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VEGF shows promise for treating pediatric vitreoretinal diseases
Studies indicate VEGF quiets familial exudative vitreoretinopathy and retinopathy of prematurity but hastens tractional changes.
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LAS VEGAS – Infants with retinal vascular diseases treated with a vascular endothelial growth factor inhibitor showed an improvement in vascular activity but a risk of tractional retinal changes in preliminary studies.
Kimberly A. Drenser, MD, PhD, discussed results of the use of Macugen (pegaptanib sodium injection, OSI/Pfizer) in six patients with familial exudative vitreoretinopathy (FEVR) and five patients with retinopathy of prematurity (ROP) during the American Academy of Ophthalmology meeting.
“Our feeling from both retinopathy of prematurity and FEVR is that [VEGF] does effectively treat vascular activity, but it does not prevent tractional changes in the eye,” she said.
VEGF for pediatric disorders
While VEGF inhibitors have demonstrated success in retinal diseases in adults, they have not been investigated previously in the treatment of pediatric disorders.
“It’s very important to understand in the developing eye that there is a codependence between vasculogenesis, angiogenesis and retinal differentiation to create what we recognize as a normal, healthy retina,” Dr. Drenser said.
She explained that many advances have been made in understanding the patterns of vasculogenesis and retinal differentiation in regards to the development of a “healthy retina.”
When that development is interrupted, a spike in VEGF can be observed in the retina, such as in eyes with ROP.
“A number of pediatric retinal diseases are characterized by this abrogation of retinal development, normal vasculogenesis and therefore aberrant angiogenesis,” Dr. Drenser said. “Interestingly, both familial exudative vitreoretinopathy and retinopathy of prematurity share some very significant characteristics such as avascular membrane, extra retinal abnormal vessels, vascular activity and exudation.”
These similarities, despite the difference in the origin of the two diseases, led Dr. Drenser to treat both with anti-VEGF therapy.
FEVR patients
The six FEVR patients received Macugen after exhibiting persistent vascular activity with exudation and no response to traditional treatments. The pathologies were all in a vision-threatening state.
“All six eyes showed a remarkable reduction in exudative vascular activity within a 4-week period after the injection,” Dr. Drenser said. She added that this improvement was sustained for a number of months without toxicity.
While exudation improved, the proliferative tissue in the periphery often began or continued to contract.
“There is an important note here that any eyes that appeared to have any vitreoretinal deduction abnormalities or even early proliferation seem to be at high risk of having tractional changes following anti-VEGF treatments,” Dr. Drenser said.
Patients were treated with surgery if this problem was encountered, she added.
ROP patients
In the ROP group, Dr. Drenser selected five patients who were unresponsive to laser treatment or had progressive posterior retinopathy of prematurity. In each patient, both eyes were treated with laser, and one eye was injected with Macugen.
“All eyes received laser,” she explained “This did not negate laser treatment but was in addition to.”
Two of the patients, Dr. Drenser said, did “very well,” while three developed retinal detachments bilaterally.
Dr. Drenser expressed concern that while there was “early impressive decrease in vascular activity” characterized by regression within a week and a delay of retinal detachment, any fibrotic tissue with proliferative changes aggressively underwent tractional change.
“It did seem to delay the onset of retinal detachment, but we did notice – similar to patients in FEVR – contractile changes early proliferative functional changes in vitreoretinal function: any fibrotic tissue proliferative changes aggressively underwent contractile change,” she said.
Complications
These complications with contractile and tractional changes in both the FEVR and ROP groups were not predicted by Dr. Drenser when entering the study.
The theory, she explained, is that transforming growth factor beta (TGF-beta), a natural antagonist of VEGF, is unopposed when VEGF is blocked.
“This unopposed TGF-beta may end up more practically exacerbating proliferative tissues and causing retinal detachments and tractional changes,” she said.
Still, anti-VEGF therapy holds some promise for the treatment of pediatric vitreoretinopathies in its ability to quiet the eyes and even lessen the bleeding for possible surgeries for detachments or complications, she said.
“Basically we think these are some early steps in looking at how we can better realize some of our new therapies for treating pediatric vitreoretinopathies, and we hope further studies in this area will help us to fine-tune the treatment modalities currently used,” Dr. Drenser said.
For more information:
- Kimberly A. Drenser, MD, PhD, can be reached at Associated Retina Consultants, 3535 West 13 Mile Road, Suite 632, Royal Oak, MI 48073; 248-288-2280; fax: 248-288-5644; e-mail: kimber@pol.net.
- Katrina Altersitz is an OSN Staff Writer who covers all aspects of ophthalmology.