Rodriguez-Martinez Ana Catalina, Tailor-Hamblin Vijay K, Higgins Bethany E, Jones Pete R, Dekker Tessa M, Henderson Robert H, Greenwood John A, Moosajee Mariya
Moorfields Eye Hospital NHS Foundation Trust, London, England, United Kingdom.
Institute of Ophthalmology, University College London, London, England, United Kingdom.
Invest Ophthalmol Vis Sci. 2025 May 1;66(5):32. doi: 10.1167/iovs.66.5.32.
Mutations affecting the CRB1 gene produce retinal dystrophies including early onset severe retinal dystrophy/Leber congenital amaurosis (EOSRD/LCA), retinitis pigmentosa (RP), cone-rod dystrophy (CORD), and macular dystrophy (MD). As treatment strategies advance toward clinical translation, there is a need to establish reliable outcome metrics and to better understand the visual deficits associated with CRB1 retinopathies. To this end, we measured visual acuity (VA) and crowding (the disruptive effect of clutter on object recognition), both key functions in spatial vision, using child-friendly computer-based tests, and gold-standard clinical measures.
Patients with molecularly confirmed biallelic CRB1 pathogenic variants were compared with age-matched controls (n = 20 in each). Best-corrected visual acuity (BCVA) was measured with both Early Treatment Diabetic Retinopathy Study (ETDRS) and the computerized VacMan procedures (using an unflanked/isolated VacMan target), which also allowed measurement of crowding when surrounding flanker elements were added.
Both acuity and crowding were significantly elevated in individuals with CRB1 retinopathy compared with controls. ETDRS acuity correlated with both the unflanked (r = 0.868, P < 0.001) and flanked VacMan thresholds (r = 0.748, P < 0.001). No statistically significant changes in crowding were observed with respect to CRB1 phenotype (EOSRD/LCA, CORD, or MD) or age of onset.
This study demonstrates for the first time that individuals with CRB1 retinopathy exhibit elevated crowding in their foveal vision compared with controls. Measuring crowding offers valuable insights into understanding functional visual deficits in CRB1 retinopathy and could be a useful metric for monitoring disease progression and treatment outcomes in inherited retinal diseases.
影响CRB1基因的突变会导致视网膜营养不良，包括早发性严重视网膜营养不良/莱伯先天性黑蒙（EOSRD/LCA）、色素性视网膜炎（RP）、锥杆营养不良（CORD）和黄斑营养不良（MD）。随着治疗策略向临床转化的推进，需要建立可靠的结果指标，并更好地了解与CRB1视网膜病变相关的视觉缺陷。为此，我们使用适合儿童的计算机测试和金标准临床测量方法，测量了视力（VA）和拥挤现象（杂乱对物体识别的干扰效应），这两者都是空间视觉的关键功能。
将分子确诊为双等位基因CRB1致病变异的患者与年龄匹配的对照组（每组n = 20）进行比较。使用早期糖尿病性视网膜病变研究（ETDRS）和计算机化的VacMan程序（使用无侧翼/孤立的VacMan目标）测量最佳矫正视力（BCVA），当添加周围侧翼元素时，该程序还可以测量拥挤现象。
与对照组相比，CRB1视网膜病变患者的视力和拥挤现象均显著升高。ETDRS视力与无侧翼（r = 0.868，P < 0.001）和有侧翼的VacMan阈值（r = 0.748，P < 0.001）均相关。关于CRB1表型（EOSRD/LCA、CORD或MD）或发病年龄，未观察到拥挤现象有统计学意义的变化。
本研究首次表明，与对照组相比，CRB1视网膜病变患者的中央凹视力中拥挤现象升高。测量拥挤现象为理解CRB1视网膜病变中的功能性视觉缺陷提供了有价值的见解，并且可能是监测遗传性视网膜疾病的疾病进展和治疗结果的有用指标。
