Mesopic and Scotopic Threshold Sensitivity in Patients with Choroideremia: Relationship with Residual Fundus Autofluorescence Area

Abstract

Purpose: To evaluate retinal sensitivity threshold under mesopic and scotopic conditions in patients with choroideremia and correlate the results with residual fundus autofluorescence area.

Methods: 22 eyes of 11 choroideremia subjects with no detectable rod (DA 0.01) or cone (LA 3.0/30Hz) ERG responses were included. Subjects underwent mesopic testing using MAIA custom-grid (121 stimuli) microperimetry (Centervue; Padova, Italy) and scotopic testing using chromatic (white, blue, red) full-field stimulus threshold (FST; Diagnosys LLC). Fundus autofluorescence images (Sonomed Escalon, Inc.) were acquired with a modified fundus camera system (Sonomed Escalon, Inc.) and the area of residual fundus autofluorescence (FAF) in the posterior pole calculated using in-built software (OphthaVision^TM). Mean and maximum microperimetry sensitivity (dB) were correlated with FST (dB) and FAF area (mm²). Rod- and cone-mediation of visual perception was determined based on the difference between blue and red stimulus thresholds (Roman et al. 2005).

Results: Residual remaining FAF areas ranged from 1.34 to 13.19 mm² (mean±SD: 5.9±4.1 mm²). There was a strong correlation of FAF area with white FST threshold (r=-0.82; p<0.001), while no association was observed with maximum or average microperimetry sensitivity (r=0.25 and 0.19, respectively; p>0.1). Microperimetry maximum sensitivity showed a strong ceiling effect (skewness: 0.426; range: 24-28 dB) compared to FST (skewness: 0.005; range: 20.4, 52.5 dB). The majority of eyes (7/8) with residual FAF areas>5mm² demonstrated rod-mediated perception (blue-red difference>19.3dB). A FAF area<4mm² was associated with either cone (6/10) or rod-mediation (4/10). Mean and maximum microperimetry sensitivity values could not diffentiate between eyes with rod or cone-mediated perception.

Conclusions: For the range of FAF area tested, microperimetry mesopic testing showed a strong ceiling effect in terms of average and maximum sensitivity. Progression of RPE degeneration in this choroideremia cohort could be accurately followed by change in scotopic FST threshold. FST allowed quantification of residual rod function in subjects with severe RPE loss. Determining rod or cone mediation of perception in these patients may allow better classification and patient selection for future gene therapy clinical trials.