Dissociation of Pupillary Post-Illumination Responses from Visual Function in Confirmed OPA1 c.983A > G and c.2708_2711delTTAG Autosomal Dominant Optic Atrophy

Abstract

Purpose: To test whether the melanopsin-containing, intrinsically photosensitive retinal ganglion cells (ipRGCs), as evaluated by examination of the pupillary light reflex (PLR), are preserved in genetically confirmed autosomal dominant optic atrophy (ADOA).

Method: Twenty-nine patients with either the c.983A > G (n = 14) or the c.2708_ 2711delTTAG mutation (n = 15) were examined with monochromatic pupillometry, using isoluminant (300 cd/m(2)), red (660 nm) or blue (470 nm) light, optical coherence tomography, automated visual field analysis, and with determination of best corrected visual acuity (BCVA). Since we examined two different mutations, initially we compared all outcome variables between the two, and finding no statistically significant difference, pooled them.

Results: Despite a poor BCVA (56 letters, ETDRS) in the ADOA patients, their post-illuminatory pupil responses did not differ significantly from those of healthy controls (blue, p = 0.45, red, p = 0.49, t-test), and no statistically significant effect was noted of peripapillary retinal nerve fiber layer thickness, ganglion cell-inner plexiform layer thickness, or age.

Conclusion: The PLR to blue light of high luminance (300 cd/m(2)) was preserved in both c.983A > G and c.2708_2711delTTAG ADOA despite severe visual loss and optic nerve atrophy. The study confirms, in a large sample of two genetically homogenous groups, that the ipRGCs are spared in ADOA.

Keywords: autosomal dominant optic atrophy; intrinsically photosensitive retinal ganglion cells; ipRGC; melanopsin; pupillary light reflex.

Figure 1

Pupillary contraction to a red light stimulus (660 nm) as a function of time (s). A constant and continuous stimulus of 300 cd/m² was applied at time 0 (first vertical gray line) and discontinued at the end of the 20th second (second vertical gray line). The stimulus was applied to one eye and the consensual, pupillary contraction of the other eye recorded. The red graph represents the mean of contractions set off by stimulation in ADOA eyes, and the black the mean of contractions set off by stimulation in control eyes. During light stimulation, contraction is larger in the red graph than in the black graph. When the light stimulus is terminated, fairly rapid re-dilatation ensues. No statistically significant difference is detected (cf. Table 2). The red graph shows the mean value from 29 subjects suffering from ADOA, the black graph the mean of 40 healthy control eyes. The AUC is the area between the horizontal line: NPD = 100% and the graph in question.

Figure 2

Pupillary contraction to a blue light stimulus (470 nm) as a function of time (s). Time period, stimulus luminance, and size of input pupil as in Figure 1. The light blue graph represents the mean of pupillary contractions set off by stimulation of the ADOA eyes, and the black graph the mean of contractions set off by stimulation in control eyes. In comparison with the graphs in Figure 1, contraction is larger during light on in both graphs, and post-light stimulus re-dilatation far slower than that due to red light. After light termination, the difference between the two graphs is negligible. Results represent mean values from 29 subjects suffering from ADOA and from 40 healthy controls.