Ten-Year Follow-up From the CRYO-ROP Study

THIS ISSUE OF THE ARCHIVES includes a trilogy of articles from the Retinopathy of Prematurity (ROP) Study Group that reports 10-year follow-up findings.^{1 - 3} An avalanche of data is presented on ophthalmological outcomes, the effect of ablative therapy for threshold ROP on visual fields, and contrast sensitivity at age 10 years in children who had ROP. While all of these reports contain useful and important information, the topic that most ophthalmologists will focus on is visual outcomes.

The study group is to be commended for rigorous dedication to continued monitoring of long-term results. That ROP is a lifelong, dynamic condition is evident from the reported data—from the preliminary results in 1988 to reports at 3 months, 1 year, 3½ years, 5½ years, and now 10 years.^{4 - 8} For example, the 10-year data confirm that eyes that underwent cryotherapy are just as likely to have 20/40 visual acuity as control eyes. This was not the case at the 5½-year follow-up, when it appeared that control eyes might be more likely to have 20/40 visual acuity than treated eyes. Longer follow-up has also revealed that the rate of retinal detachment among control eyes, which was stable at 3 months, 1 year, and 3½ years, increased at 5½ years and again at 10 years.

It is comforting to learn that cryotherapy preserves peripheral visual field in severe ROP by maintaining sight, although the field may be 7% smaller when treated eyes are compared with control eyes. Also of interest, but not surprising, are the findings that eyes with severe ROP have smaller fields than eyes of preterm children who never developed ROP and that cryotherapy had no apparent adverse effect on contrast sensitivity. However, despite the benefits of cryotherapy, 44.4% of treated eyes had an unfavorable functional outcome, a disturbing finding that the authors correctly feel reflects the severity of retinal changes at the time of treatment as well as possible intracranial problems and amblyopia that are often coincident in premature babies.

Since the study's inception and recruitment of subjects, laser treatment has become available to the neonatal intensive care nursery. The authors acknowledge that this technology has led to the predominance of laser treatment for threshold ROP over cryotherapy.^{9 - 13} The next logical question, therefore, is whether long-term follow-up of eyes undergoing laser therapy will reveal functional outcomes similar to or better than outcomes in eyes treated with cryotherapy.

Other considerations are the prospect of earlier treatment and whether threshold criteria should be lowered. The study group properly points out that if threshold criteria are lowered, many eyes will be treated that would have done well if left alone; this observation raises serious ethical considerations for any early treatment study. To help obviate this dilemma, the National Eye Institute has funded an analysis program that will consider other factors, such as birth weight, gestational age, and rate of progression as predictors of ensuing threshold disease.

If all expectant mothers received good prenatal care, the prevalence of ROP could immediately be reduced. All ophthalmologists caring for premature babies have seen the effect of illicit drugs on pregnancy and newborns, and particularly in "preemies" whose mothers may be as young as 12 to 15 years of age. Clearly, the social problems that likely contribute to ROP have not received the attention that they deserve.

Another not generally recognized observation relates to the success of cryotherapy. A computer-simulated economic model has been designed to evaluate the cost-effectiveness of cryotherapy and laser therapy compared with the natural course of the disease. Results have shown that cryotherapy at $1801(1998 dollars) and laser therapy at $678 (1998 dollars) are very cost-effective treatments that can improve quality of life immeasurably.¹⁴

As our knowledge expands, new ways to prevent ROP may evolve and new treatments may replace cryotherapy and laser therapy, both of which are destructive.^{15 - 16} Investigators are looking into the role of vascular endothelial growth factor in ROP.¹⁷ Inhibitors of vascular endothelial growth factor are being evaluated with the hope that its influence on the development of neovascularization in the retinal periphery can be ameliorated pharmacologically.

Finally, as already mentioned, patients with ROP, whether treated or not, require lifelong monitoring. The 10-year data have been well documented in this issue of the ARCHIVES. Hopefully, the study group will continue their follow-up studies, because as these 10-year-olds reach 20 years, 30 years, and beyond, additional problems may develop. Vigilance is critical because of the specters of cataracts, glaucoma, and retinal detachment that lurk on the horizon.