Interocular Asymmetry of Foveal Thickness in Parkinson Disease

Purpose. To quantify interocular asymmetry (IA) of foveal thickness in Parkinson disease (PD) versus that of controls. Design. Prospective case-control series. Methods. In vivo assessment of foveal thickness of 46 eyes of 23 PD patients and 36 eyes of 18 control subjects was studied using spectral domain optical coherence tomography (SD-OCT). Inner versus outer layer retinal segmentation and macular volumes were quantified using the manufacturer's software, while foveal thickness was measured using the raw data from each eye in a grid covering a 6 by 6 mm area centered on the foveola in 0.25 mm steps. Thickness data were entered into MATLAB software. Results. Macular volumes differed significantly at the largest (Zone 3) diameter centered on the foveola (ETDRS protocol). By segmenting inner from outer layers, we found that the IA in PD is mostly due to changes on the slope of the foveal pit at the radial distances of 0.5 and 0.75 mm (1.5 mm and 1 mm diameter). Conclusions. About half of the PD patients had IA of the slope of the foveal pit. IA is a potentially useful marker of PD and is expected to be comparable across different SD-OCT equipment. Data of larger groups may be developed in future multicenter studies.

The first evidence of visual impairment in PD and its relationship to dopaminergic dysfunction was obtained by Bodis-Wollner and Yahr. 1 Utilizing Visual Evoked Potential (VEP) measurements they noted asymmetrical delay of the VEP obtained from the two eyes in PD. Subsequently Bodis-Wollner, Yahr and Thornton 2 reported the conjoint interocular statistical correlation of VEP abnormality with PD staging (H-Y).
A number of studies using the ERG identified impaired retinal ganglion cell processing as a reason for visual impairment in PD. 3,4,5,6,7,8 Most recently it was shown that nervefiber layer (NFL) thinning correlates with the multifocal ERG in PD and confirms an association with retinal ganglion cell processing, similar to defects seen in glaucoma. 9 However, an interocular, within-subjects comparison of retinal thickness was not considered quantitatively in any previous OCT study in PD.

Supplementary 2:
The retinal area of our measurements and OCT: Through SD-OCT, morphology felt to be closely representative of gross retinal histology can be measured, imaged and reproduced. 10 The fovea, is an area approximately 1.5 mm in radius. 11,12 The very center of the fovea is called the foveola. Ganglion cells and their axons (nerve fibers) and other inner retinal neuronal elements are pushed aside and are hence absent from the foveola. There are three major forward synapses before the ganglion cells in the innermost layer receive the signals of receptors.

Supplementary 4:
Effects of race, gender, age and axial length on the IA of the fovea.

Macular volume measures
A number of OCT studies considered changes in full-retinal thickness (FRT) as a result of age, gender, race and axial length but not all came to the same conclusions. El-Ashry et al. 15 quantified minimum foveal thickness (MFT), central 1 mm average foveal thickness (AFT) and total macular volume in 100 British healthy individuals. AFT was symmetrical between the eyes of each individual and there was no effect of age, gender or race on interocular differences. In 110 eyes of 57 subjects including Europeans and Afro-Caribbeans Tick et al. 16 reported a high degree of symmetry in all examined morphometric parameters (CFT, pit depth, pit diameter and MRT). We found no interocular asymmetry difference in our, partially overlapping measures of foveal architecture. Not all but a number of studies of slope, depth and rim of the fovea came to the conclusion, that blacks have thinner retina than Caucasians. 17,18,19 Race was not significant as a main effect in our study, however there were absolute differences and race nearly reached statistical significance. We believe therefore that it is worthy of further studies to examine whether race affects primarily ORL's, including Henle's fiber layer, Bruch's membrane and the RPE. Axial length correlates with pit diameter 15 however the causality is unclear except perhaps in patients with high myopia; thusly we excluded that condition from both the control and PD groups. There is no evidence that PD primarily changes the axial length of the eye, but as a result of foveal pit changes, axial length may potentially change in PD. This possibility requires further study. Age is not a primary variable in our study: there was insignificant age difference between the subjects. IO was not studied at discrete peri-foveolar distances and no previous information is available for the effects of age, race and gender. Our results show in PD there is a perifoveolar distance dependent effect on the inner neural layers of the foveal pit. Given the different cellular composition of various layers of the foveal retina, we do believe that quantifying the effect of these variables, segmenting across the inner and outer retinal layers and perifoveolar distances would be meaningful.