Evaluation of the Long-Term Clinical Results of 3 Patients Implanted with the Argus II Retinal Prosthesis.

This study presents the long-term clinical results of Argus II retinal prosthesis implantation in eyes with light perception and projection in 3 patients with end-stage retinitis pigmentosa. No conjunctival erosion, hypotony, or implant displacement was observed during postoperative follow-up. The electrical threshold values were lower in the macular region and higher close to the tack fixation region and peripherally. Optical coherence tomography scans showed fibrosis and retinoschisis formation at the retina-implant interface in two cases. This was attributed to mechanical and electrical effects on the tissue due to the active daily use of the system and the electrodes' proximity to the retina. The patients were able to integrate the system into their daily lives and perform activities that they could not do before. Studies on retinal prostheses for the rehabilitation of hereditary retinal diseases are ongoing, so both social and clinical observations and experiences related to the implant are valuable.

Elicitation of Health State Utility Values in Retinitis Pigmentosa by Time Trade-off in the United Kingdom.

Introduction: Retinitis pigmentosa (RP) is an inherited retinal pathology associated with "night blindness" and progressive loss of peripheral vision, in some cases leading to complete blindness. Health state utility values are required for activities such as modelling disease burden or the cost-effectiveness of new interventions. The current study aimed to generate utility values for health states of varying levels of functional vision in RP, with members of the general public in the UK. Methods: Five health states were defined according to standard clinical measures of visual ability. Health state descriptions were developed following interviews with patients with RP in the UK (n=5). Further interviews were conducted for confirmation with healthcare professionals with specific experience of managing patients with RP in the UK (n=2). Interviews with members of the general public in the UK were conducted to value health states. A time trade-off (TTO) process based on the established Measurement and Valuation of Health (MVH) protocol was used. Due to the ongoing COVID-19 pandemic, all interviews were web-enabled and conducted 1:1 by a trained moderator. Results: In total, n=110 TTO interviews were conducted with members of the UK general public. Mean TTO utility values followed the logical and expected order, with increasing visual impairment leading to decreased utility. Mean values varied between 0.78 ± 0.20 ("moderate impairment"), and 0.33 ± 0.26 ("hand motion" to "no light perception"). Supplementary visual analogue scale (VAS) scores also followed the logical and expected order: mean VAS values varied between 47.95 ± 15.38 ("moderate impairment") and 17.22 ± 12.49 in ("hand motion" to "no light perception"). Discussion: These data suggest that individuals living with RP have substantially impaired quality of life. Utility values for RP have been elicited here using a method and sample that is suitable for economic modelling and health technology assessment purposes.

Suprachoroidal Retinal prostheses, longterm stability and safety results

Purpose : To report the longterm safety and stability of two suprachoroidal retinal prosthesis trials (NCT01603576, NCT03406416), comprising of seven patients, with followup ranging from two to nine years. Methods : Three patients with retinitis pigmentosa were implanted with our prototype 24 channel suprachoroidal retinal prosthesis in May-August 2012. One patient had the entire device removed following the trial in 2014 for a medical reason unrelated to the device. The other two patients had the intraocular array left in situ and the percutaneous connector removed, as planned. Ocular followup has continued since that time, albeit interrupted due to the Covid 19 pandemic. Four patients with retinitis pigmentosa were implanted with our second generation 44 channel fully implantable device in February to August 2018. They continue to use the device in the home enviroment. Ocular assessments including clinical examination, colour fundus photographs and optical coherence tomography (OCT) have been used to assess stability of the devices and retinal health longitudinally in patients (P) 1-7. Results : Electrode to retina distance OCT measurements over two to nine years, calculated by comparing group means, showed an increase over time. (Wilcoxon, p=0.03) In the prototype trial, the increase appeared linked to fibrosis and stimulation, with no progression once devices were inactivated, in the second generation trial, it seemed primarily due to passive fibrosis. Retinal thickness OCT measurements showed a slow reduction in central retinal thickness, as expected, due to progression of dystrophic disease. (Wilcoxon, p=0.11) Device position compared to the optic nerve head (ONH) was calculated and three patients demonstrated some temporal movement. P1 position returned to baseline over seven years, P2 stabilised over three months and P6 had a temporary choroidal effusion event which settled spontaneously. Function of the four Generation two fully implantable devices remains stable. Conclusions : Using fundus photography and OCT measurements we demonstrate that retinal prostheses implanted in the suprachoroidal space for up to nine years are overall stable in position and cause mild progressive fibrosis in the suprachoroidal space. Longterm assessment of the changes in the retina are all consistent with the underlying retinal dystrophy. This provides further evidence of the safety of the suprachoroidal surgical approach for retinal prostheses.

Electrophysiology-Guided Genetic Characterisation Maximises Molecular Diagnosis in an Irish Paediatric Inherited Retinal Degeneration Population.

Inherited retinal degenerations (IRDs) account for over one third of the underlying causes of blindness in the paediatric population. Patients with IRDs often experience long delays prior to reaching a definitive diagnosis. Children attending a tertiary care paediatric ophthalmology department with phenotypic (i.e., clinical and/or electrophysiologic) evidence suggestive of IRD were contacted for genetic testing during the SARS-CoV-2-19 pandemic using a "telegenetics" approach. Genetic testing approach was panel-based next generation sequencing (351 genes) via a commercial laboratory (Blueprint Genetics, Helsinki, Finland). Of 70 patient samples from 57 pedigrees undergoing genetic testing, a causative genetic variant(s) was detected for 60 patients (85.7%) from 47 (82.5%) pedigrees. Of the 60 genetically resolved IRD patients, 5% (n = 3) are eligible for approved therapies (RPE65) and 38.3% (n = 23) are eligible for clinical trial-based gene therapies including CEP290 (n = 2), CNGA3 (n = 3), CNGB3 (n = 6), RPGR (n = 5) and RS1 (n = 7). The early introduction of genetic testing in the diagnostic/care pathway for children with IRDs is critical for genetic counselling of these families prior to upcoming gene therapy trials. Herein, we describe the pathway used, the clinical and genetic findings, and the therapeutic implications of the first systematic coordinated round of genetic testing of a paediatric IRD cohort in Ireland.

COVID-19 Vaccines in Inherited Retinal Degenerations (IRD), Fears, Ideas and Real Interactions.

Purpose: In the COVID-19 pandemic era, vaccines are one of the most efficient weapons, as well established by WHO, that humans have, in all their variants (mRNA, AAV or others). Unfortunately, in western nations skepticism within different groups has been generated by the fast approval processes, driven by the urgent need to confront the rapid increase of hospitalized patients and number of deaths by regulation authorities as FDA and EMA. Moreover, several scientific and non-scientific perplexity, also amplified by the media, created hard no-vax strategies, that lead many patients to refuse vaccine administration. Also in this selected population higher rate of COVID-19 infections and severe diseases are registered and consequently there was an increase of death number. Furthermore, to avoid vaccine shots, people frequently ask exemption querying ophthalmological and systemic diseases, in this situation most patients affected with orphan ophthalmological conditions as inherited retinal degenerations have profound fears and doubt. The goal of our study was to ascertain if these fears are based on real facts and if there are interactions or severe visual impairment after each shot of vaccinations. Methods: Five hundred randomically selected patients affected by IRD at each patient was asked anonymously, number of vaccine administrations and eventually reported side effects. Results: Of 500 selected patients 61 (12,2%) did not underwent to Covid-19 vaccination, reasons were various (fear, laziness, caregiver unavailability etc.). Remaining 439 patients (87,8%) had first shot of vaccine. Only 30% of patients complained side effects of vaccine, none of them was serious. Conclusion: The number of patients is wide enough to draw some considerations: In IRD vaccination is safe, in all doses ocular side effects were reported only in one third of subjects and this is not different from the percentage shown by normal people, COVID-19 effects may be more dangerous than vaccine.

POSA249 Diagnostic Pathways, Genetic Testing, and Impact of COVID-19 on Patients in Europe with X-Linked Retinitis Pigmentosa: Results from the Cross-Sectional Explore XLRP 1 Physician Survey

Objectives: To understand the pathways by which European patients with X-linked retinitis pigmentosa (XLRP) arrive at retina specialists (RS) and geneticists for diagnosis, and the impact of COVID-19 on patient management. Methods: The EXPLORE XLRP 1 survey interviewed RS (n=20) and geneticists (n=5) in France, Germany, Italy, Spain, and the United Kingdom (UK) to record information about healthcare pathways and diagnostic approaches for patients with XLRP (n=80). Results: Patients (mostly male [91%] and aged 18–40 years [57%]) experienced an average time of 4 years between XLRP symptoms and diagnosis. In France, Spain, and Italy, patient pathways are linear: most patients see RS/geneticists by ophthalmologist referral. In Germany and the UK, patients see RS/geneticists through multiple routes, also including general practitioner and optometrist referrals. Genetic testing was used as part of XLRP diagnosis in 78% of patients. Genetic testing usually took >6 weeks to receive results, and some patients waited up to 6 months. Genetic testing was fully reimbursed for most patients, except those in Spain, where patients largely incurred the full cost. In the UK, testing costs were co-paid by 14% of patients. Despite barriers to genetic testing (e.g., costs, long waiting times for results), physicians agreed that genotypic diagnosis is helpful to predict disease progression and to enable patient involvement in clinical trials. The COVID-19 pandemic reduced the frequency of in-person clinic visits, but some physicians utilized tele-consultation and remote patient management. Conclusions: The pathways by which patients with XLRP in Europe visit RS and geneticists are complex, lengthy, and vary considerably by country. This survey reported high usage of genetic testing to confirm XLRP diagnosis, but long waiting times for test results accounts for incomplete uptake, especially among older patients. Tele-consultations and remote management have emerged as potential solutions for monitoring patients during the COVID-19 pandemic.

A COVID-19 family cluster with retinitis pigmentosa and hypogammaglobulinemia.

Hypogammaglobulinemia is a heterogeneous group of innate and acquired antibody deficiency with variable disease severity, recurrent pneumonia, and bronchiectasis. The outcome of COVID in patients with hypogammaglobulinemia is variable depending on age, comorbidities, type of immunodeficiency, and use of immunoglobulins. We report the favorable outcome of two family members diagnosed with DNAJC17-related retinitis pigmentosa and hypogammaglobulinemia syndrome and infected with SARS-CoV-2 following contact with their mother who had COVID-19. We describe the different immune dysfunction in these patients and their impact on the course and management of SARS-CoV-2 infection.

Role of Curcumin in Retinal Diseases-A review.

PURPOSE: To review the role of curcumin in retinal diseases, COVID era, modification of the molecule to improve bioavailability and its future scope. METHODS: PubMed and MEDLINE searches were pertaining to curcumin, properties of curcumin, curcumin in retinal diseases, curcumin in diabetic retinopathy, curcumin in age-related macular degeneration, curcumin in retinal and choroidal diseases, curcumin in retinitis pigmentosa, curcumin in retinal ischemia reperfusion injury, curcumin in proliferative vitreoretinopathy and curcumin in current COVID era. RESULTS: In experimental models, curcumin showed its pleiotropic effects in retinal diseases like diabetic retinopathy by increasing anti-oxidant enzymes, upregulating HO-1, nrf2 and reducing or inhibiting inflammatory mediators, growth factors and by inhibiting proliferation and migration of retinal endothelial cells in a dose-dependent manner in HRPC, HREC and ARPE-19 cells. In age-related macular degeneration, curcumin acts by reducing ROS and inhibiting apoptosis inducing proteins and cellular inflammatory genes and upregulating HO-1, thioredoxin and NQO1. In retinitis pigmentosa, curcumin has been shown to delay structural defects of P23H gene in P23H-rhodopsin transgenic rats. In proliferative vitreoretinopathy, curcumin inhibited the action of EGF in a dose- and time-dependent manner. In retinal ischemia reperfusion injury, curcumin downregulates IL-17, IL-23, NFKB, STAT-3, MCP-1 and JNK. In retinoblastoma, curcumin inhibits proliferation, migration and apoptosis of RBY79 and SO-RB50. Curcumin has already proven its efficacy in inhibiting viral replication, coagulation and cytokine storm in COVID era. CONCLUSION: Curcumin is an easily available spice used traditionally in Indian cooking. The benefits of curcumin are manifold, and large randomized controlled trials are required to study its effects not only in treating retinal diseases in humans but in their prevention too.