Avastin Offers New Hope for Treatment of ROP
Retinopathy of prematurity (ROP) is an eye disorder that affects premature infants. This disorder usually develops in both eyes and is one of the most common causes of visual loss in childhood. ROP can lead to lifelong vision impairment and blindness.
New hope for the treatment of ROP may be available in the form of the cancer drug Avastin (bevacizumab).
The University of Texas Health Science Center at Houston (UTHealth) researchers have found a single injection of Avastin into the eyes of premature babies prevented blindness more effectively than laser surgery.
The results of the multicenter clinical trial has been published in the Feb. 17 issue of The New England Journal of Medicine.
ROP was first diagnosed in 1942. It is a potentially blinding eye disorder that primarily affects premature infants weighing about 2¾ pounds (1250 grams) or less that are born before 31 weeks of gestation (A full-term pregnancy has a gestation of 38–42 weeks). The smaller a baby is at birth, the more likely that baby is to develop ROP.
ROP occurs when abnormal blood vessels grow and spread throughout the retina, the tissue that lines the back of the eye. These abnormal blood vessels are fragile and can leak, scarring the retina and causing retinal detachment. Retinal detachment is the main cause of visual impairment and blindness in ROP.
Currently, both laser treatments and cryotherapy are performed only on infants with advanced ROP, particularly stage III with "plus disease." "Plus disease" means that the blood vessels of the retina have become enlarged and twisted, indicating a worsening of the disease.
Both laser and cryotherapy treatments are considered invasive surgeries on the eye.
Helen A. Mintz-Hittner, M.D., the Alfred W. Lasher, III, Professor in the Department of Ophthalmology and Visual Science at the UTHealth Medical School, and colleagues conducted a prospective, controlled, randomized, stratified, multicenter trial to compared the use of intravitreal Avastin (an anti-vascular endothelial growth factor) to conventional laser treatment.
The researchers enrolled 150 infants (total sample of 300 eyes) with acute ROP affecting zone I and posterior zone II posterior stage 3+ (i.e., stage 3 with plus disease) retinopathy of prematurity. Only 143 infants survived to 54 weeks' postmenstrual age, and the 7 infants who died were not included in the primary-outcome analyses.
Infants were randomly assigned to receive intravitreal bevacizumab (0.625 mg in 0.025 ml of solution) or conventional laser therapy, bilaterally. The primary ocular outcome was recurrence of retinopathy of prematurity in one or both eyes requiring retreatment before 54 weeks' postmenstrual age.
Recurrence of ROP occurred in 4 infants in the Avastin group (6 of 140 eyes [4%]) and 19 infants in the laser-therapy group (32 of 146 eyes [22%], P=0.002).
The drug therapy resulted in mild anatomical retinal abnormality in just one eye of 31 infants, whereas conventional laser treatment resulted in a mild structural abnormality in 16 eyes and severe abnormality in two eyes of 33 infants.
“When I started working with babies almost 40 years ago, there was nothing we could do for those with retinopathy of prematurity,” said Mintz-Hittner, the study’s principal investigator. “We’ve gone from nothing to a real solution. It you are careful and administer this therapy appropriately in stage 3+, you can get wonderful outcomes.”
Mintz-Hittner, an attending physician at Children’s Memorial Hermann Hospital and the Robert Cizik Eye Clinic, stressed that timing is critical with this drug therapy. If administered too early, in stages 1 and 2 of the disease, it can cause retinal dystrophy. Given too late, in stages 4-5 of the disease, the drug can accelerate retina detachment.
“In that window, as the abnormal vessels begin to proliferate but before the retinal begins to detach, that’s when you want to treat,” Mintz-Hittner said.
In addition to the significantly reduced recurrence rate for patients with retinopathy of prematurity in zone I, Mintz-Hittner said, compared with conventional laser therapy, the drug therapy appears to do the best job preserving vision. Plus, when administered, there is no need to intubate the baby and there is a faster recovery.
“Our first available treatment for babies with retinopathy of prematurity was cryotherapy,” Mintz-Hittner said. “It was very painful and it wiped out all posterior ocular layers. The visual field was decreased and myopia or nearsightedness occurred. It was a long procedure – 2 to 3 hours – requiring intubation. With laser treatment, you still had to intubate, which could cause major setbacks for the baby, and field loss and myopia still occurred, but it was less painful and only destroyed the inner retinal layers.”
“With this drug therapy, we use a few drops of anesthetic to numb the eye. We take a syringe with a tiny needle and administer a small amount of the drug directly into the eye. The whole process takes two to three minutes, and you begin to see results within 24 hours,” she said. “The abnormal vessels virtually disappear and then normal vessels begin to grow out again. The field of vision is preserved and myopia is less.”
The results of the study were so promising that Children’s Memorial Hermann Hospital has discontinued the use of conventional laser therapy and now offers only the drug therapy to premature infants with this type of retinal disease.
“As compared with conventional laser therapy in treating patients with zone I retinopathy of prematurity, intravitreal bevacizumab represents a true breakthrough in disease management,” James D. Reynolds, M.D., wrote in an accompanying editorial in The New England Journal of Medicine. “…Intravitreal bevacizumab should become the treatment of choice for zone I retinopathy of prematurity.” Reynolds is with the Department of Ophthalmology at the University of Buffalo in Buffalo, N.Y.
Compared with laser therapy, Mintz-Hittner cautioned, the drug therapy does require longer follow-up, “You must follow the child for at least 16 weeks following the injection to make sure there isn’t a recurrence. Approximately 4 percent of patients (one in every 25 patients) may require a second injection. I explain to parents that it’s like a cancer. It can come back and if it isn’t treated in time, it can lead to blindness – so follow-up is very important.”
The next steps in research, Mintz-Hittner said, will be to further evaluate the drug therapy’s safety, refine the dosage and timing of follow-up and also study long-term visual function.
Efficacy of Intravitreal Bevacizumab for Stage 3+ Retinopathy of Prematurity; Mintz-Hittner HA, Kennedy KA, Chuang AZ; N Engl J Med 2011; 364:603-615
University of Texas Health Science Center at Houston press release, February 16, 2011