With advances in the treatment of age-related macular degeneration, consideration is being given to modifying the frequent dosing that is characteristic of the most recent innovation, the vascular endothelial growth factor inhibitors. The long-term results of this strategy warrant investigation.
Scott Cousins, MD, focused on the clinical treatments available to treat typical subfoveal choroidal neovascularization (CNV) and how the advances might modify treatment plans at the Current Concepts in Ophthalmology meeting here.
"Neovascular AMD is characterized by pathologic neovascularization under the retina. The driving force of neovascular AMD is angiogenesis, which is essentially the crosstalk between endothelial cells and a family of angiogenic growth factors, the most powerful of which is vascular endothelial growth factor (VEGF)," Dr. Cousins said.
"It is remarkable how the treatments have evolved over the past 7 years," he stated, when considering the progression of treatments beginning with photodynamic therapy (PDT).
PDT with verteporfin (Visudyne, Novartis Ophthalmics) was the first pharmacologic breakthrough in treating AMD; the initial administration resulted in an immediate total occlusion of the perfusion of the lesion. Evaluation, however, ultimately revealed that three to four applications were needed to achieve significant visual stability, compared with just observation, in patients with classic and predominantly classic lesions. Very few patients gained visual acuity (VA). The treatment burden and costs, however, both were acceptable to patients, Dr. Cousins noted.
VEGF inhibitors were the next big breakthrough. Pegaptanib (Macugen, OSI Eyetech/Pfizer) was the first agent introduced and was designed to bind one isoform of VEGF, namely, VEGF165. The VISION trial, a randomized prospective trial, compared sham injections and/or PDT (standard of care) with pegaptanib injections. The results confirmed the safety and efficacy of pegaptanib at a dose of 0.3 mg. Compared with standard of care, there was a statistically significant increase in the number of eyes that did not lose VA, and vision remained stable for 2 years. Treatments were well tolerated by patients.
"Intraocular injection of pegaptanib every 6 weeks for 2 years showed a significant stability in vision compared with usual care. However, the anatomic response was slow and incomplete," according to Dr. Cousins, and the treatment burden is high with frequent injections. The injections cost $1,000 per injection.
That technology was later followed by ranibizumab (Lucentis, Genentech), which blocked all five isoforms of VEGF. Ranibizumab, also administered intraocularly, was first evaluated to treat classic and predominantly classic lesions in the ANCHOR study and later minimally classic and occult lesions in the MARINA study.
"This is the drug that has caused most of the excitement over the last 2 years," he said.
The ANCHOR study, Dr. Cousins recounted, found that VA was stabilized (defined as less than a three-line loss of VA) in 96% of eyes, and 40% of eyes had a three-line improvement in vision and maintained that increase for 1 year.
"Another interesting finding in the study was the rate at which the eyes gained vision. The visual improvement occurs quickly, that is, within the first three doses of the drug," he said.
Results in the MARINA study were very similar (90% and 34%, respectively) over 2 years. Also, VA improvement occurred rapidly after three injections of the drug.