Long-term real-world outcomes of retinal microvasculature changes in proliferative diabetic retinopathy treated with panretinal photocoagulation vs. intravitreal conbercept.

PURPOSE: To compare long-term real-world outcomes of retinal microvasculature changes in proliferative diabetic retinopathy (PDR) treated with panretinal photocoagulation (PRP) vs. intravitreal conbercept (IVC) and to explore the potential factors affecting these changes. METHODS: This study retrospectively included 96 treatment-naïve PDR eyes of 96 type 2 diabetes mellitus patients [59 PRP and 37 IVC]. Baseline characteristics and treatment details were collected. Optical coherence tomography angiography (OCTA) data of macular vessel density (VD) and optic disc capillary density (CD) at baseline and at the last follow-up were compared between groups. The differences between the baseline and the last follow-up OCTA data in each group were also tested for significance. The correlation between the change in each OCTA parameter from baseline and each baseline characteristic/treatment parameter was investigated in each group. RESULTS: During a mean follow-up of two years, greater superficial (SCP) (p = 0.004) and deep capillary plexus (DCP) VD (p < 0.001) were observed in the foveal area in the PRP than in the IVC. Compared to the baseline, SCP VD in the foveal area increased in the PRP (p = 0.012), while an increased SCP VD in some sectors in the parafoveal and perifoveal areas (p < 0.05), rather than the foveal area (p = 0.908), was seen in the IVC. For both groups, eyes with a higher VD/CD at baseline tended to develop capillary dropout more intensively (all p < 0.05). In the IVC group, foveal avascular zone (FAZ) area change showed a negative correlation with baseline FAZ area (p = 0.020), and complementary PRP exerted a negative influence on FAZ area change (p = 0.002). In the PRP group, SCP VD change was positively correlated with follow-up frequency, and was negatively correlated with diastolic blood pressure (all p < 0.05); DCP VD change showed a positive correlation with PRP shot number (p = 0.019). CONCLUSION: The aforementioned microvasculature changes should be considered when PRP or IVC is adopted in PDR long-term management.

ERp29 Attenuates Nicotine-Induced Endoplasmic Reticulum Stress and Inhibits Choroidal Neovascularization.

Nicotine-induced endoplasmic reticulum (ER) stress in retinal pigment epithelium (RPE) cells is thought to be one pathological mechanism underlying age-related macular degeneration (AMD). ERp29 attenuates tobacco extract-induced ER stress and mitigates tight junction damage in RPE cells. Herein, we aimed to further investigate the role of ERp29 in nicotine-induced ER stress and choroidal neovascularization (CNV). We found that the expression of ERp29 and GRP78 in ARPE-19 cells was increased in response to nicotine exposure. Overexpression of ERp29 decreased the levels of GRP78 and the C/EBP homologous protein (CHOP). Knockdown of ERp29 increased the levels of GRP78 and CHOP while reducing the viability of ARPE-19 cells under nicotine exposure conditions. In the ARPE-19 cell/macrophage coculture system, overexpression of ERp29 decreased the levels of M2 markers and increased the levels of M1 markers. The viability, migration and tube formation of human umbilical vein endothelial cells (HUVECs) were inhibited by conditioned medium from the ERp29-overexpressing group. Moreover, overexpression of ERp29 inhibits the activity and growth of CNV in mice exposed to nicotine in vivo. Taken together, our results revealed that ERp29 attenuated nicotine-induced ER stress, regulated macrophage polarization and inhibited CNV.

Comparison of functional changes of retina after subthreshold and threshold pan-retinal photocoagulation in severe non-proliferative diabetic retinopathy.

PURPOSE: To find a new approach of pan-retinal photocoagulation (PRP) with less damage to the retina in the treatment of severe non-proliferative diabetic retinopathy (NPDR), this study compared functional changes in the retina after subthreshold and threshold PRP treatment in severe NPDR eyes. METHODS: Post hoc analysis of a randomized clinical trial was conducted in this study. Seventy eyes of 35 patients with bilateral, symmetric, severe NPDR were enrolled. Two eyes from the same patient were randomized into two groups, one eye received subthreshold PRP (S-PRP) and the other eye received threshold PRP (T-PRP). Comprehensive ophthalmological evaluations were performed on the baseline and every 3 months for 1 year. Visual field (VF) and full-field electroretinography (ERG) were performed on the baseline and repeated at month 12. RESULTS: During the 12-month follow-up, 4 eyes (11.4%) in the S-PRP group and 3 eyes (8.6%) in the T-PRP group progressed to proliferative diabetic retinopathy (PDR) stage, and there was no statistical difference in PDR progression rate between the two groups (P = 0.69). In addition, the changes in best-corrected visual acuity (BCVA) from baseline to month 12 between the two groups had no statistical difference (P = 0.30). From baseline to month 12, changes in central VF between the two groups had no statistical difference (P = 0.25), but changes in total score points of peripheral VF in the S-PRP group (- 242.1 ± 210.8 dB) and the T-PRP group (- 308.9 ± 209.7 dB) were statistically significant (P = 0.03). At month 12, ERG records showed that the amplitude of dark-adapted 0.01 ERG, dark-adapted 3.0 ERG, oscillatory potentials, light-adapted 3.0 ERG, and 30 Hz flicker ERG of both groups were significantly decreased from the baseline (P < 0.05). In addition, the amplitude of each ERG record in the S-PRP group decreased significantly less than those in the T-PRP group (P < 0.05). CONCLUSIONS: Subthreshold PRP is as effective as threshold PRP for preventing severe NPDR progress to PDR within 1 year with less damage to periphery VF and retinal function. CLINICALTRIALS: gov Identifier: NCT01759121.

CLINICAL CHARACTERISTICS OF EYES WITH DIFFERENT GRADES OF MYOPIC TRACTION MACULOPATHY: Based on the New Classification System.

PURPOSE: To analyze clinical characteristics in eyes with myopic traction maculopathy (MTM). METHODS: Nine hundred and ninety-one patients (1,334 eyes) with MTM, who visited Zhongshan Ophthalmic Center from January 2014 to December 2019, were involved. Myopic traction maculopathy was classified into six grades according to the new classification system: no macular schisis (T0), inner or outer foveoschisis (FS) (T1); inner and outer FS (T2), foveal detachment (T3), full-thickness macular hole (T4), and macular hole retinal detachment (T5). RESULTS: Seven hundred and seventy-eight (58.32%) eyes were in T0, 157 (11.77%) in T1, 177 (13.27%) in T2, 129 (9.67%) in T3, 45 (3.37%) in T4, and 48 (3.67%) in T5. With the severity of MTM, age increased and the best-corrected visual acuity became worse (P < 0.001). However, no significant differences were found on spherical equivalent refraction or axial length among different grades of MTM (P > 0.05). Moreover, significant differences on best-corrected visual acuity, spherical equivalent refraction, axial length, and staphyloma rate existed between eyes with inner FS and eyes with outer FS (P < 0.01), but not between eyes with outer FS and eyes with both inner FS and outer FS (P > 0.05). Besides, significant differences were found on spherical equivalent refraction, axial length, and staphyloma rate between full-thickness macular hole with and without macular schisis (P < 0.001). CONCLUSION: Spherical equivalent refraction and axial length were not correlated with the severity of MTM in this cohort. It might be preferable to categorize eyes with outer FS and eyes with both inner FS and outer FS as a same grade. Potential difference in the pathogenesis between full-thickness macular hole with and without macular schisis might exist.

Subthreshold Pan-Retinal Photocoagulation Using Endpoint Management Algorithm for Severe Nonproliferative Diabetic Retinopathy: A Paired Controlled Pilot Prospective Study.

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.

Dynamic changes and correlation analysis of outer retinal microstructure in macular area of central serous chorioretinopathy patients during restoration period.

PURPOSE: To investigate the dynamic changes and possible affecting variables of outer retinal microstructure in macular area of central serous chorioretinopathy (CSC) patients. METHODS: This was a retrospective study. The data of optical coherence tomography (OCT) and autofluoroscopy (AF) of 36 CSC patients admitted to our hospital from February 2012 to February 2013 were included. Dynamic variations and possible correlated variables of central retinal thickness (CRT), subretinal fluid diameter (SRFD), ellipsoid zone (EZ), interdigitation zone (IZ) and/or hyperautofluorescent spot (HAS) were analyzed. RESULTS: The outer retinal microstructure was gradually restored along with the subretinal fluid absorption during the follow-up. EZ in 94.4% (34/36) and the IZ in 100% (36/36) eyes were completely disappeared at baseline and restored (completed or incomplete) in 88.9% (8/9) and 44.4% (4/9) eyes, respectively, after 6-month follow-up. HAS was evident in 25% eyes (8/32 eyes) at baseline, and the density was initially increased and then declined during follow-up. Correlation analysis demonstrated that the restoration of EZ and IZ was correlated with the restoration period and subretinal fluid absorption. CONCLUSION: The outer retinal microstructure was restored during the subretinal fluid absorption in CSC patients, with EZ restored earlier than IZ. The restoration period and the absorption of subretinal fluid were two closely correlated variables of macular microstructure restoration.

MORPHOLOGICAL CHARACTERISTICS AND VISUAL ACUITY OF HIGHLY MYOPIC EYES WITH DIFFERENT SEVERITIES OF MYOPIC MACULOPATHY.

PURPOSE: To investigate the morphological feature, visual acuity, and prevalence of macular complications in highly myopic eyes with different categories of myopic maculopathy (MM) according to the META-PM classification system. METHODS: The clinical records of 1,132 consecutive patients (1,841 eyes) with high myopia (refractive error ≤ -6D and axial length ≥26.5 mm), who visited the High Myopia Clinic at the Zhongshan Ophthalmic Center from January 2014 to July 2017, were reviewed. Fundus photograph, optical coherence tomography, axial length, refractive error, and best-corrected visual acuity were measured in each patient. Myopic maculopathy was graded from fundus photographs according to the META-PM classification, including tessellated fundus (C1), diffuse chorioretinal atrophy (C2), patchy atrophy (C3), and macular atrophy (C4). Other macular complications, including foveoschisis, extrafoveal schisis, full-thickness macular hole, epiretinal membrane, lacquer cracks, Fuchs spot, choroidal neovascularization, macular hemorrhage, and dome-shaped macula, were also investigated. RESULTS: Among the 1,841 eyes, 58 (3.15%) had no MM (C0), 779 (42.31%) had tessellated fundus only (C1), 524 (28.46%) had diffuse chorioretinal atrophy (C2), 352 (19.12%) had patchy chorioretinal atrophy (C3), and 128 (6.95%) had macular atrophy (C4). Age increased and best-corrected visual acuity became worse with the severity of MM (P < 0.01). Axial length was significantly longer with the severity of MM from C0 to C3 (P < 0.01), and spherical equivalent was greater with the severity of MM from C0 to C3 (P < 0.01) but was not different between C3 and C4 (P > 0.05). Subfoveal and parafoveal choroidal thicknesses were significantly thinner from C0 to C3 (P < 0.01). However, no significant difference was found between C3 and C4 in parafoveal choroidal thickness (P > 0.05). The complications were different among C0 to C4 correlated with MM (P < 0.01). The complications of foveoschisis, choroidal neovascularization, hemorrhage, lacquer cracks, Fuchs spot, dome-shaped macula, and epiretinal membrane were different between C1 and C2 (P < 0.01), but none of the complications were different between C3 and C4 (P > 0.05) except Fuchs spot (P = 0.009). CONCLUSION: The morphological and functional characteristics in eyes with high myopia were positively correlated with the severity of C0 to C3 MM. However, no morphological difference was found between C3 and C4. The absence of the progressive relationship between C3 and C4 might be determined.

COMPARISON BETWEEN RELEASABLE SCLERAL BUCKLING AND VITRECTOMY IN PATIENTS WITH PHAKIC PRIMARY RHEGMATOGENOUS RETINAL DETACHMENT.

PURPOSE: To compare the efficiency of releasable scleral buckling (RSB) and pars plana vitrectomy (PPV) in the treatment of phakic patients with primary rhegmatogenous retinal detachment. METHODS: The current study was a prospective randomized clinical trial. One hundred and ten eyes from 110 patients with primary rhegmatogenous retinal detachment and proliferative vitreoretinopathy of Grade B or less were included in this study. The patients were randomly allocated into an RSB group and a PPV group. The functional and anatomical success was compared between groups. RESULTS: The primary anatomical success rate (PPV 41/43 [95.35%] and RSB 38/41 [92.68%]) and final anatomical success rate (PPV and RSB 100%) showed a nonsignificant difference. The best-corrected visual acuity, intraocular pressure, and complications were not different between the groups. However, the incidence of cataract progression was higher in the PPV group (26 of 43 [60.47%]) than in the RSB group (4 of 41 [9.76%]) at the 12-month follow-up. The subfoveal choroidal thickness increased significantly in the RSB group 3 months after surgery, but no longer differed at the postoperative 6-month and 12-month follow-ups. The axial length had increased significantly 1 month after surgery, but the difference was no longer significant at 3 months, 6 months, and 12 months. CONCLUSION: The RSB and PPV procedures have the same effects on the functional and anatomical success for patients with phakic primary rhegmatogenous retinal detachment. Nevertheless, based on the few cases of intraocular complications and cataract progression, we believe that the RSB technique should be preferentially recommended.

Anatomical and functional responses in eyes with diabetic macular edema treated with "1 + PRN" ranibizumab: one-year outcomes in population of mainland China.

BACKGROUND: To evaluate the anatomical and functional responses in eyes with diabetic macular edema (DME) treated with ranibizumab under "1 + pro re nata (PRN)" regimen. METHODS: This prospective interventional case series included 69 eyes of 69 patients with DME treated with intravitreal injections of 0.5 mg ranibizumab followed by repeated injections as needed. Best-corrected visual acuity (BCVA), central foveal thickness (CFT), subfoveal choroidal thickness (SFCT), and predictive factors for final visual outcomes were assessed. RESULTS: Logarithm of minimal angle of resolution (logMAR) BCVA improved from 0.64 ± 0.23 at baseline to 0.56 ± 0.27, 0.53 ± 0.26, 0.47 ± 0.25, 0.44 ± 0.32, 0.47 ± 0.26 and 0.46 ± 0.26 at time-point of months 1, 2, 3, 6, 9, and 12, respectively (P < 0.05 for any follow-up time-point except month 1). CFT decreased from 478.23 ± 172.31 µm at baseline to 349.74 ± 82.21 µm, 313.52 ± 69.62 µm, 292.59 ± 61.07 µm, 284.67 ± 69.85 µm, 268.33 ± 43.03 µm, and 270.39 ± 49.27 µm at above time-points, respectively (P < 0.05). The number of injections was 6.83 times over 12 months' follow-up under "1 + PRN" regimen. Multivariate analysis showed that the factors including age, BCVA at baseline, disruption of ellipsoid zone, posterior vitreous detachment (PVD), and vitreomacular traction (VMT) were correlated with the final BCVA. CONCLUSIONS: Intravitreal injections of ranibizumab under "1 + PRN" regimen is a not only effective but also safe way to improve visual acuity of DME patients. And older age, lower baseline BCVA, VMT, and disruption of ellipsoid zone are predictors for final poor BCVA while PVD is a positive predictive factor for good final BCVA. TRIAL REGISTRATION: The trial was registered retrospectively in ClinicalTrials.gov on 2 June 2019 (NCT03973138).

Effectiveness and Safety of Intravitreal Injection of Conbercept as an Initial Treatment for Exudative Circumscribed Choroidal Hemangioma.

OBJECTIVE: To investigate the effectiveness and safety of intravitreal injection of conbercept (IVC) as the initial treatment for exudative circumscribed choroidal hemangioma (CCH). METHODS: Forty-two eyes of 42 patients received 3 monthly IVC (0.5 mg/0.05 mL) as the initial treatment. Three months later, the patients were assessed for further treatment including observation, reinjection of conbercept, laser photocoagulation (if the lesion was 3,000 µm away from the macular fovea), or photodynamic therapy (PDT; if the lesion was under the macular fovea). Anatomical and functional responses including best corrected visual acuity (BCVA), central foveal thickness (CFT), and tumor size were analyzed. RESULTS: Twenty-three patients (54.76%) were sensitive to the monotherapy of IVC. Fourteen patients (33.33%) were insensitive to IVC and underwent rescue laser photocoagulation, and 5 patients (11.90%) underwent rescue PDT due to insensitivity to IVC treatment at 3 months. For subgroup analysis, although no statistical difference was found for BCVA at any follow-up time point compared to baseline, an increasing tendency of BCVA was found in the IVC group (p> 0.05). The mean CFT decreased significantly from 427.13 ± 214.74 µm at baseline to 259.83 ± 61.68 µm at 6 months in the IVC group (p< 0.05). No influence on tumor size was found in the IVC group. CONCLUSION: IVC as the initial treatment might be an option for exudative CCH.

APRPG-modified nanoliposome loaded with miR-146a-5p inhibitor suppressed choroidal neovascularization by targeting endothelial cells.

INTRODUCTION: To explore the effect and mechanism of APRPG-modified nanoliposomes loaded with miR-146a-5p inhibitor (ANL-miR-146a-5p inhibitor) on endothelial cell proliferation, migration, tube formation, and choroidal neovascularization (CNV) in mice. METHODS: ANL-miR-146a-5p inhibitors were generated by thin film hydration; in vitro, endothelial cell uptake experiment was used to detect the targeting effect of ANL-miR-146a-5p inhibitor; endothelial cells proliferation, migration, and tube formation were detected, respectively, by CCK8 assay, scratch assay, and Matrigel tube formation assay. In vivo, the mice CNV models were established by 810 nm laser photocoagulation. Mice choroidal flatmounts were performed to detect the volume of CNV after intravitreal injection of L-miR-146a-5p inhibitor, ANL-miR-146a-5p inhibitor, or normal saline; the vascular endothelial growth factor (VEGF) expression of mice choroidal tissue was detected by ELISA; HE section and electrophysiology (ERG) were performed to check the toxicity of ANL-miR-146a-5p inhibitor on mice retina. RESULTS: ANL are targeted to endothelial cells and are more targeted in inflammatory environment. At the same concentration, ANL-miR-146a-5p inhibitor's ability to inhibit endothelial cell proliferation, migration, tube formation, CNV formation, and VEGF expression is better than L-miR-146a-5p inhibitor (p < 0.05); ANL-miR-146a-5p inhibitor had no toxicity on the structure of mouse retina; ANL-miR-146a-5p inhibitor had no toxicity on the a-wave and b-wave amplitudes and b-wave implicit times (p > 0.05). CONCLUSIONS: ANL-miR-146a-5p inhibitor can more effectively down-regulate the expression level of VEGF through its targeting to endothelial cells, thereby more effectively inhibiting endothelial cell proliferation, migration, tube formation, and mice CNV formation.

Comparison between non-visualized polyps and visualized polyps on optical coherence tomography angiography in polypoidal choroidal vasculopathy.

PURPOSE: To determine the underlying reasons for the non-visualization of polyps on en face optical coherence tomography angiography (OCTA) in patients with polypoidal choroidal vasculopathy (PCV). METHODS: A cross-sectional study of consecutive treatment-naïve 30 eyes with active PCV was included. Results of fundus photography, fundus fluorescein angiography (FFA), indocyanine green angiography (ICGA), spectral domain optical coherence tomography (SD-OCT), and en face OCTA were analyzed. RESULTS: A total of 64 active polyps were found on FFA and ICGA in 30 eyes. On OCTA, 42/64 (65.6%) polyps were visualized, while 22/64 (34.4%) polyps were non-visualized. There were no significant differences in the size (P = 0.723) and filling time of polyps (P = 0.558) between the two groups. However, polypoidal lesions were less common in the non-visualized group (P < 0.001). The height of the polyps on SD-OCT was 243.95 ± 114.24 µm in the non-visualized group, which was higher than those (188.00 ± 87.93 µm) in the visualized group (P = 0.048). Moreover, more pulsatile polyps (72.7%) were found in the non-visualized group than those (2.4%) in the visualized group (P < 0.001). Four of the 22 polyps in the non-visualized group (18.2%) were located under a thick subretinal hemorrhage, and two of 22 invisible polyps (9.6%) located under and parallel to the retinal vessel in the inner layer of retina. CONCLUSIONS: Our results revealed that the height of the polyps, and not the size and pulsation of the polyps, correlated with the visualization of the polyps on OCTA. Polyps that were pulsating in early ICGA were difficult to be visualized on OCTA, which is the most possible reason for the non-visualization. Coverage with thick subretinal hemorrhage or retina vessels was another reason for the non-visualization of the polyps in active PCV on OCTA.

Comparison of vascular parameters between normal cynomolgus macaques and healthy humans by optical coherence tomography angiography.

BACKGROUND: The metabolic activity of retina is higher than other human tissues and is crucial to the vision. Cynomolgus macaques is widely used in ophthalmic disease research. The evaluation and comparison of macular and optic disc vascular circulation parameters between normal adult cynomolgus macaques and healthy adult humans using OCT-A can promote better use of nonhuman primate models in studies of ophthalmic vascular disease. METHODS: Twelve normal adult cynomolgus macaques with a mean age of 4.91 ± 0.43 years were studied for data collection. The macula of 28 adult healthy humans (14 males and 14 females), with a mean age of 25.11 ± 6.21 years and the optic discs of 9 adult healthy humans (4 males and 5 females) with a mean age of 28.56 ± 6.78 years were measured. The vessel density (VD) was measured using an RTVue XR with AngioVue. The scan sizes of the macular and optic discs were 3 × 3 mm and 4.5 × 4.5 mm, respectively. RESULTS: OCT-A can image the superficial and deep capillary plexuses and radial peripapillary capillary network. In RPC layer of the optic disc, the VD in the nasal quadrant was lower than the VD in the inferior temporal quadrant. Similarities and significant differences in VD between healthy humans and cynomolgus macaques were obtained using OCT-A. CONCLUSIONS: This study provides normal vascular parameters for adult cynomolgus macaques using OCT-A to help establish an optical parameter database for cynomolgus macaques and compare VD between healthy humans and cynomolgus macaques to promote choroid-retinopathy research. TRIAL REGISTRATION: Current Controlled Trials NCT03692169 , retrospectively registered on 26 sept 2018.

Quantitative Analysis of Retinal Microvascular Changes after Conbercept Therapy in Branch Retinal Vein Occlusion Using Optical Coherence Tomography Angiography.

PURPOSE: To quantitatively evaluate microvascular changes in eyes with macular oedema due to branch retinal vein occlusion (BRVO) using optical coherence tomography angiography (OCTA) before and after intravitreal conbercept injection and the correlation of such changes with best-corrected visual acuity (BCVA) and retinal thickness. METHODS: Twenty-eight eyes of 28 patients treated with a single intravitreal injection of conbercept for macular oedema due to BRVO were included in this study. The automatically measured values of the vessel density in the superficial (SCP) and deep retinal capillary plexus (DCP), the foveal avascular zone (FAZ) area, the FAZ perimeter, the vessel density within a 300 µm wide ring surrounding the FAZ (FD-300), the acircularity index (AI), the choriocapillaris flow area and the retinal thickness were obtained via OCTA before and at 1 month after initial injection and compared with those of age- and sex- matched healthy subjects. RESULTS: In BRVO eyes, the vascular density in the SCP and DCP, the FD-300 and the flow area of choriocapillaris were significantly lower than those in healthy eyes, while the AI and the retinal thickness were significantly increased. After treatment, the retinal thickness in eyes with BRVO was significantly decreased in all quadrants, and the mean BCVA dramatically increased from 20/162 to 20/78 (p = 0.0017). The mean flow area of choriocapillaris significantly improved after treatment. Moreover, negative correlations between the logMAR BCVA and the whole vascular density in the SCP and DCP as well as the flow area of choriocapillaris were observed. CONCLUSION: OCTA enables non-invasive, layer-specific and quantitative assessment of microvascular changes in eyes with BRVO before and after treatment, and it can be used as a valuable imaging tool for the evaluation of the follow-up in BRVO patients.

Two different initial treatment regimens of ranibizumab in myopic choroidal neovascularization: 12-month results from a randomized controlled study.

IMPORTANCE: The optimal treatment regimen for myopic choroidal neovascularization (mCNV) is essential to understand but currently poorly studied. BACKGROUND: To date, there is still no consensus on the optimal dosage and frequency of anti-vascular endothelial growth factor injections in treating mCNV. DESIGN: A prospective, single-centre, single-blind, randomized controlled study. PARTICIPANTS: Adult patients with active mCNV. METHODS: Patients were randomized 1:1 to one or three doses initial ranibizumab treatments. Additional injections were administered pro re nata (prn) over 12 mo. MAIN OUTCOME MEASURES: Number and frequency of injections. RESULTS: Fifty patients participated in the study. Patients in both 1 + prn or 3 + prn groups experienced similar best-corrected visual acuity gain and anatomical improvement, including central retinal thickness (CRT), CNV thickness, area of CNV and area of leakage. Over 12 mo, patients in the 1 + prn group received fewer ranibizumab injections (2.04 ± 1.22) compared with the 3 + prn group (3.58 ± 0.72, P<0.0001), but no statistic difference of the injection received was observed in the prn period. During the follow-up, 15 of 26 eyes in the 1 + prn group and 10 of 24 eyes in the 3 + prn group received additional injections after initial dosing (P = 0.2575). Cox regression analysis showed that 1 + prn, female, age > 55 y and CRT > 300 µm are risk factors for retreatment. CONCLUSIONS AND RELEVANCE: The eyes with a single loading dose achieved parallel anatomical and functional visual improvement, while required less injections over 1 y. The risk factors for retreatment include 1 + prn, female, older age and thick retina thickness.

A pilot prospective study of 577-nm yellow subthreshold micropulse laser treatment with two different power settings for acute central serous chorioretinopathy.

To compare the efficacy of 50% threshold power with 25% threshold power of 577-nm subthreshold micropulse laser (SMPL) for acute central serous chorioretinopathy (CSC). Prospective, interventional, non-randomized, comparative case series. A total of 54 patients (54 eyes) with acute CSC were enrolled. Twenty-four eyes received 25% threshold power and 30 eyes received 50% threshold power of 577-nm SMPL. Best-corrected visual acuity (BCVA), central macular thickness (CMT), and complete absorption of subretinal fluid (SRF) were evaluated at 1 month and 3 months. The complete absorption rate of SRF in the 50% power group was significantly greater than that in the 25% power group at 1 month (70.0% vs 25.0%, p < 0.001) and at 3 months (83.3% vs 54.2%, p < 0.001). Mean BCVA improved from 0.34 ± 0.20 LogMAR to 0.02 ± 0.13 LogMAR in the 50% power group and from 0.27 ± 0.15 LogMAR to 0.14 ± 0.21 LogMAR in the 25% power group with a significant difference between the two groups after 3 months (p = 0.027). In the 50% power group, the CMT decreased from 491.6 ± 154.8 µm at baseline to 231.3 ± 92.3 µm at 1 month and 228.2 ± 88.1 µm at 3 months, and in the 25% power group, the CMT decreased from 444.9 ± 164.1 to 306.8 ± 102.6 µm at 1 month and 254.5 ± 101.7 µm at 3 months. There was statistical difference of CMT at 1 month (p = 0.009) but no significant difference at 3 months between the two groups (p = 0.232). SMPL with 50% threshold power may be more effective than 25% threshold power for acute CSC.

Comparison of the effects of photodynamic therapy, intravitreal ranibizumab and combination for polypoidal choroidal vasculopathy under 1 + PRN regimen.

BACKGROUND: The optimal treatment for polypoidal choroidal vasculopathy (PCV) is still under debate. Little knowledge is known about the treatment effect of "1+pro re nata(PRN)" treatment regimen for PCV. The aim of this study was to compare the outcomes of photodynamic therapy (PDT), intravitreal ranibizumab injection (IVR) and combination therapy under the "1 + PRN" treatment regimen for PCV. METHODS: Fifty-seven eyes of 57 patients completed the 12 months' follow-up in this prospective study. The patients in the PDT arm(n = 23), ranibizumab arm(n = 18), or combination arm(n = 16) underwent a session of PDT, IVR or combination of both at baseline followed by additional IVR as needed. Mean change of logarithm of the minimal angle of resolution (logMAR) visual acuity (VA), central foveal thickness (CFT) and the regression rate of polyps were evaluated. Cost-benefit analysis was also performed. RESULTS: At Month 12, the mean logMAR VA improved from 0.90 ± 0.52 to 0.75 ± 0.57 in the PDT group (P < 0.05), from 0.96 ± 0.58 to 0.77 ± 0.41 in the IVR group (P < 0.05), and from 0.94 ± 0.55 to 0.72 ± 0.44 in the combination group (P < 0.05), respectively. The CFT decreased from 478.04 ± 156.70 µm, 527.5 ± 195.90 µm, and 522.63 ± 288.40 µm at the baseline to 366.43 ± 148.28 µm, 373.17 ± 134.88 µm and 328.44 ± 103.25 in the PDT group (P < 0.05), IVR group (P < 0.01), and the combination group (P < 0.05), respectively. However, no statistical difference was found between groups (P > 0.05). PDT treatment (60.87%) was superior to the IVR therapy (22.22%) in achieving complete regression of polyps (P < 0.05). Cost-benefit analysis showed that IVR treatment cost the least money for improving per 0.1logMAR units and the combination therapy demanded the least money for reducing per 100 µm of CFT. CONCLUSIONS: PDT, IVR and the combination therapy have similar efficacy in the VA improvement as well as the reduction of CFT under the "1 + PRN" treatment regimen. TRIAL REGISTRATION: Current Controlled Trials NCT03459144 . Registered retrospectively on March 2, 2018.

Correction to: Electroretinogram evaluation for the treatment of proliferative diabetic retinopathy by short-pulse pattern scanning laser panretinal photocoagulation.

The published online version contains incorrect data in Table 2 caption. Argon should not be mentioned in the caption as this is not used in this paper.

Electroretinogram evaluation for the treatment of proliferative diabetic retinopathy by short-pulse pattern scanning laser panretinal photocoagulation.

Panretinal photocoagulation (PRP) is a standard method for proliferative diabetic retinopathy (PDR) treatment. However, conventional PRP usually significantly damages the retinal structure and vision. Retinal pattern scanning laser (PASCAL) photocoagulation has emerged as a new technique with fewer complications for the treatment of retinal disorders. This study compares the therapeutic effects of short-pulse PASCAL to conventional single-spot PRP for PDR. Fifty-two PDR patients (104 eyes) were randomly assigned into a short-pulse PASCAL-PRP treatment (SP) group and a conventional PRP treatment (TP) group. The best corrected visual acuity (BCVA) and full-field flash electroretinogram (ERG) data were evaluated before and after the two treatments. The BCVA data between before and after the PRP treatments did not show any significant difference. After the PRP treatment, the b-wave amplitude (b-A) in the dark-adapted 3.0 ERG (p = 0.0005) and the amplitude in the light-adapted 3.0 flicker ERG (p = 0.009) were significantly higher in the SP group compared with that of the TP group. In addition, after the PRP treatment, the a-wave implicit time (a-T) of light-adapted 3.0 ERG prolonged significantly in the TP group compared to the SP group. Compared with the parameters before the treatments, the a-A and b-A under dark-adapted 3.0 ERG and the b-A under the light-adapted 3.0 ERG in both TP and SP groups after the treatments decreased significantly (p < 0.05). Short-pulse PASCAL-PRP significantly attenuated partial vision damage compared to conventional PRP, although it still caused limited retinal injury and mild reduction in retinal function. These findings suggest that short-pulse PASCAL-PRP is a promising technique for PDR treatment.

Activation of the UPR protects against cigarette smoke-induced RPE apoptosis through up-regulation of Nrf2.

Recent studies have revealed a role of endoplasmic reticulum (ER) stress-induced unfolded protein response (UPR) in the regulation of RPE cell activity and survival. Herein, we examined the mechanisms by which the UPR modulates apoptotic signaling in human RPE cells challenged with cigarette smoking extract (CSE). Our results show that CSE exposure induced a dose- and time-dependent increase in ER stress markers, enhanced reactive oxygen species (ROS), mitochondrial fragmentation, and apoptosis of RPE cells. These changes were prevented by the anti-oxidant NAC or chemical chaperone TMAO, suggesting a close interaction between oxidative and ER stress in CSE-induced apoptosis. To decipher the role of the UPR, overexpression or down-regulation of XBP1 and CHOP genes was manipulated by adenovirus or siRNA. Overexpressing XBP1 protected against CSE-induced apoptosis by reducing CHOP, p-p38, and caspase-3 activation. In contrast, XBP1 knockdown sensitized the cells to CSE-induced apoptosis, which is likely through a CHOP-independent pathway. Surprisingly, knockdown of CHOP reduced p-eIF2α and Nrf2 resulting in a marked increase in caspase-3 activation and apoptosis. Furthermore, Nrf2 inhibition increased ER stress and exacerbated cell apoptosis, while Nrf2 overexpression reduced CHOP and protected RPE cells. Our data suggest that although CHOP may function as a pro-apoptotic gene during ER stress, it is also required for Nrf2 up-regulation and RPE cell survival. In addition, enhancing Nrf2 and XBP1 activity may help reduce oxidative and ER stress and protect RPE cells from cigarette smoke-induced damage.