Optic disc Edema in patients with fibrous dysplasia/McCune-Albright syndrome: Craniomorphometric analysis and peripapillary retinal nerve fiber layer data

This article reports quantitative measurements of intracranial volume, optic canal area, and peripapillary retinal nerve fiber layer (RNFL) for a cohort of 124 patients with craniofacial fibrous dysplasia/McCune-Albright Syndrome (FD/MAS), previously used to determine risks for developing optic disc edema [1]. Of these, 7 subjects were diagnosed with optic disc edema. OSIRIX imaging analysis software was used to collect intracranial volume and optic canal diameter for 107 patients, via 3D multiplanar reconstruction (MPR) of ≤5 mm axial CT slices. Spectral-domain Optical Coherence Tomography (OCT) was performed with the Cirrus-HD OCT (Carl Zeiss Meditec, Inc., Dublin, CA). The Optic Disc Cube 200 × 200 protocol was used for acquisition and analysis of the RNFL for 69 patients. The data can be used to assess typical ranges for intracranial volume, optic canal area, and RNFL in the craniofacial FD/MAS population and to assess ranges concerning for optic disc edema. [1] Raborn LN, Pan KS, FitzGibbon EJ, Collins MT, Boyce AM. Optic disc edema in fibrous dysplasia/McCune-Albright syndrome: Prevalence, etiologies, and clinical implications. Bone. 2021 Feb;143:115661. doi: 10.1016/j.bone.2020.115661. Epub 2020 Sep 24. PMID: 32979536.


Value of the Data
• We demonstrate a reliable method of determining optic canal area and intracranial volume using OSIRIX imaging analysis software and the data we collected by this method for a cohort of patients with FD/MAS and craniofacial involvement. We present RNFL measurements for a range of patients, including 7 diagnosed with optic disc edema and 62 with no optic disc edema for future comparison. • This data is useful for investigators and clinicians caring for patients with FD/MAS. • This data can be used to further study the effect of FD/MAS disease severity on intracranial volume and optic canal area or to investigate the utilization of RNFL in predicting optic disc edema. • FD/MAS is a rare disease, and we provide data from the largest cohort study of optic disc edema to date which can be used for future research. • The usefulness of OCT in the population is limited by a lack of standard ranges for pediatric patients, which could hinder its usefulness in identifying optic disc edema. We present a large cohort of patients with RNFL data that can be utilized to identify RNFL dimensions concerning for optic disc edema.

Data Description
Craniomorphometric analysis and peripapillary retinal nerve fiber layer data in patients with craniofacial fibrous dysplasia.

Experimental Design, Materials and Methods
A full description of study design, methods, participant characterization, and optic disc edema diagnosis can be found in our corresponding published literature [1] . Subjects were evaluated between 20 0 0 and 2019 at the National Institutes of Health as part of an ongoing natural history study of FD/MAS (NCT0 0 0 01727). The study was approved by the Institutional Review Board of the National Institute of Dental and Craniofacial Research, and informed consent/assent was obtained from all subjects and/or guardians. All subjects were diagnosed with craniofacial FD/MAS according to previously published guidelines [2] and diagnosed with optic disc edema by neuro-ophthalmologic examination [1] . Subject ODE-2 had optic disc edema in the left eye only and optic neuropathy diagnosed in the right eye. Subject ODE-7 was diagnosed with optic disc edema prior to evaluation and was started on Acetazolamide therapy. At the time of evaluation, her optic disc edema was resolved.
Craniomorphometric analyses was performed using OSIRIX imaging analysis software and a single trained reader (KSP) to determine intracranial volume and optic canal area. All analysis utilized CT head imaging with axial slices ≤5mm. To determine intracranial volume, a region of interest (ROI) was traced manually to include intracranial area only ( Fig. 1 ). All lateral CT slices were manually traced because of variation in intracranial calvarial contour ( Fig. 1 A, B). Midline slices typically showed less intracranial calvarial contour variation and were manually traced every 3-5 slices ( Fig. 1 C, D). Using the software, remaining ROIs were automatically generated. The reader examined automated ROI tracings and manually corrected errors. Each ROI contained intracranial area that was used to determine total intracranial volume ( Fig. 1 E). Using OSIRIX, intracranial volume was calculated from the outlined ROIs (ICV = (A1, A2, . . ., Az) × CT   slice thickness). A 3D volume was rendered ( Fig. 2 ) along with volume output and is described in Table 1 . Optic canal area was also determined using OSIRIX software and CT head imaging with ≤5 mm axial slices. 3D Multiplanar Reconstruction (MPR) was utilized, which allowed for simultaneous visualization of the optic canal in axial, sagittal, and coronal planes ( Fig. 3 ). The optic canal was then aligned in each plane ( Fig. 4 ). Using coronal plane rendering of optic canal, the ROI function was used to manually trace the optic canal using digital calipers and determine the area ( Fig. 5 ). Optic canal area for each eye is listed in Table 1 . Spectral-domain Optical Coherence Tomography (OCT) was performed with the Cirrus-HD OCT (Carl Zeiss Meditec, Inc., Dublin, CA). The Optic Disc Cube 200 × 200 protocol was used for acquisition and analysis of the total RNFL and recorded in Table 2 . Both intracranial volume and optic canal area were collected by importing Computed Tomography (CT) images into OSIRIX software, which were then used to create a 3D reconstruction of the image. Intracranial area and the area of the optic canal were measured by outlining the area of interest within image crosssections. Intracranial volume was calculated via OSIRIX software which sums the intracranial area outlined in all cross-sections and multiplies by cross-section thickness. Race and ethnicity were self-reported by each subject. ODE = subject with diagnosed optic disc edema, Control = subject with no diagnosis of optic disc edema, M = male, F = female, OD = right eye, OCA = optic canal area, OS = left eye, ( * ) = subject had diagnosed optic neuropathy in right eye, ( * * ) = subject was diagnosed with ODE prior to visit and showed resolution during time of exam on Acetazolamide therapy.

Ethics Statement
Subjects were enrolled in the National Institutes of Health ongoing natural history study of FD/MAS (NCT0 0 0 01727). The study was approved by the Institutional Review Board of the National Institute of Dental and Craniofacial Research, and informed consent/assent was obtained from all subjects and/or guardians.

Declaration of Competing Interest
NIDCR receives funding from Amgen, Inc and Ultragenyx, Inc for studies in fibrous dysplasia. made possible through the NIH Medical Research Scholars Program, a public-private partnership supported jointly by the NIH and contributions to the Foundation for the NIH from the Doris Duke Charitable Foundation, Genentech, the American Association for Dental Research, the Colgate-Palmolive Company, and other private donors.

Funding
This work was supported by the Intramural Research Programs of the National Institute of Dental and Craniofacial Research and National Eye Institute , National Institutes of Health .