Stem cell factor protects against chronic ischemic retinal injury by modulating on neurovascular unit.

Retinal ischemia is a significant factor in various vision-threatening diseases, but effective treatments are currently lacking. This study explores the potential of stem cell factor (SCF) in regulating the neurovascular unit as a therapeutic intervention for retinal ischemic diseases. A chronic retinal ischemia model was established in Brown Norway rats using bilateral common carotid artery occlusion (BCCAO). Subsequent SCF treatment resulted in a remarkable recovery of retinal function, as indicated by electroretinogram, light/dark transition test, and optokinetic head tracking test results. Histological examination demonstrated a significant increase in the number of retinal neurons and an overall thickening of the retina. Immunofluorescence confirmed these findings and further demonstrated that SCF treatment regulated retinal remodeling. Notably, SCF treatment ameliorated the disrupted expression of synaptic markers in the control group's BCCAO rats and suppressed the activation of Müller cells and microglia. Retinal whole-mount analysis revealed a significant improvement in the abnormalities in retinal vasculature following SCF treatment. Transcriptome sequencing analysis revealed that SCF-induced transcriptome changes were closely linked to the Wnt7 pathway. Key members of the Wnt7 pathway, exhibited significant upregulation following SCF treatment. These results underscore the protective role of SCF in the neurovascular unit of retinal ischemia rats by modulating the Wnt7 pathway. SCF administration emerges as a promising therapeutic strategy for retinal ischemia-related diseases, offering potential avenues for future clinical interventions.

Deep Learning based Retinal Vessel Caliber Measurement and the Association with Hypertension.

PURPOSE: To develop a highly efficient and fully automated method that measures retinal vessel caliber using digital retinal photographs and evaluate the association between retinal vessel caliber and hypertension. METHODS: The subjects of this study were from two sources in Beijing, China, a hypertension case-control study from Tongren Hospital (Tongren study) and a community-based atherosclerosis cohort from Peking University First Hospital (Shougang study). Retinal vessel segmentation and arteriovenous classification were achieved simultaneously by a customized deep learning model. Two experienced ophthalmologists evaluated whether retinal vessels were correctly segmented and classified. The ratio of incorrectly segmented and classified retinal vessels was used to measure the accuracy of the model's recognition. Central retinal artery equivalents, central retinal vein equivalents and arteriolar-to-venular diameter ratio were computed to analyze the association between retinal vessel caliber and the risk of hypertension. The association was then compared to that derived from the widely used semi-automated software (Integrative Vessel Analysis). RESULTS: The deep learning model achieved an arterial recognition error rate of 1.26%, a vein recognition error rate of 0.79%, and a total error rate of 1.03%. Central retinal artery equivalents and arteriolar-to-venular diameter ratio measured by both Integrative Vessel Analysis and deep learning methods were inversely associated with the odds of hypertension in both Tongren and Shougang studies. The comparisons of areas under the receiver operating characteristic curves from the proposed deep learning method and Integrative Vessel Analysis were all not significantly different (p > .05). CONCLUSION: The proposed deep learning method showed a comparable diagnostic value to Integrative Vessel Analysis software. Compared with semi-automatic software, our deep learning model has significant advantage in efficiency and can be applied to population screening and risk evaluation.

Characteristics and surgery outcomes of macular hole diagnosed after rhegmatogenous retinal detachment repair.

PURPOSE: To report the characteristics and the visual and anatomical outcomes of secondary macular holes (SMHs) diagnosed after rhegmatogenous retinal detachment (RRD) repair and their associated factors. METHODS: Retrospective, interventional case series. All consecutive patients who were diagnosed with SMH after RRD repair at Beijing Tongren eye center from January 2016 to April 2021 were included. Patients who had their primary RRD repair in other hospitals and were referred to our center after diagnosis of SMH were also included. The minimum follow-up time after RRD repair was 6 months. RESULTS: 37 SMHs were diagnosed within a series of 5696 RRDs. Including 24 eyes referred from other hospitals after the diagnosis of SMH, 61 eyes were included. The type of primary RRD repair surgery included 22/61 (36%) eyes with scleral buckling procedure (SBP) and 39/61 (64%) eyes with pars plana vitrectomy (PPV). 21/61 (34%) eyes had recurrent RD. The median time to SMH diagnosis was 150 days (range, 7 ~ 4380 days). Macular hole (MH) closure was achieved in 77% eyes. Visual acuity (VA) improvement of at least 2 lines of Snellen's visual acuity was observed in 51% eyes. Final MH closure status was associated with preoperative MH diameter (for every 50 µm increment) (P = 0.046, OR = 0.875, 95%CI: 0.767 ~ 0.998). VA improvement was associated with final MH closure status (P = 0.009, OR = 8.742, 95%CI: 1.711 ~ 44.672). Final VA (logMAR) was associated with recurrent RD (P < 0.001, B = 0.663, 95%CI: 0.390 ~ 0.935), preoperative MH diameter (P = 0.001, B = 0.038, 95%CI: 0.017 ~ 0.058), VA at the time of SMH diagnosis (P < 0.001, B = 0.783, 95%CI: 0.557 ~ 1.009) and final MH closure status (P = 0.024, B = -0.345, 95%CI: -0.644 ~ -0.046). For patients without recurrent RD, VA improvement and final VA was associated with final MH closure status (P = 0.016 and P < 0.001, respectively), while for patients with recurrent RD, VA improvement or final VA did not associate with final MH closure status (P > 0.05). CONCLUSION: For SMH diagnosed after RRD repair, final MH closure status was associated with preoperative MH diameter. Recurrent RD, larger preoperative MH diameter, worse VA at the time of SMH diagnosis and failed MH closure are predictive factors for worse final VA. Visual outcome is associated with final MH closure status in patients without recurrent RD, but not as so in patients with recurrent RD.

Dynamic Characteristics of Asphalt Concrete as an Impervious Core in Embankment Dams under Varying Temperatures and Stress States.

To reveal the dynamic characteristics of asphalt core embankment dams (ACEDs), we carried out a dynamic triaxial experiment on hydraulic asphalt concrete (HAC) under different temperatures (T = 4 °C, 10 °C, 16 °C, and 22 °C) and stress states (Kc = 1.0, 1.2, 1.4, and 1.6; σ3 = 0.5, 0.6, 0.7, and 0.8 MPa). The results indicate that HAC's maximum dynamic elastic modulus increased with decreasing temperature, increasing principal stress ratio, and increasing confining pressure. However, the damping ratio showed the opposite trend. Moreover, in order to study the deformation capacity of HAC, 300 cyclic loads were applied to some specimens. At a temperature of 22 °C, the specimens had a tendency to deform axially, but not significantly. With a decrease in temperature, the axial deformation tendency of the specimen gradually weakened or even disappeared. However, a small number of cracks appeared in the aggregate and between the asphalt and the aggregate of the specimen. In order to quantify the dependence of dynamic parameters on temperature, the temperature influence factor of the maximum dynamic elastic modulus and the temperature sensing factor of the damping ratio were defined. The variation in the temperature influence factor of the maximum dynamic elastic modulus with temperature can be described by a logistic function. The temperature sensing factor of the damping ratio increased with an increasing principal stress ratio and peripheral pressure. Finally, maximum dynamic elastic modulus and damping ratio computational models for the interaction of temperatures and stress states were developed using the normalization method. Upon comparison, the dynamic parameters were observed to be very close to those listed in the literature, which verifies the applicability of the computational models of the maximum dynamic elastic modulus and damping ratio.

Positive correlation between hypertensive retinopathy and albuminuria in hypertensive adults.

PURPOSE: We investigated the association between albuminuria and hypertensive retinopathy (HR) in hypertensive adults. METHODS: This was a cross-sectional subgroup analysis of data from the China Stroke Primary Prevention Trial. We enrolled 2,964 hypertensive adults in this study. Keith-Wagener-Barker stages was used to assess HR. The urinary albumin to creatinine ratio (UACR) was calculated to evaluate albuminuria. RESULTS: HR was found in 76.6% (n = 2, 271) of the participants, albuminuria was found in 11.1% (n = 330). The UACR levels were significantly higher in subjects with HR than in those without HR (grade 1, ß = 1.42, 95% confidence intervals [CI]: -0.12, 2.95, p = 0.070; grade 2, ß = 2.62, 95% CI: 0.56, 4.67, p = 0.013; grade 3, ß = 5.17, 95% CI: 1.13, 9.20, p = 0.012). In the subgroup analyses, the association between HR and UACR was stronger in current smokers (p for interaction = 0.014). The correlation between HR grades 1 and 2 and UACR was stronger in subjects with higher triglyceride levels (≥ 1.7 mmol/L), but for grade 3 HR, this correlation was stronger in subjects with lower triglycerides levels (< 1.7 mmol/L, p for interaction = 0.023). The odds of albuminuria were significantly higher in subjects with HR than in those without HR (grade 1, odds ratio [OR] = 1.57, 95% CI: 1.08, 2.29, p = 0.019; grade 2, OR = 2.02, 95% CI: 1.28, 3.18, p = 0.002; grade 3, OR = 2.12, 95% CI: 0.99, 4.55, p = 0.053). In the subgroup analyses, the association between HR grades 1 and 2 and albuminuria was stronger in subjects with higher triglycerides levels (≥ 1.7 mmol/L), but for grade 3 HR, this correlation was stronger in subjects with lower triglyceride levels (< 1.7 mmol/L, p for interaction = 0.014). CONCLUSION: HR was positively correlated with albuminuria in hypertensive Chinese adults. This correlation was more remarkable when the population was stratified by triglycerides levels and smoking status. HR can be used as an indicator of early renal injury.

Association Between Diabetic Retinopathy, Brain Structural Abnormalities, and Cognitive Impairment for Accumulated Evidence in Observational Studies.

PURPOSE: To evaluate the association between diabetic retinopathy (DR) and cerebral disease or cognitive impairment. DESIGN: Systematic review and meta-analysis. METHOD: The hypothesis was formulated prior to data collection. Cross-sectional studies and cohort studies that assessed the association between any measure of DR and cerebral small vessel disease or any type of cognitive impairment in diabetic participants were included. The data were independently extracted by two investigators. This systematic review and meta-analysis adhered to the Preferred Reporting Items for Systematic Reviews and Meta-analyses and Meta-analysis of Observational Studies in Epidemiology guidelines RESULTS: A total of 27 studies were included. The combined odds ratio of 5 cross-sectional/cohort studies that reported that the associations between DR and cerebral structural changes was 1.75 (95% confidence interval [CI]: 1.36-2.25). The combined hazard ratio of 4 cohort studies that examined the association between DR and cognitive impairment events was 1.47 (95% CI: 1.22-1.78). The combined odds ratio of 14 cross-sectional/cohort studies that examined the association between DR and different cognitive impairment events was 1.43 (95% CI: 1.06-1.93). The overall coefficient (ß) of 4 studies that examined the relationship between DR and specific cognitive performance was 0.09 (95% CI: 0.00-0.18). Considering the quality of the data, we have performed subgroup analysis in studies scored >7 and studies scored ≤7, respectively, according to the Newcastle-Ottawa scale. CONCLUSION: The present meta-analysis suggests that DR is associated with an increased risk of structural abnormalities in the brain and cognitive impairment. This association remained significant after adjusting for blood glucose, and the presence of hypertension, indicating that DR is an important danger signal for cerebral abnormalities.

Clinical Spectrum of Uveitis Induced by Herpes Simplex Virus with Posterior Pole Involvement at Initial Presentation: A Case Series and Literature Review.

PURPOSE: To report four cases of herpes simplex virus-induced uveitis with posterior pole involvement at initial presentation. CASE PRESENTATIONS: In case 1, the posterior pole initially showed dense vitreous hemorrhage from the optic disc, multiple subretinal lesions around the optic disc, and retinal arterial sheath prior to retinal necrosis. In case 2, the posterior pole presented with optic disc edema, retinal venous tortuosity, and arterial sheathing around the optic disc prior to the peripheral retinal necrosis. In case 3 diagnosed with posterior herpetic uveitis, the posterior pole showed retinal arterial sheath and macular structural abnormities. In case 4, the posterior pole demonstrated optic disc swelling, along with perivascular retinal hemorrhage 4 days prior to peripheral retinal necrosis. CONCLUSIONS: Posterior pole involvement might occur either solely or before the development of peripheral retinal necrosis in patients with herpes simplex virus-induced acute retinal necrosis with and without prior central nervous system herpetic virus infection.

The impact of the COVID-19 Pandemic on rhegmatogenous retinal detachment treatment patterns.

BACKGROUNDS: To describe changes in rhegmatogenous retinal detachment (RRD) surgical procedures in Beijing during the COVID-19 Pandemic. METHODS: A retrospective cohort of RRD patients was analyzed. Patients were divided into the COVID-19 pandemic group and pre-COVID-19 group according to their presentation. The presurgery characteristics, surgical procedures, and surgery outcomes were collected. The potential factors related to the choice of pars plana vitrectomy (PPV) or scleral buckling (SB) were analyzed using logistic regression. The differences in the procedure choice under specific conditions were compared. Surgery outcomes were compared between the two groups. RESULTS: In the COVID-19 pandemic group, less patients received SB (27.8, 41.3%, p = 0.02) while more patients received PPV (72.2, 58.6%, p = 0.02); in patients who received SB, fewer patients received subretinal fluid drainage (45.4,75.7%, p = 0.01); in patients who received PPV, fewer patients received phacovitrectomy (7.0, 21.0%, p = 0.02). The choice of PPV was related to older age (1.03, p = 0.005), the presence of RRD with choroidal detachment (RRD-CD) (2.92, p = 0.03), pseudophakia (5.0, p = 0.002), retinal breaks located posterior to the equator (4.87, p < 0.001), macular holes (9.76, p = 0.005), and a presurgery visual acuity (VA) less than 0.02 (0.44, p = 0.03). Fewer phakia patients with retinal breaks located posterior to the equator (1/28, 11/30, p = 0.01) and fewer patients with chronic RRD and subretinal strand (1/9, 9/16, p = 0.03) received SB in the COVID-19 pandemic group. There were more patients with improved VA (55.7, 40.2%, p = 0.03) in the COVID-19 pandemic group. The overall single-surgery retinal attachment rate was similar in the two groups (94.9, 94.5%, p = 0.99). CONCLUSIONS: During the COVID-19 Pandemic, the main reason for the increased number of PPV in RRD treatment was that more complicated cases were presented. However, the surgeons were conservative in procedure choice in specific cases. The adjustments on RRD treatments lead to comparable surgery outcomes.

The impact of the COVID-19 pandemic lockdown on rhegmatogenous retinal detachment services-Experiences from the Tongren eye center in Beijing.

PURPOSE: To investigate the impact on services for rhegmatogenous retinal detachment (RRD) patients during the COVID-19 (2019coronal virus disease) pandemic in one tertiary center in Beijing. METHODS: A retrospective cohort study. Two reviewed consecutive RRD patients cohorts of the same length were treated during two different periods: the COVID-19 pandemic and the pre-COVID-19 group. The characteristics of patients, surgery, anesthesia methods, length of hospital stay, and the latest follow-up were recorded and analyzed. RESULTS: There were 79 patients in the COVID-19 pandemic group with a 55.9% reduction (179). Compared to patients in the pre-COVID-19, patients in the COVID-19 pandemic had a longer presurgical waiting times (28days, 3days, p<0.001), a higher percentage of patients with presurgical poor (less than 0.02) visual acuity (55.7%, 32.4%, p = 0.009), and a higher percentage of patients with presurgical choroidal detachment (34.2%, 19.6%, p = 0.01). There was no significant difference in the severity of presurgical proliferative vitreoretinopathy between the two groups (p = 0.64). Surgeries on pathological myopia patients with macular hole retinal detachment were postponed in the COVID-19 pandemic. There was a lower percentage of scleral buckling (27.8%, 41.3%, p = 0.02) and a lower rate of subretinal fluid drainage (45.4%, 75.7%, p = 0.01) in the COVID-19 pandemic. There was no significant difference in either postoperative visual acuity (p = 0.73) or the rate of single-surgery retinal attachment (p = 1) between the two groups. Patients in the COVID-19 pandemic had a shorter length of hospital stay (3hours, 35 hours, p<0.001), and a lower percentage of patients received general anesthesia (48.1%, 83.2%, p<0.001). None was infected with COVID-19 disease during the pandemic. CONCLUSION: The COVID-19 pandemic lockdown caused prolonged presurgical waiting times, shorter hospital stays, less general anesthesia, and a significant reduction of RRD surgeries. The RD were more complicated, the surgeons were more conservative on procedures and patients selection, while the surgery outcomes were comparable.

Peripheral arterial filling time and peripheral retina fluorescence features in ultra-widefield angiography.

AIM: To evaluate the peripheral arterial filling time (PAFT) and venous filling time (VFT) in eyes without known diseases that may influence filling process using ultra-widefield (UWF) fluorescein angiography (FA), and to review the peripheral retina fluorescence features. METHODS: A total of 30 eyes of 30 patients were retrospectively reviewed in this observational study. UWF-FA was performed using Optos 200Tx. PAFT and VFT was recorded. The interval between the arterial or venous filling completion and the previous photo was documented. The appearance of the far peripheral retina was described as either granular background fluorescence or mottled fluorescent band or vascular leakage. Terminal vascular patterns was described as loop pattern or branching pattern. Microvascular abnormalities such as arteriovenous shunting, vessels crossing the horizontal raphe, right angle vessels, terminal networks, capillary nonperfusion, drusen or microaneurysms were evaluated. RESULTS: The normal limits of PAFT was 3.397-8.984s and 4.399-11.753s for VFT. The appearance of the far peripheral retina, defined as granular background (63%), mottled fluorescence (20%), or vascular leakage (17%), was symmetrical between both eyes. Capillary nonperfusion (23%) and microaneurysms (40%) were more frequently found in eyes with loop pattern than in eyes with branching pattern. Other peripheral signs such as right-angle vessels (73%), and terminal networks (80%) were commonly seen on UWF-FA in the normal peripheral retina. CONCLUSION: The main courses of retinal artery and vein filling time are overlapping with each other on UWF-FA. Notably, the arterial filling process is completed in the arteriovenous phase rather than the traditionally named arterial phase. There are various manifestations in the peripheral retina of normal eyes.

Hypertensive Retinopathy and the Risk of Stroke Among Hypertensive Adults in China.

Purpose: This study aimed to investigate the association between hypertensive retinopathy and the risk of first stroke, examine possible effect modifiers in hypertensive patients, and test the appropriateness of the Keith-Wagener-Barker (KWB) classification for predicting stroke risk. Methods: In total, 9793 hypertensive participants (3727 males and 6066 females) without stroke history from the China Stroke Primary Prevention Trial were included in this study. The primary outcome was first stroke. Results: Over a median follow-up of 4.4 years, 592 participants experienced their first stroke (509 ischemic, 77 hemorrhagic, and six unclassifiable strokes). In total, 5590 participants were diagnosed with grade 1 retinopathy (57.08%), 1466 with grade 2 retinopathy (14.97%), 231 with grade 3 retinopathy (2.36%), and three with grade 4 retinopathy (0.03%). Grades 1 and 2 were merged and classified as mild retinopathy, and grades 3 and 4 were merged and classified as severe retinopathy. There was a significant positive association between hypertensive retinopathy and the risk of first stroke and first ischemic stroke, and no effect modifiers were found. The hazard ratios (HRs) for first stroke were as follows: mild versus no retinopathy, 1.26 (95% confidence interval [CI], 1.01-1.58, P = 0.040), and severe versus no retinopathy, 2.40 (95% CI, 1.49-3.84, P < 0.001). The HRs for ischemic stroke were as follows: severe versus no retinopathy, 2.35 (95% CI, 1.41-3.90, P = 0.001), and nonsignificantly increased HRs for mild versus no retinopathy, 1.26 (95% CI, 0.99-1.60, P = 0.057). Conclusions: There was a significant positive association between hypertensive retinopathy and the risk of first stroke in patients with hypertension, indicating that hypertensive retinopathy may be a predictor of the risk of stroke. A simplified two-grade classification system based on the KWB classification is recommended for predicting stroke risk.

The risk factors of the progression of rhegmatogenous retinal detachment on patients with the fourteen-day quarantine in the early period of COVID-19 outbreak.

BACKGROUNDS: The COVID-19 Pandemic has a great impact on hospitals and patients. The 14-day quarantine caused surgery of rhegmatogenous retinal detachment (RRD) postponed. We aimed to explore the risk factors of RRD progression in a group of patients whose surgery was postponed during the top-level emergency response of COVID-19. METHODS: A retrospective case series. Medical records of all consecutive patients with a diagnosis of RRD who underwent a surgical treatment at Beijing Tongren Hospital's retina service from February 16, 2020, to April 30, 2020 have been reviewed retrospectively. Medical history, symptoms, and clinical signs of progression of RRD were recorded. RRD progression was defined as the presence of either choroidal detachment or proliferative vitreoretinopathy (PVR) progression during the quarantine period. Risk factors were analyzed using the Cox proportional hazards model, survival analysis, and logistic regression. RESULTS: Seventy-nine eyes of 79 patients met the inclusion criteria and were included in the study. The median time from the patients' presentation at the clinic to admission for surgery was 14 days (3-61 days). There were 70 cases (88.6%) who did not present to the hospital within 1 week of the onset of visual symptoms. There were 69 (87.3%) macular-off cases at the presentation and 27 (34.2%) cases combined with choroidal detachment. There were 49 (62.0%) cases with PVR B, 22 (27.8%) cases with PVR C, 4 (5.1%) cases with PVR D, and 4 (5.1%) cases with anterior PVR. After the 14-day quarantine, 21 (26.6%) cases showed RRD progression, and 9 cases showed RRD regression at the time of surgery. Neither the time of onset of the visual symptom (p = 0.46) nor the time between presentation and admission (p = 0.31) was significantly different between the patients with RRD progression and patients without RRD progression. The combination of choroidal detachment (3.07, 1.68-5.60, p<0.001) and retinal breaks located posterior to the equator (3.79, 1.21-11.80, p=0.02) were factors related to the progression of RRD. CONCLUSIONS: In our study during the COVID-19 outbreak, the RRD progression risk factors included a combination of choroidal detachment and retinal breaks posterior to the equator. Ophthalmologists should schedule the surgeries for RRD patients with these signs as soon as possible.

Positive relationship of hypertensive retinopathy with carotid intima--media thickness in hypertensive patients.

OBJECTIVES: We aimed to explore the relationship of hypertensive retinopathy with carotid intima--media thickness (CIMT), and to examine the possible effect modifiers in Chinese adults with hypertension. METHODS: We conducted a cross-sectional study of 12 342 hypertensive patients with complete exit site visit data from the China Stroke Primary Prevention Trial. CIMT was measured by carotid ultrasonography. Hypertensive retinopathy was diagnosed according to the Keith--Wagener--Barker classification. RESULTS: The mean (SD) CIMT among study participants was 739.9 (111.4) µm. Compared with patients with grade 1 hypertensive retinopathy or without hypertensive retinopathy, a significantly higher CIMT level (ß, 7.63, 95% CI: 2.54--12.73) was observed in patients with grade 2-4 hypertensive retinopathy. Moreover, the association between hypertensive retinopathy (grade 2-4 versus grade 1 or normal) and CIMT was stronger in participants of younger age (<60 years; ß, 13.70, 95% CI: 5.65--21.75; versus ≥60 years; ß, 1.03, 95% CI: -5.58 to 7.63; P interaction = 0.006); or with lower total homocysteine levels [<12.1 µmol/l (median); ß, 12.70, 95% CI: 5.98--19.42; versus ≥12.1 µmol/l; ß, 2.07, 95% CI: -5.63 to 9.78; P interaction = 0.030). None of the other variables, including sex, BMI, study centers, treatment group, SBP, triglycerides, total cholesterol, fasting blood glucose, folate, serum creatinine, current smoking and alcohol drinking, significantly modified the relation of hypertensive retinopathy with CIMT levels. CONCLUSION: Hypertensive retinopathy (grade 2 and higher) was significantly associated with increased CIMT in hypertensive patients. The association was stronger in those of younger age or with lower total homocysteine levels.

Incidence of Endophthalmitis after Intravitreal Anti-Vascular Endothelial Growth Factor Injections in an Operating Room in China.

PURPOSE: To evaluate the rate of presumed endophthalmitis (EO) after intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections performed in an operating room (OR) under sterile conditions in mainland China. METHODS: Retrospective single-center study between September 2012 and December 2017 at Beijing Tongren Eye Center, Beijing, China. Intravitreal injection database was reviewed. All anti-VEGF injections were performed using a standardized sterile technique in an OR. Injection protocols included antibiotics for 3 days pre-injection, topical 5% povidone-iodine rinsing before the procedure, and post-injection antibiotics for 3 days. RESULTS: A total of 37,830 intravitreal injections were performed at Beijing Tongren Eye Center. Three cases were managed as presumed EO (0.0079%). Positive cultures were documented in 2 of 3 cases. EO incidence following ranibizumab and conbercept administration was 0.0088% (3 in 33,930) and 0% (0 in 3,900), respectively. No significant difference was detected between the two drugs (P = 0.745). CONCLUSIONS: Very low EO rates were seen in mainland China using a standardized sterile technique in an OR. However, EO could not be completely avoided.

Association Between Folic Acid Supplementation and Retinal Atherosclerosis in Chinese Adults With Hypertension Complicated by Diabetes Mellitus.

Background: This cross-section investigation included 2,199 participants with hypertension complicated by diabetes mellitus, a cohort of the China Stroke Primary Prevention Trial in which 20,702 patients with essential hypertension were given enalapril with folic acid or enalapril-only double-blind treatment for 5 years. This study aimed to explore the correlation between folic acid supplementation and retinal atherosclerosis (RA) in adults with hypertension complicated by diabetes mellitus. Methods: The diagnosis of RA was determined by non-mydriatic fundus photography and classified by the Keith-Wagener-Barker system. The statistical correlation of folic acid supplementation with RA prevalence and severity was assessed. Results: Of our cohort, 1,698 (77.6%) participants were diagnosed with RA, and the prevalence in males and females was 78.0 and 75.6%, respectively. Participants in the enalapril group had higher total homocysteine (tHcy) levels than those in enalapril-folic acid group. Compared with the enalapril group in the tHcy > 15 µmol/L group of females, the odds ratio for the enalapril-folic acid group was 0.28 (95% confidence interval, 0.11-0.67, P = 0.0061). Conclusions: The prevalence of RA was high (77.6%) in our cohort of adults with hypertension complicated by diabetes mellitus. Folic acid supplementation was significantly associated with reduced risk of RA in females with hyperhomocysteinemia. No significant association were seen in males.

UTILIZATION OF FUNDUS AUTOFLUORESCENCE, SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHY, AND ENHANCED DEPTH IMAGING IN THE CHARACTERIZATION OF BIETTI CRYSTALLINE DYSTROPHY IN DIFFERENT STAGES.

PURPOSE: To characterize Bietti crystalline dystrophy (BCD) in different stages using multiple imaging modalities. METHODS: Sixteen participants clinically diagnosed as BCD were included in the retrospective study and were categorized into 3 stages according to fundus photography. Eleven patients were genetically confirmed. Fundus autofluorescence, spectral domain optical coherence tomography, and enhanced depth imaging features of BCD were analyzed. RESULTS: On fundus autofluorescence, the abnormal autofluorescence was shown to enlarge in area and decrease in intensity with stages. Using spectral domain optical coherence tomography, the abnormalities in Stage 1 were observed to localize in outer retinal layers, whereas in Stage 2 and Stage 3, more extensive retinal atrophy was seen. In enhanced depth imaging, the subfoveal choroidal layers were delineated clearly in Stage 1; in Stage 2, destructions were primarily found in the choriocapillaris with associated alterations in the outer vessels; Stage 3 BCD displayed severe choroidal thinning. Choroidal neovascularization and macular edema were exhibited with high incidence. IVS6-8del17bp/inGC of the CYP4V2 gene was the most common mutant allele. CONCLUSION: Noninvasive fundus autofluorescence, spectral domain optical coherence tomography, and enhanced depth imaging may help to characterize the chorioretinal pathology of BCD at different degrees, and therefore, we propose staging of BCD depending on those methods. Physicians should be cautious of the vision-threatening complications of the disease.

Vertical deviation and A pattern of type III Duane retraction syndrome.

BACKGROUND: Researches in ocular electromyography (EMG) and Magnetic resonance imaging (MRI) of patients with Duane retraction syndrome (DRS) suggest that there may be additional abnormalities such as paradoxical innervation between horizontal rectus muscles and vertical rectus muscles, hypoplasia of vertical rectus muscle and that oblique muscles may also contribute to the heterogeneity of the clinical manifestation of DRS. This paper reports the results of superior rectus recession for vertical deviation and A pattern in DRS Type III and discusses the pathogenesis of the disease. METHODS: Superior and lateral rectus recession were performed in 5 cases of Huber type III DRS to treat vertical deviation and A pattern strabismus. Before operation, MRI of the brain, brainstem, cavernous sinus, and orbits were performed. RESULTS: All subjects had unilateral limitation of both abduction and adduction, with palpebral fissure narrowing and globe retraction in adduction. Three cases had A pattern of strabismus, three cases had hypertropia. The abducens nerves (CN6) were either absent or hypoplasitic in the brainstem in all patients. Two eyes had larger oculomotor foramen. Two eyes had hypoplasia of the superior rectus and the inferior rectus. There was presumably a branch of the third cranial nerve (CN3) innervating the lateral rectus (LR) in one eye. While in another eye, two branches of CN3 sent into medial rectus were revealed. After surgery, vertical deviation in the primary position was reduced in all patients and A pattern was eliminated in 3 patients. One patient developed 10Δ consecutive esotropia postoperatively. CONCLUSION: The results suggest that structural abnormalities of vertical muscle and abnormal orbital innervation may be related to vertical deviation and the presence of A pattern in DRS type III. Recession of the superior rectus muscle seems to be a safe and effective treatment for vertical deviation and A pattern strabismus in DRS Type III.

The regulatory roles of apoptosis-inducing factor in the formation and regression processes of ocular neovascularization.

The role of apoptosis in the formation and regression of neovascularization is largely hypothesized, although the detailed mechanism remains unclear. Inflammatory cells and endothelial cells both participate and interact during neovascularization. During the early stage, these cells may migrate into an angiogenic site and form a pro-angiogenic microenvironment. Some angiogenic vessels appear to regress, whereas some vessels mature and remain. The control mechanisms of these processes, however, remain unknown. Previously, we reported that the prevention of mitochondrial apoptosis contributed to cellular survival via the prevention of the release of proapoptotic factors, such as apoptosis-inducing factor (AIF) and cytochrome c. In this study, we investigated the regulatory role of cellular apoptosis in angiogenesis using two models of ocular neovascularization: laser injury choroidal neovascularization and VEGF-induced corneal neovascularization in AIF-deficient mice. Averting apoptosis in AIF-deficient mice decreased apoptosis of leukocytes and endothelial cells compared to wild-type mice and resulted in the persistence of these cells at angiogenic sites in vitro and in vivo. Consequently, AIF deficiency expanded neovascularization and diminished vessel regression in these two models. We also observed that peritoneal macrophages from AIF-deficient mice showed anti-apoptotic survival compared to wild-type mice under conditions of starvation. Our data suggest that AIF-related apoptosis plays an important role in neovascularization and that mitochondria-regulated apoptosis could offer a new target for the treatment of pathological angiogenesis.

Complications after heavy silicone oil tamponade in complicated retinal detachment.

PURPOSE: To observe the complications after heavy silicone oil (HSO) tamponade in complicated retinal detachment. METHODS: Thirty-three eyes of 33 patients with complicated retinal detachment were included in this retrospective study. Vitrectomy and HSO tamponade were performed in all patients. Other surgical procedures were performed as necessary. The main outcome measures included retinal reattachment, visual acuity, intraocular pressure, intraocular inflammation, lens opacity, and HSO emulsification. RESULTS: The patients were followed up for 3 months to 24 months (average, 8.1 ± 5.3 months). Retinal reattachment was achieved in 29 eyes (87.9%) with a first surgery and in 33 eyes (100%) with a second surgery. In all 33 eyes, HSO had been removed and the visual acuity was improved. Short-term (within 2 weeks after operations) complications included temporarily increased intraocular pressure and mild inflammation in the anterior chamber. Major long-term complications included cataract (100%) and HSO emulsification (42.4%). Other long-term complications included ocular hypertension (12.1%), retinal detachment and proliferative vitreoretinopathy (12.1%), and low intraocular pressure (9.1%). CONCLUSION: Heavy silicone oil tamponade is safe and effective to treat complicated retinal detachment. The most common complications are cataract and HSO emulsification.

Atrial natriuretic peptide reduces vascular leakage and choroidal neovascularization.

Atrial natriuretic peptide (ANP) is a hormone with diuretic, natriuretic, and vasodilatory properties. ANP blocks vascular endothelial growth factor (VEGF) production and signaling in vitro; however, its role in vascular leakage and angiogenesis is unknown. In vitro, retinal barrier permeability (transepithelial electrical resistance (TEER)) was measured in cultured retinal endothelial (HuREC) and retinal epithelial (ARPE-19) cells with VEGF (10 ng/ml), ANP (1 pM to 1 micromol/L), and/or isatin, an ANP receptor antagonist. In vivo, blood-retinal barrier (BRB) leakage was studied using the Evans Blue dye technique in rats treated with intravitreal injections of ANP, VEGF, or vehicle. Choroidal neovascularization was generated by laser injury, and 7 days later, lesion size and leakage was quantitated. ANP significantly reversed VEGF-induced BRB TEER reduction in both HuREC and ARPE-19 cells, modeling the inner and the outer BRB, respectively. Isatin, a specific ANP receptor antagonist, reversed ANP's effect. ANP reduced the response of ARPE-19 cells to VEGF apically but not basolaterally, suggesting polarized expression of the ANP receptors in these cells. ANP's TEER response was concentration but not time dependent. In vivo, ANP significantly reduced VEGF-induced BRB leakage and the size of laser-induced choroidal neovascularization lesions. In sum, ANP is an effective inhibitor of VEGF-induced vascular leakage and angiogenesis in vivo. These results may lead to new treatments for ocular diseases where VEGF plays a central role, such as age-related macular degeneration or diabetic retinopathy.