Ellipsoid Zone Integrity a Key Factor for VA in Eyes with nAMD Without Fluid

Justis Ehlers MD

New findings suggest ellipsoid zone integrity in eyes with neovascular age-related macular degeneration (nAMD) appeared to be a key driver for visual acuity outcomes in eyes without the presence of fluid.

Overall outcomes were best achieved in those eyes without fluid and ellipsoid zone integrity preservation, making it an important consideration for fluid tolerance in the management of the disease state.

“Achieving a dry retina with ellipsoid zone maintenance may provide the optimal outcome,” wrote lead study author Justis Ehlers MD, FASRS, Associate Professor, Cleveland Clinic Lerner College of Medicine.

The data were presented at the American Society of Retina Specialists 40th Annual Scientific Meeting.

The team of investigators, led by Ehlers, assessed the association of best corrected visual acuity (BCVA) with retinal fluid, exudative volatility, and ellipsoid zone integrity in eyes with nAMD, utilizing a machine learning-enhanced feature extraction system. They aimed to provide a next-generation, in-depth feature assessment to comprehensively characterize the relationship of fluid and visual acuity in patients with nAMD.

The reported data were from the treatment agnostic analysis of the Phase III HAWK nAMD clinical trial (n = 652). They measured fluidic compartment (intraretinal fluid [IRF] volume, subretinal fluid [SRF] volume) status and central subfield ellipsoid zone integrity (mean thickness from the ellipsoid zone to the retinal pigment epithelium [EZ-RPE]) using a machine learning-enhanced feature-extraction platform with manual verification.

Moreover, investigators defined ellipsoid zone integrity maintenance as EZ-RPE >20 µm and particular EZ attenuation as >0 µm to ≤20 µm. The total attenuation was defined as 0 µm.

Intraretinal fluid and subretinal fluid volatility were calculated as the volumetric standard deviation (SD) from Week 12 - 48 of the study. Using ETDRS letters, the BCVA was determined at Week 48 based on the presence or absence of fluid, underlying central subfield ellipsoid zone integrity, and retinal fluid volatility.

The results show the best BCVA outcomes were achieved in eyes without fluid and the maintenance of ellipsoid zone integrity (78 letters). Investigators noted this was significantly improved compared to eyes with subretinal fluid (68 letters; P <.0001).

In eyes without fluid, those with partial ellipsoid zone attenuation had a BCVA of 67 letters. Eyes with intraretinal fluid (61 letters) had lower BCVA compared to eyes without fluid (70 letters; P <.0001).  The worst visual acuity outcomes were observed in eyes without fluid with total ellipsoid zone attenuation (56 letters).

Further, among eyes with subretinal fluid, low volatility (SD ≤Q1) had greater BCVA than eyes with high volatility ([SD ≥Q3] 72 versus 63 letters; P = .04). There was no difference found between eyes with low and high intraretinal fluid volatility among eyes with intraretinal fluid (60 vs 58 letters, P = .58).

Ehlers noted that if subretinal fluid is persistent, a better understanding of the volatility of the subretinal fluid may be important due to the negative impact of high fluctuation on patient outcomes.

“Treatment approaches that minimize volatility should be considered,” he added.

The paper, “Higher Order OCT Feature Assessment of the Impact of Fluid Dynamics on Visual Acuity in Neovascular AMD in a Phase III Clinical Trial: The Importance of Outer Retinal Integrity,” was presented at ASRS 2022.