Visual outcome of a cohort of children with neurofibromatosis type 1 and optic pathway glioma followed by a pediatric neuro-oncology program

Abstract

We evaluated the visual outcome of a cohort of children with neurofibromatosis type 1 (NF1) and optic pathway glioma (OPG) treated according to standardized therapeutic guidelines. The study population consisted of all consecutive patients with NF1 and OPG referred to a specialized pediatric neuro-oncology program between 1994 and 2004. Treatment was instituted only in cases of progressive disease or clinical deterioration. Treatment modalities were chemotherapy (based on vincristine/ carboplatin) for children younger than 5 years and radiotherapy for all others. Ten boys and 10 girls (seven with a positive family history) entered the trial (median age at diagnosis of OPG, 29 months). At a median follow-up time of 78 months, seven patients had been treated with chemotherapy only, four with radiotherapy, and four with chemotherapy plus radiotherapy. Five patients were observed only. Currently, 18 are alive and two have died. Eight patients were treated for progressive visual loss in the face of stable disease, five for tumor volume increase without visual deterioration, and two for symptomatic tumor volume increase. At referral, six children had a visual acuity (VA) of , 30% in both eyes; eight children had 100% VA bilaterally. At referral, the visual field (VF) could be assessed in three children: One had VF loss in both eyes, one had VF loss in one eye, and one had normal VF. At last follow-up, eight children had VA , 20% in both eyes; only two children had 100% VA in both eyes. Among 11 children who had some visual function, three had VF loss in one eye and three in both eyes, and five had an intact VF. Contrast and color sensitivity were abnormal in seven and six patients, respectively. Thirteen children fell into the WHO hypovision category. In summary, among the 15 children treated, one had a definitive and two a mild improvement in VA. In conclusion, the visual outcome of this selected cohort of NF1 patients with OPG is unsatisfactory. A critical reappraisal of the therapeutic strategy adopted is needed.

Clinical and genetic aspects of neurofibromatosis 1

“…175,177 Most children with NF1 who develop optic pathway gliomas do not require treatment, but chemotherapy is the treatment of choice for progressive tumors. 20,24,26,211,212 Surgical treatment of optic pathway gliomas is usually reserved for cosmetic palliation in a blind eye, and radiotherapy is usually avoided because of the risk of inducing malignancy or moyamoya in the exposed field. 31,56 Several controlled trials for treatment of optic pathway gliomas are available to individuals with NF1.…”

“…31,56 Several controlled trials for treatment of optic pathway gliomas are available to individuals with NF1. 20,211 The less aggressive course of most brainstem and cerebellar gliomas in people with NF1 should be taken into consideration in the management of these tumors. 22,23,29,30 Bracing is usually ineffective in children with NF1 and rapidly progressive dystrophic scoliosis.…”

Functional outcome measures for NF1-associated optic pathway glioma clinical trials

“…Standard color vision testing (e.g., Ishihara) requires cooperation and the ability to read numbers or identify shapes; thus, most very young children with NF1-OPG are unable to complete testing. 22 Color vision data are rarely collected, 24 and changes in color vision over time are rarely reported in OPG studies. Testing color vision may be helpful in differentiating the cause of VA loss.…”

Screening children with NF1 for optic pathway glioma – Yes

“…12 There have been a number of papers that have shown visual and radiological stabilisation, and sometimes improvement, in children with progressing OPG treated with chemotherapy. 13,14 This prompted the Listernick group to recommend this treatment. 2 There are currently a number of phase I and II trials in the United States looking a new treatments for OPG, including Everolimus (RAD001), 15 Erlotinib (Tarceva), 16 and Sirolimus (Rapamycin).…”