Choroideremia (CHM) is an X-linked recessive inherited retinal disease characterized by progressive degeneration of photoreceptors, retinal pigment epithelium and choroid. Clinical manifestations include slowly progressive night blindness and visual field defects, for which there is no effective treatment. The development of fundus examination technology has provided more indicators for clinical diagnosis and follow-up observation, and the emergence of next generation sequencing technology has further improved the diagnostic rate of inherited retinal diseases, gradually deepening the understanding of the pathogenesis and natural history of CHM. Numerous clinical trials of CHM gene therapy have been conducted over a decade, with important advances in vector optimization for gene therapy, treatment time window selection, and management of trial adverse events. In the future, there is a need to deepen the understanding of the natural course of CHM and to adopt personalized treatment and endpoint evaluation targets for the treatment time window. Assessing differences in disease severity and individualizing treatment plans for different stages is more beneficial to prognosis.
ObjectiveTo observe and analyze the rate of visual acuity progression and binocular symmetry in patients with choroideremia (CHM). MethodsA single-center retrospective longitudinal cohort study. From April 2009 to August 2022, 38 eyes of 19 patients diagnosed with CHM through clinical and genetic testing at the Department of Ophthalmology, Peking Union Medical College Hospital, were included in this study. All patients underwent at least 2 follow-up visits with a minimum interval of 1 year between visits, and binocular best-corrected visual acuity (BCVA) results were recorded at each follow-up visit. Decimal visual acuity was converted into logarithm of the minimum angle of resolution (logMAR) for analysis. The patient group consisted of 19 males from 16 unrelated families. The age at initial visit was (39.52±13.24) years, with a (2.63±1.61) follow-up visits over a duration of (4.95±2.68) years. A total of 50 BCVA data were included. Annual progression rate of visual acuity was calculated based on longitudinal and cross-sectional data. Spearman correlation coefficient and Bland-Altman method were used to evaluate the binocular symmetry. ResultsThe rate of visual acuity progression was (0.095±0.148) logMAR units/year based on longitudinal data and (0.018±0.009) logMAR units/year based on cross-sectional data. The binocular symmetry for BCVA of the baseline values was strong; however, the binocular symmetry of progression rates for BCVA was moderate. Spearman correlation analysis showed that baseline BCVA was highly symmetric in both eyes (r=0.881, P＜0.001). The symmetry of binocular vision progression rates based on longitudinal data was moderately symmetric (r=0.528, P=0.020). Blan-altman analysis showed that 94.7% of binocular baseline BCVA differences were within 95% confidence interval (CI) of 95% limit difference (LOA), indicating good symmetry of binocular baseline BCVA. The number of binocular BCVA progression rate differences within 95%CI of 95%LOA was 89.5%, suggesting moderate symmetry in binocular BCVA progression rate. The results of Spearman correlation coefficient and Bland-Altman analysis of binocular symmetry were basically consistent. ConclusionsThe rate of visual acuity progression of patients with CHM based on longitudinal and cross-sectional data is (0.095±0.148) and (0.018±0.009) logMAR units/year, respectively. Cross-sectional data from patients of different ages should not be used to infer the progression rate of the natural history. Binocular eyes with highly symmetrical baseline visual acuity may differ in the rate of visual acuity progression.
Choroideremia (CHM) is a rare X-linked recessive genetic retinal degeneration. It mainly affects men, manifested as progressively worsening night blindness, visual field loss, and decreased central vision, which can cause blindness in middle age. Although female carriers typically exhibit mild symptoms, it is essential to understand their clinical features for early diagnosis of patients as well as genetic counseling of family members. The pathogenesis of CHM remains incompletely understood, and currently there is no approved effective treatment. To enhance clinicians’ comprehension of CHM and establish standardized clinical approaches to its diagnosis and management, Chinese Hereditary Ocular Disease Diagnosis and Treatment Group and Chinese Hereditary Ocular Disease Alliance assembled authoritative experts, through in-depth discussion, formed China's standardized suggestions on clinical diagnosis and treatment of CHM. The purpose of this advice is to provide a standardized diagnostic framework, monitoring indicators, and integrated management strategy for clinicians to use in practice to optimize the care and genetic guidance for patients with CHM.