PEDF protects retinal pigment epithelium from ferroptosis and ameliorates dry AMD-like pathology in a murine model.

Age-related macular degeneration (AMD) is the leading cause of irreversible vision damage among elderly individuals. There is still no efficient treatment for dry AMD. Retinal pigment epithelial (RPE) degeneration has been confirmed to play an important role in dry AMD. Recent studies have reported that ferroptosis caused by iron overload and lipid peroxidation may be the primary causes of RPE degeneration. However, the upstream regulatory molecules of RPE ferroptosis remain largely unknown. Pigment epithelium-derived factor (PEDF) is an important endogenic protective factor for the RPE. Our results showed that in the murine dry AMD model induced by sodium iodate (SI), PEDF expression was downregulated. Moreover, dry AMD-like pathology was observed in PEDF-knockout mice. Therefore, the aim of this study was to reveal the effects and mechanism of PEDF on RPE ferroptosis and investigate potential therapeutic targets for dry AMD. The results of lipid peroxidation and transmission electron microscope showed that retinal ferroptosis was significantly activated in SI-treated mice and PEDF-knockout mice. Restoration of PEDF expression ameliorated SI-induced retinal dysfunction in mice, as assessed by electroretinography and optical coherence tomography. Mechanistically, western blotting and immunofluorescence analysis demonstrated that the overexpression of PEDF could upregulate the expression of glutathione peroxidase 4 (GPX4) and ferritin heavy chain-1 (FTH1), which proved to inhibit lipid peroxidation and RPE ferroptosis induced by SI. This study revealed the novel role of PEDF in ferroptosis inhibition and indicated that PEDF might be a potential therapeutic target for dry AMD.

Role of immune inflammation regulated by macrophage in the pathogenesis of age-related macular degeneration.

Age-related macular degeneration (AMD) can lead to irreversible impairment of visual function, and the number of patients with AMD has been increasing globally. The immunoinflammatory theory is an important pathogenic mechanism of AMD, with macrophages serving as the primary inflammatory infiltrating cells in AMD lesions. Its powerful immunoinflammatory regulatory function has attracted considerable attention. Herein, we provide an overview of the involvement of macrophage-regulated immunoinflammation in different stages of AMD. Additionally, we summarize novel therapeutic approaches for AMD, focusing on targeting macrophages, such as macrophage/microglia modulators, reduction of macrophage aggregation in the subretinal space, modulation of macrophage effector function, macrophage phenotypic alterations, and novel biomimetic nanocomposites development based on macrophage-associated functional properties. We aimed to provide a basis and reference for the further exploration of AMD pathogenesis, developmental influences, and new therapeutic approaches.

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

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

The RBPMSCreERT2-tdTomato mouse line for studying retinal and vascular relevant diseases.

RNA-binding protein with multiple splicing (RBPMS) plays a crucial role in cardiac mesoderm specification and cardiovascular development, as well as being a typical marker for whole retinal ganglion cells (RGCs). However, there is a lack of animal models to spatiotemporally trace the location and function of RBPMS-expressing cells in vivo. In this study, we develop a tamoxifen-inducible RBPMS-tdTomato reporter mouse line to track RBPMS-expressing cells during embryogenesis and adulthood. This mouse line allows us to identify and locate RBPMS-tdTomato-positive cells among various tissues, especially in RGCs and smooth muscle cells, which assist to simulate related retinal degenerative diseases, model and examine choroidal neovascularization non-invasively in vivo. Our results show that the RBPMSCreERT2-tdTomato mouse line is a valuable tool for lineage tracing, disease modeling, drug screening, as well as isolating specific target cells.

Novel compound heterozygous variants of the SEC23A gene in a Chinese family with cranio-lenticulo-sutural dysplasia based on data from a large cohort of congenital cataract patients.

BACKGROUND: Cranio-lenticulo-sutural dysplasia (CLSD) is a rare dysmorphic syndrome characterized by skeletal dysmorphism, late-closing fontanels, and cataracts. CLSD is caused by mutations in the SEC23A gene (OMIM# 607812) and can be inherited in either an autosomal dominant or autosomal recessive pattern. To date, only four mutations have been reported to cause CLSD. This study aims to identify the disease-causing variants in a large cohort of congenital cataract patients, to expand the genotypic and phenotypic spectrum of CLSD, and to confirm the association between SEC23A and autosomal recessive CLSD (ARCLSD). METHODS: We collected detailed medical records and performed comprehensive ocular examinations and whole-exome sequencing (WES) on 115 patients with congenital cataracts. After suspecting that a patient may have CLSD based on the sequencing results, we proceeded to conduct transmission electron microscopy (TEM) on the cultured skin fibroblasts. The clinical validity of the reported gene-disease relationships for the gene and the disease was evaluated using the ClinGen gene curation framework. RESULTS: Two novel compound heterozygous variants (c.710A > C p.Asp237Ala, c.1946T > C p.Leu649Pro) of the SEC23A gene, classified as variant of uncertain significance, were identified in the proband with skeletal, cardiac, ocular, and hearing defects. The observation of typical distended endoplasmic reticulum cisternae further supported the diagnosis of CLSD. Application of the ClinGen gene curation framework confirmed the association between SEC23A and ARCLSD. CONCLUSION: This study expands the genotypic and phenotypic spectrum of CLSD, proposes TEM as a supplemental diagnostic method, and indicates that congenital cataracts are a typical sign of ARCLSD.

Systemic Risk Factors for Vitreous Hemorrhage Secondary to Polypoidal Choroidal Vasculopathy.

INTRODUCTION: It remains unclear whether systemic factors are associated with an increased risk of vitreous hemorrhage (VH) secondary to polypoidal choroidal vasculopathy (PCV), and there is no method to predict the possibility of VH occurrence in patients with PCV. This study aimed to investigate and visualize systemic risk factors for VH in patients with PCV. METHODS: Data on the sex, age, history of systematic diseases, best-corrected visual acuity, intraocular pressure, and laboratory data of patients with PCV were collected from the medical record system. Univariate and multivariate binary logistic regression analyses were applied to investigate independent risk factors for VH in patients with PCV. Receiver operating characteristic analysis and nomograms were used to visualize the independent risk factors. RESULTS: The patient population comprised 115 patients with VH secondary to PCV and 181 patients with PCV without VH. Binary logistic regression analyses showed that higher white blood cell count [WBC; odds ratios (OR) 1.247], higher aspartate aminotransferase/alanine aminotransferase ratio (AST/ALT; OR 2.339), and longer activated partial thromboplastin time (APTT; OR 1.196) were independent risk factors of VH in patients with PCV. Integrated application of APTT, AST/ALT, and WBC as markers showed the best performance for distinguishing patients with VH, with an area under the curve of 0.723. The nomogram was created for doctors to calculate the possibility of VH in a patient with PCV. CONCLUSIONS: Higher WBC, higher AST/ALT, and longer APTT are independent serum risk factors of VH secondary to PCV, which may shed light on VH prevention in patients with PCV.

Performance of the AIDRScreening system in detecting diabetic retinopathy in the fundus photographs of Chinese patients: a prospective, multicenter, clinical study.

Background: Diabetic retinopathy (DR) is the leading cause of blindness in the working-age population worldwide, and there is a large unmet need for DR screening in China. This observational, prospective, multicenter, gold standard-controlled study sought to evaluate the effectiveness and safety of the AIDRScreening system (v. 1.0), which is an artificial intelligence (AI)-enabled system that detects DR in the Chinese population based on fundus photographs. Methods: Participants with diabetes mellitus (DM) were recruited. Fundus photographs (field 1 and field 2) of 1 eye in each participant were graded by the AIDRScreening system (v. 1.0) to detect referable DR (RDR). The results were compared to those of the masked manual grading (gold standard) system by the Zhongshan Image Reading Center. The primary outcomes were the sensitivity and specificity of the AIDRScreening system in detecting RDR. The other outcomes evaluated included the system's diagnostic accuracy, positive predictive value, negative predictive value, diagnostic accuracy gain rate, and average diagnostic time gain rate. Results: Among the 1,001 enrolled participants with DM, 962 (96.1%) were included in the final analyses. The participants had a median age of 60.61 years (range: 20.18-85.78 years), and 48.2% were men. The manual grading system detected RDR in 399 (41.48%) participants. The AIDRScreening system had a sensitivity of 86.72% (95% CI: 83.39-90.05%) and a specificity of 96.09% (95% CI: 94.14-97.54%) in the detection of RDR, and a false-positive rate of 3.91%. The diagnostic accuracy gain rate of the AIDRScreening system was 16.57% higher than that of the investigator, while the average diagnostic time gain rate was -37.32% lower. Conclusions: The automated AIDRScreening system can detect RDR with high accuracy, but cannot detect maculopathy. The implementation of the AIDRScreening system may increase the efficiency of DR screening.

Effects of the Implementation of an Emergency Surgical Pattern in Patients with Rhegmatogenous Retinal Detachment: A Retrospective Observational Study.

Background: To analyze the effects of the implementation of emergency surgical patterns in patients with rhegmatogenous retinal detachment (RRD) and provide evidence for promoting emergency surgical patterns for RRD. Methods: We reviewed the electronic medical records of 346 patients (348 eyes) who underwent surgical repair of RRD at the Zhongshan Ophthalmic Center in Southern China. A total of 140 patients (140 eyes) in the routine inpatient surgery group were collected at the fundus disease department between January 2019 and December 2019, and 206 patients (208 eyes) in the emergency surgery group were collected at the ophthalmic emergency department between January 2021 and December 2021. Demographics, best-corrected visual acuity (BCVA) expressed as the logarithm of the minimum angle of resolution (logMAR), the status of the macula before surgery, time to presentation, treatment interval, and postoperative BCVA measured at least three months follow-up were compared. Results: The preoperative BCVA (logMAR) of the emergency surgery group and the inpatient surgery group were 1.0 (0.4-1.7) and 1.4 (0.7-1.7), respectively, with significant differences between groups (P < 0.001). However, patients had a shorter time to presentation (7 days vs. 21 days, P < 0.001), shorter treatment interval (2 days vs. 12 days, P < 0.01), and significantly better postoperative BCVA (logMAR 0.5 vs. logMAR 1.0, P < 0.001) in the emergency surgery group than in the inpatient surgery group. There was no significant difference in primary anatomical success between the two groups (P=0.802). The median follow-up for the emergency surgery group and the inpatient surgery group were 6.08 months and 6.2 months, respectively, with no significant differences (P > 0.05). Conclusions: Patients who underwent emergency surgical patterns of RRD had better visual outcomes after surgery than patients with routine inpatient surgery, which might be attributed to a shorter duration, shorter treatment interval, and the preoperative status of the macula in the emergency surgery pattern. Emergency surgical patterns for RRD should be considered to achieve better surgical outcomes in suitable patients.

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

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

Preoperative laser reduces silicone oil use in primary diabetic vitrectomy.

AIM: To identify the predictive factors and laser photocoagulation associated with the use of silicone oil as endotamponade during primary diabetic vitrectomy. METHODS: The medical and surgical records of 690 patients (798 eyes) who underwent primary diabetic vitrectomy at a tertiary eye hospital in China from January 2018 to December 2018 were reviewed in this retrospective cohort study. The patients' baseline characteristics and preoperative treatments were recorded. The binary Logistic regression model was used to evaluate the risk factors for the use of silicone oil as endotamponade agent during primary vitrectomy for proliferative diabetic retinopathy (PDR)-related complications. RESULTS: Among 690 patients with mean age of 52.1±10.5y (range: 18-85y), 299/690 (43.3%) were female. The 31.6% of the eyes received preoperative laser treatment, and 72.4% of the eyes received preoperative anti-VEGF adjuvant therapy. Non-clearing vitreous haemorrhage (VH) alone or combined with retinal detachment was the main surgical indication (89.5%) for primary vitrectomy. Silicone oil was used as endotamponade in 313 (39.2%) eyes. Lack of preoperative laser treatment [odds ratio (OR) 0.66, 95% confidence interval (CI): 0.48-0.92; P=0.015] and older age (OR 0.96, 95%CI: 0.95-0.98; P<0.001) were predictors of silicone oil tamponade during primary vitrectomy for PDR. CONCLUSION: The lack of preoperative laser treatment is a significant predictor of silicone oil tamponade during primary vitrectomy for PDR. However, the severity of PDR relevant to silicone oil use should be further evaluated.

Predicting Central Serous Chorioretinopathy Recurrence Using Machine Learning.

Purpose: To predict central serous chorioretinopathy (CSC) recurrence 3 and 6 months after laser treatment by using machine learning. Methods: Clinical and imaging features of 461 patients (480 eyes) with CSC were collected at Zhongshan Ophthalmic Center (ZOC) and Xiamen Eye Center (XEC). The ZOC data (416 eyes of 401 patients) were used as the training dataset and the internal test dataset, while the XEC data (64 eyes of 60 patients) were used as the external test dataset. Six different machine learning algorithms and an ensemble model were trained to predict recurrence in patients with CSC. After completing the initial detailed investigation, we designed a simplified model using only clinical data and OCT features. Results: The ensemble model exhibited the best performance among the six algorithms, with accuracies of 0.941 (internal test dataset) and 0.970 (external test dataset) at 3 months and 0.903 (internal test dataset) and 1.000 (external test dataset) at 6 months. The simplified model showed a comparable level of predictive power. Conclusion: Machine learning achieves high accuracies in predicting the recurrence of CSC patients. The application of an intelligent recurrence prediction model for patients with CSC can potentially facilitate recurrence factor identification and precise individualized interventions.

Predicting Post-Therapeutic Visual Acuity and OCT Images in Patients With Central Serous Chorioretinopathy by Artificial Intelligence.

To predict visual acuity (VA) and post-therapeutic optical coherence tomography (OCT) images 1, 3, and 6 months after laser treatment in patients with central serous chorioretinopathy (CSC) by artificial intelligence (AI). Real-world clinical and imaging data were collected at Zhongshan Ophthalmic Center (ZOC) and Xiamen Eye Center (XEC). The data obtained from ZOC (416 eyes of 401 patients) were used as the training set; the data obtained from XEC (64 eyes of 60 patients) were used as the test set. Six different machine learning algorithms and a blending algorithm were used to predict VA, and a pix2pixHD method was adopted to predict post-therapeutic OCT images in patients after laser treatment. The data for VA predictions included clinical features obtained from electronic medical records (20 features) and measured features obtained from fundus fluorescein angiography, indocyanine green angiography, and OCT (145 features). The data for OCT predictions included 480 pairs of pre- and post-therapeutic OCT images. The VA and OCT images predicted by AI were compared with the ground truth. In the VA predictions of XEC dataset, the mean absolute errors (MAEs) were 0.074-0.098 logMAR (within four to five letters), and the root mean square errors were 0.096-0.127 logMAR (within five to seven letters) for the 1-, 3-, and 6-month predictions, respectively; in the post-therapeutic OCT predictions, only about 5.15% (5 of 97) of synthetic OCT images could be accurately identified as synthetic images. The MAEs of central macular thickness of synthetic OCT images were 30.15 ± 13.28 µm and 22.46 ± 9.71 µm for the 1- and 3-month predictions, respectively. This is the first study to apply AI to predict VA and post-therapeutic OCT of patients with CSC. This work establishes a reliable method of predicting prognosis 6 months in advance; the application of AI has the potential to help reduce patient anxiety and serve as a reference for ophthalmologists when choosing optimal laser treatments.

Deep Learning for Detecting Subretinal Fluid and Discerning Macular Status by Fundus Images in Central Serous Chorioretinopathy.

Subretinal fluid (SRF) can lead to irreversible visual loss in patients with central serous chorioretinopathy (CSC) if not absorbed in time. Early detection and intervention of SRF can help improve visual prognosis and reduce irreversible damage to the retina. As fundus image is the most commonly used and easily obtained examination for patients with CSC, the purpose of our research is to investigate whether and to what extent SRF depicted on fundus images can be assessed using deep learning technology. In this study, we developed a cascaded deep learning system based on fundus image for automated SRF detection and macula-on/off serous retinal detachment discerning. The performance of our system is reliable, and its accuracy of SRF detection is higher than that of experienced retinal specialists. In addition, the system can automatically indicate whether the SRF progression involves the macula to provide guidance of urgency for patients. The implementation of our deep learning system could effectively reduce the extent of vision impairment resulting from SRF in patients with CSC by providing timely identification and referral.

Intravitreal injection of triptolide attenuates subretinal fibrosis in laser-induced murine model.

BACKGROUND: Choroidal neovascularization (CNV) is a common cause of irreversible blindness in elderly patients in developed countries, and subretinal fibrosis is an advanced stage of CNV. Currently, there is no effective clinical treatment for subretinal fibrosis. PURPOSE: To investigate whether intravitreal injection of triptolide (TP) could attenuate subretinal fibrosis and determine its underlying mechanisms. METHODS: CNV was induced by laser photocoagulation in C57BL/6J mice. Immediately after laser photocoagulation, 1 µl of free TP (10 µg), TP-nanolip-PEG (TP-loaded PEGylated nanoliposomes containing 10 µg TP), or the same volume of phosphate-buffered saline (PBS) was intravitreally administered to each respective group. Areas and ratios of subretinal fibrosis were calculated seven days after laser injury. Additionally, expression levels of M2 macrophage-related markers, molecules of the transforming growth factor (TGF)-ß1/Smad signaling pathway, and markers for epithelial-mesenchymal transition (EMT) and endothelial-to-mesenchymal transition (EndoMT) were detected both in vitro and in vivo. RESULTS: The areas of subretinal fibrosis were significantly reduced in both the free TP (10993.87 ± 2416.90 µm2) and TP-nanolip-PEG (7695.32 ± 2121.91 µm2) groups when compared with the PBS group (15971.97 ± 3203.10 µm2) (p < 0.05, n = 6). The ratio of subretinal fibrosis in the free TP monomer (20.8 ± 4.2%) and TP-nanolip-PEG (12.5 ± 4.0%) groups was lower than that in the PBS control group (41.7 ± 5.3%) (p < 0.01, n = 6). Moreover, both TP and TP-nanolip-PEG suppressed the polarization of M2 macrophages and downregulated gene expressions of TGF-ß1, Smad 2, Smad 3, α-SMA, and collagen I (p < 0.05), but upregulated the gene expression of E-cadherin (p < 0.05), thus reversing TGF-ß1 induced EMT/EndoMT and attenuating subretinal fibrosis. CONCLUSIONS: TP could attenuate subretinal fibrosis by suppressing the polarization of M2 macrophages and TGF-ß1 induced EMT/EndoMT. TP-nanolip-PEG enhanced the inhibitory effects of TP on subretinal fibrosis, suggesting its therapeutic potential for CNV-related subretinal fibrosis.

Subthreshold Micropulse Laser vs. Conventional Laser for Central Serous Chorioretinopathy: A Randomized Controlled Clinical Trial.

Purpose: To investigate the effectiveness and safety of 577-nm subthreshold micropulse laser (SML) on acute central serous chorioretinopathy (CSC). Methods: One hundred and ten patients with acute CSC were randomized to receive SML or 577-nm conventional laser (CL) treatment. Optical coherence tomography and best-corrected visual acuity (BCVA) were performed before and after treatment. Results: At 3 months, the complete resolution of subretinal fluid (SRF) in 577-nm SML group (72.7%) was lower than that in CL group (89.1%) (Unadjusted RR, 0.82; P = 0.029), but it was 85.5 vs. 92.7% at 6 months (unadjusted RR, 0.92; P = 0.221). The mean LogMAR BCVA significantly improved, and the mean central foveal thickness (CFT) significantly decreased in the SML group and CL group (all P < 0.001) at 6 months. But there was no statistical difference between the two groups (all P > 0.05). In the SML group, obvious retinal pigment epithelium (RPE) damage was shown only in 3.64% at 1 month but 92.7% in the CL group (P < 0.001). Conclusions: Although 577-nm SML has a lower complete absorption of SRF compared with 577-nm CL for acute CSC at 3 months, it is similarly effective as 577-nm CL on improving retinal anatomy and function at 6 months. Importantly, 577-nm SML causes less damage to the retina.

Quantitative evaluation of damage to retinal capillaries caused by half-dose and half-time photodynamic therapy with optical coherent tomographic angiography.

PURPOSE: To determine and compare retinal capillaries damage in patients with chronic central serous chorioretinopathy (CSC) after half-dose and half-time photodynamic therapy (PDT) based on optical coherence tomographic angiography (OCTA). METHODS: Thirty-three eyes of 33 patients and 32 eyes of 32 patients with active CSC were treated with half-dose PDT and half-time PDT respectively and followed up for 3 months. Fundus fluorescein angiography (FFA) and indocyanine green angiography (ICGA) were performed at baseline; best corrected visual acuity (BCVA) and OCTA were performed at baseline, 3-day, 7-day, 14-day, 1-month, and 3-month follow-up visits. RESULTS: Twenty-eight patients in half-dose group and 27 patients in the half-time group finished the 3-month follow-up visits. BCVA was significantly improved at post-PDT 1 month and 3 months (both P < 0.05) and central macula thickness (CMT) was significantly decreased at all post-PDT time points (all P < 0.05) in both groups. 22 patients (78.57%) in the half-dose group and 21 patients (77.78%) in the half-time group had complete absorption of subretinal fluid (SRF) at post-PDT 3 months. There was no significant difference in the above-mentioned prognostic measurements between two groups. The mean vessel densities of superficial retina (VDSR) and inner retina (VDIR) layers were decreased at all post-PDT time points in both groups. However, the decrease of VDIR and VDSR at post-PDT 3 days and 3 months in the half-dose group was much severe than those in the half-time group (P < 0.05). CONCLUSIONS: Both half-dose and half-time modifications of PDT were similarly effective in improving the BCVA and decreasing the SRF for chronic CSC. However, the retinal capillaries damage in the half-time group was less severe than that in the half-dose group, so the half-time modification may be a more appropriate parameter for patients with chronic CSC.

Determinants of macular ganglion cell-inner plexiform layer thickness in normal Chinese adults.

BACKGROUND: Demographic, systemic and ocular factors may impact macular ganglion cell-inner plexiform layer (GCIPL) thickness measurements. This study aimed to investigate the influences of multiple potential determinants of macular GCIPL thickness in normal Chinese adults. METHODS: This was a retrospective study conducted on 225 normal eyes from 225 healthy Chinese adults. GCIPL thickness were obtained using Cirrus high-definition optical coherence tomography (OCT). The age, gender, laterality, spherical equivalent (SE) refractive error, intraocular pressure (IOP), axial length (AL), central cornea thickness (CCT), circumpapillary retinal nerve fibre layer (pRNFL) thickness and OCT signal strength were recorded and their respective effect on GCIPL thickness parameters were evaluated. RESULTS: The mean (± SD) average, minimum, superotemporal, superior, superonasal, inferonasal, inferior, and inferotemporal GCIPL thickness was 84.56 ± 5.36, 81.32 ± 5.58, 83.08 ± 5.37, 85.70 ± 5.95, 87.15 ± 6.26, 85.07 ± 6.11, 82.46 ± 5.76, and 83.88 ± 5.59 µm, respectively. Determinants of thinner GCIPL thickness were older age (P = 0.001-0.117; effects enhanced if age over 40 years), thinner pRNFL (all P < 0.001), and weaker signal strength (all P < 0.001). No significant difference was found between males and females (P = 0.069-0.842), and between right eyes and the left eyes (P = 0.160-0.875) except that of superonasal GCIPL thickness (P < 0.001). There was no significant correlation between GCIPL thickness and SE, IOP, CCT, and AL (P = 0.135-0.968). CONCLUSIONS: Individual determinants associated with thinner GCIPL thickness were older age (particularly over 40 years of age), thinner pRNFL, and weaker OCT signal strength. This is relevant in comprehensively understanding the normative data and differentiating normal aging from abnormalities.

Predicting subretinal fluid absorption with machine learning in patients with central serous chorioretinopathy.

BACKGROUND: Machine learning was used to predict subretinal fluid absorption (SFA) at 1, 3 and 6 months after laser treatment in patients with central serous chorioretinopathy (CSC). METHODS: The clinical and imaging data from 480 eyes of 461 patients with CSC were collected at Zhongshan Ophthalmic Center (ZOC) and Xiamen Eye Center (XEC). The data included clinical features from electronic medical records and measured features from fundus fluorescein angiography (FFA), indocyanine green angiography (ICGA), optical coherence tomography angiography (OCTA), and optical coherence tomography (OCT). A ZOC dataset was used for training and internal validation. An XEC dataset was used for external validation. Six machine learning algorithms and a blending algorithm were trained to predict SFA in patients with CSC after laser treatment. The SFA results predicted by machine learning were compared with the actual patient prognoses. Based on the initial detailed investigation, we constructed a simplified model using fewer clinical features and OCT features for convenient application. RESULTS: During the internal validation, random forest performed best in SFA prediction, with accuracies of 0.651±0.068, 0.753±0.065 and 0.818±0.058 at 1, 3 and 6 months, respectively. In the external validation, XGBoost performed best at SFA prediction with accuracies of 0.734, 0.727, and 0.900 at 1, 3 and 6 months, respectively. The simplified model showed a comparable level of predictive power. CONCLUSIONS: Machine learning can achieve high accuracy in long-term SFA predictions and identify the features relevant to CSC patients' prognoses. Our study provides an individualized reference for ophthalmologists to treat and create a follow-up schedule for CSC patients.

Microinvasive pars plana vitrectomy versus panretinal photocoagulation in the treatment of severe non-proliferative diabetic retinopathy (the VIP study): study protocol for a randomised controlled trial.

INTRODUCTION: Diabetic retinopathy (DR) is the main cause of adult visual impairment worldwide. Severe non-proliferative DR (sNPDR) is an important clinical intervention stage. Currently, panretinal photocoagulation (PRP) is the standard treatment for sNPDR. However, PRP alone cannot completely prevent NPDR progression. One explanation might be that PRP does not remove the detrimental vitreous that plays an important role in DR progression. Microinvasive pars plana vitrectomy (PPV) was shown to be a safe and effective method to treat late-stage proliferative DR (PDR) by completely removing the pathological vitreous. However, whether PPV is effective in controlling sNPDR remains unknown. In this trial, we aim to compare the effectiveness of microinvasive PPV with that of PRP for sNPDR progression control. METHODS AND ANALYSIS: This single centre, parallel group, randomised controlled trial aims to evaluate the clinical efficacy of microinvasive PPV in preventing the progression of sNPDR compared with PRP. A total of 272 adults diagnosed with sNPDR will be randomised 1:1 to the microinvasive PPV and PRP groups. The primary outcome is the disease progression rate, calculated as the rate of sNPDR progressed to PDR from baseline to 12 months after treatment. The secondary outcomes include the change in best-corrected visual acuity, re-treatment rate, diabetic macular oedema occurrence, change in central retinal thickness, change in the visual field, cataract occurrence and change in the quality of life. ETHICS AND DISSEMINATION: The Ethics Committee of Zhongshan Ophthalmic Center approved this study (2019KYPJ108). The results will be presented at scientific meetings and submitted for publication to peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04103671.

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

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