Patient-Reported Health-Related Quality of Life in Individuals with Inherited Retinal Diseases.

Purpose: To evaluate the impact of inherited retinal diseases (IRDs) on quality of life (QoL) using multiattributable health utilities derived from primary patient data. Design: Cross-sectional observational study. Participants: Seventy adult patients (mean age, 42.7 years) with IRD recruited from state-wide services in Australia. Methods: Health utility values were calculated from the Assessment of Quality of Life 8-Dimension (AQoL-8D). Linear regressions were used to analyze the relationship between the 25-item and 39-item National Eye Institute Visual Function Questionnaires (NEI-VFQ-25 and NEI-VFQ-39, respectively) and health utilities from the AQoL-8D. Main Outcome Measures: The AQoL-8D utility values were compared between the IRD cohort and population norms. Regressions were used to determine explanatory power of the NEI-VFQ-25 and NEI-VFQ-39 for health utilities from the AQoL-8D. Results: Average health-related utility for patients with IRD was 0.58, significantly lower than population norms of 0.80. The IRD patient scores were significantly lower than population norms for all 8 domains of the AQoL-8D. Regressions showed a statistically significant relationship between the NEI-VFQ-39 and AQoL-8D, with the NEI-VFQ-39 and other clinical data explaining up to 73% of the variation in AQoL-8D values and 69% of the variation in the NEI-VFQ-25 values. Conclusions: Patients with IRD have significantly lower utility values across all dimensions of QoL, with the largest differences in independent living, senses, and relationships. The NEI-VFQ-25 and NEI-VFQ-39 are highly correlated with overall AQoL-8D utilities and, combined with other data, can reasonably estimate QoL utilities required for cost-effectiveness studies.

Heterozygous COL9A3 variants cause severe peripheral vitreoretinal degeneration and retinal detachment.

The COL9A3 gene encodes one of the three alpha chains of Type IX collagen, with heterozygous variants reported to cause multiple epiphyseal dysplasia, and suggested as contributory in some cases of sensorineural hearing loss. Patients with homozygous variants have midface hypoplasia, myopia, sensorineural hearing loss, epiphyseal changes and carry a diagnosis of Stickler syndrome. Variants in COL9A3 have not previously been reported to cause vitreoretinal degeneration and/or retinal detachments. This report describes two families with autosomal dominant inheritance and predominant features of peripheral vitreoretinal lattice degeneration and retinal detachment. Genomic sequencing revealed a heterozygous splice variant in COL9A3 [NG_016353.1(NM_001853.4):c.1107 + 1G>C, NC_000020.10(NM_001853.4):c.1107 + 1G>C, LRG1253t1] in Family 1, and a heterozygous missense variant [NG_016353.1(NM_001853.4):c.388G>A p.(Gly130Ser)] in Family 2, each segregating with disease. cDNA studies of the splice variant demonstrated an in-frame deletion in the COL2 domain, and the missense variant occurred in the COL3 domain, both indicating the critical role of Type IX collagen in the vitreous base of the eye.