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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.

Diabetic macular edema (DME) refractory to anti-VEGF drugs is a socioeconomic burden. In this retrospective study, we investigated the relationship between DME remission and hyperreflective walls in foveal cystoid spaces , a novel finding on spectral domain optical coherence tomography (SD-OCT) images in DME. In a cross-sectional study, we assessed the relationship between hyperreflective walls in foveal cystoid spaces and other OCT findings in 110 eyes of 110 DME patients. Hyperreflective walls were delineated in 27 of 171 foveal cystoid spaces. Eyes with hyperreflective walls in foveal cystoid spaces had poorer visual acuity and more severe photoreceptor disruption than did those without such findings ( P  = 0.008 and P  < 0.001, respectively). In the other longitudinal study, we evaluated the relationship between this finding and the remission in 54 eyes of 51 DME patients treated with as-needed ranibizumab injections for 24 months. Foveal cystoid spaces with hyperreflective walls were often persistent, and the cumulative rates of DME remission among eyes with and without the hyperreflective walls were 7.7% (1 eye) and 48.8% (20 eyes) at 18 months (hazard ratio, 0.092; P  = 0.025). We characterized hyperreflective walls in foveal cystoid spaces and designated them as a predictor of no DME remission under ranibizumab injections.

Purpose To evaluate the association between central serous chorioretinopathy (CSC) susceptibility genes and choroidal parameters in a large Japanese cohort. Study design Retrospective cohort study. Methods Of the 9850 individuals in the Nagahama study whose second visit was between 2013 and 2016, those with optical coherence tomography (OCT) images with enhanced depth imaging (EDI), axial length, and genome-wide single nucleotide polymorphism (SNP) genotyping data were included. We calculated subfoveal choroidal thickness (SFCT), choroidal vascularity index (CVI), normalized choroidal intensity (NCI), and vertical asymmetry of choroidal thickness. Genome-wide quantitative trait locus (QTL) analyses were performed for each parameter. We screened for four CSC susceptibility SNPs: CFH rs800292, TNFRSF10A rs13278062, GATA5 rs6061548, and VIPR2 rs3793217. Whenever an SNP was not included in the genotyping data after quality control, its proxy SNP was selected. Results In total, 4586 participants were evaluated. CFH rs800292 was significantly associated with SFCT ( P < 0.001) and CVI ( P < 0.001). VIPR2 rs3793217 was significantly associated with SFCT ( P < 0.001) but not with CVI. Whereas, TNFRSF10A rs13254617 and GATA5 rs6061548 were not significantly associated with SFCT or CVI. None of these SNPs was associated with NCI EDI and asymmetry of choroidal thickness. Conclusion CFH , VIPR2 , TNFRSF10A , and GATA5 showed different association patterns with choroidal parameters. Although the mechanism of CSC pathogenesis by choroidal changes is not fully understood, this finding suggests that each gene may be involved in different mechanisms of CSC development. Our genetic study provides a basis for understanding the role of CSC susceptibility genes.

Microcirculatory disturbance plays a pivotal role in the pathogenesis in diabetic retinopathy (DR). We retrospectively quantified the total counts and morphological features of intercapillary spaces , i.e., intercapillary areas and nonperfusion areas (NPAs), on swept-source optical coherence tomography angiography (SS-OCTA) images and to evaluate their associations with DR severity grades. We acquired 3 × 3 mm OCTA images in 75 eyes of 62 diabetic patients and 22 eyes of 22 nondiabetic subjects. In the en-face superficial images within the central 2 mm, the areas enclosed by retinal vessels were automatically detected. Their total numbers decreased in some eyes with no apparent retinopathy and most eyes with DR, which allowed us to discriminate diabetic subjects from nondiabetic subjects [area under the receiver operating characteristic curve (AUC) = 0.907]. The areas and area/perimeter ratios continuously increased in DR, indicating a continuum between healthy intercapillary areas and NPAs. The number of intercapillary spaces with a high area/perimeter ratio increased according to DR severity, which showed modest performance in discriminating moderate NPDR or higher grades (AUC = 0.868). These quantified parameters of intercapillary spaces can feasibly be used for the early detection of microcirculatory impairment and the diagnosis of referable DR.

To analyze the structure of the choriocapillaris in healthy eyes by using averaged en face images acquired using swept source optical coherence tomography angiography and to examine the changes in the macular profile in relation to age, sex, axial length, and choroidal thickness. This prospective, cross-sectional study included 81 eyes of 81 subjects without ophthalmologic or systemic diseases who underwent a full ophthalmologic examination, including 3 × 3-mm macular optical coherence tomography angiography. Four to nine choriocapillaris en face images were registered and averaged. The averaged images were then binarized and analyzed. The averaged choriocapillaris images showed a continuous capillary meshwork, whereas the unaveraged images had a granular appearance. The mean total area and size of flow voids were 0.99 ± 0.20 mm2 and 567.8 ± 201.5 μm2, respectively, and these values correlated positively with age (p = 0.002, R = 0.336 and p = 0.026, R = 0.247, respectively). Age-related gains in the mean total area and flow void size were 4.20 × 10-3 mm2 and 3.07 μm2 per year, respectively. However, the mean total area and flow void size had no significant correlation with axial length, subfoveal choroidal thickness, or sex. Multiple averaged en face swept source optical coherence tomography angiography is more effective than a single optical coherence tomography angiography scan for better visualizing the choriocapillaris. The total area and size of flow voids within a 3 × 3-mm macular area positively correlated with age. This technique can be useful for investigating the changes arising in macular diseases.

BackgroundTo compare and correlate the retinal sensitivity measurements obtained with Nidek Microperimetry-3 (MP-3) and the CenterVue Macular Integrity Assessment (MAIA) microperimeters among healthy subjects.MethodsIn this prospective comparative study, 31 eyes of 23 subjects underwent complete ophthalmological examination including retinal sensitivity assessments using two microperimeters, the MP-3 (Nidek Technologies) and the MAIA (CenterVue). The mean retinal sensitivity (dB) and its corresponding luminance (asb) and contrast (log units) were analysed between the two instruments. The interdevice reproducibility and level of agreement between the sensitivity values of the devices were assessed.ResultsThe mean retinal sensitivity (dB) measured by the MP-3 (25.02±1.06 dB, range: 20.90–26.70) was significantly (p<0.0001) lower compared with the MAIA (30.68±0.74 dB, range: 28–31.84). The luminosity levels were significantly (p<0.0001) higher with the MP3 (7.75±1.31 asb, range: 6.44–9.06) compared with the MAIA (0.92±0.14 asb, range: 0.78–1.06). The contrast sensitivity was significantly higher for the MP-3 (0.94±0.33 log units, range: 0.61–1.27) compared with the MAIA (0.23±0.03 log units, range: 0.20–0.26). Despite these absolute differences, the intraclass coefficient was 0.85 (95% CI 0.70 to 0.92) between the two devices after applying a standard correction factor to each data point (MAIA sensitivity=MP-3 sensitivity+5.65) with a mean difference between MAIA and MP-3 of 0.01.ConclusionRetinal sensitivity measures higher, but luminance and contrast sensitivity measure lower for MAIA-generated values compared with the MP-3. The relationships, however, appeared fairly consistent, and application of a standard correction factor allowed the data to be inter-related, at least for normal eyes.

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.

Glaucoma is a multifactorial optic neuropathy, possibly involving vascular dysfunction, leading to the death of retinal ganglion cells and their axons. Disc hemorrhage (DH) is known to be closely associated with the widening of retinal nerve fiber layer defect (NFLD); however, it has not been well elucidated how DH affects retinal microvasculature. We aimed to investigate the association between DH history and longitudinal changes in superficial retinal microvasculature in NFLD. We enrolled 15 glaucoma patients with DH history (32 glaucomatous NFLD locations, with or without DH history). NFLD-angle, superficial retinal vessel density (VD), and decreased superficial retinal microvasculature (deMv)-angle were assessed using optical coherence tomography angiography for at least three times over time. The mean follow-up period and OCT/OCTA scan interval were 21.3 ± 5.4 months (range, 12–28) and 6.8 ± 0.4 months (range, 2–18), respectively. Linear mixed-effects models showed that the presence of DH history was significantly associated with an additional NFLD-angle widening of 2.19 degree/year ( P  = 0.030), VD decrease of 1.88%/year ( P  = 0.015), and deMv-angle widening of 3.78 degree/year ( P  < 0.001). These changes were significantly correlated with each other ( P  < 0.001). Thus, the widening of NFLD was closely associated with deMv, and DH was associated with a subsequent decrease in superficial retinal microvasculature in NFLD.

We performed a prospective, longitudinal study to investigate the association between the preoperative intrascleral vasculature assessed using anterior segment (AS)-optical coherence tomography angiography (OCTA) and surgical outcomes of trabecular meshwork-targeted micro- or minimally invasive glaucoma surgery (MIGS). We included 37 patients with primary open-angle glaucoma. Preoperative AS-OCTA images of the sclero-conjunctiva of the nasal corneal limbus were acquired in the superficial (conjunctival) and deep (intrascleral) layers. The vessel densities (VDs) of each layer were measured separately in the entire area, limbal side, and fornix area. Surgical success was determined by postoperative intraocular pressure (IOP) and IOP reduction. Twenty-three and 14 eyes were classified as having successful and unsuccessful outcomes, respectively. The deep VDs of the entire area and fornix area were significantly lower in the successful group ( P  = 0.031 and P  = 0.009). The success rate was significantly higher for eyes with a lower deep VD than for eyes with a higher deep VD. A greater IOP reduction was significantly associated with lower deep VD in the fornix area ( P  = 0.022) and higher preoperative IOP ( P  < 0.001). These results indicate that intrascleral vasculature assessed using preoperative AS-OCTA was negatively correlated with surgical success and IOP reduction resulting from trabecular meshwork-targeted MIGS. AS-OCTA images might help predict MIGS outcomes.

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.