5 Questions With Theodore Krupin, MD

By Theodore Krupin, MD
• Professor, Department of Ophthalmology, Northwestern University Medical School, Chicago
Secretary for the American Glaucoma Society
Member of the National Glaucoma Advisory Committee for Prevent Blindness America
Coeditor of The Glaucomas, the third edition of which is in preparation and a “living” online publication under consideration
Recipient of the AAO’s Senior Honor Award, 1993

How did your working relationship with Bernard Becker, MD, of St. Louis influence you?
My work with Dr. Becker began in 1966 when I was a medical student on a research elective. My first project involved evaluating a new hyperosmotic agent, isosorbide. Our interaction continued through my medical school training, research fellowship after my internship (before I commenced military service), residency, and fellowship in his office before my year as chief resident.

Dr. Becker is one of the brightest minds in the history of ophthalmology and the consummate clinician-scientist. He constantly inquires into the pathophysiology and treatment of diseases (not only those of the eye). His intellectual curiosity leads him into laboratory investigations to answer his questions, and he has subliminally passed on this trait to numerous ophthalmologists who have trained as residents or glaucoma fellows under him. Our working relationship culminated in 1976 when I was asked to take over his clinical office and the running of the research laboratory.

Although Dr. Becker is my mentor, he also is a father figure. To this day, I cannot call him Bernie.

What prompted you to invent the Krupin Valve?
The initial concept for the Krupin Eye Valve with Disk (Hood Laboratories, Pembroke, MA) formed in 1974 when I was a resident. Filtration surgery produced a hole in the eye, and surgeons hoped that the hole would remain open and the IOP would set itself to a given level. The hole frequently closed, however, and the pressure level varied greatly. A number of tubes and setons already created had been unsuccessful. My idea was to develop a small anterior-chamber tube that would prevent the sclerostomy opening from sealing and would shunt aqueous externally under a scleral flap. I contacted John Newkirk, PhD, at Denver Biomaterials, Inc. (Golden, CO), to inquire about constructing the resistance (valve) end. He had designed a hydrocephalus shunt (his daughter had this condition).

We developed the Krupin Valve prior to the introduction of adjunctive antifibrotic agents to prevent scarring around the filtration site. While many early devices functioned, external scarring was a problem. Anthony Molteno, MD, of Dunedin, New Zealand, whose early device was also placed at the limbus, had similar results. Dr. Molteno’s work led to later modifications to the Krupin Valve implant so that the device shunts aqueous posteriorly over an episcleral plate. I should note that Dr. Newkirk originally obtained the patent for the Krupin Valve. I have no financial interest in the implant.

What do you consider to be the greatest advancements in the field of glaucoma treatment since you first entered practice?
I joined the full-time faculty at Washington University in St. Louis in 1976. Since then, we have come as a field to recognize the following: (1) elevated IOP (an abnormality of the anterior segment) is a risk factor for glaucoma and not the disease per se; (2) glaucomatous optic nerve damage and visual field loss frequently occur in eyes with statistically normal IOPs; and (3) disc cupping precedes the development of visual field loss. These observations form the foundation for the concept of glaucoma as an optic neuropathy. Separating aqueous humor dynamic dysfunction from ganglion cell/optic nerve damage has catapulted glaucoma management into the twenty-first century alongside other neurosciences, and it has raised the possibility of treating glaucoma independently of lowering IOP through neuroprotection.

Technological advances have improved our ability to measure glaucomatous functional loss. Computerized white-on-white perimetry permits the performance of standardized visual fields in every office, and advances in short-wave-length and frequency-doubling perimetry allow the early detection of functional loss. Additionally, the computerized analysis of the optic nerve and retinal nerve fiber layer has become available and clinically useful to all practices (This reminds me of our work in the mid-1980s on topography with the computerized Rodenstock Optic Nerve Head Analyzer [Rodenstock GmbH, Munich, Germany]).

Regarding glaucoma therapy, I have witnessed the development of effective IOP-lowering and better-tolerated medical agents including topical beta-adrenergic antagonists, prostaglandin agents, CAIs, and selective alpha-2 adrenergic agonists. Better lasers have expanded the treatment of open-angle and narrow-angle glaucoma; surgical iridectomies are now rarely performed. Filtration surgery has markedly improved with the adjunctive use of the antifibrotic agents 5-fluorouracil and mitomycin C. Although these agents are associated with late bleb complications, the increased formation of a bleb is dramatic. Improvements in the design of glaucoma shunts have resulted in superior outcomes for eyes with recalcitrant glaucoma, and advances in cataract surgery such as phacoemulsification and lens implantation through small, clear corneal incisions have almost eliminated the difficult management of aphakic glaucoma.

What is the current focus of your research?
Five years ago, I decided to end my laboratory bench research and limit my research focus to clinical fields. It had become very difficult to wear the dual hats of a basic scientist and clinician.

My current clinical focus includes developing and directing a multicenter (12 sites) grant-supported investigation into the possible role of the selective alpha-2 agonist brimonidine as a neuroprotective agent in patients with low-pressure glaucoma. The study is in its fourth year. I have also started another multicenter (four sites) study comparing repeat argon versus selective laser trabeculoplasty in eyes that have undergone prior 360º argon treatment.

My colleagues and I continue our corneal pachymetry studies, which began at our practice in 1997. In fact, we notified the investigators for the Ocular Hypertension Treatment Study that 25% of our ocular hypertensive patients had a central corneal thickness of more than 600 µm. Currently, we are measuring an area greater than the central cornea in glaucoma and nonglaucoma patients. Our office is also a site for the memantine neuroprotective study sponsored by Allergan, Inc. (Irvine, CA).

What developments do you hope to see in the field of glaucoma?
Patients will benefit if IOP-lowering medical therapies directed to selective downstream receptors or specific target receptors cause fewer side effects while providing a longer duration of action. Blebless surgery to bypass outflow resistance and safer, more effective means to control wound healing would be further advantages. Additionally, advanced, noninvasive, continuous IOP recording independent of corneal thickness would have a major impact on glaucoma management.

Currently, the concept of target pressure permeates glaucoma management. At present, we are only able to determine retrospectively—based on serial examinations of the optic nerve and visual field testing—what IOP is adequate to prevent either the onset or progression of a patient’s glaucomatous optic neuropathy. Advanced psycho- or electrophysical tests to detect ganglion cell dysfunction would place target pressure in the history books. As Thom Zimmerman, MD, PhD, of Louisville, Kentucky, once told me, “Glaucoma therapy is a silly millimeter of mercury.”


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