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.

For the diagnosis of early glaucoma by SD-OCT, macular parameters had high discriminating power and high reproducibility comparable with peripapillary RNFL parameters.

Exfoliation syndrome (XFS) is the commonest recognizable cause of open angle glaucoma world-wide. To better understand the etiology of XFS, we conducted a genome-wide association study (GWAS) on 1,484 patients and 1,188 controls from Japan, and followed up the most significant findings on a further 6,901 patients and 20,727 controls from 17 countries across 6 continents. We discovered a significant association between a new locus (CACNA1A rs4926244) and increased susceptibility to XFS (Odds ratio [OR] = 1.16, P = 3.36 × 10−11). Although overwhelming association at the LOXL1 locus was confirmed, the key SNP marker (LOXL1 rs4886776) demonstrated allelic reversal depending on ethnic grouping (In Japanese: ORA-allele= 9.87, P = 2.13 × 10−217; In non-Japanese: ORA-allele= 0.49, P = 2.35 × 10−31). Our findings represent the first genetic locus outside of LOXL1 which surpasses genome-wide significance for XFS, and provides insight into the biology and pathogenesis of the disease.

ABSTRACT.Purpose: To report clinical findings of three patients with unilateral peculiar choroidal excavation in the macula detected by spectral-domain (SD) optical coherence tomography (OCT). Methods: Three cases with unilateral choroidal excavation in the macula detected by SD OCT. Fluorescein angiography (FA), indocyanine green angiography (IA), ultrasonography, visual field tests and multifocal electroretinography (mfERG) were performed. Results: Although all three patients complained of metamorphopsia, visual acuity and central visual field were normal in the affected eyes. SD OCT demonstrated choroidal excavation in the macula despite a normal foveal contour along the inner retinal surface. The excavation involved the outer retinal layers up to the external limiting membrane in cases 1 and 2, while only the retinal pigment epithelium was involved in case 3. The excavation corresponded to foveal pigment mottling in cases 1 and 2 and to a parafoveal yellowish fusiform lesion in case 3. The lesions appeared hypoautofluorescent and unremarkable in FA except for circumferential hyperfluorescence in case 3 and hypofluorescent in IA. B-scan ultrasonography was unremarkable. MfERG in cases 1 and 2 was normal. Conclusions: SD OCT demonstrated two types of choroidal excavation in the macula. More case accumulation and a longer follow-up will elucidate the pathogenesis and prognosis of the lesions.

Multiple SNPs in the TLR4 gene are associated with the risk of NTG. This finding suggests that the ligands and/or cytokines involved in the TLR4 signaling network may be risk factors for the development of NTG.

The GCC is the most useful parameter to evaluate structure and function within the central 10° in glaucoma. Adjusting for RGC displacement is essential to evaluate the relationship between structure of the GCL-related layer and function at the central macula.

Among viscoelastic substances, sodium hyaluronate has become the most popular for intraocular surgeries since the introduction of Healon® (sodium hyaluronate 1%, 4 × 106 daltons) in 1979. This review focuses on the recent development of a new generation of sodium hyaluronate agents with new rheologic properties and the relevant new techniques used in cataract, glaucoma, corneal, and vitreoretinal surgeries. The introduction of sodium hyaluronate agents with different rheologic properties has improved the safety and reliability of intraocular surgeries. Although there have been numerous studies reporting the effectiveness of viscoelastic substances in intraocular surgeries, rigorous validation by multi-center randomized control trials is lacking in many cases. At present, no single viscoelastic agent is most suitable to all of the various intraocular surgical techniques. Therefore, ophthalmologic surgeons should keep up with recent developments of viscoelastic agents and relevant surgical techniques for better patient care.

The enlargement of RNFLD in NTG was closely associated with DH occurrence and the deterioration of visual field.