Affordable HIV drug shows promise in improving vision for diabetic eye disease

An inexpensive, long-approved HIV drug can improve vision in patients with a blinding complication of diabetes more effectively and a much lower cost than many existing treatments, an initial clinical trial suggests. Further, the drug is taken orally, potentially offering patients an alternative to monthly injections directly into their eyes.

The drug, lamivudine, could represent an important new option for millions of patients with diabetic macular edema (DME), a condition which causes fluid to build up in the retina of the eye. It's estimated that approximately 1 in 14 people with diabetes develop the sight-stealing eye disorder, and there are more than 37 million adults living with diabetes in the United States alone.

An oral drug that improves vision in DME would be a game changer because it would be more convenient for patients than frequent, often monthly, injections into the eye. The mechanism of action of lamivudine is also different from that of existing treatments, so we could also develop combination therapies."

Jayakrishna Ambati, MD, researcher, founding director of UVA Health's Center for Advanced Vision Science

Diabetic macular edema (DME)

Ambati's collaborators at Brazil's Universidade Federal de São Paulo, led by Dr. Felipe Pereira and Dr. Eduardo Buchele Rodrigues, enrolled two dozen adults with DME in a small randomized clinical trial. Participants were randomly assigned to receive either lamivudine or a harmless placebo, in addition to injections of the drug bevacizumab into their eyes starting after four weeks.

Participants who received lamivudine showed significant vision improvements even before their first eye injections. Their ability to read letters on an eye chart improved by 9.8 letters (about 2 lines on the eye chart) at four weeks, while the participants receiving placebo saw their ability decrease by 1.8 letters. A month after the bevacizumab injections, the lamivudine recipients had improved by a whopping 16.9 letters (more than 3 lines on the eye chart), while the placebo group, receiving bevacizumab alone, had increased by only 5.3.

The results suggest that lamivudine may work both alone and in conjunction with bevacizumab injections, though larger studies will be needed to bear that out, the researchers say. However, lamivudine alone could be lifechanging for patients in many areas of the world with limited access to specialty doctors or who are unable to afford or travel to monthly eye appointments, Ambati says.

"A $20-a-month or even cheaper oral pill that improves vision as much as or more than therapy with injections into the eye that cost up to $2,000 per month could be transformative both for patients and the health care system," he said.

The researchers believe lamivudine is effective against DME because it blocks the activity of inflammasomes, important agents of our immune systems. Inflammasomes normally act as sensors of infections, but they have also been implicated in the development of DME.

Ambati and his collaborators say future trials of lamivudine will need to enroll larger numbers of patients and follow them for longer than eight weeks. However, the researchers are encouraged by the promising signs produced by their initial test. For example, they note that lamivudine improved vision not only during the first four weeks – when the most improvement is typically seen in DME – but in the following four weeks as well.

"We have developed a safer version of lamivudine called K9, which blocks inflammasomes without the potential side effects of lamivudine," said Ambati, DuPont Guerry III Professor in the UVA School of Medicine's Department of Ophthalmology. "So, we are excited by the ongoing and planned clinical trials of K9 in DME as well."

The new findings comes hot on the heels of another discovery by Ambati suggesting that HIV drugs may substantially reduce the risk of Alzheimer's disease. His group previously found, by analyzing large health insurance databases, that the drugs, called nucleoside reverse transcriptase inhibitors or NRTIs, can also reduce the risk of diabetes and macular degeneration. 

The new clinical trial on DME was spurred by similar findings and illustrates the power of what Ambati calls "Big Data Archeology."

Findings published

Ambati and his collaborators have published their DME findings in Med, the flagship clinical journal of Cell Press. The research team consisted of Felipe Pereira, Joseph Magagnoli, Meenakshi Ambati, Talita Fernandes de Oliveira, Juliana Angélica Estevão de Oliveira, Vinicius Oliveira Pesquero, Lucas Zago Ribeiro, Dante Akira Kondo Kuroiwa, Fernando Korn Malerbi, Sergio Atala Dib, Nilva Bueno Moraes, Michel Eid Farah, Eduardo Buchele Rodrigues and Jayakrishna Ambati. Jayakrishna Ambati is the co-founder of iVeena Holdings, iVeena Delivery Systems and Inflammasome Therapeutics; a full list of the authors' disclosures is included in the paper.

Ambati's research has been supported by the National Institutes of Health's National Eye Institute and National Institute on Aging, grants R01EY031039 and R01AG082748, and by UVA's Strategic Investment Fund, grant SIF167.

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