ASSOCIATIONS BETWEEN CHOROIDAL ALTERATIONS AND EARLY NEURODEGENERATION IN DIABETES WITHOUT DIABETIC RETINOPATHY: Insights From Ultra-Widefield Optical Coherence Tomography Angiography Imaging.

PURPOSE: To identify associations between choroidal alterations and the reduction of peripapillary retinal nerve fiber layer (pRNFL) thickness in diabetes without diabetic retinopathy (nondiabetic retinopathy, NDR). METHODS: This retrospective cross-sectional study included 143 eyes from 83 patients with NDR and 124 eyes from 82 matched healthy controls. Ultra-widefield swept-source optical coherence tomography angiography was used to automatically measure retinal and choroidal thickness (ChT), retinal vascular density, and choroidal vascular metrics. Data were analyzed using Student's t-tests, generalized estimating equations, and generalized linear mixed models. RESULTS: Patients with NDR exhibited significant reductions in perifoveal ChT (e.g., perifoveal inferior region: 253.42 ± 86.59 µm vs. 281.01 ± 80.25 µm, P = 0.026 in GEE test) compared with the controls. The NDR group showed a significant decrease in the choroidal vascular index (P = 0.012 in GEE test), and an increase in the choroidal stromal index (P = 0.012 in GEE test). The average pRNFL thickness significantly decreased in patients with NDR (114.58 ± 11.88 µm vs. 120.25 ± 16.36 µm, P = 0.005 in GEE test). The thickness of the outer nuclear layer and total retina significantly decreased in patients with NDR (P < 0.05). In multivariate models, ChT was significantly correlated with pRNFL thickness (ß = 0.041, P = 0.001), even after adjusting by confounding factors (ß = 0.056, P = 0.001). CONCLUSION: In NDR, there were decreases in ChT, choroidal vascular index, pRNFL thickness, and outer nuclear layer thickness. The reduction in ChT was independently associated with the reduction in pRNFL thickness, suggesting that ChT could serve as a predictor of retinal neurodegeneration in NDR.

High-Altitude Exposure and Diabetic Retinopathy: Unveiling the Impact and Mechanisms of Alleviation.

BACKGROUND: High altitude (HA) is an extremely challenging environment for millions of people who either travel to HA regions or inhabit there permanently. SUMMARY: Significant progress has been made over the past decades in the understanding of physiological adaptations in HA conditions, and recently, more studies regarding its influence on metabolic disease have been published. However, the effect of HA on diabetic retinopathy (DR), the leading cause of blindness, remains unclear. KEY MESSAGES: The present article provides an overview of the changes in the principal physiology and clinical characteristics related to DR after HA exposure. Despite conflicting evidence, this review synthesizes the available studies and explores the potential mechanisms, such as genetic adaptations, glucose homeostasis, and related physiological changes, by which long-term exposure to HA may alleviate the progression of DR. By shedding light on this complex relationship, it also provides insights into the interplay between HA and DR, offering valuable implications for clinical practice and further research.

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.

A Newly Established Cuproptosis-Related Gene Signature for Predicting Prognosis and Immune Infiltration in Uveal Melanoma.

Uveal melanoma (UVM) is the most common primary ocular malignancy in adults and involves several types of regulated cell death. Cuproptosis is a novel method of regulating cell death by binding lipoylated TCA cycle proteins. There is still no research on the relationship between cuproptosis-related genes (CRGs) and UVM. Here, we aimed to develop a prognostic CRG signature for UVM. After a prognostic CRG signature was constructed, we determined the relationship between the signature and immune infiltration, bioinformatics analysis and experimental validation. Finally, a prognostic cuproptosis-related three-gene (CRTG) signature was constructed, which comprised ORAI2, ACADSB and SLC47A1. The risk score of the CRTG signature was negatively correlated with the overall survival (OS) and progression-free survival (PFS) of patients, which revealed strong predictive ability and its independent prognostic value. In addition, we found that the risk score was negative for chromosomes 3 and 6p, and positive for 8q, and high-risk UVM patients showed an increase in protumor immune infiltrates and a high expression of immune checkpoints. Finally, experimental validation verified that the migratory ability of MUM-2B cells was suppressed by the knockdown of the identified genes in vitro. We constructed a CRTG signature that is helpful in predicting prognosis and guiding treatment for patients with UVM.

Comprehensive Management of Infantile Hemangiomas Involving the Periorbital Region.

ABSTRACT: Periocular infantile hemangioma (pIH) is associated with a risk of vision loss and requires urgent medical intervention. We evaluated the outcomes of the comprehensive management of 44 pIH patients (aged 2-6 months) with superficial (n = 11), deep (n = 15), and mixed (n = 18) subtypes, treated with a standard propranolol dose (2 mg kg -1 d -1 ) without any obvious side effects. Obvious and slight improvements were observed in 70.5% and 29.5% of patients, respectively. Obvious improvement was found in 96.3% of patients 3 months or younger but only 29.4% of patients older than 3 months ( P = 0.036) after 4 weeks of treatment. Thirteen patients demonstrated slight improvement and were treated with an increased propranolol dose (3 mg kg -1 d -1 ) in combination with corticosteroid injections or plastic surgery, which led to good outcomes. The patients were followed up for 12 to 18 months, with no cases of amblyopia or ametropia. Oral propranolol was effective in the treatment of pIH. Earlier propranolol use was associated with better outcomes. An increased propranolol dose combined with corticosteroid injections or plastic surgery is appropriate for patients with propranolol resistance.

Global disease burden of uncorrected refractive error among adolescents from 1990 to 2019.

BACKGROUND: To estimate the global disease burden of uncorrected refractive error (URE) among adolescents and assess the contributions of various risk factors to disability-adjusted life-years (DALYs) due to URE. METHODS: Global, regional and country-level DALY numbers and rates due to URE among adolescents were acquired from the Global Burden of Disease Study 2019 database. Human Development Index (HDI), Socio-Demographic Index (SDI) and other country-level data were obtained from other open databases as potential indicators. Regression analysis was used to evaluate associations between DALY rates among adolescents and potential predictors. RESULTS: Global DALYs due to URE among adolescents rose by 8% between 1990 and 2019 but moderately decreased by 4.8% during this period after adjusting for population size. Female adolescents showed higher DALY rates. DALY rates sharply increased from 5 to 9 years of age, then rose more slowly, reaching a plateau before 20 years of age. Country-level DALY rates in 2019 were positively associated with HDI, SDI, and urbanization rates but negatively correlated with primary school dropout rates. Higher disease burden of adolescents visually impaired from URE was associated with lower primary school dropout rates (ß = - 0.257, 95% CI - 0.376 to - 0.138, P < 0.001) and higher urbanization rates (ß = 0.257, 95% CI 0.067 to 0.256, P = 0.001). CONCLUSIONS: Higher socioeconomic status, urbanization rates and education levels are associated with a heavier disease burden of URE among adolescents. The findings of this study can provide a reference for policy making on resource allocation for URE prevention and control in teenagers.

The vascular densities of the macula and optic disc in normal eyes from children by optical coherence tomography angiography.

PURPOSE: This study aims to describe the variation and characteristics of vessel density (VD) of the macula and optic disc in the normal eyes of children. METHODS: This was a retrospective study where subjects aged 5-18 years with normal eyes were enrolled. The macula and optic disc were scanned by optical coherence tomography angiography (OCTA). The influences of age, gender, and axial length (AL) on VD were analyzed. RESULTS: A total of 71 normal eyes from 71 subjects were enrolled. For the macula, the mean VD of fovea, parafovea, and perifovea at superficial retina and deep retina were 20.1%, 50.2%, 49.4%, 36.1%, 53.9%, and 48.1%, respectively. The mean foveal avascular zone (FAZ) was 0.277 mm2. For optic disc, the mean VD of radial peripapillary capillary (RPC) and inside-disc areas were 51.8% and 51.7%, respectively. Significant differences were found between the superior-hemi and inferior-hemi VD of the superficial retinal parafovea, deep retinal perifovea, and perifovea. The fovea VD of the superficial and deep retina and FAZ areas were different between genders. The inside-disc VD was positively correlated with AL, while other VDs had no significant correlation with age and AL. CONCLUSIONS: The parafovea VD of the superficial retina, parafovea, and perifovea of the deep retina had superior-hemi VD; boys had a higher fovea VD and smaller FAZ area than those of girls, the macular VD and peripapillary RPC density were steady for 5-18 year-olds. This study provided useful information for furthering the understanding of the development mode of vessel in children and the OCTA clinical applications in children.

Evaluation of early changes of macular function and morphology by multifocal electroretinograms in patients with nasopharyngeal carcinoma after radiotherapy.

OBJECTIVE: To assess the role of multifocal electroretinograms (mfERGs) and optical coherence tomography (OCT) for detecting early changes in macular functions of patients with nasopharyngeal carcinoma (NPC) after radiotherapy. METHODS: mfERGs and OCT were used to examine a NPC group (36 NPC patients after radiotherapy without clinically visible radiation retinopathy, 36 eyes) and a normal control group (25 healthy individuals, 25 eyes) with the same procedure and parameters. The two groups of mfERG were summarized by calculating ring averages, response density, N1 amplitude and P1 and N1 latencies were analysed. OCT scan thickness was summarized into ETDRS regions for comparison. RESULTS: Compared with controls, the NPC group had significantly decreased P1 response densities in 1-4 ring regions and N1 amplitudes in 1-3 rings (P < 0.01). P1 latencies were obviously prolonged in rings 1 (P < 0.01). In four quadrants (inferonasal, superonasal, inferotemporal and superotemporal) of the mfERG response waveforms, the NPC group had significantly decreased P1 response densities and N1 amplitudes mainly in the inferonasal and inferotemporal quadrants, showing statistically significant differences from the control group (P < 0.0125). But for the OCT results, there is no statistically significant difference between the NPC group and the control group. CONCLUSIONS: In NPC patients after radiotherapy, there may be changes in the mfERGs before any visible fundus lesions appeared as radiation macular oedema. Since the global OCT macular thickness analysis cannot reveal early changes, the mfERGs can objectively and quantitatively assess the earlier changes in macular function in NPC patients.

Comparison of efficacy between anti-vascular endothelial growth factor (VEGF) and laser treatment in Type-1 and threshold retinopathy of prematurity (ROP).

BACKGROUND: Retinopathy of Prematurity (ROP) is one of the most common causes of childhood blindness worldwide. Comparisons of anti-VEGF and laser treatments in ROP are relatively lacking, and the data are scattered and limited. The objective of this meta-analysis is to compare the efficacy of both treatments in type-1 and threshold ROP. METHODS: A comprehensive literature search on ROP treatment was conducted using PubMed and Embase up to March 2017 in all languages. Major evaluation indexes were extracted from the included studies by two authors. The fixed-effects and random-effects models were used to measure the pooled estimates. The test of heterogeneity was performed using the Q statistic. RESULTS: Ten studies were included in this meta-analysis. Retreatment incidence was significantly increased for anti-VEGF (OR 2.52; 95% CI 1.37 to 4.66; P = 0.003) compared to the laser treatment, while the incidences of eye complications (OR 0.29; 95% CI 0.10 to 0.82; P = 0.02) and myopia were significantly decreased with anti-VEGF compared to the laser treatment. However, there was no difference in the recurrence incidence (OR 1.86; 95% CI 0.37 to 9.40; P = 0.45) and time between treatment and retreatment (WMD 7.54 weeks; 95% CI 2.00 to 17.08; P = 0.12). CONCLUSION: This meta-analysis indicates that laser treatment may be more efficacious than anti-VEGF treatment. However, the results of this meta-analysis also suggest that laser treatment may cause more eye complications and increase myopia. Large-scale prospective RCTs should be performed to assess the efficacy and safety of anti-VEGF versus laser treatment in the future.

TLR7 deficiency contributes to attenuated diabetic retinopathy via inhibition of inflammatory response.

Diabetic retinopathy (DR) is a major microvascular complication of diabetes, resulting in neuronal dysfunction, retinal vascular leakage, and apoptosis within the retina. Innate immunity plays an important role in the pathogenesis of type 2 diabetes (T2D) and related complications. The toll-like receptors (TLRs), central to innate immunity, are essential participants in the progression and pathogenesis of the disease and its complications. In the study, streptozotocin (STZ) was combined with whole-body hypoxia for quicker induction of early-stage diabetic retinopathy (DR) in the wild type (WT) and TLR7-knockout (KO) C57BL/6 mice. The effects of TLR7 were also investigated in fructose-treated retinal pigment epithelial (RPE) cells. In the retinas of WT/DR mice, abnormal a-wave and b-wave activity, hyperfluorescence, and reduced retinal thickness were observed. DR development was associated with enhanced TLR7 expression, whose deletion dramatically reduced VEGF expression levels. And the secretion of pro-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß, IL-6, IL-18 and IL-12, was highly reduced by TLR7-deficiency in DR mice. Consistently, WT/DR mice exhibited higher phosphorylation of IκB kinase α (IKKα), inhibitor of NF-κB α (IκBα) and nuclear factor κB (NF-κB), which were found to be down-regulated in KO/DR mice. Similarly, DR-induced mitogen-activated protein kinases (MAPKs) activation was blocked by TLR7-knockout. In vitro, fructose incubation-triggered inflammation was reversed by TLR7 knockdown, accompanied with inactivated NF-κB and MAPKs pathways. And reduced reactive oxygen species (ROS) generation was observed in TLR7-knockdown cells with fructose treatment. Together, inhibiting TLR7 suppressed diabetic retinopathy by reducing inflammation and suggested a potential application in clinics.

A simple classification of cranial-nasal-orbital communicating tumors that facilitate choice of surgical approaches: analysis of a series of 32 cases.

Cranial-nasal-orbital communicating tumors involving the anterior and middle skull base are among the most challenging to treat surgically, with high rates of incomplete resection and surgical complications. Currently, there is no recognized classification of tumors with regard to the choice of surgical approaches. From January 2004 to January 2014, we classified 32 cranial-nasal-orbital communicating tumors treated in our center into three types according to the tumor body location, scope of extension and direction of invasion: lateral (type I), central (type II) and extensive (type III). This classification considerably facilitated the choice of surgical routes and significantly influenced the surgical time and amount of hemorrhage during operation. In addition, we emphasized the use of transnasal endoscopy for large and extensive tumors, individualized treatment strategies drafted by a group of multidisciplinary collaborators, and careful reconstruction of the skull base defects. Our treatment strategies achieved good surgical outcomes, with a high ratio of total resection (87.5 %, 28/32, including 16 cases of benign tumors and 12 cases of malignant tumors) and a low percentage of surgical complications (18.8 %, 6/32). Original symptoms were alleviated in 29 patients. The average KPS score improved from 81.25 % preoperatively to 91.25 % at 3 months after surgery. No serious perioperative complications occurred. During the follow-up of 3 years on average, four patients with malignant tumors died, including three who had subtotal resections. The 3-year survival rate of patients with malignant tumors was 78.6 %, and the overall 3-year survival rate was 87.5 %. Our data indicate that the simple classification method has practical significance in guiding the choice of surgical approaches for cranial-nasal-orbital communicating tumors and may be extended to other types of skull base tumors.

Expression of the SARS-CoV-2 Receptor ACE2 and Protease TMPRSS2 in Ocular Hypertension Eyes of Nonhuman Primate and Human.

PURPOSE: Coronavirus disease 2019 is a disease caused by the novel severe acute respiratory syndrome coronavirus 2. The double-positive of angiotensin-converting enzyme 2 and transmembrane protease serine type 2 have a higher risk of being infected by severe acute respiratory syndrome coronavirus 2. The susceptibility of coronavirus disease 2019 in patients with chronic diseases, especially in different tissues of ocular hypertension eyes like glaucoma, is not yet known. METHODS: An ocular hypertension model was established by laser photocoagulation in rhesus monkeys. The expression of angiotensin-converting enzyme 2 and transmembrane protease serine type 2 in three ocular hypertension eyes and the three control eyes were analyzed using immunofluorescence. RESULTS: No difference was observed between ocular hypertension and control eyes in the expression of angiotensin-converting enzyme 2 and transmembrane protease serine type 2 in the conjunctival epithelium, corneal epithelium, and ciliary muscle. In ocular hypertension eyes and control eyes, angiotensin-converting enzyme 2 and transmembrane protease serine type 2 expression were both observed in the retina. Angiotensin-converting enzyme 2 staining of retinal ganglion cells was found to be significantly higher in ocular hypertension eyes than in control eyes. However, there was no difference in angiotensin-converting enzyme 2 and transmembrane protease serine type 2 expression in retinal vessels and choroidal vessels between ocular hypertension and control eyes. In our study, the expression and distribution of angiotensin-converting enzyme 2 and TMPREE2 in human retina were similar to that of non-human primates as expected. CONCLUSION: Our study confirmed that angiotensin-converting enzyme 2 and transmembrane protease serine type 2 were expressed widely in rhesus monkey eyes. When compared with controls eyes, the expression of angiotensin-converting enzyme 2 was higher in the retinal ganglion cells in ocular hypertension eyes, suggesting that high ocular pressure may affect the patients' ocular susceptibility to severe acute respiratory syndrome coronavirus 2 infection.

Association between choroidal thickness and diabetic macular edema: a meta-analysis.

AIMS: To evaluate the association between subfoveal choroidal thickness (SFCT) and diabetic macular edema (DME). DESIGN: A systematic review and meta-analysis. METHODS: A retrospective or prospective study comparing SFCT in diabetic retinopathy (DR) patients with and without DME was included. The data were collected from published studies retrieved from PubMed, Web of Science, Embase, Ovid Medline, and Cochrane Library. The final search was conducted on July 2, 2023. Heterogeneity was assessed using I2 statistics, and a random-effects model was used for the meta analysis. This study calculated the weighted mean difference (WMD) and 95% confidence interval (CI) for SFCT. RESULTS: A total of 26 relevant studies were identified, involving a combined sample size of 3201 eyes (1302 DR-DME eyes and 1899 DR-no DME eyes). The results showed no significance between DR-DME and DR-no DME (WMD = - 3.57 µm; 95% CI -26.54 to 19.41 µm; P = 0.76). Sub-analysis based on nonproliferative diabetic retinopathy (NPDR) and proliferative diabetic retinopathy (PDR) subgroups showed that the SFCT of NPDR-DME was significantly thinner than that of NPDR-no DME eyes (WMD = - 19.80 µm; 95% CI - 34.55 to - 5.04 µm; P = 0.009), while there was no significance in SFCT between PDR-DME and PDR-no DME (WMD = - 26.45 µm; 95% CI - 104.00 to 51.11 µm; P = 0.50). CONCLUSION: The SFCT was thinner in NPDR-DME eyes compared to NPDR-no DME eyes. Thinning SFCT might cause retinal hypoxia, and play an important role in DME occurrence. Additionally, this study highlights the importance of considering DR grades and treatment history when evaluating SFCT between DME and no DME.

Identification of diabetic retinopathy classification using machine learning algorithms on clinical data and optical coherence tomography angiography.

BACKGROUND: To apply machine learning (ML) algorithms to perform multiclass diabetic retinopathy (DR) classification using both clinical data and optical coherence tomography angiography (OCTA). METHODS: In this cross-sectional observational study, clinical data and OCTA parameters from 203 diabetic patients (203 eye) were used to establish the ML models, and those from 169 diabetic patients (169 eye) were used for independent external validation. The random forest, gradient boosting machine (GBM), deep learning and logistic regression algorithms were used to identify the presence of DR, referable DR (RDR) and vision-threatening DR (VTDR). Four different variable patterns based on clinical data and OCTA variables were examined. The algorithms' performance were evaluated using receiver operating characteristic curves and the area under the curve (AUC) was used to assess predictive accuracy. RESULTS: The random forest algorithm on OCTA+clinical data-based variables and OCTA+non-laboratory factor-based variables provided the higher AUC values for DR, RDR and VTDR. The GBM algorithm produced similar results, albeit with slightly lower AUC values. Leading predictors of DR status included vessel density, retinal thickness and GCC thickness, as well as the body mass index, waist-to-hip ratio and glucose-lowering treatment. CONCLUSIONS: ML-based multiclass DR classification using OCTA and clinical data can provide reliable assistance for screening, referral, and management DR populations.

The association between decreased choriocapillary flow and electroretinogram impairments in patients with diabetes.

PURPOSE: To evaluate the association between choriocapillary flow (CCF) and electroretinogram (ERG) in patients with diabetes. METHOD: This was a cross-sectional study. Patients with type 2 diabetes and healthy controls who had undergone both flicker ERG and optical coherence tomography angiography (OCTA) were included, while patients with severe diabetic retinopathy (DR) and macular edema were excluded. Correlations among OCTA and ERG parameters were conducted by generalized linear mixed models (GLMM). RESULT: One hundred ninety-four eyes of 102 patients with diabetes and fifty-six eyes of 28 controls were included. The implicit time of 30-Hz flicker ERG successively increased, while the amplitudes, inner-retina vessel density and CCF were decreased from the control to the nondiabetic retinopathy (NDR) to DR group. In patients with diabetes, all GLMM models of ERG parameters had statistically significance (P<0.05), and CCF was correlated with ERG parameters (coefficient index=-0.601, P< 0.001 with 16 Td-s implicit time; coefficient index=-0.687, P< 0.001 with 32 Td-s implicit time; coefficient index=0.933, P=0.035 with 32 Td-s amplitude) and the thickness of retinal pigment epithelium, while in the GLMM model of CCF, it was correlated with the thickness of retinal pigment epithelium and the level of glycosylated hemoglobin(both P= 0.001). CONCLUSION: CCF decreased in patients with diabetes, and it was related with ERG. Choroidopathy and its functional impairment in the retina may occur very early in patients with diabetes by influencing the outer retina.

Changes in the choroid detected by ultrawide-field optical coherence tomography angiography in type 2 diabetes mellitus patients without diabetic retinopathy.

AIM: The study objective was to investigate the choroidal changes in type 2 diabetes mellitus (T2DM) patients without diabetic retinopathy (DR). METHODS: This was a cross-sectional study. Controls without diabetes and T2DM patients without DR (NDR) were included. Ultrawide-field (24 × 20 mm2) optical coherence tomography angiography (OCTA) was performed to analyse choroidal thickness and vessel density. All OCTA images were divided into 3 × 3 grids. The grid centre was considered the central area, while the rest was defined as the peripheral area. RESULTS: No differences between groups were observed in the flow density of the choriocapillaris (CC), choroidal thickness (ChT) and choroidal vascular index (CVI) of the large and medium choroidal vessel (LMCV) in the central area. In the eight peripheral areas, the mean flow density of the CC did not differ between the groups, while the mean CVI and ChT were decreased in the NDR group (P< 0.05). In each peripheral area, the mean CVI and ChT were decreased in the NDR group (P< 0.05, except in the infratemporal area and nasal area for ChT and in the infratemporal area for CVI). In the correlation analysis, both mean peripheral CVI and ChT correlated with age and the duration of diabetes. CONCLUSION: Early choroidal lesions tended to be peripheral in the LMCV in patients with diabetes without DR and correlated with age and the duration of diabetes.

Long-Term Real-World Outcomes of Corneal Changes in Proliferative Diabetic Retinopathy: Panretinal Photocoagulation vs. Intravitreal Conbercept.

PURPOSE: To compare long-term real-world outcomes of corneal thickness (CT) alterations in proliferative diabetic retinopathy (PDR) patients treated with panretinal photocoagulation (PRP) and intravitreal conbercept (IVC). METHODS: This retrospective study included 69 eyes of 69 patients with PDR (42 PRP and 27 IVC). Full corneal thickness (FCT), corneal epithelial thickness (CET) and corneal stromal thickness (CST) measured by anterior segment optical coherence tomography at baseline were compared between groups. These CT changes at last follow-up from baseline were also compared between groups and within each group. RESULTS: During a mean follow-up of more than two years, the IVC group demonstrated a significantly increased corneal thickness from baseline compared to the PRP group in some areas (PRP vs. IVC: FCT 0-2 mm: -0.59 ± 9.31 vs. 5.59 ± 9.23 µm, p = 0.009; CST 0-2 mm: -2.05 ± 8.79 vs. 3.48 ± 7.52 µm, p = 0.015; CST 2-5 mm: -1.78 ± 13.27 vs. 5.68 ± 14.53 µm, p = 0.046). In within-group comparisons, a significantly increased FCT from baseline was found in the 0-2 mm area in the IVC group (p = 0.004), but no significant change was observed in the PRP group (p = 0.691). For CET changes, a significantly increased CT was observed in the 0-2 mm, 2-5 mm and 5-7 mm areas in both groups respectively (all p < 0.05). Regarding CST, an increased CT was found in the 0-2 mm area in the IVC group (p = 0.037), while a decreased trend was observed in 0-2 mm and 2-5 mm areas in the PRP group (all p > 0.05). CONCLUSION: When using PRP or IVC in the long-term management of PDR, CT changes should be considered. This may provide evidence for corneal protection during PDR treatment.

Retinal and Choroidal Alterations in Diabetic Retinopathy Treatment using Subthreshold Panretinal Photocoagulation with Endpoint Management Algorithm: A Secondary Analysis of a Randomized Clinical Trial.

INTRODUCTION: The aim of this study was to compare retinal and choroidal alterations in eyes with severe nonproliferative diabetic retinopathy (NPDR) after panretinal photocoagulation (PRP), using conventional pattern scan laser (PASCAL) and PASCAL with endpoint management (EPM). METHODS: This was a post hoc analysis of a paired randomized clinical trial. Bilateral treatment-naïve eyes of an individual with symmetric severe NPDR were randomly allocated into the threshold PRP group and subthreshold EPM PRP group. Patients had follow-up visits at 1, 3, 6, 9, and 12 months post-treatment. The retinal thickness (RT), choroidal thickness (CT), choroidal area, and choroidal vascularity index (CVI) were compared between the two groups and among different time points within the same group. RESULTS: Seventy eyes of 35 patients with diabetes mellitus (DM) were finally included for analysis at the 6- and 12-month visits, respectively. At 3 and 6 months post-treatment, the RT in the subthreshold EPM PRP group was significantly thinner than that in the threshold PRP group. CT, stromal area, and luminal area were reduced earlier in the threshold PRP group than in the subthreshold EPM PRP group. CVI was not significantly different within the same group or between groups at most time points. CONCLUSION: At 12 months post-treatment, retinal thickening and choroidal disturbance may be slightly less severe and more delayed in eyes receiving PRP using PASCAL with EPM than in those receiving PRP using conventional PASCAL. The EPM algorithm may be a good alternative in PRP when treating severe NPDR. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT01759121.

Use of a tissue clearing technique combined with retrograde trans-synaptic viral tracing to evaluate changes in mouse retinorecipient brain regions following optic nerve crush.

Successful establishment of reconnection between retinal ganglion cells and retinorecipient regions in the brain is critical to optic nerve regeneration. However, morphological assessments of retinorecipient regions are limited by the opacity of brain tissue. In this study, we used an innovative tissue cleaning technique combined with retrograde trans-synaptic viral tracing to observe changes in retinorecipient regions connected to retinal ganglion cells in mice after optic nerve injury. Specifically, we performed light-sheet imaging of whole brain tissue after a clearing process. We found that pseudorabies virus 724 (PRV724) mostly infected retinal ganglion cells, and that we could use it to retrogradely trace the retinorecipient regions in whole tissue-cleared brains. Unexpectedly, PRV724-traced neurons were more widely distributed compared with data from previous studies. We found that optic nerve injury could selectively modify projections from retinal ganglion cells in the hypothalamic paraventricular nucleus, intergeniculate leaflet, ventral lateral geniculate nucleus, central amygdala, basolateral amygdala, Edinger-Westphal nucleus, and oculomotor nucleus, but not the superior vestibular nucleus, red nucleus, locus coeruleus, gigantocellular reticular nucleus, or facial nerve nucleus. Our findings demonstrate that the tissue clearing technique, combined with retrograde trans-synaptic viral tracing, can be used to objectively and comprehensively evaluate changes in mouse retinorecipient regions that receive projections from retinal ganglion cells after optic nerve injury. Thus, our approach may be useful for future estimations of optic nerve injury and regeneration.

Radiation optic neuropathy diagnosis in nasopharyngeal carcinoma patients with radiation encephalopathy.

AIM: To develop a suitable radiation optic neuropathy (RON) diagnostic model based on optical coherence tomography angiography (OCTA) and to reveal the correlation between endocrine and OCTA indexes in nasopharyngeal carcinoma (NPC) patients with radiation encephalopathy (RE). METHODS: This retrospective cross-sectional study included seventy-seven male NPC patients with RE following radiotherapy (41 non-RON and 36 RON). Endocrine and OCTA indexes were collected. The macular and peripapillary vessel density (VD) were automatically analyzed using AngioVue 2.0 of the RTVue XR Avanti device. The OCTA indexes were included in the multivariable binary logistic regression model between non-RON and RON. For all RE patients, a multiple linear regression was performed between each of the OCTA indexes and the endocrine indexes. RESULTS: Compared to non-RON, enlarged foveal avascular zone (FAZ) area, reduced superficial vascular plexus (SVP) VD and radial peripapillary capillary plexus density, reduced full retinal thickness, ganglion cell complex thickness and peripapillary retinal nerve fiber layer thickness were observed in RON. Foveal VD in the SVP was included in the RON diagnostic model. Free triiodothyronine (FT3) showed a significantly negative correlation with the FAZ area but showed a significantly positive correlation with foveal VD in the SVP and deep vascular plexus, peripapillary VD and thickness and parafoveal and perifoveal thickness. CONCLUSIONS: OCTA may be useful for diagnosing RON in male NPC patients with RE following radiotherapy. Reduced FT3 and foveal VD in SVP may be sensitive in screening RON in these patients.