Natural Course of Pachychoroid Pigment Epitheliopathy

PURPOSE: To investigate the natural course of pachychoroid pigment epitheliopathy (PPE). DESIGN: A retrospective cohort study. SUBJECTS: From the Kyoto central serous chorioretinopathy (CSC) cohort consisting of 548 patients with CSC as of September 2020, we included consecutive unilateral patients with acute or chronic CSC between January 2013 and December 2016. METHODS: All patients underwent complete ophthalmic examination, including multimodal imaging such as fundus autofluorescence, spectral-domain optical coherence tomography, and fluorescein angiography/indocyanine green angiography and/or optimal coherence tomography angiography. The fellow eyes of eyes diagnosed with CSC were screened for PPE, and their natural course was evaluated. We also evaluated the association of ARMS2 rs10490924, CFH rs800292, TNFRSF10A rs13278062, and GATA5 rs6061548 genotypes with the natural course. MAIN OUTCOME MEASURES: Incidence of CSC, pachychoroid neovasculopathy, and pachychoroid geographic atrophy (GA). RESULTS: In total, 165 patients with unilateral CSC (mean age, 55.7 ± 12.6 years; female, 22.4%) were included from the Kyoto CSC cohort. Among them, 148 (89.7%) were diagnosed as having PPE in their non-CSC eye. Survival analysis revealed that 16.8% of PPE eyes developed CSC during the 6-year follow up, whereas non-PPE eyes did not. Although genetic factors did not have significant association with CSC development (P > 0.05, log-rank test), choroidal vascular hyperpermeability (CVH) and subfoveal choroidal thickness (SFCT) were significantly associated with CSC incidence (P = 0.001, log-rank test). Survival analysis showed that eyes without CVH and eyes with SFCT < 300 μm did not develop CSC during the 6-year follow-up. Pachychoroid neovasculopathy developed in only 1 eye with PPE during a follow-up of 46.4 months. Pachychoroid GA did not develop in any of the studied eyes. CONCLUSIONS: This study revealed a natural history of PPE in a relatively large Japanese cohort. Choroidal vascular hyperpermeability and SFCT were significant risk factors for the development of CSC in PPE eyes. Although the current results cannot be generalized for all eyes with PPE, these findings present an important clinical implication

Integrating Preprocessing Operations into Deep Learning Model: Case Study of Posttreatment Visual Acuity Prediction

Designing a deep neural network model that integrates clinical images with other electronic medical records entails various preprocessing operations. Preprocessing of clinical images often requires trimming of parts of the lesions shown in the images, whereas preprocessing of other electronic medical records requires vectorization of these records; for example, patient age is often converted into a categorical vector of 10-year intervals. Although these preprocessing operations are critical to the performance of the classification model, there is no guarantee that the preprocessing step chosen is appropriate for model training. The ability to integrate these preprocessing operations into a deep neural network model and to train the model, including the preprocessing operations, can help design a multi-modal medical classification model. This study proposes integration layers of preprocessing, both for clinical images and electronic medical records, in deep neural network models. Preprocessing of clinical images is realized by a vision transformer layer that selectively adopts the parts of the images requiring attention. The preprocessing of other medical electrical records is performed by adopting full-connection layers and normalizing these layers. These proposed preprocessing-integrated layers were verified using a posttreatment visual acuity prediction task in ophthalmology as a case study. This prediction task requires clinical images as well as patient profile data corresponding to each patient's posttreatment logMAR visual acuity. The performance of a heuristically designed prediction model was compared with the performance of the prediction model that includes the proposed preprocessing integration layers. The mean square errors between predicted and correct results were 0.051 for the heuristic model and 0.054 for the proposed model. Experimental results showed that the proposed model utilizing preprocessing integration layers achieved nearly the same performance as the heuristically designed model

Effectiveness of Reduced-fluence Photodynamic Therapy for Chronic Central Serous Chorioretinopathy

[Purpose] To investigate the 2-year effectiveness of reduced-fluence photodynamic therapy (rf-PDT) for chronic central serous chorioretinopathy (cCSC). [Design] Retrospective cohort study. [Participants] A total of 223 consecutive patients with newly diagnosed cCSC with active serous retinal detachment (SRD) were included from May 2007 to June 2017 and followed up for at least 2 years. Patients who underwent ocular treatment other than cataract surgery before the beginning of recruitment and those who had macular neovascularization at baseline were excluded. [Methods] All patients underwent a comprehensive ophthalmic evaluation, including measurements of best-corrected visual acuity (BCVA), slit-lamp examination, dilated fundus examination, color fundus photography, fundus autofluorescence, fluorescein angiography, indocyanine green angiography, and spectral-domain OCT. An inverse probability of treatment weighting (IPTW) methodology was applied to balance 18 baseline characteristics between patients who received rf-PDT (rf-PDT group) and those who did not receive treatment (controls). Inverse probability of treatment weighting survival analysis and regression were performed. [Main Outcome Measures] The proportion of patients whose BCVA at 24 months was the same or improved compared with the baseline visual acuity (VA) (VA maintenance rate). [Results] A total of 155 eyes (rf-PDT group: 74; controls: 81) were analyzed. The patients’ backgrounds were well balanced after IPTW with standardized differences of < 0.10. An IPTW regression analysis revealed that the VA maintenance rate was significantly higher in the rf-PDT group than in the controls (93.6% vs. 70.9%, P < 0.001, 12 months; 85.7% vs. 69.8%, P = 0.019, 24 months). The rf-PDT group tended to show better VA improvement, but was not statistically significant (–0.06 vs. –0.008, P = 0.07, 12 months; –0.06 vs. –0.03, P = 0.32, 24 months). An IPTW Cox regression showed a significantly higher rate of complete SRD remission in the rf-PDT group (hazard ratio, 5.05; 95% confidence interval, 3.24–7.89; P < 0.001). [Conclusions] The study suggests the beneficial effect of rf-PDT for cCSC for both VA maintenance and higher proportion of complete SRD remission in the clinical setting

Distribution of Choroidal Thickness and Choroidal Vessel Dilation in Healthy Japanese Individuals: The Nagahama Study

[Purpose] To report fundamental epidemiologic data for choroidal parameters such as choroidal thickness and index of choroidal vascularity in Japanese individuals and to evaluate their correlations with age, sex, systemic parameters, and other ocular parameters. [Design] Population-based cohort study. [Participants] A total of 9850 individuals participated in the first follow-up of the Nagahama Prospective Cohort for Comprehensive Human Bioscience (the Nagahama Study) conducted between 2013 and 2016. [Methods] All participants underwent standardized ophthalmic examinations, including OCT with enhanced depth imaging (EDI; RS-3000 Advance; Nidek). We manually segmented the choroidoscleral interface to measure subfoveal choroidal thickness (SFCT) and calculated the normalized choroidal intensity obtained with EDI (NCIEDI) and choroidal vascularity index (CVI). These are indices of choroidal brightness in OCT and reportedly represent the dilation of choroidal vessels. After summarizing the age-sex stratified distributions of SFCT, NCIEDI, and CVI, their associations with age, sex, axial length (AL), and spherical equivalent (SE) were evaluated using linear regression analysis with adjustments for possible confounders. [Main Outcome Measures] Distribution of SFCT, NCIEDI, and CVI in the healthy Japanese population and their characteristics. [Results] Age-sex standardized SFCT, NCIEDI, and CVI were 291.2 μm, 0.653, and 66.88%, respectively. In both men and women, SFCT was associated negatively with age (P < 0.001) and NCIEDI was associated positively with age (P < 0.001). Although both SFCT and NCIEDI did not differ significantly between men and women overall (P = 0.87 and P = 0.21, respectively), among younger participants (35–50 years of age), men showed significantly greater SFCT than women (P < 0.001). Only in men was CVI associated positively with age (P < 0.001). In the multivariable analysis, SFCT was associated significantly with age, sex, AL, SE, and the interaction term of age and sex (P < 0.001). Independent of SFCT, NCIEDI and CVI were associated significantly with age (P < 0.001). [Conclusions] We report normative Japanese SFCT, NCIEDI, and CVI data using a large general Japanese cohort. The association analysis of SFCT with NCIEDI and CVI suggested that younger individuals have a more lumen-rich choroid for their choroidal thickness than older individuals

Association of SIX1/SIX6 locus polymorphisms with regional circumpapillary retinal nerve fibre layer thickness: The Nagahama study

SIX1 and SIX6 are glaucoma susceptibility genes. Previous reports indicate that the single nucleotide polymorphism (SNP) rs33912345 in SIX6 is associated with inferior circumpapillary retinal nerve fibre layer (cpRNFL) thickness (cpRNFLT). Although the region of visual field defect in glaucoma patients is directly related to cpRNFL thinning, a detailed sector analysis has not been performed in genetic association studies. In the present study, we evaluated 26 tagging SNPs in the SIX1/SIX6 locus ±50 kb region in a population of 2, 306 Japanese subjects with 4- and 32-sector cpRNFLT analysis. While no SNPs showed a significant association with cpRNFLT in the 4-sectored analysis, the finer 32-sector assessment clearly showed a significant association between rs33912345 in the SIX1/SIX6 locus with inferior cpRNFL thinning at 292.5–303.8° (β = −4.55, P = 3.0 × 10−5). Furthermore, the fine-sectored cpRNFLT analysis indicated that SIX1/SIX6 polymorphisms would affect cpRNFL thinning at 281.3–303.8°, which corresponds to parafoveal scotoma in a visual field test of glaucoma patients

CFHandVIPR2as susceptibility loci in choroidal thickness and pachychoroid disease central serous chorioretinopathy

中心性漿液性網脈絡膜症に関わる遺伝子変異を発見 --日本人に多い特殊なタイプの加齢黄斑変性の原因も解明--. 京都大学プレスリリース. 2018-05-31.Central serous chorioretinopathy (CSC) is a common disease affecting younger people and may lead to vision loss. CSC shares phenotypic overlap with age-related macular degeneration (AMD). As recent studies have revealed a characteristic increase of choroidal thickness in CSC, we conducted a genome-wide association study on choroidal thickness in 3, 418 individuals followed by TaqMan assays in 2, 692 subjects, and we identified two susceptibility loci: CFH rs800292, an established AMD susceptibility polymorphism, and VIPR2 rs3793217 (P = 2.05 × 10−10 and 6.75 × 10−8, respectively). Case–control studies using patients with CSC confirmed associations between both polymorphisms and CSC (P = 5.27 × 10−5 and 5.14 × 10−5, respectively). The CFH rs800292 G allele is reportedly a risk allele for AMD, whereas the A allele conferred risk for thicker choroid and CSC development. This study not only shows that susceptibility genes for CSC could be discovered using choroidal thickness as a defining variable but also, deepens the understanding of differences between CSC and AMD pathophysiology

Genetic variants linked to myopic macular degeneration in persons with high myopia: CREAM Consortium

Purpose To evaluate the roles of known myopia-associated genetic variants for development of myopic macular degeneration (MMD) in individuals with high myopia (HM), using case-control studies from the Consortium of Refractive Error and Myopia (CREAM). Methods A candidate gene approach tested 50 myopia-associated loci for association with HM and MMD, using meta-analyses of case-control studies comprising subjects of European and Asian ancestry aged 30 to 80 years from 10 studies. Fifty loci with the strongest associations with myopia were chosen from a previous published GWAS study. Highly myopic (spherical equivalent [SE] -5.0 diopters [D]) cases with MMD (N = 348), and two sets of controls were enrolled: (1) the first set included 16,275 emmetropes (SE -0.5 D); and (2) second set included 898 highly myopic subjects (SE -5.0 D) without MMD. MMD was classified based on the International photographic classification for pathologic myopia (META-PM). Results In the first analysis, comprising highly myopic cases with MMD (N = 348) versus emmetropic controls without MMD (N = 16,275), two SNPs were significantly associated with high myopia in adults with HM and MMD: (1) rs10824518 (P = 6.20E-07) in KCNMA1, which is highly expressed in human retinal and scleral tissues; and (2) rs524952 (P = 2.32E-16) near GJD2. In the second analysis, comprising highly myopic cases with MMD (N = 348) versus highly myopic controls without MMD (N = 898), none of the SNPs studied reached Bonferroni-corrected significance. Conclusions Of the 50 myopia-associated loci, we did not find any variant specifically associated with MMD, but the KCNMA1 and GJD2 loci were significantly associated with HM in highly myopic subjects with MMD, compared to emmetropes

Genome-wide association meta-analysis of corneal curvature identifies novel loci and shared genetic influences across axial length and refractive error

Corneal curvature, a highly heritable trait, is a key clinical endophenotype for myopia - a major cause of visual impairment and blindness in the world. Here we present a trans-ethnic meta-analysis of corneal curvature GWAS in 44,042 individuals of Caucasian and Asian with replication in 88,218 UK Biobank data. We identified 47 loci (of which 26 are novel), with population-specific signals as well as shared signals across ethnicities. Some identified variants showed precise scaling in corneal curvature and eye elongation (i.e. axial length) to maintain eyes in emmetropia (i.e. HDAC11/FBLN2 rs2630445, RBP3 rs11204213); others exhibited association with myopia with little pleiotropic effects on eye elongation. Implicated genes are involved in extracellular matrix organization, developmental process for body and eye, connective tissue cartilage and glycosylation protein activities. Our study provides insights into population-specific novel genes for corneal curvature, and their pleiotropic effect in regulating eye size or conferring susceptibility to myopia.</p