Study Finds Several Poor Prognostic Indicators in Patients with Neovascular Age-Related Macular Degeneration Switched from Lucentis to Fixed-Dose Eylea

Patients with neovascular age-related macular degeneration have shown a suboptimal response to ranibizumab over time. Several studies have established that switching from ranibizumab to aflibercept enhanced visual acuity and resulted in anatomic improvement in many of these patients, but the factors determining visual outcomes remained unclear.

Many patients with neovascular age-related macular degeneration (nAMD) have shown a suboptimal response to ranibizumab (Lucentis, Novartis) over time. Several studies have established that switching from ranibizumab to aflibercept (Eylea, Bayer HealthCare/ Regeneron) enhanced visual acuity and resulted in anatomic improvement in many of these patients, but the factors determining visual outcomes remained unclear.

Several factors present at the point of switching that predict a poor outcome in these patients were recently identified in a retrospective interventional British study published in Ophthalmology. These indicators of poor prognosis include:

  • Increasing age
  • Increasing central subfield thickness
  • Presence of intraretinal fluid
  • Pigment epithelial detachment
  • Subfoveal thickening

In addition, the study showed that, although switching to Eylea reduced central subfield thickness significantly and seemed to promote retinal dehydration, it did not improve visual acuity in the group of nAMD patients that were evaluated.

The study investigators reviewed the records of 431 consecutive nAMD patients who were switched from intravitreal Lucentis, pro re nata, to fixed injections of Eylea every 8 weeks (without a loading phase of three injections) at Moorfields Eye Hospital in London from November, 2013, to October, 2014. All patients completed at least 12 months of follow-up, and the mean number of Eylea injections given at month 12 was 6.8 ± 1.75.

To determine the prognostic indicators of final visual outcome 12 months after switching, the study investigators evaluated demographic data, visual acuity, and spectral-domain optical coherence tomography characteristics over time. Their evaluations revealed that central subfield thickness decreased significantly (P < 0.001) during the study. Moreover, at 12-month follow-up, 48.3% of eyes had no macular fluid, compared with 8.5% at baseline. However, no significant difference was found in visual acuity between baseline and month 12 (P = 0.79) in the 447 eyes studied.

According to the investigators, the principal message of the study was that nAMD patients switched from as-needed Lucentis to Eylea every 8 weeks without a loading phase showed anatomic improvement after 12 months without significant visual benefit. They attributed this anatomic improvement to Eylea’s superior binding affinity to vascular endothelial growth factor (VEGF) compared with that of Lucentis. They also noted that, unlike Lucentis, Eylea binds to VEGF-B and placental growth factor, and this difference may also have contributed to the improvement. However, they acknowledged that tachyphylaxis to Lucentis may also explain the anatomic improvement they found, although the average timing of the switch between anti-VEGF agents seemed inadequate to promote tachyphylaxis to Lucentis in the study patients.