Comparison of 27-gauge beveled-tip and 25-gauge flat-tip microincision vitrectomy surgery in the treatment of proliferative diabetic retinopathy: a randomized controlled trial.

PURPOSE: To compare the effectiveness and safety of a 27-gauge (27G) beveled-tip microincision vitrectomy surgery (MIVS) with a 25-gauge (25G) flat-tip MIVS for the treatment of proliferative diabetic retinopathy (PDR). METHODS: A prospective, single-masked, randomized, controlled clinical trial included 52 eyes (52 patients) with PDR requiring proliferative membrane removal. They were randomly assigned in a 1:1 ratio to undergo the 27G beveled-tip and or 25G flat-tip MIVS (the 27G group and the 25G group, respectively). During surgery, the productivity of cutting the membrane, the number of vitrectomy probe (VP) exchanges to microforceps, total operation time, vitrectomy time and intraoperative complications were measured. Best-corrected visual acuity (BCVA), intraocular pressure (IOP) and postoperative complications were also assessed to month 6. RESULTS: Forty-seven eyes (47 patients) completed the follow-up, including 25 in the 27G group and 22 in the 25G group. During surgery in the 27G group, cutting the membrane was more efficient (P = 0.001), and the number of VP exchanges to microforceps was lower (P = 0.026). The occurrences of intraoperative hemorrhages and electrocoagulation also decreased significantly (P = 0.004 and P = 0.022). There were no statistical differences in the total operation time or vitrectomy time between the two groups (P = 0.275 and P = 0.372), but the former was slightly lower in the 27G group. Additionally, the 27G group required fewer wound sutures (P = 0.044). All the follow-up results revealed no significant difference between the two groups. CONCLUSIONS: Compared with the 25G flat-tip MIVS, the 27G beveled-tip MIVS could be more efficient in removing the proliferative membrane while reducing the occurrence of intraoperative hemorrhages and electrocoagulation using appropriate surgical techniques and instrument parameters. Its vitreous removal performance was not inferior to that of the 25G MIVS and might offer potential advantages in total operation time. In terms of patient outcomes, advanced MIVS demonstrates equal effectiveness and safety to 25G flat-tip MIVS. TRIAL REGISTRATION: The clinical trial has been registered at Clinicaltrials.gov (NCT0544694) on 07/07/2022. And all patients in the article were enrolled after registration.

Deep learning-based postoperative visual acuity prediction in idiopathic epiretinal membrane.

BACKGROUND: To develop a deep learning (DL) model based on preoperative optical coherence tomography (OCT) training to automatically predict the 6-month postoperative visual outcomes in patients with idiopathic epiretinal membrane (iERM). METHODS: In this retrospective cohort study, a total of 442 eyes (5304 images in total) were enrolled for the development of the DL and multimodal deep fusion network (MDFN) models. All eyes were randomized into a training dataset with 265 eyes (60.0%), a validation dataset with 89 eyes (20.1%), and an internal testing dataset with the remaining 88 eyes (19.9%). The input variables for prediction consisted of macular OCT images and diverse clinical data. Inception-Resnet-v2 network was utilized to estimate the 6-month postoperative best-corrected visual acuity (BCVA). Concurrently, a regression model was developed using the clinical data and OCT parameters in the training data set for predicting postoperative BCVA. The reliability of the models was subsequently evaluated using the testing dataset. RESULTS: The prediction DL algorithm exhibited a mean absolute error (MAE) of 0.070 logMAR and root mean square error (RMSE) of 0.11 logMAR in the testing dataset. The DL model demonstrated a robust promising performance with R2 = 0.80, notably superior to R2 = 0.49 of the regression model. The percentages of BCVA prediction errors within ± 0.20 logMAR amounted to 94.32% in the testing dataset. CONCLUSIONS: The OCT-based DL model demonstrated sensitivity and accuracy in predicting postoperative BCVA in iERM patients. This innovative DL model exhibits substantial potential for integration into surgical planning protocols.

Risk of diabetic retinopathy and retinal neurodegeneration in individuals with type 2 diabetes: Beichen Eye Study.

Objective: Our aim was to evaluate associations of different risk factors with odds of diabetic retinopathy (DR) diagnosis and retinal neurodegeneration represented by macular ganglion cell-inner plexiform layer (mGCIPL). Methods: This cross-sectional study analyzed data from individuals aged over 50 years examined between June 2020 and February 2022 in the community-based Beichen Eye Study on ocular diseases. Baseline characteristics included demographic data, cardiometabolic risk factors, laboratory findings, and medications at enrollment. Retinal thickness in both eyes of all participants was measured automatically via optical coherence tomography. Risk factors associated with DR status were investigated using multivariable logistic regression. Multivariable linear regression analysis was performed to explore associations of potential risk factors with mGCIPL thickness. Results: Among the 5037 included participants with a mean (standard deviation, SD) age of 62.6 (6.7) years (3258 women [64.6%]), 4018 (79.8%) were control individuals, 835 (16.6%) were diabetic individuals with no DR, and 184 (3.7%) were diabetic individuals with DR. The risk factors significantly associated with DR status were family history of diabetes (odds ratio [OR], 4.09 [95% CI, 2.44-6.85]), fasting plasma glucose (OR, 5.88 [95% CI, 4.66-7.43]), and statins (OR, 2.13 [95% CI, 1.03-4.43]) relative to the control individuals. Compared with the no DR, diabetes duration (OR, 1.17 [95% CI, 1.13-1.22]), hypertension (OR, 1.60 [95% CI, 1.26-2.45]), and glycated hemoglobin A1C (HbA1c) (OR, 1.27 [95% CI, 1.00-1.59]) were significantly correlated with DR status. Furthermore, age (adjusted ß = -0.19 [95% CI, -0.25 to -0.13] µm; P < 0.001), cardiovascular events (adjusted ß = -0.95 [95% CI, -1.78 to -0.12] µm; P = 0.03), and axial length (adjusted ß = -0.82 [95% CI, -1.29 to -0.35] µm; P = 0.001) were associated with mGCIPL thinning in diabetic individuals with no DR. Conclusion: Multiple risk factors were associated with higher odds of DR development and lower mGCIPL thickness in our study. Risk factors affecting DR status varied among the different study populations. Age, cardiovascular events, and axial length were identified as potential risk factors for consideration in relation to retinal neurodegeneration in diabetic patients.

Probable Treatment Targets for Diabetic Retinopathy Based on an Integrated Proteomic and Genomic Analysis.

Purpose: Using previously approved medications for new indications can expedite the lengthy and expensive drug development process. We describe a bioinformatics pipeline that integrates genomics and proteomics platforms to identify already-approved drugs that might be useful to treat diabetic retinopathy (DR). Methods: Proteomics analysis of vitreous humor samples from 12 patients undergoing pars plana vitrectomy for DR and a whole genome dataset (UKBiobank TOPMed-imputed) from 1330 individuals with DR and 395,155 controls were analyzed independently to identify biological pathways associated with DR. Common biological pathways shared between both datasets were further analyzed (STRING and REACTOME analyses) to identify target proteins for probable drug modulation. Curated target proteins were subsequently analyzed by the BindingDB database to identify chemical compounds they interact with. Identified chemical compounds were further curated through the Expasy SwissSimilarity database for already-approved drugs that interact with target proteins. Results: The pathways in each dataset (proteomics and genomics) converged in the upregulation of a previously unknown pathway involved in DR (RUNX2 signaling; constituents MMP-13 and LGALS3), with an emphasis on its role in angiogenesis and blood-retina barrier. Bioinformatics analysis identified U.S. Food and Drug Administration (FDA)-approved medications (raltitrexed, pemetrexed, glyburide, probenecid, clindamycin hydrochloride, and ticagrelor) that, in theory, may modulate this pathway. Conclusions: The bioinformatics pipeline described here identifies FDA-approved drugs that can be used for new alternative indications. These theoretical candidate drugs should be validated with experimental studies. Translational Relevance: Our study suggests possible drugs for DR treatment based on an integrated proteomics and genomics pipeline. This approach can potentially expedite the drug discovery process by identifying already-approved drugs that might be used for new indications.

Advances in biomaterials as a retinal patch for the repair of rhegmatogenous retinal detachment.

Rhegmatogenous retinal detachment (RRD) is the most common retinological emergency that can cause blindness without surgical treatment. RRD occurs when liquefied vitreous accumulates between the neurosensory retina and the retinal pigment epithelium via retinal breaks, which are caused by the separation of the vitreous from the retina with aging. Currently, the main treatment option is pars plana vitrectomy, which involves surgical removal of the vitreous and laser photocoagulation around retinal breaks to generate firm chorioretinal adhesion, as well as subsequent filling of the vitreous cavity with long-lasting substitutes (expansile gas or silocone oil) to prevent the connection between the subretinal space and the vitreous cavity via the breaks before the chorioretinal adhesion firm enough. However, the postoperative face-down position and the not very satisfactory first retinal reattachment rate place a heavy burden on patients. With the development of technology and materials engineering, researchers have developed biomaterials that can be used as a retinal patch to seal retinal breaks and prevent the connection of subretinal space and vitreous cavity via breaks, thus replacing the long-lasting vitreous substitutes and eliminating the postoperative face-down position. Preclinical studies have demonstrated that biomaterial sealants have enough biocompatibility and efficacy in the in vitro and in vivo experiments. Some sealants have been used in clinical trials on a small scale, and the results indicate promising application prospects of the biomaterial sealants as retinal patches in the repair of RRD. Herein, we review the recent advances in biomaterials as retinal patches for the repair of RRD, focusing on the biomaterial categories, methods, and procedures for sealing retinal breaks, as well as their biocompatibility and efficacy, current limitations, and development perspectives.

Low expression of RBP4 in the vitreous humour of patients with proliferative diabetic retinopathy who underwent Conbercept intravitreal injection.

Intravitreal injection of anti-VEGF antibodies has been widely used in the treatment of proliferative diabetic retinopathy (PDR). However, anti-VEGF drugs can exacerbate fibrosis and eventually lead to retinal detachment. To explore proteins closely related to fibrosis, we conducted proteomic analysis of human vitreous humour collected from PDR patients who have or have not intravitreal Conbercept (IVC) injection. Sixteen vitreous humour samples from PDR patients with preoperative IVC and 20 samples from those without preoperative IVC were examined. An immunodepletion kit was used to remove high-abundance vitreous proteins. Conbercept-induced changes were determined using a tandem mass tag-based quantitative proteomic strategy. Enzyme-linked immunosorbent assays were performed to confirm the concentrations of selected proteins and validate the proteomic results. Based on a false discovery rate between 0.05% and -0.05% and a fold-change > 1.5, 97 proteins were altered (49 higher levels and 48 lower levels) in response to IVC. Differentially expressed proteins were found in the extracellular and intracellular regions and were found to be involved in VEGF binding and VEGF-activated receptor activity. Protein-protein interactions indicated associations with fibrosis, neovascularisation and inflammatory signalling pathways. We found the low levels of RBP4 in the vitreous humour of PDR patients with IVC injection, as revealed by ELISA and proteomic profiling. Moreover, RBP4 significantly restored the mitochondrial function of HRMECs induced by AGEs and down regulated the level of glycolysis. Our study is the first to report that RBP4 decreases in the vitreous humour of PDR patients who underwent Conbercept treatment, thereby verifying the role of RBP4 in glucose metabolism. Results provide evidence for the potential mechanism underlying Conbercept-related fibrosis.

Biocompatibility and Efficacy of a Linearly Cross-Linked Sodium Hyaluronic Acid Hydrogel as a Retinal Patch in Rhegmatogenous Retinal Detachment Repairment.

To prevent the migration of retinal pigment epithelium (RPE) cells into the vitreous cavity through retinal breaks after the pars plana vitrectomy for the repair of rhegmatogenous retinal detachment (RRD), sealing retinal breaks with an appropriate material appears to be a logical approach. According to a review of ocular experiments or clinical trials, the procedure for covering retinal breaks with adhesives is complex. A commercially available cross-linked sodium hyaluronic acid (HA) hydrogel (Healaflow®) with the injectable property was demonstrated to be a perfect retinal patch in RRD clinical trials by our team. Based on the properties of Healaflow®, a linearly cross-linked sodium HA hydrogel (HA-engineered hydrogel) (Qisheng Biological Preparation Co. Ltd. Shanghai, China) with the injectable property was designed, whose cross-linker and cross-linking method was improved. The purpose of this study is to report the characteristics of an HA-engineered hydrogel using Healaflow® as a reference, and the biocompatibility and efficacy of the HA-engineered hydrogel as a retinal patch in the rabbit RRD model. The HA-engineered hydrogel exhibited similar dynamic viscosity and cohesiveness and G' compared with Healaflow®. The G' of the HA-engineered hydrogel varied from 80 to 160 Pa at 2% strain under 25°C, and remained constantly higher than G″ over the range of frequency from 0.1 to 10 Hz. In the animal experiment, clinical examinations, electroretinograms, and histology suggested no adverse effects of the HA-engineered hydrogel on retinal function and morphology, confirming its favorable biocompatibility. Simultaneously, our results demonstrated the efficacy of the HA-engineered hydrogel as a retinal patch in the RRD model of rabbit eyes, which can aid in the complete reattachment of the retina without the need for expansile gas or silicone oil endotamponade. The HA-engineered hydrogel could play the role of an ophthalmologic sealant due to its high viscosity and cohesiveness. This pilot study of a small series of RRD models with a short-term follow-up provides preliminary evidence to support the favorable biocompatibility and efficacy of the HA-engineered hydrogel as a promising retinal patch for sealing retinal breaks in retinal detachment repair. More cases and longer follow-up studies are needed to assess its safety and long-term effects.

Neuroprotection of retinal cells by Caffeic Acid Phenylethyl Ester（CAPE) is mediated by mitochondrial uncoupling protein UCP2.

Oxidative stress due to mitochondrial produced reactive oxygen species is a major cause of damage seen in many retinal degenerative diseases. Caffeic acid phenylethyl ester （CAPE） is protective agent in multiple tissues and is reported to have anti-oxidant properties. Systemically applied CAPE protected retinal ganglion cells from ischemic injury induced by increased intraocular pressure. CAPE provided complete protection for ARPE19 retinal pigment epithelial cells against tert-butyl hydrogen peroxide and reduced both basal and LPS-stimulated ROS production. The major effect of CAPE was mediated by the mitochondrial uncoupling protein UCP2 since both pharmacological inhibition of UCP2 and siRNA-induced knockdown removed the ability of CAPE to block ROS production. Based on common structural features, CAPE may be acting as a mimetic of the natural UCP2 homeostatic regulator 4-hydroxy-2-nonenal. CAPE may provide a valuable tool to treat oxidative stress-related damage in retinal and other degenerative diseases.

The Association between Fourier Parameters and Clinical Parameters in Myopic Children Undergoing Orthokeratology.

Purpose: To explore how Fourier parameters are associated with axial length growth (ALG) and clinical parameters in children who underwent orthokeratology.Materials and Methods: A total of 267 children received orthokeratology. Baseline cycloplegic autorefraction was performed. Axial length was measured at baseline and one year after the lens dispatch, and the difference was defined as ALG. Corneal topography was performed at the same two visits. Central treatment zone (CTZ) was identified from the difference between the two tangential maps, and its center distance to corneal center was defined as decentration. A relative refractive corneal power (RCRP) map was derived by subtracting the center value from every point on the one-year axial map. It was decomposed into 3 Fourier components: a mean (F0), a single-cycle sinewave (F1), and a double-cycle sinewave (F2). Linear regressions were used to reveal the association between ALG and these parameters.Results: At baseline, the age was 10.18 ± 1.48 year, spherical equivalent (SE) was - 3.10 ± 1.15D, astigmatism was 1.17 ± 0.58D, and axial length was 24.69 ± 0.81 mm. The mean ALG was 0.181 ± 0.22 mm. In multiple regression, ALG was negatively associated with F1 (p < .001), not F0 and F2. Amplitude-wise, F0 and F1 were correlated with decentration (p < .01) and SE (p < .01), and F2 was associated with astigmatism (p < .001). Direction-wise, F1 was correlated with decentration (p < .001) and F2 was associated with astigmatism (p < .001).Conclusions: Among Fourier parameters, F0 and F1 were negatively associated with ALG in myopic children undergoing orthokeratology. Their associations to SE and CTZ decentration may partially explain the effect on ALG retardation.