Pupillographic findings in chronic progressive external ophthalmoplegia

Background: Chronic progressive external ophthalmoplegia (CPEO) as a mitochondrial disease entity is characterized by slowly progressive ocular immobility and ptosis and may be associated with other neurological or systemic symptoms (CPEOplus). Pupil involvement is usually not reported to be a feature of CPEO. However, systematic data on pupillary function in CPEO does not exist to date. We aimed to characterize the pattern of pupillary function in a clinically homogeneous series of genetically proven CPEO patients.

Methods: Infrared video pupillography was performed in 15 CPEOplus patients and 22 age- and sex-matched controls. 11 patients harbored single and one patient multiple mitochondrial (mt) DNA deletions, and 3 patients mtDNA point mutations at positions A3243G and G5835A, respectively. We determined diameter (PD), early and late redilation velocities (DV) as sympathetic parameters, relative reflex amplitude (RA) and constriction velocity (CV) as parasympathetic parameters, and the pupillary unrest index (PUI) as a measure of vigilance. In addition, the relative difference of pupil diameters between darkness and after light adaptation (DPD) was measured.

Results: Mean age at examination was 49.9±15.8yrs in CPEO (6 male; 9 female) and 49.3±14.3yrs in controls (9 male; 13 female). Age of disease onset was 30.6±15.7yrs and mean disease duration 19.4±13.8yrs. Early and late DV (1.40±0.36 vs. 1.09±0.23mm/s, p<0.01; and 0.58±0.12 vs. 0.42±0.12mm/s, p<0.001), RA (20.8±4.8 vs. 16.3±3.7%, p<0.01), CV (4.4±0.9 vs. 3.7±0.6mm/s, p<0.01), and PUI (7.4±2.6 vs. 4.7±2.6mm/min, p<0.01) were significantly higher in CPEO compared to controls. No difference in PD (6.6±1.1 vs. 6.7±1.0mm) was found, whereas DPD (-16.1±5.6 vs. -10.9±5.7%, p<0.05) was significantly higher in CPEO patients.

Conclusions: Our results suggest a sympathetic and parasympathetic hyperactivity as signs of autonomic dysfunction in CPEO, whereas vigilance seems to be reduced and light adaptation restricted. Alternatively, increased DV, CV, and RA might be due to stroma abnormalities of the iris with reduced matrix resistance. Formerly, atrophy of the iris stroma has been reported as one sign of widespread ocular pathology in a single autopsy case of MELAS syndrome due to the A3243G mutation.