Improving morphological outcome in lamellar macular hole surgery by using highly concentrated autologous platelet-rich plasma

Purpose To evaluate the use of highly concentrated autologous platelet-rich plasma (PRP) in lamellar macular hole (LMH) surgery with regard to function and morphology. Methods We included 12 eyes of 12 patients with progressive LMH in this interventional case series. After 23/25-gauge pars plana vitrectomy, 0.1ml highly concentrated autologous platelet-rich plasma was applied under air tamponade. Induction of posterior vitreous detachment and peeling of tractive epiretinal membranes were performed whenever present. Phacovitrectomy was undertaken in cases of phakic lens status. Postoperatively, all patients were instructed to rest in a supine position for the first two postoperative hours. Best-corrected visual acuity (BCVA) testing, microperimetry, spectral-domain optical coherence tomography (SD-OCT), and fundus photography were carried out preoperatively and 6 months postoperatively. Results Foveal configuration was restored in 10 of 12 patients (83.3%) at 6 months postoperatively. Two patients who had not undergone ILM peeling showed a recurring defect at 6-month follow-up. Best-corrected visual acuity improved significantly from 0.29 ± 0.08 to 0.14 ± 0.13 logMAR (Wilcoxon: p=0.028). Microperimetry remained unchanged (23.38 ± 2.53 preoperatively; 23.0 ± 2.49 dB postoperatively; p=0.67). No patient experienced vision loss after surgery, and no significant intra- or postoperative complications occurred. Conclusion The application of PRP in the surgical therapy of LMH results in good morphological and functional outcomes. Additional peeling of the ILM seems to be mandatory when using PRP to prevent the recurrence of LMH. Strict postoperative supine positioning for 2 h avoids PRP dislocation. Larger sample sizes are needed to confirm the results.

Predicting the individual probability of macular hole closure following intravitreal ocriplasmin injections for vitreomacular traction release using baseline characteristics

The primary objective was to create and establish a new formula that predicts the individual probability of macular hole closure for eyes with full thickness macular holes (FTMH) accompanied by vitreomacular traction (VMT) which received enzymatic vitreolysis using intravitreally administered ocriplasmin. The secondary objective was to evaluate the forecast reliability of a previously published formula for VMT resolution in VMT-only eyes (OddsIVO-Success = eIntercept × ORyears × ORln(µm); ProbabilityIVO-Success = OddsIVO-Success/(OddsIVO-Success + 1)) on VMT resolution using the current dataset of eyes with FTMH accompanied by VMT. Retrospective analysis of the OASIS, ORBIT, and INJECT-studies. Patients with FTMH and VMT with complete information (n = 213) were included. The effect of gender, age, FTMH diameter, lens status and the presence of epiretinal membranes (ERM) on FTMH closure was assessed using separate univariate logistic regression analyses. With regard to VMT release separate univariate regression analyses were carried out and results were compared with formerly published data of VMT resolution in eyes with VMT only. Overall, 126 eyes (63%) experienced VMT resolution within 28 days. Younger age (p < 0.0001) and VMT diameter (p = 0.041) had a significant impact on VMT release. Overall, 81 eyes (38%) treated with ocriplasmin showed FTMH closure within 28 days. Univariate analysis of the different predictors analyzed revealed that FTMH diameter < 250 µm had a significant impact on treatment success (p = 0.0495). It was not possible to calculate and establish a new multivariate formula that can predict the individual FTMH closure probability for eyes with FTMHs and VMT. However, the results of VMT release prediction in eyes with FTMHs accompanied by VMT matched the prediction of VMT release in eyes with VMT only when using the previously published formula. All in all, predictors for calculating the individual probability of VMT resolution on the one hand and FTMH closure on the other hand are different suggesting diverse pathophysiological mechanisms.

Effect of Air Tamponade among Patients with Epiretinal Membranes and Intraretinal Cystoid Changes Undergoing Vitrectomy with Membrane Peeling – A Prospective Randomized Trial

Background The effect of air tamponade among patients undergoing vitrectomy with membrane peeling for removal of epiretinal membranes (ERM) is controversially discussed. The aim of the present study was to analyze differences in outcomes between air tamponade and balanced salt solution (BSS) in a study population with preoperative intraretinal cystoid changes. Patients and Methods This randomized study included patients scheduled for pars plana vitrectomy with membrane peeling owing to ERM and intraretinal cystoid changes. Air tamponade or BSS at the end of surgery was applied according to preoperative randomization. Optical coherence tomography and best-corrected distance visual acuity (DCVA) measurements were performed before surgery, 5 days after surgery, and 3 months after surgery. Results From 96 patients included, 85 eyes had full follow-up and could be included for analysis. Median improvement of DCVA was + 16 EDTRS letters (IQR: 8 to 22) among patients with BSS, while it was + 13 EDTRS letters (IQR: 8 to 17) among patients with air tamponade. There was a trend for better improvement of DCVA when BSS was left at the end of surgery, compared to air tamponade, but not reaching statistical significance. Conclusions There were no statistically significant differences concerning resorption of preoperative intraretinal cystoid changes, improvement of visual acuity, and final DVCA between air tamponade and BSS.

In-Depth Molecular Characterization of Neovascular Membranes Suggests a Role for Hyalocyte-to-Myofibroblast Transdifferentiation in Proliferative Diabetic Retinopathy

BackgroundRetinal neovascularization (RNV) membranes can lead to a tractional retinal detachment, the primary reason for severe vision loss in end-stage disease proliferative diabetic retinopathy (PDR). The aim of this study was to characterize the molecular, cellular and immunological features of RNV in order to unravel potential novel drug treatments for PDR.MethodsA total of 43 patients undergoing vitrectomy for PDR, macular pucker or macular hole (control patients) were included in this study. The surgically removed RNV and epiretinal membranes were analyzed by RNA sequencing, single-cell based Imaging Mass Cytometry and conventional immunohistochemistry. Immune cells of the vitreous body, also known as hyalocytes, were isolated from patients with PDR by flow cytometry, cultivated and characterized by immunohistochemistry. A bioinformatical drug repurposing approach was applied in order to identify novel potential drug options for end-stage diabetic retinopathy disease.ResultsThe in-depth transcriptional and single-cell protein analysis of diabetic RNV tissue samples revealed an accumulation of endothelial cells, macrophages and myofibroblasts as well as an abundance of secreted ECM proteins such as SPARC, FN1 and several types of collagen in RNV tissue. The immunohistochemical staining of cultivated vitreal hyalocytes from patients with PDR showed that hyalocytes express α-SMA (alpha-smooth muscle actin), a classic myofibroblast marker. According to our drug repurposing analysis, imatinib emerged as a potential immunomodulatory drug option for future treatment of PDR.ConclusionThis study delivers the first in-depth transcriptional and single-cell proteomic characterization of RNV tissue samples. Our data suggest an important role of hyalocyte-to-myofibroblast transdifferentiation in the pathogenesis of diabetic vitreoretinal disease and their modulation as a novel possible clinical approach.

Genetic Profile and Associated Characteristics of 150 Korean Patients with Retinitis Pigmentosa

Purpose. Retinitis pigmentosa (RP) shows great diversity between genotypes and phenotypes, and it is important to identify the causative genes. This study aimed to analyze the molecular profiles, associated ocular characteristics, and progression of RP in Korean patients. Methods. All the genetic variants in patients with RP, identified using targeted next-generation sequencing (NGS) with a panel of 88 RP-related genes between November 2018 and November 2019, were retrospectively reviewed. All the patients underwent comprehensive ophthalmological evaluations, and their clinical and family histories were recorded. The best-corrected visual acuity (BCVA) deterioration and photoreceptor disruption progression rates were determined based on the major causative mutational genes using nonlinear mixed models, and the differences among them were investigated using the interaction effect. Results. Among the 144 probands, 82 variants in 24 causative genes were identified in 77 families (53.5%). Most of the RP cases were associated with autosomal recessive variants (N = 64 (44.4%)), followed by autosomal dominant (N = 10 (6.9%)) and X-linked variants (N = 3 (2.1%)). The four most frequently affected genes were EYS (N = 15 (10.4%)), USH2A (N = 12 (8.3%)), PDE6B (N = 9 (6.3%)), and RP1 (N = 8 (5.6%)). Epiretinal membranes and cystoid macular edema were frequently noted in the patients with USH2A (75.0%) and PDE6B (50.0%) variants, respectively. During the follow-up period, the BCVA and photoreceptor disruption changes were significantly different among the patients carrying the four common causative genes ( P = 0.014 and 0.034, resp.). Patients with PDE6B variants showed faster BCVA changes (0.2 LogMAR/10 years), and those with USH2A variants showed the fastest ellipsoid zone disruptions (−170.4 µm/year). Conclusion. In conclusion, our genetic analysis using targeted NGS provides information about the prevalence of RP-associated mutations in Korean patients. Delineating clinical characteristics according to genetic variations may help clinicians identify subtype features and predict the clinical course of RP.

Changes of Visual Acuity and Macular Thickness after Phacovitrectomy with Posterior Capsulectomy of Epiretinal Membrane

Purpose: To investigate the functional and structural recovery period of idiopathic epiretinal membranes after phacovitrectomy with posterior capsulectomy.Methods: From March 2012 to January 2015, 57 patients diagnosed with idiopathic epiretinal membranes with cataracts who underwent combined vitrectomy and cataract surgery with pars plana posterior capsulectomy were enrolled. The best-corrected visual acuity and central foveal thickness were analyzed retrospectively.Results: The average best-corrected visual acuity before surgery was 0.30 ± 0.23 logarithm of minimal angle of resolution (logMAR), and the mean central foveal thickness was 442 ± 93 μm. As of the 12-month follow-up, the average postoperative best-corrected visual acuity had improved to 0.08 ± 0.11 logMAR, and the central foveal thickness after surgery had decreased to 386 ± 58 μm at 12 months.Conclusions: After removing the potential influence of cataracts and posterior capsular opacity, the recovery of idiopathic epiretinal membranes continued up to 12 months after surgery.