Severe Visual Loss in Neovascular AMD Common, Despite Anti-VEGF Treatments

AMD patients undergoing anti-VEGF injections require close monitoring for visual acuity loss.

Severe visual loss (SVL) of 15 early treatment diabetic retinopathy study (ETDRS) letters or more is common among patients who have undergone intravitreal treatments for neovascular age-related macular degeneration (nAMD), according to a study published in Retina. As it frequently occurs within 9 months of diagnosis and 2 months after the last injection, clinicians should closely follow patients at this time,  and institute a proactive regimen, researchers suggest. 

This retrospective, observational study included 1019 eyes that received intravitreal injections (IVI) for nAMD between December 2017 and March 2021 at the intravitreal injection center of the Azienda Ospedaliero-Universitaria Policlinico in Bari, Italy. 

The team found severe visual loss between 2 consecutive IVIs in 229 eyes (15.1%), of which 9 had SVL in both eyes, and 47 had multiple episodes of severe visual loss. The study also included 101 treatment naïve eyes (mean follow-up time, 133 weeks), and 128 eyes that had undergone at least 1 IVI administered elsewhere. 

A median of 6 (range 1-38) IVIs were performed before the occurrence of severe visual loss. Ranibizumab was injected in 52.8%, and aflibercept in 31.9% of the visits that preceded the vision loss. The median time lapse between the vision loss and the last injection was 8.8 weeks (range 3-109). In the treatment-naïve subgroup, the median interval between the first injection and visit with severe visual loss was 34.3 weeks (range 4-145 weeks).

The researchers found initial visual acuity (VA) declined from a mean of 59±17 to 35±19 ETDRS letters. It improved to 46±22 ETDRS letters at 3 months and remained stable at 6 months (P =.21). The drop in VA at 3 and 6 months was significant compared with the pre-dropped VA (P <.05). However, this visual loss was not statistically significant in a subgroup of patients with poor pre-dropped VA, which may be explained by a floor effect, according to the authors. 

Patients developing a sporadic letter loss (defined as a ≥15 letter loss followed by an improvement in the subsequent visit of more than 10 letters) had a worse mean VA at year two than patients without sporadic vision loss.

To find the reason for the drop in vision, the researchers searched for the onset or increase of different optical coherence tomography (OCT) biomarkers between the severe visual loss and the former visits. The OCT evaluation revealed several potential biomarkers including fibrosis (50.7%), intraretinal fluid (33.2%), subretinal fluid (25.3%), sub-retinal pigment epithelium (RPE) fluid (9.2%), subretinal hemorrhage (4.8%), subfoveal atrophy (10.9%), subretinal hyperreflective material (7.9%), RPE tear (4.8%), and ellipsoid zone band loss (4.4%). 

Mean central macular thickness (CMT) change between the pre-visit and the vision-loss visit was not statistically significant (42.7 μm; 95% CI, 24.7-60.6 μm). Eyes with no substantial change in CMT had better visual prognosis than those with an increase of more than 20% or a decrease of less than 5%.

The results of this report are in agreement with post hoc analyses, which showed that patients who experience sustained or sporadic severe visual loss have worse visual outcomes. Avoiding longer intervals between consecutive visits in the course of 8 weeks in the first year of treatment may prevent these SVL, according to the researchers.

“Patients developing a sporadic letter loss (defined as a ≥15 letter loss followed by an improvement in the subsequent visit of more than 10 letters) had a worse mean VA at year two than patients without sporadic vision loss,” the researchers report. “Therefore, sudden and severe letter loss between treatments could be crucial for the final visual outcome.”

The limitations of this study include its retrospective nature and the fact that patients who discontinued IVI were not included in the sample.


Grassi MO, Monteleone G, Pozharitskiy N, et al. Severe visual loss during anti-vegf intravitreal injections in neovascular age-related macular degeneration timing, prognosis and optical coherence tomography findings. Retina. Published online March 9, 2023.doi:10.1097/IAE.0000000000003774