A recent study published within the journal Npj Parkinson’s Disease investigated whether increased thinning rate within the parafoveal ganglion cell-inner plexiform layer (pfGCIPL) and peripapillary retinal nerve fiber layer (pRNFL) indicates the progression of the Parkinson’s disease (PD).

Study: Association of retinal neurodegeneration with the progression of cognitive decline in Parkinson’s disease. Image Credit: BioFoto / Shutterstock

Background

Retinal changes are robustly related to neurodegenerative diseases, comparable to PD. The changes in retinal layer thickness could be assessed using high-resolution optical coherence tomography (OCT). Amongst different retinal layers, the ganglion cell-inner plexiform layer (GCIPL) could be used as a biomarker to find out cognitive decline and neurodegeneration.

Several studies have shown that visual disability could be used to predict dementia and cognitive impairment in PD patients. A key advantage of OCT is that it may discover PD patients with or without visual impairment. A reduced thickness of pfGCIPL and pRNFL has been related to cognitive decline. 

As a consequence of the present disagreement between different OCT technologies and devices, it has been difficult to develop a universal cut-off value for retinal thickness that correlates with PD progression. To beat this shortcoming, the speed of retinal thinness is used to predict the clinical consequence of PD. 

In regards to the Study

The important thing objective of this study was to validate that the next rate of thinning of pfGCIPL and pRNFL occurs in PD compared to the control group. Moreover, the association between the aforementioned thinning rates and clinical scores of PD progression was also assessed. 

Two longitudinal databases, from Cruces University Hospital and Araba University Hospital, were utilized in this study. Within the test group, participants were enrolled between February 2015 and December 2021. This study excluded participants who tested positive for PD-causing genetic mutations in LRRK2, PARK2, and SNCA. Within the control group, participants who had a minimum of one first-degree relative with a PD diagnosis were excluded.

All participants were screened to find out and eliminate subjects with potential confounding aspects (e.g., eye diseases and retinal alterations) that would influence retinal OCT measures or clinical outcomes. Since participants with cataract or corneal alterations didn’t affect OCT scans, they were included within the study cohort. The participants’ demographic details were also obtained.

Study Findings

The mean age of the test or PD group and control group participants was 64.8 years and 61.4 years, respectively. Due to this fact, the participants within the control group were younger than the PD group. The control group had significantly more female participants than male participants. 

Using linear mixed-effects models adjusted for age at baseline and sex. Color represents the estimated atrophy rate in each foveo-centered area. Absolute rates are represented in the primary two columns. The relative increase in PD vs. control is represented on the third column, and the corresponding significant p-values for group effect are represented in gray scale. Abbreviations: GCIPL: ganglion cell-inner plexiform layers; PD, Parkinson’s disease.

The study confirmed the next rate of retinal thinning in PD patients in comparison with the control group. This thinning rate was significant in pfGCIPL and the temporal sector of the pRNFL. Importantly, a various rate of retinal neurodegeneration in several individuals with PD was highlighted. PD patients with higher baseline pfGCIPL atrophy are generally related to slower rates of pfGCIPL thinning over time. The cognitive and motor analyses conducted here indicated that patients with higher baseline pfGCIPL atrophy usually tend to develop severe PD with longer disease duration.

Among the many PD patients, those with baseline retinal atrophy and slower pfGCIPL thinning exhibited a significantly faster cognitive decline. A decoupled progression was observed between macular changes and cognitive decline, which entails the opportunity of macular neurodegeneration to precede cognitive deterioration. Consistent with the findings documented here, previous studies have also indicated the association between retinal OCT and clinical outcomes in PD. The present study revealed that assessment of inner retinal thickness could indicate motor disability and disease duration in PD.

Conclusions

Some limitations of this study include a comparatively short follow-up time, an irregular follow-up schedule across participants, and a limited variety of follow-up visits per participant. One other shortcoming was using OCT images obtained from clinical settings, which had image quality issues. Another discrepancies also prevailed in datasets, comparable to age and sex differences in participants of the 2 study cohorts. The possible existence of inherent noise inside the dataset could cause statistical insignificance between the study groups.

Despite the constraints, this study indicated the presence of enhanced retinal neurodegeneration in PD patients. One other significant finding unveiled the association between early pfGCIPL atrophy and a slower rate of pfGCIPL thinning with rapid cognitive decline in PD patients.

In sum, pfGCIPL atrophy may very well be the mechanism underlying brain degeneration that results in cognitive decline. Hence, pfGCIPL could be used as a potent biomarker to evaluate cognitive decline rates over time in PD patients. In the long run, alteration in temporal pRNFL should be further investigated to higher understand its potential as a biomarker for cognitive decline.