NEI study: More benefit seen from earlier ROP treatment

Infants in the ETROP study had a reduction in unfavorable visual acuity outcomes after early treatment protocol was administered.

Issue: February 1, 2004

ByNicole Nader

Premature infants at high risk of vision loss from retinopathy of prematurity retain better vision when therapy is administered early instead of when treatment is held until the traditional threshold, a large clinical study has found. The study, sponsored by the National Eye Institute, used an improved risk assessment model to identify infants at risk for developing vision loss from ROP.

“The results of this study allow us to improve treatment for ROP and hopefully the quality of life for children who most need sight-saving therapy,” Paul Sieving, MD, PhD, director of the NEI, said in a press release describing the findings of the Early Treatment of Retinopathy of Prematurity (ETROP) study.

Previous treatment standards advised delaying treatment of ROP until the likelihood of retinal detachment was around 50%, or “at threshold.” Threshold ROP was defined as at least five contiguous or eight cumulative sectors (clock hours) of stage 3 ROP in zone 1 or zone 2 in the presence of plus disease (severe dilation and tortuosity of posterior retinal blood vessels).

In this study, patients received treatment of laser ablation or cryotherapy at high-risk prethreshold ROP. Prethreshold ROP was defined as zone 1 with any stage of ROP that was less than threshold; zone 2 with stage 2 ROP and plus disease; zone 2 with stage 3 ROP without plus disease; or zone 2 with stage 3 ROP with plus disease but fewer than five contiguous or eight cumulative clock hours.

Treatment of prethreshold ROP led to a reduction in unfavorable visual acuity outcomes from 19% to 14%, the study authors found. The study was published in the December issue of Archives of Ophthalmology.

New methods

The ETROP study used a computerized risk model to identify high-risk infants early in the disease. The model assessed factors including birth weight, ethnicity, whether the patient is a single- or multiple-birth infant, gestational age, ophthalmic exam findings and whether the infant was born in a hospital that participated in the study.

“This new risk assessment model proved invaluable in the early detection of infants who have a high risk of blindness and may require treatment. It also allowed us to better identify and monitor those patients who are less likely to require treatment,” Robert J. Hardy, PhD, a University of Texas School of Public Health researcher who helped develop the improved risk model, said in the press release.

Infants with a birth weight less than 1,251 g who were born between October 2000 and September 2002 were identified for prethreshold IOP. Those appropriately identified were enrolled in the multicenter study.

A pediatric ophthalmologist uses an indirect ophthalmoscope to examine an infant for signs of ROP.

(Photo courtesy of the National Eye Institute, National Institutes of Health.)

A premature infant is given an eye examination to check for ROP.

(Photo courtesy of the Children’s Hospital, Buffalo, N.Y.)

Treatment, analysis

Three hundred seventeen infants with bilateral high-risk prethreshold ROP had one eye randomized to early treatment with the fellow eye serving as a control eye with standard treatment. In the 84 asymmetric cases, the eye with high-risk prethreshold ROP was randomized to early treatment or conventional treatment, the study authors said.

Researchers evaluated infants’ treatment outcomes at 9 months. Visual acuity was assessed with the Teller acuity card procedure (a method used in the Multicenter Trial of Cryotherapy for ROP). This examination evaluated visual acuity by the spatial frequency to which an infant showed a consistent fixation response. Outcomes were divided into four categories of response: normal (greater than or equal to 3.70 cycles per degree), below normal (1.85 to less than 3.70 cycles per degree), poor (less than 1.85 cycles per degree but measurable with a standard visual acuity card) and blind.

Structural outcomes of the retina were also assessed with a dilated fundus examination and ophthalmologic examination at 6 and 9 months. Refractive errors were determined by cycloplegic retinoscopy.

Researchers compared outcomes for the two treatment groups of eyes with the scientific statistical analysis method x².

Outcomes

The eyes assigned to early treatment had a significantly reduced likelihood of poor vision, from 19.5% to 14.5%, at about 1 year of age. Early treatment also considerably reduced the likelihood of structural damage to the eye from 15.6% to 9.1%.

Laser or cryotherapy therapy was particularly necessary in patients with type 1 ROP (defined as zone 1, any stage ROP with plus disease), zone 1 (stage 3 ROP without plus disease) or zone 2 (stage 2 or 3 ROP with plus disease).

An artist’s conception of the interior of a normally developing premature infant eye.	An artist’s conception of the interior of an infant’s eye shows the formation of an ROP ridge.
(Images courtesy of the Oregon Health Sciences University.)

“It is crucial that infants with high-risk ROP be identified early and be given timely treatment,” said William Good, MD, of the Smith-Kettlewell Eye Research Institute in San Francisco, the chair of the ETROP study. “The results also clearly indicate that for certain subgroups of eyes, watchful waiting and not immediate treatment is the best approach.”

Researchers recommend a watch-and-wait approach to therapy for patients who have type 2 ROP (zone 1, stage 1 or 2 ROP without plus disease or zone 2, stage 3 ROP without plus disease). Treatment should only be considered for such patients if their ROP progresses to type 1 or threshold ROP.

Researchers will follow patients until age 6 years to monitor whether treatment benefits continue into childhood.

For Your Information:

Paul A. Sieving, MD, PhD can be reached at the National Eye Institute, 2020 Vision Place, Bethesda, MD 20892-3655; 301-496-2234; fax: 301-496-9970; Web site: www.nei.nih.gov.

Robert J. Hardy, PhD, can be reached at the University of Texas School of Public Health at Houston, 1200 Herman Pressler Drive, Houston, TX 77030; 713-500-9524; e-mail: Robert.J.Hardy@uth.tmc.edu.

William Good, MD, can be reached at the Smith-Kettlewell Eye Research Institute, 2318 Fillmore St., San Francisco, CA 94115; 415-202-1500; fax: 415-345-8455; e-mail: good@ski.org.

Reference:

The Early Treatment for Retinopathy of Prematurity Cooperative Group. Revised Indications for the Treatment of Retinopathy of Prematurity. Arch Ophthalmol. 2003;121:1684-1694.