Retinal detachment is the term used to describe detachment of the neurosensory retina from the underlying membrane, the retinal pigment epithelium. The separation of the two layers takes place within the fissure formed by the invagination of the...

Glomerular nephropathy resulting from the genetic defects in COL4A3/4/5 genes including the classical Alport syndrome is the second most common hereditary kidney disease characterized by persistent haematuria progressing to the need for kidney replacement therapy, frequently associated with sensorineural deafness, and occasionally with ocular anomalies. Diagnosis and management of COL4A3/4/5 glomerulopathy is a great challenge due to its phenotypic heterogeneity, multiple modes of inheritance, variable expressivity, and disease penetrance of individual variants as well as imperfect prognostic and progression factors and scarce and limited clinical trials, especially in children. As a joint initiative of the European Rare Kidney disease reference Network (ERKNet), European Renal Association (ERA Genes&Kidney), and European Society for Paediatric Nephrology (ESPN) Inherited renal disorders working group, a team of experts including adult and paediatric nephrologists, kidney geneticists, audiologists, ophthalmologists, and a kidney pathologist were selected to perform a systematic literature review on 21 clinically relevant PICO (Patient or Population covered, Intervention, Comparator, Outcome) questions. The experts formulated recommendations and formally graded them at a consensus meeting with input from patient representatives and a voting panel of nephrologists representing all regions of the world. Genetic diagnostics comprising joint analysis of COL4A3/4/5 genes is already the key diagnostic test during the initial evaluation of an individual presenting with persistent haematuria, proteinuria, kidney failure of unknown origin, focal segmental sclerosis of unknown origin, and possibly cystic kidney disease. Early renin-angiotensin system blockade is the standard of care therapy; sodium-glucose cotransporter-2 inhibitors may be added in adults with proteinuria and chronic kidney disease. Relatives with heterozygous COL4A3/4/5 variants should only be considered as the last possible resource for living kidney donation. This guideline provides guidance for the diagnosis and management of individuals with pathogenic variants in COL4A3/4/5 genes.

This analysis of the pivotal phase III HAWK and HARRIER trials aimed to provide insights on the timing of presentation, management, and outcomes of intraocular inflammation (IOI)-related adverse events (AEs), as reported by investigators in these trials. Post hoc analysis of investigator-reported IOI-related AEs in HAWK and HARRIER. Of 1088 brolucizumab-treated eyes (3 mg or 6 mg), 49 eyes experienced at least 1 IOI-related AE and were included in this analysis. Reports of IOI-related AEs were analyzed and descriptive statistics were provided for outcome measures. Incidence and description of eyes with IOI-related AEs, timing of presentation, management, clinical outcomes, and brolucizumab treatment after the first IOI-related AE. A total of 70 IOI-related AEs were reported in 49 eyes. Prior to the onset of first IOI-related AE, eyes received a mean (standard deviation [SD]) of 3.9 (2.2) brolucizumab injections. Median (25th-75th percentile) time to first IOI-related AE from the last administered brolucizumab injection was 18.0 (4.0-29.0) days. Of the 70 AEs, 61 (87.1%) were treated, the majority with topical corticosteroids; systemic and intraocular corticosteroids were used for 3 AEs each. Overall, inflammation resolved completely in 39 (79.6%) eyes, resolved with sequelae in 5 (10.2%) eyes, and did not resolve in 5 (10.2%) eyes by end-of-study. Overall, mean (SD) best-corrected visual acuity (BCVA) change from baseline to end-of-study, before AE to the lowest BCVA in 3 months after AE, and from before AE to end-of-study were -0.84 (20.6), -16.31 (17.6), and -0.22 (18.9) ETDRS letters, respectively. Of the 36 (73.5%) eyes that continued on brolucizumab after first IOI-related AE, 24 completed the trials and 12 discontinued; mean (SD) BCVA change in these eyes was 2.6 (17.6), 7.8 (13.2), and -7.7 (21.3) ETDRS letters, respectively, from baseline to end-of-study. The remaining 13 (26.5%) eyes were not treated with brolucizumab after first IOI-related AE and had mean (SD) BCVA change of -10.4 (25.5) ETDRS letters from baseline to end-of-study. Findings of this analysis highlight the need for continued vigilance and monitoring for any signs of IOI-related events in patients receiving brolucizumab.

While randomized controlled trials (RCTs) are based on strict inclusion/exclusion criteria, non-interventional studies (NISs) might provide additional information to guide management in patients more representative to the real-world setting. The aim of this study was to compare baseline characteristics of patients receiving intravitreal treatment in the NIS OCEAN with those from published RCTs. The ongoing OCEAN study enrolled patients treated with ranibizumab for neovascular age-related macular degeneration (nAMD), diabetic macular oedema (DME) or branch/central retinal vein occlusion (B/CRVO). Baseline patient characteristics were compared by indication within the OCEAN cohort. Furthermore, the characteristics were set in reference to those of published RCTs in the same indications. Confidence intervals (CIs) were calculated and assessed for statistically significant differences as indicated by non-overlapping CIs. Patient characteristics in the NIS OCEAN were evaluated for 3,614 patients with nAMD, 1,211 with DME, 204 with BRVO and 121 with CRVO. Between these groups, significant differences in mean age, gender distributions, and mean baseline VA were seen, reflecting known differences between the indications. Compared to the patient characteristics of published RCTs (trials selected by literature search: nAMD: 13 RCTs, DME: 9, RVO: 5), the OCEAN patients’ mean age was significantly higher in every indication. The gender distributions across the trials were comparable, with only few differences between OCEAN and the RCTs. Regarding the mean baseline VA, notable differences were found in nAMD and in DME, with VA significantly higher in some RCTs and lower in others. The described differences underline the complementarity of NISs and RCTs. OCEAN covers a broader spectrum and more variability of patients than do RCTs. As baseline values may have impact on the treatment response (ceiling effect), there is an ongoing need for research in all patient subgroups. Country-specific assessments of patient populations can better reflect the real-world situation. NISs can deliver insights that RCTs may not, as NISs can include non-typical patients, patients with comorbidities, a broader age spectrum and patients of various disease stages. The NIS OCEAN was registered on www.clinicaltrials.gov (identifier: NCT02194803 ).

: Purpose:  The ‘Scleral buckling versus primary vitrectomy in rhegmatogenous retinal detachment study’ (SPR study) is a randomized multicentre trial comparing primary vitrectomy (PV) and scleral buckling surgery (SB) for rhegmatogenous retinal detachment (RRD). This subanalysis was conducted to identify risk factors associated with anatomical outcomes.Methods:  Relating the anatomical success results at the 1‐year follow‐up visit to pre‐ and intraoperative findings using multivariate statistical methods.Results:  In the phakic subtrial, anatomical success was negatively associated with the number of breaks (p < 0.0001), break extension > 1 clock hour (p = 0.0005) and intraoperative use of cryotherapy (p = 0.0484). It was positively associated with retinal breaks with irregular edges (p = 0.0353) and subretinal fluid drainage (p = 0.0155). In the pseudophakic/aphakic subtrial, anatomical success was negatively associated with the number of retinal breaks (p = 0.0004) and previous YAG capsulotomy (p = 0.0256), and the combined effect of the surgical procedure and intraoperative use of laser (p = 0.0229).Conclusion:  Primary anatomical success is an important result for patients undergoing RRD surgery. Our data demonstrate that the final anatomical outcome is related to a higher preoperative number of breaks and cryotherapy in phakic eyes. Additional risk factors varied between phakic and pseudophakic subgroups. Our findings may be used to facilitate the prognosis of future patients with RRD.