ROP: Past, present, and future

San Francisco-"If you want to travel fast, go alone. If you want to travel far, go together," says an African proverb cited by John T. Flynn, MD.

Delivering the Marshall M. Parks lecture during a pediatrics symposium at the annual meeting of the American Academy of Ophthalmology, Dr. Flynn credited numerous others who have contributed to the understanding of retinopathy of prematurity (ROP) in the past, are currently active, and whose work is laying the groundwork for future breakthroughs.

Dr. Flynn is the Anne S. Cohen Professor of Pediatric Ophthalmology and vice chairman, Department of Ophthalmology, Edward Harkness Eye Institute, Columbia University College of Physicians and Surgeons in New York. He is also chief, Division of Pediatric Ophthalmology.

More than two dozen causes were proposed until an important clue emerged in 1948, when medical oxygen arrived in Australia.

Dame Kate Campbell observed numerous cases of RLF in a nursery where infants were given 50% oxygen for 28 days, whether they needed it or not, but few if any cases in another nursery where oxygen use was much more limited. Her published findings immediately attracted the attention of other investigators and led to the first randomized clinical trial in American ophthalmology, led by V. Everett Kinsey, PhD, and reported in 1956. Although this work established conclusively that oxygen played an independent role in the causation of RLF, it did not establish a safe level of oxygen use.

During this uncertain period, a false step occurred, Dr. Flynn said, as hospitals and isolette manufacturers around the country adopted a guideline setting a maximum of 40% oxygen concentration. RLF cases declined but were replaced by brain damage and neonatal death. Since no effective therapy existed, Dr. Flynn and others were motivated to study the natural history of RLF with tools such as indirect ophthalmoscopy, fluorescein angiography, and ophthalmic photography.

Reflecting on the first tests, done in an era before Institutional Review Boards set safety standards, Dr. Flynn summed up his team's apprehension: "We didn't know whether the baby would die of fluorescein or we would die of fright."

Researchers soon began meeting to share their work and develop a disease classification system based on retinal zones; they also renamed the condition ROP. The International Classification of Retinopathy of Prematurity (ICROP) was published in 1984 and expanded in 1987.

Studies also demonstrated the effectiveness of cryotherapy, which reduced unfavorable outcomes by 50% with no serious side effects, and results that have remained stable for more than 15 years. Since the ICROP-2 classification was published, the retina-vitreous community in the United States has never organized a randomized trial to compare the effectiveness of surgical therapies, he said.

Looking onward

Moving to the present, Dr. Flynn said the Early Treatment for Retinopathy of Prematurity study has shown improved visual acuity outcomes and minimal side effects in high-risk babies. The study also defined two types of risk, based on the presence or absence of plus disease.

Dr. Flynn praised several investigators, including Lois Smith, MD, PhD, of Children's Hospital Boston, who has led research on aspects of ROP. He also acknowledged Michael F. Chiang, MD, a colleague at Columbia University, who is exploring ways to provide services in isolated areas.

A hypothesis proposed by vascular biologist Tailoi Chan-Ling, PhD, of the University of Sydney, Australia, also could break new ground. She theorized that significant differences in clinical presentation and therapeutic outcome may depend on whether vasculogenesis or angiogenesis is perturbed during vessel development.