Longitudinal Imaging of the Parafoveal Cone Mosaic in Congenital Achromatopsia

IF 3.2 Q1 OPHTHALMOLOGY

Ophthalmology science Pub Date : 2025-03-14 DOI:10.1016/j.xops.2025.100765

Nickolas Chen MD , Katie M. Litts PhD , Danica Nikezic BS , Christopher S. Langlo MD, PhD , Brian P. Higgins BS , Byron L. Lam MD , Gerald A. Fishman MD , Frederick T. Collison OD , Mark E. Pennesi MD, PhD , Christine N. Kay MD , Sergey Tarima PhD , Joseph Carroll PhD

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Abstract

Purpose

To assess longitudinal changes in parafoveal cone density in individuals with congenital achromatopsia (ACHM).

Design

Retrospective longitudinal study.

Participants

Nineteen individuals (7 women and 12 men) with genetically confirmed ACHM. To be eligible, each had adaptive optics scanning light ophthalmoscope (AOSLO) images of the photoreceptor mosaic from ≥2 time points.

Methods

For each individual, follow-up AOSLO montages were aligned to their baseline montage. Notably, 100 × 100 μm regions of interest (ROIs) were extracted from the split-detection modality at locations 1°, 5°, and 10° temporal (T) from the peak cone density in each montage. All ROIs from follow-up visits were then manually aligned to their respective baseline ROI for that location. Cones were identified in each ROI by one observer, reviewed by a second observer, and confirmed together in a masked fashion. Cone density was calculated, and a linear mixed model was used to assess changes in density over time. A Wald test was performed to determine if the cone density changes were statistically significant.

Main Outcome Measures

Parafoveal cone spacing (at 1°, 5°, and 10° T) as a function of time.

Results

The mean (± standard deviation [SD]) age at baseline was 21.6 ± 10.7 years and the mean (±SD) follow-up period was 3.83 ± 2.93 years (range, 0.46–8.66 years). At 1° T, we observed a significant decrease of 352 cones/mm² per year (P = 0.0003). At 5° T, the linear mixed model showed a nonstatistically significant decrease of 58 cones/mm² per year (P = 0.504). At 10° T, we observed a significant decrease of 139 cones/mm² per year (P = 0.0188). For a 100 × 100 μm ROI, these density changes correspond to a reduction of between about 0.5 and 4 cones per year, depending on the location.

Conclusions

Parafoveal cone density estimates in ACHM show a small decrease over time. These observed changes are within the previously reported longitudinal repeatability values for normal retinas, suggesting the observed average cone loss may not be clinically meaningful. Further studies with longer follow-up times and more genetically heterogeneous and age-diverse populations are needed to better understand factors contributing to changes in foveal and parafoveal cone structure in ACHM over time.

Financial Disclosure(s)

Proprietary or commercial disclosures may be found in the Footnotes and Disclosures at the end of this article.

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先天性色盲中凹旁视锥镶嵌的纵向成像

目的评估先天性色弱（ACHM）患者视网膜旁视锥密度的纵向变化。每个人都有≥2个时间点的感光镶嵌体的自适应光学扫描光眼底镜（AOSLO）图像。值得注意的是，从每张蒙太奇图像中锥体密度峰值的 1°、5° 和 10°颞角 (T) 位置处的分光检测模式中提取 100 × 100 μm 的感兴趣区 (ROI)。然后将随访的所有 ROI 与该位置各自的基线 ROI 手动对齐。每个 ROI 中的锥体由一名观察者识别，由另一名观察者复核，并以屏蔽方式共同确认。计算锥体密度，并使用线性混合模型评估密度随时间的变化。结果基线年龄平均（± 标准差 [SD]）为 21.6 ± 10.7 岁，随访时间平均（±SD）为 3.83 ± 2.93 年（范围为 0.46-8.66 年）。在 1° T 时，我们观察到锥体数量每年显著减少 352 个/mm2（P = 0.0003）。在 5° T 时，线性混合模型显示每年减少 58 个锥状体/mm2，但无统计学意义（P = 0.504）。在 10° T 时，我们观察到每年每平方毫米有 139 个锥状体显著减少（P = 0.0188）。对于 100 × 100 μm 的 ROI，这些密度变化相当于每年减少约 0.5 到 4 个视锥，具体取决于位置。这些观察到的变化在之前报道的正常视网膜纵向重复性值范围内，表明观察到的锥体平均损失可能没有临床意义。为了更好地了解导致ACHM患者眼窝和眼窝旁视锥结构随时间变化的因素，还需要进行随访时间更长、遗传异质性更强、年龄更多样化的进一步研究。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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