Visual Field Loss in Children With Sporadic and Neurofibromatosis Type 1 (NF1)-Associated Optic Pathway Gliomas: Baseline Characteristics From a Multicenter, Prospective Natural History Study

Prior retrospective studies, limited by selection bias and lack of standardization, have reported a high prevalence of visual field (VF) loss in children with both sporadic and neurofibromatosis type 1-associated optic pathway gliomas (NF1-OPGs). Here we report the feasibility of Goldmann kinetic perimetry (GVF) testing and detail baseline VF function in a cohort of children with and without neurofibromatosis type 1 (NF1) enrolled in a prospective multicenter OPG natural history study.

Visual field loss in children with sporadic and neurofibromatosis type 1 (NF1)-associated optic pathway gliomas: Baseline characteristics from a multicenter, prospective natural history study Gena Heidary, Saprina Truong, Jiamu He, Sarah Whitecross, Arielle S. Garcia, Keshini Devakandan, Gui-Shuang Ying, Michael J. Fisher, Grant T. Liu, Nicole J. Ullrich, Arun R. Reginald , Robert A. Avery Boston Children’s Hospital, HMS Neuro-ophthalmology Service Children’s Hospital of Philadelphia The Hospital for Sick Children (SickKids) Toronto NANOS March 13, 2023 Disclosures • Grant support: NIH R01EY029687 (RAA, GH, ARR) • Children’s Tumor Foundation (GH, RAA) 2 Background • Visual dysfunction in the setting of optic pathway gliomas (OPGs) has been well documented with respect to visual acuity loss • Data regarding the impact of OPGs on visual fields are limited but needed – To provide reliable, quantifiable outcome measures of visual function – To characterize the relationship between visual acuity loss and visual field loss – Visual field loss may be the only morbidity in more posterior tumors – Visual field dysfunction impacts quality of life • reading, mobility, driving 3 • Retrospective study from 10 centers on visual outcomes from NF1-OPGs (Fisher MJ et al, Neuro Oncol 2012; 14:790-97.) • Follow up study of visual field outcomes using formal perimetric techniques – 25 children of the cohort of 115 patients – 76% with visual field deficits at final visit – 44% showed stability of VF changes, 19% showed improvement of VF function, and 38% had worsening of VFs – Posterior tumor extent associated with worse VF 4 Background • Natural History Study of NF1-OPGs – Rob Avery, Michael Fisher, Grant Liu – 25 centers, prospective study visual morbidity newly diagnosed NF1-OPGs • Biomarkers of Vision Loss in Children with Optic Pathway Gliomas – Rob Avery (CHOP), Gena Heidary (BCH) , Arun Reginald (SickKids) – 3 centers, prospective study visual morbidity OPGs – Goal enrollment 300 children < 18 years of age 5 Background • Natural History Study of NF1-OPGs – Rob Avery, Michael Fisher, Grant Liu – 25 centers, prospective study visual morbidity newly diagnosed NF1OPGs • Biomarkers of Vision Loss in Children with Optic Pathway Gliomas – Rob Avery, Gena Heidary, Arun Reginald – 3 centers, prospective study visual morbidity OPGs – Goal enrollment 300 children < 18 years of age 6 Aims • To detail baseline VF function in a cohort of children with and without neurofibromatosis type 1 (NF1) enrolled in a prospective multicenter OPG natural history study • To determine the feasibility of GVF testing in pediatric patients with OPGs 7 Methods • First half (<18 years) enrolled in a prospective longitudinal study of visual biomarkers in children with NF1- and sporadic-OPGs from 3 institutions were included • Standardized ophthalmologic assessments included visual acuity and perimetry with a GVF protocol • VF characteristics were analyzed across sex, age, tumor location, and type (NF1 vs. sporadic) on a per-subject basis 8 Methods • GVF Standardized Protocol – 16 meridia tested – III4e and I4e target size – V4e if unable to perform III4e • Analysis – Qualitative description – Quantitative • Visual field extent by meridian • Area of visual field using planimetry • Inter visit reproducibility 9 Results: Baseline Clinical Characteristics Age at visit (Months) N Mean (SD) Median (1st quartile, 3rd quartile) Min, Max All (N=150) Completed GVF (N=86) Not completed GVF (N=63) 149 117.3 (51.0) 117.0 [79.0, 159.0] [6.0, 214.0] 86 133.6(45.3) 137.0 [97.2, 167.8] [6.0, 213.0] 63 95.1(50.3) 89.0 [63.0, 120.5] [20.0, 214.0] Age at visit (Years) Mean (SD) Median (1st quartile, 3rd quartile) Min, Max 9.8(4.3) 9.8 [6.6, 13.2] [0.5, 17.8] 11.1(3.8) 11.4 [8.1, 14.0] [0.5, 17.8] 7.9(4.2) 7.4 [5.2, 10.0] [1.7, 17.8] Gender Male Female 73 (48.7%) 77 (51.3%) 45 (52.3%) 41 (47.7%) 28 (44.4%) 35 (55.6%) OPG type Sporadic NF1 66 (44.0%) 84 (56.0%) Tumor extent Optic Nerve (1) Chiasm/hypothalamus (2) Optic tract (3) 20 (13.3%) 32 (21.3%) 35 (23.3%) 39 (45.3%) 47 (54.7%) 26 (41.3%) 37 (58.7%) P-value* <0.001 <0.001 0.43 0.74 10 Results: Risk of VF Loss • VF loss was present in 52/86 (60%) at baseline exam # of subjects VF loss (%) Odds ratio (95% CI) P-value 0.09 0.16 Age at visit (Years) As continuous (per year increase) By age groups ≤8 >8, ≤11 >11, ≤14 >14 86 52 (60.5%) 1.11(0.98,1.24) 21 19 25 21 12(57.1%) 8(42.1%) 16(64.0%) 16(76.2%) Ref 0.55(0.15,1.91) 1.33(0.41,4.38) 2.40(0.63,9.03) 0.34 0.64 0.20 Gender Male Female 45 41 29(64.4%) 23(56.1%) Ref 0.71(0.30,1.68) 0.43 OPG type Sporadic NF1 39 47 27(69.2%) 25(53.2%) Ref 0.51(0.21,1.23) 0.13 Tumor extent Optic Nerve Chiasm/hypothalamus Optic tract 20 32 34 8(40.0%) 18(56.3%) 34(100%) Ref 1.93(0.62,6.00) 4.88(1.48,16.10) 0.02 0.26 0.009 11 Conclusions • GVF testing in pediatric patients with OPGs is feasible using a standardized protocol • The prevalence of VF loss at baseline was high and frequently associated with tumor extension to the optic tracts • Our data provide further support that standardized kinetic perimetry should be considered as an outcome measure for OPG clinical trials 12 Future Goals • Visual fields – To characterize extent of visual field loss longitudinally – To evaluate the structure-function relationship between visual fields, visual acuity and OCT – To describe inter visit reproducibility to provide guidelines for interpretation of visual field progression • Other characteristics associated with OPGs – NANOS Poster 349 Tais Estrela et al. : The Relationship between Choroidal Abnormalities and Visual Outcomes in Pediatric Patients with NF1associated Optic Pathway Gliomas: A Longitudinal Study 13