Pupillary responses in non-proliferative diabetic retinopathy

Abstract

The goal of this study was to determine the extent of rod-, cone-, and melanopsin-mediated pupillary light reflex (PLR) abnormalities in diabetic patients who have non-proliferative diabetic retinopathy (NPDR). Fifty diabetic subjects who have different stages of NPDR and 25 age-equivalent, non-diabetic controls participated. PLRs were measured in response to full-field, brief-flash stimuli under conditions that target the rod, cone, and intrinsically-photosensitive (melanopsin) retinal ganglion cell pathways. Pupil responses were compared among the subjects groups using age-corrected linear mixed models. Compared to control, the mean baseline pupil diameters were significantly smaller for all patient groups in the dark (all p < 0.001) and for the moderate-severe NPDR group in the light (p = 0.003). Pairwise comparisons indicated: (1) the mean melanopsin-mediated PLR was significantly reduced in the mild and moderate-severe groups (both p < 0.001); (2) the mean cone-mediated PLR was reduced significantly in the moderate-severe group (p = 0.008); (3) no significant differences in the mean rod-mediated responses. The data indicate abnormalities in NPDR patients under conditions that separately assess pupil function driven by different photoreceptor classes. The results provide evidence for compromised neural function in these patients and provide a promising approach for quantifying their neural abnormalities.

Figure 1. Mean waveforms obtained under the melanopsin (top left), rod (lower left), and cone (lower right) paradigms stratified by subject group.

The upper right panel shows responses measured with a long wavelength flash (450 cd/m²) presented in the dark, for comparison to the melanopsin-mediated condition. The long wavelength 450 cd/m² flash is not typically included in the standard set of conditions (rod, cone, melanopsin) and data from this condition will not be considered further. The red traces represent the mean waveform for the moderate-severe NPDR group, the green traces represent the mean waveform for the mild NPDR group, the blue traces represent the mean waveform for the no NPDR group, and the black traces represent the mean waveform for the control group. The vertical dashed lines in the top panels indicate the range over which the melanopsin-mediated (sustained) amplitude was measured. The stimulus onset and offset are represented by the boxes along the x-axes.

Figure 2. Steady-state (baseline) pupil diameters for each subject measured under dark-adapted (top) and light-adapted (bottom) conditions.

The horizontal line represents the mean for each group and the gray region represents the 5^th to 95^th percentile of each group. Significant differences from the control group are indicated by the symbols above the groups.

Figure 3. Relative PLR amplitudes obtained under the melanopsin (top), rod (middle), and cone (bottom) paradigms.

The horizontal solid line represents the mean for each group and the gray region represents the 5^th to 95^th percentile of each group. Significant differences from the control group are indicated by the symbols above the groups and the horizontal dashed lines represent the noise level.