Nancy A. Melville

April 11, 2014

PALM SPRINGS, California — Ocular complications, particularly cataract and dry eye syndrome, are common in survivors of childhood bone marrow transplantation, and the monitoring of such patients should include careful ocular screening, according to a new study.

"With medical advances, children requiring bone marrow transplant for various hematologic malignancies, solid tumors, and nonmalignant diseases have increasing survival rates," said first author Julie Calderwood, MD, senior ophthalmology resident at the University of Tennessee Health Science Center in Memphis.

"It's important for pediatric and general ophthalmologists to be aware that potential ocular complications can have a long-term impact," she said.

The results of the study were presented here at the American Association for Pediatric Ophthalmology and Strabismus 2014.

Ocular findings have previously been seen in adults who have undergone bone marrow transplantation, but research on the effects in children has been lacking.

To investigate the issue, Dr. Calderwood and her colleagues conducted a retrospective review of children older than 7 years and adolescents who underwent bone marrow transplantation at St. Jude Children's Research Hospital in Memphis from 1995 to 2009.

The study involved 63 girls and 85 boys who had an ophthalmic examination before bone marrow transplantation and at least 1 follow-up exam after the transplantation. Three of the 148 patients had evidence of cataract prior to transplantation, and were therefore excluded from the cataract analysis.

Mean age at the time of transplantation was 13.5 years. The most common indications for transplantation were acute lymphocytic leukemia (49 patients), acute myeloid leukemia (31 patients), and aplastic anemia (15 patients).

At a mean follow-up of 3.8 years (range, 0.7 months to 12.4 years), 40 (27.5%) of the children developed cataracts and 4 (10%) required cataract surgery.

The strongest predictors of cataract development were hematologic malignancy (= .012), survival status (P = .0006), cytomegalovirus recipient status (P = .045), and cytarabine (P = .0251).

The risk for cataract development increased with length of survival. For patients who survived 15 years after transplantation, the probability of developing a cataract was 42.88%.

At follow-up, 57 (38.5%) patients had developed dry eye syndrome. After adjustment, the strongest predictive factors for the condition were older age at transplantation (P = .0085), chronic graft-vs-host disease (P = .0008), and survival status (P = .012).

In addition, 5 (3.4%) patients developed herpes zoster ophthalmicus and 7 (4.7%) developed ocular chronic graft-vs-host disease.

Seven children (4.7%) developed infectious retinitis; 2 cases were caused by Candida and 1 case by Aspergillus.

Nine (6.1%) patients developed papilledema, and 3 (2%) developed bone marrow transplantation retinopathy.

Although ionizing radiation has been shown to play a role in the development of cataracts, this study showed that radiation was only a risk factor in the initial analysis; the association lost significance in the multivariate analysis. This might be because smaller doses of fractionated irradiation are currently used, Dr. Calderwood pointed out.

She explained that the higher risk in patients with hematologic malignancies was likely the result of the large number of patients with acute lymphoblastic leukemia. Previous studies have shown that patients with acute lymphoblastic leukemia had a higher incidence of cataract development, which was thought to be secondary to pretransplant treatment with systemic corticosteroids.

We did not find a significant association between the use of systemic steroids and cataract development, but "we did not look at individual steroid dosages, which varied for the different treatment protocols," Dr. Calderwood said

She speculated that the higher risk for dry eyes in older children might be explained by a decreasing ability to regenerate conjunctival cells.

Most patients who developed dry eye or ocular chronic graft-vs-host disease saw improvement with artificial tears, punctual plugs, or topical corticosteroids; however, studies have shown that pediatric bone marrow transplant patients who develop dry eye might not revert to normal tear function and could require treatment into adulthood.

Although there were few posterior complications, the investigators recommend ophthalmic examinations before bone marrow transplantation to evaluate pre-existing pathology.

"Serial examinations should be performed while patients are immunosuppressed, especially if opportunistic infections are found in other systems, because the ocular manifestations of such infections can be devastating," they write.

"The percent incidence of cataract was surprising to me," said Kathy Lee, MD, a pediatric ophthalmologist at St. Luke's Children's Hospital in Boise, Idaho.

She told Medscape Medical News that the findings on cataracts are, in fact, higher than she would have expected. "My clinical impression is that the incidence of cataract is less now that alternatives to systemic steroids are used for immunosuppression."

Although ocular complications are recognized as being associated with bone marrow transplant, this study offers an important, well-powered assessment of the risks, she pointed out.

"The side effects described are well appreciated following bone marrow transplant in children," Dr. Lee explained.

The study "contributes to our understanding by presenting these findings for a large number of children and adolescents," she told Medscape Medical News.

Dr. Calderwood and Dr. Lee have disclosed no relevant financial relationships.

American Association for Pediatric Ophthalmology and Strabismus (AAPOS) 2014: Abstract 70. Presented April 5, 2014.

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