Biallelic variants in coenzyme Q10 biosynthesis pathway genes cause a retinitis pigmentosa phenotype

The aim of this study was to investigate coenzyme Q10 (CoQ10) biosynthesis pathway defects in inherited retinal dystrophy. Individuals affected by inherited retinal dystrophy (IRD) underwent exome or genome sequencing for molecular diagnosis of their condition. Following negative IRD gene panel analysis, patients carrying biallelic variants in CoQ10 biosynthesis pathway genes were identified. Clinical data were collected from the medical records. Haplotypes harbouring the same missense variant were characterised from family genome sequencing (GS) data and direct Sanger sequencing. Candidate splice variants were characterised using Oxford Nanopore Technologies single molecule sequencing. The CoQ10 status of the human plasma was determined in some of the study patients. 13 individuals from 12 unrelated families harboured candidate pathogenic genotypes in the genes: PDSS1, COQ2, COQ4 and COQ5. The PDSS1 variant c.589 A > G was identified in three affected individuals from three unrelated families on a possible ancestral haplotype. Three variants (PDSS1 c.468-25 A > G, PDSS1 c.722-2 A > G, COQ5 c.682-7 T > G) were shown to lead to cryptic splicing. 6 affected individuals were diagnosed with non-syndromic retinitis pigmentosa and 7 had additional clinical findings. This study provides evidence of CoQ10 biosynthesis pathway gene defects leading to non-syndromic retinitis pigmentosa in some cases. Intronic variants outside of the canonical splice-sites represent an important cause of disease. RT-PCR nanopore sequencing is effective in characterising these splice defects

Pars plana vitrectomy for diabetic macular edema. Internal limiting membrane delamination vs posterior hyaloid removal. A prospective randomized trial

To access publisher full text version of this article. Please click on the hyperlink in Additional Links field.BACKGROUND: Diabetes mellitus, as well as subsequent ocular complications such as cystoid macular edema (CME), are of fundametal socio-economic relevance. Therefore, we evaluated the influence of internal limiting membrane (ILM) removal on longterm morphological and functional outcome in patients with diabetes mellitus (DM) type 2 and chronic CME without evident vitreomacular traction. METHOD: Forty eyes with attached posterior hyaloid were included in this prospective trial and randomized intraoperatively. Prior focal (n = 31) or panretinal (n = 25) laser coagulation was permitted. Group I (n = 19 patients) underwent surgical induction of posterior vitreous detachment (PVD), group II (n = 20 patients) PVD and removal of the ILM. Eleven patients with detached posterior hyaloid (group III) were not randomized, and ILM removal was performed. One eye had to be excluded from further analysis. Examinations included ETDRS best-corrected visual acuity (BCVA), fluorescein angiography (FLA) and OCT at baseline, 3 and 6 months postoperatively. Main outcome measure was BCVA at 6 months, secondary was foveal thickness. RESULTS: Mean BCVA over 6 months remained unchanged in 85% of patients of group II, and decreased in 53% of patients of group I. Results were not statistically significant different [group I: mean decrease log MAR 95% CI (0.06; 0.32), group II: (-0.02; 0.11)]. OCT revealed a significantly greater reduction of foveal thickness following PVD with ILM removal [group I: mean change: 95% CI (-208.95 μm; -78.05 μm), group II: (-80.90 μm: +59.17 μm)]. CONCLUSION: Vitrectomy, PVD with or without ILM removal does not improve vision in patients with DM type 2 and cystoid diabetic macular edema without evident vitreoretinal traction. ILM delamination shows improved morphological results, and appears to be beneficial in eyes with preexisting PVD

An international collaborative evaluation of central serous chorioretinopathy: different therapeutic approaches and review of literature. The European Vitreoretinal Society central serous chorioretinopathy study

Purpose: To study and compare the efficacy of different therapeutic options for the treatment of central serous chorioretinopathy (CSCR). Methods: This is a nonrandomized, international multicentre study on 1719 patients (1861 eyes) diagnosed with CSCR, from 63 centres (24 countries). Reported data included different methods of treatment and both results of diagnostic examinations [fluorescein angiography and/or optical coherent tomography (OCT)] and best-corrected visual acuity (BCVA) before and after therapy. The duration of observation had a mean of 11 months but was extended in a minority of cases up to 7 years. The aim of this study is to evaluate the efficacy of the different therapeutic options of CSCR in terms of both visual (BCVA) and anatomic (OCT) improvement. Results: One thousand seven hundred nineteen patients (1861 eyes) diagnosed with CSCR were included. Treatments performed were nonsteroidal anti-inflammatory eye drops, laser photocoagulation, micropulse diode laser photocoagulation, photodynamic therapy (PDT; Standard PDT, Reduced-dose PDT, Reduced-fluence PDT), intravitreal (IVT) antivascular endothelial growth factor injection (VEGF), observation and other treatments. The list of the OTHERS included both combinations of the main proposed treatments or a variety of other treatments such as eplerenone, spironolactone, acetazolamide, beta-blockers, anti-anxiety drugs, aspirin, folic acid, methotrexate, statins, vitis vinifera extract medication and pars plana vitrectomy. The majority of the patients were men with a prevalence of 77%. The odds ratio (OR) showed a partial or complete resolution of fluid on OCT with any treatment as compared with observation. In univariate analysis, the anatomical result (improvement in subretinal fluid using OCT at 1 month) was favoured by age <60 years (p < 0.005), no previous observation (p < 0.0002), duration less than 3 months (p < 0.0001), absence of CSCR in the fellow eye (p = 0.04), leakage outside of the arcade (p = 0.05) and fluid height >500 \u3bcm (p = 0.03). The OR for obtaining partial or complete resolution showed that anti-VEGF and eyedrops were not statistically significant; whereas PDT (8.5), thermal laser (11.3) and micropulse laser (8.9) lead to better anatomical results with less variability. In univariate analysis, the functional result at 1 month was favoured by first episode (p = 0.04), height of subretinal fluid >500 \u3bcm (p < 0.0001) and short duration of observation (p = 0.02). Finally, there was no statistically significant difference among the treatments at 12 months. Conclusion: Spontaneous resolution has been described in a high percentage of patients. Laser (micropulse and thermal) and PDT seem to lead to significant early anatomical improvement; however, there is little change beyond the first month of treatment. The real visual benefit needs further clarification

Vitreous levels of Lipocalin-2 on patients with primary rhegmatogenous retinal detachment

Purpose To measure vitreous levels of Lipocalin2 (LCN2) in patients with rhegmatogenous retinal detachment (RRD) and investigate potential association with presence of proliferative vitreoretinopathy (PVR). Materials and methods Collection of undiluted vitreous samples from 24 patients suffering from RRD and 10 control patients undergoing vitrectomy for: Vitreomacular traction (VMT) (n = 2), idiopathic epiretinal membrane (iERM) (n = 6) and full thickness macular hole (FTMH) (n = 2). Quantitative analysis of LCN2 has been made with flow cytometry. Lens status, duration of symptoms, quadrants of detachment, as well as level of PVR, were assessed. Statistical analysis included Mann-Whitney test, Kruskal-Wallis test, t-test, Spearman's correlation coefficient and Fisher's exact test. Results Median LCN2 was significantly higher in the RRD group as compared to control (p<0.001). Within the RRD group there was a positive correlation between LCN2 and PVR grade (rs = 0.94, p<0.001). Median LCN2 was 35,759 pg/ml (IR = 55,347) in grade C PVR, 9,387 pg/ml (IR = 3721) in grade B, 4,917 pg/ml (IR = non computable) in grade A and 3,921 pg/ml (2132) in the no PVR group. Median LCN2 was also significantly higher in pseudophakic patients as compared to phakic patients (p = 0.007). LCN2 also correlates with the extend of detachment (≤2 vs >2 quadrants, p<0.001) as well as with duration of symptoms (rs = 0.87, p<0.001). After multivariate linear regression analysis, only PVR was independently related with LCN2 concentration. In particular, increased PVR grading was associated with increased LCN2 concentration (coefficient b = 2.97, 95% confidence interval = 1.89 to 4.67, p<0.001). Conclusion A positive correlation between vitreous levels of LCN2 and PVR grading reveals a potential role in the pathogenesis and progression of PVR. Further studies could elucidate if LCN2 could be a therapeutic target. © 2019 Batsos et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Evaluation of the choriocapillaris after photodynamic therapy for chronic central serous chorioretinopathy. A review of optical coherence tomography angiography (OCT-A) studies

Purpose: Emerging evidence suggests that choroidal microcirculation and microstructural changes after verteporfin photodynamic therapy (vPDT) for chronic central serous chorioretinopathy (CSC) can be shown in detail using OCT-Angiography (OCT-A). The use of OCT-A for the examination of choriocapillaris (CC) has attracted significant attention as the technique offers potential explanations for the effects of vPDT on choroidal tissue. Methods: A meticulous literature search was performed in the PubMed database without restriction on year of publication until June 2021. The reference list of all electronically retrieved articles was carefully reviewed for potentially relevant articles that had not been identified. Results: We identified and reviewed 11 studies reporting a comprehensive update on microvasculature and morphologic changes of the CC layer as seen on OCT-A in chronic CSC. The reviewed articles extensively analyze both the qualitative and quantitative characteristics of the CC flow pattern after applying vPDT safety-enhanced protocols. The changes in the CC plexus indicate the potential of beneficial or deleterious treatment effect on choroidal tissue remodeling. The reviewed series have revealed variability of flow pattern, vessel density, and perfusion of the CC over time. Conclusion: The CC plexus alterations during the post-vPDT period in chronic CSC may imply the treatment effect on choroidal tissue, indicating the potential of anatomical or functional recovery over time. The reviewed literature may confirm the diagnostic value of OCT-A in the assessment of the pathophysiology of eyes with CSC. [Figure not available: see fulltext.] © 2022, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature

Guidelines for the Management of Wet Age-Related Macular Degeneration: Recommendations from a Panel of Greek Experts

Purpose: To propose guidelines for the management of patients with wet age-related macular degeneration (wAMD), taking into account the results of large multicenter studies and clinical experience of retina experts. Method: A team of retina experts developed a consensus paper after three consecutive meetings. The group was focused on guidelines to help clinical decision-making around the definition of successful treatment and the definition of non-response to therapy. Results: Parameters suggestive of a successful response to treatments included: any gain in best corrected visual acuity (BCVA) or vision loss that is less than 5–10 Early Treatment Diabetic Retinopathy Study (ETDRS) letters, reduction of central retinal thickness, partial or complete absorption of subretinal fluid (SRF), reduction of intraretinal fluid, reduction of pigment epithelial detachment or restoration of the anatomy of outer retinal layers. Non-response to current treatment was considered in the case of loss of BCVA greater than 10 ETDRS letters, increased retinal edema or increase of SRF as evidenced by optical coherence tomography or new bleeding in biomicroscopy. Conclusion: The introduction of anti-VEGF agents revolutionized the treatment of wAMD. Given the complexity of the disease, the emerging new agents and the difference of cases recruited in clinical trials compared to those appearing in every-day practice, it is essential to individualize treatment options taking into account the results of clinical trials. © 2016, The Author(s)