Effects of intravitreal conbercept before panretinal photocoagulation on lipid exudates in diabetic macular documented by optical coherence tomography.

AIM: To evaluate the effects of intravitreal conbercept (IVC) as adjunctive treatments before panretinal photocoagulation (PRP) to decrease hyperreflective dots (HRDs) in Chinese proliferative diabetic retinopathy (PDR) patients. METHODS: Fifty-nine enrolled patients were categorized into 2 groups: single dose IVC (0.5 mg/0.05 mL) 1wk before PRP (Plus group) or PRP only (PRP group). Six months later, we measured the best corrected visual acuity (BCVA), central macula thickness (CMT) by optical coherence tomography and counted the number of HRDs in different retina layers. RESULTS: The average CMT significantly decreased in Plus group but increased in PRP group. The average BCVA in the Plus group was also significantly better than that in the PRP group. Total HRDs decreased in the Plus group but increased in PRP group significantly. IVC pre-treatment has beneficial effects on reducing HRDs forming in the inner retina layer while the PRP alone increased the HRDs in the outer retina layer. CONCLUSION: IVC is a promising adjunctive treatment to PRP in the treatment of PDR. Single dose IVC one week before PRP is suggested to improve retina blood-retina barrier, decrease lipid exudate and inhibit HRDs development in PDR.

Downregulation of circRNA DMNT3B contributes to diabetic retinal vascular dysfunction through targeting miR-20b-5p and BAMBI.

BACKGROUND: Diabetic retinopathy, a vascular complication of diabetes mellitus, is the leading cause of visual impairment and blindness. circRNAs act as competing endogenous RNA, sponging target miRNA and thus influencing mRNA expression in vascular diseases. We investigated whether and how circDNMT3B is involved in retinal vascular dysfunction under diabetic conditions. METHODS: qRT-PCR was performed to detect expression of circDNMT3B, miR-20b-5p, and BAMBI in retinal microvascular endothelial cells under diabetic conditions. Western blot, Cell Counting Kit-8, Transwell, Matrigel tube formation, and retinal trypsin digestion assays were conducted to explore the roles of circDNMT3B/miR-20b-5p/BAMBI in retinal vascular dysfunction. Bioinformatics analysis and luciferase reporter, siRNA, and overexpression assays were used to reveal the mechanisms of the circDNMT3B/miR-20b-5p/BAMBI interaction. Electroretinograms were used to evaluate visual function. FINDINGS: Upregulation of miR-20b-5p under diabetic conditions promoted proliferation, migration, and tube formation of human retinal microvascular endothelial cells (HRMECs), which was mediated by downregulated BAMBI. Under diabetic conditions, circDNMT3B, which acts as a sponge of miR-20b-5p, is downregulated. circDNMT3B overexpression reduced retinal acellular capillary number and alleviated visual damage in diabetic rats. Changes in expression of circDNMT3B and miR-20b-5p were confirmed in the proliferative fibrovascular membranes of patients with diabetic retinopathy. INTERPRETATION: Downregulation of circDNMT3B contributes to vascular dysfunction in diabetic retinas through regulating miR-20b-5p and BAMBI, providing a potential treatment strategy for diabetic retinopathy. FUNDING: National Natural Science Foundation of China, National Key Basic Research Program of China, Shanghai Municipal Science and Technology Major Project, and ZJLab.

Characteristics of retinal vein occlusion with final vision better than 78 letters after sequential therapy with ranibizumab and triamcinolone acetate.

AIM: To analyze the reasons that may lead to the different vision result by combining the ranibizumab and triamcinolone acetate (TA) in sequence to treat macular edema in retinal vein occlusion (RVO). METHODS: Ranibizumab and TA were combined in sequence to treat 43 patients with macular edema secondary to RVO. Six months after the treatment, patients with central fovea thickness (CFT) less than 300 µm in optical coherence tomography (OCT) were collected into Groups I and II, based on vision acuity (VA) better than 78 letters or less than 60 letters. The age, baseline VA, duration from onset to treatment, CFT at the baseline, sub-retinal fluid (SRF), sub-foveal exudates and injection times of TA and ranibizumab were taken into comparison. RESULTS: The mean age of the subjects was 46.4y in Group I but 57.5y in Group II. The difference of age was significant between groups (P<0.01). The mean baseline VA was 51.4 letters in Group I and 43.9 letters in Group II (P<0.05). The baseline CFT were 670.9 µm in Group I with SRF in 54.3% patients and 678.1 µm in Group II with SRF in 52.9% (P>0.05). The mean number of injections of TA was 0.9 and the mean number of injections of ranibizumab was 2.3 in Group I but 1.7 and 2.9 respectively in Group II. The treatment times of ranibizumab had no difference between the 2 groups (P>0.05) but the difference of TA injection times was significant, P<0.05. Subfoveal exudates at final stage happened in no subjects in Group I but in 45.83% subjects in Group II. CONCLUSION: This combined treatment is safer than TA injection and cheaper than ranibizumab injection alone. Younger patients and earlier treatment will help to get better vision outcome. Subfoveal exudates at the final stage have significant relationship with vision outcome. No relationship existed between the baseline CFT, SRF and the vision outcome.

Neuroprotective effects of naloxone against light-induced photoreceptor degeneration through inhibiting retinal microglial activation.

PURPOSE: To determine the role of microglial activation in light-induced photoreceptor degeneration and the neuroprotective effects of naloxone as a novel microglial inhibitor. METHODS: Sprague-Dawley rats were exposed to intense blue light for 24 hours. Daily intraperitoneal injection of naloxone or PBS as a control was given 2 days before exposure to light and was continued for 2 weeks. Apoptotic cells were detected by the TUNEL assay, and anti-OX42 antibody was used to label retinal microglia. Western blot was applied to evaluate the retinal interleukin (IL)-1beta protein levels. Retinal histologic examination and electroretinography (ERG) were also performed to evaluate the effects of naloxone on light-induced photoreceptor degeneration. RESULTS: TUNEL-positive cells were noted in the outer nuclear layer (ONL) of the retina as early as 2 hours and peaked at 24 hours after exposure to light. OX42-positive microglia occurred in the ONL and subretinal space at 6 hours, peaked at 3 days, and changed morphologically from the resting ramified to the activated amoeboid. Expression of IL-1beta protein was also significantly increased at 3 days. Compared with the control, the number of microglia in the outer retina was significantly decreased in the naloxone-treated group at 3 days, and the thickness of ONL and the amplitudes of dark-adapted a- and b-waves were also well preserved at 14 days. CONCLUSIONS: The activation and migration of microglia and the expression of neurotoxic factor (IL-1beta) coincide with photoreceptor apoptosis, suggesting that activated microglia play a major role in light-induced photoreceptor degeneration. Inhibiting microglial activation by naloxone significantly reduces this degeneration.