Dry-eye syndrome after allogeneic stem-cell transplantation in children.
OBJECTIVE
To report the prevalence of dry-eye syndrome (DES) in children and young adults treated with allogeneic stem-cell transplantation (SCT) during childhood; to relate DES to conditioning regimes, including total body irradiation (TBI) and chemotherapy, and to immunosuppressive drugs and graft-versus-host disease (GVHD).


METHODS
This cross-sectional study included 60 children/young adults transplanted because of leukaemia, various haematological disorders and inborn errors of metabolism between 1986 and 2004, with a follow-up time of 7.0 years (median, range 2-18). Clinical assessments, performed at a median age of 15.6 years (range 5.5-23.5), included an inquiry form on dry-eye symptoms, corneal status including fluorescein staining, 'break-up time' (BUT) and Schirmer test.


RESULTS
A total of 37 of 60 patients had DES defined as presence of corneal epithelial lesions with a pathological BUT and/or Schirmer test. Twenty-nine had had staining <1-10% of the corneal surface while eight patients had staining > or =10-25% of the corneal surface. All 37 patients with objective signs of DES, graded and not graded, had significant associations to subjective symptoms of dry eyes including dry eyes, red eyes, ocular irritation, secretion and sensitivity to light. Frequent occasions (above median; n = 7) of high cyclosporine A trough levels above 250 ng/ml were associated significantly with DES (P = 0.002). However, there was no association between DES and conditioning with single-dose (s-TBI) or fractionated TBI (f-TBI), busulfan or other chemotherapy. There were no associations between prolonged corticosteroid treatment or chronic GVHD and DES in the present study. DES was more common in patients with malignant diseases (P = 0.02). Malignant disease increased the risk of DES in girls but not in boys. Increased age at SCT increased the risk for DES in boys but not in girls (P = 0.02). Although severe keratitis occurred in three patients, nobody suffered corneal perforation.


CONCLUSIONS
DES with epithelial punctata keratopathy was common in children/young adults treated with SCT and more common if the patients were exposed to repeated high trough levels of cyclosporine A; however, DES was not associated with irradiation, corticosteroids or GVHD in the present study. Patients with objective DES also had subjective symptoms of dry eyes, which facilitate diagnosis. Girls with malignant diseases and boys who underwent SCT at later ages seem to demand higher attention and more frequent check-ups regarding DES. Patients with diagnosed severe DES needed frequent and continuous ophthalmological care to maintain treatment motivation.
Fahnehjelm
Kristina Teär
KT
Department of Clinical Neuroscience, Karolinska Institut, Stockholm, Sweden. kristina.fahnehjelm@ki.se
Törnquist
Alba-Lucia
AL
Winiarski
Jacek
J
D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000009:adverse effects / Q000627:therapeutic use; D000367:Age Factors; D002648:Child; D002675:Child, Preschool; D003316:Corneal Diseases / Q000175:diagnosis / Q000209:etiology; D003430:Cross-Sectional Studies; D015352:Dry Eye Syndromes / Q000139:chemically induced / Q000209:etiology* / Q000503:physiopathology / Q000628:therapy; D005260:Female; D005500:Follow-Up Studies; D006086:Graft vs Host Disease / Q000150:complications; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects; D007223:Infant; D008297:Male; D009369:Neoplasms / Q000150:complications; D012737:Sex Factors; D013194:Staining and Labeling; D033581:Stem Cell Transplantation / Q000009:adverse effects*; D013666:Tears / Q000378:metabolism; D019172:Transplantation Conditioning / Q000009:adverse effects; D014184:Transplantation, Homologous; D014792:Visual Acuity
D000305:Adrenal Cortex Hormones; D007166:Immunosuppressive Agents