Retinal Vascular Structure Predicts Early Treatment Response in nAMD Eyes

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The structure of the retinal vasculature may be able to predict the initial treatment response to intravitreal therapy in patients with treatment-naïve nAMD.

A new prospective study suggests the potential for the retinal vascular structure to independently predict the initial response to intravitreal therapy in patients with treatment-naive neovascular age-related macular degeneration (nAMD).1

The analyses demonstrated a 9% higher risk of a suboptimal clinical response in those with a higher venular length-diameter ratio (LDR) and a tendency towards suboptimal response in eyes with a higher retinal arteriolar fractal dimension prior to treatment. Thus, these models of 2 retinal structural markers could explain approximately 20%-22% of clinical outcomes in eyes with nAMD.

“If the visual and functional prognosis of patients with nAMD can be categorized prior to initiation of treatment, it might be possible to provide a personalized treatment regimen tailored for the individual patient,” wrote the investigative team, led by Jakob Grauslund, PhD, Department of Ophthalmology, Odense University Hospital.1 “Hence, options like early post-loading observation or intensification of treatment might be considered in patients with a priori identified optimal and suboptimal responses, respectively.”

Intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) agents have shown strong efficacy and safety for nAMD, but the frequency of injections poses a substantial burden for patients and the health care system.2 The identification of non-invasive predictive factors may allow for precision in the monitoring and treatment of patients, although it is current unclear which factors predict good treatment response. Grauslund and colleagues hypothesized that the measurement of retinal vessel geometric variables may provide markers of underlying disease severity in nAMD.

For this analysis, the team sought to determine if non-invasive measurements of retinal vessel geometric variables prior to anti-VEGF injection were able to predict the initial clinical response in eyes with treatment-naive nAMD. A total of 58 eyes of 58 patients with treatment-naive nAMD were followed between October 2016 - January 2017 at the investigator’s hospital. All patients provided a full medical history and underwent dilated ophthalmoscopy; at baseline, optical coherence tomography (OCT) and fundus photography were collected; best-corrected visual acuity was measured according to the Early Treatment Diabetic Retinopathy Study (ETDRS) scale.

All patients received 3 monthly intravitreal injections with 2.0 mg aflibercept, and examinations were repeated 1 month after the last injections. Based on a patient’s BCVA, fundus photography, and OCT, a retinal expert categorized eyes as full treatment responders (FTR) or none/partial responders (N/PR). The analysis defined FTR as a loss of <5 ETDRS letters, no residual intra- or subretinal fluid, and no macular hemorrhage.

OF 54 eyes attending follow-up visits, 24 (44.4%) eyes were categorized as FTR and 30 (55.6%) were categorized as N/PR. Those with FTR were older (81.5 vs. 77 years; P = .04), had lower retinal arteriolar fractal dimension (1.21 vs. 1.24; P = .02), and venular LDR (7.3 vs. 15.9 units; P = .006), but did not differ with respect to other retinal vascular parameters.

A multiple logistic regression model adjusted for age, sex, smoking, and diabetes revealed a lower chance of FTR was predicted independently by a higher retinal venular LDR (odds ratio [OR], 0.91; 95% CI, 0.82 - 0.99; P = .03) and marginally by a higher retinal arteriolar fractal dimension (OR, 0.83; 95% CI, 0.68 - 1.00; P = .05). Investigators found no difference in BCVA between groups at follow-up (67 vs. 67 ETDRS letters, P = .82).

Between baseline and follow-up, data showed overall increments in the central retinal venular equivalent (+3.3µm; P = .001) and the arteriolar LDR (+1.0; P = .04), but did not differ significantly between patients with FTR and N/PR. No other overall or within-group differences in retinal vascular measurements after initial treatment were observed by investigators.

Investigators highlighted the inclusion of validated retinal structural measurements and the inclusion of a treatment-naive cohort as strengths of the study but noted the limited number of patients and the measurement of only the initial treatment response may have been limitations to clinical implementation.

“Hence, prior to clinical implementation, the results should be confirmed by long-term studies presenting precision and validity,” investigators wrote.1


  1. Leth-Møller Christensen K, Kristjansen DB, Vergmann AS, Torp TL, Peto T, Grauslund J. Retinal vascular structure independently predicts the initial treatment response in neovascular age-related macular degeneration [published online ahead of print, 2023 May 17]. Acta Ophthalmol. 2023;10.1111/aos.15709. doi:10.1111/aos.15709
  2. Finger, R.P., Daien, V., Eldem, B.M., Talks, J.S., Korobelnik, J.F., Mitchell, P. et al. (2020) Anti-vascular endothelial growth factor in neovascular age-related macular degeneration – a systematic review of the impact of anti-VEGF on patient outcomes and healthcare systems. BMC Ophthalmology, 20, 294.