To determine the relationship between large-sized and medium-sized choroidal vessels and choriocapillaris using the three-dimensional choroidal vascularity index (3D CVI) and percentage of flow deficits (FD%).Methods: Prospective observational study. The main outcome measures included choroidal volume parameters (3D CVI, mean choroidal thickness, total choroidal volume, choroidal luminal volume, and choroidal stromal volume), choriocapillaris parameters (FD %, average area of FD, and FD count), and age and axial length.Results: A total of 63 healthy individuals with an average age of 40.60 ± 12.32 years were included in this study. Univariate analysis showed that FD% (R = 0.295, P = 0.019) and area of FD (R = 0.276, P = 0.028) were significantly positively associated with 3D CVI, and FD count was negatively associated with 3D CVI (R = 20.297, P = 0.018). After adjusting for age and axial length, a significant correlation between FD% and 3D CVI (R = 0.264, P = 0.039) and between area of FD and 3D CVI remained (R = 0.267, P = 0.037). However, no significant correlation was found between FD count and 3D CVI after adjusting for axial length (R = 20.220, P = 0.085).Conclusion: In healthy individuals, choroidal vessel dilatation as suggested by elevated 3D CVI may lead to decreased choriocapillaris perfusion, which was correlated with an enlarged area of FD in choriocapillaris.

Purpose: To compare peripapillary choroidal vascularity among Leber's Hereditary Optic Neuropathy (LHON) patients at different stages of natural course and healthy controls using optical coherence tomography (OCT), and to evaluate peripapillary choroidal vascularity changes in LHON patients before and after gene therapy.Methods: 57 LHON patients and 15 healthy controls were enrolled in this prospective clinical study. LHON patients were divided into three duration groups based on stage of disease progression. Both patients and healthy controls underwent OCT scans focused on the optic disc at baseline with Heidelberg Spectralis, and patients underwent OCT at 1, 3, and 6 months after gene therapy. OCT images were converted and binarized using ImageJ software. Choroidal thickness (CT), total choroidal area (TCA), and choroidal vascularity index (CVI) in each quadrant of OCT images were measured to evaluate peripapillary choroidal vascularity.Results: At baseline, the average CT was not significantly different between LHON patients at different stages and between healthy controls (P = 0.468). Although average TCA and average CVI were slightly higher in LHON patients at different stages than in healthy controls, the difference was not statistically significant (P = 0.282 and 0.812, respectively). After gene therapy, The average TCA at 1 month after gene therapy was significantly higher than that before gene therapy (P = 0.003), while no significant differences were found in the average CT or average CVI in LHON patients before and 1,3 and 6 months after gene therapy using pairwise comparisons (all P > 0.05).Conclusions: No significant difference was found in choroidal vascularity of LHON patients at different stages and healthy controls. Choroidal vascularity seems to stay stable after gene therapy.

ObjectiveIn order to automatically and rapidly recognize the layers of corneal images using in vivo confocal microscopy (IVCM) and classify them into normal and abnormal images, a computer-aided diagnostic model was developed and tested based on deep learning to reduce physicians’ workload.MethodsA total of 19,612 corneal images were retrospectively collected from 423 patients who underwent IVCM between January 2021 and August 2022 from Renmin Hospital of Wuhan University (Wuhan, China) and Zhongnan Hospital of Wuhan University (Wuhan, China). Images were then reviewed and categorized by three corneal specialists before training and testing the models, including the layer recognition model (epithelium, bowman’s membrane, stroma, and endothelium) and diagnostic model, to identify the layers of corneal images and distinguish normal images from abnormal images. Totally, 580 database-independent IVCM images were used in a human-machine competition to assess the speed and accuracy of image recognition by 4 ophthalmologists and artificial intelligence (AI). To evaluate the efficacy of the model, 8 trainees were employed to recognize these 580 images both with and without model assistance, and the results of the two evaluations were analyzed to explore the effects of model assistance.ResultsThe accuracy of the model reached 0.914, 0.957, 0.967, and 0.950 for the recognition of 4 layers of epithelium, bowman’s membrane, stroma, and endothelium in the internal test dataset, respectively, and it was 0.961, 0.932, 0.945, and 0.959 for the recognition of normal/abnormal images at each layer, respectively. In the external test dataset, the accuracy of the recognition of corneal layers was 0.960, 0.965, 0.966, and 0.964, respectively, and the accuracy of normal/abnormal image recognition was 0.983, 0.972, 0.940, and 0.982, respectively. In the human-machine competition, the model achieved an accuracy of 0.929, which was similar to that of specialists and higher than that of senior physicians, and the recognition speed was 237 times faster than that of specialists. With model assistance, the accuracy of trainees increased from 0.712 to 0.886.ConclusionA computer-aided diagnostic model was developed for IVCM images based on deep learning, which rapidly recognized the layers of corneal images and classified them as normal and abnormal. This model can increase the efficacy of clinical diagnosis and assist physicians in training and learning for clinical purposes.

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AIM: To evaluate the functional and structural changes of photoreceptors in patients and asymptomatic carriers with Leber hereditary optic neuropathy (LHON) using full-field electroretinography (FERG) and optical coherence tomography (OCT). METHODS: Individuals diagnosed with LHON at the Renmin Hospital of Wuhan University and their family members were included in this cross-sectional observational study. The FERG a-wave amplitude of affected patients and asymptomatic carriers was analyzed. The thickness of the outer nuclear layer (ONL), inner and outer segment (IS/OS) and total photoreceptors in the macular fovea and parafovea were measured. RESULTS: This study included 14 LHON patients (mean age: 20.00±9.37y), 12 asymptomatic carriers (mean age: 39.83±6.48y), and 14 normal subjects (mean age: 24.20±1.52y). The FERG results showed that the dark-adapted 3.0 electroretinography and light-adapted 3.0 electroretinography a-wave amplitudes of patients and carriers were significantly decreased (P<0.001). The ONL and photoreceptors layers were slightly thicker in patients than in normal subjects (P<0.05), whereas they were thinner in carriers (P<0.05). There were no differences in IS/OS thickness among the groups (P>0.05). CONCLUSION: Photoreceptors function is significantly impaired in LHON-affected patients and asymptomatic carriers. Meanwhile, photoreceptors morphology is slightly altered, mainly manifesting as a change in ONL thickness.

PurposeTo characterize features of retinal never fiber in Leber Hereditary Optic Neuropathy (LHON) using multicolor (MC) imaging and color fundus photography (CFP).MethodsNinety-two eyes of patients with LHON underwent MC imaging, optic disc spectral domain optical coherence tomography (SD-OCT), and CFP. Two independent observers graded RNFL visibility scores and two other experts determined never fiber bundle defects from four-quadrant readings. CFP, standard MC, infrared reflectance (IR), green reflectance (GR), blue reflectance (BR), and green-blue-enhanced (BG) imaging were compared.ResultsAgreement on never fiber bundle defects was substantial for CFP, standard MC, GR, BR, and BG images relative to IR. It was shown that BR (2.71 ± 0.55) had the best mean RNFL visibility score, BG (2.69 ± 0.52), GR (2.69 ± 0.56), standard MC (2.04 ± 0.79), CFP (1.80 ± 0.82), and IR (0.45 ± 0.59) followed. Agreement on temporal area defects was relatively improved. Youden's indices for CFP (78.21%), standard MC (84.48%), GR (90.92%), BR (89.64%), and BG (90.99%) indicated good detection of defects in the papillomacular bundle (PMB)/ high suspicion of patients with LHON, particularly for BG and GR. According to the proportion of never fiber bundle defects, standard MC, GR, BR, and BG can roughly determine the LHON clinical stage, especially in subacute and chronic stages, and standard MC is superior for patients with LHON of all stages. The stage judged by MC was consistent with the course inferred by pRNFL thickness.ConclusionAs an adjunct to SD-OCT, the MC image, particularly the GR and BG can delineate RNFL more effectively than CFP. The MC image may be a useful adjunct to OCT for detecting or monitoring never fiber bundle defects, providing inexpensive and rapid methods that can quickly identify patients with high suspicion of LHON.

Background Leber's hereditary optic neuropathy (LHON) is a maternally inherited mitochondrial genetic disease, caused mainly by G11778A mutations. Analysis of retinal sublayer structure by spectral domain optical coherence tomography(SD-OCT) is of great significance for elucidating the pathogenesis of LHON. Purpose To analyze the thicknesses of the outer plexiform layer (OPL), outer nuclear layer (ONL), photoreceptor inner and outer segment (IS/OS), and macula thickness (MT) in symptomatic and asymptomatic carriers of G11778A mutants with LHON using SD-OCT. Methods In this cross-sectional study, a total of 70 symptomatic carriers with the G11778A mutation were enrolled in Renmin Hospital of Wuhan University. Family members of symptomatic carriers were recruited as asymptomatic carriers for a final total of 36 participants. We also recruited 29 age- and sex-matched normal subjects. Results MT of symptomatic carriers was thinner than for asymptomatic carriers, while asymptomatic carriers were thinner than normal subjects. In carriers of the G11778A mutation, OPL thickness was increased, and ONL thickness was decreased compared to normal cases. Correlation analysis showed that MT was significantly correlated with peripapillary retinal nerve fiber layer (pRNFL) and disease duration, while ONL thickness in parafoveal nasal areas thinned as the disease progressed. The three groups showed no significant differences in IS/OS thicknesses. Conclusions The thicknesses of OPL, ONL and MT differed between normal subjects and symptomatic and asymptomatic carriers of G11778A mutations with LHON. MT and ONL thinning, in addition to OPL thickening, were observed in symptomatic and asymptomatic carriers, a finding which should be further validated and explored in basic science research. Additional longitudinal studies are needed to determine the usefulness of these findings to the diagnosis and monitoring of LHON.