Sensitivity, Specificity, and Cutoff Identifying Optic Atrophy by Macular Ganglion Cell Layer Volume in Syndromic Craniosynostosis

Abstract

PurposeDetermine sensitivity, specificity, and cut-off of macular ganglion cell layer (GCL) volume consistent with optic atrophy in children with syndromic craniosynostosis (CS). Investigate whether obstructive sleep apnea (OSA), Chiari malformation, history of elevated intracranial pressure (ICP), CS diagnosis, age, or sex independently alter GCL volume with CS. DesignRetrospective cross-sectional study. SubjectsPatients with syndromic CS evaluated at Boston Children’s Hospital (2010 – 2022) with reliable macular optical coherence tomography (OCT) scans. MethodsLatest ophthalmic examination that included OCT macula scans was identified. Age at examination, sex, ethnicity, best-corrected logMAR visual acuity, cycloplegic refraction, and funduscopic optic nerve appearance were recorded in addition to history of primary or recurrent elevated ICP, Chiari malformation and OSA. Spectral domain-OCT software quantified segmentation of macula retinal layers, and was manually checked. Main Outcome MeasuresPrimary outcome was determining sensitivity, specificity and optimal cutoff of GCL volume consistent with optic atrophy. Secondary outcome was determining possible independent association of previously elevated ICP, OSA, Chiari, CS diagnosis, logMAR acuity, age, or sex with altered GCL volume. ResultsMedian age at examination was 11.9 years (interquartile range (IQR), 8.5-14.8 years). Fifty-eight of 61 patients had reliable macula scans, 74% were female, and diagnoses were Apert (n=14); Crouzon (n=17); Muenke (n=6); Pfeiffer (n= 6); and Saethre-Chotzen (n=15). Optimal cutoff identifying optic atrophy was GCL volume <1.02mm3 with a sensitivity of 83% and specificity of 77%. Univariate analysis demonstrated significantly lower macular GCL volume with optic atrophy on fundus exam (P<0.001), Apert syndrome (P<0.001), history of elevated ICP (P=0.015), Chiari malformation (P=0.001), OSA (P<0.001), in males (P=0.027) and with worse logMAR acuity (-0.36, P<0.001). Multivariable median regression analysis confirmed that only OSA (P=0.005), optic atrophy on fundus exam (P=0.003), and worse logMAR acuity (P=0.042) independently associated with lower GCL volume. ConclusionsMacular GCL volume <1.02mm3 predicted optic atrophy in patients with CS with sensitive of 83% and specificity of 77%. OSA, a treatable often concomitant disorder, was independently associated with lower GCL volume. Surveillance for optic neuropathy by GCL volume proved effective in a population where cognitive skills can limit acquisition of other key ophthalmic measures.