Visual outcome, ocular findings, and visual processing skills after allogeneic stem cell transplantation in children

Background: Stem cell transplantation (SCT) offers a chance of cure in children with leukaemia and other life-threatening haematological, immunological, and metabolic diseases that do not respond to conventional treatment. Pre and post SCT, these children receive irradiation, and/or chemotherapy and immunosuppressive agents which like the primary disease may adversely affect the eye, the central nervous system as well as the posterior visual pathways and potentially threaten vision. The most commonly described ocular problems after SCT in childhood are cataract, dry eye syndrome (DES), and conjunctival or corneal graft-versus-host-disease (GVHD).

Aims: To determine the visual outcome, the frequency of ocular complications, visual fields, visual evoked potentials, and visual processing skills in a group of children/young adults who underwent SCT in childhood and to investigate the possible impact of the underlying disease, conditioning regimen, and treatment post SCT.

Subjects and methods: An ocular examination, including best corrected visual acuity (BCVA), refraction, slit lamp and fundus examination, tear break-up time, Schirmer s test, intraocular pressure; digital fundus photography, Rarebit visual field perimetry, visual evoked potentials, and visual processing skill tests, were performed in 79 children (37 boys, 42 girls; age median 7 years range 2 18) during 2004 2007.

Results: A best corrected visual acuity (BCVA) of 0.5 was achieved in 96% of the eyes. There was an increased risk of cataract and cataract surgery after conditioning including irradiation compared to chemotherapy (p < 0.001). There was an increased risk of developing cataract earlier if the child received single dose total body irradiation (TBI) compared to fractionated TBI (p < 0.01). Cataract development did not correlate with prolonged exposure to corticosteroids or chronic GVHD. Thirty-two percent of the patients showed objective signs of DES, defined as corneal staining with a short break-up time and/or pathological Schirmer. Malignant disease increased the risk of DES in girls. Frequent occasions of high cyclosporine A levels showed a significant association with DES. Single dose TBI and cataract surgery significantly correlated to a lower mean hit rate on visual field examination. Digital measurements of optic discs demonstrated significantly larger optic disc cup areas and smaller rim disc areas than reference material. Pathological visual evoked potentials (VEP) were observed in 15% of patients and were significantly associated with decreased BCVA. VEP may be of clinical use in patients with malignant diseases and/or patients conditioned with TBI. Four children with mucopolysaccharidosis I-Hurler showed a reduction of corneal opacities after early SCT but a decreased BCVA and high hyperopia were still present. In fanconi anaemia (FA) patients small optic discs were observed in six of ten eyes. Visual perceptual skills were subnormal in FA patients.

Conclusion: Various ocular complications are common in children treated with SCT. Regardless of the prevalence of anterior and posterior abnormalities, the ultimate visual outcomes were excellent in the majority of the patients. The choice of conditioning regimen but also the character of the underlying disease had an impact on the prevalence of complications. Awareness of and systematic and close follow-up of these sometimes severe complications, as well as early intervention are necessary to preserve good visual perception in this continuously increasing group of patients.

List of scientific papers

I. Fahnehjelm KT, Törnquist AL, Olsson M, Winiarski J (2007). "Visual outcome and cataract development after allogeneic stem-cell transplantation in children." Acta Ophthalmol Scand 85(7): 724-33. Epub 2007 Aug 28
https://pubmed.ncbi.nlm.nih.gov/17725615

II. Fahnehjelm KT, Törnquist AL, Winiarski J (2008). "Dry-eye syndrome after allogeneic stem-cell transplantation in children." Acta Ophthalmol 86(3): 253-8. Epub 2007 Dec 18
https://pubmed.ncbi.nlm.nih.gov/18093259

III. Törnquist AL, Olsson M, Martin L, Winiarski J, Fahnehjelm KT (2010). "Visual field results and optic disc morphology in patients treated with allogeneic stem-cell transplantation in childhood." Acta Ophthalmol Jan 8: Epub ahead of print
https://pubmed.ncbi.nlm.nih.gov/20064124

IV. Törnquist AL, Martin L, Winiarski J, Fahnehjelm KT (2010). "Ocular manifestations in Fanconi Anaemia." British Journal of Ophthalmology (Submitted)

V. Fahnehjelm KT, Törnquist AL, Malm G, Winiarski J (2006). "Ocular findings in four children with mucopolysaccharidosis I-Hurler (MPS I-H) treated early with haematopoietic stem cell transplantation." Acta Ophthalmol Scand 84(6): 781-5
https://pubmed.ncbi.nlm.nih.gov/17083538

VI. Törnquist AL, Andersson T, Winiarski J, Fahnehjelm KT (2010). "Visual evoked potentials in short and long term survivors after allogeneic stem cell transplantation in childhood." (Manuscript)