Peripapillary Retinal Nerve Fiber Layer (pRNFL) Thickness - A Novel Biomarker of Neurodegeneration in Late-Infantile CLN2 Disease.

IF 3.1 Q1 OPHTHALMOLOGY Eye and Brain Pub Date : 2024-11-13 eCollection Date: 2024-01-01 DOI:10.2147/EB.S473408

Nikolaos Gkalapis, Simon Dulz, Carsten Grohmann, Miriam Nickel, Christoph Schwering, Eva Wibbeler, Martin Stephan Spitzer, Angela Schulz, Yevgeniya Atiskova

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Abstract

Purpose: To investigate the presence of peripapillary retinal nerve fiber layer (pRNFL) degeneration in patients with late-infantile neuronal ceroid lipofuscinosis type 2 (CLN2) disease and to evaluate the role of optical coherence tomography (OCT) assessed pRNFL thickness as a biomarker for CLN2 disease progression.

Patients and methods: Forty eyes of 20 patients with genetically and enzymatically confirmed diagnosis of late-infantile CLN2 disease were included in this retrospective cohort study. All patients received 300 mg of intracerebroventricular enzyme replacement treatment (cerliponase alfa) once every two weeks. OCT imaging was performed under general anesthesia using spectral domain OCT (Heidelberg Engineering, Heidelberg, Germany). PRNFL thickness and central retinal thickness (CRT) values were manually confirmed with the Heidelberg Eye Explorer software. Corresponding pediatric data were extracted from the DEM-CHILD database. Spearman correlation coefficient values (rs) were calculated between pRNFL and CRT values, age at examination, the Weill Cornell Late Infantile Neuronal Ceroid Lipofuscinosis (Weill Cornell LINCL) Scale and the Hamburg Motor and Language (HML) Scale.

Results: Fourteen of 20 patients underwent serial examinations resulting in a total of 84 OCT Scans and 42 Weill Cornell LINCL and HML Scale scores. Mean age was 6.90 years and mean follow-up time was 1.38 years. Mean global pRNFL (G-pRNFL) thickness was 77.02 μm presenting a significant decrease compared to normative values from healthy children (106.45 μm; p < 0.0001). G-pRNFL displayed significant correlations towards age at examination (r_s = - 0.557, p < 0.01), the Weill Cornell LINCL Scale (r_s = 0.849, p < 0.01), and the HML Scale (r_s = 0.833, p < 0.01). Repeated measurements indicated decreases in pRNFL thickness over time in most patients.

Conclusion: Patients with late-infantile CLN2 disease exhibit early onset progressive pRNFL loss regardless of outer retinal degeneration, highlighting the potential of pRNFL as an independent ocular biomarker for retinal pathology in late-infantile CLN2 disease.

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毛细血管周围视网膜神经纤维层（pRNFL）厚度--晚期婴幼儿CLN2疾病神经退行性变的新型生物标记物

目的：研究晚发型神经元类脂膜脂质沉着症2型（CLN2）患者视网膜周围神经纤维层（pRNFL）是否存在变性，并评估光学相干断层扫描（OCT）评估的pRNFL厚度作为CLN2疾病进展的生物标志物的作用：这项回顾性队列研究共纳入了20名经遗传学和酶学确诊为晚发型CLN2疾病患者的40只眼睛。所有患者均接受了每两周一次、每次 300 毫克的脑室内酶替代治疗（cerliponase alfa）。在全身麻醉的情况下，使用光谱域 OCT（德国海德堡海德堡工程公司）进行 OCT 成像。PRNFL 厚度和视网膜中央厚度 (CRT) 值由海德堡 Eye Explorer 软件手动确认。相应的儿科数据来自 DEM-CHILD 数据库。计算了pRNFL和CRT值、检查时的年龄、威尔-康奈尔晚期婴儿神经元类色素沉着症量表（Weill Cornell LINCL）和汉堡运动与语言量表（HML）之间的斯皮尔曼相关系数（rs）：20 位患者中有 14 位接受了连续检查，共获得 84 次 OCT 扫描和 42 次威尔-康奈尔 LINCL 和 HML 量表评分。平均年龄为 6.90 岁，平均随访时间为 1.38 年。全球 pRNFL（G-pRNFL）平均厚度为 77.02 μm，与健康儿童的标准值（106.45 μm；p < 0.0001）相比明显下降。G-pRNFL 与检查时的年龄（rs = - 0.557，p < 0.01）、威尔康奈尔 LINCL 量表（rs = 0.849，p < 0.01）和 HML 量表（rs = 0.833，p < 0.01）呈显著相关。重复测量结果表明，大多数患者的 pRNFL 厚度会随着时间的推移而下降：结论：晚发型CLN2患者无论是否存在视网膜外层变性，其pRNFL都会表现出早发的进行性损失，这凸显了pRNFL作为晚发型CLN2患者视网膜病变的独立眼部生物标记物的潜力。

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来源期刊

Eye and Brain OPHTHALMOLOGY-

CiteScore

7.90

自引率

2.30%

发文量

审稿时长

16 weeks

期刊介绍： Eye and Brain is an international, peer-reviewed, open access journal focusing on basic research, clinical findings, and expert reviews in the field of visual science and neuro-ophthalmology. The journal’s unique focus is the link between two well-known visual centres, the eye and the brain, with an emphasis on the importance of such connections. All aspects of clinical and especially basic research on the visual system are addressed within the journal as well as significant future directions in vision research and therapeutic measures. This unique journal focuses on neurological aspects of vision – both physiological and pathological. The scope of the journal spans from the cornea to the associational visual cortex and all the visual centers in between. Topics range from basic biological mechanisms to therapeutic treatment, from simple organisms to humans, and utilizing techniques from molecular biology to behavior. The journal especially welcomes primary research articles or review papers that make the connection between the eye and the brain. Specific areas covered in the journal include: Physiology and pathophysiology of visual centers, Eye movement disorders and strabismus, Cellular, biochemical, and molecular features of the visual system, Structural and functional organization of the eye and of the visual cortex, Metabolic demands of the visual system, Diseases and disorders with neuro-ophthalmic manifestations, Clinical and experimental neuro-ophthalmology and visual system pathologies, Epidemiological studies.