31.
Vitrectomy vs. New Treatment Strategies for ROP
Mike T. Trese (Royal Oak)
I. Visual Outcomes after Lens-Sparing Vitrectomy for Stage 4A Retinopathy of Prematurity
Purpose: To assess the visual outcomes of patients with stage 4A retinal detachments (RDs)
from retinopathy of prematurity (ROP).
Design: Retrospective review of a consecutive case series of children referred to the pediatric
retina service of Associated Retinal Consultants, Royal Oak, Michigan.
Participants: Forty-five eyes of 39 children.
Methods: The stage of RD for each patient was determined during an examination under anesthesia.
All patients underwent a lens-sparing pars plana vitrectomy (PPV) with membrane peeling.
Postoperative anatomic status was determined by ophthalmoscopy either during an office
examination or during an examination under anesthesia. Visual outcomes were ascertained by
consulting pediatric ophthalmologists using either Teller or Allen acuities. Main outcome measures: Anatomic and visual
outcomes.
Results: Formalized visual acuity (VA) measurement was performed in 23 eyes of 20 children, and was not performed in
22 eyes of 19 children. All 23 eyes that were formally tested had successful retinal reattachment. The macula appeared to
be normal and without distortion in 19 of 23 eyes (83%) during the follow-up period. Average logarithm of the minimum
angle of resolution VA was 20/58. Three eyes had acuities of 20/200, and 4 had acuities of 20/100. All other eyes were 20/80
or better. Average age at time of VA was 3.51 years.
Conclusions: Patients with ROP and stage 4A RDs can be treated successfully with respect to anatomic and visual outcomes
utilizing lens-sparing PPV.
II. The Block-ROP Study (Avastin for ROP)
Retinopathy of prematurity (ROP) continues to be a leading cause of blindness in children in developed countries around the
world, and an increasing cause of blindness in developing countries. The current standard of treatment is ablation of the
peripheral avascular retina. The treatment for ROP has evolved from cryotherapy, as established by the CRYO-ROP study, to
laser treatment as indirect laser delivery systems have become available. Screening and intervention is now directed by the
criteria established by the ETROP study. The ETROP Study demonstrated superior results compared to the Cryo-ROP study
but also recommends earlier treatment with laser ablation. In the children requiring laser treatment the peripheral retina is
ablated and destroyed for future use. The ablated retina is not functional and is not amenable to regeneration. In addition,
morbidity from laser can include cataract as well as anterior segment ischemia, which can lead to phthisis (death of the
eye).
The mechanism of development of retinopathy of prematurity is in large part dependent on vascular endothelial growth factor
(VEGF). The normal biochemistry of the developing eye is altered due to the change in environment when a baby is premature.
Specifically, the relatively hyperoxic environment that the premature baby is introduced to shuts down the production of VEGF (Phase 1) and leads to delayed retinal maturation. The second phase, when the developing fetus will normally
be reducing VEGF levels, becomes dysregulated due large areas of avascular retina creating tissue hypoxia. This results in
abnormally high levels of VEGF and heralds the pathological changes seen in ROP. With the advent of FDA approved drugs
for anti-VEGF treatment, the possibility of treating eyes with anti-VEGF drug has become possible. Drugs that are available
include the drug pegaptinib (Macugen) for partial blockage of VEGF-A, or complete blockage of VEGF-A with drugs such as
ranibizumab (Lucentis) and bevacizumab (Avastin). For purposes of this study, we have chosen to study the drug Avastin as
we feel that it has less retinal penetration and is more likely to restore VEGF homeostasis within the developing retina.
Avastin is limited in its ability to penetrate tissues as it is a full antibody, whereas Lucentis is an antibody fragment and was
designed to have better tissue penetration. VEGF is required in the developing retina for normal angiogenesis and our goal
is to block the excessive levels of VEGF trapped within the overlying vitreous which is responsible for the abnormal vasculature
in ROP. Additionally, Avastin has widely been used for other VEGF dependent diseases such as age-related macular
degeneration and diabetic macular edema in adult eyes and found to be both safe and effective.
In this study, in a controlled and careful fashion, we will examine the use of a reduced dose of the drug Avastin in premature
infants’ eyes for the problem of retinopathy of prematurity. The current adult dose used in the United States is 1.25 milligrams
in .05 ml volume. This dose has been shown to be efficacious in the treatment of choroidal neovascularization and
diabetic macular edema. The drug itself is FDA approved for use in colon cancer, and has been used in ophthalmology for
several years now for its anti-VEGF effect in VEGF-dependent diseases such as choroidal neovascularization and diabetic
macular edema.
Although retinopathy of prematurity may actually involve higher levels of vascular endothelial growth factor than seen in
other retinal diseases, the vascular endothelial growth factor activity is endogenously down-regulated at the time of the due
date. There is evidence that endogenous TGF beta, which elevates at the due date may be a factor down-regulating the vascular
endothelial growth factor. Because of this, it is likely that children will only require one or perhaps two injections of
anti-VEGF drug. This differs from patients undergoing treatment for chronic diseases, such as the treatment of choroidal neovascular
membranes and diabetic macular edema, where it may be required to do injections for two years or more into the
vitreous cavity. In this study the infant will be exposed to a single dose of Avastin at a reduced concentration. The drug itself
hopefully will induce reduction in vascular activity and perhaps control the disease, not requiring destruction of the entire
peripheral retina. In addition, this drug therapy may be much less expensive than laser therapy, which would make it
amenable for treatment in developing countries where lasers are less accessible.