A new case study found a statistically significant decrease in retinal sensitivity with incomplete retinal pigment epithelium and outer retinal atrophy lesions in patients with intermediate age-related macular degeneration.

“There is an unmet need for prognostic biomarkers and clinical endpoints, approved by regulatory authorities, in early and intermediate age-related macular degeneration (iAMD),” researchers note in BMJ Open Ophthalmology. Spectral domain optical coherence tomography (SD-OCT) has identified incomplete retinal pigment epithelium and outer retinal atrophy (iRORA) lesions as precursors to geographic atrophy and disease progression, but “detailed knowledge of its impact on retinal function is very limited, yet essential for its validation as a potential clinical outcome measure.”

Because “conventional functional tests such as clinical-grade microperimetry (MP) are inadequate due to the discrepancy between available test stimuli sizes and the tiny iRORA lesion sizes,” adaptive optics scanning light ophthalmoscope microperimetry (AOSLO-MP) was used to evaluate retinal sensitivity. AOSLO-MP uses a high-resolution system to “facilitate functional sensitivity testing of small retinal areas down to the size of individual photoreceptors.” Researchers compared retinal sensitivity gauged with AOSLO-MP to sensitivity gauged with macular integrity assessment microperimetry (MAIA-MP), in areas with and without iRORA lesions, to determine how the lesions affect retinal function.

Four patients between the ages of 60 and 85 with large sub-retinal pigment epithelium drusen associated with iAMD were included in the analysis. They underwent routine ophthalmological examinations, including best-corrected visual acuity and SD-OCT. iRORA lesions were identified and graded. Retinal sensitivity was then assessed using both microperimetry methods. The study provided details on each patient’s morphology. 

Patient 1

AOSLO-MP: 9.4 dB retinal sensitivity threshold at the iRORA lesion vs. 34.7 dB at the control region

MAIA-MP: 4 dB corresponding retinal sensitivity difference

Patient 2

AOSLO-MP: 15.8 dB difference in retinal sensitivity between the iRORA lesion and control.

MAIA-MP: not completed

Patient 3

AOSLO-MP: 19.3 dB sensitivity loss between iRORA lesion and control region

MAIA-MP: 10 dB sensitivity loss

Patient 4

AOSLO-MP: not completed

MAIA-MP: 8 dB sensitivity loss between iRORA lesion and control

“When averaged across all four test eyes, the loss of sensitivity at the iRORA site relative to the control site was 20.1±4.8 dB for AOSLO-MP and 7.3±3.1 dB for MAIA-MP,” researchers note.

While further large-scale studies are necessary to validate the findings, AOSLO-MP’s magnitude provided a more precise assessment of retinal sensitivity loss compared to MAIA-MP in these cases. The researchers conclude that iRORA lesions could be surrogate markers for retinal dysfunction.