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Purpose: The aim of this study was to report the efficacy and safety profile of subthreshold pan-retinal photocoagulation (PRP) using endpoint management (EPM) algorithm compared with conventional threshold PASCAL PRP for the treatment of severe nonproliferative diabetic retinopathy (NPDR). Methods: This was a prospective, single-center, paired randomized controlled trial of 56 eyes of 28 participants with bilateral symmetric severe NPDR. One eye of the participant was randomly assigned to receive the subthreshold EPM PRP, while the other eye of the same participant received the threshold PASCAL PRP. The primary outcome measures included the difference in the 1-year risk of progression to PDR between 2 groups, and mean changes of the logarithm of the minimal angle of resolution (logMAR) visual acuity (VA). The second outcome measures included central foveal thickness (CFT), 1-year risk of progression to PDR, and visual field (VF) parameters. Results: The subthreshold EPM PRP group and the threshold PASCAL PRP group had similar 1-year risk of progression to PDR during the 12-month follow-up visits (17.86 vs. 14.29%, p > 0.05). Slightly decreased VA was found in both groups (0.08 vs. 0.09 logMAR VA); however, no statistical difference was found for neither group (p > 0.05). Similar results were found for thickened CFT for both groups (23.59 vs. 28.34 μm, p > 0.05). Specifically, although substantial loss of VF was found in the threshold PASCAL PRP group (p < 0.05), no obvious damage to VF was seen in the subthreshold EPM PRP group (p > 0.05). Conclusion: The subthreshold EPM PRP is noninferior to the conventional threshold PASCAL PRP in the treatment of severe NPDR during 12-month follow-up and could be an alternative treatment option for patients with severe NPDR. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to investigate the safety and efficacy of intravitreal injection of Tc-MDP, a decay product of Tc-MDP, on the development of laser-induced choroidal neovascularization (CNV) in rhesus monkeys. Methods: Experimental CNV was induced by argon laser with a small high-energy laser spot. Monkeys were given 50 μL of Tc-MDP at a concentration of 0.005 μg/mL ( n = 6) or 0.01 μg/mL ( n = 6) by intravitreal injection once a week immediately after laser injury for a period of 56 days. Control animals were treated with the same volume of PBS ( n = 6) in the same way. Eyes were monitored by ophthalmic examination, color fundus photography, fluorescence fundus angiography (FFA), optical coherence tomography (OCT) and histology. Incidences of grade 4 CNV lesions as well as the leakage areas of grade 4 CNVs on the late-phase of fluorescein angiograms were measured in a standardized, randomized and masked fashion fortnightly. The maximum widths and heights of grade 4 CNVs were also calculated by histology at the end of the experiment. Toxicity of Tc-MDP on the retina was evaluated by electroretinogram (ERG) and histologic analysis. Results: Tc-MDP reduced the incidences of grade 4 CNVs by 33.33 % and 39.40 % in the 0.005 μg/mL and 0.01 μg/mL groups, respectively, compared with the PBS group on day 28 ( P < 0.05; n = 6). The leakage areas of grade 4 CNVs were smaller in the 0.005 μg/mL (0.7136 ± 0.0283 mm, p <0.01; n = 6) and 0.01 μg/mL (0.4351 ± 0.0349 mm, p < 0.01; n = 6) groups than those in the PBS control group (0.9373 ± 0.0455 mm; n = 6) in a dose-dependent manner on day 28. OCT and histology also showed that the sizes of CNVs were smaller in the Tc-MDP treated groups than those in the PBS group. Although intravitreal injection of Tc-MDP led to mild inflammatory reaction in the anterior chamber, histology and ERG findings demonstrated that Tc-MDP did not cause any change in histological structure or function of the retina ( p>0.05). Conclusions: Intravitreal injection of Tc-MDP can inhibit the development of laser-induced CNV without toxic effect on retina, suggesting that Tc-MDP has therapeutic potential for CNV related diseases. [ABSTRACT FROM AUTHOR]

Purpose The purpose of this study is to evaluate the functional and morphological changes in subretinal xenografts of human retinal progenitor cells (hRPCs) in B6 mice treated with Cyclosporin A (CsA; 210 mg/l in drinking water). Methods: The hRPCs from human fetal eyes were isolated and expanded for transplantation. These cells, with green fluorescent protein (GFP) at 11 passages, were transplanted into the subretinal space in B6 mice. A combination of invasive and noninvasive approaches was used to analyze the structural and functional consequences of the subretinal injection of the hRPCs. The process of change was monitored using spectral domain optical coherence tomography (SDOCT), histology, and electroretinography (ERG) at 3 days, 1 week, and 3 weeks after transplantation. Cell counts were used to evaluate the survival rate with a confocal microscope. ERGs were performed to evaluate the physiologic changes, and the structural changes were evaluated using SDOCT and histological examination. Results: The results of the histological examination showed that the hRPCs gained a better survival rate in the mice treated with CsA. The SDOCT showed that the bleb size of the retinal detachment was significantly decreased, and the retinal reattachment was nearly complete by 3 weeks. The ERG response amplitudes in the CsA group were less decreased after the injection, when compared with the control group, in the dark-adapted and light-adapted conditions. However, the cone-mediated function in both groups was less affected by the transplantation after 3 weeks than the rod-mediated function. Conclusions: Although significant functional and structural recovery was observed after the subretinal injection of the hRPCs, the effectiveness of CsA in xenotransplantation may be a novel and potential approach for increasing retinal progenitor cell survival.

Purpose: The purpose of this study is to evaluate the functional and morphological changes in subretinal xenografts of human retinal progenitor cells (hRPCs) in B6 mice treated with Cyclosporin A (CsA; 210 mg/l in drinking water)., Methods: The hRPCs from human fetal eyes were isolated and expanded for transplantation. These cells, with green fluorescent protein (GFP) at 11 passages, were transplanted into the subretinal space in B6 mice. A combination of invasive and noninvasive approaches was used to analyze the structural and functional consequences of the subretinal injection of the hRPCs. The process of change was monitored using spectral domain optical coherence tomography (SDOCT), histology, and electroretinography (ERG) at 3 days, 1 week, and 3 weeks after transplantation. Cell counts were used to evaluate the survival rate with a confocal microscope. ERGs were performed to evaluate the physiologic changes, and the structural changes were evaluated using SDOCT and histological examination., Results: The results of the histological examination showed that the hRPCs gained a better survival rate in the mice treated with CsA. The SDOCT showed that the bleb size of the retinal detachment was significantly decreased, and the retinal reattachment was nearly complete by 3 weeks. The ERG response amplitudes in the CsA group were less decreased after the injection, when compared with the control group, in the dark-adapted and light-adapted conditions. However, the cone-mediated function in both groups was less affected by the transplantation after 3 weeks than the rod-mediated function., Conclusions: Although significant functional and structural recovery was observed after the subretinal injection of the hRPCs, the effectiveness of CsA in xenotransplantation may be a novel and potential approach for increasing retinal progenitor cell survival.

Objective: To investigate the morphological and functional changes of the laser-induced choroidal neovascularization (CNV) in rhesus monkeys., Methods: Experimental study. Eight adult rhesus monkeys weighted 4 to 7 kg were used in this study. CNVs were induced with small high-energy laser spots at short pulse duration by an argon green laser. Eyes were monitored weekly by color fundus photography, fluorescence fundus angiography (FFA) , and optical coherence tomography (OCT) . Fluorescein leaking intensities of grade 4 CNV lesions were analyzed by the method of ANOVA for repeated measures. Electroretinogram (ERG) was performed before laser photocoagulation and 56 days after laser photocoagulation and the data were analyzed with paired t-test., Results: (1) FFA revealed that the mean intensities of grade 4 CNV lesions were 89.44 ± 26.28, 97.56 ± 26.47, 110.22 ± 29.76, 100.26 ± 29.24, 91.77 ± 28.11, 77.76 ± 24.85 and 63.23 ± 22.34 on day 14, day 21, day 28, day 35, day 42, day 49, and day 56 respectively and the differences were statistically significant (F = 39.715, P < 0.01) . The differences between any time-point and its previous time-point were also statistically significant (t14-21 = 4.824, P < 0.01; t21-28 = 5.225, P < 0.01; t28-35 = 7.378, P < 0.01;t35-42 = 2.954, P < 0.05; t42-49 = 5.386, P < 0.01; t49-56 = 6.138, P < 0.01). (2) OCT images showed retinal edema, subretinal fluid and hyper-reflective lesions of CNVs in the laser sites and histopathology showed that fibrovascular tissues together with proliferating retinal pigment epithelium cells were seen in the laser sites. (3) ERG data revealed that implicit time of dark-adapted b wave (t = 4.23, P < 0.01) increased while the amplitudes of dark-adapted a wave (t = 6.35, P < 0.01) , dark-adapted b wave (t = 3.12, P < 0.01) and light-adapted b wave (t = 3.93, P < 0.01) decreased 56 days after laser photocoagulation compared with those before laser photocoagulation., Conclusion: The laser-induced CNV in non-human primate model shows continuous leakage on FFA examination and reduced amplitudes as well as increased implicit time on ERG examination, suggesting that laser-induced CNV primate model not only could be used to study the pathogenesis of CNV formation but also could be used for screening of drug effectiveness.