Purpose: Cataracts in patients with diabetes mellitus (DM) are a major cause of blindness in developed and developing countries. This study aims to examine whether the generation of reactive oxygen species (ROS) via the increased expression of glucose transporters (GLUTs) and the receptor for advanced glycation end products (RAGE) influences the cataract development in DM. Methods: Lens epithelial cells (LECs) were isolated during cataract surgery from patients without DM or with DM, but without diabetic retinopathy. In a rat model, fructose (10% fructose, 8 or 12 weeks) with or without dapagliflozin (1.2 mg/day, 2 weeks) treatment did induce DM, as verified by blood pressure and serum parameter measurements. Immunofluorescence stainings and immunoblottings were used to quantify the protein levels. Endogenous O₂˙¯ production in the LECs was determined in vivo with dihydroethidium stainings. Results: We investigated that GLUT levels in LECs differed significantly, thus leading to the direct enhancement of RAGE-associated superoxide generation in DM patients with cataracts. Superoxide production was significantly higher in LECs from rats with fructose-induced type 2 DM, whereas treatment with the sodium-glucose cotransporter 2 (SGLT2) inhibitor dapagliflozin prevented this effect in fructose-fed rats. Protein expression levels of the sodium/glucose cotransporter 2 (SGLT2), GLUT1, GLUT5, the nicotinamide adenine dinucleotide phosphate reduced form (NADPH) oxidase subunit p67-phox, NOX2/4 and RAGE were upregulated in fructose-fed animals, whereas dapagliflozin treatment reversed these effects. Conclusions: In rats with fructose-induced DM, dapagliflozin downregulates RAGE-induced NADPH oxidase expression in LECs via the inactivation of GLUTs and a reduction in ROS generation. These novel findings suggest that the SGLT2 inhibitor dapagliflozin may be a candidate for the pharmacological prevention of cataracts in patients with DM.

Purpose: Cataracts are a major cause of visual acuity deterioration in diabetes mellitus (DM) in developed and developing countries. Studies have demonstrated that overproduction of AKR1B1 and receptor for advanced glycation end products (RAGE) plays a major role in the pathogenesis of diabetic cataracts, but it is unclear whether the prevalence of diabetic cataracts is related to epithelial–mesenchymal transition (EMT) in lens epithelial cells. This study aimed to analyze the role of EMT in cataract formation of DM patients. Methods: Immunofluorescence and immunohistochemistry assays were used to estimate AKR1B1, RAGE, AMPK, and EMT levels in epithelial human lens of DM or non-DM cataracts. Results: Immunohistochemical staining demonstrated that pathologic phases and N-cadherin expression levels were significantly higher in epithelial human lens of DM (+) compared to DM (−) cataracts. Immunofluorescent staining showed that AKR1B1 and RAGE were significantly higher in epithelial human lens of DM (+) compared to DM (−) cataracts. Interestingly, acetyl superoxide dismutase 2 (AcSOD2) levels were significantly higher in DM patients’ lens epithelial cells (LECs), whereas AMPKT172 phosphorylation was significantly increased in non-DM patients. This indicates that AMPKT172 might be related to superoxide reduction and diabetic cataract formation. Conclusions: Our results suggest that AKR1B1 overexpression can decrease AMPK activation, thereby increasing AcSOD2 and RAGE-induced EMT in epithelial human lens of DM cataracts. These novel findings suggest that AKR inhibitors may be candidates for the pharmacological prevention of cataracts in patients with DM.

Purpose: The aim of this study was to evaluate the 12-month outcomes, efficacy, and safety of three consecutive monthly intravitreal ranibizumab injections for myopic choroidal neovascularization (CNV). Methods: We retrospectively reviewed the medical records of 25 consecutive eyes that received a loading dose of three consecutive monthly intravitreal injections of ranibizumab for myopic CNV between February, 2008, and March, 2010, with a follow-up of 12 months. Eyes with persistent or recurrent CNV after 3 months received additional ranibizumab injections as needed. Patients' demographic data, best corrected visual acuity (BCVA), CNV findings on fluorescent angiography (FAG), central macular thickness (CMT) on optical coherence tomography (OCT), total number of treatments, and complications were recorded. Results: Mean baseline BCVA was 0.73 logarithm of the minimum angle of resolution (logMAR) (standard deviation [SD] 0.63), and improved significantly to 0.42 logMAR (SD 0.43) at 1 month, 0.38 logMAR (SD 0.47) at 2 months, 0.34 logMAR (SD 0.43) at 3 months, and 0.34 logMAR (SD 0.40) at 12 months (all P <0.001, Wilcoxon signed-rank test). The average number of injections was 3.44 (SD 0.92). At 12 months, mean improvement was 2.88 lines (SD 2.35), and 20 eyes (80%) showed a gain of at least one line after treatment. At 3 months, OCT showed significant reduction in CMT ( P =0.012, two-tailed t -test), and FAG showed significant reduction of mean CNV size from 0.3 (SD 0.16) to 0.19 (SD 0.12) disc area ( P =0.007, two-tailed t -test). No angiographic leakage was evident at 3 months in 21 eyes (84%); four eyes (16%) required additional injections for persistent leakage. Two eyes (8%) had recurrent CNV during follow-up and required retreatment. No complications were noted after treatment. Conclusions: An initial loading dose of three ranibizumab injections is safe and effective in treating myopic CNV, with visual improvement maintained over 12 months.

Background: To compare the surgical outcomes of the inverted internal limiting membrane (ILM) flap technique and ILM insertion for macular hole (MH) without retinal detachment in eyes with extremely high myopia. Methods: In this retrospective study, we analyzed 22 eyes with an axial length ≥ 30.0 mm that had underwent MH surgery between April 2015 and August 2021. The surgical procedures involved either an inverted ILM flap or ILM insertion. The outcomes were compared between the two techniques. Closure of the MH was confirmed by optical coherence tomography (OCT). The best-corrected visual acuity (BCVA) was measured before and after surgery. Associated complications were documented. Results: The median of axial length was 30.64 mm (range, 30.0-34.42). The MH closed in 100% (22/22) eyes and did not recur with a median follow-up of 12.5 months. For the inverted ILM flap technique, the median BCVA improved significantly from 0.80 logarithm of the minimum angle of resolution (logMAR) (range, 0.40-2.00) before surgery to 0.70 logMAR (range, 0.09–1.52) after surgery (p = 0.002). In addition, the median of final BCVA was better for the inverted ILM flap than ILM insertion (0.7 logMAR V.S. 1.00 logMAR; p = 0.016). Conclusions: In eyes with extremely high myopia, despite comparable effects on MH closure for both ILM insertion and the inverted ILM flap, the later technique achieved significantly better visual outcomes.

This retrospective study aimed to evaluate the visual outcomes and foveal restoration in eyes with rhegmatogenous retinal detachment (RRD) and macular hole (MH) following surgery using the inverted internal limiting membrane (ILM) flap technique. We collected data on eyes with coexisting RRD and MH that underwent surgery using the inverted ILM flap technique between January 2016 and December 2018. The primary outcome measures were visual acuity (VA) and optical coherence tomography findings. Of 308 eyes with MH originating from various causes, 8 (2.6%) eyes diagnosed with coexisting RRD and MH treated using the inverted ILM flap technique were included. The average patient age and axial length were 65.00 ± 12.01 years and 23.66 ± 0.77 mm, respectively. The mean preoperative best-corrected VA (BCVA) was 1.84 (spherical equivalent [SE], counting finger) ± 0.32 logMAR and the mean final BCVA had improved significantly to 1.05 (SE, 20/223) ± 0.67 logMAR (P = .017). The primary retinal reattachment, MH closure, and secondary retinal attachment rates were 75% (6/8), 87.5% (7/8), and 100% (7/7), respectively. The inverted ILM flap technique led to significant improvements in anatomical and visual outcomes in patients with coexisting RRD and MH.