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Aims/introduction: To conduct a multicenter survey of visually impaired patients with diabetes mellitus (DM) and to identify the physical and ocular characteristics that lead to blindness in Japan., Materials and Methods: Visually impaired patients with diabetes mellitus in Japan were divided into blind and low-vision groups according to the World Health Organization classification. Data on parameters related to diabetes mellitus and ocular complications in the right and left eyes were collected from 19 highly advanced medical facilities and compared between the two groups., Results: Among 408 visually impaired persons (blind group: 257, low-vision group: 151), 72.1% were under 70 years of age. The rates of neovascular glaucoma (NVG) (right eye, P = 0.041; left eye, P = 0.0031) or proliferative diabetic retinopathy (PDR) (right eye: P = 0.014, left eye: P = 0.0047) and the rate of proliferative membrane beyond half of the retinal area (right eye: P = 0.0263, left eye: P = 0.037) were significantly higher in the blind group. The direct cause of visual impairment was retinal atrophy, common in both groups. Neovascular glaucoma and diabetic macular edema were equally prevalent in the blind and low-vision groups, respectively., Conclusions: In Japan, blind patients with diabetes mellitus are characterized by severe conditions such as neovascular glaucoma and progressive proliferative diabetic retinopathy upon their initial visit to an advanced care facility. These results highlight the importance of monitoring retinopathy through regular ophthalmological examinations, internal medicine, and appropriate therapeutic intervention., (© 2024 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Purpose: The aim of this study was to compare the timing of peripapillary vascular damage between functional and structural parameters and examine their involvement with neurovascular coupling at different stages of diabetic retinopathy (DR)., Methods: One hundred ninety eyes of 143 patients with type 2 diabetes mellitus (DM) and 88 healthy control eyes were enrolled. Eyes of DM patients were divided into 3 stages with no diabetic retinopathy (NDR), non-proliferative diabetic retinopathy (NPDR), and proliferative diabetic retinopathy (PDR). NPDR and PDR eyes were treatment-naive. OCT angiography was used to calculate radial peripapillary capillary (RPC)-flux index (FI) and RPC-perfusion density (PD). Spectral domain OCT was used to measure retinal nerve fiber layer (RNFL) thickness within the corresponding RPC areas., Results: RPC-FI significantly decreased in NDR eyes compared to control eyes and thereafter remained unchanged among DM (NDR, NPDR, and PDR) eyes. In contrast, RPC-PD stayed unaltered between control and NDR eyes and significantly decreased in NPDR followed by PDR eyes at similar levels. From control to NPDR eyes, RNFL thickness showed positive correlations with both RPC-FI and RPC-PD, indicative of functional and structural neurovascular coupling. These vascular parameters were also correlated with each other in control and NPDR eyes but not NDR eyes, consistent with the difference in the timing of vascular damage between functional and structural parameters., Conclusions: Circulatory dysfunction preceded structural loss while maintaining peripapillary neurovascular coupling during progression of DR stages. RPC-FI would likely be more sensitive than RPC-PD in detecting early vascular damage in DR., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose/Aim of the study: To explore the possible role of vascular adhesion protein-1 (VAP-1) via its enzymatic function as a semicarbazide-sensitive amine oxidase (SSAO) in the pathogenesis of proliferative diabetic retinopathy (PDR)., Materials and Methods: The levels of soluble VAP-1/SSAO and the unsaturated aldehyde acrolein (ACR)-conjugated protein, N ε -(3-formyl-3, 4-dehydropiperidino) lysine adduct (FDP-Lys), were measured in vitreous fluid samples of PDR and non-diabetic patients using ELISA. Recombinant human VAP-1/SSAO (rhVAP-1/SSAO) was incubated with spermine, with or without semicarbazide or RTU-1096 (a specific inhibitor for VAP-1/SSAO). Immunofluorescence assays were performed to assess the localization of VAP-1/SSAO and FDP-Lys in fibrovascular tissues from patients with PDR. The impact of ACR on cultured retinal capillary endothelial cells was assessed using a cell viability assay and total glutathione (GSH) measurements., Results: The levels of sVAP-1/SSAO and FDP-Lys were elevated in the vitreous fluid of patients with PDR. Incubation of rhVAP-1 with spermine resulted in the generation of hydrogen peroxide and FDP-Lys and the production was inhibited by semicarbazide and RTU-1096. In fibrovascular tissues, FDP-Lys and VAP-1/SSAO were present in endothelial cells. ACR stimulation reduced GSH levels in the cultured endothelial cells in a dose-dependent manner and caused cellular toxicity., Conclusions: Our results indicate the pathological role of sVAP-1/SSAO to generate hydrogen peroxide and toxic aldehyde ACR, both of which are associated with oxidative stress, as a consequence of spermine oxidation in eyes with PDR.

Purpose: To examine the expression of alphaB-crystallin and its colocalization with vascular endothelial growth factor in the epiretinal membrane of human proliferative diabetic retinopathy., Methods: Ten epiretinal membranes of proliferative diabetic retinopathy and three normal retinas surgically excised were included in this study. Paraformaldehyde-fixed, paraffin-embedded tissue sections were processed for immunohistochemistry with alphaB-crystallin, vascular endothelial growth factor, and CD31 antibodies., Results: AlphaB-crystallin was expressed in all epiretinal membranes examined. The immunolocalization of alphaB-crystallin was detected in the cytoplasm of CD31-positive endothelial cells, but not in normal retinal blood vessels. Furthermore, alphaB-crystallin immunoreactivity was colocalized in vascular endothelial growth factor-positive endothelial cells in proliferative diabetic retinopathy membranes., Conclusion: AlphaB-crystallin was expressed in proliferative diabetic retinopathy membranes, and colocalized with vascular endothelial growth factor-positive neovessels. AlphaB-crystallin may play a potential role in the pathogenesis of epiretinal membranes in proliferative diabetic retinopathy, together with vascular endothelial growth factor.

Purpose: The aim of this study was to compare the timing of peripapillary vascular damage between functional and structural parameters and examine their involvement with neurovascular coupling at different stages of diabetic retinopathy (DR). Methods: One hundred ninety eyes of 143 patients with type 2 diabetes mellitus (DM) and 88 healthy control eyes were enrolled. Eyes of DM patients were divided into 3 stages with no diabetic retinopathy (NDR), non-proliferative diabetic retinopathy (NPDR), and proliferative diabetic retinopathy (PDR). NPDR and PDR eyes were treatment-naive. OCT angiography was used to calculate radial peripapillary capillary (RPC)-flux index (FI) and RPC-perfusion density (PD). Spectral domain OCT was used to measure retinal nerve fiber layer (RNFL) thickness within the corresponding RPC areas. Results: RPC-FI significantly decreased in NDR eyes compared to control eyes and thereafter remained unchanged among DM (NDR, NPDR, and PDR) eyes. In contrast, RPC-PD stayed unaltered between control and NDR eyes and significantly decreased in NPDR followed by PDR eyes at similar levels. From control to NPDR eyes, RNFL thickness showed positive correlations with both RPC-FI and RPC-PD, indicative of functional and structural neurovascular coupling. These vascular parameters were also correlated with each other in control and NPDR eyes but not NDR eyes, consistent with the difference in the timing of vascular damage between functional and structural parameters. Conclusions: Circulatory dysfunction preceded structural loss while maintaining peripapillary neurovascular coupling during progression of DR stages. RPC-FI would likely be more sensitive than RPC-PD in detecting early vascular damage in DR. [ABSTRACT FROM AUTHOR]