Department of Ophthalmology, Copenhagen University Hospital, Rigshospitalet, Glostrup, Denmark.
Department of Clinical Genetics, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
Acta Ophthalmol. 2024 Sep;102(6):e893-e905. doi: 10.1111/aos.16656. Epub 2024 Feb 13.
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.
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.
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.
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.
描述经基因验证的丹麦先天性静止性夜盲症（ACHM）患者的表型，特别关注结构或功能参数上的进展迹象，以及可能的基因型-表型相关性。
确定了 48 名患者，他们的疾病相关变异位于五个不同的基因中：CNGA3、CNGB3、GNAT2、PDE6C 和 PDE6H。对 11 名患者进行了纵向评估，27 名患者参与了重新进行的深入表型分析，包括视力评估、光学相干断层扫描（OCT）、眼底自发荧光、色觉评估、对比敏感度、中值微视野和全视野视网膜电图。对 48 名患者的所有 OCT 图像进行了基于 OCT 图像的 foveal 形态评估，使用基于高反射光感受器带完整性的分级系统，即内节椭圆带（ISe）。根据纵向数据和与年龄的相关性评估进展迹象。
我们发现 OCT 分级与年龄之间存在统计学上的显著正相关（Spearman ρ=0.62，p<0.0001），在 11 名随访时间≥5 年的患者中，有 2 名患者观察到 foveal 形态的变化。我们没有发现年龄与功能参数（视力、视网膜敏感度和对比敏感度）之间存在任何有说服力的相关性，也没有发现结构与功能参数之间的相关性，或者任何明确的基因型-表型相关性。
一些 ACHM 患者在 OCT 特征上表现出进行性的 foveal 变化迹象，这与年龄的增加有关。这在可能的新治疗方法方面具有重要意义。然而，尽管 foveal 结构发生变化，功能特征（如视力）仍保持稳定。因此，从患者的角度来看，ACHM 仍然可以被认为是一种非进行性疾病。
