Purpose Evaluation of phenotype and treatment outcome of retinal haemangioblastomas (RH) in von Hippel–Lindau (VHL) disease and correlation of these features with the genotype of VHL germline mutation carriers. Methods Retrospective analysis of a longitudinal cohort of 21 VHL germline mutation carriers and RH. Clinical and genetic data were obtained to analyse the correlation of genotype with phenotype and treatment outcomes. Results All patients were categorized in two genotypic categories: missense mutations (MM) and truncating mutations (TM). Mean follow‐up duration was 16.3 years and did not differ significantly between mutation groups (p = 0.383). Missense mutations (MM) carriers ( n = 6) developed more progression‐related complications compared to TM carriers ( n = 15) (p = 0.046). Vitreoretinal surgery was more often applied in MM carriers (p = 0.036). Moderate (visual acuity (VA)20/80 to 20/200) to severe (VA < 20/200) visual impairment was observed in 53.3% of the eyes of MM carriers and 28.1% of the eyes of TM carriers at last recorded visit. Conclusion Missense mutations in VHL patients seem to have a higher prevalence of progression‐related complications. Missense mutations (MM) carriers required therefore more often vitreoretinal surgical treatment with a worse treatment outcome. Genetic analysis may play a role in determining a pro‐active treatment strategy and prognosis for RH.

Purpose The advances in medicine have led to an increased number of people living with some form of immunodeficiency. Most ocular infections in immunocompromised patients may lead to irreversible blindness. We identify the causes of uveitis in immunocompetent and immunocompromised patients. Methods A retrospective cohort study of 1354 consecutive patients. All patients underwent a standard work‐up for uveitis. Results An immunocompromised state was identified in 171/1354 patients (13%), of whom 40 had Human immunodeficiency virus (HIV) infection, 52 received immunosuppressive medications, 28 had concurrent malignant disorder and 20 had other causes for their immunosuppression. In addition, 93/1354 patients (7%) had diabetes mellitus (DM). The prevalence of intraocular infections was much higher in immunocompromised patients than in immunocompetent patients and DM (p < 0.001). Causes of uveitis differed between the diverse immunocompromised groups. The non‐HIV immunocompromised patients showed primarily intraocular herpes simplex and varicella zoster virus infections, whilst HIV‐positive patients exhibited frequently cytomegalovirus (CMV) retinitis and syphilis. Patients with generalized malignancies were characterized by a lower prevalence of infections and higher prevalence of sarcoidosis. Patients with DM typically showed sarcoidosis and bacterial intraocular infections. The percentage of undetermined uveitis diagnoses was markedly lower in immunosuppressed patients (p < 0.001). Conclusion In immunocompromised patients with uveitis, infections were diagnosed in 46% of cases in contrast to 12% in the immunocompetent patients. The causes of uveitis differed among the various types of immunosuppression. Immunocompromised patients with uveitis require a rapid assessment for the most expected infections.

Importance Approximately twenty per cent of Von Hippel–Lindau patients with retinal haemangioblastomas (RH) suffer from visual impairment. Various treatment options are available for peripheral RH. However, management of peripheral RH is complex due to multifocality and bilaterality. Objective To summarize published evidence on efficacy and safety of different interventions for peripheral RH and to provide treatment recommendations for specialists. Evidence review Comprehensive searches were performed using Medline, Embase, Web of Science and Google Scholar database on 4 March 2020. English publications that described outcomes related to efficacy or complications in at least two patients with peripheral RH were included. Efficacy and safety were estimated by complete tumour eradication rate, pretherapeutic and treatment‐related complication rate. Odds ratios (OR) with 95% confidence intervals (CI) were calculated to calculate the risk estimate of complications between treatment options. Findings Twenty‐seven articles were included in this review describing nine different treatment options for peripheral RH: laser photocoagulation (n = 230), cryotherapy (n = 50), plaque radiotherapy (n = 27), vitreoretinal surgery (n = 88), photodynamic therapy (PDT; n = 14), transpupillary thermotherapy (TTT; n = 10), external beam radiotherapy (n = 3), systemic treatment (n = 7) and intravitreal anti‐VEGF (n = 2). Complete tumour eradication was achieved in 86.7% (95% CI: 83.5–89.9%) of all eyes. For the different treatments, this was after laser photocoagulation 89.9% (86.1–93.7%), cryotherapy 70.2% (57.0–83.4%), plaque radiotherapy 96.3% (89.1–100.0%), vitreoretinal surgery (100.0%), PDT 64.3% (38.3–90.3%) and TTT 80.0% (53.8–100.0%). No complete tumour eradication was achieved after systemic therapy, external beam radiotherapy or intravitreal anti‐VEGF. Photodynamic therapy and vitreoretinal surgery showed the highest complication rate after treatment compared to the other treatments (OR 10.5 [95% CI: 2.9–38.4]) and (OR 5.9 [95% CI: 3.4–9.9]), respectively. Cases that had pretherapeutic complications showed a higher treatment‐related complication rate (OR 14.8 [95% CI: 7.3–30.0]) than cases without complications before treatment. Conclusions and Relevance These findings suggest that laser photocoagulation is the safest and most effective treatment method for peripheral RH up to 1.5 mm in diameter. Vitreoretinal surgery has the highest success rate for complete tumour eradication and may be the most suitable treatment option in the presence of pretherapeutic complications and for larger tumours.

Purpose Evaluating the phenotype, complications and treatment outcome of retinal hemangioblastomas (RH) and correlating this features with the genotype of Von Hippel‐Lindau (VHL) germline mutation carriers. Methods Retrospective analysis of the medical and genetic records of 21 individuals with a VHL germline mutation and a diagnosis of RH. Germline mutation status was correlated to phenotype, complications, treatment methods and outcomes. Mutations were categorized in two genotypic categories: the truncating mutation (TM) group and the missense mutation (MM) group. Results From the 36 VHL germline mutation carriers, 21 VHL patients developed RH. Prevalence of RH in VHL disease was higher in TM carriers (15 of 21, 68.2%) vs. 40% of the MM carriers (6 of 15). The mean age of diagnosis of RH was 25.7 years. There was no significant difference in age of diagnosis of RH between genotypic categories (P = 0.931). Mean follow‐up duration was 16.3 years and did not differ significantly between the mutation groups (P = 0.383). Bilateral involvement was observed in 66.7% of the patients. Missense mutation (MM) carriers (n = 6) developed more RH (more than 5 RH: 50.0% vs. 38.5%), had a larger extent of peripheral retinal involvement of ocular VHL disease (66.7% vs. 35.7% all quadrants involved) and developed more progression‐related complications compared to TM carriers (n = 15) (100% vs. 46.7%). Complete tumor regression at last recorded visit was achieved in fifteen patients (71.4%). Moderate (VA 20/80 to 20/200) to severe (less than VA 20/200) visual impairment was observed in 53.3% of the eyes of MM carriers and 28.1% of the eyes of TM carriers at last recorded visit. Conclusions Germline mutation status might play a role in the course of progression of RH in VHL disease. In our observational study, VHL missense mutation carriers had a more complicated progression of RH than carriers of a truncating mutation.