Real-World Outcomes of Intravitreal Anti-Vascular Endothelial Growth Factor Treatment for Diabetic Macular Edema in Türkiye: MARMASIA Study Group Report No. 1.

Objectives: This study aimed to report the demographic and clinical characteristics of diabetic macular edema (DME) patients treated with intravitreal injection (IVI) of anti-vascular endothelial growth factors (anti-VEGF) and provide an overview of outcomes during routine clinical practice in Türkiye. Materials and Methods: This retrospective, real-world study included 1,372 eyes (854 patients) treated with a pro re nata protocol by 21 ophthalmologists from 8 tertiary clinics on the Asian side of the Marmara region of Türkiye (MARMASIA Study Group). Five cohort groups were established by collecting the patients' baseline and 3, 6, 12, 24, and 36-month follow-up data, where each subsequent cohort may include the previous. Changes in best-corrected visual acuity (BCVA, approximate ETDRS letters) and central macular thickness (CMT, µm), number of visits and IVI, and rates of anti-VEGF switch and intravitreal dexamethasone implant (IDI) combination were evaluated. Results: The 3, 6, 12, 24, and 36-month cohorts included 1372 (854), 1352 (838), 1185 (722), 972 (581), and 623 (361) eyes (patients), respectively. The mean baseline BCVA and CMT were 51.4±21.4 letters and 482.6±180.3 µm. The mean changes from baseline in BCVA were +7.6, +9.1, +8.0, +8.6, and +8.4 letters, and in CMT were -115.4, -140.0, -147.9, -167.3, and -215.4 µm at the 3, 6, 12, 24, and 36-month visits (p<0.001 for all). The median cumulative number of anti-VEGF IVI was 3.0, 3.0, 5.0, 7.0, and 9.0, respectively. The overall anti-VEGF switch and IDI combination rates were 18.5% (253/1372 eyes) and 35.0% (480/1372 eyes), respectively. Conclusion: This largest real-life study of DME from Türkiye demonstrated BCVA gains inferior to randomized controlled trials, mainly due to the lower number of IVI. However, with the lower baseline BCVA and higher IDI combination rates in our cohorts, these gains were relatively superior to other real-life study counterparts.

The effects of crocetin on oxidative stress induced ARPE-19 cells by H2O2.

The anti-apoptotic and antioxidant effects of crocetin was aimed to investigate on the oxidative damage model of ARPE-19 cells. The oxidative damage in ARPE cells was developed by H2O2 treatment at 800 µM. Different doses of crocetin (1-80 µM) were applied for 24 h, and the effects on viability were evaluated to find out the optimum drug dose. At first, three effective doses of crocetin (10, 20, 40 µM) on cell viability were selected for further analyses. The levels of superoxide dismutase (SOD), malondialdehyde (MDA) and glutathione (GSH) were determined, and the expression of pro-apoptotic Bax gene and anti-apoptotic Bcl-2 gene were evaluated. The most effective crocetin dose on cell viability was found to be 10 µM. After the H2O2 treatment, SOD and GSH were decreased and MDA were increased significantly (p = 0.011, 0.037, 0.018, respectively). Following the crocetin treatment at 10 µM, SOD and GSH activities were improved compared to the no drug group; and MDA level was declined remarkably (p = 0.022, 0.019, 0.029, respectively). The Bcl-2 level was significantly decreased (p < 0.01), while the Bax1 and Nrf2 expression and ROS level was increased significantly in the damage model group (p < 0.01). After the drug treatment, the Bax1 and Nrf2 expression level were decreased in all groups (p < 0.01). The increase in Bcl-2 expression was significant in crocetin 40 µM (p < 0.05) and the decrease in ROS level were significant in 20 µM and 40 µM doses of crocetin (p < 0.05). It has been shown that crocetin might be used as an antioxidant and anti-apoptotic agent on the hindering the effect of the oxidative damage. Following the development of the oxidative stress in the cells, crocetin reversed the damage signals. By the in vitro tests, it was shown that crocetin might be considered as an effective molecule to be used in the AMD treatment.

Comparison of before versus after intravitreal bevacizumab injection, growth factor levels and fibrotic markers in vitreous samples from patients with proliferative diabetic retinopathy.

PURPOSE: In diabetic retinopathy patients, intravitreal bevacizumab (IVB) injections are widely used to facilitate dissection of retinal fibrovascular membranes during surgery, reduce the rate of perioperative hemorrhage, and prevent recurrent neovascularization. Previous studies have shown that IVB may worsen fibrosis and thereby impair vision. The aim of this study was to determine which markers are associated with fibrosis. METHODS: Twenty-three patients with proliferative diabetic retinopathy (PDR) underwent pars plana vitrectomy (PPV) with IVB pretreatment for intraocular hemorrhage (IOH) and/or tractional retinal detachment (TRD). Vitreous samples were obtained at the time of IVB injection and again at the beginning of PPV, about a week later. Using Western blot analysis, the concentrations of vascular endothelial growth factor (VEGF), placental growth factor (PIGF), insulin like growth factor-1 (IGF-1), angiogenin-1 (Ang-1), and vascular endothelial cadherin (VE-cadherin) were measured in vitreous samples. RESULTS: After treatment with IVB, VEGF, PIGF, and VE-cadherin concentrations in the vitreous significantly decreased (p < 0.001, p < 0.001, and p = 0.001, respectively), whereas the concentrations of IGF-1 increased (p = 0.001). There were no significant changes in Ang-1 concentrations in the vitreous after IVB injection (p = 0.732). There were no statistically significant differences in VEGF-A, PIGF, VE-cadherin, IGF, and Ang-1 levels before and after IVB injection when the IOH and TRD groups underwent subgroup analysis (p = 0.696, p = 0.516, p = 0.498, p = 0.188, and p = 0.243, respectively). CONCLUSION: The levels of VEGF and other cytokines changed in the vitreous after IVB. The adverse effects associated with IVB, such as fibrosis, may result from modulation of vitreous cytokine concentrations. In the treatment of PDR, drugs that optimize the effects of PIGF, IGF-1, and VE-cadherin to reduce these side effects may be useful.

Do serum vitamin D levels correlate with Macular Edema or with Diabetic Retinopathy?

PURPOSE: To compare serum vitamin D (25(OH)D) levels according to the presence of diabetic macular edema (DME) in Diabetes Mellitus (DM) patients with different retinopathy conditions. METHODS: The files of all DM patients presenting for examination at the ophthalmology clinic between October 2018 and March 2020 were retrospectively examined. Data was collected from the files and included a comprehensive ophthalmological examination, laboratory results from fasting blood tests, and the internal medicine outpatient clinic examination. Patients were divided into two groups according to the presence of DME, they were divided into three groups in terms of retinopathy and DME, and in terms of retinopathy severity and presence of DME, they were divided into five groups. RESULT: Ninety one (51.1%) of the age-sex matched participants were female and 87 (48.9%) were male. There was a statistically significant difference in vitamin D levels between the group with DME and the group without DME (p ≤ 0.001). In the comparison made according to the presence of retinopathy and DME; a significant difference was found between the DME group and the group with retinopathy but no DME (p ≤ 0.001). When the severity of retinopathy and the presence of DME were evaluated, a significant difference was found between the proliferative diabetic retinopathy (PDR) group with DME and the PDR group without DME in terms of vitamin D levels (p = 0.004). CONCLUSION: Our study shows that the presence of DME is associated with lower serum 25(OH)D levels.

Limited Vitrectomy in Patients with Idiopathic Macular Hole

Background: Partial posterior hyaloidectomy is suggested to minimize traction on the vitreous base and thus reduce the risk of iatrogenic breaks in patients with macular hole and epiretinal membrane. Aims: To evaluate the safety and efficacy of limited vitrectomy in patients with macular hole. Study Design: Retrospective cohort study. Methods: Fifty-two consecutive patients who underwent macular hole surgery without complete peripheral vitreous removal were included in the study. The improvement in visual acuity, the incidence of retinal breaks and detachment, anatomical results, and intraoperative and postoperative complications of this technique were evaluated. Results: The median visual acuity was 0.2 (0.1-0.4) before surgery and 0.5 (0.3-0.6) after surgery (p<0.001). None of the patients had retinal breaks or detachments. A sulfur hexafluoride was used in 24 patients (46.2%), and perfluoropropane was used in 28 patients (53.8%). Three patients (5.76%) had revision surgery because of recurrence of the macular hole. We did not observe proliferative vitreoretinopathy or surgery-related major complications in any patient during the follow-up period. Conclusion: Limited vitrectomy without removal of the peripheral vitreous seems to be effective and safe with minimal risk of peripheral retinal breaks and detachment.