Visual Acuity Maintained Long-Term with Pro Re Nata Regimen for nAMD, Study Finds


The study evaluated 10-year outcomes of anti-VEGF therapy using a PRN treatment regimen for eyes with neovascular AMD in real-world clinical practice.

Close-up of eyeball | Image Credit: Perchek Industries/Unsplash

Credit: Perchek Industries/Unsplash

Visual acuity can be maintained long-term with anti-vascular endothelial growth factor (VEGF) therapy using a pro re nata (PRN) treatment regimen for neovascular age-related macular degeneration (nAMD), according to new research.1

Outcomes from more than 50,000 intravitreal injections revealed gains in visual acuity were most beneficial in eyes with lower baseline visual acuity, while eyes were able to maintain visual acuity in the long term after sufficient adherence to the PRN regimen.

“Although visual acuity was maintained, the initial gain in visual acuity observed in our study was lower than that reported in clinical trials with fixed monthly treatment and/or monitoring,” wrote the investigative team, led by Hannele Uusitalo-Järvinen, MD, PhD, of the Tays Eye Centre at Tampere University. “However, the short-term visual outcome was in accordance with several previous real-life studies with a similar number of year intravitreal injections at year 1 and at year 2.”

Evidence is clear on the benefit of anti-VEGF therapy for nAMD, with pivotal randomized clinical trials showing visual acuity gains after fixed monthly ranibizumab and bevacizumab, and fixed bimonthly aflibercept.2 In real-world practice, however, fixed treatment regimens are linked to a substantial burden on patients and caregivers. More flexible treatment regimens, including PRN and treat-and-extend, were designed to reduce the number of potentially unnecessary injections and clinic visits, respectively.

Uusitalo-Järvinen and team indicated that regardless of the chosen treatment regimen, there are challenges in applying outcomes from an RCT into a real-world setting.1 This study described the 10-year outcomes of nAMD eyes treated with anti-VEGF intravitreal injections in routine clinical practice using a PRN regimen. Electronic medical records from the study site were searched for all patients with nAMD receiving intravitreal injections between January 2008 and December 2020.

Outcome measures consisted of the mean change in visual acuity from baseline, the proportion of eyes gaining ≥5 Early Treatment Diabetic Retinopathy Study (ETDRS) letters, and the proportion of eyes with stable vision, visual acuity ≥20/40 Snellen, and ≤20/200 Snellen. In addition, the analysis measured the number of annual visits and annual intravitreal injections for each treatment year.

Overall, a total of 3844 treatment-naive eyes of 3008 patients with nAMD were included in the study, with a baseline age of 80 years and 69% female patients. A total of 50,146 intravitreal injections were administered, mostly bevacizumab (87%) followed by aflibercept (12%) and ranibizumab (2%). The mean baseline visual acuity was 55 ETDRS letters.

After analysis, investigators found the mean change in visual acuity from baseline was +2, +2, ±0, –2, –2, and –4 ETDRS letters at years 1, 2, 3, 5, 7, and 10 of the study, respectively. The largest benefit in visual acuity change was observed in patients with low baseline visual acuity.

Analyses showed the proportion of eyes retaining stable vision within 15 letters of baseline was 88%, 87%, 82%, 80%, 76%, and 72% at the end of years 1, 2, 3, 5, 7, and 10 of the study, respectively. The proportion of eyes gaining ≥5 letters was 38%, 38%, 34%, 32%, 36%, and 37% at the end of years 1, 2, 3, 5, 7, and 10 of the study, respectively.

The number of annual intravitreal anti-VEGF injections was 6 injections through years 1–7 and 5 injections at year 10, while the frequency of annual non-injection visits during the first treatment year increased from 3 to 4.

Notably, Uusitalo-Järvinen and colleagues identified no statistically significant difference in visual acuity gains between eyes that received ≥10 injections and those that received <10 injections during the first treatment year, after adjusting for baseline visual acuity.

“This may suggest that some eyes gain visual acuity with less frequent injections while some eyes need more frequent injections,” investigators wrote. “Using PRN treatment regimen with frequent visits it is possible to find the eyes which need more frequent injections.”


  1. Hujanen P, Ruha H, Lehtonen E, et alTen-year real-world outcomes of antivascular endothelial growth factor therapy in neovascular age-related macular degeneration using pro re nata regimen BMJ Open Ophthalmology 2023;8:e001328. doi: 10.1136/bmjophth-2023-001328
  2. Comparison of Age-related Macular Degeneration Treatments Trials (CATT) Research Group, Martin DF, Maguire MG, et alRanibizumab and bevacizumab for treatment of neovascular age-related macular degeneration: 2-year results. Ophthalmology 2012;119:1388–98. doi:10.1016/j.ophtha.2012.03.053CrossRefPubMedGoogle
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