BNN27 is a novel 17‐spiroepoxy derivative of the neurosteroid Dehydroepiandrosterone with neuroprotective properties. The purpose of this study was the detection and quantification of BNN27 after single intraperitoneal administration, in the serum and retina of normal rodents. Forty‐two C57BL/6 mice and 48 Sprague–Dawley rats were used for the quantification of BNN27 in the blood serum and retina, respectively. BNN27 was injected intraperitoneally (i.p.) at concentrations of 100 and 30 mg/kg of body weight (b.w.), respectively. The blood was collected with retro‐orbital bleeding and the retina was isolated after enucleation at various time points. The molecule concentrations were measured with Liquid chromatography‐mass spectrometry (LC‐MS). Non‐compartmental analysis was used to determine pharmacokinetic parameters. BNN27 was found to have an elimination constant k_el = 0.465 h⁻¹ and mean residence time (MRT) 2.154 h in the mouse serum. The maximum concentration (C_max) in the retina was detected at 2 h () after intraperitoneal administration and was equal to 1100 ng/g. BNN27 is rapidly eliminated from both blood and retina. In the retina specifically, it is undetectable 6 h after injection. BNN27 shows a rapid systemic elimination as anticipated by its small size and lipophilicity. It is measurable in small peripheral tissues such as the rat retina, after one single i.p. injection, using a simple method such as LC‐MS. Its detection in the retina corroborates the existing biological data that the molecule crosses the blood–retinal barrier, highlighting it as a potential neuroprotective agent for retinal disease.

Background: Virtual clinics (VCs) have proven to be an effective solution for the increasing strain on Medical Retina (MR) services, although imaging quality issues (IQIs) persist. Our aim was to compare the quality of two ultra-wide-field (UWF) imaging modalities (Optos and Clarus) in real-world MR-VC settings. Methods: We conducted a real-world, prospective study. Data were collected from 6 Moorfields NHS Trust MR-VCs between September and October 2024. We obtained patient demographics and characteristics, primary diagnosis, UWF imaging types and images obtained, and follow-up outcomes. Results: Optos (California RG/RGB, and Monaco) was used for 56.7% (n = 152) and Zeiss Clarus 500 for 43.3% (n = 116) of the total cohort (n = 268). No statistically significant difference (p = 0.14) was found between the two in terms of the rates of IQIs. FAF (p = 0.001) acquisition was significantly higher when Optos was used. Of the patients affected by IQIs, 10 were examined in a face-to-face clinic (F2FC). No difference in IQI rates was observed when pathology-related poor image quality was considered (p = 0.561). A significantly (p = 0.001) higher rate of F2F follow-ups was found for red-flag pathologies and unexplained vision loss, with a statistically significantly higher rate of virtual follow-ups for non-red-flag pathologies (p = 0.001). Conclusions: A total of 7.5% of the clinical decisions were impacted by IQIs; 11.1% of F2FC follow-ups. Neither UWF imaging modality type was inferior in terms of IQI rates. FAF acquisition was higher with Optos, likely representing greater user-dependency for Clarus. The outcomes were not influenced by FAF acquisition, indicating that routine acquisition is not required in MR-VCs and instead should be obtained when clinically required.

Purpose: To describe the radial outer retina reflectivity (RORR) sign in patients carrying pathogenic variants in the X‐linked lysosome‐associated membrane protein‐2 ( LAMP2 ) gene and to review the histologic characteristics of LAMP2 expression in the human retina. Methods: International multicentre observational case series and experimental laboratory study of patients with LAMP2 deficiency. Baseline demographics and multimodal retinal imaging including colour and fundus autofluorescence (FAF), optical coherence tomography (OCT) with en face reconstruction and fluorescein angiography were obtained. Sections through the retina of a human donor eye were processed for immunofluorescence combining antibodies against LAMP2 with markers for Müller glia, rod and cone photoreceptors. Sections were imaged using high‐resolution multichannel confocal microscopy. Assessment of en face OCT reflectivity profiles at 5–50 μm internal to the plane of external limiting membrane (ELM) was performed as well as histologic localisation of LAMP2. Results: We recruited 11 cases with pathogenic variants in LAMP2 across five countries. Six cases demonstrated peripheral radial streaks of hyper‐ and hypopigmentation with UWF imaging. The RORR sign was best visualised 10–25 μm internal to ELM in 9 cases. We hypothesise the radial pattern to be secondary to X‐chromosome inactivation. LAMP2 immunoreactivity was observed internal and external to the ELM. Conclusion: Our findings expand the phenotypic spectrum of LAMP2 ‐associated retinopathy by demonstrating the RORR sign using en face OCT. Histologic sections revealed LAMP2 expression in the neuroretina.