Comparison of photodynamic therapy with two different parameters combined with subconjunctival injection of bevacizumab for corneal neovascularization.

BACKGROUND: To the best of our knowledge, no studies have been performed to determine the optimal parameters of photodynamic therapy (PDT) combined with subconjunctival injection of bevacizumab for corneal neovascularization. This study aimed to compare the effect of photodynamic therapy with two different sets of parameters combined with subconjunctival injection of bevacizumab for corneal neovascularization. METHODS: Patients with stable corneal neovascularization (CNV) unresponsive to conventional treatment (topical steroid) were included in this study. Patients were divided into two groups, receiving PDT with two different sets of parameters (group 1 receiving fluence of 50 J/cm2 at 15 min after intravenous injection of verteporfin with, group 2 receiving fluence of 150 J/cm2 at 60 min after intravenous injection of verteporfin with). Subconjunctival injection of bevacizumab was performed immediately after PDT. All patients were followed for 6 months. Best-corrected visual acuity and intraocular pressure were evaluated, and slit-lamp biomicroscopy as well as digital photography were performed. Average diameter and cumulative length of corneal neovascular were measured to evaluate the corneal neovascularization. RESULTS: Seventeen patients (20 eyes) were included in this study. At the last visit, the vision was improved in 12 eyes (60 %), steady in 4 eyes (20 %) and worsen in 4 eyes (20 %). The intraocular pressure (IOP) of all patients remained in normal range. A significant decrease in corneal neovascularization was showed in all the eyes after treatment. At 6 months after the combined treatment, the average diameter and cumulative length of vessels significantly decreased to 0.041 ± 0.023 mm (P < 0.05) and 18.78 ± 17.73 mm (P < 0.05), respectively, compared with the pretreatment data (0.062 ± 0.015 mm, 31.48 ± 18.21 mm). The reduction was more remarkable in group 2 compared to group 1.In group 1, the average diameter was 0.062 ± 0.013mm before and 0.056 ± 0.017mm after, the cumulative length of vessels was 38.66 ± 22.55mm before and 31.21 ± 17.30 after. In group 2, the date were 0.061 ± 0.016mm before and 0.029 ± 0.020mm after, 25.60 ± 8.95 mm before and 8.61 ± 8.26 mm. The reported complications included epithelial defect in four eyes, small white filaments in two eyes and corneal epithelial erosion in two eyes. CONCLUSION: The PDT combined with subconjunctival injection of bevacizumab was effective for the chronic corneal neovascularization. A more promising treatment outcome was observed when PDT was performed at 60 min after intravenous injection of verteporfin with fluence of 150 J/cm2. No serious complications or systemic events were observed throughout the follow-up period.

A randomized non-inferiority trial of 577nm subthreshold micropulse laser versus half-dose photodynamic therapy for acute central serous chorioretinopathy.

PURPOSE: To compare the effectiveness of 577nm subthreshold micropulse laser (SML) with half-dose photodynamic therapy (Hd-PDT) for acute central serous chorioretinopathy (CSC). METHOD: A non-inferiority clinical trial was performed with a non-inferiority margin of eight letters. Sixty-eight eyes of 68 patients with acute CSC were randomized to the Hd-PDT group or 577 nm SML group. Best-corrected visual acuity (BCVA ), the subretinal fluid (SRF), and the central foveal thickness (CFT) were evaluated at 6 months. RESULTS: The visual acuity significantly improved from 70.38 ± 10.37 at baseline to 83.24 ± 3.03 at 6 months after treatment in the SML group (P < 0.001), from 71.09 ± 10.50 to 84.35 ± 2.09 in the PDT group (P < 0.001). SML was non-inferior to the PDT (mean difference: -0.41, 95% CI: -5.51 - 4.68, P = 0.0021). At the endpoint, CFT was significantly reduced in the two groups, but no statistical difference (P = 0.7694). The complete resolution of SRF reached 82.35% (28/34) in the SML group and 91.18% (31/34) in the PDT group, respectively,but no statistical difference (P = 0.3724). CONCLUSIONS: SML was non-inferiority to half-dose PDT in improving the visual acuity for CSC, and it is a viable alternative, especially when the verteporfin in PDT is unavailable.

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.

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.

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.

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.

Changes of microstructure of central serous chorioretinopathy on OCT and its relationship with prognosis.

PURPOSE: To quantitatively evaluate the relationship between retinal microstructure and prognosis in patients with central serous chorioretinopathy(CSC) using optical coherence tomography(OCT). METHODS: Three hundred and ninty-eight affected eyes of patients with central serous chorioretinopathy were included in this retrospective study. The OCT images of all patients were analyzed in baseline, and logistic regression analysis were performed with 11 independent variables, and subretinal fluid absorption in 3 months after therapy as dependent variable. The correlation between shortage of ellipsoid baseline and height of foveal subretinal fluid, width of foveal subretinal fluid were analyzed respectively. The difference of duration and baseline logMAR visual acuity in eyes with and without double layer sign or subretinal hyper-reflective materials were analyzed respectively. The difference of therapeutic outcome among different therapeutic methods was also analyzed in eyes with double-layer sign and subretinal hyper-reflective materials respectively. RESULTS: In the regression analysis with subretinal fluid absorption in 3 months after therapy as dependent variable, disintegrity of ellipsoid zone was statistically significant(P<0.0001,B=1.288). There is no correlation between disintegrity of the ellipsoid zone and the width or height of subretinal fluid. The duration of disease in eyes with double layer sign or subretinal hyper-reflective materials was longer than those without these features(P<0.001, P<0.0001). In the eyes with the double-layer sign or subretinal hyper-reflective material, the difference of logMAR visual acuity 3 months after treatment between 2 therapeutic methods was not statistically significant. CONCLUSIONS: Using optical coherence tomography to evaluate microstructure changes in eyes with central serous chorioretinopathy quantitatively, we found that subretinal fluid was easier to absorb completely in eyes with less disintegrity of ellipsoid zone. Double layer sign and subretinal hyper-reflective materials are more common in eyes with longer duration of disease.

Twenty-year outcome in neovascular age-related macular degeneration treated with photodynamic therapy and intravitreal bevacizumab/ranibizumab injections: A case report.

A 64-year-old female presented with acute painless vision loss in the left eye was diagnosed with neovascular age-related macular degeneration. During the 20-year follow-up, the patient experienced subretinal fluid, subretinal hemorrhage, pigmentary epithelium detachment, intraretinal fluid, subretinal scar formation and macular atrophy. A total of 3 PDT treatments, 3 intravitreal bevacizumab and 16 ranibizumab injections were performed in the left eye. At the last visit, she remained best-corrected visual acuity of 20/200 with foveal macular atrophy and subfoveal fibrotic scar.

Application of Artificial Intelligence in Precision Medicine for Diabetic Macular Edema.

Diabetic macular edema (DME) is the primary cause of central vision impairment in patients with diabetes and the leading cause of preventable blindness in working-age people. With the advent of optical coherence tomography and antivascular endothelial growth factor (anti-VEGF) therapy, the diagnosis, evaluation, and treatment of DME were greatly revolutionized in the last decade. However, there is tremendous heterogeneity among DME patients, and 30%-50% of DME patients do not respond well to anti-VEGF agents. In addition, there is no evidence-based and universally accepted administration regimen. The identification of DME patients not responding to anti-VEGF agents and the determination of the optimal administration interval are the 2 major challenges of DME, which are difficult to achieve with the coarse granularity of conventional health care modality. Therefore, more and more retina specialists have pointed out the necessity of introducing precision medicine into the management of DME and have conducted related studies in recent years. One of the most frontier methods is the targeted extraction of individualized disease features from optical coherence tomography images based on artificial intelligence technology, which provides precise evaluation and risk classification of DME. This review aims to provide an overview of the progress of artificial intelligence-enabled precision medicine in automated screening, precise evaluation, prognosis prediction, and follow-up monitoring of DME. Further, the challenges ahead of real-world applications and the future development of precision medicine in DME will be discussed.

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

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

Clinical and Genetic Analysis of RDH12-Associated Retinopathy in 27 Chinese Families: A Hypomorphic Allele Leads to Cone-Rod Dystrophy.

Purpose: The purpose of this study was to elucidate the genetic basis of 2 distinct phenotypes associated with biallelic variants in RDH12. Methods: Patients with biallelic variants in RDH12 were recruited from our genetic eye clinic. Ocular phenotypes were evaluated. Genotype-phenotype correlations were further clarified using in-house and existing databases. Results: In total, 22 biallelic RDH12 variants, including 5 novel variants, were identified in 29 patients from 27 families. Two distinct phenotypes were observed: early-onset and generalized retinal dystrophy with severe impairment of rods and cones in 24 patients (82.8%, 24/29), and late-onset cone-rod dystrophy (CORD) with central macular atrophy in 5 patients from 5 unrelated families (17.2%, 5/29), in which a hypomorphic allele (c.806C>G/p.Ala269Gly) was shared by all 5 patients. During follow-up, patients with late-onset CORD were relatively stable and did not progress to the severe form, which was considered to be an independent manifestation of RDH12-associated retinopathy caused by specific genotypes. Conclusions: The hypomorphic allele is responsible for the unique late-onset CORD in 5 families with recessive RDH12-associated retinopathy, in contrast to the well-known severe and generalized retinopathy. Determining the therapeutic value of interventions may depend on understanding the molecular mechanisms underlying manifestation of this hypomorphic variant only in the central macular region, with relative preservation of the peripheral retina.

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.

Automated detection of retinal exudates and drusen in ultra-widefield fundus images based on deep learning.

BACKGROUND: Retinal exudates and/or drusen (RED) can be signs of many fundus diseases that can lead to irreversible vision loss. Early detection and treatment of these diseases are critical for improving vision prognosis. However, manual RED screening on a large scale is time-consuming and labour-intensive. Here, we aim to develop and assess a deep learning system for automated detection of RED using ultra-widefield fundus (UWF) images. METHODS: A total of 26,409 UWF images from 14,994 subjects were used to develop and evaluate the deep learning system. The Zhongshan Ophthalmic Center (ZOC) dataset was selected to compare the performance of the system to that of retina specialists in RED detection. The saliency map visualization technique was used to understand which areas in the UWF image had the most influence on our deep learning system when detecting RED. RESULTS: The system for RED detection achieved areas under the receiver operating characteristic curve of 0.994 (95% confidence interval [CI]: 0.991-0.996), 0.972 (95% CI: 0.957-0.984), and 0.988 (95% CI: 0.983-0.992) in three independent datasets. The performance of the system in the ZOC dataset was comparable to that of an experienced retina specialist. Regions of RED were highlighted by saliency maps in UWF images. CONCLUSIONS: Our deep learning system is reliable in the automated detection of RED in UWF images. As a screening tool, our system may promote the early diagnosis and management of RED-related fundus diseases.

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.

Comparison of the Effect of Pan-Retinal Photocoagulation and Intravitreal Conbercept Treatment on the Change of Retinal Vessel Density Monitored by Optical Coherence Tomography Angiography in Patients with Proliferative Diabetic Retinopathy.

BACKGROUND: This study compares the change of retinal vessel density (VD) after pan-retinal photocoagulation (PRP) and intravitreal conbercept (IVC) treatment in proliferative diabetic retinopathy (PDR) eyes with optical coherence tomography angiography (OCTA). METHODS: A total of 55 treatment-naïve PDR eyes were included in this retrospective study. Of these, 29 eyes were divided into a PRP group, and 26 eyes were divided into an IVC group based on the treatment they received. OCTA was performed to measure macular and papillary VD at each follow-up in both groups. RESULTS: The macular VD for superficial capillary plexus (SCP), deep capillary plexus (DCP), choriocapillaris (CC) and papillary VD for radial peripapillary capillary (RPC) between the two groups demonstrated no significant difference at baseline and month 12 (p > 0.05). The paired t-test results showed that the macular VD for SCP, DCP, CC and papillary VD for the RPC at month 12 did not differ to the baseline in each group (p > 0.05). CONCLUSIONS: During the 12-month follow-up, there was no significant change of macular and papillary VD between the PRP and IVC treatment in PDR eyes. Additionally, compared to the baseline, there were no significant changes of macular and papillary VD after either the PRP or IVC treatment. Considering the decrease in VD as DR progress, both treatments have potential protection of macular and papillary VD loss in PDR.

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.