© Peta Bell and Grzegorz Krzeszowiec

None of his ideas are proven, Rosenthal concedes; they’re still only hypotheses. And in any one patient, multiple problems on or under the eye’s surface could be contributing to the discomfort. Nonetheless, he and his supporters are taking direct aim at lingering scepticism over whether nerve-mediated eye pain is even a real phenomenon. As Borsook points out, few doctors now doubt the existence of similar sensations in an amputated arm or leg.

“Yes, if you have your limb blown off, I see something missing and it’s more tangible that you have pain and I’ve heard about phantom pain,” he says. “But if you’ve just had a small incision in your body and you have incredible pain – it could be a tooth removal or the eye, and you still look normal – you know, what’s wrong with you?”

Most ophthalmologists, Galor says, have been trained to identify evidence of cataracts or defects in the retina, not the less visible signs of abnormal nerve function. The idea that many patients with dry eye symptoms have chronic pain, then, is “completely new and radical”, she says. “They look at it like, ‘If I don’t see it, it doesn’t exist’.”

Patient advocates hail Rosenthal’s 2009 study, ‘Corneal pain without stain: is it real?’ as a breakthrough in advancing the argument that debilitating pain could occur without the clinical signs detected by using fluorescent stains on the cornea and other standard tests. Citing his pioneering work, Galor calls Rosenthal “the father of this field”.

After his initial study on chronic eye pain, however, Rosenthal says the ophthalmology community largely censored his views. Even his own charity, the Boston Foundation for Sight, was roiled by internal conflicts. When the foundation fired his son, Bill, in 2011, Rosenthal was briefly arrested for trespassing in Bill’s office to gather up some belongings, according to a police report of the incident. Bill sued over his dismissal and recently reached an undisclosed settlement with the foundation. Then in 2012, after a 20-year tenure, Rosenthal was forced out of the foundation too – an abrupt firing that he alleges was linked to his focus on eye pain and what some at the charity referred to as his “off the wall” treatments.

“Boston Foundation for Sight has had numerous disputes with Dr Rosenthal over the past many years, some of which involved his son,” responds foundation spokesperson Karen Schwartzman. “All disputes were settled to the satisfaction of all parties in May 2015.

“With respect to Dr Rosenthal’s ideas about the neuropathic origins of severe and lasting eye pain, we hope his work will encourage research on this paradigm to the benefit of patients suffering from severe eye pain.”

Based on his clinical observations at the foundation, Rosenthal wrote a paper describing 21 patients who underwent LASIK or similar laser-based surgeries and subsequently had severe eye pain lasting more than two years. After two ophthalmology journals rejected the article, he published it himself on the website of the Boston EyePain Foundation, another nonprofit that he launched in 2013 to continue his work. Since then, he has regularly posted patients’ stories and railed against what he alleges is the medical community’s willful suppression of mounting evidence that much of what is considered dry eye disease is instead a broken alarm mediated by faulty nerves and circuits in the brain.

David Sullivan, a Harvard ophthalmologist and founder of the Tear Film & Ocular Surface Society, is cautious about the details of Rosenthal’s hypotheses, which he says are based mainly on clinical observations and may or may not be supported by further studies. “But I think the bottom line is this whole area of pain and sensation is very, very important,” he says. And so far, he concedes, doctors don’t have answers for many patients.

In his crusade for a solution, Rosenthal is finding himself increasingly accompanied by other researchers who say the general outlines of his ideas fit many of their own observations. Twenty years ago, for example, a group led by Japanese ophthalmologist Kazuo Tsubota described an unusual form of dry eye disease in which patients had no injury to the corneal surface and no drop in tear production but an unstable tear film and intense pain. “This is a very interesting group because the symptoms, very bad. But signs? Almost nothing,” says Tsubota, who practices at Tokyo’s Keio University School of Medicine. “I love Perry Rosenthal’s idea because his hypothesis can explain our findings.”

Donald Korb, an expert on meibomian gland dysfunction, says Rosenthal likewise opened his eyes to the concept of neuropathic pain. “When I think back about how ignorant I was seven years ago, I’m appalled,” says Korb, a clinical professor of optometry at the University of California at Berkeley and a long-time friend of Rosenthal’s.

“What I like about the argument that Perry has put forward is that it’s shaking the field to ask the question, ‘Is this a true neuropathic syndrome with pain?’” Borsook says. “And if it is, then the current treatment of [eye] drops is not that useful.”

Eye drops are by far the most common over-the-counter remedy for dry eye, representing a multi-billion dollar global industry. The only prescription drug to win widespread regulatory approval so far, however, is ciclosporin – sold as Restasis by Dublin, Ireland-based Allergan and billed as an anti-inflammatory medication that can increase tear production. Within the past decade, more than a dozen other companies have failed in their bids to win FDA approval for a dry eye drug, although a handful of candidates are showing promise in clinical trials.

The links between corneal nerves and the brain may be more difficult to study, but Galor says most treatment strategies based on the prevailing understanding of dry eye disease haven’t shown a sufficient connection between treating the signs and resolving the symptoms. Other efforts have recruited patients who may be suffering from vastly different conditions. “We need to rethink the biology of dry eye when we design our studies,” she says.

Several groups already are. Galor says she is finding “fantastic” success with patient-derived autologous tears, or drops made from a patient’s own blood serum and filled with growth factors that might aid nerve regeneration. Others are refining the use of anticonvulsant drugs to reduce the spontaneous activity of neurons.

Sullivan is investigating a lubricating, anti-friction protein called lubricin that may reduce symptoms by preventing the tear film from becoming abnormally concentrated and unstable. Tsubota and Korb have reported promising results with goggle-like moisture chambers for some of their patients, and Korb has developed a device called LipiFlow that uses heat and pressure to relieve painfully clogged meibomian glands.

If he can secure funding, Borsook hopes to conduct an MRI imaging study of LASIK patients that might show differences in the brains of those with chronic eye pain. “There’s certainly a neuroscience interest in it,” he says, “but the biggest thing is, can you help patients get to a point where doctors believe them?”