In Treatment-Resistant AMD, Contrast Sensitivity Improved after Switch from Ranibizumab to Aflibercept


Higher log contrast sensitivity correlated with decrease in central retinal thickness.

Donald Nixon, MD

Switching ranibizumab-resistant patients with neovascular age-related macular degeneration (nAMD) to aflibercept (Eylea/Regeneron—Bayer) may improve outcomes, according to a recent study.

Led by Canadian researchers Donald Nixon, MD, FRCSC, DABO, (pictured) assistant professor of ophthalmology at the Northern Ontario School of Medicine, and Nicholas Flinn of Trimed Eye Center, the study also found that measuring contrast sensitivity can detect subtle functional changes in vision that visual acuity testing may miss.

Patients don’t always see things in the high contrast used on Snellen visual acuity charts, and common tasks like cooking, reading, or recognizing friends depend on several components of vision besides high-contrast visual acuity, like contrast sensitivity.

These considerations led Nixon and Flinn to use mean change in contrast sensitivity as the main outcome measure in their 12-week study of visual outcomes after switching treatment to aflibercept in 40 randomly selected ranibizumab-resistant nAMD patients (49 eyes). The mean age of the study’s patients at baseline was 80.2 ± 6.8 years (range, 68—93 years). 68% of patients were men.

To be included in the prospective, interventional study, patients had to show persistent retinal fluid during spectral-domain optical coherence tomography (SD-OCT) after having received at least 3 intravitreal injections of ranibizumab (Lucentis/Roche) in the previous 6 months (mean number of injections, 5.1). Once patients entered the study, the investigators switched their treatment to aflibercept 2 mg, once monthly. If both eyes of a single patient met the inclusion criteria, treatment was switched for both eyes, and data for both eyes were included in the study dataset.

The investigators used Pelli-Robson testing to measure contrast sensitivity at 1 month and converted this measurement to the logarithm of contrast sensitivity (log CS). Scores on this test of < 1.65 log units indicate impaired visual function, and a six-letter change in contrast sensitivity equates to a 15-letter (3-line) change in visual acuity.

In addition, the pair also measured best-corrected visual acuity and converted this measurement to the logarithm of the minimum angle of resolution (logMAR VA) by using standard methods. They also measured central retinal thickness (CRT) by using SD-OCT and scored visual function by using the National Eye Institute 25-item Visual Function Questionnaire.

In analyzing their data, investigators used a two-sided paired t-test to compare the means of continuous variables. As a result, they found that after 12 weeks, mean contrast sensitivity improved from 1.32 log units at baseline to 1.40 log units at study end (P < 0.05). Visual acuity remained stable throughout the study period; mean logMAR VA was 0.52 at baseline and 0.53 at study end. Visual function score improved in 65% of patients. Mean CRT decreased from 354 μm at baseline to 332 μm at study end (−22 μm, P < 0.05). And improvement in log CS correlated with change in CRT (P < 0.05).

As a result, the pair concluded that 12 weeks after the switch to aflibercept in these ranibizumab-resistant patients, contrast sensitivity improved and central retinal thickness decreased to a statistically significant degree compared with baseline values. In addition, they recommended using contrast sensitivity as an independent outcome end point in future nAMD studies to provide a more complete understanding of visual response to treatment.

A report on the study, “Evaluation of contrast sensitivity and other visual function outcomes in neovascular age-related macular degeneration patients after treatment switch to aflibercept from ranibizumab,” was published on April 18, 2017, in Clinical Ophthalmology.

Related Coverage:

Study Finds 25% of Patients with AMD Remain Undiagnosed After Dilated Eye Exam

Aflibercept Vs. Ranibizumab: Similar QOL Benefits, Varied Costs for Treating Diabetic Macular Edema

Machine Learning Could Change Understanding of AMD Progression, Severity

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