The Impact of Hyperglycemia on VEGF Secretion in Retinal Endothelial Cells

AbstractBackground:Diabetic retinopathy is a serious sight-threatening complication which is manifested by excessive angiogenesis in diabetic patients.Aim:We hypothesize that cultured Rhesus monkey retinal endothelial cells (RhRECs) respond to high glucose with a change in cell proliferation and vascular endothelial growth factor (VEGF) secretion.Materials and methods:In our study, 20 000 cells per well were treated without glucose or with 5.5 mM, 18.5 mM and 30 mM glucose for 24 hours. Viable cells were counted using trypan blue dye exclusion method. VEGF concentrations were measured in cell media by ELISA method.Results:The number of viable cells incubated with 5.5 mM glucose increased significantly by 53.7% after 24 hours. In comparison, the number of viable cells decreased by 2.8% at 18.5 mM of glucose and by 20.4% at 30 mM of glucose after 24 hours of incubation. In contrast to this effect of glucose on the number of viable cells, a significant increase in VEGF levels (pg/mL) in the cell media with a glucose concentration of 0 mM compared to 5.5 mM of glucose was found. VEGF secretion in cell medium with 18.5 and 30 mM of glucose increased non-significantly in comparison with euglycemic levels.Conclusion:Our results show that viability of retinal endothelial cells and VEGF release are highly responsive to changes in glucose concentration. Such glucose-induced changes in retinal endothelial cells may negatively impact the integrity of the microvasculature in the diabetic retina leading to angiogenesis and microaneursym.</jats:p

An international collaborative evaluation of central serous chorioretinopathy: different therapeutic approaches and review of literature. The European Vitreoretinal Society central serous chorioretinopathy study

Purpose: To study and compare the efficacy of different therapeutic options for the treatment of central serous chorioretinopathy (CSCR). Methods: This is a nonrandomized, international multicentre study on 1719 patients (1861 eyes) diagnosed with CSCR, from 63 centres (24 countries). Reported data included different methods of treatment and both results of diagnostic examinations [fluorescein angiography and/or optical coherent tomography (OCT)] and best-corrected visual acuity (BCVA) before and after therapy. The duration of observation had a mean of 11&nbsp;months but was extended in a minority of cases up to 7&nbsp;years. The aim of this study is to evaluate the efficacy of the different therapeutic options of CSCR in terms of both visual (BCVA) and anatomic (OCT) improvement. Results: One thousand seven hundred nineteen patients (1861 eyes) diagnosed with CSCR were included. Treatments performed were nonsteroidal anti-inflammatory eye drops, laser photocoagulation, micropulse diode laser photocoagulation, photodynamic therapy (PDT; Standard PDT, Reduced-dose PDT, Reduced-fluence PDT), intravitreal (IVT) antivascular endothelial growth factor injection (VEGF), observation and other treatments. The list of the OTHERS included both combinations of the main proposed treatments or a variety of other treatments such as eplerenone, spironolactone, acetazolamide, beta-blockers, anti-anxiety drugs, aspirin, folic acid, methotrexate, statins, vitis vinifera extract medication and pars plana vitrectomy. The majority of the patients were men with a prevalence of 77%. The odds ratio (OR) showed a partial or complete resolution of fluid on OCT with any treatment as compared with observation. In univariate analysis, the anatomical result (improvement in subretinal fluid using OCT at 1&nbsp;month) was favoured by age &lt;60&nbsp;years (p&nbsp;&lt;&nbsp;0.005), no previous observation (p&nbsp;&lt;&nbsp;0.0002), duration less than 3&nbsp;months (p&nbsp;&lt;&nbsp;0.0001), absence of CSCR in the fellow eye (p&nbsp;=&nbsp;0.04), leakage outside of the arcade (p&nbsp;=&nbsp;0.05) and fluid height &gt;500&nbsp;\u3bcm (p&nbsp;=&nbsp;0.03). The OR for obtaining partial or complete resolution showed that anti-VEGF and eyedrops were not statistically significant; whereas PDT (8.5), thermal laser (11.3) and micropulse laser (8.9) lead to better anatomical results with less variability. In univariate analysis, the functional result at 1&nbsp;month was favoured by first episode (p&nbsp;=&nbsp;0.04), height of subretinal fluid &gt;500&nbsp;\u3bcm (p&nbsp;&lt;&nbsp;0.0001) and short duration of observation (p&nbsp;=&nbsp;0.02). Finally, there was no statistically significant difference among the treatments at 12&nbsp;months. Conclusion: Spontaneous resolution has been described in a high percentage of patients. Laser (micropulse and thermal) and PDT seem to lead to significant early anatomical improvement; however, there is little change beyond the first month of treatment. The real visual benefit needs further clarification

Vision-Related Quality of Life in Patients with Diabetic Macular Edema Treated with Intravitreal Aflibercept: The AQUA Study

Purpose: To examine vision-related quality of life in patients with diabetic macular edema (DME) treated with intravitreal aflibercept (EYLEA, Regeneron Pharmaceuticals, Inc, Tarrytown, NY). Design: AQUA was a multicenter, open-label, single-arm, phase 4 study. Participants: Adults 18 years of age or older with type 1 or 2 diabetes mellitus and DME. Methods: Patients received intravitreal aflibercept 2 mg every 8 weeks for 52 weeks, after 5 initial doses every 4 weeks. Main Outcome Measures: The primary outcome was the change in 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25) total score from baseline to week 52. Secondary outcomes included the change in NEI VFQ-25 near and distant activities subscale scores, best-corrected visual acuity (BCVA; Early Treatment Diabetic Retinopathy Study [ETDRS] letters), and central retinal thickness (CRT) from baseline to week 52. Change in NEI VFQ-25 score at week 52 for better-seeing eyes (BSEs) and worse-seeing eyes (WSEs) also was evaluated. Results: A total of 553 patients comprised the full analysis set, and 560 patients comprised the safety analysis set. At baseline, the mean NEI VFQ-25 total score was 70.12, mean BCVA was 61.5 ETDRS letters, and mean CRT was 464.81 \u3bcm. A mean of 8.8 injections were administered over 52 weeks. At week 52, the mean improvement from baseline in the NEI VFQ-25 total score was +6.11 (standard deviation [SD], 11.46); the corresponding improvements in near and distant activities were +11.37 (SD, 18.01) and +7.33 (SD, 17.32), respectively. Similarly, improvements in patients whose BSE and WSE were treated were 7.74 (SD, 13.59) and 5.48 (SD, 9.70), respectively. At week 52, mean change in BCVA was +10.0 ETDRS letters (SD, 8.0 ETDRS letters), and mean change in CRT was \u2013175.38 \u3bcm (SD, 132.62 \u3bcm). Overall, 53.6% of patients reported treatment-emergent adverse events (TEAEs), of whom 26.8% experienced an ocular TEAE in the study eye. The most common serious ocular TEAE was endophthalmitis (0.5% [n = 3]). Five deaths (0.9%) were reported, but were not considered treatment related. Conclusions: Intravitreal aflibercept was associated with clinically meaningful improvements in NEI VFQ-25 total score over 52 weeks in patients with DME; these were even more pronounced for near than for distant activities. Adverse events were consistent with the known safety profile of intravitreal aflibercept

A noninterventional study to monitor patients with diabetic macular oedema starting treatment with ranibizumab (POLARIS)

Purpose: Antivascular endothelial growth factor agents are increasingly used in diabetic macular oedema (DME); however, there are few studies exploring their use in DME in real-world settings. Methods: POLARIS was a noninterventional, multicentre study to monitor 12-month outcomes in patients starting ranibizumab treatment in routine practices. The primary outcome was mean change in visual acuity (VA) from baseline to month 12 (last observation carried forward approach). Other outcomes included mean change in central retinal thickness (CRT) and resource utilization. Visual acuity (VA) outcomes were also stratified by country, baseline visual acuity score (VAS), sex, age and injection frequency. Results: Outcomes were analysed from all treated patients (n = 804) and from first-year completers (patients who had a visual acuity assessment at 12 months; n = 568). The mean (SD) baseline VAS was 59.4 (15.9) letters, and the mean change in visual acuity was 4.4 letters (95% confidence interval: 3.3–5.4) at month 12 (study eye; first-year completers). The mean number of injections (study eye) was 4.9, and the mean number of all visits (any eye) was 10 (58% were injection visits) over 12 months (first-year completers). The mean (SD) baseline CRT was 410.6 (128.8) μm, and the mean change in CRT was −115.2 μm at month 12 (study eye; first-year completers). Visual acuity (VA) outcomes were generally comparable across most countries and subgroups and were greatest in patients with the lowest baseline VAS (≤60 letters). Conclusion: POLARIS showed that real-world outcomes in DME patients starting treatment with ranibizumab were lower than those observed in clinical studies, in spite of extensive monitoring.</p

A noninterventional study to monitor patients with diabetic macular oedema starting treatment with ranibizumab (POLARIS)

Purpose: Antivascular endothelial growth factor agents are increasingly used in diabetic macular oedema (DME); however, there are few studies exploring their use in DME in real-world settings. Methods: POLARIS was a noninterventional, multicentre study to monitor 12-month outcomes in patients starting ranibizumab treatment in routine practices. The primary outcome was mean change in visual acuity (VA) from baseline to month 12 (last observation carried forward approach). Other outcomes included mean change in central retinal thickness (CRT) and resource utilization. Visual acuity (VA) outcomes were also stratified by country, baseline visual acuity score (VAS), sex, age and injection frequency. Results: Outcomes were analysed from all treated patients (n = 804) and from first-year completers (patients who had a visual acuity assessment at 12 months; n = 568). The mean (SD) baseline VAS was 59.4 (15.9) letters, and the mean change in visual acuity was 4.4 letters (95% confidence interval: 3.3–5.4) at month 12 (study eye; first-year completers). The mean number of injections (study eye) was 4.9, and the mean number of all visits (any eye) was 10 (58% were injection visits) over 12 months (first-year completers). The mean (SD) baseline CRT was 410.6 (128.8) μm, and the mean change in CRT was −115.2 μm at month 12 (study eye; first-year completers). Visual acuity (VA) outcomes were generally comparable across most countries and subgroups and were greatest in patients with the lowest baseline VAS (≤60 letters). Conclusion: POLARIS showed that real-world outcomes in DME patients starting treatment with ranibizumab were lower than those observed in clinical studies, in spite of extensive monitoring. © 2018 The Authors. Acta Ophthalmologica published by John Wiley &amp; Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation

Strategy for the management of complex retinal detachments: the European vitreo-retinal society retinal detachment study report 2

OBJECTIVE: To study the outcome of the treatment of complex rhegmatogenous retinal detachments (RRDs). DESIGN: Nonrandomized, multicenter, retrospective study. PARTICIPANTS: One hundred seventy-six surgeons from 48 countries spanning 5 continents reported primary procedures for 7678 RRDs. METHODS: Reported data included clinical manifestations, the method of repair, and the outcome. MAIN OUTCOME MEASURES: Failure of retinal detachment repair (level 1 failure rate), remaining silicone oil at the study's conclusion (level 2 failure rate), and need for additional procedures to repair the detachments (level 3 failure rate). RESULTS: The main categories of complex retinal detachments evaluated in this investigation were: (1) grade B proliferative vitreoretinopathy (PVR; n = 917), (2) grade C-1 PVR (n = 637), (3) choroidal detachment or significant hypotony (n = 578), (4) large or giant retinal tears (n = 1167), and (5) macular holes (n = 153). In grade B PVR, the level 1 failure rate was higher when treated with a scleral buckle alone versus vitrectomy (P = 0.0017). In grade C-1 PVR, there was no statistically significant difference in the level 1 failure rate between those treated with vitrectomy, with or without scleral buckle, and those treated with scleral buckle alone (P = 0.7). Vitrectomy with a supplemental buckle had an increased failure rate compared with those who did not receive a buckle (P = 0.007). There was no statistically significant difference in level 1 failure rate between tamponade with gas versus silicone oil in patients with grade B or C-1 PVR. Cases with choroidal detachment or hypotony treated with vitrectomy had a significantly lower failure rate versus treatment with scleral buckle alone (P = 0.0015). Large or giant retinal tears treated with vitrectomy also had a significantly lower failure rate versus treatment with scleral buckle (P = 7×10(-8)). CONCLUSIONS: In patients with retinal detachment, when choroidal detachment, hypotony, a large tear, or a giant tear is present, vitrectomy is the procedure of choice. In retinal detachments with PVR, tamponade with either gas or silicone oil can be considered. If a vitrectomy is to be performed, these data suggest that a supplemental buckle may not be helpful. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article