Tsung-Tien Wu

Chronic hyperglycemia triggers an abnormal rise in reactive oxygen species (ROS) that leads to blindness in patients with diabetes mellitus (DM) and cataracts. In this study, the effects of dapagliflozin, metformin and resveratrol on ROS production were investigated in lens epithelial cells (LECs) of animals with fructose-induced DM. LECs were isolated from patients without DM, or with DM devoid of diabetic retinopathy. Animals were treated with 10% fructose for 8 weeks to induce DM, which was verified by monitoring blood pressure and serum parameters. For drug treatments, 1.2 mg/day of dapagliflozin was given for 2 weeks, 500 mg/kg/day of metformin was given, and 10 mg/kg/day of resveratrol was given. Dihydroethidium was used to stain endogenous O₂˙⁻ production in vivo of the LECs. Superoxide production was expressed in the cataract of DM, or patients without DM. Sodium–glucose cotransporter 2 (SGLT2), glucose transporter 1 (GLUT1), GLUT5, the reduced form of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunit p47/p67-phox, NOX4 and RAGE were significantly increased in LECs with DM. In addition, the dapagliflozin treatment reduced GLUT5, p47/p67-phox, NADPH oxidase 4 (NOX4) and receptor for advanced glycation end products (RAGE) expressions. On the contrary, metformin or resveratrol inhibited p47-phox, GLUT5, and SGLT2 expressions, but not nuclear factor erythroid 2–related factor 2 (NRF2). In summary, dapagliflozin, metformin or resveratrol down-regulated p47-phox expression through SGLT2 inactivation and ROS reduction. These important findings imply that SGLT2 can be blocked to ameliorate oxidative stress in the cataracts of DM patients.

Purpose: We evaluated the outcomes of fluid-gas exchange (FGE) for long-term flap closure of idiopathic macular hole (MH) after the inverted internal limiting (ILM) flap technique. Methods: We included eyes showed flap closure without complete MH closure, connection of the apart macular tissue, 1 month postoperatively after the inverted ILM flap technique. The eyes stayed at flap closure at 2 months postoperatively further underwent in-office FGE with 16% C3F8. Results: Among 10 eyes, 5 eyes (50%) showed flap closure at 2 months postoperatively further underwent FGE for complete MH closure while the remaining 5 eyes (50%) progressed directly at 2 months postoperatively. The improvement in vision of all flap closure from baseline was significant (p=0.015), with the mean baseline vision was 1.19 [Snellen equivalent (SE), 20/307] ± 0.52 logMAR and the mean final vision being 0.63 (SE, 20/85) ± 0.38 logMAR. The group that underwent FGE showed a better final vision of 0.45 (SE, 20/75) ± 0.23 logMAR than the group that didn’t undergo FGE (0.81 [SE, 20/128] ±0.44 logMAR). All eyes achieved complete MH closure, including the eyes that underwent FGE in a mean period of 5.60 months (range 3-10 months) after the inverted ILM flap technique. The eyes that underwent FGE achieved higher rate of foveal restoration [complete external limiting membrane (ELM): 80%; complete ellipsoid zone (EZ): 60%] than those that didn’t receive FGE (complete ELM: 40%; complete EZ: 10%). Conclusions: Eyes that underwent FGE accelerated complete MH closure and showed better final vision and fovea l restoration.

Studies demonstrated that the receptor of advanced glycation end products (RAGE) induced epithelial-mesenchymal transition (EMT) formation in the lens epithelial cells (LECs) of diabetic cataracts. This work investigated how 3H-1,2-dithiole-3-thione (D3T) reduces EMT formation in LECs of the fructose-induced diabetes mellitus (DM). LECs were isolated during cataract surgery from patients without DM or with DM. In a rat model, fructose (10% fructose, eight weeks) with or without D3T (10 mg/kg/day) treatment induced DM, as verified by blood pressure and serum parameter measurements. We observed that the formation of advanced glycation end products (AGEs) was significantly higher in epithelial human lens of DM (+) compared to DM (−) cataracts. Aldose reductase (AKR1B1), AcSOD2, and 3-NT were significantly enhanced in the rat lens epithelial sections of fructose-induced DM, however, the phosphorylation level of AMPK^T172 showed a reversed result. Interestingly, administration of D3T reverses the fructose-induced effects in LECs. These results indicated that AMPK^T172 may be required for reduced superoxide generation and the pathogenesis of diabetic cataract. Administration of D3T reverses the fructose-induced EMT formation the LECs of fructose-induced DM. These novel findings suggest that the D3T 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.

Background We evaluated the surgical outcomes of vitrectomy with non-fovea-sparing internal limiting membrane (ILM) peeling for myopic foveoschisis with a follow-up of at least 3 years. Methods In this retrospective study, 32 consecutive eyes with high myopia with or without foveal detachment underwent vitrectomy and centripetal, non-fovea-sparing ILM peeling with gas tamponade for myopic foveoschisis. Outcome measures were visual acuity (VA) and optical coherence tomography findings. Results Mean axial length was 29.39±1.92 mm; mean follow-up was 42.66 (±8.29) months. Foveoschisis and foveal detachment completely resolved in all eyes postoperatively. Mean central foveal thickness (CFT) improved significantly from 631.88±191.72 to 232.65±69.67 µm, and mean best-corrected visual acuity improved significantly from 0.90 (Snellen equivalent (SE), 20/160)±0.43 logarithm of minimum angle of resolution (logMAR) to 0.43 (SE, 20/54)±0.29 logMAR (both pConclusion Centripetal, non-fovea-sparing ILM peeling with gas tamponade may achieve myopic foveoschisis resolution and vision improvement without macular hole formation during at least 3-year follow-up.

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.

To evaluate changes in the microcirculation of various retinal layers and choroid following successful repair of macula-off rhegmatogenous retinal detachment (RRD) using optical coherence tomography angiography (OCTA).

To report our 3-year experience of 23-gauge transconjunctival sutureless vitrectomy (TSV) for acute postoperative endophthalmitis at a tertiary referral center in southern Taiwan. This retrospective chart review study included 19 patients with acute postoperative endophthalmitis who underwent 23-gauge TSV from January 2011 to January 2015 at Kaohsiung Veterans General Hospital, Taiwan. Bacterial and fungal cultures from aqueous samples, vitreous samples, or both were performed. Nineteen patients (12 male; 7 female) were included. The mean age was 72.4 ± 8.29 years. Acute postoperative endophthalmitis was noted in 18 patients after cataract surgery and in 1 patient after 23-gauge vitrectomy for a rhegmatogenous retinal detachment. Upon presentation, visual acuity was less than hand movement for 80% of the patients. Chief complaints included blurred vision (19 patients, 100%), followed by pain (10 patients, 52.6%) and red eye (4 patients, 21%). All patients were administered an intravitreal injection (IVI) of antibiotics and 23-gauge TSV, and the average number of IVIs was 2.68 ± 1.73 (1-9 IVIs). The interval between their initial eye symptoms and vitrectomy was 4.11 ± 4.73 days (0-2 days), and the interval between diagnosis with endophthalmitis and a vitrectomy was 1.11 ± 1.52 days (0-6 days). The final visual acuity was no light perception for 1 patient (5.3%), between 6/60 and 6/12 for 8 patients (42.1%), and 6/12 or better for 9 patients (47.4%). No retinal detachment or hypotony was noted postoperatively in any case. 23-gauge vitrectomy is safe and effective for the management of acute postoperative endophthalmitis. Early diagnosis and treatment with 23-gauge vitrectomy may provide a good visual outcome.

Purpose: To evaluate and compare the 12‐month outcomes of two different initial dosing regimens of intravitreal ranibizumab for myopic choroidal neovascularization (CNV).Methods: We retrospectively reviewed the medical records of 46 consecutive, treatment‐naive eyes which received intravitreal ranibizumab for subfoveal and juxtafoveal CNV secondary to pathologic myopia with a follow‐up of 12 months. Two groups were created according to different initial dosing regimens: group 1 included 25 eyes treated by a single intravitreal injection; group 2 included 21 eyes treated by three consecutive monthly injections. Additional injections were performed if needed. Patients' demographic data, best‐corrected visual acuity (BCVA), recurrence of CNV and total number of treatments were recorded and evaluated.Results: There was no significant difference between two groups among baseline demographic data. At 12 months, the mean logMAR BCVA improved from 0.58 to 0.23 in group 1 and from 0.55 to 0.22 in group 2 (both p < 0.001; Wilcoxon signed‐rank test). The mean logMAR BCVA at 12 months did not differ significantly. The average number of injections was 2.32 (SD 1.22) in group 1 and 3.57 (SD 1.12) in group 2 (p = 0.001; two‐tailed t‐test). During the follow‐up, 17 of 25 eyes in group 1 and 5 of 21 eyes in group 2 received additional injections (p = 0.004).Conclusions: Similar visual improvement was achieved in both groups. Although the eyes with a loading dose of 3 monthly injections required a higher number of total injections over 1 year, there was a much lower rate of retreatment needed.

Purpose: We sought to evaluate the effects of intraoperative adjunctive autologous serum in idiopathic full-thickness macular hole surgeries, and to compare the surgical outcomes with a no-serum control group. Methods: In this retrospective, case–control study, 38 consecutive eyes received vitrectomy with internal limiting membrane removal for idiopathic full-thickness macular holes. Two groups were created according to the use of autologous serum. Outcome measures were visual acuity (VA), closure of the macular hole confirmed by optical coherence tomography, and surgical complications. Results: Anatomical closure of the macular hole was achieved in 18 of 19 eyes (94.7%) in the vitrectomy with the autologous serum group, and in 18 of 19 eyes (94.7%) in the control group. The closure rates did not differ significantly between 2 groups (P=1.000; the Fisher's exact test). At the final follow-up, the mean logMAR VA improved significantly in both groups (SD, standard deviation) [from 1.08 (0.21) to 0.47 (0.21) in vitrectomy with the serum group and from 1.01 (0.32) to 0.44 (0.30) in the control group (both Pt test)]. There was no significant difference between these 2 groups in terms of visual outcomes (P=0.738; 2-tailed t test). There were no surgical complications, such as retinal detachment and endophthalmitis. Conclusions: The outcome of macular hole surgery did not differ both anatomically and functionally regardless of the use of adjuvant autologous serum. There seemed to be no additive effect with autologous serum.