Background/Aims: Retinal haemangioblastomas (RH) remain a major cause of visual impairment in patients with von Hippel-Lindau (VHL) disease. Identification of genotype-phenotype correlation is an important prerequisite for better management, treatment and prognosis. Methods: Retrospective, single-centre cohort study of 200 VHL patients. Genetic data and date of onset of RH, central nervous system haemangioblastomas (CNSH), pheochromocytoma/paraganglioma (PPGL), clear cell renal cell carcinoma (ccRCC) and pancreatic neuroendocrine neoplasm (PNEN) were collected. The number and locations of RH were recorded. Results: The first clinical finding occurred at an age of 26 AE 14 years (y) [mean AE SD]. In 91 AE 3% (95% CI 88-94) of the patients, at least one RH occur until the age of 60y. A total of 42 different rare VHL gene variants in 166 patients were detected. A higher age-related incidence of RH, CNSH, ccRCC and PNEN was detected in patients with a truncating variant (TV) compared to patients with a single amino-acid substitution/deletion (AASD) (all p < 0.01), while it is reverse for PPGL (p < 0.01). Patients with a TV showed 0.10 AE 0.15 RH per y during their lifetime compared to 0.05 AE 0.07 in patients with AASD (p < 0.02). The median enucleation/phthisis-free survival time in patients with a TV was 56y (95% CI 50-62) compared to 78y (95% CI 75-81) in patients with AASD (p < 0.02). Conclusion: Compared to patients with AASD, patients with a TV develop RH, CNSH, ccRCC and PNEN earlier. They experience a higher number of RH and bear a higher risk of enucleation/phthisis. Thus, patients with a TV might be considered for a more intensive ophthalmological monitoring.

To compare spectral-domain (SD) and swept-source (SS) optical coherence tomography angiography (OCTA) for imaging retinal capillary hemangioblastomas (RCHs) in von Hippel-Lindau disease (VHLD). Methods: Prospective single-center cross-sectional study. Tumor size (TS) of perfused RCHs was assessed clinically in relation to the optic disc size. For both technologies, SD-OCTA and SS-OCTA, corresponding images with a scan size of 3 × 3 mm 2 and 6 × 6 mm 2 , respectively, were overlaid according to the set of marker positions to determine the TS. Results: From 200 patients with VHLD, 48 patients showed 84 RCHs. SD-OCTA images of 39 RCHs (46.4%) and SS-OCTA images of 48 RCHs (57.2%) were suitable for analysis. The average in OCTA-measured TS of 1.60 ± 2.58 mm 2 (range, 0.01-10.43) was congruent to the clinically assessed TS in 81.3% of cases (r = 0.86, P < 0.0001). TS measured in SD-OCTA compared to SS-OCTA showed similar values and a high correlation (all P < 0.0001). Nevertheless, despite the similarities, a slight trend in SS-OCTA was observed whereby with increasing TS, an elevated TS was detected compared to SD-OCTA (3 × 3-mm 2 scans: mean difference of 0.03 ± 0.04 mm 2 , 6 × 6-mm 2 scans: 0.08 ± 0.19 mm 2). However, within the same imaging technology method, TS values almost did not differ (SD-OCTA: mean difference of 0.01 ± 0.02 mm 2 , SS-OCTA: 0.001 ± 0.01 mm 2). Conclusions: OCTA may serve as an additional tool for diagnosis and monitoring of RCHs. Nevertheless, due to the differences between the technologies, the values cannot be used interchangeably. Translational Relevance: SD-OCTA and SS-OCTA are suitable to detect and monitor RCHs and provide a more detailed assessment about the TS than this is clinically possible.

The aim of this study was to investigate HIF-1α, HIF-2α, and ProExC expression in conjunctival intraepithelial neoplasia (CIN), to differentiate between metaplasia and dysplasia, and to access their value as diagnostic and prognostic immunohistochemical markers. Recurrence and progression into SCC (squamous cell carcinoma) were defined as endpoints. Methods Forty-three specimens including CIN I (2), CIN II (9), CIN III (29), with and without metaplasia, and metaplasia alone (3), as well as 21 conjunctival control specimens, were stained with antibodies against HIF-1α, HIF-2α, and ProExC. The percentage of positively stained cells were calculated and used for further analysis. Results The mean percentages of HIF-1α and HIF-2α were not increased in CIN. In comparison, the expressions of these markers were even significantly elevated in control specimens (p < 0.001). Upper epithelial cells in CIN were more often ProExC-positive compared with normal conjunctiva or metaplasia (p = 0.06 and p = 0.07). Cox proportional-hazards analysis was performed for characterization of factors influencing the combined endpoint and showed a significant elevated hazard ratio for staining with ProExC (p = 0.04) compared with HIF-1α (p = 0.26) and HIF-2α (p = 0.49). Conclusion Our study shows that HIF-1α and HIF-2α do not serve as diagnostic or prognostic markers in CIN. ProExC seems to be a potential indicator for CIN, but not a reliable diagnostic marker. However, control specimens occasionally also display a high percentage of ProExC-positive cells and staining over the entire epithelial layer.

Zusammenfassung Hintergrund Die Symptome des akuten Winkelblocks, ein Notfallereignis, das ohne rechtzeitige Therapie zur irreversiblen Erblindung führen kann, sind vielfältig. Diese können initial als internistische oder neurologische Erkrankungen gedeutet werden, wenn Kopfschmerzen, Pupillenstarre oder Übelkeit im Vordergrund stehen. Ziel unserer Studie war es, die Rate belastender und invasiver Diagnostik durch primäre Vorstellung bei Nichtophthalmologen bei akutem primären Winkelblock zu erfassen. Methode Retrospektive Single-Center-Studie von Patienten mit akutem primärem Winkelblock. Zur Identifizierung dieser wurden alle Patienten erfasst, bei denen im Universitätsklinikum Freiburg, Klinik für Augenheilkunde im Zeitraum 2014–2018 eine chirurgische Iridektomie (5-133.0) oder Iridotomie durch Laser (5-136.1) durchgeführt wurde. Anschließend erfolgte durch Akteneinsicht die Datenanalyse zur Prüfung der Ein- und Ausschlusskriterien sowie des Krankheitsverlaufs. Ergebnisse Eingeschlossen wurden 91 Patienten mit akutem primären Winkelblock. Davon stellten sich 28 % (n = 25) initial bei nichtophthalmologischen Fachdisziplinen vor. In dieser Patientengruppe erhielten 56 % (n = 11) eine nichtzielführende Diagnostik, wobei bei 32 % (n = 8) eine kraniale Bildgebung und bei 8 % (n = 2) eine Lumbalpunktion durchgeführt wurde. Schlussfolgerung Bei akutem primären Winkelblock zeigt sich eine hohe Rate an nicht wegweisender Diagnostik durch Nichtophthalmologen, weshalb dieses Krankheitsbild fächerübergreifend präsent sein sollte. Bei unspezifischen Symptomen, wie Kopfschmerzen, Übelkeit und Erbrechen sowie Pupillenstarre, muss an die Möglichkeit eines akuten Augeninnendruckanstiegs durch einen akuten Winkelblock gedacht und das frühzeitige Hinzuziehen eines Ophthalmologen erwogen werden.