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Purpose: To compare volumetric optical coherence tomography (OCT) biomarkers in bevacizumab responsive and bevacizumab refractory diabetic macular edema (DME) patients switched to the dexamethasone implant to ultimately identify possible prognostic indicators.Methods: Retrospective analysis of DME patients treated with bevacizumab were done. Patients were divided into those who showed response to bevacizumab (bevacizumab only group) and others who were switched to the dexamethasone implant due to lack of response to bevacizumab (switching group). Volumetric OCT biomarkers such as central macular thickness (CMT), inner and outer cystoid macular edema (CME) volume, serous retinal detachment (SRD) volume, retinal volume (CME + SRD volume) within the 6-mm Early Treatment of Diabetic Retinopathy Study circle were calculated. OCT biomarkers were followed up throughout treatment.Results: Among total of 144 eyes, 113 patients were included in the bevacizumab only group and 31 patients were included in the switching group. Compared to the bevacizumab only group, the switching group showed higher baseline CMT (558.00 ± 209.60 µm vs. 454.96 ± 125.88 µm, p = 0.003), larger inner CME (6.02 ± 1.43 mm3 vs. 5.12 ± 0.87 mm3, p = 0.004) and SRD volume (0.32 ± 0.40 mm3 vs. 0.11 ± 0.09 mm3, p = 0.015) and higher proportion of patients with SRD (58.06% vs. 31.86%, p = 0.008). In the switching group, CMT, inner CME and SRD volume all showed significant reduction after switching to the dexamethasone implant.Conclusions: DME with large SRD and inner nuclear layer edema volume may be more effectively treated with the dexamethasone implant than bevacizumab.

Purpose To determine the mechanism of infection, clinical features, and risk factors of endophthalmitis after scleral fixation of an intraocular lens (IOL). Methods We included fifteen patients with infectious endophthalmitis after scleral fixation of an IOL between April 2004 and December 2017, as well as four patients found through a literature search. Thus, a total of nineteen patients were analyzed. Results Among nineteen eyes, infectious endophthalmitis developed at a mean of 23 months (range: 1day-10 years) after scleral fixation surgery. Nine eyes (47.4%) had early-onset endophthalmitis (≤6 weeks), and ten eyes (52.6%) had delayed-onset endophthalmitis (>6 weeks). Eleven eyes (57.9%) had presumed microbial influx due to suture exposure. Those with delayed-onset endophthalmitis showed a higher rate of suture-related infection (80.0% vs. 33.3%) and culture of gram-negative bacteria (70.0% vs. 12.5%) than did those with early-onset endophthalmitis. Conclusion Infectious endophthalmitis can develop late after scleral fixation of an IOL, usually related to the exposed sutures, and the visual prognosis is poor. Eyes that have sutured scleral fixation should be monitored regularly, and preventive measures should be performed if an exposed suture is found.

Purpose of Review Obstructive sleep apnea (OSA) patients are at significantly increased risks for cardiovascular and cerebrovascular morbidities. Recently, there has been heightened interest in the association of OSA with numerous ocular diseases and possible improvement of these conditions with the initiation of OSA treatment. We reviewed the current evidence with an emphasis on the overlapping pathogeneses of both diseases. Recent Findings Currently available literature points to a substantial association of OSA with ocular diseases, ranging from those involving the eyelid to optic neuropathies and retinal vascular diseases. Since the retina is one of the highest oxygen-consuming tissues in the body, the intermittent hypoxia and hypercapnia ensuing in OSA can have deleterious effects on ocular function and health. Tissue hypoxia, autonomic dysfunction, microvascular dysfunction, and inflammation all play important roles in the pathogenesis of both OSA and ocular diseases. Whether OSA treatment is capable of reversing the course of associated ocular diseases remains to be determined. It is anticipated that future therapeutic approaches will target the common underlying pathophysiologic mechanisms and promote favorable effects on the treatment of known associated ocular diseases. Summary Emerging evidence supports the association of ocular diseases with untreated OSA. Future studies focusing on whether therapeutic approaches targeting the common pathophysiologic mechanisms will be beneficial for the course of both diseases are warranted.

Purpose: To investigate factors associated with refractive outcomes after phacovitrectomy for epiretinal membrane (ERM).Methods: Retrospective review of patients undergoing phacovitrectomy for ERM was done. The main outcome measure was predictive refraction error (PE), defined as observed refraction error – target refraction error, calculated by the SRK/T, Haigis, and SRK II formulae. PE was measured at postoperative 1, 3, and 6 months. Simple and multiple linear regression analysis were used to evaluate factors associated with PE.Results: A total of 53 eyes of 53 patients were included. The mean PEs at postoperative 1, 3, and 6 months were all negative, implying myopic shift in all patients regardless of the intraocular lens formula used. Haigis formula showed the least myopic shift among the three formulae (p = 0.001, Friedman test). There was no significant difference in PE depending on preoperative central macular thickness (CMT) in subgroup analysis. On stepwise multiple linear regression analysis, ERM etiology (β = 0.759, p = 0.004, SRK/T formula; β = 0.733, p = 0.008, Haigis formula; β = 0.933, p < 0.001, SRK II formula), preoperative anterior chamber depth (β = –0.662, p = 0.013, Haigis formula; β = –0.747, p = 0.003, SRK II formula), and decrease of CMT (β = –0.003, p = 0.025, SRK/T formula) were significantly associated with PE at postoperative 6 months.Conclusions: Myopic shift in PE was observed after combined phacovitrectomy for epiretinal membrane. ERM etiology, preoperative anterior chamber depth, and decrease of CMT were significantly associated with PE at postoperative 6 months. There was no difference in PE after surgery between the two groups defined by CMT (≥500 and

Background: Diabetic Retinopathy (DR), one of the major microvascular complications commonly occurring in diabetic patients, can be classified into Proliferative Diabetic Retinopathy (PDR) and Non-Proliferative Diabetic Retinopathy (NPDR). Currently available therapies are only targeted for later stages of the disease in which some pathologic changes may be irreversible. Thus, there is a need to develop new treatment options for earlier stages of DR through revealing pathological mechanisms of PDR and NPDR. Objective: The purpose of this study was to characterize proteomes of diabetic through quantitative analysis of PDR and NPDR. Methods: Vitreous body was collected from three groups: control (non-diabetes mellitus), NPDR, and PDR. Vitreous proteins were digested to peptide mixtures and analyzed using LC-MS/MS. MaxQuant was used to search against the database and statistical analyses were performed using Perseus. Gene ontology analysis, related-disease identification, and protein-protein interaction were performed using the differential expressed proteins. Results: Twenty proteins were identified as critical in PDR and NPDR. The NPDR group showed different expressions of kininogen-1, serotransferrin, ribonuclease pancreatic, osteopontin, keratin type II cytoskeletal 2 epidermal, and transthyretin. Also, prothrombin, signal transducer and activator of transcription 4, hemoglobin subunit alpha, beta, and delta were particularly up-regulated proteins for PDR group. The up-regulated proteins related to complement and coagulation cascades. Statherin was down-regulated in PDR and NPDR compared with the control group. Transthyretin was the unique protein that increased its abundance in NPDR compared with the PDR and control group. Conclusion: This study confirmed the different expressions of some proteins in PDR and NPDR. Additionally, we revealed uniquely expressed proteins of PDR and NPDR, which would be differential biomarkers: prothrombin, alpha-2-HS-glycoprotein, hemoglobin subunit alpha, beta, and transthyretin.

Several reports have suggested that genetic susceptibility contributes to the development and progression of diabetic retinopathy. We aimed to identify genetic loci that confer susceptibility to diabetic retinopathy in Japanese patients with type 2 diabetes. We analysed 5 790 508 single nucleotide polymorphisms (SNPs) in 8880 Japanese patients with type 2 diabetes, 4839 retinopathy cases and 4041 controls, as well as 2217 independent Japanese patients with type 2 diabetes, 693 retinopathy cases and 1524 controls. The results of these two genome-wide association studies (GWAS) were combined with an inverse variance meta-analysis (Stage-1), followed by de novo genotyping for the candidate SNP loci (P

PURPOSE: To investigate the efficacy of intravitreal bevacizumab injections (IVBs) for vitreous haemorrhage (VH) in proliferative diabetic retinopathy (PDR) with prior complete panretinal photocoagulation (PRP). METHODS: A multicentre cohort study of eyes with new VH in PDR after documented previous complete PRP was performed. Eyes were grouped according to IVB treatment at baseline, and cumulative rate of vitrectomy and spontaneous clear-up rate were compared as the main outcome. Eyes requiring vitrectomy within 1 month, or with tractional retinal detachment (TRD), or with spontaneous clear-up within 1 month, were excluded. RESULTS: In total, 44 eyes with IVB and 92 control eyes without IVB were followed up to 20.1 months. Cumulative probability of vitrectomy was lower in the IVB group at 12 months (0.16 vs 0.42, IVB vs controls), and throughout the follow-up period (p = 0.005). Cumulative probability of spontaneous clear-up was higher in the IVB group at 12 months (0.81 vs 0.68, IVB vs controls), and throughout the follow-up period (p = 0.013). Best-corrected visual acuity (BCVA) at 1 month after onset of VH was significantly better in the IVB group (0.513 vs 0.942 logarithm of the minimal angle of resolution, p = 0.002); however, the difference of BCVA lost significance with further follow-up. IVB treatment was the only factor significantly associated with vitrectomy risk on multivariate analysis (p = 0.047, hazard ratio 0.506). CONCLUSION: In VH after prior complete PRP, IVB was effective in decreasing vitrectomy requirement, although overall visual benefit was short-term. IVB can be considered to defer vitrectomy in PDR VH eyes with prior complete PRP and no TRD.

Recent advances in genetic sequencing techniques have improved the overall diagnostic yield for finding genetic causes for inherited retinal dystrophies (IRD). Rod-cone dystrophy is the most common...

We evaluated phenotype and genotype correlation of central serous chorioretinopathy (CSC) patients with or without irregular pigment epithelial detachment (PED) on optical coherence tomography (OCT). For CSC, a flat, irregular protrusion of retinal pigment epithelium (RPE) with hyper-reflective sub-RPE fluid on OCT was defined as an irregular PED. Participants were classified into 5 subgroups; (1) total CSC (n = 280) (2) CSC with irregular PED (n = 126) (3) CSC without irregular PED (n = 154) (4) typical choroidal neovascularization (CNV) (n = 203) and (5) polypoidal choroidal vasculopathy (PCV) (n = 135). Ten known major AMD-associated single-nucleotide polymorphisms (SNPs) were analyzed. Age, sex adjusted logistic regression was performed for the association between subgroups. Association analysis between CSC without irregular PED and CNV revealed that significant difference for rs10490924 in ARMS2, rs10737680 in CFH, and marginally significant difference for rs800292 in CFH. Between CSC without irregular PED and PCV, rs10490924, rs10737680, and rs800292 were significantly different. In contrast, CSC with irregular PED and CNV revealed no SNP showing significant difference. Between CSC with irregular PED and PCV, only rs10490924 was significantly different. CSC with irregular PED and CSC without irregular PED revealed significant difference for rs800292, and marginal difference for rs10737680. These findings suggest CSC patients with irregular PED are genetically different from those without irregular PED and may have genetic and pathophysiologic overlap with AMD patients.

To compare the clinical features, treatments, and outcomes between bullous and chronic variants of central serous chorioretinopathy (CSC).Retrospective, observational case series.Sixty-two eyes of 44 patients with bullous-variant CSC (bvCSC) and 97 eyes of 85 patients with nonbullous CSC.We conducted a national survey between September 1, 2020, and March 31, 2021, of members of the Korean Retina Society and obtained data of patients with bvCSC from 11 retinal centers. A comparator group comprised consecutive chronic CSC patients without bullous detachment.Baseline demographics and patient characteristics were compared between groups. Secondary outcomes included factors associated with visual prognosis within the bvCSC group.Compared with the nonbullous CSC group, the bvCSC group presented at a younger age (49 vs. 52 years; P = 0.047) and with more bilateral involvement (41% vs. 14%; P0.001). Systemic corticosteroid use was more prevalent in the bvCSC group, both in terms of any exposure (50% vs. 20%; P = 0.001) and long-term exposure (36% vs. 9%; P 0.001). The bvCSC group had distinct imaging features (all P0.05): retinal folding (64% vs. 1%), subretinal fibrin (75% vs. 13%), multiple retinal pigment epithelium tears (24% vs. 2%), and multifocal fluorescein leakages with terminal telangiectasia (36% vs. 1%). Although bvCSC patients had worse vision at diagnosis (20/80 vs. 20/44; P = 0.003), treatment response was more robust (fluid resolution by final follow-up, 84% vs. 68%; P = 0.034) even with conservative management, resulting in similar final vision (20/52 vs. 20/45; P = 0.52). History of kidney-related (odds ratio [OR] 5.4; 95% confidence interval [CI] 1.3-18.5; P = 0.045) and autoimmune/rheumatoid diseases (OR 25.4, 95% CI 2.8-195.0; P = 0.004) showed associations with the bvCSC group. Apart from vision at diagnosis (OR 0.1, 95% CI 0.05-0.36; P 0.001), a history of renal transplantation was most predictive of visual prognoses for bvCSC eyes (OR 0.2, 95% CI 0.04-0.75; P = 0.020).Bullous-variant CSC may be associated with pathogenic risk factors based on underlying medical conditions and systemic corticosteroid use. Poor vision at diagnosis and history of renal transplantation were associated with poor visual outcome.

BACKGROUND: Atypical Usher syndrome (USH) is poorly defined with a broad clinical spectrum. Here we characterize the clinical phenotypic of disease caused by variants in CEP78, CEP250, ARSG, and ABHD12. MATERIALS AND METHODS: Chart review evaluating demographic, clinical, imaging, and genetic findings of 19 patients from 18 families with a clinical diagnosis of retinal disease and confirmed disease causing variants in CEP78, CEP250, ARSG, or ABHD12. RESULTS: CEP78-related disease included sensorineural hearing loss (SNHL) in 6/7 patients and demonstrated a broad phenotypic spectrum including: vascular attenuation, pallor of the optic disc, intraretinal pigment, retinal pigment epithelium mottling, areas of mid-peripheral hypo-autofluorescence, outer retinal atrophy, mild pigmentary changes in the macula, foveal hypo-autofluorescence, and granularity of the ellipsoid zone. Nonsense and frameshift variants in CEP250 showed mild retinal disease with progressive, non-congenital SNHL. ARSG variants resulted in a characteristic pericentral pattern of hypo-autofluorescence with one patient reporting non-congenital SNHL. ABHD12 related disease showed rod-cone dystrophy with macular involvement, early and severe decreased best corrected visual acuity, and non-congenital SNHL ranging from unreported to severe. CONCLUSIONS: This study serves to expand the clinical phenotypes of atypical USH. Given the variable findings, atypical USH should be considered in patients with peripheral and macular retinal disease even without the typical RP phenotype especially when SNHL is noted. Additionally, genetic screening may be useful in patients that have clinical symptoms and retinal findings even in the absence of known SNHL given the variability of atypical USH.

Objectives To investigate peripapillary retinal nerve fiber layer (pRNFL) changes in patients with progressive supranuclear palsy (PSP). Methods We included 21 PSP patients (36 eyes) who underwent peripapillary optical coherence tomography (OCT) scans at 2.5 ± 1.3 years of disease, without ophthalmologic co-morbidities. We compared pRNFL thicknesses in PSP eyes with age-matched 22 controls (22 eyes) using generalized estimating equation model adjusting for intra-subject inter-eye correlations, age and sex. We also analyzed the correlation between the pRNFL thickness and clinical severity using Spearman’s correlation. In twelve PSP patients with 3 T brain MRI volumetric scan within 1 year of OCT exam, we investigated the correlation between the pRNFL thickness and brain atrophy using Pearson’s correlation. Results PSP patients had global pRNFL thinning compared to controls (beta = − 6.436, p = 0.025). Global pRNFL thickness correlated with Hoehn & Yahr stages (r = − 0.487, p = 0.025), and nasal pRNFL thinning showed a trend of correlation (uncorrected p p = 0.008) and urinary incontinence (uncorrected p = 0.031), although not significant after Bonferroni correction (all 28 items). The patients had significant atrophy in the posterior cingulate cortex, third ventricle, pallidum, and midbrain with reduced midbrain-to-pons ratio, but no correlation was found between pRNFL thickness and brain volumes. Conclusion The pRNFL seems to be affected in PSP, which is more severe with advanced disease stages. Retinal investigation in a larger longitudinal cohort would help elucidate the pathophysiological role of retinal thinning in PSP.

Purpose The purpose of this study was to characterize the phenotypic spectrum of ophthalmic findings in patients with Alagille syndrome. Methods We conducted a retrospective, observational, multicenter, study on 46 eyes of 23 subjects with Alagille syndrome. We reviewed systemic and ophthalmologic data extracted from medical records, color fundus photography, fundus autofluorescence, optical coherence tomography, visual fields, electrophysiological assessments, and molecular genetic findings. Results Cardiovascular abnormalities were found in 83% of all cases (of those, 74% had cardiac murmur), whereas 61% had a positive history of hepatobiliary issues, and musculoskeletal anomalies were present in 61% of all patients. Dysmorphic facies were present in 16 patients, with a broad forehead being the most frequent feature. Ocular symptoms were found in 91%, with peripheral vision loss being the most frequent complaint. Median (range) Snellen visual acuity of all eyes was 20/25 (20/20 to hand motion [HM]). Anterior segment abnormalities were present in 74% of the patients; of those, posterior embryotoxon was the most frequent finding. Abnormalities of the optic disc were found in 52%, and peripheral retinal abnormalities were the most frequent ocular finding in this series, found in 96% of all patients. Fifteen JAG1 mutations were identified in 16 individuals; of those, 6 were novel. Conclusions This study reports a cohort of patients with Alagille syndrome in which peripheral chorioretinal changes were more frequent than posterior embryotoxon, the most frequent ocular finding according to a number of previous studies. We propose that these peripheral chorioretinal changes are a new hallmark to help diagnose this syndrome.

To reveal the macular inner retinal change linked to axonal degeneration in Parkinson’s disease (PD), we performed macular optical coherence tomography scan and diffusion tensor imaging of the retrobulbar optic nerve on both eyes of 36 drug-naive PD patients. Thicknesses of inner retinal layers were automatically measured, and correlation analysis was conducted between the retinal thickness and diffusion parameters of the optic nerve. PD patients showed thinning of the inner retinal layers compared to control data. Thicknesses of the ganglion cell and inner plexiform layers were both correlated positively with fractional anisotropy and negatively with diffusivity indices of ipsilateral optic nerve (FDR-adjusted p

Recent advances in genetic sequencing techniques have improved the overall diagnostic yield for finding genetic causes for inherited retinal dystrophies (IRD). Rod-cone dystrophy is the most common IRD and is characterized by the primary involvement of the rod photoreceptors. Over 80 causal genes have been identified so far giving clinicians insight into the pathogenesis.Case report of a rod-cone dystrophy patient with a novel mutation inA 66-year-old male presented with slowly progressing night blindness, constricted visual field and relatively stable visual acuity. Fundus examination showed diffuse intraretinal pigment in the mid- and peripheral retina, diffuse retinal pigment epithelial atrophy, and intact macula in both eyes. There has been mild macular edema in both eyes which remained stable with the use of topical dorzolamide eyedrops. Whole exome sequencing found, and a subsequent vision panel confirmed, the pathogenic variant to be a homozygous frameshift mutation inWe report a case of progressive rod-cone dystrophy caused by a novel mutation in

To identify genetic variants associated with diabetic retinopathy (DR), we performed a large multiethnic genome-wide association study. Discovery included eight European cohorts (n = 3,246) and seven African American cohorts (n = 2,611). We meta-analyzed across cohorts using inverse-variance weighting, with and without liability threshold modeling of glycemic control and duration of diabetes. Variants with a P value

Importance Advanced age-related macular degeneration (AMD) is a leading cause of blindness in Western countries. Causal, modifiable risk factors need to be identified to develop preventive measures for advanced AMD. Objective To assess whether smoking, alcohol consumption, blood pressure, body mass index, and glycemic traits are associated with increased risk of advanced AMD. Design, Setting, Participants This study used 2-sample mendelian randomization. Genetic instruments composed of variants associated with risk factors at genome-wide significance (P

Background Dyslipidemia, particularly high-density lipoprotein cholesterol (HDL-C), has recently been implicated in the pathogenesis of age-related macular degeneration (AMD), the leading cause of vision loss. However, epidemiological studies have yielded conflicting results. Methods We investigated the causal role of plasma lipid levels in AMD in multiethnic populations comprising 16 144 advanced AMD cases and 17 832 controls of European descent, together with 2219 cases and 5275 controls of Asian descent, using Mendelian randomization in three models. Model 1 is a conventional meta-analysis which does not account for pleiotropy of instrumental variable (IV) effects. Model 2 is a univariate, inverse variance weighted regression analysis that accounts for potential unbalanced pleiotropy using MR-Egger method. Finally, Model 3 is a multivariate regression analysis that addresses pleiotropy by MR-Egger method and by adjusting for effects on other lipid traits. Results A 1 standard deviation (SD) higher HDL-cholesterol level was associated with an odds ratio (OR) for AMD of 1.17 (95% confidence interval: 1.07–1.29) in Europeans (P = 6.88 × 10–4) and of 1.58 (1.24–2.00) in Asians (P = 2.92 × 10–4) in Model 3. The corresponding OR estimates were 1.30 (1.09–1.55) in Europeans (P = 3.18 × 10–3) and 1.42 (1.11—1.80) in Asians (P = 4.42 × 10–3) in Model 1, and 1.21 (1.11–1.31) in Europeans (P = 3.12 × 10–5) and 1.51 (1.20–1.91) in Asians (P = 7.61 × 10–4) in Model 2. Conversely, neither LDL-C (Europeans: OR = 0.96, P = 0.272; Asians: OR = 1.02, P = 0.874; Model 3) nor triglyceride levels (Europeans: OR = 0.91, P = 0.102; Asians: OR = 1.06, P = 0.613) were associated with AMD. We also assessed the association between lipid levels and polypoidal choroidal vasculopathy (PCV) in Asians, a subtype of AMD, and found a similar trend for association of PCV with HDL-C levels. Conclusions Our study shows that high levels of plasma HDL-C are causally associated with an increased risk for advanced AMD in European and Asian populations, implying that strategies reducing HDL-C levels may be useful to prevent and treat AMD.

Polypoidal choroidal vasculopathy (PCV), a subtype of age-related macular degeneration (AMD) more frequently seen in East Asians, has both common and distinct clinical manifestations with typical neovascular AMD (tAMD). We aim to examine the extent to which common genetic variants are shared between these two subtypes. We performed the meta-analysis of association in a total of 1062 PCV patients, 1157 tAMD patients and 5275 controls of East Asian descent from the Genetics of AMD in Asians Consortium at the 34 known AMD loci. A total of eight loci were significantly associated with PCV, including age-related maculopathy susceptibility 2 (ARMS2)-HtrA serine peptidase 1 (HTRA1), complement factor H (CFH), C2-CFB-SKIV2L, CETP, VEGFA, ADAMTS9-AS2 and TGFBR1 (P

International audience; 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 x 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 x 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.

To investigate the contrast sensitivity function in drug-naive Parkinson’s disease (PD) patients and its predictive value with longitudinal follow-up data. We included newly diagnosed non-demented PD patients who performed contrast sensitivity test between 2013 and 2014. Contrast sensitivity function at drug-naive state in PD patients was compared with age-matched normal control data of our center. Correlation between contrast sensitivity function and parkinsonian motor and non-motor features including the Mini-Mental State Exam (MMSE) score at the time of diagnosis were analyzed by linear regression. With longitudinal follow-up data after initiating anti-parkinsonian therapy, the risk conferred on subsequent visual hallucinations and cognitive impairment requiring anti-dementia drugs was analyzed by dichotomizing PD group based on the initial contrast sensitivity function. Forty-eight patients were finally included, and mean follow-up periods were 43 months. Contrast sensitivity function in drug-naive PD patients was significantly worse than controls. Contrast sensitivity function correlated with sleep disturbance (p = 0.001) and global cognitive status reflected by the MMSE score (p = 0.020). It also associated with further decline in the MMSE during the follow-ups (p = 0.029). Patients with below average contrast sensitivity function at the time of diagnosis showed higher risk of cognitive decline requiring anti-dementia drugs (adjusted odds ratio = 4.68, p = 0.04) and of visual hallucinations (adjusted odds ratio = 12.54, p = 0.04) than those above average function during the follow-up. Contrast sensitivity impairment in drug-naive PD patients associates with clinical demand for therapeutic intervention of cognitive decline as well as development of visual hallucinations in the early course of the disease.

Objectives We investigated retinal change and its relationship with neurodegeneration markers in a prodromal Parkinson cohort. Methods A total of 30 patients with idiopathic rapid eye movement sleep behavior disorder were recruited. Participants underwent olfactory testing, macular optical coherence tomography, microperimetry, contrast sensitivity test, and brain N-(3-[18 F]fluoropropyl)-2-carbomethoxy-3-(4-iodophenyl) nortropane positron emission tomography. We measured the ganglion cell complex thicknesses and investigated its correlation with olfactory function and striatal dopamine transporter availability. A linear mixed-effect model was applied with adjustment for multiple comparisons. Results The parafoveal ganglion-cell-complex thickness in this cohort lay between our healthy control and drug-naive Parkinson's disease group data. Idiopathic rapid eye movement sleep behavior disorder patients also had contrast sensitivity impairment as in Parkinson's disease with a nonsignificant change in macular sensitivities. Macular ganglion cell complex thickness correlated with olfactory scores and with striatal dopamine transporter availabilities. Conclusions Macular ganglion cell complex thinning may be a marker of neurodegeneration in prodromal Parkinson's disease. © 2019 International Parkinson and Movement Disorder Society.

To analyze retinal thickness changes in multiple system atrophy (MSA) and correlate changes with disease severity and subtypes of MSA. A total of 36 MSA (27 MSA-P and 9 MSA-C) patients and 71 healthy control subjects underwent general ophthalmologic examination and optical coherence tomography (OCT) scans. Peripapillary retinal nerve fiber layer (RNFL) thickness and perifoveal retinal thickness were analyzed separately. The generalized estimating equation model was used with age as a covariate to adjust for within-patient inter-eye correlations and the effect of age on retinal or RNFL thickness. Correlation analysis between RNFL, perifoveal thickness, and clinical parameters, the Unified MSA Rating Scale (UMSARS) and Global Disability Score (GDS), was also done. MSA patients showed significantly decreased peripapillary RNFL thickness in the inferior (P = 0.047) and inferotemporal (P = 0.017) sectors and significant perifoveal thinning in the superior outer sector (P = 0.042) compared to healthy controls. Both RNFL and perifoveal thinning were more marked and widespread in MSA-P than MSA-C patients. The UMSARS and GDS showed significant negative correlation with center and total macular perifoveal thickness and also the inferior and nasal outer sectors. Peripapillary RNFL and perifoveal retinal thinning were observed in MSA patients and retinal thinning correlated with the clinical severity of MSA. Structural changes in the retina may reflect the degree and pattern of neurodegeneration occurring in MSA.

To identify genetic variants associated with diabetic retinopathy (DR), we performed a large multiethnic genome-wide association study. Discovery included eight European cohorts (n = 3,246) and seven African American cohorts (n = 2,611). We meta-analyzed across cohorts using inverse-variance weighting, with and without liability threshold modeling of glycemic control and duration of diabetes. Variants with a P value

Objective To compare the accuracy of refractive outcomes between combined pars plana vitrectomy (PPV) and cataract surgery and delayed cataract surgery after PPV in cases with rhegmatogenous retinal detachment (RD). Design Retrospective case series. Participants Thirty-eight eyes underwent combined phacovitrectomy (combined group) and 25 eyes underwent delayed cataract surgery after PPV (delayed group). Methods RD height was measured using optical coherence tomography. Refractive outcomes were evaluated using mean absolute error (MAE; the difference between final refractive error and target refractive error). Results Combined group showed significant myopic shift (mean error; –0.40 ± 1.07 vs 0.07 ± 0.56 D, p = 0.028) and large MAE (0.81 ± 0.81 vs 0.48 ± 0.29 D, p = 0.028) compared with delayed group. Multiple logistic regression analysis revealed that only RD height was significantly associated with MAE greater than 2 D after combined surgery (in 100-µm unit, odds ratio 3.23, 95% CI 1.04–10.02, p = 0.042). RD height was also significantly correlated with the difference in axial length (AL) between 2 eyes of the patients ( p = 0.006, r = 0.406) and the difference in AL measured at pre- versus post-RD repair in the delayed group ( p r = 0.774). Conclusions Combined phacovitrectomy in patients with rhegmatogenous RD induced significant myopic shift because of underestimation of AL, especially in patients with high RD height. Thus, in cases with high temporal RD or large AL differences between eyes, either delayed cataract surgery or combined cataract surgery using the contralateral AL is recommended.

ObjectiveTo analyze the relationship between retinal thinning and nigral dopaminergic loss in de novo Parkinson disease (PD).MethodsForty-nine patients with PD and 54 age-matched controls were analyzed. Ophthalmologic examination and macula optical coherence tomography scans were performed with additional microperimetry, N-(3-[18F]fluoropropyl)-2-carbomethoxy-3-(4-iodophenyl) nortropane PET, and 3T MRI scans were done in patients with PD only. Retinal layer thickness and volume were measured in subfields of the 1-, 2.22-, and 3.45-mm Early Treatment of Diabetic Retinopathy Study circle and compared in patients with PD and controls. Correlation of inner retinal layer thinning with microperimetric response was examined in patients with PD, and the relationships between retinal layer thickness and dopamine transporter densities in the ipsilateral caudate, anterior and posterior putamen, and substantia nigra were analyzed.ResultsRetinal layer thinning was observed in the temporal and inferior 2.22-mm sectors (false discovery rate–adjusted p < 0.05) of drug-naive patients with PD, particularly the inner plexiform and ganglion cell layers. The thickness of these layers in the inferior 2.22-mm sector showed a negative correlation with the Hoehn and Yahr stage (p = 0.032 and 0.014, respectively). There was positive correlation between macular sensitivity and retinal layer thickness in all 3.45-mm sectors, the superior 2.22-mm sector, and 1-mm circle (p < 0.05 for all). There was an association between retinal thinning and dopaminergic loss in the left substantia nigra (false discovery rate–adjusted p < 0.001).ConclusionRetinal thinning is present in the early stages of PD, correlates with disease severity, and may be linked to nigral dopaminergic degeneration. Retinal imaging may be useful for detection of pathologic changes occurring in early PD.

To investigate the changes in inner foveal contour after surgery for macular hole (MH) and its clinical implications. This retrospective observational case series included 66 eyes from 66 patients who underwent surgery for MH. Notching of tissue was defined as an abrupt alteration in the inner contour of the parafoveal tissue based on postoperative optical coherence tomography (OCT) image. The distance between the parafoveal edges of the outer plexiform layer (OPL) was defined as the inter-OPL distance. The inter-OPL distance was divided into nasal, temporal, superior, and inferior lengths. The difference in the lengths of each direction between the early and late postoperative period was compared between directions with and without notching. The early and late postoperative examination was performed at 4.6±2.9 weeks and 6.2±0.6 months, respectively. Notching of tissue was noted in 54 eyes (81.8%). In 53 eyes with a measurable inter-OPL distance, the notching of tissue was noted in 45 eyes (84.9%) regardless of preoperative MH size. The mean amount of foveal tissue elongation that occurred during the designated period was 104.6±68.8 and 78.4±72.9 μm in the directions with and without the notching of tissue (P

Objective To investigate the prevalence and risk factors of age-related macular degeneration (AMD) in the Korean population. Design A cross-sectional study using a complex, stratified, multistage, probability-cluster survey, which can produce nationally representative estimates. Participants Using the database of Korean National Health and Nutrition Examination Survey from 2008 through 2011, 14 352 participants 40 years of age or older with gradable fundus photographs were included. Methods Age-related macular degeneration was determined by fundus photograph. Prevalences of AMDs were estimated. Risk factor analyses were conducted using logistic regression analyses (LRAs). Main Outcome Measures Prevalence and risk factors of AMD. Results The prevalence of AMD was 6.62% (95% confidence interval [CI], 6.15%–7.09%) in the Korean population: 6.02% (95% CI, 5.56%–6.48%) were early AMD and 0.60% (95% CI, 0.45%–0.75%) were late AMD. The prevalence of early AMD in women (6.73%; 95% CI, 6.11%–7.35%) was higher than that in men (5.25%; 95% CI, 4.61%–5.89%; P P P P = 0.027), occupation ( P P = 0.027), hepatitis B surface antigen carrier status ( P P = 0.032; waist circumference, P = 0.041, in separate analyses), and higher serum high-density lipoprotein (HDL) level ( P = 0.046), but not with smoking status. Late AMD had positive associations with age groups ( P P = 0.022), and lower BMI ( P = 0.037). Conclusions The results suggest that there are 1.21 million individuals with early AMD and 121 000 individuals with late AMD in Korea. Nonoverweight status and higher HDL levels, generally assumed as positive health indicators, as well as anemia and hepatitis B infection had harmful associations with AMD in our study, implying a possible different pathophysiologic process of AMD in Asians compared with that of white persons.

Visual symptoms are a common feature in patients with Parkinson's disease (PD), and retinal dopamine loss and dysfunctions in foveal vision have been described in PD patients. Because visual hallucination (VH) is a specific feature of PD which is differentiated from other parkinsonian disorders, defective visual information processing from both the central and peripheral pathways is suggested to be the pathophysiological mechanisms of VH in PD. Decreased visual acuity as well as impaired contrast sensitivity and color vision is known to be related to the appearance of VH in PD. However, these functional studies were also affected by cognitive or cortical dysfunctions; thus, structural imaging can more reliably reflect visual afferent dysfunction. Recently, optical coherence tomography (OCT) scans have been used to investigate the structural changes in the retina in vivo. Segmental measures of the vertical retinal layers by OCT provide structural evidence for retinal dopamine loss and foveal dysfunction in PD. Retinal nerve fiber layer (RNFL) thinning in PD was shown to be significantly associated with VH and correlated with PD duration and severity. Thus, there is a possibility that the retina could be a biomarker for disease progression and risk of VH in PD. A standard protocol for OCT studies in PD with more accurate measures of the retinal layers needs to be developed in the future.

PurposeTo analyze the associations of retinal and choroidal thickness on enhanced-depth imaging optical coherence tomography (EDI-OCT) with clinical, ophthalmic and genetic factors in the normal elderly population (aged 65 years or older).MethodsIn this prospective, population-based cohort study, people aged 65 years or older were enrolled in the baseline study of the Korean Longitudinal Study on Health and Aging (KLoSHA) Eye Study. All participants underwent spectral domain-OCT scan using the EDI technique. A topographic map of the retina was obtained and subfoveal choroidal thickness (SFCT) was measured manually. Blood samples from all subjects were genotyped for major age-related macular degeneration (AMD)-associated single nucleotide polymorphisms (SNPs) the major AMD-associated SNPs; CFH Y402H rs1061170, CFH I62V rs800292, ARMS2 A69S rs10490924. A statistical analysis was conducted to compare the retinal thickness, choroidal thickness, and AMD risk genotypes.ResultsAmong the three hundred eighty people enrolled, the mean age was 76.6 years (range 65-99 years). Factors that showed correlation with either tomographic retinal parameters, retinal nerve fiber layer, or SFCT, were age and gender. Significant age-related decrease in thickness was observed in the RNFL, mean central thickness (MCT) and SFCT. Gender differences existed in central foveolar thickness (CFT) and MCT, where it was thicker in men. While chorioretinal parameters were not related with other genotypes, CFH rs1061170 risk genotype was significantly associated with thin SFCT. The group containing the AMD- risk allele (CT) had a 14.7% reduction in the SFCT compared to the non-risk TT group.ConclusionsIn addition to the well-known association with AMD, CFH rs1061170 is a significant genetic risk factor associated with choroidal thinning in normal eyes of the elderly population. Such findings may provide further insight into the pathogenesis of age-related macular degeneration as well as normal aging. In addition, our study provides the first normative data on retinal and choroidal thickness in population-based aged groups with a mean age over seventy-five.

Livedoid vasculopathy (LV) is characterized by a long history of ulceration of the feet and legs and histopathology indicating a thrombotic process. We report a case of acute central retinal artery occlusion in a 32-year-old woman who had LV. She showed no discernible laboratory abnormalities such as antiphospholipid antibodies and no history of cerebrovascular accidents. Attempted intra-arterial thrombolysis showed no effect in restoring retinal arterial perfusion or vision. The central retinal artery occlusion accompanied by LV in this case could be regarded as a variant form of Sneddon's syndrome, which is characterized by livedo reticularis and cerebrovascular accidents.

Defective visual information processing from both central and peripheral pathways is one of the suggested mechanisms of visual hallucination in Parkinson's disease (PD). To investigate the role of retinal thinning for visual hallucination in PD, we conducted a case-control study using spectral domain optical coherence tomography. We examined a representative sample of 61 patients with PD and 30 healthy controls who had no history of ophthalmic diseases. General ophthalmologic examinations and optical coherence tomography scans were performed in each participant. Total macular thickness and the thickness of each retinal layer on horizontal scans through the fovea were compared between the groups. In a comparison between patients with PD and healthy controls, there was significant parafoveal inner nuclear layer thinning, whereas other retinal layers, including the retinal nerve fiber layer, as well as total macular thicknesses were not different. In terms of visual hallucinations among the PD subgroups, only retinal nerve fiber layer thickness differed significantly, whereas total macular thickness and the thickness of other retinal layers did not differ. The retinal nerve fiber layer was thinnest in the group that had hallucinations without dementia, followed by the group that had hallucinations with dementia, and the group that had no hallucinations and no dementia. General ophthalmologic examinations did not reveal any significant correlation with hallucinations. There were no significant correlations between retinal thicknesses and duration or severity of PD and medication dosages. The results indicate that retinal nerve fiber layer thinning may be related to visual hallucination in nondemented patients with PD. Replication studies as well as further studies to elucidate the mechanism of thinning are warranted.