How did you come to choose retina as a profession?
I chose ophthalmology/retina by pure chance. In 1989, I was working on blood substitutes at the Department of Physiology at the University of Wuerzburg. A senior physician from the Department of Ophthalmology at the University of Bonn wrongly thought that the blood substitutes could be used in retinal detachment surgery in the same way that perfluorcarbons are used. The head of the Ophthalmology Department, Manfred Spitznas, MD, heard about the debate between the senior physician and myself regarding this issue. Dr. Spitznas called me one day and invited me to interview at Bonn. He convinced me to become an ophthalmologist during this interview. Dr. Spitznas, who had been working at the Jules Stein Hospital for 2 years, was a man with a vision toward both basic research and innovative surgery. At this time, retina was a mandatory subspecialty at Bonn, and he promoted a sound education in surgical and medical retina as well as the investigation of retinal disease on a pathobiochemical level. I have fond memories of cultivated debates between us as tutor and student. In my mind, quality and ambition in retina research and therapy are connected with Dr. Spitznas. I am grateful that I had the opportunity to work with him.

What has been the toughest decision you have had to make as a retina specialist?
The most difficult decision that I ever had to make was whether to pursue combination therapy treatments for retina diseases or to follow widely accepted monotherapeutic strategies, which would mean disregarding my pathophysiologic and pathobiochemical findings and/or considerations about these therapies. At the time, antivascular endothelial growth factor (anti-VEGF) drugs were regarded as wonder therapies capable of healing wet age-related macular degeneration (AMD). After I carefully assessed the available data and scientific rationales, I decided to treat various retina diseases, particularly AMD, with a stringent combination regime. I made this decision in the interest of my patients. Recent developments have shown me that it was the right decision. Nevertheless, scientific life was not always easy after I started treating patients with combination therapy. Many in the retina community criticized me, and at moments I feared that I might not have made the right decision. Those doubts are in the past now. I am very glad that I never disregarded my primary goals, which were to offer the best possible therapy to my patients and the rigorous pursuit of a scientific idea.

Considering that the combination therapy trials performed so far have only included small patient groups, have not been randomized, and have had various designs, what is your advice to clinicians who would like to employ combination strategies for their own patients in light of the plethora of information presented at meetings, in journals, and in publications such as Retina Today?
The number of articles on different combination therapies has been growing steadily. We will soon have access to prospective randomized data on triple therapy for AMD, a regimen that we designed. The results of our case series were published in Retina about 2 years ago. The randomized trial based on the design of our case series is the RADICAL (Reduced Fluence Visudyne Anti-VEGF-Dexamethasone In Combination for AMD Lesions) trial. For AMD treatment, I recommend the triple therapy design used in our study, which consists of a reduced light dose photodynamic therapy (PDT), followed by an intravitreal application of bevacizumab (Avastin, Genentech) or ranibizumab (Lucentis, Genentech), and then dexamethasone.

It is important to remember that not every therapeutic strategy can be tested at the highest evidence level. The high evidence level is left to drug licensing procedures. Therefore, a therapeutic design should be based on clinical experience. Ophthalmologists still have much to learn from internal medicine, where combining different drugs to treat numerous diseases has been common practice for a long time.

How do you expect combination therapies to evolve in the future?
I strongly believe that a combination strategy is the only way to address the pathophysiology of diabetic retinopathy or AMD. I am convinced that combination therapies will become the standard of care for these diseases and that they will be prescribed on a personalized, customized basis. Over the past 2 years, many publications have shown that a combination approach can be successful and have a better long-term effect than monotherapies. Examples include the laser and intravitreal drug combination for diabetic patients, or the combination of choroidal neovascularization-destructing devices and anti-VEGF drugs and/or dexamethasone. Combination strategies also offer a cost benefit. In a recent publication, William E. Smiddy, MD, of the Bascom Palmer Eye Institute in Miami, showed that as-needed bevacizumab cost $84 per line-year compared with $766 per line-year for protocol usage of ranibizumab. In general, combination treatments ranged between $71 and $269 per line-year; triple therapy (PDT followed by dexamethasone plus bevacizumab) cost the least.

5. If you could choose to live anywhere in the world, where would it be and why?
It would definitively be the United States of America. Skiing is my favorite sport, and the United States offers the most attractive ski resorts as well as the most varied landscapes to be found anywhere on the planet. However, the main reason I would move to the United States is the open-mindedness of the scientific community. In America, putting good ideas to practice is much more important than political and tactical considerations. Maybe this is the principal reason why the United States is the leading country in the world, not only economically but also academically. During the difficult times when we were trying to establish the combination therapy for AMD, the frankness of my colleagues in the United States always encouraged me to pursue my goals both in the laboratory and in my everyday clinical work. I would like to take this opportunity to thank my US colleagues once again for the inspiration and encouragement they have always provided.