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Background: Voretigene neparvovec (Luxturna®) is the first approved gene therapy for RPE65-linked Leber congenital amaurosis (LCA). Though individual effects are highly variable, most recipients report improved vision in everyday life. To describe such effects, visual navigation tests are now frequently used in clinical trials. However, it is still unclear how their results should be interpreted compared to conventional parameters of visual function., Methods: Seven LCA patients underwent a multi-luminance visual navigation test (Ora-VNCTM) before and 3 months after receiving Luxturna gene therapy. Their performance was rated based on the luminance level at which they passed the course. Differences between the first and second test were correlated to changes in visual acuity, full-field stimulus thresholds, chromatic pupil campimetry, and dark-adapted perimetry., Results: A few patients displayed notable improvements in conventional measures of visual function whereas patients with advanced retinal degeneration showed no relevant changes. Independent of these results, almost all participants improved in the visual navigation task by one or more levels. The improvement in the mobility test was best correlated to the change in full-field stimulus thresholds. Other measures of visual functions showed no clear correlation with visual navigation., Discussion: In patients who passed the test's more difficult levels, improved visual navigation can be attributed to the reactivation of rods. However, the performance of patients with low vision seemed to depend much more on confounding factors in the easier levels. In sum, such tests might only be meaningful for patients with better preserved visual functions., (© 2023. The Author(s).)

Background/aims: Voretigene neparvovec (VN) is the first and only subretinal gene therapy approved by the Food and Drug Administration and European Medicines Agency. Real-world application has started in 2018 in patients with vision impairment due to biallelic retinal pigment epithelium ( RPE ) 65 mutation-associated inherited retinal degenerations. Herein, we evaluated the development of retinal atrophy within in a single-centre patient cohort treated with VN., Methods: 13 eyes of eight patients treated with VN were retrospectively analysed for areas of retinal atrophy over a period of 6-24 months following surgery. Ultrawide field images were used to measure the area of atrophy. Fundus autofluorescence imaging is presented as an instrument for early detection of signs of retinal atrophy in these patients., Results: Atrophic changes beyond the retinotomy site were observed in all eyes. Areas of atrophy developed within the area of detachment (bleb) in all eight patients and outside the bleb in three patients. Changes in autofluorescence preceded the development of retinal atrophy and were already evident 2 weeks after surgery in the majority of patients. The areas of atrophy increase with time and progression continued over year 1. Functional outcomes remained stable (VA, FST, visual field)., Conclusion: Subretinal injection of VN can lead to RPE atrophy with consequent photoreceptor loss in and outside of the bleb area. Fundus autofluorescence is an important tool to monitor atrophic changes in patients after gene therapy. Interestingly, while areas of atrophy also included central areas, the functional benefits of the treatment did not appear to be affected and remained stable., Competing Interests: Competing interests: DF is on the advisory board of and/or consulting and/or receiving honoraria/grant money/travel support from following companies: Adelphi Values, Advent France Biotechnology, Alphasights, Arctos Medical, Atheneum, Axiom Healthcare Strategies, Biogen, Cambridge Consultants, Decision Resources, Dialectica, Frontera Therapeutics, Janssen Research & Development, Navigant, Novartis, Roche, RegenxBio, Sirion, System Analytic, and STZeyetrial. He is director of Fischer Consulting Limited and holds a patent (50%) on a gene therapy product for X-linked Retinitis Pigmentosa. FW reports personal fees from Novartis, outside the submitted work. KS reports personal fees from Novartis, outside the submitted work. SK reports grants from Charlotte & Tistou Kerstan Foundation, during the conduct of the study; personal fees from Novartis, outside the submitted work. No other disclosures were reported., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Voretigene neparvovec is a gene therapeutic agent for treatment of retinal dystrophies caused by bi-allelic RPE65 mutations. In this study, we report on a novel and objective evaluation of a retinotopic photoreceptor rescue., Methods: Seven eyes of five patients (14, 21, 23, 24, 36 years, 1 male, 4 females) with bi-allelic RPE65 mutations have been treated with voretigene neparvovec. The clinical examinations included visual acuity testing, dark-adapted full-field stimulus threshold (FST), dark-adapted chromatic perimeter (DAC) with a 30-degree grid, and a 30 degrees grid scotopic and photopic chromatic pupil campimetry (CPC). All evaluations and spectral domain optical coherence tomography were performed at baseline, 1 month and 3 months., Results: All except the oldest patient had a measurable improvement of the rod function assessed via FST, DAC or scotopic CPC at 1 month. The visual acuity improved slightly or remained stable in all eyes. A cone function improvement as measured by photopic CPC was observed in three eyes. The gain of the dark-adapted threshold with blue FST and the DAC stimuli (cyan) average correlated strongly with age (R 2 >0.7). The pupil response improvement in the scotopic CPC correlated with the baseline local retinal volume (R 2 =0.5)., Conclusions: The presented protocols allow evaluating the individual spatial and temporal effects of gene therapy effects. Additionally, we explored parameters that correlated with the success of the therapy. CPC and DAC present new and fast ways to assess functional changes in retinotopic maps of rod and cone function, measuring complementary aspects of retinal function., Competing Interests: Competing interests: DF is or has been on the advisory board of and/or consulting and/or receiving honoraria/grant money/travel support from following companies: Adelphi Values, Advent France Biotechnology, Alphasights, Atheneum, Axiom Healthcare Strategies, Biogen, Decision Resources, Dialectica, EyeServ, Frontera Therapeutics, Janssen Research & Development, Navigant, Novartis, Roche, RegenxBio, Sirion and STZeyetrial. DF is director of Fischer Consulting Limited and holds a patent (50%) on a gene therapy product for X-linked Retinitis Pigmentosa. DF is the lead investigator of the global (ex-US) post-authorisation, multicentre, multinational, longitudinal, observational safety registry study for patients treated with voretigene neparvovec (CLTW888A12401) and a part of the data reported here are included in that study. EZ is or has been on the advisory board of and/or consulting and/or receiving honoraria/grant money/travel support from following companies: SMERUD, Atheneum, Axiom Healthcare strategies, Biogen, Decision Resources, Janssen Research & Development, Navigant, RegenxBio, ProQR, Gyroscope, Astellas and STZ eyetrial. KaS has received grants and/or travel reimbursement from Novartis, ProQR and ORA. SK and FW received personal fees from Novartis. BaW and TP received other support from Novartis., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Purpose: Leber congenital amaurosis type 2 (LCA2) and early-onset severe retinal dystrophy (EOSRD) are linked to visual impairment with nyctalopia and visual acuity reduction in early childhood. In 2017, the first gene therapy voretigene neparvovec (Luxturna™) for patients with LCA and EOSRD cause by bi-allelic mutations in the RPE65 gene has been approved. Here we report on an example of short-term change in the foveal morphology after functionally successful gene therapy with voretigene neparvovec in a 15-year old patient., Methods: The clinical examinations included best corrected visual acuity (BCVA), spectral domain optical coherence tomography (OCT) and adaptive optics retinal imaging., Results: During follow-up over a period of 3 months after the treatment, an improvement of the central foveal morphology could be observed in OCT, with a clear demarcation of the external limiting membrane and changes in the photoreceptor mosaic on adaptive optics retinal imaging. These morphological rescue parameters correlated in part with the improvement in foveal-mediated vision after the treatment and adaptive optics imaging. Although the visual acuity improved only slightly at month 3, objective central cone evaluation with chromatic pupil campimetry showed an increase in the central sensitivity. In daily life, the patient reported her visional experience after the treatment as 'brighter'., Conclusion: Rapid changes in the correlates of photoreceptor morphology after successful gene therapy in patients with LCA/EORD can be quantifiable on individual level., (© 2021 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Background: Interventional pain therapy aims to treat pain which is refractory to pharmacologic and noninterventional treatment. Due to the partly lacking evidence and recommendations it remains unclear when interventional methods should be applied within the treatment pathway. This study assesses the current state of interventional methods in Germany and their leading indications comparing with the recommendations found in the literature., Methods: An online survey was conducted among German physicians specialized in pain therapy concerning the number of interventions they perform per quarter, which supporting measures they use, and their indications for sympathetic blocks, sensory blocks, intrathecal administration, and spinal cord stimulation., Results: A total of 109 physicians (23.5 %) participated in the survey. Blocks are most often performed on the stellate ganglion (94 %) and on the superior cervical ganglion (82 %). They are supported by anatomical landmarks and less often by imaging control. Both classic neuropathic pain diagnoses (e.g., complex regional pain syndrome) and diagnoses with a neuropathic pain component (e.g., peripheral arterial disease, tumor pain, and back pain) were considered as indications to perform interventional procedures., Conclusion: Although there is no clear evidence on interventional procedures in the current literature, these methods are often performed by the respondents. Anatomic landmarks are most frequently used for orientation. The German pain physicians who responded consider especially neuropathic pain as an indication to perform interventional procedures for pain therapy.