Important Findings in the Early Detection of Rare Eye Toxicity from a Lifesaving Drug

With collaboration from Reliant Medical Group and a Dark Adaptometry device loaned by Maculogix, Inc., MCPHS Optometry Professor Dr. Larry Baitch found eye-opening results in his research into a potential screening method for hydroxychloroquine retinal toxicity.

“Plaquenil is a very important drug in rheumatology, immunology and orthopedics,” says Larry Baitch, OD, PhD, FAAO, Professor & Associate Dean for Research, School of Optometry, MCPHS-Worcester. “It is a symptom-relieving drug for people who have autoimmune diseases such as lupus (systemic lupus erythematosus) and rheumatoid arthritis.” Plaquenil®, generically known as hydroxychloroquine, reduces symptomatic episodes of autoimmune diseases, which can sometimes be life-threatening. However, hydroxychloroquine is a derivative of chloroquine, which is a derivative of quinine—an anti-malarial drug that was discontinued due to causing blindness. “When they came up with hydroxychloroquine (Plaquenil), it was a much safer drug,” says Dr. Baitch., “But it still has a remote potential for toxicity to the retina of the eye. If retinal toxicity exists and is left undetected and unaddressed, it may lead to vision loss, which can be serious. However, if caught early, those effects on the eye can be reversible.” Dr. Baitch goes on to explain that such cases are rare and usually occur in patients who have taken high cumulative doses of hydroxychloroquine for extended periods of time. But the widely known toxicity of Plaquenil for high-risk patients formed the basis of Dr. Baitch’s research, which began in December and aimed at detecting signs of toxicity earlier than previous tests have allowed, using Maculogix’s Dark Adaptometry device, AdaptDx®.

Maculogix is a company founded by Greg Jackson, PhD, with a mission to eliminate blindness caused by age-related macular degeneration (AMD). As Chief Technology Officer of Maculogix, Dr. Jackson invented the AdaptDx, a dark adaptometry device that can test for AMD within six-and-a-half minutes—a drastic clinical improvement from the two-hour test previously performed with the Goldmann-Weekers dark adaptometer. Jackson demonstrated his invention to Dr. Baitch at an exposition in 2018. Ensuing their conversation, Maculogix donated the AdaptDx to MCPHS in honor of Founding Dean of the School of Optometry and University Trustee, Dr. Les Walls, who coincidentally is a board member of Maculogix. Because of another advantage of the AdaptDx—its ability to detect macular degeneration up to three years before it presents any signs in the retina or symptoms, such as visual distortion—Dr. Baitch thought to use this dark adaptometer for the purpose of detecting the prevalent issue of hydroxychloroquine toxicity.

Dark adaptometry is the measurement of an eye’s ability to recover its sensitivity in darkness after being exposed to light. “There are two types of cells in the eye: the rods and the cones. In bright light, the rods turn off and the cones are active,” Dr. Baitch explains. “[In darkness]...eventually the rods kick in and they take over in our visual sensitivity.” For people with macular degeneration, the rods take longer to take over from the cones, resulting in impaired night vision. To measure the point in which the rods take over, otherwise known as the Rod Intercept (RI), dark adaptometers expose an eye to bright light followed by complete darkness. Dr. Baitch analyzed the RI value for patients taking hydroxychloroquine to determine whether they showed delays of dark adaptation despite presenting no other signs or symptoms. To obtain his cohort of patients, Dr. Baitch connected with Reliant Medical Group, namely Robert Yood, MD, FACP, FACR, Medical Director for Research, Bradley Daines, MD, Chief of Reliant Ophthalmology and Elinor Mody, MD, Chief of Rheumatology at Reliant. Dr. Yood, who is also a rheumatologist, shares Dr. Baitch’s interest in the toxicity of Plaquenil, thus dedicated resources to the otherwise unfunded project “out of tremendous goodwill,” says Dr. Baitch. To support the collaboration, Maculogix loaned an additional AdaptDx dark adaptometry system to Reliant for the project’s duration. With an impressive electronic medical records system, they came up with a substantial number of their patients taking Plaquenil, and a significant portion of them qualifying for Dr. Baitch’s study given his inclusion-exclusion criteria (patients with co-morbidities such as eye diseases, cataract surgery, or diabetes were excluded from the study). Despite other intervening circumstances, like restrictions due to COVID-19, they tested 35 patients in total.

A key assistant to Dr. Baitch's research has been his study coordinator, MCPHS undergraduate student Alondra Msallem, ‘24 candidate for BS in Premedical & Health Studies - Optometry Pathway. Dr. Baitch says Msallem has been very involved, testing patients, recruiting subjects, and talking to doctors. “She’s been going back and forth to Reliant and MCPHS and has been integral in this research,” he says. “And she’s an undergraduate. She hasn’t even graduated from college yet.” In November 2020, Msallem won the MCPHS Center for Undergraduate Research Mini-Grant, which has been partially funding the project. At the recent 2nd Annual MCPHS Center for Undergraduate Research Conference, she presented a lecture entitled, “Use of Dark Adaptometry for Early Diagnosis of Hydroxychloroquine Retinopathy.”

Having just wrapped up the pilot study of his research, Dr. Baitch and the research group will soon be announcing their findings. But what will the results mean for patients who rely on hydroxychloroquine? Dr. Baitch says that the gained knowledge will help physicians to facilitate the management of Plaquenil toxicity. It will be the job of both the rheumatologist and the eye-care practitioner to closely monitor patients known to be at a high risk of vision loss. While it will be the role of the rheumatologist to determine, on an individual basis, whether the risk of the medication outweighs the benefits, it will be the role of the eye care practitioner to see such patients for regular eye exams, as well as visual field testing and optical coherence tomography (OCT) to detect potential effects of hydroxychloroquine in the retina.

As the School of Optometry’s Associate Dean for Research, Dr. Baitch is involved with many research projects, but he is especially excited about this one. He hopes that this pilot study will lead to a multi-site national study with MCPHS as the principal investigators. “The model of optometric education is changing, and we at MCPHS are certainly at the forefront of it,” says Dr. Baitch. He mentions how eye care has already transformed with the accessibility of patients ordering glasses and contact lenses online, and with telemedicine in general. He encourages optometry students to realize that with this evolving field of medicine comes so many paths that they can take whether it be in a hospital, commercial, research, academic, or military setting. He adds, “So, we’re really trying to give a more global perspective to the education that they get here.”