Disease applications for clinical optoretinography

Abstract

Purpose : Optoretinography (ORG) has revealed light-evoked changes in photoreceptor OS length. These are hypothetically driven by electrostatic/osmotic OS changes that accompany phototransduction. The ORG could thus be a biomarker of photoreceptor health. This study aimed to assess the feasibility of ORG measurements in patients with vision loss and quantify potential differences.

Methods : An OCT system [Vienola et al.,Optica, 2022] was used to image subjects after dark adaptation. Serial B-scans were obtained at 400 Hz over approximately 80 ms, with a 554 nm wavelength LED flash delivered to the retina after 40 ms. B-scans were used to compute OS phase velocities before and after the stimulus flash. One control (#16) and three patients were imaged: unexplained vision loss with an abnormal cone ERG (#27); an ABCA4 mutation with classic Stargardt maculopathy but normal ERG (#23); unexplained vision loss with anti-retinal antibodies, no cancer- or melanoma-associated retinopathy, and a missing B-wave on ERG (#28). This study approved by UC Davis IRB; follows the Declaration of Helsinki.

Results : The control subject #16 OS undergoes a rapid contraction after stimulus, then a slower elongation (Fig. 1b,1f), quantified by the parameters v_min (the most negative rate of OS length change) and v_20_40 (mean rate of elongation between 20 and 40 ms after stimulus onset), plotted below in 1i-j (blue). Figs 1d, 1h show the corresponding response of #27, which differs qualitatively. Panels 1i-j (red) suggest that v_min is similar but v_20_40 differs. Other differences were observed in #23 and #28. For other patients we imaged (not reported here), ORG signals were not detectable.

Conclusions : Feasibility of ORG in visually impaired patients was demonstrated. Moreover, distinct components of the ORG response appeared to be affected in patients. When no ORG signal was observable, we do not know if it was due to dysfunction or fixational noise or retinal disorganization. Future work includes developing methods to mitigate fixational eye movement phase noise and quantitative methods that do not depend on intact retinal structure.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.

 

Fig1:ORG responses from control and patient measurements. (a, e, c, g) depict B-scans from two eccentricities, annotated for ORG measurement locations. (b, d, f, h) show ORG responses; qualitative differences are visible between subjects. (i, j) show v_min and v_20_40 from both subjects. v_min is similar, while v_20_40 is lower in the patient.