Anti-vascular endothelial growth factor therapy in diabetic macular edema: real-life outcomes from a multicenter study in Turkey over 36 months.

PURPOSE: This study aimed to report the visual and anatomical outcomes of intravitreal anti-VEGF treatment for diabetic macular edema (DME) in a real-world clinical setting from Turkey over 36 months. METHODS: This is a retrospective, multicenter (7 sites) study. The medical records of 1072 eyes (both previously treated and naive eyes) of 706 consecutive patients with visual impairment due to center-involving DME treated with intravitreal anti-VEGF injections between April 2007 and February 2017 were reviewed. The eyes were divided into mutually exclusive three groups based on the duration of follow-up (12, 24, or 36 months). Primary outcome measures were changes in visual acuity (VA) and central macular thickness (CMT) from baseline to final visit in each cohort, frequency of visits and intravitreal anti-VEGF injections. As secondary endpoints, VA outcomes were assessed in subgroups stratified by baseline VA [<70 ETDRS letters and ≥70 ETDRS letters] and loading dose status of anti-VEGF injections. RESULTS: VA increased by a mean of 8.2 letters (12-month cohort, p < 0.001), 5.3 letters (24-month cohort, p < 0.001), and 4.4 letters (36-month cohort, p = 0.017) at final visits. The eyes with <70 VA letters achieved more significant VA improvement at final visits in all cohorts compared with eyes with >70 VA letters (p < 0.001). The mean decreases in CMT from baseline to last visits at 12-, 24-, and 36- month cohorts were -100.5 µm, -107.7 µm, and -114.3 µm, respectively (p < 0.001). The mean number of injections given were 4.6, 2.3, and 1.8 during years 1 to 3, respectively. Patients who received loading dose showed greater VA gains than those who did not in all follow-up cohorts. CONCLUSION: Our study revealed that anti-VEGF treatment improved VA and CMT over a follow-up of 36 months. Although these real-life VA outcomes following anti-VEGF therapy for DME were similar to other real-life studies, they were inferior to those noted in randomized controlled trials, mainly due to undertreatment.

Macular pigment optical density change analysis in primary open-angle glaucoma and pseudoexfoliation glaucoma.

PURPOSE: We aimed to investigate whether macular pigment optical density (MPOD) has a diagnostic value by comparing MPOD and retinal nerve fiber layer (RNFL), ganglion cell layer++ (GCL++) of patients with primary open-angle glaucoma (POAG) and pseudoexfoliation (PEX) glaucoma and normal individuals. METHODS: We included in the study 54 eyes of 34 patients with diagnosis POAG, 40 eyes of 25 patients with PEX glaucoma and 40 eyes of 20 normal individuals. The MPOD measurements of the cases were performed in the MPOD mode of the fundus fluorescein angiography (Carl Zeiss Visucam Meditec, Germany) device while the pupils were in dilated status. RNFL and GCL++ measurements of all individuals included in the study were done by swept source optical coherence tomography (DRI Triton swept source optical coherence tomography; Topcon, Tokyo, Japan). Intraocular pressures of all three groups were measured by Applanation tonometer. The relationship between MPOD, RNFL and GCL++ values were examined. Patients with additional ophthalmic disease, intraocular surgery, history of chronic drug use, and smokers were excluded in the study. RESULTS: MPOD mean and MPOD max values were significantly higher in patients with PEX glaucoma than POAG and control group (p < 0.05). MPOD mean and MPOD max measurements were not different when compared to POAG patients and control group (p > 0.05). RNFL and GCL++ measurements were found significantly thinner in patients with POAG and PEX glaucoma compared to the control group (p < 0.001). There was no correlation between MPOD values and RNFL or GCL++. MPOD max values show a very high correlation with age in a statistically significant positive direction (r = 0.90, p < 0.001). The average age of PEX glaucoma group was higher than the control group (p = 0.006). There was no age difference between the PEX glaucoma group and the POAG group (p > 0.05). Also, there was no difference in age between POAG and control groups. In POAG and PEX glaucoma groups, mean intraocular pressure values are significantly higher than the control group. CONCLUSIONS: In our study, no MPOD change was observed in the POAG group, while a statistically significant increase in MPOD was found in the PEX glaucoma group. As a result of these findings, we think that PEX syndrome also affects the posterior segment. Well-organized, large, prospective, and randomized studies should be developed for preventive treatment to the negative effects of PEX syndrome on all eye tissues.

Inflammation and diabetic retinopathy.

Purpose: To investigate the relationship between inflammation in the vitreous and diabetic retinopathy. Methods: Vitreous samples from 21 patients with proliferative diabetic retinopathy (PDR), 21 patients with nonproliferative diabetic retinopathy (NPDR), and 21 nondiabetic patients with idiopathic epiretinal membranes (control) were studied. The interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), matrix metalloproteinase (MMP)-2, MMP-9, and adiponectin levels in the vitreous were detected in all samples with enzyme-linked immunosorbent assay (ELISA). Samples were stored at -80 °C until analyzed. Results: The TNF-α levels in the vitreous were not statistically significant between all groups (p>0.005). The mean IFN-γ levels were statistically significantly higher in patients with PDR (70.98 pg/ml) and patients with NPDR (46.61 pg/ml) than in nondiabetic patients (22.02 pg/ml). There was a difference in the IFN-γ levels in the vitreous between patients with PDR and patients with NPDR (p<0.005). The MMP-2 and MMP-9 concentrations in the vitreous were not different between all groups (p>0.05). There was a correlation between the IFN-γ and TNF-α levels. We investigated the statistically significantly decreased levels of adiponectin in the proliferative (p<0.05) and nonproliferative (p<0.05) diabetic eyes compared to the nondiabetic eyes. Conclusions: Increased levels of IFN-γ and TNF-α in the vitreous were found in patients with diabetes compared to nondiabetic patients. Decreased levels of adiponectin in the vitreous were found in patients with diabetes compared to nondiabetic patients. The data support the hypothesis that inflammation is associated with diabetic retinopathy.

Bone Marrow-derived Mesenchymal Stem Cell Therapy in Retinitis Pigmentosa.

BACKGROUND: To determine the effectiveness of bone marrow-derived mesenchymal stem cell therapy on visual acuity and visual field in patients with retinitis pigmentosa. OBJECTIVE: Stem cell treatment in retinitis pigmentosa provides improvement in visual acuity and visual field. METHOD: Forty-seven eyes of 27 patients diagnosed with retinitis pigmentosa were included in our study. Allogeneic bone marrow-derived mesenchymal stem cells were administered by deep subtenon injection. Complete routine ophthalmological examinations, optical coherence tomography (Zeiss, Cirrus HD-OCT) measurements, and visual field (Humphrey perimetry, 30-2) tests were performed on all patients before the treatment and on the 1st, 3rd, and 6th month after treatment. The best corrected visual acuities of the patients were determined by the Snellen chart and converted to logMAR. Visual evoked potential (VEP) and electroretinogram (ERG) examinations of the patients before the treatment and on the 6th month after the treatment were performed (Metrovision) data were compared. RESULTS: Visual acuities were 0.74 ± 0.49 logMAR before treatment and 0.61 ± 0.46 logMAR after treatment. Visual acuity had a statistically significant increase (p < 0.001). The visual field deviation was found to be -27.16 ± 5.77 dB before treatment and -26.59 ± 5.96 dB after treatment (p = 0.005). The ganglion cell layer was 46.26 ± 12.87 µm before treatment and 52.47 ± 12.26 µm after treatment (p = 0.003). There was a significant improvement in Pattern VEP 120º P100 amplitude compared to that before the treatment (4.43 ± 2.42 µV) and that after the treatment (5.09 ± 2.86 µV) (p = 0.013). ERG latency measurements were 18.33 ± 15.39 µV before treatment and 20.87 ± 18.64 µV after treatment for scotopic 0.01 (p = 0.02). ERG latency measurements for scotopic 3.0 were 20.75 ± 26.31 µV before treatment and 23.10 ± 28.60 µV after treatment (p = 0.014). CONCLUSION: Retinitis pigmentosa is a progressive, inherited disease that can result in severe vision loss. In retinitis pigmentosa, the application of bone marrow-derived mesenchymal stem cells by deep subtenon injection has positive effects on visual function. No systemic or ophthalmic side effects were detected in the patients during the 6-month follow-up period.

Early effects of cardiopulmonary bypass surgery on retinal nerve fiber layer and ganglion cell layer.

PURPOSE: To determine the effects of cardiopulmonary bypass surgery on retinal nerve fiber layer, ganglion cell layer, and macula by optic coherens tomography (OCT). METHOD: Sixty-six eyes of 33 patients aged between 44 and 74 who were indicated for cardiopulmonary bypass surgery in the cardiovascular surgery clinic were included in the study. Routine ophthalmologic examinations of all patients were performed before and 1 week after surgery. In addition, 3D(H) Macula+5 Line Cross 12 × 9 mm mod and Peripapilar 3D Disk 6 × 6 mm mod data were analyzed with OCT (Topcon, Triton Swept Source-OKT, Tokyo, Japan) device. Peripapillary total, superior, inferior retinal nerve fiber layer (RNFL), optic disc cavity volume, cup-to-disc ratio, macular ganglion cell layer (GCL), macular thickness were compared before and after surgery. RESULTS: After cardiopulmonary bypass surgery, thickening was detected in the total RNFL (p<0.001), superior RNFL (p = 0.01) and inferior RNFL (p<0.001) layers. There was no change in the values of GCL, macular thickness, optic disc cupping volume, cup-to-disc ratio after surgery (p>0.05). There was a positive correlation (r = 0.392 p<0.05) between the patients' blood oxygen (PO2) values during bypass surgery with their post-surgical GCL+ values, and a negative correlation between optic disc cup volumes (r=-0.349 p<0.05). CONCLUSION: RNFL thickening has been detected in patients undergoing cardiopulmonary bypass surgery. This thickening may occur secondary to ischemic edema that occurs during surgery. Considering the late complications of ischemic edema in the RNFL, oxygen levels should be kept at an optimum level during surgery and long-term ophthalmologic follow-ups should be performed.

Corneal characteristics in patients with retinitis pigmentosa.

BACKGROUND: To evaluate corneal topography and specular microscopic findings in patients with retinitis pigmentosa. METHODS: One hundred and two eyes of 51 patients with retinitis pigmentosa and 60 eyes of 30 healty subjects were included in our study. A detailed ophthalmological examination involving best corrected visual acuity (BCVA) was performed. A rotating Scheimpflug imaging system, was used to evaluate all eyes for topographic and aberrometrics parameters. Specular microscopy measurements were also noted. RESULTS: The retinitis pigmentosa group consisted of 51 patients (29 male and 22 female, mean age of 35.61±13.55 (18-65) years and the control group also consisted of 30 healty subjects (29 male and 22 female, mean age of 33.67±9.92 (20-58) years. There was no difference between the groups in terms of age (p = 0.624) and gender (p = 0.375). Spherical equivalents were higher in the RP group (p<0.001). Central keratoconus index (CKI) (p<0.001), Belin Ambrosio enhanced ectasia display total deviation value (BAD-D) (p = 0.003), index of surface variance (ISV) (p<0.001), index of vertical asymmetry (IVA) (p<0.001), Ambrosio related thickness (ART max) (p = 0.018), index of height asymmetry (IHA) (p = 0.009), index of height decentration (IHD) (p<0.001), maximum anterior elevation (p<0.001), front elevation in thin location (p = 0.05), progression index average (p = 0.015), root mean square (RMS) total (p = 0.010) and RMS-higher order aberration (RMS-HOA) (p<0.001) values were higher in RP group. There was a weak negative correlation between BCVA and ART max measurements (r=-0.256, p = 0.009) in RP group. We detected keratoconus-suspect in 6 eyes and clinically manifest keratoconus in one eye in the RP group. CONCLUSIONS: Patients with retinitis pigmentosa may have corneal morphological disorders that may affect vision. In our study, corneal topographic pathologies including keratoconus and possible keratoconus were detected in RP patients.

A rare case: Branch retinal vein occlusion associated with the use of tamoxifen.

Tamoxifen-induced ocular complications including cataracts, keratopathies, retinopathy, impaired visual acuity, ocular irritation, optical neuritis, and retinal vein occlusion are uncommonly reported in the literature. Herein, we report on a premenopausal patient with right-side breast carcinoma who received adjuvant tamoxifen therapy (20 mg/day) for 1.5 years and developed sudden visual loss. Fundal examination revealed an obstruction in the branch of the retinal vein. The diagnosis was confirmed by fluorescein angiography and optical coherence tomography. Thus, tamoxifen was switched to an aromatase inhibitor. Tamoxifen-induced ocular complications should be kept in mind when visual symptoms are seen in patients undergoing tamoxifen therapy. In such cases, a complete ocular examination should be performed.

The importance of serum lipids in exudative diabetic macular edema in type 2 diabetic patients.

To evaluate the relationship between serum lipid levels and exudative diabetic maculopathy in patients with nonproliferative diabetic retinopathy, 27 patients with exudative diabetic macular edema were included in group A and 27 patients without exudative diabetic macular edema were included in group B. All 54 patients have nonproliferative diabetic retinopathy. Blood cholesterol, triglyceride, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, very low-density lipoprotein (VLDL) cholesterol, hemoglobin A1c (HbA1c), and hemoglobin levels were measured in patients in group A and group B. The mean concentration of cholesterol in group A (224.30 +/- 49.49 mg/dL), in group B (197.78 +/- 41.49 mg/dL); triglyceride in group A (199.11 +/- 90.51 mg/dL), in group B (160.78 +/- 65.30 mg/dL); HDL in group A (43.48 +/- 10.62 mmol/L), in group B (42.37 +/- 10.92 mmol/L); LDL in group A (150.59 +/- 43.96 mg/dL), in group B (124.37 +/- 40.28 mg/dL); VLDL in group A (40.52 +/- 16.54 mg/dL), in group B (37.89 +/- 23.70 mg/dL); HbA1c in group A (9.62 +/- 2.50), in group B (7.36 +/- 1.62 g/dL); and hemoglobin in group A (13.46 +/- 1.6 g/dL), in group B (13.90 +/- 1.77 g/dL). Serum cholesterol (P = 0.38), LDL (P = 0.026), and HbA1c (P = 0.000) levels were different between the two groups. Triglyceride, HDL, VLDL, and hemoglobin levels were not different between the two groups. We must consider regulation of high blood sugar and elevated total serum cholesterol or LDL levels in patients with macular edema and high hard exudates.

The role of the cytokines in the pathogenesis of pseudoexfoliation syndrome.

AIM: To examine the mechanism of the development of pseudoexfoliation (PSX) syndrome via both cytokine formation and endothelial vasorelaxing and growth factors that will provide us new therapeutic insights for the treatment. METHODS: This is a cross sectional study included two groups; Group 1: control patients with nuclear cataract (n=20, aged 51-80 years). Group 2: PSX patients with nuclear cataract (n=18, aged 50-90 years). Patients with other ophthalmic problems and systemic diseases were excluded. Vascular endothelial growth factor (VEGF), interleukin-6 (IL-6) and interleukin-1ß (IL-1ß) and nitrotyrosine levels were determined through serum samples by Enzyme-linked immunosorbent assay (ELISA) method. Nitrite-nitrate levels were measured with photometric endpoint determination. RESULTS: There were no significant differences between the groups in terms of age, VEGF, IL-1ß, nitrite-nitrate and nitrotyrosine. The significant results were the mean IL-6 levels that were higher in PSX group 2 (37.68±29.52 pg/mL) compared to that in control group 1 (15.32±10.08 pg/mL) (P<0.001). CONCLUSION: Several interacting and extending biochemical pathways may lead to the promotion of VEGF and IL-6 expressions. IL-6 which is the only altered marker in our study may indirectly cause an increase of vascular permeability and neovascularization. We suggest inflammation as a factor that can be involved in etiopathogenesis of PSX.

The role of oxidative stress and antioxidants in the pathogenesis of age-related macular degeneration.

OBJECTIVE: To investigate the role of oxidant/antioxidant status and protein oxidation in the development of age-related macular degeneration. METHOD: The activities of serum superoxide dismutase and glutathione peroxidase and the levels of serum malondialdehyde, advanced oxidation protein products, glutathione and vitamin C were measured in 25 patients with age-related macular degeneration and 25 control subjects without age-related macular degeneration. RESULT: The malondialdehyde and advanced oxidation protein product levels in the serum were significantly higher in the age-related macular degeneration patient group than in the control group (p<0.05). The superoxide dismutase activity in the serum was significantly lower in the age-related macular degeneration patient group than in the control group (p<0.05). The levels of vitamin C and glutathione and the activity of glutathione peroxidase in the serum were unchanged between groups (p>0.05). CONCLUSION: The results of the present study suggest that decreased effectiveness of the antioxidant defense system and increased oxidative stress may play a role in the pathogenesis of age-related macular degeneration.

The role of oxidative stress and antioxidants in the pathogenesis of age-related macular degeneration

OBJECTIVE: To investigate the role of oxidant/antioxidant status and protein oxidation in the development of age-related macular degeneration. METHOD: The activities of serum superoxide dismutase and glutathione peroxidase and the levels of serum malondialdehyde, advanced oxidation protein products, glutathione and vitamin C were measured in 25 patients with age-related macular degeneration and 25 control subjects without age-related macular degeneration. RESULT: The malondialdehyde and advanced oxidation protein product levels in the serum were significantly higher in the age-related macular degeneration patient group than in the control group (p<0.05). The superoxide dismutase activity in the serum was significantly lower in the age-related macular degeneration patient group than in the control group (p<0.05). The levels of vitamin C and glutathione and the activity of glutathione peroxidase in the serum were unchanged between groups (p>0.05). CONCLUSION: The results of the present study suggest that decreased effectiveness of the antioxidant defense system and increased oxidative stress may play a role in the pathogenesis of age-related macular degeneration.