In Brief
• The SEATTLE Phase IIb/III clinical trial of emixustat (Acucela) did not meet its primary endpoint of showing a significant difference in the growth of lesions in geographic atrophy compared to placebo. Acucela said it will further analyze the SEATTLE data with its partner, Otsuka Pharmaceutical. Acucela also has an ongoing pilot study of emixustat for proliferative diabetic retinopathy and is considering an initiation study in Stargardt disease.

• SanBio has been granted a U.S. patent for its proprietary modified stem cells, SB623, for the treatment of retinal degeneration. SanBio developed SB623 to promote regenerative processes in the central nervous system and provide therapeutic options for debilitating neurological disorders, including retinal degeneration by enhancing photoreceptor function.

• The Food and Drug Administration has approved an update to prescribing information for Eylea (aflibercept, Regeneron Pharmaceuticals). The label language clarification recognizes that while most patients receiving Eylea will require dosing once every eight weeks after an initial monthly dosing period, some patients will still require monthly dosing.

• A retrospective analysis of the Phase III RIDE and RISE clinical trials, published in Ophthalmology, showed that people with less advanced diabetic macular edema and who responded better to initial treatment with ranibizumab (Lucentis, Genentech) needed fewer injections over the long-term, suggesting that treating people with DME earlier may help reduce long-term treatment burden.
The sequence of events in diabetic retinopathy is not what it has long been thought to be, researchers at the University of Iowa reported in the journal PNAS.1

For years, scientists believed patients developed retinopathy and, as a result of vascular damage, later developed neuropathy. Management had focused on early detection and treatment of retinopathy to prevent blindness and, subsequently, the nerve damage that neuropathy causes.

However, in this new study the Iowa researchers discovered that the sequence of events occurring in the retina from diabetes is just the opposite.

“What we’re finding here, unfortunately, is that the nerve damage actually does come first, before the vessel damage,” says Michael Abramoff, MD, PhD, professor of ophthalmology and visual sciences at the Stephen A. Wynn Institute for Vision Research and senior author on the study. “Even people with diabetes who never get retinopathy can still develop this damage, and after many years damage may be severe, similar to glaucoma.”

Says Elliott Sohn, MD, first author on the study: “Essentially, the order of damage in the retina from diabetes is different from what we originally thought, and preventing the effects of retinopathy by itself would not protect the nerves in the retina.”

In the study, Drs. Sohn and Abramoff and colleagues from Iowa and the University of Amsterdam studied 45 people with diabetes and little to no diabetic retinopathy over a four-year span. They found “significant, progressive loss of the nerve fiber and ganglion cell layer,” proof of damage to the nerve before vascular changes typically found in the retina from diabetes.

At the same time, researchers found corresponding thinning of the nerve fiber layer in six donor eyes from patients with diabetes and little to no diabetic retinopathy. The layer was considerably thinner than the layer in six donor eyes from patients who did not have diabetes. Similar results were found in diabetic mouse models in this study.

Having a better understanding of the sequence of damage may lead to new treatments that focus on preventing the nerve damage and hopefully also prevent diabetic retinopathy, Dr. Abramoff says.

REFERENCE
1. Sohn EH, van Dijk HW, Jiao C, et al. Retinal neurodegeneration may precede microvascular changes characteristic of diabetic retinopathy in diabetes mellitus. PNAS. April 25, 2016 (Epub ahead of print).

Early Success With Stem Cells for AMD
Retina surgeons in Japan and the United Kingdom have reported the first successful stem cell transplants in individuals with age-related macular degeneration.

At the Association for Research in Vision and Ophthalmology 2016 meeting in Seattle, researchers from the Institute for Biomedical Research and Innovation Hospital in Kobe reported on a 70-year-old woman with exudative AMD who had stem cells implanted from her arm in 2014.1

Project leader Masayo Takahashi, MD, explained that the woman had already failed at existing treatments. The investigators collected a small piece of skin from the patient’s arm and modified into induced pluripotent stem cells (iPSC). The iPSCs were then transformed it into retinal pigment epithelium sheets that were transplanted into the patient’s eye. The transplanted cells survived without any adverse events for more than a year and resulted in slightly improved vision.

The woman maintained visual acuity at 18/200 without any additional anti-VEGF therapy, and her score on the Visual Function Questionnaire-25 improved from 40.7 to 58.3.
 Quotable
 “What we’re finding here, unfortunately, is that the nerve damage actually does come first, before the vessel damage,”
             - Michael Abramoff, MD, PhD


At the same time, retinal surgeons at Moorfields Eye Hospital in London reported on the first patient to undergo a stem cell treatment for wet AMD. The surgeons completed the first surgery last August with no complications.

This approach involved transplanting cells in the RPE with stem cells using a specially engineered patch inserted behind the retina in an operation that takes one to two hours. In all, the trial is recruiting 10 patients over 18 months and will follow the patients for a year.

“There is real potential that people with wet age-related macular degeneration will benefit in the future from transplantation of these cells,” says retinal surgeon Professor Lyndon Da Cruz from Moorfields Eye Hospital, who is performing the operations and is co-leading the London Project.  RS

REFERENCE
1. Kurimoto Y, Hirami Y, Fujihara M, et al. Transplantation of autologous induced pluripotent stem cell-derived retinal pigment epithelium cell sheets for exudative age related macular degeneration: a pilot clinical study. Paper presented at the annual meeting of the Association for Research in Vision and Ophthalmology. May 3, 2016; Seattle, WA.