Key Takeaways

  • In an exploratory analysis of 7 eyes, baseline DARC measurements showed a stronger association with future directional macular atrophy growth than 3 OCT-derived biomarkers
  • DARC signals were observed beyond existing areas of atrophy, supporting further study of the technology as a potential marker of cellular stress before structural loss becomes apparent

A retinal imaging approach designed to detect cellular stress and apoptosis may help identify where macular atrophy (MA) will progress in patients with age-related macular degeneration (AMD), according to a peer-reviewed study published in Expert Review of Ophthalmology.

The study evaluated UK-based Novai’s Detection of Apoptosing Retinal Cells (DARC) technology alongside established optical coherence tomography (OCT)-derived biomarkers. Investigators reported that baseline DARC measurements showed a significantly stronger association with the future direction of MA growth than ellipsoid zone (EZ) loss, EZ-retinal pigment epithelium (RPE) difference, and hyperreflective foci (HRF) density.

DARC combines a fluorescently labeled Annexin A5 probe with retinal imaging and image analysis to identify stressed and apoptotic retinal cells. The technology is intended to detect cellular changes before irreversible structural damage becomes evident with conventional imaging.

The exploratory analysis included 7 eyes selected from the phase 2 DARC study (ISRCTN10751859). Investigators evaluated subsequent MA growth using longitudinal retinal imaging over a mean follow-up of 48.4 months. DARC activity, EZ loss, EZ-RPE difference, and HRF density were assessed around the center of the MA lesion using an angular plot method designed to characterize the direction as well as the extent of atrophy expansion.

Across the 7 cases, DARC demonstrated a significantly stronger correlation with subsequent directional MA growth than EZ loss (P = .0191), EZ-RPE difference (P = .0267), and HRF density (P = .0252).

Investigators also observed DARC activity outside the visible boundaries of existing atrophy. According to the authors, the finding is consistent with DARC detecting retinal cellular stress and apoptosis before the corresponding structural damage becomes apparent on OCT.

The study also highlighted a potential limitation of HRF as an early predictive marker. HRF density could not be quantified at baseline in 3 eyes because atrophy was not yet present. For those eyes, HRF measurements were instead evaluated from the time atrophy developed. DARC measurements were available at baseline.

The authors emphasized the exploratory nature of the findings. The analysis was based on only 7 eyes and included a post hoc assessment of data collected during the earlier phase 2 study. They noted that larger studies and prospective validation will be needed to establish the clinical utility of DARC. The technology also detects cellular stress rather than a disease-specific biological process, which could affect its specificity.