What could cancer therapies reveal about managing retinal disease?

Joan Miller notes that retinal surgeons are generally quite receptive to new concepts. 

“We’re open to exploring novel surgical methods,” she stated. “We are continually striving to advance the field and technology. It’s an exceptionally inventive specialty.”

Miller exemplifies this mindset. Such independent thought has characterized her extensive, esteemed career as a researcher, clinician, and leader.

Miller, the David Glendenning Cogan Professor of Ophthalmology and head of the Department of Ophthalmology at Harvard Medical School, is recognized for creating two significant treatments for age-related macular degeneration (AMD), the leading cause of vision impairment in individuals over 50. Her therapies are administered to millions of patients globally each year.

However, she didn’t start at the solution. Her work, partially funded by the National Institutes of Health, began with a thought-provoking idea: Could cancer remedies be adapted for retinal diseases? 

One variant of AMD, termed wet macular degeneration, arises from abnormal blood vessels that proliferate in and beneath the retina, causing tissue damage. Upon completing her training at Harvard Medical School in 1991, the prevailing treatment involved cauterizing the vessels. 

“It appears that where these abnormal blood vessels arise in retinal conditions like wet macular degeneration, the mechanisms are remarkably similar to those in cancer,” Miller remarked. 

Consequently, she modified a procedure called photodynamic therapy, which was then undergoing clinical trials for metastatic skin cancer. Her method utilized a unique dark-green dye injected into a vein in the arm. Once the dye reached the eye, a low-powered laser was directed onto the affected area.

This activated the dye, damaging the abnormal vessels yet preserving the macula (a crucial region central to the retina). The treatment received FDA approval in 2000 and was the first to demonstrate a reduction in vision loss in AMD cases. 

Nevertheless, Miller sought to comprehend why the abnormal vessels formed in the first place. The underlying cause was identified as vascular endothelial growth factor (VEGF), a signaling protein that encourages vessel formation. Miller demonstrated that VEGF was released when the retina lacked oxygen, resulting in the development of abnormal blood vessels.

Her findings had a profound influence, leading to the creation of anti-VEGF therapies now utilized by millions of adults and children with sight-threatening retinal disorders — not just wet AMD — worldwide.

One individual who profoundly influenced Miller’s own journey was Alice McPherson, the nation’s inaugural female retinal surgeon. Miller recalls meeting McPherson (who passed away in 2023 at the age of 97) at various conferences, feeling “full of admiration,” and eager to bombard her with questions about her profession.

Today, Miller has her own remarkable list of milestones: the first female physician to serve as a professor of ophthalmology at Harvard Medical School, the first female chair of the HMS Department of Ophthalmology, and the first woman to chair the ophthalmology division at Mass Eye and Ear. 

Women were a noticeable minority during Miller’s undergraduate experience at MIT and in ophthalmology during her initial years in the field. Yet, she claims she never experienced challenges attributed to her gender — until she entered leadership as a department chair in 2003.

“People didn’t acknowledge my remarks, or they were put off by my delivery,” she reflected.

As she navigated the complexities of her new role, she eventually recognized her position as a role model for medical students, postdocs, and more junior faculty. It also allowed her to implement positive changes informed by her own experiences.

Miller had welcomed three children during her medical training and found herself lacking in the flexibility she desired. Managing parenthood alongside a demanding career is challenging, she stated, yet she aspired to streamline things for those who would follow in her footsteps. 

“I believe we were trailblazers in creating a supportive leave policy that does not impose financial constraints,” she mentioned. “As chair, I was particularly attentive to granting individuals — predominantly women, but also men — leeway in their career trajectories, permitting them to temporarily reduce clinical obligations or initially focus on clinical work before incorporating research. That has been remarkably gratifying.” 

Miller is now preparing for a new phase in her life and career.

She is resigning as chair of ophthalmology at Mass Eye and Ear after a 22-year tenure to concentrate on patient care and research. She has not lost any federal research funding despite recent cuts, though one grant renewal requested her team to exclude an international collaborator.

“It seems irrational,” she remarked.

She has always cherished her partnerships with colleagues from around the globe, including a decade-long collaboration with researchers in Portugal.

“I would be disheartened to see that partnership dissolve because we achieve much greater results together, collaborating and learning from experts internationally,” she asserted.

Miller believes that the American federal funding model for fundamental research has been crucial to her career: She arrived in the U.S. from Canada for her undergraduate studies and remained for medical school, convinced she was in an ideal environment to tackle significant challenges. 

“I came from Canada and have truly thrived and gained from the professional atmosphere in Boston,” she expressed. “I could not have accomplished what I have in merging research and surgical practice back in Canada. Their system tends to prioritize surgical duties, leaving little time for additional pursuits.” 

Miller frequently receives letters from retina patients expressing gratitude for her contributions to the “other things.”

“You work on something in a lab, and more often than not, it doesn’t yield results, leading to some skepticism,” Miller explained. “However, to witness it work so effectively and integrate into routine practice, profoundly impacting patients’ lives has been incredibly fulfilling.”