Unilateral nAMD Without Drusen in Other Eye: A Distinct Clinical Entity?

Patients with unilateral neovascular age-related macular degeneration (nAMD) are at high risk for the development of choroidal neovascularization in the fellow eye: the five-year incidence rate of this is 42%.

Factors that contribute to the development of nAMD in the fellow eye include the presence, number, location, and size of drusen, which many experts consider the precursors of advanced forms of AMD such as nAMD. Thus, unilateral nAMD without drusen in the fellow eye may be clinically distinct from nAMD with drusen in the fellow eye.

The characteristics and outcomes of the subgroup of unilateral nAMD patients with no drusen in the fellow eye, however, are poorly understood. To understand these characteristics and outcomes better, a Dutch and German team retrospectively reviewed the charts of 381 patients diagnosed with nAMD between January, 2010, and July, 2015, at Leiden University Medical Center in Leiden, the Netherlands.

As a result, they determined that 29 of these patients, or 8%, had nAMD in one eye without drusen in the fellow eye. This subgroup was treated with intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) agents, including aflibercept (Eylea/Regeneron), 2 mg, bevacizumab (Avastin/Roche), 1.25 mg, and ranibizumab (Lucentis/Roche), 0.5 mg.

The first-choice agent was bevacizumab, given monthly for three months. A switch in agent was considered if the response was insufficient a month after the third bevacizumab injection. In those with polypoidal choroidal vasculopathy, photodynamic therapy supplemented anti-VEGF injections.

The main outcome measures of the study were best-corrected visual acuity (BCVA), as determined by Early Treatment Diabetic Retinopathy Study (ETDRS) criteria, and change in central retinal thickness. The team measured both outcomes at baseline, at the first follow-up visit, and after 6, 12, and 24 months of follow up. However, only 17 of the 29 patients, or 59%, had a 24-month follow-up visit.

By the end of the study, the investigators determined that mean central retinal thickness had decreased from a baseline of 408 μm to 99 μm (P < 0.001). However, they found no statistically significant change in mean BCVA in the group as a whole during follow-up.

At the final follow-up visit, they determined that BCVA had remained stable or improved in 22 patients, or 76%; five patients, or 17%, gained 15 ETDRS letters or more, and seven patients, or 23%, lost five ETDRS letters or more.

By the last follow-up visit, the mean increase in BCVA in the group as a whole was 2.5 letters, which the investigators characterized as “relatively low” in comparison with that in a 2012 study and a 2015 study. Those studies found a statistically significant increase in BCVA of six to eight letters from the baseline value after 24 months of a pro re nata anti-VEGF regimen.

However, the Dutch and German team added that the mean number of injections and the significant decrease in central retinal thickness in their study were comparable to those found in one of the earlier studies. According to the team, this similarity suggests different prognoses in different AMD subgroups as well as the need for different treatment strategies to obtain a statistically significant improvement in BCVA.

“This study seems to point out that for a subgroup of nAMD patients the presence of drusen is not a prerequisite to develop nAMD,” concluded the investigators, adding that the pathophysiology of this form of nAMD may differ from that of drusen-associated AMD.

A report of the study, “Neovascular age-related macular degeneration without drusen in the fellow eye: clinical spectrum and therapeutic outcome,” was recently published online in Clinical Ophthalmology.

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