To date, there has been a global lack of data regarding the prevalence of conditions falling under the Inherited Retinal Diseases (IRD) classification, the impact on the individuals and families affected, and the cost burden to economies. The absence of an international patient registry, and equitable access to genetic testing, compounds this matter. The resulting incomplete knowledge of the impact of IRDs hinders the development and commissioning of clinical services, provision of treatments, and planning and implementation of clinical trials. Thus, there is a need for stronger evidence to support value for money to regulatory bodies for treatments approved, and progressing through clinical trials. To ensure a strategic approach to future research and service provision, it is necessary to learn more about the IRD landscape. This review highlights two recent cost-of-illness reports on the socio-economic impact of 10 IRDs in the Republic of Ireland (ROI) and the United Kingdom (UK), which demonstrate the comprehensive impact of IRDs on individuals affected, their families, friends and society. Total costs attributable to IRDs in the ROI were estimated to be £42.6 million in 2019, comprising economic (£28.8 million) and wellbeing costs (£13.8 million). Wellbeing costs were estimated using the World Health Organization (WHO) burden of disease methodology, a non-financial approach, where pain, suffering and premature mortality are measured in terms of disability-adjusted-life-years (DALYs). In the UK, wellbeing costs attributable to IRDs were £196.1 million, and economic costs were £327.2 million amounting to £523.3 million total costs in 2019. Accounting for over one-third of total costs, the wellbeing burden of persons affected by IRDs should be emphasized and factored into reimbursement processes for therapies and care pathways. This targeted review presents the most current and relevant data on IRD prevalence in the ROI and the UK, and the impacts (financial and non-financial) of IRDs in terms of diagnosis, wellbeing, employment, formal and informal care, health system costs, deadweight losses and issues surrounding payers and reimbursement. This review demonstrates IRD patients and their families have common issues including, the need for timely equitable access to genetic testing and counselling, equality in accessing employment, and a revision of the assessment process for reimbursement of therapies currently focused on the cost-of-illness to the healthcare system. This review reveals that IRD patients do not frequently engage the healthcare system and as such suggests a cost-of-illness model from a societal perspective may be a better format.

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The Impact of Inherited Retinal Diseases in the Republic of Ireland (ROI) and the United Kingdom (UK) from a Cost-of-Illness Perspective.

Background Age-related macular degeneration (AMD) is the leading cause of visual loss in older people. Advanced AMD takes two forms, neovascular (wet) and atrophic (dry). Stargardt disease (STGD) is the commonest form of inherited macular dystrophy. Objective To carry out a systematic review of treatments for dry AMD and STGD, and to identify emerging treatments where future NIHR research might be commissioned. Design Systematic review. Methods We searched MEDLINE, EMBASE, Web of Science and The Cochrane Library from 2005 to 13 July 2017 for reviews, journal articles and meeting abstracts. We looked for studies of interventions that aim to preserve or restore vision in people with dry AMD or STGD. The most important outcomes are those that matter to patients: visual acuity (VA), contrast sensitivity, reading speed, ability to drive, adverse effects of treatment, quality of life, progression of disease and patient preference. However, visual loss is a late event and intermediate predictors of future decline were accepted if there was good evidence that they are strong predictors of subsequent visual outcomes. These include changes detectable by investigation, but not necessarily noticed by people with AMD or STGD. ClinicalTrials.gov, the World Health Organization search portal and the UK Clinical Trials gateway were searched for ongoing and recently completed clinical trials. Results The titles and abstracts of 7948 articles were screened for inclusion. The full text of 398 articles were obtained for further screening and checking of references and 112 articles were included in the final report. Overall, there were disappointingly few good-quality studies (including of sufficient size and duration) reporting useful outcomes, particularly in STGD. However we did identify a number of promising research topics, including drug treatments, stem cells, new forms of laser treatment, and implantable intraocular lens telescopes. In many cases, research is already under way, funded by industry or governments. Limitations In AMD, the main limitation came from the poor quality of much of the evidence. Many studies used VA as their main outcome despite not having sufficient duration to observe changes. The evidence on treatments for STGD is sparse. Most studies tested interventions with no comparison group, were far too short term, and the quality of some studies was poor. Future work We think that the topics on which the Health Technology Assessment (HTA) and Efficacy Mechanism and Evaluation (EME) programmes might consider commissioning primary research are in STGD, a HTA trial of fenretinide (ReVision Therapeutics, San Diego, CA, USA), a visual cycle inhibitor, and EME research into the value of lutein and zeaxanthin supplements, using short-term measures of retinal function. In AMD, we suggest trials of fenretinide and of a potent statin. There is epidemiological evidence from the USA that the drug, levodopa, used for treating Parkinson’s disease, may reduce the incidence of AMD. We suggest that similar research should be carried out using the large general practice databases in the UK. Ideally, future research should be at earlier stages in both diseases, before vision is impaired, using sensitive measures of macular function. This may require early detection of AMD by screening. Study registration This study is registered as PROSPERO CRD42016038708. Funding The National Institute for Health Research HTA programme.

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Treatments for dry age-related macular degeneration and Stargardt disease: a systematic review.

This focused review aims to explore pediatric non-viral keratitis and to compare associated risk factors, etiologies, antibiotic susceptibilities, empiric treatments and outcomes. The authors performed a literature research for articles, published on PubMed, Google Scholar, Scopus and Embase online library, relevant to pediatric keratitis etiology, risk factors, antibiotic susceptibilities, treatment and outcomes. From the bibliography of selected articles, additional relevant articles were also considered. Of 34 articles identified, 21 were suitable for the purpose of this review. Several risk factors are noted in the field of pediatric keratitis. Trauma is the most common in developing countries, while contact lenses wear is seen in developed economies. Previous ocular conditions and systemic diseases also contribute. Associated malnourishment and vitamin A deficit are fraught with a catastrophic prognosis. Among causative organisms, bacteria are more common than fungi and protozoa. Gram-positive organisms are predominant where contact lenses use is infrequent. Pseudomonas aeruginosa is often the leading pathogen in developed countries and is strongly associated with contact lens wear or malnourishment. Fungi are common in the tropics and associated with trauma. Levofloxacin seems the more effective empirical treatment when bacteria are suspected, but there is no agreement on a standard of care. There are differences in etiologic patterns between developing and developed countries and different regions globally. Risk factors follow the same trend; however, there is no standard regimen being followed for empirical treatment of pediatric infectious keratitis. Associated malnourishment and vitamin A deficiency result in poorer outcomes.

https://link.springer.com/content/pdf/10.1007/s10792-020-01451-z.pdf

A global perspective of pediatric non-viral keratitis: literature review

Vitamin A is an essential fat-soluble vitamin that occurs in various chemical forms. It is essential for several physiological processes. Either hyper- or hypovitaminosis can be harmful. One of the most important vitamin A functions is its involvement in visual phototransduction, where it serves as the crucial part of photopigment, the first molecule in the process of transforming photons of light into electrical signals. In this process, large quantities of vitamin A in the form of 11-cis-retinal are being isomerized to all-trans-retinal and then quickly recycled back to 11-cis-retinal. Complex machinery of transporters and enzymes is involved in this process (i.e., the visual cycle). Any fault in the machinery may not only reduce the efficiency of visual detection but also cause the accumulation of toxic chemicals in the retina. This review provides a comprehensive overview of diseases that are directly or indirectly connected with vitamin A pathways in the retina. It includes the pathophysiological background and clinical presentation of each disease and summarizes the already existing therapeutic and prospective interventions.

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The Role of Vitamin A in Retinal Diseases

Highly Variable Disease Courses in Siblings with Stargardt Disease.

Stargardt’s disease (STGD) and Retinitis Pigmentosa (RP) are inherited retinal degenerations that may be affected, in opposite way, by diet. Dietary profile was assessed in 24 patients with STGD and in 56 patients with RP. We documented in only 6 out of 24 (25 %) STGD patients a daily intake of vitamin A within the recommended range while 14/24 (58.3 %) reported a high daily intake and 4/24 (16.7 %) showed a low daily intake. With regard to RP, 4/56 (7.1 %) reported to be within the recommended range, 37/56 (66.1 %) reported high daily intake and 15/56 (26.8 %) showed low daily intake of vitamin A. Interestingly, STGD patients with low vitamin A intake (<600 µg RAE/day) showed significantly better visual acuity with respect to those introducing higher intake of vitamin A. The present study suggests insuitable nutrient intakes among patients with STGD and RP, especially for daily intake of vitamin A. The results may be used to provide tailored nutritional interventions in these patients.

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Dania Biagini

Papers

Dietary profile of patients with Stargardt's disease and Retinitis Pigmentosa: is there a role for a nutritional approach?