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Visual change possible after first response to ranibizumab in AMD eyes
Vision does not always parallel angiographic reactions, investigators found.
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Patients treated with ranibizumab for neovascular age-related macular degeneration may experience some visual fluctuation after the initial response, according to two physicians.
“One cannot always use month 4 visual acuity to advise our patients as to how they will do at the end of 2 years,” Seenu M. Hariprasad, MD, said at the American Society of Retina Specialists annual meeting. He presented 2-year results for a subgroup of patients treated with Lucentis (ranibizumab, Genentech) injections in the MARINA trial.
“Ranibizumab month 4 vision response from baseline was maintained over 24 months on average, but the key is that some patients who had an initial decrease in vision later gained some letters compared to baseline,” he said.
Lawrence S. Morse, MD, PhD, similarly presented 2-year results for a subgroup of ranibizumab-treated patients in the ANCHOR study.
In agreement with Dr. Hariprasad, Dr. Morse said, “Early response does not predict future response.”
“Some patients who lost visual acuity at 4 months after treatment responded later with continued monthly injections of ranibizumab,” he said.
MARINA subgroup study
The phase 3 MARINA trial evaluated outcomes for 716 neovascular AMD patients who were treated with monthly 0.3-mg ranibizumab injections, monthly 0.5-mg ranibizumab injections or monthly sham injections. Investigators found that patients who received ranibizumab tolerated the drug well and improved in vision.
“The visual acuity benefit of ranibizumab vs. sham was evident as early as 1 month and increased over time up to 12 months,” Dr. Hariprasad said.
“About 90% at the end of 2 years had vision stabilization with the [U.S. Food and Drug Administration]-approved [0.5-mg] dose of ranibizumab,” he said. “Furthermore, for the first time in history, greater than three lines of vision gain could be achieved up until 2 years in 33% of patients using the FDA-approved dose.”
Dr. Hariprasad and colleagues separated the 240 patients who received the 0.5-mg dose of ranibizumab into four groups: 48 patients (20%) who had gained 15 or more letters of vision at 4 months were assigned to group one; 131 patients (55%) who had gained one to 14 letters were assigned to group two; 53 patients (22%) who had lost zero to 14 letters were assigned to group three; and eight patients (3%) who had lost 15 or more letters were assigned to group four.
“What we see is that the change from baseline to month 4 really results in stabilization through 1 year and 2 years in all the four visual acuity subgroups. But keep in mind that this is an average. This does not represent individual patient variability,” Dr. Hariprasad said.
MARINA 2-year results
At 2 years, the investigators noted that some patients who had lost vision at month 4 gained up to 15 or more letters of visual acuity. Specifically, 23% of patients who had lost zero to 14 letters of vision at 4 months gained one to 14 letters, and 8% gained 15 or more letters.
Of patients who had originally lost 15 or more letters of vision, 13% gained one to 14 letters and 12% gained 15 or more letters.
“If we take the big line vision gainers, those who gained greater than 15 letters of vision, at the end of 2 years, about 2% of those patients actually turn around and lose greater than three lines of vision,” Dr. Hariprasad said.
“At the individual level, we may not always be able to infer visual acuity at the end of 2 years,” he said.
Dr. Hariprasad also noted that it may not be possible to predict visual acuity based on choroidal neovascularization area, lesion size or leakage. The total area of CNV and lesion size was stable across all four groups at 3, 12 and 24 months. Additionally, the reduction in leakage was consistent in all four groups at these time points.
“No apparent relationship was evident between early month 4 vision response and fluorescein angiographic responses over time in the area of choroidal neovascularization and the area of leakage,” Dr. Hariprasad said.
ANCHOR subgroup study
The phase 3 ANCHOR study compared outcomes for 423 neovascular AMD patients who were treated with monthly 0.3-mg ranibizumab injections with as-needed sham photodynamic therapy, monthly 0.5-mg
ranibizumab injections with as-needed sham PDT or quarterly PDT with Visudyne (verteporfin, Novartis/QLT) and monthly sham injections. Investigators, similar to the MARINA trial, found that patients treated with ranibizumab tolerated the drug and gained visual acuity, Dr. Morse said.
“The superiority of ranibizumab to PDT in visual acuity was evident by 1 month and increased over time to the 12-month point,” he said. “This was maintained for the 24 months of the study.”
The 139 patients who received the 0.5-mg dose of ranibizumab were divided into the same four groups as the ranibizumab-treated MARINA trial patients. Specifically, 45 patients (32%) who had gained 15 or more letters at 4 months were assigned to group one; 65 patients (47%) who had gained one to 14 letters were assigned to group two; 26 patients (19%) who had lost zero to 14 letters were assigned to group three; and three patients (2%) who had lost 15 or more letters were assigned to group four.
ANCHOR 2-year results
“Delayed responders and the gradual responders with continuous treatment with ranibizumab did achieve increasing visual acuity results,” Dr. Morse said.
At 2 years, 27% of patients who had originally lost zero to 14 letters of vision at 4 months gained one to 14 letters and 8% gained 15 or more letters.
Conversely, 2% of those who had gained 15 or more letters at 4 months lost 15 or more letters at 2 years; 5% of these patients lost one to 14 letters.
Dr. Morse and colleagues, similar to Dr. Hariprasad’s group, evaluated the time course of changes in the area of CNV and leakage and found no relationship between these factors and visual acuity.
“Visual acuity cannot be explained totally by the angiographic characteristics,” Dr. Morse said.
However, the ANCHOR investigators found that patients across the four subgroups differed in the total area of leakage at baseline.
“The poor response group and the non-response group had on average much larger baseline areas of leakage compared to the smaller lesions that were typical of the rapid responders,” Dr. Morse said.
For more information:
- Seenu M. Hariprasad, MD, can be reached at the Department of Ophthalmology and Visual Science, University of Chicago, 5841 S. Maryland Ave., MC 2114, Chicago, IL 60637; 773-795-1326; e-mail: retina@uchicago.edu. Dr. Hariprasad is a member of the Genentech speaker’s bureau.
- Lawrence S. Morse, MD, PhD, can be reached at the University of California-Davis Department of Ophthalmology & Vision Science, 4860 Y St., Suite 2400, Sacramento, CA 95817; 916-734-6603; e-mail: lsmorse@ucdavis.edu. Dr. Morse is a member of the Genentech medical advisory board and speaker’s bureau and has received research support from Genentech.
- Jessica Loughery is an OSN Staff Writer who covers all aspects of ophthalmology.