Evaluating the impact of ocular UV exposure for the development for pseudoexfoliation syndrome in a South Indian population.

CLINICAL RELEVANCE: Pathophysiology of pseudoexfoliation syndrome (XFS) can be influenced by environmental factors such as solar exposure/occupational factors and genetic factors. BACKGROUND: The study aims to assess the association of lifetime ocular UV exposure and its impact on the risk of development of XFS. METHODS: All eligible subjects underwent a comprehensive ocular examination. XFS was defined as precipitates on the pupillary border, cornea, and angle of anterior chamber or lens in at least one eye without any clinical signs of glaucoma. A standardised questionnaire was administered to assess the lifetime UV exposure. Conjunctival ultraviolet autofluorescence (CUVAF) photography was taken to detect the conjunctival changes with exposure to UV radiation. Ascorbic acid concentration in the aqueous humour was measured. RESULTS: A total of 404 subjects of which 274 (controls) and 130 (XFS cases) were studied. There were 204 males (50.5%) and 200 females (49.5%).Lifetime UV exposure (OR: 1.14, 95% CI: 1.02-1.30, p: 0.032), CUVAF damage (OR: 1.03, 95% CI: 1.01-1.06, p: 0.008) and outdoor worker (OR: 1.87, 95% CI: 1.18-3.00, p: 0.008) were positively associated with XFS. Usage of spectacles (OR: 0.63, 95% CI: 0.39-0.95, p: 0.030) and ascorbic acid concentration in aqueous (OR: 0.47, 95% CI: 0.23-0.99, p: 0.038) were found to be protective against XFS. CONCLUSION: Besides genetic factors, environmental factors such as lifetime ocular UV exposure and outdoor work are significantly associated with the risk of XFS. CUVAF can be used as a non-invasive tool to detect preclinical sun damage in outdoor workers.

Correlation of Aqueous Humor Lysyl Oxidase Activity with TGF-ß Levels and LOXL1 Genotype in Pseudoexfoliation.

PURPOSE: Pseudoexfoliation (PXF) is a microfibrillopathy involving disordered elastogenesis. Abnormal extracellular matrix (ECM) production underlies the pathophysiology of PXF. The enzyme Lysyl oxidase (LOX) and its isoforms are known to cross-link the elastin and collagen. Though the etiopathogensis of PXF is not well understood, studies report on the genetic risk involving LOXL1 gene. This study aims to screen LOXL1 coding variants rs1048661 and rs3825942 in the South Indian population and the implication of the single nucleotide polymorphism (SNP) with LOX activity. The levels of transforming growth factor ß (TGF-ß) in aqueous humor and its correlation with the LOX activity were also examined. METHODS: Blood, plasma, and aqueous aspirates were prospectively collected from PXF cases with and without glaucoma and cataract cases as controls. DNA was extracted from 48 PXF cases without glaucoma, 12 PXF cases with glaucoma, and 40 age-matched cataract-alone controls without PXF/glaucoma for analyzing LOX SNPs. LOX activity was measured in aqueous humor and plasma of 30 PXF cases without glaucoma, 24 age-matched cataract-alone controls without PXF/glaucoma, and 14 PXF cases with glaucoma. Protein levels of LOX, LOXL1, LOXL2, and total TGF-ß were estimated in plasma and aqueous humor by ELISA. RESULTS: The specific activity of LOX in aqueous humor was found to be significantly lowered in PXF cases compared with cataract-alone controls (p = 0.014). This decrease in LOX activity in PXF cases was associated with high-risk GG haplotype. However, this was not statistically significant and a larger sample size is warranted. TGF-ß1 and TGF-ß2 negatively correlated with LOX activity in aqueous humor (p = 0.028; p = 0.046, respectively). CONCLUSIONS: The LOXL1 SNPs, rs1048661 and rs3825942, are associated with PXF in the South Indian population correlating with lowered LOX activity in the aqueous humor. The increased level of total TGF-ß in the aqueous humor of PXF cases is possibly associated with LOX regulation which needs further investigation.

Importance of population-based studies in clinical practice.

In the last decade, there have been reports on the prevalence of glaucoma from the Vellore Eye Survey, Andhra Pradesh Eye Diseases Survey, Aravind Comprehensive Eye Survey, Chennai Glaucoma Study and West Bengal Glaucoma Study. Population-based studies provide important information regarding the prevalence and risk factors for glaucoma. They also highlight regional differences in the prevalence of various types of glaucoma. It is possible to gather important insights regarding the number of persons affected with glaucoma and the proportion with undiagnosed disease. We reviewed the different population-based studies from India and compare their findings. The lacunae in ophthalmic care that can be inferred from these studies are identified and possible reasons and solutions are discussed. We also discuss the clinical relevance of the various findings, and how it reflects on clinical practice in the country. Since India has a significantly high disease burden, we examine the possibility of population-based screening for disease in the Indian context.

Management of complications in glaucoma surgery.

Surgical option for glaucoma is considered when other modalities are not working out to keep the intraocular pressure under control. Since the surgical procedures for glaucoma disrupt the integrity of the globe, they are known to produce various complications. Some of those complications can be vision-threatening. To minimize the morbidity, it is very important that one should know how to prevent them, recognize them and treat them. The objective of this article is to provide insight into some of those complications that will help the ophthalmologists in treating glaucoma patients in their clinical practice.

Gender variation in ocular biometry and ultrasound biomicroscopy of primary angle closure suspects and normal eyes.

PURPOSE: To compare A-scan biometry and ultrasound biomicroscopy of primary angle closure suspects (PACS) with age-matched normal Indian eyes. PATIENTS AND METHODS: Subjects with primary angle closure suspects (n=57 eyes) and normal eyes (n=57 eyes) underwent A-scan biometry and ultrasound biomicroscopy. Anterior chamber depth (ACD), anterior chamber angle (ACA), axial length (AXL), lens thickness, relative lens position (RLP), central corneal thickness (CCT), angle opening distance 500, trabecular-ciliary process distance (TCPD), iris-ciliary process distance, iris thickness, and scleral-ciliary process angle were measured. The subjects were divided into males, females, and combined groups for analysis. The parameters were compared using independent sample t test with Bonferroni correction for multiple comparisons. RESULTS: In the combined group, the PACS subjects presented a significantly low ACD, AXL, CCT, AOD500, TCPD, ACA (P<0.001), and RLP (P=0.04). In males, RLP was anterior (P=0.002) and in females, the lens thickness (P<0.001) was significantly thicker among the PACS group. CONCLUSIONS: ACD, AXL, CCT, TCPD, ACA, and angle opening distance 500 of the PACS group were significantly lower than in normals. In females, the lens in PACS was thicker than in normals. Lens in males was more anterior-placed in PACS group than in normals.

Genetic homogeneity for inherited congenital microcoria loci in an Asian Indian pedigree.

PURPOSE: Congenital microcoria is a rare autosomal dominant developmental disorder of the iris associated with myopia and juvenile open angle glaucoma. Linkage to the chromosomal locus 13q31-q32 has previously been reported in a large French family. In the current study, a three generation Asian Indian family with 15 congenital microcoria (pupils with a diameter <2 mm) affected members was studied for linkage to candidate microsatellite markers at the 13q31-q32 locus. METHODS: Twenty-four members of the family were clinically examined and genomic DNA was extracted. Microsatellite markers at 13q31-q32 were PCR amplified and run on an ABI Prism 310 genetic analyzer and genotyped with the GeneScan analysis. Two point and multipoint linkage analyses were performed using the MLINK and SUPERLINK programs. RESULTS: Peak two point LOD scores of 3.5, 4.7, and 5.3 were found co-incident with consecutive markers D13S154, DCT, and D13S1280. Multipoint analysis revealed a 4 cM region encompassing D13S1300 to D13S1280 where the LOD remains just over 6.0 Thus we confirm localization of the congenital microcoria locus to chromosomal locus 13q31-q32. In addition, eight individuals who had both microcoria and glaucoma were screened for glaucoma genes: myocilin (MYOC), optineurin (OPTN) and CYP1B1. Using direct sequencing a point mutation (144 G>A) resulting in a Q48H substitution in exon 1 of the MYOC gene was observed in five of the eight glaucoma patients, but not in unaffected family members and 100 unrelated controls. CONCLUSIONS: We have confirmed the localization of the congenital microcoria locus (MCOR) to 13q31-q32 in a large Asian Indian family and conclude that current information suggests this is a single locus disorder and genetically homogeneous. When combined with the initial linkage paper our haplotype and linkage data map the MCOR locus to a 6-7 cM region between D13S265 and D13S1280. The DCT locus, a member of the tyrosinase family involved in pigmentation, maps within this region. Data presented here supports the hypothesis that congenital microcoria is a potential risk factor for glaucoma, although this observation is complicated by the partial segregation of MYOC Q48H (1q24.3-q25.2), a mutation known to be associated with glaucoma in India. Fine mapping and candidate gene analysis continues with the hope that characterizing the micocoria gene will lead to a better understanding of microcoria and glaucoma causation. The relationship between microcoria, glaucoma, and the MYOC Q48H mutation in this family is discussed.