Imaging features that predict a treatment response in retinal vascular diseases

(Image Credit: AdobeStock/Jevgenij)

Varun Chaudhary, MD, FRCSC, addressed the big questions in treating patients with retinal vascular diseases: who will and will not respond to treatment and what clues are predictive on imaging, at the Retina 2024 meeting in Maui. He is professor and head of ophthalmology, at McMaster University, Chief of Ophthalmology, at Hamilton Regional Eye Institute, McMaster University, Medical Director, Retina Reading Center at McMaster University and Chair of the Retina Evidence Trials InterNational Alliance (RETINA) Study Group.

Ultrawide imaging has been most helpful in this regard, in that 82% of the retina can be visualized.

Chaudhary cited an exploratory univariable and multivariable analysis of several baseline factors predictive of proliferative diabetic retinopathy (PDR) and diabetic macular edema (DME) development.¹ In that study, the most clinically relevant finding was the increasing baseline retinal nonperfusion (RNP) seen on fluorescein angiography (FA), which was associated with increased risks of development of those 2 retinal diseases.

He recounted an earlier study² that showed that baseline macular leakage on FA was associated with a suboptimal clinical course with anti-vascular endothelial growth factor (VEGF) treatment, ie, 4 treatment-free intervalsof 4 months or longer within 2 years were not achievable.

Regarding RNP, a prognostication threshold of 118.3 disc areas had specificity of 84.9 for PDR.³

Treatment effects

A discussion of modifying RNP with treatment showed that anti-VEGF therapies had varying effects on the areas of retinal nonperfusion depending on the study, ranging from stability to positive to negative effects. A meta-analysis of RCT data conducted by Chaudhary and RETINA study group demonstrated a small but positive impact of anti-VEGF treatment on RNP progression compared to control. However, the evidence synthesis also highlighted that none of the studies included were powered to assess RNP as a primary outcome.

To help move the field forward, the MAGIC Trial was launched where Charles C Wykoff, MD, PhD, is the Principal Investigator and Chaudhary is a study team member. This phase-2, multi-center, open-label, randomized controlled trial, examined the change in the area of retinal perfusion over 96 weeks associated with intravitreal faricimab 2.0-mg injections (Vabysmo, Genentech). The trial is expected to complete recruitment early 2024.

Other biomarkers

These recently identified potential biomarkers include predominantly peripheral lesions (PPLs). An FA study concluded that PPLs were associated with greater risk of disease worsening over 4 years; the results suggested that ultra-widefield FA to evaluate the peripheral retina may improve the ability to predict disease worsening in eyes with non-proliferative DR.⁵

A thicker baseline central subfield thickness is associated with higher risk for developing foveal thinning/atrophy, but reductions may not improve vision.

DME morphology, another biomarker, has been visualized that included serous retinal detachments, cystoid macular edema, and diffuse retinal thickening using spectral-domain optical coherence tomography (SD-OCT).⁶

A few studies reported that baseline disorganization of the retinal inner layers is associated with worse vision at 12 months in DME treated with anti-VEGF and the Dexamethasone implant (Ozurdex, Allergan) and macular laser.⁷

Other biomarkers include a disrupted core outer segment tip (COST), ellipsoidal zone (EZ), external limiting membrane (ELM), hyperreflective foci (HRF).

Chaudhary and the RETINA study team shared results of their recent meta-analysis in which they were able to quantify the predictive value of all baseline OCT biomarkers in terms of final vision. The results demonstrate that out of 31 unique biomarker studies, some key biomarkers such as baseline DRIL, HRF, COST disruption, EZ/ELM disruption are predictive of worse final VA after treatment in DME. The presence of posterior vitreous detachment was the only biomarker that predicted visual benefit.

The take-aways from the presentation regarding imaging contributions are as follows.

• Using FA, RNP is fundamental to DR and associated with greater risk of progression, anti-VEGF treatment may alter progression of nonperfusion, increased leakage and PPLs are associated with greater risk of progression.
• Using SD-OCT, the baseline OCT biomarkers may provide insight into treatment response to different agents, and the first meta-analysis was performed to quantify the ability of baseline biomarkers to predict VA outcomes in DME undergoing treatment.

Finally, Chaudhary pointed out that the differential impact of pharmacotherapies on prognostic imaging features needs further evidence generation and may guide a personalized approached to DR management.

References:

1. Wykoff CC, Do DV, Goldberg Ra, et al. Ocular and systemic risk factors for disease worsening among patients with NPDR. Post hoc analysis of the PANORAMA Trial. Ophthalmology Retina. 2023:1-10.

2. Huang W-H, Lai C-C, Huang JC-C, et al. Foveal microvascular integrity association with anti-VEGF treatment response for diabetic macular edema. Invest Ophthalmol Vis Sci. 2021;62:41.

3. Nicholson L, Ramu J, Chan EW, et al. Retinal nonperfusion characteristics on ultra-widefield angiography in eyes with severe nonproliferative diabetic retinopathy and proliferative diabetic retinopathy. JAMA Ophthalmol. 2019;137:626-31.

4. Nanji K, Sarohia GS, Xie J, et al. Anti-vascular endothelial growth factor therapy and retinal non-prefusion in diabetic retinopathy: A meta-analysis of randomized trials. Acta Ophthalmol. 2023; doi: 10.1111/aos.15673

5. Marcus DM, Silva PS, Liu D, et al. Association of predominantly pe4ripheral lesion on ultra-widefield imaging and the risk of diabetic retinopathy worsening over time. JAMA Ophthalmol. 2022;140:946-954. doi:10.1001/jamaophthalmol.2022.3131

6. Szeto SK, Lai TY, Vujosevic S, et al.Optical coherence tomography in the management of diabetic macular oedema. Prog Retin Eye Res. 2023; doi: 10.1016/j.preteyeres.2023.101220

7. Sun JK, Lin MM, Lammer J, et al. Disorganization of the retinal inner layers as a predictor of visual acuity in eyes with center-involved diabetic macular edema. JAMA Ophthalmol. 2014;132:1309-16; doi: 10.1001/jamaophthalmol.2014.2350.