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An Ophthalmology Crisis: Retinopathy of Prematurity
Soaring numbers of preterm births and new screening criteria make a problematic situation worse.
FRANK CELIA, CONTRIBUTING WRITER

Prescient retinal and pediatric ophthalmologists have been sounding warnings for at least 4 years regarding the higher incidence of preterm births and the corresponding higher occurrence of retinopathy of prematurity (ROP). This preterm birth phenomenon, coupled with fewer specialists who are willing to screen infants for ROP, will eventually result in higher rates of childhood blindness due to lack of early detection. It appears that 2006 may be the year that the rest of ophthalmology, and indeed the rest of the medical world, confronts the grim reality of this equation.

This article will address the issues that affect ophthalmologists who screen for ROP, as well as the consequences for opting out of screening for medicological reasons.

HIGHER STANDARDS, FEWER VOLUNTEERS

In February, new screening guidelines for preterm births increased the number of infants requiring exams and the frequency of those exams, thus making a bad problem worse. In July, the American Academy of Ophthalmology (AAO) presented hard data supporting what everyone pretty much knew: retinal and pediatric subspecialists avoid these patients largely for fear of malpractice suits (the Academy hopes these data will help convince Congress to institute meaningful tort reform). That same month, the Institute of Medicine (IOM) issued a report highlighting the negative health consequences of a 30% nationwide jump in premature births during the last 2 decades, and calling on fertility doctors to curtail multiple births, which contribute to high preterm birth incidence. Medical advances have enhanced premature infant survival rates, but not lowered the frequency of complications. For example, the last 5 years have seen a doubling in severe ROP cases.

Many believe telemedicine, implemented with cameras and digital imaging, could alleviate the manpower shortage in ROP screening, traditionally a bedside exam. Though telemedicine shows great promise — in many respects, it is superior to the bedside exam — even its strongest proponents admit its true value is yet unproven and it would provide, at best, only a partial solution.

ROP'S HISTORY

Retinopathy of prematurity is a potentially blinding disease in which normal retinal development can become compromised following a premature birth. This leads to abnormal blood vessel growth, bleeding, scar tissue, and eventually retinal detachment; the latter being the primary cause of blindness and visual impairment in this disease.

Discovered in the 1940s, ROP was widely thought to be associated with too much oxygen in infants' incubators. Later, it was determined that while excessive oxygen was indeed a factor, it was not the sole cause, and that, in fact, too little oxygen could lead to problems also.

By the 1980s, international experts had devised an easy-to-implement framework for diagnosing and staging the disease. Given a properly controlled and monitored oxygen environment, the 2 main risk factors have been found to be low birthweight and young gestational age.

After careful screening and monitoring, infants with "threshold" disease move on to treatment with cryotherapy or laser photocoagulation. With timely intervention, treatment outlook is extremely positive, says Antonio Capone, Jr., MD, director, Fellowship in Vitreoretinal Diseases and Surgery, of Associated Retinal Consultants in Royal Oak, Mich. Even without treatment, 85% of ROP cases spontaneously regress, and of the 15% that do progress, 85% of those respond well to cryotherapy or laser photocoagulation. In other words, in any given cohort of 100 ROP patients, if screening and treatment occur in a timely fashion, only about 2 infants will develop permanent vision loss. However, because such a large percentage of ROP cases spontaneously regress with no therapy at all, and current treatments entail side effects, risk of overtreatment remains a concern.

TRACKING ROP PATIENTS

Surgeons say the main challenge of ROP is identification and early treatment. So multifarious and unpredictable is its progression, that a delay of even 1 week may be devastating. However, keeping track of these infants presents a challenge. Preterm and low birthweight infants almost always suffer from serious, life-threatening coexisting conditions (1 in 5 do not survive a year).

Often, these infants are transferred from one neonatal intensive care unit (NICU) to another without prior notification. An infant's last name typically represents the mother's maiden name regardless of marital status, while at discharge, the name usually reverts to the father's last name, making tracking a patient difficult. Finally — and perhaps most significantly — parents, burdened as they are with myriad doctor appointments, may allow a "routine" eye exam to take a backseat to, say, a visit with the cardiologist.

Figures are inexact, but it is thought that 500 to 600 infants a year go blind because of ROP, the majority of cases believed to have been preventable, according to the American Academy of Ophthalmology.

A BAD SITUATION BECOMES WORSE

Two factors combine to bring this situation to a head: the rapidly increasing number of preterm births and a new set of screening criteria that calls for more infants to be screened more frequently.

One in 8 children is born premature — more than half a million a year, according to the IOM. Increasing popularity and effectiveness of infertility treatments that spur multiple births explains a small fraction of the problem, but no one is sure how to predict or prevent the remaining premature births.

According to the IOM report, African-American women appear to have a higher risk (18%), with Caucasian and Hispanic women being about equally at risk (12%), to deliver a premature infant. Other risk factors include low socio-economic status, being 16 years of age or younger or older than 35, poor diet, stress, lack of prenatal care, and smoking. Noting that this problem costs the nation some $26 billion annually, the report strongly suggests increased research efforts.

Generally speaking, the criteria for evaluating premature infants for ROP progression risk includes gestational age, birthweight, zone of observed disease (higher zones are more peripheral, thus indicating better prognosis), stage of disease (a lower stage represents a less severe disease), and the presence of vascular tortuosity (or "plus" disease). Disease location in clock hours is also pertinent to evaluation.

CHANGES IN GESTATIONAL CRITERIA AFFECT ROP EXAMINATIONS

In February, new recommendations unveiled in a joint statement by the AAO, the American Association for Pediatric Ophthalmology and Strabismus (AAPOS) and the American Academy of Pediatrics (AAP) changed the gestational age criterion from younger than or equal to 28 weeks to younger than or equal to 32 weeks.

Additionally, the new recommendations changed the circumstances and frequency of follow-up exams. Under the previous recommendations put in place in 2001, infants with a high risk of progression were to be re-examined within 1 or 2 weeks. Under the new recommendations, infants must be examined within 1 week. Formerly, ROP had to present in zone 1 to be classified as high risk. Now ROP can present in zone 2 and still qualify as high risk. Under new guidelines, plus disease plays a bigger role. A child with zone 1 disease and plus disease is considered a threshold case, regardless of the stage of the disease. Under old recommendations, this infant would require stage 3 disease before he or she was deemed threshold. Moreover, plus disease can develop very rapidly — in less than 1 week in some cases — meaning some infants require a screen as often as every 48 hours under the new criteria.

"In 2004, under the old guidelines, there were 60000 infants who met the screening criteria," says Darius M. Moshfeghi, MD, director of Pediatric Vitreoretinal Surgery and Ocular Oncology at Stanford University. Applying only the new gestational age criterion to that same infant population would increase that number to 80000," he says. "That is a 33% increase. That's huge."

Also worth noting: both sets of recommendations include an escape clause of sorts, adding that other infants "felt to be at high risk" should also undergo follow-up exams. "That [clause] is the one that is most often forgotten," says Dr. Moshfeghi, "except by lawyers."

LEGAL FEARS

Few things tug at the heartstrings of a jury like a permanently ill child, no matter who is at fault. Plaintiffs' attorneys see conditions like ROP as fertile ground for large judgments. In the last decade, several well publicized, multimillion dollar verdicts against ophthalmologists in ROP malpractice cases have been noted by the profession. Verdicts and settlements in the $5 or $10 million range are particularly worrisome to physicians because they risk exceeding their practice's insurance coverage. These are cases that can destroy practices and end careers.

"Most practices will have $1 million of insurance for 3 occurrences, or maybe as much as $3 million for 3 occurrences," says Dr. Capone. "But there are suits that have gone above $8 million. If that happens, you are done. Game over. You want to do what is right [by providing ROP treatment], but you also want to survive."

Complicating matters, reimbursement for ROP screening is low — sometimes ophthalmologists are paid as little as $20 per exam. Screening these infants has, for some, become a matter of noblesse oblige.

However, demand is outpacing the number of ophthalmologists willing to make such sacrifices; every year more and more qualified screeners opt out. As a result, hospitals are resorting to drastic measures. "Some people get strong-armed into it," says Michael T. Trese, MD, president of Associated Retinal Consultants. "The hospital tells doctors that if they want to keep hospital privileges, they had better be available for the NICU." Other hospitals go the opposite route, paying screeners a retainer to provide this service.

DECREASES IN SPECIALISTS TREATING ROP

Survey results released by the AAO in July show only half of pediatric retinal specialists currently treat ROP, and 20% of those who do, say they plan on stopping. Half of those who no longer treat ROP ceased within the last decade. Among them, 67% cited medical liability as the most influential factor in their decision. Also high on the grievance list — in most states, parents can sue until their child is 19 years of age.

Cause for concern no doubt exists, but a healthy dose of realism is also necessary, says Anne M. Menke, RN, PhD, risk manager of Ophthalmic Mutual Insurance Company (OMIC) and perhaps the country's foremost authority on ROP malpractice. "The fear is out of proportion to the facts," she concludes.

Evaluation of OMIC's records since 1987 reveals that claims involving ROP are extremely rare, representing approximately 0.5% of all their cases (though this may be partially due to the subspecialty's small size). The few final payouts from defendant physicians to plaintiffs for ROP lawsuits do tend to be higher than OMIC's average, about threefold higher, but even that amounts to average payouts of $330000 in ROP cases — bearing in mind only 22% of malpractice cases result in judgments against physicians. The highest ROP payout by an ophthalmologist insured by OMIC was $575000 — by no means a paltry sum, but not a practice-destroyer.

"Another thing to keep in mind is, if it is a jury verdict rather than a settlement, you won't know what the plaintiff is actually getting," Menke says. "These verdicts are often reduced by caps on damages."

Large verdicts make for sensational headlines and are touted on plaintiffs' attorney Web sites, but actual figures paid are often much lower. Also, ophthalmologists, usually one of several defendants (invariably including a hospital, whose deep pockets are the attorneys' primary target), are only responsible for a percentage of that sum.

As an example, Menke cites a recently resolved ROP case involving a $15 million verdict against defendants, of which the ophthalmologist was responsible for $1.5 million. The case was eventually overturned by the state Supreme Court; the physician never paid a penny. But for those who never got past the initial headlines, the message is: "$15 million verdict in ROP case," and nothing more, an overly simplified view that generates unwarranted fear, she says.

USING TELEMEDICINE TO SCREEN INFANTS

Justified or not, anxiety about ROP screening exists, leading to missed exams. Some NICUs, particularly those in rural areas, allow infants to go unscreened. Victor H. Gonzalez, MD, founder of Valley Retina Institute, a private practice in McAllen, Texas, says that while ROP should be rare in the United States, he still sees infants who present with stage 5 disease. Some infants do go on to present with stage 5 disease despite treatment, but to present with stage 5 at initial diagnosis means that an infant did not undergo an initial screening.

Using retinal cameras to screen infants from off-site locations is undergoing investigation, with many studies yielding positive results. The most prominent, international Photographic Screening Study for ROP (Photo-ROP), has been the topic of several presentations at ophthalmology meetings and is said to be scheduled for publication sometime this year.

In the study, skilled screener findings were compared to RetCam image findings (Clarity Medical Systems, Pleasanton, Calif). Results indicated that RetCam screening is 100% sensitive and 97% specific when compared to skilled screeners at detecting clinically significant ROP. The major finding of this study was that RetCam patients were referred for intervention 2 weeks earlier than those screened at bedside. This is considered an enormous advantage given the importance of timely intervention.

PRO AND CONS OF TELEMEDICINE

Cameras offer practitioners a number of other potential advantages. Since it is unnecessary for physicians to travel to the NICU for exam sessions, labor costs are decreased and scheduling conflicts with NICU nurses are avoided. In addition, photographs are better diagnostic tools than hand-made drawings, allowing for superior progression tracking and reliable evidence in the event of legal action. Photographs create what can be termed an "increased uniformity of expertise."

Dr. Capone explains that infants who are in the most danger, the ones who are smallest and have the most complications, are usually transferred to the big metro/university hospitals, while the healthier premies are left in the suburbs. These 2 groups of infants present with very different kinds of ROP, and thus, there are doctors who never have the opportunity to see the full range of the disease and are less experienced. Photographs allow doctors in the suburbs to see these more extreme cases, visual diagnosis being the standard of care here. Dr. Capone sees this as one of telemedicine's biggest advantages.

But cameras are expensive, around $75000 for the RetCam. Additionally, not all infants can be effectively photographed. Those with dark pigmentation and very small eyes present a challenge. Hence, every NICU still requires bedside examiners at some point. Cameras are less effective at imaging periphery disease (though advocates note such disease poses the least threat to vision). Although it saves on labor costs and enhances diagnostics, telemedicine will do little to prevent infants from getting lost in the shuffle and missing office visits, the true crux of ROP's legal difficulty.

Finally, it is unclear how the neonatology world will take to retinal cameras on its turf. "I cannot overstate the importance of having the nursing staff buy into [telemedicine]," says Dr. Gonzalez, who has implemented a successful telemedicine ROP screening program at his private practice. "Nurses are the ones who will make it work."

There is a learning curve. One report found 21% of photographs taken by a NICU nursing staff unreadable, but this was deemed a human error rather than a technical one, says Michael F. Chiang, MD, assistant professor of ophthalmology and biomedical informatics at Columbia University, which is conducting a study in this field.

This type of telemedicine is still in its infancy, mostly occurring at large academic centers. More studies are needed prior to mainstream acceptance. "There are very important potential benefits [to telelmedicine], but there are also a number of important barriers to developing systems that work and are economically self-sustaining," says Dr. Chiang. Telemedicine looks promising on paper, but additional research studies may be required to persuade hospital administrators, he notes.

Some NICUs appear to be taking notice. Dr. Moshfeghi, who spearheads the SUNDROP (Stanford University Network for the Diagnosis of ROP) telemedicine program, says he receives calls from interested units in the Bay Area about once a week. Right now, telemedicine appears as the only solution at hand, but perhaps another tactic might be convincing hospitals to treat ROP screening in a manner similar to audiology.

He says that currently, the chances of discharging an infant who is actively bleeding are higher than for one who has not undergone audio screening. "That kind of mentality has to be brought to bear in ROP screening," concludes Dr. Moshfeghi.

Frank Celia is a freelance medical journalist based in the Philadelphia area.