Objective: To assess longitudinal changes of retinal thickness measurements and their role as biomarkers of disease progression in patients with Lewy body diseases (LBDs).

Background: Neuroprotective agents in Parkinson’s disease (PD) and other (LBDs) are currently being tested in clinical trials. However, tools to monitor the effectiveness of these treatments are still limited. Several cross-sectional studies using Optical Coherence Tomography (OCT) have shown that patients with LBD have thinner GCIPL and peripapillary retinal nerve fiber layer (pRNFL) compared with controls. However, the rate of GCIPL and pRNFL thinning and their role as biomarkers of disease worsening is unknown.

Method: We performed a prospective, longitudinal and observational study in n=50 patients with LBDs and n=17 controls. Unified Parkinson’s Disease Rating Scale (UPDRS), Montreal Cognitive Assessment (MoCA) and retinal layer thicknesses with OCT were measured at baseline and at 3 years of follow-up. Disease worsening was considered when UPDRS III score increased 5-points or more or when MoCA score declined 4 points or more across the two time points. The retinal GCIPL and pRNFL thickness reduction rates were estimated using a Linear Mixed-Models and the significance of changes were determined by comparing Akaike Information Criterion. We estimated the association of GCIPL and pRNFL thickness at baseline with the risk of subsequent disease worsening by using relative risk adjusted for baseline age, sex, disease duration, UPDRS III score and LEDD.

Results: In a linear mixed model, the GCIPL thickness in the parafoveal region (1- to 3-mm ring) presented the highest reduction rates in patients with LBD. The annualized atrophy rate was 0.73 µm in patients and 0.23 µm in controls (p<0.0001). Patients in the lowest parafoveal GCIPL tertile (< 88.7 µm) had twice the risk of general cognition worsening at 3 years compared to patients with parafoveal GCIPL thickness greater than 88.7 µm (RR 2.40, 95% CI 1.01 – 5.68, p=0.046). We did not identify meaningful associations between pRNFL and disease worsening, nor parafoveal GCIPL thickness and motor deterioration.

Conclusion: Our results provide evidence of the usefulness of monitoring parafoveal GCIPL thickness by OCT for prediction of the risk of cognitive worsening over time in patients with Lewy body diseases.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/retinal-thinning-and-disease-worsening-in-lewy-body-diseases/