural) and in Adilabad and Mahabubnagar districts (poor rural). This was one of the most rigorous population-based surveys conducted in a low-income setting. Findings from this study significantly contributed to the development of eye care policies in India. ^,

Between 2009 and 2010, a feasibility study called APEDS II was conducted to trace participants examined in APEDS I to estimate migration and mortality rates and to identify participants willing to be re-examined. The 3 rural areas were revisited wherein 5,447 (70.1%) of the 7,771 rural participants examined in APEDS I were traced. Re-examination of this cohort of participants after 15 years (range 13-17 years) between 2012 and 2016 constitutes APEDS III. In this manuscript, we report the incidence of PACD among participants aged ≥40 years at baseline, that is, in APEDS I. Details of the design and methodology for APEDS III have been described previously, and relevant details are summarized here.

A comprehensive eye examination was performed on all participants using similar methods to APEDS I. The study team was trained on the procedures. All 4 clinical investigators underwent interobserver agreement assessments with the principal investigator (PI, a glaucoma specialist) for lens grading, gonioscopy, and optic disc assessment prior to joining the study. There was only one investigator at any given time. Agreement between the PI and other investigators in the binary classification of the anterior chamber angle into occludable or open was high (kappa coefficient range 0.78-0.85). The vertical cup-to-disc ratio (CDR) was assessed subjectively in units of 0.05, with a kappa coefficient ranging between 0.69 and 0.81.

Participants with a presenting distance or near visual acuity >logMAR 0.0 underwent streak retinoscopy followed by subjective refraction and acceptance. Each eye was tested separately and then binocularly. Refraction was performed by a trained optometrist or vision technician. Intraocular pressure (IOP) was measured with Goldmann applanation tonometer (Haag-Streit, Bern, Switzerland). One more reading was taken if the initial reading was >21 mm Hg. Gonioscopy was performed in a dark room with a short and narrow light beam (1-2 mm) to avoid pupillary constriction. An NMR-K 2-mirror lens (Ocular Instruments, Bellevue Washington, USA) and a Sussman 4 mirror lens (Ocular Instruments) was used. The angle was considered occludable if the pigmented posterior trabecular meshwork was not visible for ≥180 degrees of the angle circumferences in the primary position, without manipulation under dim illumination.

All participants underwent pupillary dilatation; participants with occludable angles were dilated after laser iridotomy. The optic disc and peripapillary area were assessed with a 78-diopter (D) lens (Volk Optical, Mentor, OH, USA) at the slit lamp, and the entire fundus was assessed by indirect ophthalmoscopy using a 20-D lens (Volk Optical).

Participants unable to attend the study centre due to frailty or physical morbidity were examined at home using similar methods; that is, they had visual acuity assessment, slit lamp examination, IOP measurement with a Perkins tonometer (Perkins Mk3; Haag-Streit, Bern, Switzerland), gonioscopy with NMR-K 2-mirror as well as Sussman 4 mirror lens and optic disc assessment with a 78-D lens at the slit lamp. Indirect ophthalmoscopy using a 20-D lens was performed to examine the posterior segment. The anterior segments of those who were bedridden were examined with a handheld slit lamp (BA 904; Haag-Streit).

Automated visual field analysis using a Humphrey Visual Field (HVF) analyzer (Humphrey Instruments Inc., San Leandro, California, USA) was attempted for all participants with any of the following optic disc features: asymmetry in CDR of >0.2 between the eyes, a vertical CDR of ≥0.65; neuroretinal rim <0.2 at any clock hour; notch in the disc; disc hemorrhage; and obvious peripapillary nerve fiber layer defect in either eye. Visual fields were also assessed if the IOP was ≥22 mm Hg in either eye, or if there was an IOP difference of ≥6 mm Hg between the 2 eyes, using the threshold central 24-2 strategy (stimulus size III). If the visual field was abnormal or unreliable, the test was repeated. The criteria used to determine glaucomatous visual field defects included a field defect that correlated with optic disc damage and met ≥2 of Anderson’s 3 criteria.

Definitions

Definitions for an occludable angle and PACG were based on the International Society for Geographical and Epidemiological Ophthalmology (ISGEO) classification which uses 97.5th and 99.5th percentiles of IOP and vertical CDR of the normal population. In APEDS I, visual field testing was not performed in the entire sample, so normative data could not be used. Hence, as in our previous publication on prevalence, we used normative data from the Chennai Glaucoma Study (CGS) for the 97.5th and 99.5th percentile cutoffs for the IOP and CDR. The CGS and the APEDS populations were both located in south India and are mainly of similar ethnicity (Dravidians). The 97.5th and the 99.5th percentile cutoffs for IOP were 21 and 24 mm Hg, respectively, whereas those for CDR were 0.7 and 0.8, respectively, for the rural population.

Glaucoma was classified according to 3 levels of evidence. In Level I, the diagnosis was based on structural damage and functional changes, that is, CDR or CDR asymmetry ≥97.5th percentile for the normal population, and a neuroretinal rim width reduced to 0.1 CDR (between 10 and 1 o’clock or 5 and 7 o’clock) with definite visual field defects consistent with glaucoma. Level 2 was based on advanced structural damage with unproven field loss. This comprised participants in whom visual fields could not be determined or were unreliable, with a CDR or CDR asymmetry of ≥99.5th percentile for the normal population. Category 3 included persons with an IOP of ≥99.5th percentile for the normal population, whose optic discs could not be examined because of media opacity. In this category, additional criteria such as visual acuity, clinical evidence of glaucoma filtering surgery, and information in medical records were also taken into consideration.

A PACS was defined as an eye with an occludable angle. PAC was defined as an eye with PACS and peripheral anterior synechiae and/or elevated IOP without glaucomatous optic disc damage. PACG was defined as PAC with evidence of glaucoma as defined by the ISGEO. The entire spectrum of PACD consisted of PACS, PAC, and PACG.

The definitions and relevant denominators for each are shown in Table 1 . For each participant, the form of PACD was defined on the basis of the more affected eye.

Table 1

Definitions and Denominators for Angle Closure Disease

Form of Angle Closure Disease	Population at Risk (Denominator)	Incidence
PACS	Normal at baseline (X)	PACS at follow-up (A)
PAC	Normal (X) or PACS (Y) at baseline	PAC at follow up (B)
PACG	Normal (X) or PACS (Y) or PAC (Z) at baseline	PACG at follow-up (C)
PACD	Normal at baseline (X)	PACS or PAC or PACG at follow up (A+B+C)

 

PAC = primary angle closure, PACD = primary angle closure disease, PACG = primary angle closure glaucoma, PACS = primary angle closure suspect.

At baseline, hyperopia was defined as a spherical equivalent of ≥0.5 D in phakic eyes, and myopia was defined as a spherical equivalent of –0.5 D or greater in phakic eyes. Nuclear sclerosis was graded using the LOCS III classification system; nuclear opalescence higher than Grade 2 was considered to be nuclear sclerosis. Hypertension was determined by either one or a combination of the following factors: history of high blood pressure diagnosed by a physician, current use of antihypertensive medication, and/or a blood pressure reading of ≥140/90 mm Hg. Diabetes mellitus (DM) was determined by a history of DM and/or diabetic retinopathy on clinical examination.

Two hundred seventy-three of the 1,470 participants (18.5%) were excluded for the following reasons: (1) participants had the following diagnosis at the baseline: PACD (n = 32), POAG (n = 13), and suspicion of glaucoma on the basis of the clinical appearance of the optic disc (n = 1); (2) participants had undergone cataract surgery in the intervening period (n = 180); and (3) no data were available on gonioscopy at baseline (n = 45) or an iridotomy had been performed (n = 2) ( Figure 1 ).

Flow chart showing the number of participants included in analysis.

Results

A total of 2,790 participants aged ≥40 years were examined in APEDS I. After a mean 15 years, 1,470 (52.6%) were re-examined in APEDS III. The mean (SD) age of these participants was 50.2 (SD 8.1) years; median (first, third quartiles) age was 48 (44, 55) years and ranged between 40 and 82 years at baseline, that is, APEDS I. The distribution of participants by age group was as follows: 774 (52.6%) 40-49 years, 454 (30.8%) 50-59 years, and 242 (16.4%) 60 years and older. There were 670 (45.5%) men. Perimetry was performed in 380 participants, 256 (67.3%) of whom underwent repeat tests as per the study protocol.

We compared baseline demographic characteristics of participants and (1) all non-participants (ie, those who had died since APEDS I and those who did not respond in APEDS III) and (2) those who did not respond in APEDS III (“non-responders,” ie, participants who migrated, could not be traced, or refused to participate) ( Table 2 ). Comparing participants with all non-participants, the latter were older, were more likely to be male, to have nuclear sclerosis and myopia but not hyperopia, to have hypertension and DM, and a leaner body mass index. There was also no difference in baseline PACD between participants and non-participants. Comparing participants with non-responders, participants were more likely to be younger, to be male, nonmyopic, and not to have nuclear sclerosis.

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