目的:描述丹麦基因验证色盲(ACHM)患者的表型,特别关注结构或功能参数的进展迹象,和可能的基因型-表型相关性。
方法:确定了48例患者,在五个不同的基因中具有致病变异:CNGA3,CNGB3,GNAT2,PDE6C和PDE6H。11例患者可以进行纵向评估,27例患者参加了由视力评估组成的新的深入表型鉴定,光学相干断层扫描(OCT),眼底自发荧光,色觉评价,对比敏感度,介孔显微视野和全场视网膜电图。使用基于超反射光感受器带完整性的分级系统,根据OCT图像对所有48名患者的中心凹形态进行评估。内段椭球区(ISE)。根据纵向数据和与年龄的相关性评估进展迹象。
结果:我们发现OCT分级与年龄之间存在统计学上显著的正相关(Spearmanρ=0.62,p<0.0001),我们观察到11例随访≥5年的患者中有2例的中央凹形态变化。我们没有发现年龄和功能参数(视敏度,视网膜敏感度和对比敏感度),我们也没有发现结构和功能参数之间的相关性,或任何明确的基因型-表型相关性。
结论:一些ACHM患者表现出随着年龄增长OCT特征进行性中央凹改变的迹象。这与可能的新疗法有关。然而,功能特征,比如视力,尽管中央凹结构发生变化,但仍保持稳定。因此,从病人的角度来看,ACHM仍然可以被认为是非进行性病症。
OBJECTIVE: To describe the phenotype of Danish patients with genetically verified achromatopsia (ACHM) with special focus on signs of progression on structural or functional parameters, and possible genotype-phenotype correlations.
METHODS: Forty-eight patients were identified, with disease-causing variants in five different genes: CNGA3, CNGB3, GNAT2, PDE6C and PDE6H. Longitudinal evaluation was possible for 11 patients and 27 patients participated in a renewed in-depth phenotyping consisting of visual acuity assessment, optical coherence tomography (OCT), fundus autofluorescence, colour vision evaluation, contrast sensitivity, mesopic microperimetry and full-field electroretinography. Foveal morphology was evaluated based on OCT images for all 48 patients using a grading system based on the integrity of the hyperreflective photoreceptor band, the inner segment ellipsoid zone (ISe). Signs of progression were evaluated based on longitudinal data and correlation with age.
RESULTS: We found a statistically significant positive correlation between OCT grade and age (Spearman ρ = 0.62, p < 0.0001) and we observed changes in the foveal morphology in 2 of 11 patients with ≥5 years of follow-up. We did not find any convincing correlation between age and functional parameters (visual acuity, retinal sensitivity and contrast sensitivity) nor did we find correlation between structural and functional parameters, or any clear genotype-phenotype correlation.
CONCLUSIONS: Some patients with ACHM demonstrate signs of progressive foveal changes in OCT characteristics with increasing age. This is relevant in terms of possible new treatments. However, functional characteristics, such as visual acuity, remained stable despite changing foveal structure. Thus, seen from a patient perspective, ACHM can still be considered a non-progressive condition.