The effects of anti-vascular endothelial growth factor agents on human retinal pigment epithelial cells under high glucose conditions.

AIM: To investigate the effects of high glucose levels and anti-vascular endothelial growth factor (VEGF) agents (bevacizumab, ranibizumab and aflibercept) on retinal pigment epithelium (RPE) cells. METHODS: ARPE-19 cells were cultured at different glucose levels (5.5 mmol/L, 25 mmol/L, and 75 mmol/L). Cell viability was evaluated by MTT assay at 3d after treatment with D-glucose. Cell migration ability was measured by wound healing assay at 3d. A cell death detection kit was used to assess apoptosis at 3 and 14d. Cell proliferation was assessed by EdU assay at 3d. The culture medium was treated with anti-VEGF agents at clinically relevant concentrations. The experiment was then repeated at a different glucose level. RESULTS: The viability and migration of ARPE-19 cells were significantly decreased in the presence of 75 mmol/L as compared to 5.5 mmol/L glucose. The percentage of TUNEL-positive cells was significantly increased and the proliferative potential was decreased with 75 mmol/L compared to 5.5 mmol/L glucose. There were no significant differences in the results between 25 mmol/L and 5.5 mmol/L glucose. In the presence of 75 mmol/L glucose, the groups treated with anti-VEGF showed decreased cell viability and proliferation and increased apoptosis. However, there were no significant differences between the anti-VEGF groups. CONCLUSION: High glucose level decreases the viability, wound healing ability, and proliferation of RPE cells, while increasing apoptosis. Furthermore, anti-VEGF agents interfered with the physiological functions of RPE cells under high-glucose conditions, accompanied by decreases in cell viability and proliferation.

The effect of cilostazol on electrophysiologic changes in non-proliferative diabetic retinopathy patients.

PURPOSE: To evaluate the effects of cilostazol, an antiplatelet and vasodilation agent, on the retinal function of patients with non-proliferative diabetic retinopathy (NPDR) using a full-field electroretinogram (ffERG). METHODS: A total of 20 eyes from 20 patients were enrolled as the cilostazol-treated group, and 16 eyes from 16 patients were enrolled as the control group to assess the functional effects of cilostazol. Ophthalmologic examinations including fundus fluorescein angiography (FFA), fundus color photography, optical coherence tomography (OCT), and ffERG responses were recorded at baseline and after 1 year of cilostazol treatment. The number of microaneurysms on FFA, the number of exudates on fundus photographs, and central macular thickness (CMT) on OCT were compared between the two groups. Recording of ffERG was also performed at baseline and repeated after 1 year of treatment. The mean implicit times and amplitudes of a- and b-waves in each ffERG response were analyzed to evaluate the retinal function. RESULTS: CMT and the numbers of microaneurysms and exudates showed no significant change in the cilostazol-treated group. There was no significant change in ffERG parameters between baseline and 1 year after the treatment in each group. The mean changes in implicit times from the cilostazol-treated group were significantly less than in the control group in b-waves from dark-adapted 3 ERG (p = 0.017) and 10 ERG responses (p = 0.047). On the other hand, the mean changes in amplitudes were not significant after 1 year of cilostazol treatment, but there were slight increases in amplitudes of dark-adapted 0.01 ERG and 10 ERG in the cilostazol-treated group. CONCLUSIONS: These results suggest that cilostazol administration could reduce the implicit times of ffERG in patients with NPDR. It may be beneficial to preserve the retinal function in the diabetic retina, and additional research with larger populations and extended duration are needed to clarify the efficacy and safety of cilostazol for these patients.

Anti-Human VEGF Repebody Effectively Suppresses Choroidal Neovascularization and Vascular Leakage.

Age-related macular degeneration (AMD) is the leading cause of vision loss and blindness among people over the age of 60. Vascular endothelial growth factor (VEGF) plays a major role in pathological angiogenesis in AMD. Herein, we present the development of an anti- human VEGF repebody, which is a small-sized protein binder consisting of leucine-rich repeat (LRR) modules. The anti-VEGF repebody selected through a phage-display was shown to have a high affinity and specificity for human VEGF. We demonstrate that this repebody effectively inhibits in vitro angiogenic cellular processes, such as proliferation and migration, by blocking the VEGF-mediated signaling pathway. The repebody was also shown to have a strong suppression effect on choroidal neovascularization (CNV) and vascular leakage in vivo. Our results indicate that the anti-VEGF repebody has a therapeutic potential for treating neovascular AMD as well as other VEGF-involved diseases including diabetic retinopathy and metastatic cancers.

Development of Thyroid-Associated Ophthalmopathy in Patients Who Underwent Total Thyroidectomy.

PURPOSE: To report clinical characteristics of thyroid-associated ophthalmopathy (TAO) in patients who previously underwent total thyroidectomy for thyroid cancer or a benign mass of the thyroid. MATERIALS AND METHODS: Of the patients who were diagnosed with TAO from March 2008 to March 2012, we performed a retrospective chart review on those who had undergone total thyroidectomy for thyroid cancer or a benign mass of the thyroid before the occurrence of ophthalmopathy. RESULTS: Of the 206 patients diagnosed with TAO, seven (3.4%) met the inclusion criteria. The mean age of the subjects was 47.4 years, and all were female. Six patients were diagnosed with papillary thyroid cancer, and one was diagnosed with a benign mass. The duration between total thyroidectomy and onset of TAO ranged from 3-120 months (median 48 months). Ophthalmic manifestations varied among cases. Except for the patient who was diagnosed with a benign mass, all patients showed hyperthyroid status and were under Synthroid hormone treatment at the time of TAO development. Five of these six patients had positive levels of thyroid-stimulating hormone (TSH) receptor autoantibodies. CONCLUSION: TAO rarely develops after total thyroidectomy, and the mechanism of TAO occurrence is unclear. However, most patients showed abnormalities in thyroid function and TSH receptor autoantibodies.

Change in quality of life of patients undergoing silicone stent intubation for nasolacrimal duct stenosis combined with dry eye syndrome.

AIMS: To investigate the effect of silicone stent intubation (SI) on the quality of life of patients diagnosed with nasolacrimal duct stenosis and dry eye syndrome. METHODS: This study is a prospective, interventional case series. Consecutive 30 patients diagnosed with nasolacrimal duct stenosis and reflex tearing due to dry eye syndrome were included. Eligible subjects underwent SI and were asked to complete the Glasgow Benefit Inventory (GBI) questionnaire. Surgical outcomes and GBI scores were investigated 6 months postoperatively. RESULTS: The surgical success rate determined by the patients' subjective symptoms was 76.7% (23/30). Mean total GBI score was +17.19 (95% CI 8.34 to 26.03). The general subscale score was +20.36 (95% CI 10.19 to 30.54), the social support scale score was +21.54 (95% CI 11.37 to 31.71) and the physical health score was -0.56 (95% CI -8.92 to 7.80). CONCLUSIONS: SI could be an effective treatment option for reflex tearing in patients diagnosed with dry eye syndrome and nasolacrimal duct stenosis.