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Unsupervised machine learning has received increased attention in clinical research because it allows researchers to identify novel and objective viewpoints for diseases with complex clinical characteristics. In this study, we applied a deep phenotyping method to classify Japanese patients with age-related macular degeneration (AMD), the leading cause of blindness in developed countries, showing high phenotypic heterogeneity. By applying unsupervised deep phenotype clustering, patients with AMD were classified into two groups. One of the groups had typical AMD features, whereas the other one showed the pachychoroid-related features that were recently identified as a potentially important factor in AMD pathogenesis. Based on these results, a scoring system for classification was established; a higher score was significantly associated with a rapid improvement in visual acuity after specific treatment. This needs to be validated in other datasets in the future. In conclusion, the current study demonstrates the usefulness of unsupervised classification and provides important knowledge for future AMD studies.

Next-generation sequencing (NGS) has greatly advanced the studies of causative genes and variants of inherited diseases. While it is sometimes challenging to determine the pathogenicity of identified variants in NGS, the American College of Medical Genetics and Genomics established the guidelines to help the interpretation. However, as to the genetic screenings for patients with retinitis pigmentosa (RP) in Japan, none of the previous studies utilized the guidelines. Considering that EYS is the major causative gene of RP in Japan, we conducted stepwise genetic screening of 220 Japanese patients with RP utilizing the guidelines. Step 1–4 comprised the following, in order: Sanger sequencing for two major EYS founder mutations; targeted sequencing of all coding regions of EYS; whole genome sequencing; Sanger sequencing for Alu element insertion in RP1 , a recently determined founder mutation for RP. Among the detected variants, 2, 19, 173, and 1 variant(s) were considered pathogenic and 8, 41, 44, and 5 patients were genetically solved in step 1, 2, 3, and 4, respectively. Totally, 44.5% (98/220) of the patients were genetically solved, and 50 (51.0%) were EYS -associated and 5 (5.1%) were Alu element-associated. Among the unsolved 122 patients, 22 had at least one possible pathogenic variant.

Recently, several research groups have reported a newly recognized clinical entity of choroidal neovascularization, termed pachychoroid neovasculopathy. However, its characteristics have yet to be well described. The purpose of this study was to investigate the clinical and genetic characteristics of pachychoroid neovasculopathy regardless of treatment modality. This study included 99 eyes of 99 patients with treatment-naïve pachychoroid neovasculopathy. Mean initial best-corrected visual acuity (BCVA) was 0.20 ± 0.32 logMAR, and did not change ( P  = 0.725) during follow-up period (mean ± SD, 37.0 ± 17.6 months). Subretinal hemorrhage (SRH) (≥ 4 disc areas in size) occurred in 20 eyes (20.2%) during follow-up. Age, initial BCVA, central retinal thickness, SRH (≥ 4 disc areas in size) and treatment (aflibercept monotherapy) were significantly associated with the final BCVA ( P  = 0.024, < 0.001, 0.031, < 0.001, and 0.029, respectively). Multiple regression analysis showed initial BCVA and presence of SRH to be significant predictors of final BCVA (both P  < 0.001). Polypoidal lesions were more common in the SRH group than in the non-SRH group (85.0% vs 48.1%, P  = 0.004). There was no significant difference in the frequency of the risk allele in ARMS2 A69S, CFH I62V, CFH Y402H between these groups ( P  = 0.42, 0.77, and 0.85, respectively). SRH (29.1% vs 9.1%, P  = 0.014) and choroidal vascular hyperpermiability (65.5% vs 43.2%, P  = 0.027) were seen more frequently in the polypoidal lesion (+) group than in the polypoidal lesion (−) group. There was considerable variation in lesion size and visual function in patients with pachychoroid neovasculopathy, and initial BCVA and presence of SRH at the initial visit or during the follow-up period were significant predictors of final BCVA.

Inherited retinal dystrophy (IRD) patients often experience photophobia. However, its mechanism has not been elucidated. This study aimed to investigate the main wavelength of light causing photophobia in IRD and difference among patients with different phenotypes. Forty-seven retinitis pigmentosa (RP) and 22 cone-rod dystrophy (CRD) patients were prospectively recruited. We designed two tinted glasses: short wavelength filtering (SWF) glasses and middle wavelength filtering (MWF) glasses. We classified photophobia into three types: (A) white out, (B) bright glare, and (C) ocular pain. Patients were asked to assign scores between one (not at all) and five (totally applicable) for each symptom with and without glasses. In patients with RP, photophobia was better relieved with SWF glasses {“white out” (p < 0.01) and “ocular pain” (p = 0.013)}. In CRD patients, there was no significant difference in the improvement wearing two glasses (p = 0.247–1.0). All RP patients who preferred MWF glasses had Bull’s eye maculopathy. Meanwhile, only 15% of patients who preferred SWF glasses had the finding (p < 0.001). Photophobia is primarily caused by short wavelength light in many patients with IRD. However, the wavelength responsible for photophobia vary depending on the disease and probably vary according to the pathological condition.

The aim of this retrospective, observational study was to examine the intraretinal locations of ruptured retinal arterial macroaneurysms (RMAs) and investigate the associations with the visual prognosis. Fifty patients (50 eyes) with untreated RMA rupture who visited the Department of Ophthalmology at Kyoto University Hospital (April 2014–July 2019) were included. The intraretinal position of the ruptured RMAs relative to the affected retinal artery was examined using optical coherence tomography (OCT) and color fundus photography (CFP). The relative RMA positions were anterior to (anterior type, 44%), at the same level as (lateral type, 20%), or posterior to (posterior type, 34%) the affected artery. At the initial visit, the posterior type showed greater subretinal hemorrhage thickness than did the lateral and anterior types ( P  = 0.016 and 0.006, respectively), and poorer visual acuity (VA) than did the anterior type ( P  = 0.005). At the final visit, the length of the foveal ellipsoid zone band defect was longer ( P  = 0.005) and VA was poorer ( P  < 0.001) for the posterior type than for the anterior type. The intraretinal positions of ruptured RMAs vary, affect the thickness of foveal subretinal hemorrhage and predict future damage to the foveal photoreceptors. The visual prognosis may be poor for posteriorly ruptured RMAs.

ObjectivesWe investigated in vivo light-induced photoreceptor damage in retinitis pigmentosa (RP) using spectral-domain optical coherence tomography (SD-OCT) images.MethodsWe retrospectively reviewed patients with genetic diagnosis of EYS-associated RP. The outer nuclear layer (ONL) thickness under retinal vessels was measured on SD-OCT vertical scans. As a control, we measured adjacent ONL thickness 100 μm superior and inferior from the vessel. Same measurements were performed in healthy subjects. We calculated the ratio of ONL thickness under vessel divided by the average of adjacent ONL thickness and defined as ONL preservation ratio. In patients with RP, the length of ellipsoid zone (EZ) from the fovea was also measured with SD-OCT vertical scans.ResultsThirty EYS-associated RP patients and 25 healthy subjects were included. In both groups, ONL thickness overshadowed by retinal vessels was not significantly different from that of adjacent area. However, ONL preservation ratio of RP was larger than that of healthy control in both superior and inferior retina (1.03 vs 0.97; p < 0.01, 1.15 vs 0.95; p < 0.01, respectively). In RP, ONL preservation ratio was significantly larger in the inferior retina than superior retina (p < 0.01). Furthermore, in RP patients, the EZ length from the fovea was always shorter in the inferior than superior retina and there was a significant difference (p < 0.01).ConclusionsPatients with EYS-associated RP exhibited inferior-dominant photoreceptor death and the relative ONL preservation under retinal vessels. These results suggest that longitudinal environment light exposure may be correlated with the photoreceptor death.

The aim was to establish and evaluate a new clustering method for visual field (VF) test points to predict future VF in retinitis pigmentosa. A Humphrey Field Analyzer 10-2 test was clustered using total deviation values from 858 VFs. We stratified 68 test points into 24 sectors. Then, mean absolute error (MAE) of the sector-wise regression with them (S1) was evaluated using 196 eyes with 10 VF sequences and compared to pointwise linear regression (PLR), mean sensitivity of total area (MS) and also another sector-wise regression basing on VF mapping for glaucoma (29 sectors; S2). MAE with S1 were smaller than with PLR when between the first-third and first-seventh VFs were used. MAE with the method were significantly smaller than those of S2 when between the first-sixth and first-ninth VFs were used. The MAE of MS was smaller than those with S1 only when first to 3rd and first to 4th VFs were used; however, the prediction accuracy became far larger than any other methods when larger number of VFs were used. More accurate prediction was achieved using this new sector-wise regression than with PLR. In addition, the obtained cluster was more useful than that for glaucoma to predict progression.

Though vascular endothelial growth factors (VEGF) and other proangiogenic factors, such as angiopoietins (Ang), may be involved in the development of neovascular age-related macular degeneration (nvAMD), only drugs that inhibit the VEGF family are available for the treatment. The newly approved anti-VEGF drug faricimab, which also inhibits Ang-2, is expected to be effective in patients with AMD refractory to conventional anti-VEGF drugs. Therefore, we prospectively investigated the efficacy of faricimab in the treatment of aflibercept-refractory nvAMD. Patients with nvAMD who had been treated with aflibercept in the last year and required bimonthly injections were recruited. 25 eyes showed persistent exudative changes immediately before the faricimab injection (baseline). In these 25 eyes, switching to faricimab did not change visual acuity or central retinal thickness 2 months after the injection; however, 56% of eyes showed reduction or complete absorption of fluid. Notably, 25% of the eyes that showed dry macula at month 2 had no fluid recurrence for up to 4 months. These results indicate that faricimab could benefit some patients with aflibercept-refractory nvAMD.

Prism adaptation test (PAT) was shown to be an effective assessment for esotropia (ET) surgeries. However, the effectiveness of long-term PAT for ET remains uncertain. This study aimed to evaluate the effectiveness of the long-term PAT for patients with ET by comparing the preoperative deviations before PAT (simple PACT), after short-time PAT (15–30 min/set), and after long-term PAT (1–6 months). This prospective, longitudinal study enrolled 24 consecutive patients who underwent strabismus surgery for ET after long-term PAT. Ocular deviation was measured by prism and alternate cover test (PACT) at pre-PAT, post-short‑time PAT, and post-long‑term PAT. We analyzed the correlation between the effect of long-term PAT and preoperative parameters. The pre-PAT, post-short-time-PAT, and post-long-term-PAT deviations were 13.0 ± 5.2° (23.0 ± 9.0 Δ), 14.4 ± 5.9° (25.7 ± 10.4 Δ), and 15.8 ± 6.3° (28.2 ± 11.0 Δ), respectively. The post-long-term-PAT deviation was larger than that at pre-PAT ( p  = 0.001). Multivariable analysis revealed that the long-term PAT effect was correlated with PAT duration and short-time PAT effect. Our findings suggest that long-term PAT reveals latent deviation and is associated with surgical success in patients with ET. Future comparative studies with control groups are needed to validate these findings.

Internal limiting membrane (ILM) peeling requires a delicate handling technique. It is also important that ophthalmologists can use the ILM forceps handle of their preference. This study objectively and subjectively evaluated the handling of the novel Finesse Reflex Handle (Reflex) in comparison with that of a conventional handle. The force required to close the forceps tips, evaluated using a digital force gauge, was significantly lesser for Reflex than for the conventional handle (3.14 ± 0.09 N vs. 3.84 ± 0.06 N, P  < 0.001). Twenty-one ophthalmologists with various levels of experience answered a questionnaire after using both handles, and the total questionnaire score for Reflex was higher than that for the conventional handle (35.0 ± 3.7 vs. 30.0 ± 6.9, P  = 0.01). Furthermore, the duration of experience as an ophthalmologist was negatively correlated with the vertical motion, assessed by video analysis, for the conventional handle ( P  = 0.02, r =  − 0.50) but not for Reflex ( P  = 0.26). In conclusion, objective and subjective analyses revealed that compared with the conventional handle, the novel Reflex handle had more favourable handling characteristics. Most ophthalmologists preferred the handling of Reflex. Reflex may compensate for a lack of surgical experience.