A Retrospective Longitudinal Study of 460 Patients with ABCA4-Associated Retinal Disease.

PURPOSE: To investigate the distribution of genotypes and natural history of ABCA4-associated retinal disease in a large cohort of patients seen at a single institution. DESIGN: Retrospective, single-institution cohort review. PARTICIPANTS: Patients seen at the University of Iowa between November 1986 and August 2022 clinically suspected to have disease caused by sequence variations in ABCA4. METHODS: DNA samples from participants were subjected to a tiered testing strategy progressing from allele-specific screening to whole genome sequencing. Charts were reviewed, and clinical data were tabulated. The pathogenic severity of the most common alleles was estimated by studying groups of patients who shared 1 allele. Groups of patients with shared genotypes were reviewed for evidence of modifying factor effects. MAIN OUTCOME MEASURES: Age at first uncorrectable vision loss, best-corrected visual acuity, and the area of the I2e isopter of the Goldmann visual field. RESULTS: A total of 460 patients from 390 families demonstrated convincing clinical features of ABCA4-associated retinal disease. Complete genotypes were identified in 399 patients, and partial genotypes were identified in 61. The median age at first vision loss was 16 years (range, 4-76 years). Two hundred sixty-five families (68%) harbored a unique genotype, and no more than 10 patients shared any single genotype. Review of the patients with shared genotypes revealed evidence of modifying factors that in several cases resulted in a > 15-year difference in age at first vision loss. Two hundred forty-one different alleles were identified among the members of this cohort, and 161 of these (67%) were found in only a single individual. CONCLUSIONS: ABCA4-associated retinal disease ranges from a very severe photoreceptor disease with an onset before 5 years of age to a late-onset retinal pigment epithelium-based condition resembling pattern dystrophy. Modifying factors frequently impact the ABCA4 disease phenotype to a degree that is similar in magnitude to the detectable ABCA4 alleles themselves. It is likely that most patients in any cohort will harbor a unique genotype. The latter observations taken together suggest that patients' clinical findings in most cases will be more useful for predicting their clinical course than their genotype. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Portable wide-field digital imaging for screening of neonatal visual impairment causes in Rio de Janeiro, Brazil: a budget impact analysis.

OBJECTIVE: To estimate the budget impact of portable wide-field digital imaging incorporation on screening neonatal causes of childhood blindness and visual impairment in Rio de Janeiro, Brazil. DESIGN: Budget impact analysis. SETTING: Rio de Janeiro, Brazil. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was the direct cost of indirect binocular ophthalmoscopy, red reflex test and portable wide-field digital image screening comprising all babies born in Rio de Janeiro's government maternity wards. The secondary outcome was the budget impact of implementing portable wide-field digital image screening in Rio de Janeiro, Brazil. RESULTS: Considering 100% coverage of maternity wards, the total budget impact between 2020 and 2024 would be US$3 820 706.04, ranging from US$3 139 844.34 to US$6 099 510.35. The additional cost would be US$3 124 457.28, ranging from US$2 714 492.26 to US$4 880 608.63. CONCLUSION: The cost of universal digital imaging screening corresponds to less than 1% of the government health budget of the city of Rio de Janeiro. The information provided in this study may help government decision-makers evaluate the feasibility of implementing this new strategy in the municipal setting. Further health economic evaluations should be performed to verify the affordability of the implementation of this screening strategy in the Brazilian scenario, taking into account scarce human resources.

Cost-Utility Analysis of Wide-Field Imaging as an Auxiliary Technology for Retinopathy of Prematurity Care in Brazil.

Purpose: To evaluate the cost-utility of wide-field imaging (WFI) as a complementary technology for retinopathy of prematurity (ROP) screening from the Brazilian Unified Health System's perspective. Introduction: ROP is one of the leading causes of avoidable childhood blindness worldwide, especially in middle-income countries. The current ROP screening involves indirect binocular ophthalmoscopy (IBO) by ROP expert ophthalmologists. However, there is still insufficient ROP screening coverage. An alternative screening strategy is the combination of WFI with IBO. Methods: A cost-utility analysis was performed using a deterministic decision-tree simulation model to estimate incremental cost-utility for ROP care. Two screening strategies were compared: (1) IBO and (2) combination of WFI of all eligible preterm infants and IBO for type 2 ROP or worse and for non-readable images. Eligible population included preterm infants <32 weeks of gestational age or birth weight equal to or <1,500 g. The temporal horizon was lifetime. Visual outcome data was converted to utility, and the health benefits were estimated on quality-adjusted life-years (QALY). Incremental cost per QALY gained was calculated from the health system perspective. Costs were estimated considering equipment, maintenance, consumables, and staff. A micro-costing approach was used for WFI. Two technician nurses were trained for imaging execution and had their time evaluated. Two ROP expert ophthalmologists had their time evaluated for imaging reading. One-way sensitivity analysis and probabilistic sensitivity analysis were performed. Results: Combined screening strategy resulted in a cost-effective program considering 90% ROP screening coverage. Costs per examination: (1) screening with IBO: US dollar (US $) 34.36; (2) screening with combination: US $58.20; (3) laser treatment: US $642.09; (4) long-term follow-up: ranged from US $69.33 to 286.91, based on the infant's visual function. Incremental cost per QALY gained was US $1,746.99/QALY per infant screened with the combination strategy. One-way sensitivity analysis resulted in cost-effectiveness for all parameters. Probabilistic sensitivity analyses yielded a 100% probability of combination being cost-effective in a willingness-to-pay threshold of US $1,800/QALY. Conclusion: The combined strategy for ROP screening was cost-effective. It enhances access for appropriate ROP care in middle-income countries and dminishes opportunity costs for ophthalmologists.