Avastin

“Cure for Retinopathy of Prematurity?”

Bevacizumab, the generic name for the brand drug Avastin, has slowly, over the last few years, gained in popularity as the drug to not simply augment, but completely replace the well-established and conservative treatment of peripheral retinal ablation (laser surgery).  Bevacizumab is the brainchild of Genentech/Roche.  It was manufactured as a treatment for certain cancers, together with a host of other chemotherapeutic agents.

At first, Avastin was used “off label” together with surgical therapies.  Its efficacy became apparent as some ophthalmologists at academic centers throughout the United States recognized the drugs capacity to prevent the neovascularization of new tortuous blood vessels responsible for the proliferation of ROP to the extent of retinal detachment.

In February of 2011, Helen Mintz-Hittner of the University of Texas published an article in the New England Journal of Medicine, singing the praises of Avastin.  She and her colleagues penned a new acronym (BEATROP) which followed several long-term well accepted groups whose goal was the elimination of blindness due to ROP such as CRYOROP and ETROP.   In essence, she told the medical world through this study that Bevacizumab was the cure for ROP.  The destructive, inefficient laser surgery (photocoagulation) and its predecessors (cryotherapy) would no longer be required to salvage vision for premature infants at risk for the disease.  Her study utilized only 150 children and failed to consider the long-term effect of Avastin upon the visual systems as other organs.

The concern expressed by experts extensively involved in the treatment and study of ROP over the course of the last three decades was that too many medical practitioners involved in the diagnosis and treatment of ROP would opt for the drug in lieu of the well-established cure rates demonstrated in repeated long-term studies following surgical options where “cure” rates were in the 90+ percentile for good vision following laser in high risk children.

In recent months, several of the nationally accredited clinicians and researchers involved in the ETROP and CRYOROP studies have expressed concern for the Avastin only therapy.  Again, no long-term high patient population studies had been published.  Experts such as Earl Palmer M.D., at the Casey Eye Institute at the Oregon Health & Science University remain fearful that given the relative cost differential between surgery and Avastin (the drug in much less expensive), the ease of use and relative need for serial screening examination, treaters would indiscriminately choose Bevacizumab.  Palmer is authoring with others, an article warning treaters to avoid the leap to Avastin by utilizing existing therapies until the long-term effects of Avastin are studied and understood.

The week after Dr. Helen Mintz-Hittner’s study was published, Michael Shapiro (no relation to this author), at the University of Illinois in Chicago published in Pediatric Retina, “A Discussion about the Practice of Pediatric Retina with Photographs.” In essence, Dr. Shapiro, while congratulating Dr. Mintz-Hittner and her group for their undertaking, expressed concern for “later recurrences (of ROP) that would be missed by examination at 55 weeks post menstrual age.”  Dr. Shapiro was fearful that Avastin may indeed “cure” some children with ROP, but may only delay the disease’s progression in other children to a time long after they have been discharged from the hospital and long after repeated serial retinal screening have ceased. It is a known caveat among those who treat the disease, that careful repeated examinations are crucial in discovering the property time window for progression of ROP to an extent where laser intervention would arrest the growth of neovascularization (new vessels).  Should a child treated only with Avastin who appeared to respond to the drug be discharged home after care had ceased, progression of the disease could recur many months later.  Without continual screening, once ROP recurred, it would progress to Stage 5, or total detachment, where no current therapies have shown meaningful promise for preservation of long-term vision in a large percentage of the ROP population.

Thus, the message is clear that while Avastin holds great promise in the treatment of ROP in the years ahead and now in conjunction with therapies such as photocoagulation and cryotherapy, it should not be the exclusive basis for treatment of the disease.