Choroidal neovascularization (CNV) patients with predominantly classic lesions may go on to develop fibrous scarring and subsequent rapid vision loss, a new study suggests. The investigation, published in Ophthalmology Retina, also found vision gains were achieved regardless of fibrosis status after 24 months of anti-VEGF treatment. Additionally, patients with extrafoveal fibrosis had the most significant visual gains by the study’s end.

Researchers examined the relationship between baseline CNV subtype and fibrosis development using HARBOR data that included 1,097 patients with wet AMD who were randomized to ranibizumab 0.5mg and 2mg injections for 24 months. The study also looked at associations among CNV subtype—predominantly classic, minimally classic or occult—fibrosis and best-corrected visual acuity (BCVA).

Using fluorescein angiography interpreted by three readers, the study clarified the presence of fibrosis if the median area of subretinal fibrous tissue or disciform scar was greater than zero and if there was any detectable fibrosis. The study also used red-free fundus photography to determine the fibrous locations, which were defined as not detected, any subfoveal, extrafoveal only or remote location only or not reported (other).

The investigation found the baseline distribution of CNV lesions was similar to findings in clinical practice, with 15.5% of patients having predominantly classic, 46.4% minimally classic and 38.1% occult CNV lesions. At month 24, a total of 513 patients had no detected fibrosis, 295 had any subfoveal fibrosis, 86 subjects had extrafoveal only fibrosis and 10 patients were found to have other fibrosis.

At two years, detectable fibrosis was found in 78.2%, 50.7% and 19.8% of patients with baseline predominantly classic, minimally classic and occult CNV lesions, respectively.

Patients achieved meaningful visual gains at months 12 and 24 regardless of the two-year status, the researchers noted. At month 12, patients who were later classified as having subfoveal fibrosis at month 24 gained 8.5 ETDRS letters compared with those with extrafoveal only fibrosis, who gained 16.7 letters. Patients with fibrosis not detected at two years gained 9.2 letters.

At month 24, patients with any subfoveal fibrosis gained 8.3 letters, those with extrafoveal only gained 14.5 letters and patients with fibrosis not detected at month 24 gained 8.2 letters. At both time points, visual gains in patients with any subfoveal fibrosis were no different from patients with undetected fibrosis.

Also of note: more patients with extrafoveal only fibrosis achieved gains of 15 or more letters compared with patients with any subfoveal fibrosis or fibrosis that wasn’t detected. This pattern was observed for all baseline lesion subtypes. Additionally, patients with fibrosis not detected at two years achieved similar visual gains from baseline over the course of the study compared with those who had any subfoveal fibrosis.

Also, more patients with predominantly classic CNV at baseline were classified as having any subfoveal (65.5%) vs. extrafoveal only (9.2%) fibrosis, which was consistent with real-world observations, the researchers noted. This trend also was observed in those with minimally classic and occult lesions (14.2% vs. 5.2%).

The findings may be beneficial in guiding treatment decisions in light of the possible development of new therapies that target subretinal fibrosis, the researchers noted in their paper.

Adrean SD, Morgenthien E, Ghanekar A, Ali FS. Subretinal fibrosis in HARBOR varies by choroidal neovascularization subtype. Ophthalmology Retina. February 27, 2020. [Epub ahead of print].