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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Protocol for laser-induced chronic ocular hypertension and intracameral injection in nonhuman primates.

Laser-induced hypertension in nonhuman primates is used to mimic human glaucoma, the leading cause of irreversible blindness. In this protocol, we detail steps for laser-induced ocular hypertension in nonhuman primates by laser photocoagulation of the trabecular meshwork and subsequent intracameral injection. We further describe recording and evaluation of intraocular pressure changes and peripapillary retinal nerve fiber layer thickness. This protocol can assist researchers improve the success rate and repeatability of the procedure and reduce the number of nonhuman primates needed. For complete details on the use and execution of this protocol, please refer to Sun et al. (2022).

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.

Erratum: Long-term and potent IOP-lowering effect of IκBα-siRNA in a nonhuman primate model of chronic ocular hypertension.

[This corrects the article DOI: 10.1016/j.isci.2022.104149.].

Effects of curcumin nanoparticles on proliferation and VEGF expression of human retinal pigment epithelial cells.

AIM: To investigate the effects of curcumin (Cur) nanoparticles loaded with chitosan derivatives grafted by deoxycholic acid (Chit-DC) on human retinal pigment epithelial (hRPE) cell proliferation and vascular endothelial growth factor (VEGF) mRNA expression. METHODS: Cur nanoparticles were synthesized with Chit-DC as the carrier and Cur as the supported drug. Cell counting kit-8 (CCK-8) method was used to detect the effects of different concentrations of Cur/Chit-DC, Chit-DC, and Cur on the proliferation of hRPE cells for different times. The changes of Cur/Chit-DC and Cur on hRPE cell cycle were determined by flow cytometry. Semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the mRNA expression levels of VEGF in hRPE cells treated with Cur, Chit-DC and Cur/Chit-DC at 10 µg/mL for 24h. RESULTS: Different concentrations of Chit-DC nanoparticle treated hRPE cells had no significant difference in terms of optical density (OD) values compared with the control group at 24h and 48h. Moreover, there was no change in the cell morphology under a light microscope. After 24h treatment with Cur/Chit-DC and Cur, the percentage of G0-G1 phase cells increased and the percentage of S phase cells decreased in all concentration groups. Cur/Chit-DC and Cur in all concentration groups inhibited the proliferation of hRPE cells in a time and dose dependent manner, and reduced the expression level of VEGF mRNA. CONCLUSION: The Cur/Chit-DC nanoparticles can release Cur continuously and have sustained release function. Both Cur/Chit-DC nanoparticles and Cur could inhibit hRPE cells cultured in vitro, and could reduce the expression level of VEGF mRNA in hRPE cells.

Nomogram-based prediction of clinically significant macular edema in diabetes mellitus patients.

AIMS: The aim of the study was to construct and validate a risk nomogram for clinically significant macular edema (CSME) prediction in diabetes mellitus (DM) patients using systemic variables. METHODS: In this retrospective study, DM inpatients who underwent routine diabetic retinopathy screening were recruited and divided into training and validation sets according to their admission date. Ninety-three demographic and systemic variables were collected. The least absolute shrinkage and selection operator was used to select the predictive variables from the training set. The selected variables were used to construct the CSME prediction nomogram. Internal and external validations were performed. The C-index, calibration curve and decision curve analysis (DCA) were reported. RESULTS: A total of 349 patients were divided into the training set (240, 68.77%) and the validation set (109, 31.23%). The presence of diabetic peripheral neuropathy (DPN) symptoms, uric acid, use of insulin only or not for treatment, insulin dosage, urinary protein grade and disease duration were chosen for the nomogram. The C-index of the prediction nomogram was 0.896, 0.878 and 0.837 in the training set, internal validation and external validation, respectively. The calibration curves of the nomogram showed good agreement between the predicted and actual outcomes. DCA demonstrated that the nomogram was clinically useful. CONCLUSIONS: A nomogram with good performance for predicting CSME using systemic variables was developed. It suggested that DPN symptoms and renal function may be crucial risk factors for CSME. Moreover, this nomogram may be a convenient tool for non-ophthalmic specialists to rapidly recognize CSME in patients and to transfer them to ophthalmologists for early diagnosis and treatment.

Hyperreflective material serves as a potential biomarker of dyslipidemia in diabetic macular edema.

PURPOSE: The aim of this study was to investigate the vision-affected optical coherence tomography (angiography) (OCT/OCTA)-based morphological characteristics of diabetic macular edema (DME) and to explain their possible underlying mechanisms from a systemic perspective. METHODS: Diabetic patients with DME were included in this retrospective study. The clinical profiles and OCT/OCTA morphological characteristics were recorded. Linear mixed-model analyses were performed between best-corrected visual acuity (BCVA) and each OCT/OCTA morphological characteristic. Linear and logistic mixed-model analyses were performed between each vision-affected morphological characteristic and the clinical characteristics. RESULTS: Eighty-five eyes of 85 patients were included. The number of hyperreflective dots (HDs) (p<0.001) and hyperreflective foci (HF) (p = 0.006) was positively correlated with LogMAR BCVA in the univariate analysis. The number of HDs (p = 0.008) remained correlated with LogMAR BCVA in the multivariate analysis. Eyes with an increased number of HF (p = 0.01) were more likely to have hard exudates within a fovea area diameter of 3 mm, while the relationship between the number of HDs and the presence of hard exudates did not reach significance. In the multivariate analysis, the increased level of total cholesterol (TC) (p = 0.004) and the reduced level of serum albumin (p = 0.014) were associated with an increased number of HDs, and the level of serum TC (p = 0.039) was positively associated with the number of HF. CONCLUSION: Hyperreflective material may be a predictor for BCVA and serves as a potential biomarker of dyslipidemia in DME. It was postulated that HF are mainly related to hard exudates and HDs are partially associated with microglial cell activation.

Long-term and potent IOP-lowering effect of IκBα-siRNA in a nonhuman primate model of chronic ocular hypertension.

Glaucoma is one of the most common causes of irreversible blindness. It is acknowledged that lowering intraocular pressure (IOP) is the effective treatment to slow glaucoma disease progression. The main obstacle of existing drugs is that the effect of reducing IOP does not last long. Degradation of IκB stimulates the transcription of NF-κB, which could upregulate the expression of matrix metalloproteinases (MMPs). Whether a IκB-targeted gene therapy works in glaucoma is unclear. Here, we established a chronic ocular hypertension (COHT) model in rhesus monkey by laser photocoagulation and verified that intracameral delivery of IκBα-siRNA showed long-lasting and potent effects of reducing IOP without obvious inflammation in monkeys with COHT. We also verified that IκBα-siRNA could increase the expressions of MMP2 and MMP9 by knocking down IκBα in vitro and in vivo. Our results in nonhuman primates indicated that IκBα-siRNA may become a promising therapeutic approach for the treatment of glaucoma.

Incidence and Characteristics of Retinopathy of Prematurity Patients With Late Gestational Age and Large Birth Weight in South China.

Purpose: To investigate the incidence and characteristics of retinopathy of prematurity (ROP) premature infants with late gestational age (GA) and large birth weight (BW) and show a 7-year trend of ROP incidence in South China. Methods: This retrospective, cross-sectional study included premature infants who received ROP screening in a 7-year period (from 2010 to 2016) at the Sun Yat-sen Memorial Hospital (SYSMH), Guangzhou, South China. Infants were screened if they had GA <37 weeks or BW <2,500 g. All screened infants were divided into two groups: Group 1 (with both GA ≥ 35 weeks and BW ≥ 1,750 g) and Group 2 (others). The characteristics of ROP infants in Group 1 were analyzed and compared with those in Group 2. Results: A total of 911 premature infants were screened, with 282 infants in Group 1 and 629 in Group 2. Both the incidences of any ROP (6.7 vs. 8.3%, p = 0.50) and Type 1 ROP (1.4 vs. 1.7%, p = 0.72) in Group 1 were comparable with those in Group 2. Lower proportions of respiratory distress (15.8 vs. 71.2%, p < 0.001), blood transfusion (5.3 vs. 32.7%, p = 0.028), and oxygen administration (31.6 vs. 86.5%, p < 0.001) among ROP patients in Group 1 than those in Group 2 were revealed. Vaginal delivery [OR: 4.73 (1.83-12.26)] was identified as a factor associated with ROP among the infants in Group 1. Forty percent (6/15) of Type 1 ROP in this study would have been missed under the current screening criteria in China (GA ≤ 34 weeks and/or BW ≤ 2,000 g). Trends of increased incidence of Type 1 ROP and decreased BW were exhibited in the 7-year study period. Conclusions: These findings indicate that even the premature infants with late GA and large BW also have a high risk of developing ROP, especially for those delivered by vagina. The findings may provide a significant reference for ROP screening and neonatal care in South China and other regions with similar conditions.