No abstract

ABSTRACT.Objective: To report the 5-year progression to primary angle closure glaucoma (PACG) in a population-based cohort of primary angle closure (PAC) subjects. Methods: A total of 37 patients diagnosed as PAC during a population-based study in 1995 were invited for re-examination in 2000. Patients underwent a complete ophthalmic examination including ocular biometry. Progression to PACG was based on optic disc damage and field defects on automated perimetry. Results: In all, 28 of 32 PAC subjects who could be contacted presented for examination. Eight (28.5%; 95% CI 12-45%) had progressed to PACG; two of seven with appositional and six of 21 with synechial closure. All were advised laser peripheral iridotomy (LPI) in 1995; one of the nine who underwent LPI progressed compared to seven of 19 who refused LPI. Four of those originally diagnosed with appositional closure developed peripheral anterior synechiae. One eye of a person previously diagnosed with appositional PAC was reclassified as a primary angle closure suspect (PACS). There was no significant difference in biometric parameters between those who progressed and those who did not. None developed acute PACG or blindness due to glaucoma. Conclusion: In this population-based study of primary angle closure, the 5-year incidence of PACG was eight patients (28.5%; 95% CI 12-45%). We were unable to identify any features that predicted progression.

Exfoliation syndrome (XFS) is the commonest known risk factor for secondary glaucoma and a significant cause of blindness worldwide. Variants in two genes, LOXL1 and CACNA1A have been previously associated with XFS. To further elucidate the genetic basis of XFS, we collected a global sample of XFS cases to refine the association at LOXL1, which previously showed inconsistent results between populations, and to identify new variants associated with XFS. We identified a rare, protective allele at LOXL1 (p.407Phe, OR = 25, P =2.9 × 10−14) through deep resequencing of XFS cases and controls from 9 countries. This variant results in increased cellular adhesion strength compared to the wild-type (p.407Tyr) allele. A genome-wide association study (GWAS) of XFS cases and controls from 24 countries followed by replication in 18 countries identified seven genome-wide significant loci (P < 5 × 10−8). Index variants at the new loci map to chromosomes 13q12 (POMP), 11q23.3 (TMEM136), 6p21 (AGPAT1), 3p24 (RBMS3) and 5q23 (near SEMA6A). These findings provide biological insights into the pathology of XFS, and highlight a potential role for naturally occurring rare LOXL1 variants in disease biology.

Diagnostic ability of peripapillary vessel density parameters of OCTA, especially the inferotemporal sector measurement, was good in POAG and PACG. Diagnostic abilities of vessel density measurements were comparable to RNFL measurements in both POAG and PACG.

No abstract

Primary angle closure glaucoma (PACG) is a major cause of blindness worldwide. We conducted a genome-wide association study (GWAS) followed by replication in a combined total of 10,503 PACG cases and 29,567 controls drawn from 24 countries across Asia, Australia, Europe, North America, and South America. We observed significant evidence of disease association at five new genetic loci upon meta-analysis of all patient collections. These loci are at EPDR1 rs3816415 (odds ratio (OR) = 1.24, P = 5.94 × 10(-15)), CHAT rs1258267 (OR = 1.22, P = 2.85 × 10(-16)), GLIS3 rs736893 (OR = 1.18, P = 1.43 × 10(-14)), FERMT2 rs7494379 (OR = 1.14, P = 3.43 × 10(-11)), and DPM2-FAM102A rs3739821 (OR = 1.15, P = 8.32 × 10(-12)). We also confirmed significant association at three previously described loci (P < 5 × 10(-8) for each sentinel SNP at PLEKHA7, COL11A1, and PCMTD1-ST18), providing new insights into the biology of PACG.

Citation: Kumar RS, Anegondi N, Chandapura RS, et al. Discriminant function of optical coherence tomography angiography to determine disease severity in glaucoma. Invest Ophthalmol Vis Sci. 2016;57:6079-6088. DOI:10.1167/iovs.16-19984 PURPOSE. To determine the discriminant function of optical coherence tomography angiography (OCTA) by disease severity in glaucoma.METHODS. In this prospective, observational cross-sectional study, all subjects underwent visual fields, retinal nerve fiber layer (RNFL) measurements, and OCTA imaging. Local fractal analysis was applied to OCTA images (radial peripapillary capillaries [RPC] layer). Vessel density en face and inside the disc and spacing between large and small vessels were quantified. Stepwise logistic regression was performed and a glaucoma severity score (range, 0-1: 0, normal; 1, severe glaucoma) was developed by using global and regional (superotemporal [ST], inferotemporal [IT], temporal, superonasal [SN], inferonasal, and nasal) vascular parameters. Glaucoma severity score was compared with visual field and RNFL indices. RESULTS.One hundred ninety-nine eyes (112 subjects) with glaucoma (28 eyes preperimetric; 83 early, 43 moderate, and 45 severe glaucoma) and 74 normal (54 subjects) eyes were enrolled. Preperimetric and glaucomatous eyes had significantly altered (P < 0.001) global vascular parameters as compared to normal; regionally, ST, then SN and IT sectors (in that order) showed more change in glaucomatous eyes. Vascular parameters showed better discriminant ability (area under the curve [AUC], sensitivity, and specificity of 0.70, 69.2%, and 72.9%, respectively) than structural parameters between normal and preperimetric glaucomatous eyes. Vascular parameters had comparable AUC (P > 0.05) to visual fields for perimetric glaucoma. Glaucoma severity score identified preperimetric glaucoma and early glaucoma better than did visual fields.CONCLUSIONS. Vascular parameters could be a useful adjunct tool to evaluate/diagnose glaucoma. Longitudinal studies are needed to determine their use in early detection and prognostication.Keywords: optical coherence tomography, glaucoma, visual field, angiography G laucoma is the leading cause of irreversible blindness worldwide.1,2 It is characterized by progressive degeneration of the optic nerve and loss of retinal ganglion cells, with corresponding visual field (VF) defects on standard automated perimetry.1,2 While raised intraocular pressure (IOP) is currently the only known modifiable risk factor for glaucoma, there is evidence that vascular insufficiency in the optic nerve head (ONH) also plays an important role in the pathogenesis of glaucoma.3-5 Currently, a number of methods are available for measuring ONH perfusion.6-11 Fluorescein angiography is invasive. It provides only superficial ONH perfusion and not deep perfusion.6 Noninvasive methods such as laser Doppler flowmetry and laser speckle flowgraphy have demonstrated decreased ONH perfusion in glaucomatous eyes, but have moderate repeatability.8,10 Doppler O...

No abstract