Lingam Vijaya

Ocular biometry in occludable angles and angle closure glaucoma: a population based survey

Aim: To compare ocular biometric values in a population based sample of eyes with occludable angles, angle closure glaucoma, and normal subjects. Method: 2850 subjects from a population based glaucoma prevalence study underwent complete ocular examination including indentation gonioscopy. Ocular biometry was performed in all subjects classified to have occludable angles (n = 143); angle closure glaucoma (n = 22), and a random subgroup of 419 normal subjects. Ocular biometry readings between the groups were compared and statistically analysed using “t,” “z,” and Mann-Whitney U tests. Results: The mean age among subjects with occludable angles (54.43 (SD 9.53) years) and angle closure glaucoma (57.45 (8.5) years) was significantly higher (p<0.001) than normal subjects (49.95 (9.95) years). Axial length was shorter (p<0.001) in the occludable angle group (22.07 (0.69) mm) compared to the normal group (22.76 (0.78) mm). Anterior chamber depth (ACD) was shallower (p<0.001) among subjects with occludable angles (2.53 (0.26) mm) than normal subjects (3.00 (0.30) mm). Lens thickness (LT) was greater (p<0.001) in people with occludable angles (4.40 (0.53) mm) compared to normal subjects (4.31 (0.31) mm). No significant difference was noted in axial length, ACD (p = 0.451), and LT (p = 0.302) between angle closure glaucoma and occludable eyes. Conclusion: South Indian eyes with angle closure glaucoma and occludable angles seem to have significantly shorter axial lengths, shallower anterior chambers and greater lens thickness compared to the normal group.

Genome-wide association analyses identify three new susceptibility loci for primary angle closure glaucoma

Primary angle closure glaucoma (PACG) is a major cause of blindness worldwide. We conducted a genome-wide association study including 1,854 PACG cases and 9,608 controls across 5 sample collections in Asia. Replication experiments were conducted in 1,917 PACG cases and 8,943 controls collected from a further 6 sample collections. We report significant associations at three new loci: rs11024102 in PLEKHA7 (per-allele odds ratio (OR) = 1.22; P = 5.33 × 10−12), rs3753841 in COL11A1 (per-allele OR = 1.20; P = 9.22 × 10−10) and rs1015213 located between PCMTD1 and ST18 on chromosome 8q (per-allele OR = 1.50; P = 3.29 × 10−9). Our findings, accumulated across these independent worldwide collections, suggest possible mechanisms explaining the pathogenesis of PACG.

Effect of corneal parameters on measurements using the pulsatile ocular blood flow tonograph and Goldmann applanation tonometer

Aims: To investigate the effect of central corneal thickness and corneal curvature on intraocular pressure measurements using the pulsatile ocular blood flow tonograph and the Goldmann applanation tonometer, and to assess the agreement between the pulsatile ocular blood flow tonograph and the Goldmann applanation tonometer in intraocular pressure measurement. Methods: 479 subjects underwent intraocular pressure measurements with the Goldmann applanation tonometer and the pulsatile ocular blood flow tonograph. Of these, 334 patients underwent additional measurement of central corneal thickness with an ultrasonic pachymeter and corneal curvature measurement with a keratometer. Results: The intraocular pressure measurements obtained with both the Goldmann applanation tonometer and the pulsatile ocular blood flow tonograph varied with central corneal thickness and mean keratometric reading. Intraocular pressure measured using the Goldmann applanation tonometer increased by 0.027 mm Hg per µm increase in central corneal thickness. Intraocular pressure measured using the pulsatile ocular blood flow tonograph increased by 0.048 mm Hg per μm increase in central corneal thickness. For an increase of 1 mm of mean corneal curvature there was rise in intraocular pressure of 1.14 mm Hg measured by the Goldmann applanation tonometer and of 2.6 mm Hg measured by the pulsatile ocular blood flow tonograph. When compared to the Goldmann applanation tonometer, the pulsatile ocular blood flow tonograph underestimated at low intraocular pressure and overestimated at higher intraocular pressure. Conclusion: Central corneal thickness and corneal curvature affected measurements obtained with the pulsatile ocular blood flow tonograph more than they affected measurements obtained with the Goldmann applanation tonometer.

Pseudoexfoliation in south India

Aim: To study the profile of pseudoexfoliation in a population based study. Method: 2850 consecutive subjects aged 40 years or older from a population based survey in a rural area of southern India underwent complete ophthalmic evaluation including history, visual acuity testing, refraction, slit lamp examination, applanation tonometry, gonioscopy, and dilated examination of the lens (including LOCS II grading of cataract), fundus, and optic disc. Patients with pseudoexfoliation syndrome were identified and their data were analysed with respect to age, sex, intraocular pressure, gonioscopic grading, cataract, and optic neuropathy. Results: 108 subjects had pseudoexfoliation syndrome (3.8 %). There was a significant increase in prevalence with age but no sex predilection. The condition was unilateral in 53 cases (49.1%) and bilateral in 55 cases (50.9%). 18 cases with pseudoexfoliation (16.7%) had high intraocular pressure (>21 mm Hg), 16 cases (14.8%) had occludable angles, and 14 cases (13%) had pseudoexfoliation glaucoma. There was a significantly higher prevalence of cataract among people with pseudoexfoliation compared to those without pseudoexfoliation (p = 0.014). Conclusion: The prevalence of pseudoexfoliation syndrome in the rural population of south India was 3.8%. Raised intraocular pressure was seen in 16.7% of people with pseudoexfoliation and glaucoma was present in 13%.

Evaluation of tonometric correction factors.

To investigate the efficacy of currently available correction factors in correcting intraocular pressure (IOP) measurements for the errors induced by the normal variations in corneal structural characteristics. Materials and Methods:Central corneal thickness (CCT) and corneal radius of curvature were measured on 324 individuals (175 normal: group 1 and 149 had either open angle glaucoma or ocular hypertension: group 2). IOP was measured in all normal subjects with the Goldmann applanation tonometer and the highest recorded IOP was obtained from patient charts for subjects with either open angle glaucoma or ocular hypertension. Regression analysis was performed on IOP, CCT, and corneal radius of curvature. The corrected IOP was also calculated using the models proposed by Ehlers and Orssengo & Pye. Linear regression analysis was used to calculate the residual association between corneal parameters and corrected IOP. Results:There was a significant positive correlation between IOP measured using Goldmann applanation tonometer and the CCT in both groups. There was no significant correlation between corneal radius of curvature and IOP in either group. There was a significant negative correlation in both the groups between CCT and corrected IOP calculated using the models of Ehlers and Orssengo & Pye. This indicates that the Ehlers and Orssengo & Pye models may significantly overestimate the effect of CCT on IOP measurement. Conclusion:The effect of CCT and IOP as observed in the present study and by other studies in literature is less than predicted by both the Ehlers formula and the Orssengo & Pye model. Correcting IOP for the effect of CCT using these models could be erroneous and lead to overcorrection of IOP, thus resulting in erroneously low corrected IOP eyes with thicker cornea and erroneously high corrected IOP in eyes with thinner cornea.

Glaucoma in India: estimated burden of disease.

Over the last decade the prevalence of glaucoma has been reported by the Vellore Eye Survey, Andhra Pradesh Eye Disease Study, Aravind Comprehensive Eye Survey, Chennai Glaucoma Study, and West Bengal Glaucoma Study. There have been some differences largely because of methodologic variations. We use the reported age and gender stratified prevalence estimates from these studies and the Indian population census estimates to calculate the number of persons with glaucoma or at risk of the disease in the country. On the basis of the available data, we estimate that there are approximately 11.2 million persons aged 40 years and older with glaucoma in India. Primary open angle glaucoma is estimated to affect 6.48 million persons. The estimated number with primary angle-closure glaucoma is 2.54 million. Those with any form of primary angle-closure disease could comprise 27.6 million persons. Most of those with disease are undetected and there exist major challenges in detecting and treating those with disease. In the light of the existing manpower and resource constraints, we evaluate options for improving case detection rates in the country.

Prevalence and causes of blindness in the rural population of the Chennai Glaucoma Study

Aim: To study the prevalence and causes of blindness in a rural south Indian population. Methods: 3924/4800 enumerated (81.75%) subjects, aged 40 years or more from rural Tamil Nadu, underwent comprehensive ophthalmic examination—visual acuity, refraction, intraocular pressure, gonioscopy, cataract grading (LOCS II), retinal examination, and SITA Standard where indicated. Blindness was defined using WHO criteria as best corrected visual acuity of less than 3/60 and/or visual field of less than 10 degrees in the better eye. The influence of age, sex, literacy, and occupation was assessed using multiple logistic regression. Results: 753 subjects (19.2%; 321 males, 432 females) presented with a visual acuity of <3/60; 132 subjects (3.36%, 95% CI: 2.80 to 3.93) were diagnosed to be blind. Cataract was responsible in 74.62% of eyes; glaucoma, cystoid macular oedema, optic atrophy, and corneal scars accounted for 3.79% each. Bilateral causes of blindness were cataract (78.63%), glaucoma (4.29%), optic atrophy (3.42%), cystoid macular oedema, and corneal scars (2.56% each). In 19 eyes (7.2%) the blindness was probably related to cataract surgery. Blindness was positively associated with increasing age (p<0.0001). Conclusion: 3.36% of the studied rural population was bilaterally blind, with cataract being the single most important cause.

Methods and design of the Chennai Glaucoma Study.

PURPOSE To describe the methodology of a population-based study to estimate the prevalence of glaucoma in a rural and urban South Indian population and to study the genetics of glaucoma in this population. METHODS A sample size of 4758 each for rural and urban populations in the Indian state of Tamil Nadu was calculated. Eligible subjects aged 40 years and above from the rural study area covering 32 contiguous villages and the urban area comprising five random clusters in Chennai city are enumerated. Demographic data are collected in the field. A detailed clinical examination, including glaucoma diagnostic procedures, is conducted at the examination centre. Pedigree ascertainment and genetic studies are performed for subjects with occludable angles or glaucoma. Data are recorded in a computerised database. CONCLUSIONS This study is expected to result in an estimation of the prevalence and a better understanding of the genetics of glaucoma in this region.

A 32 kb critical region excluding Y402H in CFH mediates risk for age-related macular degeneration

Complement factor H shows very strong association with Age-related Macular Degeneration (AMD), and recent data suggest that multiple causal variants are associated with disease. To refine the location of the disease associated variants, we characterized in detail the structural variation at CFH and its paralogs, including two copy number polymorphisms (CNP), CNP147 and CNP148, and several rare deletions and duplications. Examination of 34 AMD-enriched extended families (N = 293) and AMD cases (White N = 4210 Indian = 134; Malay = 140) and controls (White N = 3229; Indian = 117; Malay = 2390) demonstrated that deletion CNP148 was protective against AMD, independent of SNPs at CFH. Regression analysis of seven common haplotypes showed three haplotypes, H1, H6 and H7, as conferring risk for AMD development. Being the most common haplotype H1 confers the greatest risk by increasing the odds of AMD by 2.75-fold (95% CI = [2.51, 3.01]; p = 8.31×10−109); Caucasian (H6) and Indian-specific (H7) recombinant haplotypes increase the odds of AMD by 1.85-fold (p = 3.52×10−9) and by 15.57-fold (P = 0.007), respectively. We identified a 32-kb region downstream of Y402H (rs1061170), shared by all three risk haplotypes, suggesting that this region may be critical for AMD development. Further analysis showed that two SNPs within the 32 kb block, rs1329428 and rs203687, optimally explain disease association. rs1329428 resides in 20 kb unique sequence block, but rs203687 resides in a 12 kb block that is 89% similar to a noncoding region contained in ΔCNP148. We conclude that causal variation in this region potentially encompasses both regulatory effects at single markers and copy number.

Low frequency of myocilin mutations in Indian primary open-angle glaucoma patients.

Glaucoma is one of the major causes of blindness in the Indian population. Mutations in the myocilin (MYOC) gene have been reported in different populations. However, reports on MYOC mutations in Indian primary open‐angle glaucoma (POAG) patients and juvenile open‐angle glaucoma (JOAG) patients are sparse. We therefore screened 100 unrelated POAG/JOAG patients for MYOC mutations. Patients with POAG/JOAG were clinically diagnosed. Genomic DNA from such patients was collected and studied for MYOC mutations by direct sequencing. Nucleotide variations were compared with unrelated healthy controls by restriction enzyme digestion. Secondary structure prediction for the sequence variants was performed by Chou–Fasman method. A novel mutation in exon 1 (144 G→Α) resulting in Gln48His substitution was observed in 2% of the patients. Four other polymorphisms were also observed. The novel mutation was seen in four other affected family members of a JOAG patient. The novel mutation was found to alter the secondary structure in the glycosaminoglycan initiation site of the protein. MYOC mutations were found in 2% of the population studied. MYOC gene may not be playing a significant role in causing POAG in the Indian population.