Consider PDGF treatment prior to anti-VEGF therapy

Take-home message: Patients with age-related macular degeneration patients who had received anti-platelet derived growth factor (PDGF) therapy prior to anti-VEGF treatment fared better than those who did not in a pilot study.

Reviewed by Pravin U. Dugel, MD

Pre-treatment with an anti-platelet-derived growth factor (PDGF) prior to anti-vascular endothelial growth factor (VEGF) therapy is being explored as a novel approach in a pilot study.

The treatment strategy led to better visual acuity in treatment-resistant neovascular age-related macular degeneration (AMD) patients after 18 months in a 24-month pilot study, said Pravin U. Dugel, MD.

Every time an anti-VEGF is injected, PDGF is upregulated, explained Dr. Dugel, managing partner, Retinal Consultants of Arizona, Phoenix, and clinical professor, USC Eye Institute, Keck School of Medicine, Los Angeles.

“This PDGF upregulation will allow for a protective armor of pericytes to cover the neovascular complex, making it more resistant to further anti-VEGF therapy,” Dr. Dugel said. “It makes sense to consider pre-treatment [with an anti-PDGF] to render the neovascular complex more sensitive and vulnerable to further VEGF therapy.”

This is what prompted the study done at Dr. Dugel’s practice, which involved 30 patients with AMD, 27 of whom were treatment-resistant and who had persistent or recurrent fluid and no improvement in visual acuity. The average patient age was 80 years old. Patients had an average of 25 prior injections, and the treatment interval was less than 6 weeks in almost 90% of patients.

Dr. Dugel previously reported a 6-month visual acuity improvement of 3.7 letters of vision for patients with no pre-treatment compared with 15.1 letters of vision for patients who did receive pre-treatment.

The 18-month results showed a mean improvement of 1.6 letters of vision for no pre-treatment compared with a mean of 20.3 letters of vision for the group that did receive a pre-treatment.

Multimodal imaging as predictor

Multimodal imaging as predictor

The best predictor of response was multimodal imaging, said Dr. Dugel, noting that patients were analyzed based on optical coherence tomography (OCT), fluorescein angiography, and optical coherence angiography. The patients that fared best tended to be dry by conventional OCT and had no leakage by fluorescein angiography, but they did show flow by optical coherence angiography.

“There appears to be an OCT and vision disconnect,” Dr. Dugel said.

Normalized vessels may be necessary for this wound-healing response after the pruning of immature vessels, and there may be a “Goldilocks” principle of flow-where neither too little nor too much is ideal.

“We do have a large structure and function disconnect,” Dr. Dugel said, “but we’re in the precipice of an imaging revolution that will bridge the disconnect and force us to reconsider our goals in patients with macular degeneration.”

Pravin U. Dugel, MD

E: pdugel@gmail.com

This article was adapted from Dr. Dugel’s presentation during Retina Subspecialty Day at the 2015 meeting of the American Academy of Ophthalmology. Dr. Dugel reports financial interest with Abbott Medical Optics, Acucela, Alcon Laboratories, Alimera Sciences, Allergan, Digisight, Genentech, Novartis, Ophthotech, Ora, Regeneron, and ThromboGenics.