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Clinical Update: Pediatrics
Considering PPV in the Treatment of Juvenile Uveitis
Over the past few years, retina surgeons have debated the role of pars plana vitrectomy (PPV) in treating chronic and stubborn juvenile uveitis. The surgery has become increasingly efficacious and safe for children, and some specialists have become interested in using PPV as an alternative to long-term medication management in younger patients.
Although the evidence on the efficacy of PPV compared with medication has consisted largely of case studies, a retrospective analysis of PPV in juvenile uveitis published in Eye stirred up interest in the procedure.1
“The paper created a flurry of entries on blogs from the American Uveitis Society. It became clear that a lot of ophthalmologists and uveitis specialists were stunned by our results,” said senior author C. Stephen Foster, MD, president and CEO of the Massachusetts Eye Research and Surgery Institution and clinical professor of ophthalmology at Harvard Medical School.
A Risk of Blindness
One reason the study garnered so much interest is precisely because the stakes are so high. Although the prevalence of uveitis is much lower among children than in adults, the rate of visual loss in children is higher because they often present later in the course of their disease and are more likely to be subject to complications.
Severe visual loss occurs in 25 to 33 percent of childhood uveitis cases, said J. Fernando Arevalo, MD, director of the Clinica Oftalmologica Centro and professor of ophthalmology at the Universidad de Los Andes in Caracas, Venezuela. “Because there are often relatively few symptoms in children, they often have established pathology and decreased visual acuity by the time they get to an ophthalmologist.”
The PPV Study
Patients in the study conducted by Dr. Foster and his colleagues had been diagnosed with uveitis for a mean of 19 months. After PPV with endolaser or cryotherapy, 27 of the 28 eyes had no sign of active uveitis after surgery and a mean follow-up of 13 months. The diagnoses of the patients included pars planitis, idiopathic panuveitis and juvenile idiopathic arthritis–associated iridocyclitis. Although many patients still required postsurgical immunomodulatory therapy, the amount of medication needed decreased.
After surgery, inflammation levels decreased and visual acuity improved. Before surgery, the median BCVA was 20/158; after six months of follow-up, 28 eyes had a median BCVA of 20/60. The only child who did not benefit from PPV had panuveitis associated with retinal vasculitis. This case was treated with intravenous infliximab (Remicade), the researchers said.
Complications were limited to two cases of retinal tears during PPV surgery, which were successfully treated intraoperatively, and one retinal detachment that was later treated with a scleral buckle. Four eyes with preoperative clear lenses also developed cataracts within six months of PPV, a rate similar to previously published reports on the surgery, Dr. Foster said.
The authors acknowledge the limitations of their study, including its retrospective nature, the small number of patients and selection bias, since those who underwent PPV had uveitis that was poorly controlled by medication. Nonetheless, they decided to publish their data to raise awareness of PPV as an option for chronic juvenile uveitis, and to spark interest in clinical trials that might compare it with medication management, Dr. Foster said.
Drugs vs. Surgery
The cornerstone of treatment for pediatric uveitis is corticosteroids, but these drugs can have significant side effects when used long term. Most uveitis specialists try to limit the use of steroids as much as possible. “With continued steroid use, you pay inevitable consequences,” Dr. Foster said.
In chronic cases of pediatric uveitis, many ophthalmologists often move to immunosuppressants, such as methotrexate (Rheumatrex) or tumor necrosis factor–inhibiting drugs for second- and third-line treatment. These medications have potential side effects as well, including susceptibility to infection and lowered blood counts.
While PPV has long been considered an alternative to medication management in select cases of pediatric uveitis, such as those that involve cataracts and Toxocara endophthalmitis, the improved results from PPV make it a more viable choice for a wider range of juvenile uveitis cases, Dr. Arevalo said.
In his experience, he said that many patients who undergo PPV have a decrease in inflammation as well as an improvement in visual acuity. How well a patient responds to PPV can often depend on how long inflammation and cystoid macular edema have been present, he said. The incidence of complications, such as intravitreal hemorrhage, infections and retinal detachment, occur at a rate of less than 5 percent, he noted.
It is notable that those who favor the use of PPV report that the surgery is not likely to become widespread—at least not in the near term—because it requires specialized expertise in uveitis as well as retinal surgery involving the vitreous, Dr. Arevalo said.
About the Surgery
Retina experts who are considering PPV for a young patient should be aware of several issues.
Patient selection. PPV is not an answer for all or even most children with chronic uveitis, Dr. Foster said. In his practice, most children with chronic uveitis receive chemotherapy after failing steroids. He recommends that children who receive PPV should be carefully selected; the best patients are those whose uveitis is poorly controlled by medication for an extended time and who are most likely to have therapeutic benefit from the surgery.
Study coauthor Peter Chang, MD, who is now associate resident at New York Eye and Ear Infirmary, said that another indication for surgery “would be compliance—if we are worried that patients would not be able to follow up with a doctor every six weeks.”
Technique. Dr. Foster maintains that any well-trained vitreoretinal specialist or ocular immunologist with experience in vitreoretinal surgery should be able to perform PPV in children with stubborn uveitis. The general techniques for PPV in children are similar to those used for adults, although surgeons should take extra care to avoid provoking cataract formation.
The pediatric vitreous is also different from adult vitreous, he said. “The vitreous in a child is firmer and more tenacious than in an adult. It’s much less likely to follow the port of the instrument during surgery, and so you have to gently but steadily move the vitreous cutter to the surface of the retina. If you gobble up the vitreous as in adult surgery, you increase the risk of traction on the retina and subsequent retinal tear in children.”
Janet L. Davis, MD, professor of ophthalmology at Bascom Palmer Eye Institute, noted that in pediatric patients, there is often a distinct boundary between abnormal, inflamed anterior vitreous and the clear, gel-like posterior vitreous. “In those cases, the posterior hyaloid can be extremely difficult to elevate,” she said. “Unless visualization agents such as triamcinolone are used and special techniques including retinal picks, brushes and high-flow aspiration are employed, the posterior hyaloid cannot be easily detached in most children, and in the case of normal posterior vitreous gel, it may not be able to be detached at all without retinal injury.” Without visualization agents, she added, “It won’t be possible to tell whether the hyaloid was elevated or not, and even then, you can sometimes be fooled.” Plus, she noted that it’s unclear whether elevation of the hyaloid is necessary for a therapeutic effect or whether a very good core vitrectomy is sufficient.
Pars planitis. Dr. Davis added another caveat: “When operating on children with pars planitis, you have to be sure that the usual surgery-safe zones are free of inflammatory exudates. Putting instruments through any portion of the pars plana covered with exudates is potentially hazardous. If lens opacity, synechiae or patient cooperation prevent a good preoperative evaluation of the pars plana, make a plan to directly visualize the pars plana before inserting the instruments,” she said, noting that high-resolution ultrasound of the anterior segment can be used if a direct view cannot be obtained.
Early Referral Is Essential
Whether or not a child is treated with PPV or medication management following an initial trial of steroids, it’s vital to reduce the burden of blindness secondary to childhood uveitis by early referral, Dr. Foster said.
The decision to perform PPV in a child with chronic uveitis must be weighed carefully, he added. The retina or uveitis specialist must consider the possibility of reduced inflammation, better eyesight and less reliance on chemotherapy or biologics with PPV against the risks of surgery. In general, PPV should be considered only in difficult cases where management with steroids and/or biologics has not controlled symptoms, or when the child has been taking biologics or chemotherapy chronically, Dr. Foster said.
“In children with chronic or especially violent uveitis, the best advice I can give is to be comfortable with earlier referral to a uveitis specialist or to comanage the case with an immunologist or rheumatologist,” Dr. Foster said. A child who continues to have chronic symptoms after initial treatment with steroids needs to be under the care of a specialist—an ophthalmologist who is comfortable with vitrectomy using an endolaser or a rheumatologist or hematologist who can prescribe and monitor systemic immunomodulatory therapy, he said.