Relative Ellipsoid Zone Reflectivity Decline May Indicate Macular Degeneration Progression

Macular degeneration with drusen
Macular degeneration, ophthalmoscope image. Numerous yellow drusen spots are seen on the retina, the light-sensitive membrane that lines the back of the eyeball. The macula is the area of the retina responsible for central vision, which is the sharpest. It is not known what causes macular degeneration, although old age, poor nutrition and overexposure to the ultraviolet radiation in sunlight have all been implicated. The main symptom is a loss of central vision, meaning reading and delicate tasks become difficult or impossible. Some distortion of peripheral vision may also occur. There is no effective treatment for this kind of degeneration.
The presence of reticular pseudodrusen was associated with a more rapid relative ellipsoid zone reflectivity decrease than drusen or pigmentary abnormality.

In patients with intermediate age-related macular degeneration (iAMD), the relative ellipsoid zone reflectivity (rEZR) declines more quickly when reticular pseudodrusen (RPD) are present and expanding, according to research published in Ophthalmology Retina. These findings indicate that rEZR may be a useful biomarker for AMD progression.

Researchers analyzed the rate of change of rEZR in the central 20° of the macula among patients with AMD and bilateral large drusen. They enrolled 280 eyes of 140 participants (77% women) from the sham treatment arm of the Laser Intervention in the Early Stages of AMD ( Identifier: NCT01790802) study. The team performed comprehensive eye exams including spectral-domain optical coherence tomography (SD-OCT) on all participants, every 6 months over the 3 year study duration. The primary outcome was to determine whether rEZR could serve as a biomarker for AMD progression .

Investigators note that 48 eyes developed late atrophic (n=40) or neovascular (n=8) AMD over the course of the study. They determined that EZ reflectivity decreased as age increased (β coefficient = -0.04 gray value per decade; P <.001). External limiting membrane (ELM) reflectivity was nearly constant with increasing age (β coefficient = 0.0003 gray value per decade; P =.317) and rEZR decreased with increased age (-8.4 arbitrary units (AU) per decade; P <.001).

The team notes an average -2.1 AU per year decline in rEZR (P <.001). Eyes with drusen and RPD at baseline had worse rEZR at baseline and quicker rEZR decline over time compared with eyes that did not have RPD at baseline, according to the report.

“If the decline of rEZR over time is independent of the physical impact of RPD the rEZR measure may be a useful biomarker of AMD progression and an outcome measure for novel interventions in the early stages of AMD,” according to the researchers. “This measure may be especially useful for evaluating new interventions that target the photoreceptor mitochondria or might have an impact on photoreceptor health.”

Study limitations include the potential impact of RPD lesions on rEZR measurements.

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.  


Thiele S, Wu Z, Isselmann B, Pfau M, Guymer RH, Luu CD. Natural history of the relative ellipsoid zone reflectivity in age-related macular degeneration. Ophthalmol Retina. Published online June 13, 2022. doi:10.1016/j.oret.2022.06.001