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Up Front | Oct 2006

5 Questions with Terrence P. O’Brien, MD

How did your undergraduate major in zoology lead you to an MD and a specialty in ophthalmology?
I was actually interested in biological chemistry, which at the time was part of the biology department's zoology section. The faculty included several internationally prominent researchers who were making some of the field's seminal discoveries. Their enthusiasm was contagious and solidified my desire to continue studying the human body and the diseases that affect it.

Once I decided to pursue a career in medicine, I quickly realized that ophthalmology was the "queen of all subspecialties." I was, and still am, fascinated by the human eye, not only because it is beautiful, but also because of its incredible function. I appreciate that we can directly visualize the effect of treatments on the eye's various structures and functions, a capability that helps us to develop better methods for diagnosing, managing, and preventing blinding diseases.

How has your background in biological chemistry helped your research into the causes of the recent Fusarium keratitis outbreak?
For the past 6 months, my colleague Eduardo C. Alfonso, MD, and I have been conducting environmental and molecular tests with Renu Moisturloc and contact lenses in our laboratory. We have identified several factors that contributed to the outbreak, including the manufacturer's decision to change the disinfectant and add a new surfactant simultaneously, an increased uptake and subsequent release of the disinfectant by the contact lens' material, and increased corneal staining. Fusarium is an opportunistic fungus that took advantage of the perfect storm created by the interaction of these factors.

What is the current state of ophthalmic antifungal therapies?
Unfortunately, the research and development of antifungal therapies have lagged behind that of antibacterial drugs. Currently, natamycin is the only topical antifungal drug approved by the FDA for use in the eye. The agent's efficacy is limited, however, because it is a suspension that does not penetrate into the deeper layers of the cornea. Nevertheless, topical natamycin is the first agent of choice for treating filamentous fungi, including the Fusarium species. Right now, the combination of topical natamycin with an oral azole agent can help resolve fungal infections in select patients.

Although in vitro testing of a newer triazole antifungal drug has been encouraging, its in vivo use has demonstrated variable efficacy. Clearly, the recent outbreak of Fusarium keratitis has highlighted a need for more effective treatments for ocular fungal infections.

What do you think are the most promising developments in ocular drug delivery systems?
We have newer agents that are more effective against a number of blinding diseases and, more importantly, better methods for delivering the novel compounds to the targeted areas efficiently and safely.

Gene therapy has been the great hope for managing or curing many disease states, but the complex interactions between the genes and their products continue to present many challenges. Probably the most exciting ophthalmic devices are those that can be implanted in the subretinal space with minimally invasive procedures to allow a sustained release of drugs directly to the retina.

You held the inaugural Tom Clancy Professorship of Ophthalmology at the Wilmer Eye Institute in Baltimore. What motivated the noted author to endow this position?
Mr. Clancy has publicly disclosed how his high refractive error affected his vision and prevented him from serving in the military. Using advanced customized technology, I was able to improve his uncorrected vision dramatically without causing extreme aberrations and to eliminate his need for his trademark heavy, "bullet-proof" spectacles. The last time I saw Mr. Clancy, he was completing his latest thriller while overlooking the Chesapeake Bay and wearing a pair of lightweight, prescription-free sunglasses.

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