Incidence of diabetic retinopathy in anti-tnf treated rheumatic disease patients with type 2 diabetes.

OBJECTIVE: This study aimed to evaluate the impact of anti-TNF (biological) therapies on the incidence and progression of diabetic retinopathy. MATERIALS AND METHODS: A cross-sectional analysis of 50 diabetic patients with rheumatic diseases (group 1) was performed. An age-, sex-, and HbA1c-matched control group (group 2) was formed from a pool of diabetic patients who underwent regular eye examinations. The presence or absence of diabetic retinopathy was also assessed. Comorbidities such as hypertension, coronary artery disease, and hyperlipidemia were also evaluated as possible confounding factors. RESULTS: Hundred eyes of 50 patients were evaluated in each group. Only three patients in group 1 had non-proliferative retinopathy. The median duration of rheumatic disease was 9 years, whereas that of diabetes was 11 years. The mean duration of anti-TNF therapy was 4 years. In the control group of diabetes-only patients, 13 patients developed some form of newly diagnosed diabetic retinopathy during the last five years. The calculated retinopathy occurrence between the groups was statistically significant (p < 0.05). In this study, the incidence rate ratio for patients receiving anti-TNF treatment was calculated as 0.4 in the study. CONCLUSION: TNF inhibitors, with their anti-inflammatory effects, positively impact diabetic complications by reducing the incidence of retinopathy. To our knowledge, this is the first study to evaluate retinopathy development after anti-TNF therapy.

The effects of loading ranibizumab on vision-related quality of life in the treatment of low-risk neovascular age-related macular degeneration.

Background: The loss of central vision plays a major role in the quality of life (QoL). This study evaluates the changes in QoL in the treatment of low-risk neovascular age-related macular degeneration (AMD). Objectives: The aim of this study was to evaluate the changes in vision-related QoL in patients receiving intravitreal ranibizumab loading dose for low-risk neovascular AMD. Design: A prospective study. Methods: Forty-two eyes of 42 patients receiving ranibizumab injections for neovascular AMD were included in this prospective study. The changes in best-corrected visual acuity (BCVA), central macular thickness (CMT) of the patients before the treatment, and 1 month after three loading doses were evaluated. Turkish version of the National Eye Institute 25-Item Vision Function Questionnaire (NEI VFQ-25 TR) was conducted. The changes of QoL scores through the NEI VFQ-25 TR questionnaire were compared with visual acuity (VA) and CMT measurements before the injections and 1 month after the loading dose. Results: Forty-two patients (19 females and 23 males) were included in the study, and the mean age was 72.69 ± 7.12 years. After the treatment, a statistically significant improvement in BCVA (0.98 ± 0.44, 0.76 ± 0.42 logMAR, p < 0.001) and a significant decrease in CMT (357.90 ± 71.71, 274.50 ± 58.35 µm, p < 0.001) was observed. The QoL composite score was found to be statistically significantly higher after the treatment (64.27 ± 11.47, 68.56 ± 11.39, p < 0.001). General vision (p < 0.001), ocular pain (p = 0.025), near activities (p < 0.001), distance activities (p = 0.027), vision-specific mental health (p = 0.014), vision-specific role difficulties (p < 0.001), and peripheral vision (p = 0.046) were significantly higher after the treatment. Conclusion: NEI VFQ-25 TR is a useful questionnaire for evaluating changes in visual functions and psychosocial characteristics of low-risk neovascular AMD patients before and after the injections.

Carvacrol protects the ARPE19 retinal pigment epithelial cells against high glucose-induced oxidative stress, apoptosis, and inflammation by suppressing the TRPM2 channel signaling pathways.

PURPOSE: The concentration of plasma high glucose (HGu) in diabetes mellitus (DM) induces the retinal pigment epithelial cell (ARPE19) death via the increase of inflammation, cytosolic (cytROS), and mitochondrial (mitROS) free oxygen radical generations. Transient potential melastatin 2 (TRPM2) cation channel is stimulated by cytROS and mitROS. Hence, the cytROS and mitROS-mediated excessive Ca2+ influxes via the stimulation of TRPM2 channel cause to the induction of DM-mediated retina oxidative cytotoxicity. Because of the antioxidant role of carvacrol (CRV), it may modulate oxidative cytotoxicity via the attenuation of TRPM2 in the ARPE19. We aimed to investigate the modulator action of CRV treatment on the HGu-mediated TRPM2 stimulation, oxidative stress, and apoptosis in the ARPE19 cell model. MATERIAL AND METHODS: The ARPE19 cells were divided into four groups as normal glucose (NGu), NGu + Carv, HGu, and HGu + CRV. RESULTS: The levels of cell death (propidium iodide/Hoechst rate) and apoptosis markers (caspases 3, 8, and 9), cytokine generations (IL-1ß and TNF-α), ROS productions (cytROS, mitROS, and lipid peroxidation), TRPM2 currents, and intracellular free Ca2+ (Fluo/3) were increased in the HGu group after the stimulations of hydrogen peroxide and ADP-ribose, although their levels were diminished via upregulation of glutathione and glutathione peroxidase by the treatments of CRV and TRPM2 blockers. CONCLUSION: Current results confirmed that the HGu-induced overload Ca2+ influx and oxidative retinal toxicity in the ARPE19 cells were induced by the stimulation of TRPM2, although they were modulated via the inhibition of TRPM2 by CRV. CRV may be noted as a potential therapeutic antioxidant to the TRPM2 activation-mediated retinal oxidative injury.

Rituximab Attenuated Lipopolysaccharide-Induced Oxidative Cytotoxicity, Apoptosis, and Inflammation in the Human Retina Cells via Modulating the TRPM2 Signaling Pathways.

PURPOSE: We investigated the possible protective effects of rituximab (RTX) on LPS-induced oxidant, inflammatory, and apoptotic adverse actions via the inhibition of TRPM2 channel in the adult retinal pigment epithelial-19 (ARPE-19) cells. METHODS: In the cultured ARPE-19 cells, we induced five main groups as control, RTX (10 µg/ml), LPS (1 µg/ml), LPS+RTX, and LPS+TRPM2 blockers (ACA or 2/APB). RESULTS: The levels of apoptosis, cell death, mitochondrial free reactive oxygen radicals (mitROS), cytosolic ROS, lipid peroxidation, caspase -3, caspase -8, caspase -9, ADP-ribose-induced TRPM2 current density, TNF-α, IL-1ß, cytosolic free Zn2+, and Ca2+ were increased by LPS, although their levels were diminished by the treatments of RTX and TRPM2 blockers. CONCLUSIONS: The LPS-induced mitROS, inflammatory cytokine, and apoptosis levels were modulated via TRPM2 inhibition in the human retinal epithelial cells by the RTX treatment. The RTX may be considered as a new therapeutic approach to LPS-induced human retinal epithelial cell injury.

Selenium and Resveratrol Attenuated Diabetes Mellitus-Mediated Oxidative Retinopathy and Apoptosis via the Modulation of TRPM2 Activity in Mice.

Diabetes mellitus induces optic nerve injury via the excessive generation of mitochondria reactive free oxygen radical (mitROS). TRPM2 channel is activated by mitROS, although it is inhibited by selenium (Se) and resveratrol (RSV). The activation of TRPM2 induces apoptosis and oxidative injury in the optic nerve. The inhibition of TRPM2 may decrease the optic nerve injury action of diabetes mellitus after the treatments of Se and RSV. Present study aimed to investigate the protective actions of Se and RSV on the excessive Ca2+ influx and mitROS generation-mediated optic nerve oxidative injury via the modulation of TRPM2. Fifty-six C57BL/6j male mice were divided into seven groups as control, Se, RSV, streptozotocin (STZ), STZ + Se, STZ + RSV, and STZ + Se + RSV. The STZ-mediated stimulation of TRPM2 increased the cytosolic Ca2+, lipid peroxidation, mitROS, cytosolic ROS, apoptosis, caspase-3, caspase-8, and caspase-9 concentrations in the mice, although their concentrations were decreased in the optic nerve by the treatments of Se and RSV. The STZ-induced decrease of optic nerve viability, glutathione, glutathione peroxidase, vitamin A, and vitamin E concentrations was also upregulated by the treatments of Se and RSV. The STZ-induced increase of TRPM2, PARP-1, caspase-3, and caspase-9 protein band expressions was diminished by the treatments of Se and RSV. In conclusion, STZ induced the optic nerve oxidative injury and apoptosis via the upregulation of TRPM2 stimulation, although the treatments of Se and RSV decreased the injury and apoptosis via the downregulation of TRPM2 activity.

Effects of the Presence of Pseudoexfoliation on Intraocular Pressure and Retinal Nerve Fiber Layer Thickness in Patients with Macular Degeneration Receiving Intravitreal Ranibizumab.

AIMS: In the present study, we aimed to compare the effect of intravitreal ranibizumab (IVR) treatment on intraocular pressure (IOP) and retinal nerve fiber layer (RNFL) thickness in patients with age-related macular degeneration (AMD) with and without pseudoexfoliation (PEX). MATERIALS AND METHODS: A total of 24 patients, 12 with PEX (12 eyes) and 12 without PEX (12 eyes), receiving IVR treatment for neovascular AMD between June 2017 and June 2019, were included in the study. Exclusion criteria were composed of the history of glaucoma, uveitis, intravitreal steroid administration, pars plana vitrectomy surgery, and less than three IVR injections. Such criteria as age, gender, follow-up times, number of injections administered, IOP, and RNFL thickness before the first injection and one month after the last injection were also recorded. RESULTS: Age, gender, follow-up time, and the number of injections were similar in groups with and without PEX (p > 0.05). While mean post-treatment IOP values were not significantly higher in the PEX group (14.50 ± 3.06 vs. 12.91 ± 1.83 mmHg, p = 0.065), the values were significant for the non-PEX group (13.25 ± 2.76 vs. 11.83 ± 2.69 mmHg, p = 0.01), and these values were within normal IOP limits. Additionally, RNFL thickness was significantly thinner after treatment in both groups (91.41 ± 7.14 vs. 94.00 ± 6.76 in those with PEX; 95.58 ± 5.91 vs. 97.66 ± 6.89 in those without PEX; p < 0.05). The decrease in RNFL thickness in the PEX group was 2.58 ± 1.62 µ and in the non-PEX group was 2.08 ± 1.98 µ. However, there was no statistically significant difference between the two groups in terms of RNFL thinning (p = 0.505). DISCUSSION: Ranibizumab may reduce RNFL thickness in patients with PEX. Longer-term studies including larger populations are necessary for understanding IOP and RNFL changes after anti-vascular endothelial growth factor (anti-VEGF) injection.

The Effect of Ranibizumab Loading Treatment on Vision-Related Quality of Life in Diabetic Macular Edema.

AIMS: To investigate the changes in vision-related quality of life after a loading dose of three consecutive intravitreal ranibizumab (IVR) injections in patients with unilateral diabetic macular edema (DME). MATERIALS AND METHODS: Fifty-two eyes of 52 patients who received IVR injections in only one eye with DME were included in our study. The following characteristics of the patients were recorded: gender, education status, marital status, work status, presence of chronic disease. The changes in best-corrected visual acuity (BCVA) and central macular thickness (CMT) were evaluated at baseline (before treatment) and 1 month after the third intravitreal injection (after treatment). Patients were administered the Turkish form of the National Eye Institute 25-Item Visual Functions Questionnaire (NEI VFQ-25 TR). The quality of life scores assessed by the NEI VFQ-25 TR, the BCVA, intraocular pressure (IOP), and CMT measurements were compared at baseline (before treatment) and 1 month after the third intravitreal injection (after treatment). RESULTS: We enrolled 52 patients (25 females, 27 males) in our study; mean age was 64.35 ± 9.26 years. After treatment, BCVA improved significantly (p = 0.001), and macular thickness decreased significantly (p < 0.001). All NEI VFQ-25 TR subscale scores were significantly higher after treatment (p < 0.05). However, no significant correlation was found between the change in BCVA and CMT and the change in NEI VFQ-25 TR subscale and composite scores. The increase in near activities scores was significantly higher in males (p = 0.020) and in the retired group (p = 0.022). There were no significant differences in the changes in NEI VFQ-25 TR subscale and composite scores in relation to educational status. DISCUSSION: Significant improvements in BCVA, macular edema, and vision-related quality of life were found in DME patients who received IVR injections with a loading dose, as shown by the NEI VFQ-25 TR. Interestingly, a significant improvement in quality of life was observed even though the patients could see well with the fellow eye. In conclusion, the NEI VFQ-25 TR is a useful scale to evaluate the changes in visual function and psychosocial characteristics of DME patients after treatment.

Ocular Findings Among Patients With Vitamin D Deficiency.

Objective The aim of this study was to evaluate the ocular findings in patients with low vitamin D levels. Methods All patients who attended the Internal Medicine Clinic between March 2018 and February 2020 with vitamin low D levels but had been untreated for the same were included in our study. The exclusion criteria were as follows:history of intraocular surgery, trauma, steroid use, secondary glaucoma, and history of rheumatologic diseases. The patients were classified into three groups: group 1 had severe deficiency with vitamin D levels below 10 µg/L; group 2 had vitamin deficiency with levels of 10-20 µg/L; and group 3 had vitamin D insufficiency with levels of 20-30 µg/L. A comparison among groups was performed in terms of intraocular pressure (IOP), retinal nerve fiber layer (RNFL) thickness, central macular thickness (CMT), dry eyes, cataract, glaucoma, macular degeneration, and refractive error. The evaluation of statistical data was performed with the SPSS Statistics software version 22 (IBM, Armonk, NY). Results There were a total of 98 patients and 196 eyes, who were classified into three groups. There were 41 patients in group 1, 45 in group 2, and 12 in group 3. Groups were similar in terms of age (p=0.25) and gender (p=0.46). The average age among the cohort was 51 ± 13.08 years; 65 (66.3%) of the patients were female and 33 (33.7%) were male. There was no statistically significant difference in terms of IOP (p=0.55), dry eyes (p=0.35), cataract (p=0.22), glaucoma (p=0.50), macular degeneration (p=0.64), and refractive error (p=0.46) among the groups. There was a statistically significant difference in CMT between group 1 and other groups (p=0.002 and p=0.002, respectively). Also, there was a statistically significant difference in RNFL thickness between group 1 and group 2 (p=0.01). When compared in terms of quadrants, a significant difference was found only with regard to the nasal quadrant. Conclusion Based on our findings, lower levels of 25-hydroxyvitamin D might be related to thinning in CMT. Regarding RNFL thickness, while there was a significant difference between groups 1 and 2, there was no difference between groups 1 and 3, and hence the association between lower levels of 25-hydroxyvitamin D and thinning in RNFL thickness could not be clearly established. Hence, we have assumed that lower levels of 25-hydroxyvitamin D might cause thinning in the macula and nasal quadrant of RNFL, and vitamin D deficiency might affect the nasal quadrant of RNFL primarily. Further long-term studies with a larger number of patients might clarify the relationship between vitamin D deficiency and the thinning in CMT, RNFL quadrants, and RNFL thickness.

May ganglion cell complex analysis be a marker for glaucoma susceptibility in unilateral Fuchs' uveitis syndrome?

PURPOSE: To compare retinal nerve fiber layer (RNFL) thickness and ganglion cell-inner plexiform layer thickness (GCIPLT) in the affected eyes to fellow unaffected eyes of patients with unilateral Fuchs' uveitis syndrome (FUS) and analyze their change over time. METHODS: Twenty seven unilateral FUS patients who did not have concomitant systemic or ocular disease were retrospectively enrolled. Central macular thickness (CMT), RNFL thickness, and GCIPLT measurements were evaluated. Data was analyzed using the non-parametric Brunner-Langer model (LD-F2 design) and Wilcoxon signed-rank test. RESULTS: The mean age of the patients was 40.2 ± 10.2 years. The median disease duration was 11 (2-62) months. The median best-corrected visual acuity (BCVA) of the affected eyes and the fellow eyes was 0.22 (0.00-2.50) vs. 0.00 (0.0-0.10) logMAR at the initial visit and 0.05 (0.00-2.50) vs. 0.00 (0.0-0.30) logMAR at the final visit. The change in BCVA was found significant in the affected eyes, but not in the fellow eyes (p < 0.001 and p = 0.287, respectively). The median CMT in the affected eyes at the final visit was not statistically different from the value at the initial visit (255 (157-306) vs. 245 (140-310) µm, p = 0.256). The change in RNFL thickness over time in the affected eyes was similar to the fellow unaffected eyes of the patients with unilateral FUS at all quadrants, with non-significant time and group effects (p > 0.05). However, median GCIPLT in all quadrants (except superonasal) in the affected eyes was statistically lower than the fellow eyes at the initial and final visits (p < 0.05). The most affected quadrant of the ganglion cell complex was inferonasal in the involved eyes (79 (42-97) vs. 75 (43-87) µm) at initial and final visits (p = 0.033 for time effect and p < 0.001 for group effect, respectively). CONCLUSION: Median CMT and RNFL thickness did not change during follow-up in the affected eyes of patients with unilateral FUS. Median GCIPLT in the affected eyes declined over time in all quadrants. Ganglion cell loss was also most prominent in the inferonasal quadrant in the affected eyes. FUS patients should be followed up long-term in terms of ganglion cell loss, especially in the inferonasal quadrant.