Early ophthalmologic features of Parkinson’s disease: a review of preceding clinical and diagnostic markers

Abstract

Non-motor symptoms in Parkinson's disease are an important cause of morbidity and may even precede the onset of the motor features of the disease. Visual abnormalities are among the most frequent non-motor symptoms observed during the early stages of the disease. Some of the visual symptoms of Parkinson's disease can likely be explained by the presence of dopaminergic neurons within the retina, where the progressive loss of dopamine and the accumulation of α-synuclein within the retinal layers leads to visual dysfunction, while some are caused by abnormalities in cortical visual processing. Many of these visual symptoms can be overlooked or go unrecognized. We review the visual symptoms in Parkinson's disease, including visual-processing and ocular motility abnormalities, stereopsis deficits, and visual hallucinations, focusing on the early stages of the disease. We focus on the reciprocal influence between the visual symptoms and the progression of the disease, analyzing the influence of dopaminergic therapy on the visual abnormalities. Finally, we discuss the possible role of some of these visual symptoms as possible markers or early diagnostic signs of the disease.

Retinal α-synuclein deposits in Parkinson’s disease patients and animal models

“…In recent years, there has been an expansion of studies investigating the use of in vivo assessments of retinal structure, electrophysiological, and visual function as novel means for identifying patients at risk that need further neurological examination and for longitudinal follow-up of disease progression in PD patients. These have been extensively reviewed elsewhere (e.g., [7,10,22,49,70,138,148]) and fall beyond the scope of this review. Often, the results of these studies have been related to dopaminergic depletion and αSYN accumulation in the retina.…”

Retinal Thickness and Microvascular Pattern in Early Parkinson's Disease

“…PD is traditionally related to a progressive loss of dopaminergic neurons in the substantia nigra pars compacta, leading to motor symptoms, such as bradykinesia, resting tremor, and rigidity (1). Moreover, PD patients may experience non-motor symptoms such as mood dysfunction, personality disorders (2,3), autonomic failure (4), cognitive impairment (5), sleep disorders (6), and visual disturbances (7), probably related to alpha-synuclein (αSYN) inclusions in both central and peripheral nervous systems (8,9). While motor symptoms occur when at least 50-60% of dopaminergic neurons have been lost, non-motor symptoms may occur many years before onset of motor manifestations, playing an intriguing role as biomarker in the diagnosis of "Prodromal PD" (10).…”

“…While motor symptoms occur when at least 50-60% of dopaminergic neurons have been lost, non-motor symptoms may occur many years before onset of motor manifestations, playing an intriguing role as biomarker in the diagnosis of "Prodromal PD" (10). Among non-motor symptoms, visual disorders are extremely common, also in the early stage of disease, affecting up to 78% of patients with PD (7). Ocular symptoms include impairment of color vision (11,12), contrast sensitivity (7,(11)(12)(13)(14), and visual acuity (15,16).…”

“…Among non-motor symptoms, visual disorders are extremely common, also in the early stage of disease, affecting up to 78% of patients with PD (7). Ocular symptoms include impairment of color vision (11,12), contrast sensitivity (7,(11)(12)(13)(14), and visual acuity (15,16). Several optical coherence tomography (OCT) studies showed a thinning of intraretinal layers in PD patients compared to HCs, especially in retinal nerve fiber layer (RNFL), ganglionic cell layer (GCL), and inner plexiform layer (IPL) (17)(18)(19)(20).…”

Dopamine, Alpha-Synuclein, and Mitochondrial Dysfunctions in Parkinsonian Eyes

“…The retina, however, has long been overlooked compared to other brain regions in PD, so the information available is rather limited. However, recent experimental evidence indicates ocular changes in PD as promising biomarkers in the eye that can be potentially used for early diagnosis, to track disease progression, and to evaluate novel therapeutic strategies (Guo et al, 2018;Turcano et al, 2019;Veys et al, 2019). Although the specificity and predictive value of OCT and ERG changes in PD patients are still under debate, due to overlap with normal aging and other neurological and ophthalmological diseases, a better characterization of retinal dysfunctions during neurodegenerative diseases combined with imaging of protein aggregates may indeed represent a valuable approach for early diagnosis of PD.…”