Influence of vitreomacular interface score on treatment outcomes of anti-VEGF therapy for neovascular age-related macular degeneration

[Background] To quantitatively evaluate the vitreomacular interface of eyes with neovascular age-related macular degeneration (AMD) and to investigate its association with the 1-year treatment outcome following intravitreal injections of aflibercept (IVA). [Methods] This prospective observational case series included 59 eyes of 59 consecutive patients with treatment-naïve neovascular AMD who were treated with three monthly IVA and subsequent four bi-monthly IVA and were followed up for 1 year. We estimated posterior vitreous detachment at 1, 9, and 25 macular points within an area of 6 × 6 mm2 at the center of the fovea using the built-in enhanced vitreous visualization mode of swept-source optical coherence tomography. One year after the initial IVA, we classified the eyes into either wet or dry groups. [Results] The wet and dry groups included 12 and 47 eyes, respectively. The resistance rate against IVA was 20.3%. The 25-point interface score was higher in the wet group than in the dry group (23.0 ± 4.3 vs. 18.6 ± 9.8, P = 0.03), whereas there were no significant between-group differences in the 9-point and 1-point scores (P = 0.21, and 0.47, respectively) or in the other studied parameters. Multivariable analysis revealed that the 25-point vitreomacular interface score was strongly correlated with subfoveal choroidal thickness (P = 0.02, β =  − 0.31). [Conclusions] Our findings suggest that wide-ranged separation of the posterior vitreous membrane from the retina induces poor response to IVA

Novel scotoma detection method using time required for fixation to the random targets

We developed a novel scotoma detection system using time required for fixation to the random targets, or the” eye-guided scotoma detection method “. In order to verify the” eye-guided scotoma detection method “, we measured 78 eyes of 40 subjects, and examined the measurement results in comparison with the results of measurement by Humphrey perimetry. The results were as follows: (1) Mariotte scotomas were detected in 100% of the eyes tested; (2) The false-negative rate (the percentage of cases where a scotoma was evaluated as a non-scotoma) was less than 10%; (3) The positive point distribution in the low-sensitivity eyes was well matched. These findings suggested that the novel scotoma detection method in the current study will pave the way for the realization of mass screening to detect pathological scotoma earlier.[Author summary] Conventional perimeters, such as the Goldmann perimeter and Humphrey perimeter, require experienced examiners and space occupying. With either perimeter, subjects’ eye movements need to be strictly fixed to the fixation target of the device. Other perimeters can monitor fixation and automatically measure the visual field. With the eye-guided scotoma detection method proposed in the current study, subjects feel less burdened since they do not have to fixate on the fixation target of the device and can move their eyes freely. Subjects simply respond to visual targets on the display; then, scotomas can be automatically detected. The novel method yields highly accurate scotoma detection through an algorithm that separates scotomas from non-scotomas

New femoral remains of <i>Nacholapithecus kerioi</i>: Implications for intraspecific variation and Miocene hominoid evolution

The middle Miocene stem kenyapithecine Nacholapithecus kerioi (16-15 Ma; Nachola, Kenya) is represented by a large number of isolated fossil remains and one of the most complete skeletons in the hominoid fossil record (KNM-BG 35250). Multiple fieldwork seasons performed by Japanese-Kenyan teams during the last part of the 20th century resulted in the discovery of a large sample of Nacholapithecus fossils. Here, we describe the new femoral remains of Nacholapithecus. In well-preserved specimens, we evaluate sex differences and within-species variation using both qualitative and quantitative traits. We use these data to determine whether these specimens are morphologically similar to the species holotype KNM-BG 35250 (which shows some plastic deformation) and to compare Nacholapithecus with other Miocene hominoids and extant anthropoids to evaluate the distinctiveness of its femur. The new fossil evidence reaffirms previously reported descriptions of some distal femoral traits, namely the morphology of the patellar groove. However, results also show that relative femoral head size in Nacholapithecus is smaller, relative neck length is longer, and neck-shaft angle is lower than previously reported for KNM-BG 35250. These traits have a strong functional signal related to the hip joint kinematics, suggesting that the morphology of the proximal femur in Nacholapithecus might be functionally related to quadrupedal-like behaviors instead of more derived antipronograde locomotor modes. Results further demonstrate that other African Miocene apes (with the exception of Turkanapithecus kalakolensis) generally fall within the Nacholapithecus range of variation, whose overall femoral shape resembles that of Ekembo spp. and Equatorius africanus. Our results accord with the previously inferred locomotor repertoire of Nacholapithecus, indicating a combination of generalized arboreal quadrupedalism combined with other antipronograde behaviors (e.g., vertical climbing)

Incidence of central serous chorioretinopathy (2011–2018): a nationwide population-based cohort study of Japan

国の診療報酬請求データベースを用いて特殊な網膜剥離の発症率を明らかに --NDBオンサイトリサーチセンター（京都）を活用した初の成果--. 京都大学プレスリリース. 2021-07-19.[Aims] The aim of this study was to elucidate the epidemiological background of central serous chorioretinopathy (CSC), including its incidence and treatment pattern. [Methods] This was a population-based longitudinal cohort study using a nationwide health insurance claims database of the Japan Ministry of Health, Labour and Welfare (MHLW). As Japan employs universal health coverage, the database covers more than 95% of claims issued in Japan. We accessed all data stored in the database with permission from the MHLW. We traced all individuals aged 30 years or older and identified individuals with new onset of CSC between January 2011 and December 2018. CSC cases were categorised by age and sex for each year, and incidence rate was calculated. We also identified major treatments for CSC to elucidate the initial treatment pattern. [Results] During the 8-year period, 247 930 incidences of CSC were identified, among which 75.9% were men. The crude incidence rate (per 100 000 person-years) in the general population aged 30 years or older was 34.0 (95% CI 33.9 to 34.2), in men was 54.2 (95% CI 53.9 to 54.4) and in women was 15.7 (95% CI 15.5 to 15.8). The mean age of onset was lower in men than in women (50.5±12.5 years vs 54.7±13.5 years). Most of the patients with newly diagnosed CSC (86.8%) did not receive major treatment. [Conclusions] The current study provides the nationwide population-based evidence to clarify the detailed epidemiology of CSC. These results could help to understand the pathogenesis and mechanisms of CSC in the future

Choriocapillaris flow deficit in a pachychoroid spectrum disease using en face optical coherence tomography angiography averaging

[Purpose] To investigate the choriocapillaris changes associated with pachychoroid pigment epitheliopathy (PPE) in comparison with healthy eyes. [Methods] Nine 3 × 3 mm macular optical coherence tomography angiography images were acquired in patients with PPE and age-matched healthy participants. Multiple en face image averaging of the choriocapillaris was binarized for quantitative image analysis of the flow voids. In PPE eyes, we evaluated the presence of pachyvessels and the association between the location of the choriocapillaris flow deficit and pachyvessels. [Results] Thirty-two eyes with PPE and 30 eyes of healthy participants were included. In PPE eyes, the mean total area (1.16 ± 0.18 vs. 0.91 ± 0.16, p < 0.001) and average size of the flow voids (790 ± 144 vs. 520 ± 138; p < 0.001) were significantly larger than those in control eyes. Composite images of the choriocapillaris and choroid showed choriocapillaris flow deficits just above and outside the pachyvessels. The mean proportion of the flow void area overlying the pachyvessels against the whole flow void area of the choriocapillaris was 21.3% ± 10.2% (9.38%-44.42%) in PPE eyes. [Conclusions] In PPE eyes, the blood flow area of the choriocapillaris decreased diffusely within the macular area compared to control eyes, and the choriocapillaris flow deficit was not necessarily related to pachyvessel location

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

Pachychoroid neovasculopathy and age-related macular degeneration.

Pachychoroid neovasculopathy is a recently proposed clinical entity of choroidal neovascularization (CNV). As it often masquerades as neovascular age-related macular degeneration (AMD), it is currently controversial whether pachychoroid neovasculopathy should be distinguished from neovascular AMD. This is because its characteristics have yet to be well described. To estimate the relative prevalence of pachychoroid neovasculopathy in comparison with neovascular AMD and to investigate the phenotypic/genetic differences of the two diseases, we evaluated 200 consecutive Japanese patients who agreed to participate in the genetic study and diagnosed with pachychoroid neovasculopathy or neovascular AMD. Pachychoroid neovasculopathy was observed in 39 individuals (19. 5%), which corresponds to one fourth of neovascular AMD. Patients with pachychoroid neovasculopathy were significantly younger (p = 5. 1 × 10[−5]) and showed a greater subfoveal choroidal thickness (p = 3. 4 × 10[−14]). Their genetic susceptibility to AMD was significantly lower than that of neovascular AMD; ARMS2 rs10490924 (p = 0. 029), CFH rs800292 (p = 0. 013) and genetic risk score calculated from 11 AMD susceptibility genes (p = 3.8 × 10[−3]). Current results implicate that the etiologies of the two conditions must be different. Thus, it will be necessary to distinguish these two conditions in future studie

Comparison of a Novel Head-Mounted Objective Auto-perimetry (Gaze Analyzing Perimeter) and Humphrey Field Analyzer

アイトラッキングを利用した新しい自動視野計の性能が明らかに --簡便な検査で緑内障などの早期発見に期待--. 京都大学プレスリリース. 2024-05-31.Purpose: To evaluate the agreement between 24-2 visual field (VF) test results obtained using the gaze analyzing perimeter (GAP; Findex) and the Humphrey field analyzer (HFA; Carl Zeiss Meditec). Design: Cross-sectional study. Participants: Patients underwent HFA 24-2 for suspected or confirmed VF loss and were treated at the Kyoto University Hospital between December 2022 and July 2023. Methods: Patients underwent consecutive VF tests on the same eye using HFA and GAP 24-2 tests. Bland–Altman analysis was used to compare GAP and HFA results. Examination points where the sensitivity measured using GAP was ≥ 10 dB higher than that measured using HFA were re-evaluated by referring back to the original gaze data; 2 ophthalmologists assessed whether the gaze moved linearly toward the new test target. Main Outcome Measures: Mean deviation (MD) and elapsed time on an individual basis and sensitivity on an examination point basis. Results: Forty-seven eyes of 47 patients were analyzed. The correlation coefficient of the MD using HFA and GAP was 0.811 (95% confidence interval [CI]: 0.683–0.891). Bland–Altman analysis showed good agreement between HFA and GAP tests. The mean difference (95% limits of agreement) in MD between HFA and GAP results was −0.63 dB (−5.81 to 4.54 dB). Although no statistically significant differences were observed in the elapsed time (P = 0.99), measurements completed within 200 seconds were observed only in the GAP group (11 cases, 23.4%), who had significantly better HFA MD value than others (P = 0.001). On an examination point basis for sensitivity, the correlation coefficient between HFA and GAP was 0.691 (95% limits of agreement, 0.670–0.711). Original gaze data assessment revealed that the gaze moved linearly toward the new test target for 70.2% of the examination points with a sensitivity discrepancy. Conclusions: The results indicate that the GAP provides VF assessment outcomes comparable to those of the HFA. The GAP exhibited advantages in terms of testing time, particularly in patients with minimal VF impairment. Furthermore, the GAP records all eye movements, enabling the objective determination of VF abnormalities based on gaze patterns and facilitating easy posthoc verification. Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article

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