Alan L. Robin

Glaucoma in a rural population of southern India: The Aravind comprehensive eye survey

PURPOSE To determine the prevalence of glaucoma and risk factors for primary open-angle glaucoma in a rural population of southern India. DESIGN A population-based cross-sectional study. PARTICIPANTS A total of 5150 subjects aged 40 years and older from 50 clusters representative of three southern districts of Tamil Nadu in southern India. METHODS All participants had a comprehensive eye examination at the base hospital, including visual acuity using logarithm of the minimum angle of resolution illiterate E charts and refraction, slit-lamp biomicroscopy, gonioscopy, applanation tonometry, dilated fundus examinations, and automated central 24-2 full-threshold perimetry. MAIN OUTCOME MEASURES Definite primary open-angle glaucoma (POAG) was defined as angles open on gonioscopy and glaucomatous optic disc changes with matching visual field defects, whereas ocular hypertension was defined as intraocular pressure (IOP) greater than 21 mmHg without glaucomatous optic disc damage and visual field defects in the presence of an open angle. Manifest primary angle-closure glaucoma (PACG) was defined as glaucomatous optic disc damage or glaucomatous visual field defects with the anterior chamber angle partly or totally closed, appositional angle closure or synechiae in the angle, and absence of signs of secondary angle closure. Secondary glaucoma was defined as glaucomatous optic nerve damage and/or visual field abnormalities suggestive of glaucoma with ocular disorders that contribute to a secondary elevation in IOP. RESULTS The prevalence (95% confidence interval) of any glaucoma was 2.6% (2.2, 3.0), of POAG it was 1.7% (1.3, 2.1), and if PACG it was 0.5% (0.3, 0.7), and secondary glaucoma excluding pseudoexfoliation was 0.3% (0.2,0.5). On multivariate analysis, increasing age, male gender, myopia greater than 1 diopter, and pseudoexfoliation were significantly associated with POAG. After best correction, 18 persons (20.9%) with POAG were blind in either eye because of glaucoma, including 6 who were bilaterally blind and an additional 12 persons with unilateral blindness because of glaucomatous optic neuropathy in that eye. Of those identified with POAG, 93.0% had not been previously diagnosed with POAG. CONCLUSIONS The prevalence of glaucoma in this population is not lower than that reported for white populations elsewhere. A large proportion of those with POAG had not been previously diagnosed. One fifth of those with POAG had blindness in one or both eyes from glaucoma. Early detection of glaucoma in this population will reduce the burden of blindness in India.

Blindness and vision impairment in a rural south Indian population: the Aravind Comprehensive Eye Survey

OBJECTIVE To determine the prevalence of blindness and vision impairment in a rural population of southern India. DESIGN A population-based cross-sectional study. PARTICIPANTS A total of 17200 subjects aged 6 years or older, including 5150 subjects aged 40 years or older from 50 clusters representative of three southern districts of Tamil Nadu in southern India. METHODS All participants had preliminary screenings consisting of vision using a LogMAR illiterate E chart and anterior segment hand light examinations at the village level. Subjects aged 40 years or older were offered comprehensive eye examinations at the base hospital, including visual acuity using LogMAR illiterate E charts and refraction, slit-lamp biomicroscopy, gonioscopy, applanation tonometry, dilated fundus examinations, and automated Humphrey central 24-2 full threshold perimetry; subjects younger than 40 years of age who had any signs or symptoms of ocular disease were also offered comparable examinations at the base hospital. MAIN OUTCOME MEASURES Visual impairment was defined as best-corrected visual acuity <6/18, and blindness was defined using both Indian (<6/60) and World Health Organization (<3/60) definitions. RESULTS Comprehensive examinations at the base hospital were performed on 5150 (96.5%) of 5337 persons 40 years of age or older. Among those 40 years of age and older, presenting visual acuity at the <3/60 level was present in 4.3% (95% confidence interval [CI]: 3.8, 4.9) and 11.4% (95% CI: 10.6, 12.3) at the <6/60 level. After best correction, the corresponding figures were 1.0% (95% CI: 0.79, 1.2) and 2.1% (95% CI: 1.7, 2.5). Over 70% of subjects improved their vision by at least one line, and nearly a third by three lines after refraction. Age-related cataract was the most common potentially reversible blinding disorder (72.0%) among eyes presenting with blindness. CONCLUSIONS Blindness and vision impairment remain major public health problems in India that need to be addressed. Cataracts and refractive errors remain the major reversible causes for the burden of vision impairment in this rural population.

A Comparison of Neodymium:YAG end Argon Laser Iridotomies

A prospective short-term clinical study evaluated argon and Q-switched neodymium:YAG laser iridotomies in 40 eyes of 20 patients with primary chronic angle-closure glaucoma. All patients had bilateral iridotomies with one eye randomly assigned to argon laser and the fellow eye to neodymium:YAG laser therapy. In all eyes a patent iridotomy was created in one treatment session. A mean of 12 +/- 11 and 0.033 +/- 0.025 J were needed for iridotomy formation in argon and neodymium:YAG treated eyes respectively. No neodymium:YAG and six (30%) argon iridotomies had marked closure requiring retreatment. Immediate postoperative intraocular pressure elevation greater than 10 mmHg was seen in seven (35%) argon and six (30%) neodymium:YAG-treated eyes. Nine (45%) eyes treated with the neodymium:YAG laser had bleeding from the iridotomy site. No acute lens damage was found in the neodymium:YAG eyes while seven (35%) lenses in the argon group had focal opacities. Seven (35%) neodymium:YAG and five (25%) argon treated eyes had focal nonprogressive corneal opacities above the iridotomy site. Specular microscopy showed a significant central corneal endothelial loss in argon laser treated eyes. No eyes had detectable retinal damage.

Confocal laser scanning ophthalmoscope. Reproducibility of optic nerve head topographic measurements with the confocal laser scanning ophthalmoscope.

BACKGROUND Glaucoma is an optic neuropathy in which changes in the appearance of both the optic nerve head and the surrounding tissues are important in both diagnosing its presence and progression. Accurate methods to objectively document the appearance of the optic nerve are necessary. The confocal laser scanning ophthalmoscope (Zeiss) is a new prototype instrument that may have the capability to accurately perform this function. METHODS The authors performed a prospective pilot study evaluating the ability of the confocal laser scanning ophthalmoscope to reproduce three-dimensional optic nerve images. Each retinal image contained 600,000 bytes of information. Thirty discrete images of the right optic nerves of 19 visually normal volunteers were obtained. Depth measurements were compared from the same 100 x 100 micron areas (neighborhoods). RESULTS Image comparisons found the variability of depth measurements for the entire image were within 102 microns (95% confidence interval). Sixty percent of the depth measurements were reproducible within 100 microns. Variability of the depth measurements was greatest where the neuroretinal rim sloped at the edge of the optic cup and lowest in the peripapillary area. CONCLUSION The confocal laser scanning ophthalmoscope has the potential to be a safe, rapid, and reproducible method of imaging ocular structures.

Brimonidine Tartrate: A One-month Dose Response Study

BACKGROUND Brimonidine tartrate is a relatively selective alpha2-agonist that effectively reduces mean intraocular pressure (IOP) and the incidence of IOP spikes after laser trabeculoplasty. The authors were interested in evaluating the dose response of brimonidine when applied topically for a longer duration in patients with elevated IOPs. METHODS The authors conducted a 1-month, multicentered, double-masked, randomized, placebo-controlled, parallel clinical study in 194 patients with ocular hypertension or glaucoma (mean IOP, 25.6 +/- 3.2 mmHg). The authors administered three concentrations of brimonidine (0.08%, 0.2%, and 0.5%) or placebo bilaterally every 12 hours for 1 month. The authors evaluated the following parameters: IOP, heart rate, blood pressure, visual acuity, pupil size, basal tear secretion as well as patient comfort at baseline, day 1, week 1, week 3, and week 4. RESULTS All concentrations of brimonidine significantly reduced IOP, compared to baseline and placebo, at all follow-up visits. Maximum mean IOP decreases from baseline of 20.8%, 27.2%, and 30.1% were observed for the 0.08%, 0.20%, and 0.5% treatment groups, respectively. On days 1 and 21, the 0.2% and 0.5% treatment groups exhibited significantly greater IOP decreases than did the 0.08% group. After the initial steep decline in IOP, the effect decreased slightly and stabilized at day 14 at the level that was maintained throughout the study. The most frequent side effects reported were fatigue and dry mouth. No significant changes in heart rate were reported. Statistically significant decreases in mean blood pressure without clinical symptoms were observed within the 0.2% and 0.5% treatment groups. CONCLUSION Brimonidine 0.2% is well tolerated, efficacious, and shows potential as an agent in the long-term treatment of elevated IOP.

Copy number variations on chromosome 12q14 in patients with normal tension glaucoma

We report identification of a novel genetic locus (GLC1P) for normal tension glaucoma (NTG) on chromosome 12q14 using linkage studies of an African-American pedigree (maximum non-parametric linkage score = 19.7, max LOD score = 2.7). Subsequent comparative genomic hybridization and quantitative polymerase chain reaction (PCR) experiments identified a 780 kbp duplication within the GLC1P locus that is co-inherited with NTG in the pedigree. Real-time PCR studies showed that the genes within this duplication [TBK1 (TANK-binding kinase 1), XPOT, RASSF3 and GNS] are all expressed in the human retina. Cohorts of 478 glaucoma patients (including 152 NTG patients), 100 normal control subjects and 400 age-related macular degeneration patients were subsequently tested for copy number variation in GLC1P. Overlapping duplications were detected in 2 (1.3%) of the 152 NTG subjects, one of which had a strong family history of glaucoma. These duplications defined a 300 kbp critical region of GLC1P that spans two genes (TBK1 and XPOT). Microarray expression experiments and northern blot analysis using RNA obtained from human skin fibroblast cells showed that duplication of chromosome 12q14 results in increased TBK1 and GNS transcription. Finally, immunohistochemistry studies showed that TBK1 is expressed in the ganglion cells, nerve fiber layer and microvasculature of the human retina. Together, these data link the duplication of genes on chromosome 12q14 with familial NTG and suggest that an extra copy of the encompassed TBK1 gene is likely responsible for these cases of glaucoma. However, animal studies will be necessary to rule out a role for the other duplicated or neighboring genes.

An Objective Evaluation of Eyedrop Instillation in Patients With Glaucoma

OBJECTIVES To evaluate the performance of patients with ocular hypertension and glaucoma who are experienced in the instillation of topical ocular hypotensive medications. METHODS We conducted a prospective, open-label study at a single private practice site. We enrolled 139 patients with a diagnosis of glaucoma or ocular hypertension who used 1 or more topical ocular hypotensive medications for at least 6 months and who instilled their own medications. Patients were questioned regarding their use of topical ocular hypotensive medications, and we used a video recording to evaluate patient performance of eyedrop instillation with 2 bottle designs. RESULTS Patients reported relatively good performance on eyedrop instillation. One hundred twenty-nine of 139 patients (92.8%) reported no problem putting in their eyedrops, and 86 of 139 (61.9%) believed that they never missed their eye when administering the drops. The proportions of patients who were able to instill a single drop into the eye without touching the bottle to the eye were 14 of 64 (21.9%) with a 15-mL bottle and 36 of 117 (30.8%) with a 2.5-mL bottle. CONCLUSIONS Under a single direct observation, patients experienced in the use of topical ocular hypotensive agents performed relatively poorly when instilling a single eyedrop into the eye without touching the bottle tip to the eye or the ocular adnexae. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00522600.

Increased Intraocular Pressure in the Immediate Postoperative Period After Extracapsular Cataract Extraction

We evaluated the immediate intraocular pressure increase after extracapsular cataract surgery in 58 eyes. Two to three hours postoperatively, 34 eyes (59%) developed an intraocular pressure greater than or equal to 25 mm Hg. We found an intraocular pressure of at least 40 mm Hg in seven eyes. Mean intraocular pressure two to three hours postoperatively was 8.9 +/- 9.8 mm Hg greater than the preoperative intraocular pressure. The use of intraocular sodium hyaluronate had no apparent effect on intraocular pressure.

Algorithm for interpreting the results of frequency doubling perimetry

PURPOSE To evaluate an algorithm for the identification of glaucomatous visual field defects with the screening mode of frequency doubling technology. METHODS Screening-mode frequency doubling technology and Swedish interactive threshold algorithm perimetry were performed on 137 of 150 consecutive patients referred to a glaucoma specialist. We created an algorithm for the frequency doubling technology that gave increased importance to both more severe defects and defects closer to fixation. These values were then compared with the results of the Swedish interactive threshold algorithm visual fields evaluated by the glaucoma hemifield test, two masked glaucoma specialists, and a published definition of glaucomatous damage to determine sensitivity and specificity of the frequency doubling technology screening mode for detecting glaucoma.

Pseudoexfoliation in a rural population of southern India: the Aravind Comprehensive Eye Survey

PURPOSE To determine the prevalence and risk factors for pseudoexfoliation in a rural population of southern India. DESIGN A population-based cross-sectional study of pseudoexfoliation with and without glaucoma in rural southern India. METHOD A total of 5,150 subjects aged 40 years and older from 50 clusters representative of three southern districts of Tamil Nadu in southern India. RESULTS All participants had a comprehensive eye examination at the base hospital, including visual acuity using logarithm of minimal angle of resolution (logMAR) illiterate E charts and refraction, slit-lamp biomicroscopy, gonioscopy, applanation tonometry, dilated fundus examinations, and automated central 24-2 full-threshold perimetry. Pseudoexfoliation (PXF) was diagnosed by the presence of typical white deposits on the anterior lens surface; additional sites included the cornea, iris, anterior vitreous face, posterior capsule, and intraocular lens in cataract-operated eyes and changes in the angle determined through gonioscopy, including increased pigmentation, PXF deposition, and PXF material within the angle. CONCLUSIONS The prevalence (95% confidence interval) of PXF was 6.0% (5.3, 6.6). The prevalence increased with age (P <.001) and was greater in males (P =.01). Of subjects with PXF, 25.7% remained bilaterally blind after best correction; 89.3% of this bilateral blindness was the result of cataracts. The prevalence of glaucoma among subjects with PXF was 7.5%; exfoliation was present in 26.7% of those identified as primary open-angle glaucoma. On multivariate analysis, increasing age and male gender were significantly associated with PXF. Pseudoexfoliation appears to be a relatively common disorder in older individuals in southern India. Ophthalmologists in India may wish to focus on the detection of PXF, especially considering the relatively large burden of cataracts in this population, the risks for operative complications related to PXF, and the fact that PXF may be used as a marker to aid in the detectection of glaucoma.