Dry eye patients with severely reduced nerve fiber density at the level of neurotrophic keratitis, present with signs and symptoms similar to conventional dry eye patients

Abstract

Purpose : Studies on patients with dry eye disease (DED) have demonstrated decreased nerve density via in vivo confocal microscopy (IVCM). However, this reduced nerve fiber density is also present in patients with neurotrophic keratitis (NK) who traditionally lack symptoms. Herein we aim to compare DED patients with reduced nerve fiber density traditionally seen in NK to conventional DED patients.

Methods : This retrospective cross-sectional study investigated patients who had signs and symptoms of DED. IVCM images were analyzed for total nerve density (TND) of three images using ImageJ/NeuronJ. Those with 7,457 µm/mm² or less TND (based on patients with NK+1 SD) were grouped into the very low nerve density group (VLND-DED) while the others were grouped into a DED group. IVCM images were also analyzed for dendritiform cell (DCs) density, DC size, and number of DC dendrites. IVCM data as well as clinical data were compared between the groups.

Results : The age and sex distribution of patients in the VLND-DED group (n=33; 59.1±3.5 yrs; 75.0% female) was not different from that of the DED group (n=202; 58.0±1.2, p=0.738; 78.7% female, p=0.636). The average TND was 4,493.42±341.79 µm/mm² for the VLND-DED group and 14,906.53±268.21 for the DED group. The DC density in the VLND-DED group (med: 58.33 cells/mm² [IQR:98.96]) was not significantly different from that of the DED group (med: 35.42 [IQR:66.67]; p=0.099). However, the DC size and number DC dendrites were significantly higher in the VLND-DED group (med: 135.63 µm² [IQR:87.0] and med: 0.8/IC [IQR:1.4] respectively) compared to the DED group (med: 84.53 [IQR:55.91], p<0.001 and med: 0.4/IC [IQR:0.87], p=0.007, respectively). Aggravation of symptoms by dry environments (OSDI question 11) was lower in the VLND-DED group (med: 1.0 [IQR:3.0]) compared to those in the DED group (med: 3.0 [IQR:3]; p=0.022). No other symptoms or signs were significantly different between the groups. There was also a higher proportion of patients who reported ocular surgery in the VLND-DED group (72.7%) compared to the DED group (42.6%, p=0.001).

Conclusions : DED patients with significant neve compromise at NK levels can show signs and symptoms similar to conventional DED patients, and may be patient with NK stage 0. Interestingly, thest patients have more mature DCs, a sign of chronic inflammation.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.