PURPOSE: To report the technique and result of keratopigmentation using a femtosecond laser for the treatment of functional visual disabilities caused by peripheral iridectomies. DESIGN: Case report. METHODS: Two eyes of 2 patients underwent femtosecond laser-assisted keratopigmentation (FLAK) for moderate to severe visual dysfunction secondary to peripheral iridectomies. The main outcomes measures of the study were changes in visual-related symptoms, cosmesis, and intraoperative surgical complications. RESULTS: Following FLAK, the visual-related symptoms (ghosting, glare, and monocular diplopia) improved in both cases with significant improvement to total elimination of symptoms. No patient lost any lines of visual acuity, and no significant complications were observed during the follow-up period. The cosmetic appearance was reported as very good. CONCLUSIONS: FLAK is minimally invasive and results in a significant decrease in the subjective glare and photophobia and even in resolution of monocular diplopia. The cosmetic outcome was also favorable. This technique allows surgeons to correct visual disabilities associated with iris defects with a high success rate while avoiding more aggressive intraocular surgery.

Bell's palsy is a common cranial neuropathy causing acute unilateral lower motor neuron facial paralysis. Immune, infective and ischaemic mechanisms are all potential contributors to the development of Bell's palsy, but the precise cause remains unclear. Advancements in the understanding of intra-axonal signal molecules and the molecular mechanisms underpinning Wallerian degeneration may further delineate its pathogenesis along with in vitro studies of virus-axon interactions. Recently published guidelines for the acute treatment of Bell's palsy advocate for steroid monotherapy, although controversy exists over whether combined corticosteroids and antivirals may possibly have a beneficial role in select cases of severe Bell's palsy. For those with longstanding sequaelae from incomplete recovery, aesthetic, functional (nasal patency, eye closure, speech and swallowing) and psychological considerations need to be addressed by the treating team. Increasingly, multidisciplinary collaboration between interested clinicians from a wide variety of subspecialties has proven effective. A patient centred approach utilising physiotherapy, targeted botulinum toxin injection and selective surgical intervention has reduced the burden of long-term disability in facial palsy.

PURPOSE: Unilateral peripheral prisms for homonymous hemianopia (HH) expand the visual field through peripheral binocular visual confusion, a stimulus for binocular rivalry that could lead to reduced predominance and partial suppression of the prism image, thereby limiting device functionality. Using natural-scene images and motion videos, we evaluated whether detection was reduced in binocular compared with monocular viewing. METHODS: Detection rates of nine participants with HH or quadranopia and normal binocularity wearing peripheral prisms were determined for static checkerboard perimetry targets briefly presented in the prism expansion area and the seeing hemifield. Perimetry was conducted under monocular and binocular viewing with targets presented over videos of real-world driving scenes and still frame images derived from those videos. RESULTS: With unilateral prisms, detection rates in the prism expansion area were significantly lower in binocular than in monocular (prism eye) viewing on the motion background (medians, 13 and 58%, respectively, p = 0.008) but not the still frame background (medians, 63 and 68%, p = 0.123). When the stimulus for binocular rivalry was reduced by fitting prisms bilaterally in one HH and one normally sighted subject with simulated HH, prism-area detection rates on the motion background were not significantly different (p > 0.6) in binocular and monocular viewing. CONCLUSIONS: Conflicting binocular motion appears to be a stimulus for reduced predominance of the prism image in binocular viewing when using unilateral peripheral prisms. However, the effect was only found for relatively small targets. Further testing is needed to determine the extent to which this phenomenon might affect the functionality of unilateral peripheral prisms in more real-world situations.

The field of gene therapy for retinal blinding disorders is experiencing incredible momentum, justified by hopeful results in early stage clinical trials for inherited retinal degenerations. The premise of the use of the gene as a drug has come a long way, and may have found its niche in the treatment of retinal disease. Indeed, with only limited treatment options available for retinal indications, gene therapy has been proven feasible, safe, and effective and may lead to durable effects following a single injection. Here, we aim at putting into context the promise and potential, the technical, clinical, and economic boundaries limiting its application and development, and speculate on a future in which gene therapy is an integral component of ophthalmic clinical care.

Importance: Little is known about the long-term risk of dying of uveal melanoma after treatment with radiotherapy. Objective: To determine the long-term risk of dying of this disease, we evaluated melanoma-related mortality rates up to 25 years after proton beam therapy in a large series of patients with uveal melanoma. Design, Setting, and Participants: In this analysis, we included 3088 patients with uveal melanoma, identified from a hospital-based cohort and treated with proton irradiation between January 1975 and December 2005. Vital status and cause of death were ascertained through active follow-up and searches of government databases (the Social Security Death Index and the National Death Index) through December 31, 2008. Cumulative rates of melanoma-related mortality were calculated using the Kaplan-Meier method. Patient and tumor characteristics of known prognostic significance for melanoma-associated death were evaluated, including patient age and tumor dimensions. Main Outcomes and Measures: The primary outcome measure was cumulative rates of melanoma-specific mortality, and secondary measures included annual melanoma-specific mortality hazard rates and cumulative all-cause mortality rates. Results: Of 1490 deceased patients, 620 (41.6%) died of ocular melanoma. In addition, 19 patients were alive, but their melanoma metastasized, by the end of the observation period (mean follow-up after diagnosis of metastasis, 5.3 years). All-cause mortality rates in this cohort were 49.0% (95% CI, 47.0-51.1) at 15 years, 58.6% (95% CI, 56.4%-60.8%) at 20 years, and 66.8% (95% CI, 64.2%-69.4%) at 25 years. Melanoma-related mortality rates were 24.6% (95% CI, 22.8-26.4) at 15 years after treatment, 25.8% (95% CI, 24.0-27.8) at 20 years after treatment, and 26.4% (95% CI, 24.5-28.5) at 25 years after treatment. The 20-year mortality rate was 8.6% (95% CI, 6.2-11.9) for younger patients (≤60 years) with small tumors (≤11 mm) and 40.1% (95% CI, 36.1-44.3) for older patients (>60 years) with large tumors (>11 mm). Conclusions and Relevance: In this large series of patients with ocular melanoma treated conservatively with proton beam irradiation, the cumulative melanoma-related mortality rates continued to increase up to 23 years after treatment. Annual rates decreased considerably (to <1%) 14 years after treatment. Information regarding the long-term risk of dying of uveal melanoma may be useful to clinicians when counseling patients.

By generating the second messenger cGMP in retinal rods and cones, ROS-GC plays a central role in visual transduction. Guanylate cyclase-activating proteins (GCAPs) link cGMP synthesis to the light-induced fall in [Ca(2+)]i to help set absolute sensitivity and assure prompt recovery of the response to light. The present report discloses a surprising feature of this system: ROS-GC is a sensor of bicarbonate. Recombinant ROS-GCs synthesized cGMP from GTP at faster rates in the presence of bicarbonate with an ED50 of 27 mm for ROS-GC1 and 39 mm for ROS-GC2. The effect required neither Ca(2+) nor use of the GCAPs domains; however, stimulation of ROS-GC1 was more powerful in the presence of GCAP1 or GCAP2 at low [Ca(2+)]. When applied to retinal photoreceptors, bicarbonate enhanced the circulating current, decreased sensitivity to flashes, and accelerated flash response kinetics. Bicarbonate was effective when applied either to the outer or inner segment of red-sensitive cones. In contrast, bicarbonate exerted an effect when applied to the inner segment of rods but had little efficacy when applied to the outer segment. The findings define a new regulatory mechanism of the ROS-GC system that affects visual transduction and is likely to affect the course of retinal diseases caused by cGMP toxicity.

OBJECTIVE: Tumor Necrosis Factor (TNF) mediates retinal ganglion cell death in glaucoma. Anti-TNF drugs are neuroprotective in an animal model of glaucoma. It is unclear whether medications with anti-TNF properties such as bupropion have an impact on the risk of developing open-angle glaucoma (OAG) in humans. The purpose of this study is to determine whether bupropion use alters the risk of developing OAG. METHODS: Claims data for beneficiaries age ≥35 years with no pre-existing OAG enrolled in a large nationwide U.S. managed care network continuously for ≥4 years between 2001-2011 was analyzed to identify patients who had been newly-diagnosed with OAG. The amount of bupropion use as captured from outpatient pharmacy claims over a four-year period was also quantified for each beneficiary. Multivariable Cox regression modeling assessed the impact of bupropion and other antidepressant medications on the risk of developing OAG with adjustment for sociodemographic characteristics of the enrollees along with medical and ocular comorbidities. RESULTS: Of 638,481 eligible enrollees, 15,292 (2.4%) developed OAG. After adjustment for confounding factors including use of other antidepressant medication classes, each additional month of bupropion use was associated with a 0.6% reduced risk of OAG (HR = 0.994, (95% CI: 0.989-0.998), p = 0.007). Compared to nonusers, those with 24-48 months of bupropion use had a 21% reduced hazard (HR=0.79, (CI: 0.65-0.94), p = 0.0099) of OAG. This association did not differ among persons taking bupropion for depression or for other reasons (p-interaction = 0.82). There was no significant association between use of tricyclic antidepressants (HR = 1.000, (CI: 0.997-1.004), p = 0.95) or selective serotonin reuptake inhibitors (HR = 0.999, (CI: 0.997-1.001), p = 0.39) and development of OAG. CONCLUSION: These findings suggest bupropion use may be beneficial in reducing the risk of OAG. If prospective studies confirm the findings of this analysis, this may identify a novel therapeutic target for OAG.

Meibomian gland dysfunction is a leading cause of ocular surface disease. However, little is known about the regulatory processes that control the development and maintenance of this sebaceous gland. Here, we identify a novel function for CD147, a transmembrane protein that promotes tissue remodeling through induction of matrix metalloproteinases, in regulating meibocyte differentiation and activity. We found that CD147 localized along basal cells and within discrete membrane domains of differentiated meibocytes in glandular acini containing gelatinolytic activity. Induction of meibocyte differentiation in vitro promoted CD147 clustering and MMP9 secretion, whereas RNAi-mediated abrogation of CD147 impaired MMP9 secretion, concomitant with a reduction in the number of proliferative cells and cytoplasmic lipids. Meibomian glands of CD147 knockout mice had a lower number of acini in both the superior and inferior tarsal plates of the eyelids, and were characterized by loss of lipid-filled meibocytes compared with control mice. Together, our data provide evidence showing that gelatinolytic activity in meibocytes is dependent on CD147, and supports a role for CD147 in maintaining the normal development and function of the meibomian gland.

Detachment of photoreceptors from the retinal pigment epithelium is seen in various retinal disorders, resulting in photoreceptor death and subsequent vision loss. Cell death results in the release of endogenous molecules that activate molecular platforms containing caspase-1, termed inflammasomes. Inflammasome activation in retinal diseases has been reported in some cases to be protective and in others to be detrimental, causing neuronal cell death. Moreover, the cellular source of inflammasomes in retinal disorders is not clear. Here, we demonstrate that patients with photoreceptor injury by retinal detachment (RD) have increased levels of cleaved IL-1β, an end product of inflammasome activation. In an animal model of RD, photoreceptor cell death led to activation of endogenous inflammasomes, and this activation was diminished by Rip3 deletion. The major source of Il1b expression was found to be infiltrating macrophages in the subretinal space, rather than dying photoreceptors. Inflammasome inhibition attenuated photoreceptor death after RD. Our data implicate the infiltrating macrophages as a source of damaging inflammasomes after photoreceptor detachment in a RIP3-dependent manner and suggest a novel therapeutic target for treatment of retinal diseases.

We have previously characterized human neuronal progenitor cells (hNP) that can adopt a retinal ganglion cell (RGC)-like morphology within the RGC and nerve fiber layers of the retina. In an effort to determine whether hNPs could be used a candidate cells for targeted delivery of neurotrophic factors (NTFs), we evaluated whether hNPs transfected with an vector that expresses IGF-1 in the form of a fusion protein with tdTomato (TD), would increase RGC survival in vitro and confer neuroprotective effects in a mouse model of glaucoma. RGCs co-cultured with hNPIGF-TD cells displayed enhanced survival, and increased neurite extension and branching as compared to hNPTD or untransfected hNP cells. Application of various IGF-1 signaling blockers or IGF-1 receptor antagonists abrogated these effects. In vivo, using a model of glaucoma we showed that IOP elevation led to reductions in retinal RGC count. In this model, evaluation of retinal flatmounts and optic nerve cross sections indicated that only hNPIGF-TD cells effectively reduced RGC death and showed a trend to improve optic nerve axonal loss. RT-PCR analysis of retina lysates over time showed that the neurotrophic effects of IGF-1 were also attributed to down-regulation of inflammatory and to some extent, angiogenic pathways. This study shows that neuronal progenitor cells that hone into the RGC and nerve fiber layers may be used as vehicles for local production and delivery of a desired NTF. Transplantation of hNPIGF-TD cells improves RGC survival in vitro and protects against RGC loss in a rodent model of glaucoma. Our findings have provided experimental evidence and form the basis for applying cell-based strategies for local delivery of NTFs into the retina. Application of cell-based delivery may be extended to other disease conditions beyond glaucoma.

PURPOSE: Retinitis pigmentosa is a Mendelian disease with a very elevated genetic heterogeneity. Most mutations are responsible for less than 1% of cases, making molecular diagnosis a multigene screening procedure. In this study, we assessed whether direct testing of specific alleles could be a valuable screening approach in cases characterized by prevalent founder mutations. METHODS: We screened 275 North American patients with recessive/isolate retinitis pigmentosa for two mutations: an Alu insertion in the MAK gene and the p.Lys42Glu missense in the DHDDS gene. All patients were unrelated; 35 reported Jewish ancestry and the remainder reported mixed ethnicity. RESULTS: We identified the MAK and DHDDS mutations homozygously in only 2.1% and 0.8%, respectively, of patients of mixed ethnicity, but in 25.7% and 8.6%, respectively, of cases reporting Jewish ancestry. Haplotype analyses revealed that inheritance of the MAK mutation was attributable to a founder effect. CONCLUSION: In contrast to most mutations associated with retinitis pigmentosa-which are, in general, extremely rare-the two alleles investigated here cause disease in approximately one-third of North American patients reporting Jewish ancestry. Therefore, their screening constitutes an alternative procedure to large-scale tests for patients belonging to this ethnic group, especially in time-sensitive situations.Genet Med 17 4, 285-290.

BACKGROUND: Graft failure because of immune rejection remains a significant problem in organ transplantation, and lymphatic and blood vessels are important components of the afferent and efferent arms of the host alloimmune response, respectively. We compare the effect of antihemangiogenic and antilymphangiogenic therapies on alloimmunity and graft survival in a murine model of high-risk corneal transplantation. METHODS: Orthotopic corneal transplantation was performed in hemevascularized and lymph-vascularized high-risk host beds, and graft recipients received subconjunctival vascular endothelial growth factor (VEGF)-trap, anti-VEGF-C, sVEGFR-3, or no treatment, beginning at the time of surgery. Fourteen days after transplantation, graft hemeangiogenesis and lymphangiogenesis were evaluated by immunohistochemistry. The frequencies of Th1 cells in regional lymphoid tissue and graft-infiltrating immune cells were evaluated by flow cytometry. Long-term allograft survival was compared using Kaplan-Meier curves. RESULTS: VEGF-trap significantly decreased graft hemangiogenesis as compared to the control group and was most effective in reducing the frequency of graft-infiltrating immune cells. Anti-VEGF-C and sVEGFR3 significantly decreased graft lymphangiogenesis and lymphoid Th1 cell frequencies as compared to control. VEGF-trap (72%), anti-VEGF-C (25%), and sVEGFR-3 (11%) all significantly improved in the 8-week graft survival compared to control (0%), although VEGF-trap was significantly more effective than both anti-VEGF-C (P < 0.05) and sVEGFR-3 (P < 0.05). CONCLUSION: In a clinically relevant model of high-risk corneal transplantation in which blood and lymphatic vessels are present and treatment begins at the time of transplantation, VEGF-trap is significantly more effective in improving long-term graft survival as compared to anti-VEGF-C and sVEGFR-3, but all approaches improve survival when compared to untreated control.

PURPOSE: To report on the accuracy of the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes for identifying patients with polymyalgia rheumatica (PMR) and concurrent noninfectious inflammatory ocular conditions in a large healthcare organization database. METHODS: Queries for patients with PMR and uveitis or scleritis were executed in two general teaching hospitals' databases. Patients with ocular infections or other rheumatologic conditions were excluded. Patients with PMR and ocular inflammation were identified, and medical records were reviewed to confirm accuracy. RESULTS: The query identified 10,697 patients with the ICD-9-CM code for PMR and 4154 patients with the codes for noninfectious inflammatory ocular conditions. The number of patients with both PMR and noninfectious uveitis or scleritis by ICD-9-CM codes was 66. On detailed review of the charts of these 66 patients, 31 (47%) had a clinical diagnosis of PMR, 43 (65%) had noninfectious uveitis or scleritis, and only 20 (30%) had PMR with concurrent noninfectious uveitis or scleritis confirmed based on clinical notes. CONCLUSIONS: While the use of ICD-9-CM codes has been validated for medical research of common diseases, our results suggest that ICD-9-CM codes may be of limited value for epidemiological investigations of diseases which can be more difficult to diagnose. The ICD-9-CM codes for rarer diseases (PMR, uveitis and scleritis) did not reflect the true clinical problem in a large proportion of our patients. This is particularly true when coding is performed by physicians outside the area of specialty of the diagnosis.

Cone photoreceptors function under daylight conditions and are essential for color perception and vision with high temporal and spatial resolution. A remarkable feature of cones is that, unlike rods, they remain responsive in bright light. In rods, light triggers a decline in intracellular calcium, which exerts a well studied negative feedback on phototransduction that includes calcium-dependent inhibition of rhodopsin kinase (GRK1) by recoverin. Rods and cones share the same isoforms of recoverin and GRK1, and photoactivation also triggers a calcium decline in cones. However, the molecular mechanisms by which calcium exerts negative feedback on cone phototransduction through recoverin and GRK1 are not well understood. Here, we examined this question using mice expressing various levels of GRK1 or lacking recoverin. We show that although GRK1 is required for the timely inactivation of mouse cone photoresponse, gradually increasing its expression progressively delays the cone response recovery. This surprising result is in contrast with the known effect of increasing GRK1 expression in rods. Notably, the kinetics of cone responses converge and become independent of GRK1 levels for flashes activating more than ∼1% of cone pigment. Thus, mouse cone response recovery in bright light is independent of pigment phosphorylation and likely reflects the spontaneous decay of photoactivated visual pigment. We also find that recoverin potentiates the sensitivity of cones in dim light conditions but does not contribute to their capacity to function in bright light.

PURPOSE: To report a case of ocular ischemic syndrome presenting as retinal vasculitis in a patient with Moyamoya syndrome. METHODS: A retrospective chart review was conducted to record clinical data including fluorescein angiography, optical coherence tomography, and serologic testing. A review of the literature from 1969 to 2014 of ocular involvement in Moyamoya syndrome was performed. RESULTS: A 51-year-old woman with long history of bilateral retinal vasculitis and refractory cystoid macular edema was eventually diagnosed with Moyamoya syndrome after sustaining a perioperative cerebrovascular accident. Moyamoya syndrome has been associated in the literature with ocular ischemic syndrome, presenting with narrowed retinal arteries, dilated veins, and midperipheral retinal hemorrhages, but retinal vasculitis with cystoid macular edema has not been reported. CONCLUSION: Moyamoya-related ocular ischemic syndrome can present as retinal vascular leakage and macular edema. Ophthalmologists should be cognizant that signs of the disease may be first observed in the eye before manifestations in the cerebrovascular system.

BACKGROUND: Retinopathy of prematurity (ROP) is a vision-threatening disease in premature infants. Serum adiponectin (APN) concentrations positively correlate with postnatal growth and gestational age, important risk factors for ROP development. Dietary ω-3 (n-3) long-chain polyunsaturated fatty acids (ω-3 LCPUFAs) suppress ROP and oxygen-induced retinopathy (OIR) in a mouse model of human ROP, but the mechanism is not fully understood. OBJECTIVE: We examined the role of APN in ROP development and whether circulating APN concentrations are increased by dietary ω-3 LCPUFAs to mediate the protective effect in ROP. DESIGN: Serum APN concentrations were correlated with ROP development and serum ω-3 LCPUFA concentrations in preterm infants. Mouse OIR was then used to determine whether ω-3 LCPUFA supplementation increases serum APN concentrations, which then suppress retinopathy. RESULTS: We found that in preterm infants, low serum APN concentrations positively correlate with ROP, and serum APN concentrations positively correlate with serum ω-3 LCPUFA concentrations. In mouse OIR, serum total APN and bioactive high-molecular-weight APN concentrations are increased by ω-3 LCPUFA feed. White adipose tissue, where APN is produced and assembled in the endoplasmic reticulum, is the major source of serum APN. In mouse OIR, adipose endoplasmic reticulum stress is increased, and APN production is suppressed. ω-3 LCPUFA feed in mice increases APN production by reducing adipose endoplasmic reticulum stress markers. Dietary ω-3 LCPUFA suppression of neovascularization is reduced from 70% to 10% with APN deficiency. APN receptors localize in the retina, particularly to pathologic neovessels. CONCLUSION: Our findings suggest that increasing APN by ω-3 LCPUFA supplementation in total parental nutrition for preterm infants may suppress ROP.

Organismal development requires the precise coordination of genetic programs to regulate cell fate and function. MEF2 transcription factors (TFs) play essential roles in this process but how these broadly expressed factors contribute to the generation of specific cell types during development is poorly understood. Here we show that despite being expressed in virtually all mammalian tissues, in the retina MEF2D binds to retina-specific enhancers and controls photoreceptor cell development. MEF2D achieves specificity by cooperating with a retina-specific factor CRX, which recruits MEF2D away from canonical MEF2 binding sites and redirects it to retina-specific enhancers that lack the consensus MEF2-binding sequence. Once bound to retina-specific enhancers, MEF2D and CRX co-activate the expression of photoreceptor-specific genes that are critical for retinal function. These findings demonstrate that broadly expressed TFs acquire specific functions through competitive recruitment to enhancers by tissue-specific TFs and through selective activation of these enhancers to regulate tissue-specific genes.

OBJECTIVE: The deficiency of very low-density lipoprotein receptor resulted in Wnt signaling activation and neovascularization in the retina. The present study sought to determine whether the very low-density lipoprotein receptor extracellular domain (VLN) is responsible for the inhibition of Wnt signaling in ocular tissues. APPROACH AND RESULTS: A plasmid expressing the soluble VLN was encapsulated with poly(lactide-co-glycolide acid) to form VLN nanoparticles (VLN-NP). Nanoparticles containing a plasmid expressing the low-density lipoprotein receptor extracellular domain nanoparticle were used as negative control. MTT, modified Boyden chamber, and Matrigel (™) assays were used to evaluate the inhibitory effect of VLN-NP on Wnt3a-stimulated endothelial cell proliferation, migration, and tube formation. Vldlr(-/-) mice, oxygen-induced retinopathy, and alkali burn-induced corneal neovascularization models were used to evaluate the effect of VLN-NP on ocular neovascularization. Wnt reporter mice (BAT-gal), Western blotting, and luciferase assay were used to evaluate Wnt pathway activity. Our results showed that VLN-NP specifically inhibited Wnt3a-induced endothelial cell proliferation, migration, and tube formation. Intravitreal injection of VLN-NP inhibited abnormal neovascularization in Vldlr(-/-), oxygen-induced retinopathy, and alkali burn-induced corneal neovascularization models, compared with low-density lipoprotein receptor extracellular domain nanoparticle. VLN-NP significantly inhibited the phosphorylation of low-density lipoprotein receptor-related protein 6, the accumulation of β-catenin, and the expression of vascular endothelial growth factor in vivo and in vitro. CONCLUSIONS: Taken together, these results suggest that the soluble VLN is a negative regulator of the Wnt pathway and has antiangiogenic activities. Nanoparticle-mediated expression of VLN may thus represent a novel therapeutic approach to treat pathological ocular angiogenesis and potentially other vascular diseases affected by Wnt signaling.

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

PurposeTo study the correlation between glaucomatous visual field (VF) defects assessed by standard automated perimetry (SAP) and peripapillary retinal nerve fiber layer (RNFL) thinning measured by spectral domain optical coherence tomography (OCT) using a modified OCT-based peripapillary RNFL structure-function map.Patients and methodsPerimetric glaucoma patients and age-matched normal control subjects were recruited from a university hospital clinic. All eyes underwent testing with the Spectralis spectral domain OCT and SAP on the same day. An OCT-based correspondence map, which correlated VF areas with peripapillary RNFL sectors was created to evaluate the relationship between glaucomatous RNFL thinning and VF loss in six nerve fiber layer bundle areas. Correlations of RNFL thinning with corresponding VF defects were examined using Spearman rank-order correlations. To demonstrate the association between localized VF defects and RNFL thickness, the theoretical curves were made according to an established log-linear model. The measured RNFL thickness values and VF defects were presented in the same scatterplot for each sector.ResultsFifty-six glaucoma patients and 85 normal subjects were included in the study. Significant association between localized VF loss and RNFL thinning was found in corresponding areas. Data from the current study fit well with established log-linear models, which compare RNFL thickness values with VF defects.ConclusionAnalysis of RNFL thinning in eyes with localized glaucomatous VF defects showed good structure-function correlation in a new OCT-based structure-function correspondence map.