Ocular Complications After HSCT in Children

Roxanne Nelson

February 28, 2013

Ocular complications are common in children who undergo hematopoietic stem cell transplantation (HSCT), but most appear to be mild and have no long-term serious outcomes, according to data published online today in JAMA Ophthalmology.

This conclusion comes from a prospective study of 49 children who underwent HSCT; 13 of them (27%) developed an ocular complication. The most common conditions were dry eye syndrome and retinal hemorrhage.

The researchers, led by Viera Kalinina Ayuso, MD, from the University Medical Center Utrecht, the Netherlands, recommend that all children be screened before undergoing HSCT to look for ocular abnormalities that could require prophylactic treatment.

They were unable to conclude that a more aggressive screening program is useful, but recommend that ophthalmologists and pediatricians be aware of the higher risk in these children.

Long-term Data Absent

Smita Bhatia, MD, MPH, who was approached for independent comment by Medscape Medical News, pointed out that Dr. Ayuso and colleagues only looked at patients up to a year after transplantation. "So we can't really extrapolate what the residual long-term effects will be," said Dr. Bhatia, who is the Ruth Ziegler Chair in Population Sciences at City of Hope in Duarte, California.

She explained that many large studies have found a high risk for cataract formation in both children and adults over the long term. "They are also at a high risk for dry eye, which is a very common symptom and is usually related to graft vs host disease [GVHD]," she said.

Cataracts are a long-term complication that occur several years after transplantation, Dr. Bhatia explained. "The Children's Oncology Group guidelines recommend annual ophthalmologic exams to evaluate for cataracts and other complications," she added.

Recipients at Risk

HSCT offers the only potential for a cure for many hematologic cancers, and success and survival rates after this procedure in children continue to improve. But even if the cancer is cured, the recipients remain at risk for psychologic and chronic health conditions.

As previously reported by Medscape Medical News, one study found that 74% of survivors reported at least 1 chronic health condition, whereas only 29% of their siblings did (P < .001). In addition, 25% of the survivors reported severe or life-threatening conditions, compared with only 8% of their siblings (P < .001).

Viral Reactivation Common

In their study, Dr. Ayuso and colleagues focused on eventual ocular involvement during systemic viral reactivations. They note that opportunistic infections due to immunosuppression in the first few months after HSCT can affect the eyes, but no systematic prospective studies have examined this.

Their prospective study, conducted at the Wilhelmina Children's Hospital in Utrecht, involved 28 children who underwent HSCT for malignant conditions (including acute lymphoblastic leukemia, acute myelogenous leukemia, juvenile myelomonocytic leukemia, and non-Hodgkin's lymphoma) and 21 children who underwent HSCT for nonmalignant conditions (including metachromatic leukodystrophy, myelodysplastic syndromes, and common variable immunodeficiency).

All 49 children underwent ophthalmologic evaluations before HSCT, before discharge from the HSCT unit, and 3, 6, and 12 months after HSCT. Eye examinations were also preformed during systemic viral reactivation.

Four children (8%) had abnormal results on the ophthalmologic evaluation conducted before HSCT: 1 patient had mild dry eye syndrome, 1 had simultaneous retinal hemorrhage and dry eye syndrome, 1 had optic disc edema, and 1 had chorioretinal scarring.

In the year after HSCT, 7 patients (14%) developed dry eye syndrome, 6 (12%) developed retinal hemorrhages, 3 (6%) developed optic disc edema, 2 (4%) developed chorioretinal lesions, 1 (2%) developed vitritis, and 1 (2%) developed increased intraocular pressure.

In all 6 patients who developed retinal hemorrhages, they were intraretinal. These did not threaten vision, but were associated with a deep thrombocytopenia in all patients.

In the 3 months after HSCT, systemic viral reactivations occurred 9 patients with cytomegalovirus, 6 with varicella-zoster virus, 4 with human herpesvirus 6, 3 with adenovirus, and 2 patients with Epstein–Barr virus. Four of these patients developed more than 1 different viral reactivation. In addition, optic disc edema developed in 3 patients and bilaterally increased intraocular pressure of 25 mm Hg developed in 1 patient.

More Common With Malignant Disease

Three to 12 months after transplantation, new-onset dry eye syndrome was observed in 7 patients (14%); the median time to developing dry eye syndrome was 5 months after HSCT. In 4 of these patients, the dry eye syndrome was accompanied by characteristic systemic manifestations of acute (2 patients) and/or chronic GVHD in at least 1 other organ (3 patients).

Overall, patients with any ocular complication after HSCT were significantly older than those without complications (median age, 13.3 vs 3.4 years; < .001).

Children with malignancies had a higher risk for ocular complications than those with nonmalignant conditions; 12 of the 13 patients (92%) with ocular abnormalities after HSCT had a malignant disease.

Of those with malignant disease, 12 of 28 (42%) developed ocular abnormalities; of those with nonmalignant disease, 1 of 21 patients (4%) did (relative risk, 10.5; P = .003).

Most of the detected abnormalities were relatively mild and did not threaten vision, the researchers note, but the "potential risk of development of vision-threatening complications in this population remains."

Thus, the primary "goal of post-transplantation screening within the first year after HSCT should be a limitation of eventual damage and long-term visual sequelae," they write.

The study was financially supported by the following Dutch nongovernment scientific funds: Dr. F.P. Fisher Stichting, Stichting Nederlands Oo-gheelkundig Onderzoek, and ODAS Stichting. The authors have disclosed no relevant financial relationships.

JAMA Ophthalmol. Published online February 28, 2013. Abstract