Erythropoietin appears effective in stabilizing dry AMD

October 1, 2015

The neuroprotective effects of intraocular treatment with erythropoietin in the reduction of geographic atrophy progression and vision loss were reviewed in an off-label study.

 

Take-home message: The neuroprotective effects of intraocular treatment with erythropoietin in the reduction of geographic atrophy progression and vision loss were reviewed in an off-label study.

 

 

By Laird Harrison; Reviewed by Stephen H. Sinclair, MD

Philadelphia-Erythropoietin can significantly slow geographic atrophy progression and vision loss in eyes with age-related macular degeneration (AMD), according to Stephen H. Sinclair, MD.

“A major percentage of my patients show virtually no progression at all,” said Dr. Sinclair, adjunct professor of ophthalmology, Drexel University School of Medicine, Philadelphia.

The findings could help clinicians address a condition that has so far defied treatment, he said.

The research stems from Dr. Sinclair’s long-term interest in erythropoietin-a drug normally used to treat anemia-as an intravitreal treatment for the microvascular and neuronal deterioration that occurs with diabetic retinopathy.

According to his investigations, erythropoietin functions as an endogenous retinal survival factor. The agent inhibits vascular endothelial growth factor (VEGF) production and interleukins 1 and 6, and confers some neuroprotection, he said.

The drug has no apparent intraocular toxicity and does not cause angiogenesis intraocular or leakage systemically from the eye, he added.

Dr. Sinclair’s research in diabetic retinopathy patients appears promising.

“I published a paper on an early phase I trial in a small series of patients who had failed everything-surgery, laser, anti-VEGF, and steroids-showing that this significantly turned the retinopathy around and improved the vision,” he said.

The hope is that a pharmaceutical company may be found that is interested in pursuing the diabetic retinopathy work further, he noted.

In the meantime, Dr. Sinclair wondered how patients with geographic atrophy secondary to AMD would respond to the treatment. In an additional series, he has offered patients with this condition the off-label application of erythropoietin (Procrit, Johnson & Johnson) as compassionate use.

Dr. Sinclair and his colleagues treated 32 eyes in 28 patients with 5 international units, compounded for intravitreal injections at 6-week intervals, and compared them with 21 fellow eyes demonstrating similar geographic atrophic degeneration, and followed the vision and atrophy changes for a minimum of 1 year (average 1.46 years).

They used Dr. Sinclair’s invention (Omnifield device, Sinclair Technologies) that measures acuity at fixation and at 24 intercepts across the central 20° diameter visual field.

During treatment, the thresholded acuity at fixation improved by an average of 0.09 LogMAR in the treated eye and worsened by 0.08 LogMAR in the fellow eye.

The best acuity determined at any intercept within 6° of fixation (the central functional field of view) improved by an average of 0.05 LogMAR in the treated eye and worsened by 0.06 LogMAR in the fellow eye.

The global macular acuity (the weighted average of acuities within 10° of fixation) improved by an average of 0.11 LogMAR, while in the fellow eyes they worsened by 0.12 LogMAR. The difference was statistically significant (p = 0.013.)

“This is very significant,” Dr. Sinclair sai. “Epo is not just stopping neuronal death, but we’re getting some regeneration in the areas that are not dead from the progressive atrophy.”

Among the untreated eyes, none gained 0.3 LogMar, but among the treated eyes 32% gained that much acuity.

“That’s equivalent to ranibizumab [Lucentis, Genentech] in wet AMD in terms of vision improvement,” Dr. Sinclair said. “Several patients have pleaded for me to treat their other eyes.”

But the treatment did not work on everyone. Five percent of those treated lost 0.3 LogMar.

“So, what I try to point out here is, there is a lot of variability,” he said.

The optical coherence tomography and fluorescein angiography findings also showed important differences.

At baseline, the area of geographic atrophy was growing at a rate of 2.52 mm2 per year in all the eyes. After treatment, the geographic atrophy enlargement rate was reduced to 1.76 mm2 per year in the treated eyes, while the fellow eyes continued at a rate of 2.56 mm2.

More significant than the total area of atrophy, in Dr. Sinclair’s opinion, is the location of the atrophy with regard to the fovea.

“Since most areas of geographic atrophy start parafoveal and extend through the fovea over time, what you would to know are the characteristics that predict the progression of the edges that are closest to the fovea,” he said.

By this measure, the treated eyes also fared better. Dr. Sinclair has also invented a method to overlay and register optical coherence tomography, fundus autofluorescence, and fluorescein images that could track the rates and characteristics of the edges.

When the Omnifield results were overlaid on the images, the disruption of the photoreceptor ellipsoid junction-as well as redundancy or thickening of the retinal pigment epithelium-appeared to be associated with faster rates of edge progression and vision loss without treatment.

“We are now examining the treated eyes for those characteristics,” Dr. Sinclair said.

“It seems that this acuity perimetry [invention] helps a lot more in understanding the vision parameters in relation to the structural changes,” he said. “In using chart acuity we could never understand what was happening with the vision.

“By using my acuity field [device] and the ability to overlay it on top of the structural changes, we can understand what’s going on with the drugs and the progression, so we can try to predict both the vision and structural changes to define better when to intervene.”

 

Stephen H. Sinclair, MD

E: ssinclair@stephensinclairmd.com

This article was adapted from Dr. Sinclair’s presentation at the 2015 meeting of the American Society of Retina Specialists. Dr. Sinclair did not indicate any proprietary interest in the subject matter.