Diplopia Is Frequent and Associated with Motor and Non-Motor Severity in Parkinson’s Disease: Results from the COPPADIS Cohort at 2-Year Follow-Up

Abstract

Background and objective: Diplopia is relatively common in Parkinson’s disease (PD) but is still understudied. Our aim was to analyze the frequency of diplopia in PD patients from a multicenter Spanish cohort, to compare the frequency with a control group, and to identify factors associated with it. Patients and Methods: PD patients who were recruited from January 2016 to November 2017 (baseline visit; V0) and evaluated again at a 2-year ± 30 days follow-up (V2) from 35 centers of Spain from the COPPADIS cohort were included in this longitudinal prospective study. The patients and controls were classified as “with diplopia” or “without diplopia” according to item 15 of the Non-Motor Symptoms Scale (NMSS) at V0, V1 (1-year ± 15 days), and V2 for the patients and at V0 and V2 for the controls. Results: The frequency of diplopia in the PD patients was 13.6% (94/691) at V0 (1.9% in controls [4/206]; p < 0.0001), 14.2% (86/604) at V1, and 17.1% (86/502) at V2 (0.8% in controls [1/124]; p < 0.0001), with a period prevalence of 24.9% (120/481). Visual hallucinations at any visit from V0 to V2 (OR = 2.264; 95%CI, 1.269–4.039; p = 0.006), a higher score on the NMSS at V0 (OR = 1.009; 95%CI, 1.012–1.024; p = 0.015), and a greater increase from V0 to V2 on the Unified Parkinson’s Disease Rating Scale–III (OR = 1.039; 95%CI, 1.023–1.083; p < 0.0001) and Neuropsychiatric Inventory (OR = 1.028; 95%CI, 1.001–1.057; p = 0.049) scores were independent factors associated with diplopia (R2 = 0.25; Hosmer and Lemeshow test, p = 0.716). Conclusions: Diplopia represents a frequent symptom in PD patients and is associated with motor and non-motor severity.

Diplopia in Movement Disorders: A Systematic Review of the Literature

“…The rest of the articles were manually screened by the authors in order to meet the eligibility criteria. In the end, a total of seventeen articles remained: nine were observational cross-sectional studies [ 3 , 4 , 6 , 7 , 8 , 9 , 10 , 11 , 12 ], two were prospective cohort studies [ 13 , 14 ], two were retrospective studies [ 15 , 16 ] and four were case reports [ 17 , 18 , 19 , 20 ]. Table 1 shows detailed information about the included studies on diplopia in Parkinson’s disease.…”

“…One study compared patients with PD, PD dementia, and healthy controls [ 11 ], two studies compared PD patients with diplopia, PD patients without diplopia, and healthy controls (HC) [ 12 , 13 ], four studies examined patients with PD compared to healthy controls [ 4 , 10 , 13 , 14 ], six studies examined PD patients with and without diplopia [ 3 , 6 , 7 , 8 , 15 , 16 ], and four were case reports of PD patients with diplopia [ 17 , 18 , 19 , 20 ].…”

“…Mechanisms of diplopia are heterogenous and include convergence insufficiency [ 6 , 15 , 17 ], strabismus, ocular pathology as well as other mechanisms related to motor fluctuations [ 18 ], the presence of visual hallucinations [ 3 , 4 , 6 , 7 , 8 , 12 , 13 ], and the treatment of Parkinson’s disease [ 8 , 19 , 20 ].…”

“…Nebe et al reported that nine out of fourteen patients with selective diplopia had visual hallucinations while three more patients developed visual hallucinations in the following 3 years from the onset of diplopia [ 8 ]. Visual hallucinations were present in 45.7% vs. 9.4% of patients with PD and diplopia compared to those without diplopia at the first visit and in 53.5% vs. 13% at the third visit, in a 2-year follow-up study by Santos García D. et al [ 13 ]. A total of 19.2% of PD patients with diplopia reported the co-occurrence of diplopia with visual hallucinations [ 6 ] while nine patients reported diplopia as a type of visual illusion in a study by Sasaki C. et al [ 7 ].…”

“…Patients with diplopia frequently complain of visual disorientation and difficulties with daily activities such as walking and reading [ 50 ]. Patients with PD and diplopia had worse motor and non-motor status as well as a higher dependency on activities of daily living (ADL) compared to those without diplopia [ 13 ]. Hamedani A.L.…”