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Ranibizumab effectively managed pigment epithelial detachments in patients with wet age-related macular degeneration regardless of size at baseline.
Take-Home Message: Ranibizumab effectively managed pigment epithelial detachments in patients with wet age-related macular degeneration regardless of size at baseline.
By Lynda Charters; Reviewed by Nikolas J. London, MD
La Jolla, CA-Pigment epithelial detachments (PEDs) are a common and striking feature of age-related macular degeneration (AMD), said Nikolas J. London, MD.
“These detachments can be the first sign that we see on optical coherence tomography during the initial evaluation of a patient with AMD, and what patients can fixate on during treatment,” said Dr. London, who is in private practice, La Jolla, CA.
The efficacy of ranibizumab 0.5 and 2 mg (Lucentis, Genentech) in treating PED associated with wet AMD was demonstrated in a HARBOR Study subgroup analysis.
More than 50% of patients had complete resolution of PED at the 24-month evaluation; the PED size at baseline did not prevent excellent functional and visual outcomes; and the 2-mg dose of ranibizumab did not produce significantly better results compared with the 0.5-mg dose in these patients, Dr. London recounted.
PEDs also vary in their responses to treatment with ranibizumab, he noted.
“Some respond beautifully to treatment, and some are stubborn [and] remain unchanged,” he said.
What is unknown is whether PEDs should be targeted as an outcome measure, added Dr. London, who argued that they should not.
Dr. London discussed the HARBOR Study subgroup analysis on behalf of the study authors.
This clinical trial was a phase III evaluation of treatment-naïve subfoveal wet AMD in 1,007 patients. Two doses of ranibizumab were evaluated, 0.5 and 2 mg, and administered monthly or as needed following three monthly loading doses.
Patients were randomly assigned evenly among the four treatment groups. They were examined monthly for 24 months, with measurement of primary endpoints at 12 months and secondary endpoints at 24 months.
“An important factor in the as-needed arms was the presence of PED was a reason to administer another ranibizumab injection,” said Dr. London, adding that this is different from prior studies.
In his discussion of treatment efficacy, Dr. London focused on the 0.5-mg dose since the higher dose did not provide additional benefit in the HARBOR Study and is not the FDA-approved dose.
More than one-half of patients, 598 (54.5%), had a PED at the baseline. Investigators looked at the reduction in the thickness of the PED as a result of treatment with ranibizumab over the 24 months of the study.
“We saw a reduction in thickness of the PEDs of [more than] 50% in both the monthly and as-needed treatment groups,” Dr. London said. “About half of all patients had complete resolution of the PED by the 24-month time point. This response was a bit more robust in the patients who received monthly injections compared with the patients who received as-needed treatment (55.5% versus 46.8%. respectively).”
Along with the reduction in PED size, visual acuity levels improved significantly in all treatment groups regardless of the presence or absence of PED at baseline.
HARBOR Study investigators questioned whether PED size was a factor in the study outcomes, and the study population gave the investigators an opportunity to consider a wide range of sizes-i.e., from 35 to almost 1,400 µm in height.
To address this question, PEDs were divided into four quartiles: small, medium, large, and extra-large, with the following respective measurements: 35 to 164 µm; 164.5 to 233 µm; 233.25 to 351 µm, and 352 to 1,395.5 µm.
The groups were analyzed to identify any differences in the outcomes.
The authors found that vision improved with ranibizumab regardless of the size of the PED at baseline across all four quartiles.
“Interestingly, the group with extra-large PEDs treated with either monthly or as-needed injections had the poorest gains in visual acuity in the study,” Dr. London said. “However, none of the differences in the gains among the four groups of PEDs based on size reached statistical significance. PED size did not appear to be correlated with visual acuity outcomes.”
Regarding treatment burden, patients in the as-needed, 0.5-mg group received a similar number of injections regardless of PED size. Dr. London noted a trend for more injections in the quartile with larger PEDs, but the presence of a PED was the reason for re-treatment.
When investigators looked at the 2-mg dose, they saw some additional reductions in PED thickness. However, those reductions were not statistically significant compared with the lower 0.5-mg dose. There was also no additional gain in vision with the higher dose despite slightly increased fluid reduction.
The take-home points from this subgroup analysis of patients with AMD with PED treated with ranibizumab were:
“These findings are consistent with most of our treatment regimens, at least with my regimens,” he said. “I treat the fluid in my patients with AMD and not the PED.
“Treating the PED may expose patients more to the medication, which might increase the overall risk to the patients,” Dr. London concluded.
Nikolas J. London, MD
This article was adapted from Dr. London’s presentation at the 2014 meeting of the American Academy of Ophthalmology. Dr. London is a consultant to Genentech.