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By the time patients reach clinic, they have usually spent years searching for an explanation for debilitating eye pain that no one can see.

They describe pain that burns, stabs and throbs. Some compare it to having shards of glass lodged in their eye. Others are so sensitive to light that even ordinary daylight can feel intolerable.

And yet, conventional eye exams often reveal little to explain the severity of their symptoms.

Resolving that disconnect between what patients feel and what physicians can see, and helping these patients with excruciating eye pain, has become Hamrah鈥檚 career-long mission.

鈥淢y patients are suffering from something they can feel, but nobody else can see,鈥� Hamrah said. 鈥淭heir pain is real, even when it鈥檚 invisible.鈥�

It is a frustration that hits close to home for Hamrah, whose exposure to the corrosive impact of chronic eye issues began early.

As a child, he saw his grandfather lose his vision following complications from cataract surgery. Later, his brother underwent multiple eye surgeries to correct strabismus, a condition caused by misaligned eyes.

Those experiences, and watching the ophthalmologist who cared for his family, kickstarted his search for answers and shaped his career ambitions, long before he understood where they would ultimately lead.

"I decided I wanted to be an ophthalmologist when I was four years old," Hamrah said. 鈥淯nderstanding the eye through both my grandfather鈥檚 complications and my brother鈥檚 strabismus muscle surgeries, I became interested in eyes at a very early age.鈥�

That fascination evolved into a career spent questioning what physicians think they know about the eye and developing new ways to see what previously remained hidden.

Challenging conventional wisdom

Hamrah carried that curiosity to medical school at the University of Cologne in Germany, where he found himself drawn to research questions without obvious answers.

One of his first major projects examined presumed ocular histoplasmosis syndrome, a retinal disease whose underlying cause had long been debated.

Over six months, he analyzed retinal tissue collected during surgery, seeking to determine whether the fungus Histoplasma capsulatum could be detected in affected eyes. At the time, many researchers believed the organism played a direct role in causing the retinal disease.

His findings challenged the prevailing belief that active fungal infection was present in the eye, suggesting instead that the disease was more likely the result of an earlier immune response or inflammatory process triggered by prior exposure to the fungus. This work marked a turning point in his career, clarifying the disease鈥檚 underlying mechanisms.

That work culminated in an invitation, still as a medical student, to present his countervailing findings before hundreds of other ophthalmologists as a podium presentation.  

For someone naturally uncomfortable with public speaking, it was more intimidating than the research itself.

"As a private person, it was very challenging to go on a podium to speak to such a large group as a medical student," he said. 鈥淲hen I walked into that room, I had hiccups for two days.鈥�

The experience not only helped build his confidence, but reinforced his drive to break free from assumptions and investigate accepted wisdom.   

Hamrah鈥檚 instinctual skepticism became especially important as a postdoctoral fellow at Harvard鈥檚 Schepens Eye Research Institute, where he set out to study how immune cells travel from the cornea to the lymphatic system.

At the time, scientists generally believed that immune cells known as antigen-presenting cells were confined largely to the outer edges of the cornea. Because maintaining a clear cornea is essential to vision, the tissue had long been regarded as an unusually protected immunological environment.

But Hamrah found something different. His research showed that the central cornea also contains dendritic cells, immune cells that help recognize potential threats and activate the body鈥檚 immune response.

Despite initial skepticism from his colleagues, he continued to investigate until the evidence became undeniable.

The trailblazing discovery helped inaugurate a new understanding of the cornea as not just a passive window through which light enters the eye, but a biologically active environment with its own complex immune surveillance system.

"You don't have to always follow what conventional wisdom says," Hamrah said.

It鈥檚 a principle that captures his trademark approach to research, and one that would lead him toward even harder questions in the years to come.

Making the invisible visible

Twenty years ago, patients who complained of chronic eye pain were simply diagnosed with dry eye disease.

As Hamrah treated those patients, he began noticing symptoms that did not fit neatly into the traditional explanation.

Their pain could be extreme, while the surface of the eye appeared relatively normal.

And importantly, many failed to respond to conventional dry-eye therapies.

鈥淥ne patient explained their pain to me as having a match lit under your eyelid 24/7,鈥� he said. 鈥淚t doesn鈥檛 go away, it never subsides and it wears the patient down.鈥�

That discrepancy made him wonder if physicians were looking in the wrong place. Rather than focusing on the tear film and surface of the eye, he began investigating the role of damaged nerves in eye pain.

The cornea has the highest number of nerves than any other tissue in the human body. Hamrah showed that when these nerves are damaged by inflammation, infection, surgery or other causes, they often transmit abnormal pain signals. Such damaged signaling can persist even when there is little visible evidence on a standard examination.

That phenomenon is now recognized as neuropathic corneal pain.

Hamrah helped uncover the complex relationship between corneal nerves, immune cells and chronic eye pain, showing that many patients diagnosed with severe dry eye disease were actually suffering from nerve-related pain disorders. His work redefined how physicians diagnose and treat conditions such as neuropathic corneal pain and helped establish the emerging field of neuropathic ocular pain.

鈥淭he cornea is not just a passive tissue, it鈥檚 an active immune system. Understanding that the nervous and immune systems work in symphony was a big breakthrough."

Pedram Hamrah, MD

Building on that discovery, he has since identified more than 25 immune cell subtypes in the cornea, an achievement demonstrating that immune cells play a vital role in maintaining and supporting corneal nerves.

鈥淢any patients suffer significantly from the severity of their pain,鈥� Hamrah said. 鈥淢y goal has always been to understand eye pain well enough that we can prevent it, treat it effectively and ultimately improve patients' lives.鈥�

From discovery to treatment  

In 2025, that ambition brought him to the USF Health Morsani College of Medicine, where he today serves as a professor of , co-director of cornea services and director of Clinical and Translational Research.

鈥淚 realized that USF Health is a place where there鈥檚 transformation occurring,鈥� he said. 鈥淭his is a place looking to build the future.鈥�

His research at USF covers the full path from laboratory discovery to patient care. His team is studying how inflammation alters corneal nerves, identifying biomarkers to develop new tests diagnosing nerve-related eye pain and advancing potential treatments through clinical trials.

Hamrah has also focused on establishing a new center to accelerate clinical research in ophthalmology. Known as the USF Health (INSIGHT), the institute is building infrastructure to move discoveries more quickly from the laboratory into patient care, fast-tracking clinical trials and advancing new ways to diagnose and treat chronic eye disease.

He hopes the work currently underway will deliver the first FDA-approved therapies for ocular pain while expanding access to advanced treatments.

"Through scientific innovation, we can help millions of people at once, rather than help one patient at a time,鈥� he said.

As Hamrah continues building clinical research programs at USF, those patients are the driving force behind his work, which remains deeply personal.

He remembers one patient who arrived at the clinic wearing multiple pairs of sunglasses, unable to function outside a dark room and struggling with thoughts of suicide after years of debilitating pain.

Years later, Hamrah saw the patient return to the clinic transformed 鈥� smiling, ready to go back to college, begin dating and travel again.

"He hadn't gone anywhere outside of his room for four years before," Hamrah said. 鈥淚t was rewarding to see someone flourish and become a person again.鈥�

For Hamrah, that is how each scientific breakthrough is ultimately measured: not only by what it reveals about the eye, but by whether it brings patients closer to reclaiming a life they thought they鈥檇 lost.

"I always say to my trainees, you don't want to identify a problem," he said. "You want to solve the problem."