Jordan W Swanson1, Tomas S Aleman2, Wen Xu1, Gui-Shuang Ying3, Wei Pan3, Grant T Liu2, Shih-Shan Lang4, Gregory G Heuer4, Phillip B Storm4, Scott P Bartlett1, William R Katowitz5, Jesse A Taylor1. 1. Craniofacial Surgery Center and Division of Plastic Surgery, The Children's Hospital of Philadelphia and the University of Pennsylvania, Philadelphia. 2. Scheie Eye Institute and the Department of Ophthalmology, Perelman Center for Advanced Medicine and the University of Pennsylvania, Philadelphia3Division of Ophthalmology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania. 3. Scheie Eye Institute and the Department of Ophthalmology, Perelman Center for Advanced Medicine and the University of Pennsylvania, Philadelphia. 4. Division of Neurosurgery, The Children's Hospital of Philadelphia and the University of Pennsylvania, Philadelphia. 5. Division of Ophthalmology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
Abstract
IMPORTANCE: Detecting elevated intracranial pressure in children with subacute conditions, such as craniosynostosis or tumor, may enable timely intervention and prevent neurocognitive impairment, but conventional techniques are invasive and often equivocal. Elevated intracranial pressure leads to structural changes in the peripapillary retina. Spectral-domain (SD) optical coherence tomography (OCT) can noninvasively quantify retinal layers to a micron-level resolution. OBJECTIVE: To evaluate whether retinal measurements from OCT can serve as an effective surrogate for invasive intracranial pressure measurement. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study included patients undergoing procedures at the Children's Hospital of Philadelphia from September 2014 to June 2015. Three groups of patients (n = 79) were prospectively enrolled from the Craniofacial Surgery clinic including patients with craniosynostosis (n = 40). The positive control cohort consisted of patients with hydrocephalus and suspected intracranial hypertension (n = 5), and the negative control cohort consisted of otherwise healthy patients undergoing a minor procedure (n = 34). MAIN OUTCOMES AND MEASURES: Spectral-domain OCT was performed preoperatively in all cohorts. Children with cranial pathology, but not negative control patients, underwent direct intraoperative intracranial pressure measurement. The primary outcome was the association between peripapillary retinal OCT parameters and directly measured elevated intracranial pressure. RESULTS: The mean (SD) age was 34.6 (45.2) months in the craniosynostosis cohort (33% female), 48.9 (83.8) months in the hydrocephalus and suspected intracranial hypertension cohort (60% female), and 59.7 (64.4) months in the healthy cohort (47% female). Intracranial pressure correlated with maximal retinal nerve fiber layer thickness (r = 0.60, P ≤ .001), maximal retinal thickness (r = 0.53, P ≤ .001), and maximal anterior retinal projection (r = 0.53, P = .003). Using cut points derived from the negative control patients, OCT parameters yielded 89% sensitivity (95% CI, 69%-97%) and 62% specificity (95% CI, 41%-79%) for detecting elevated intracranial pressure. The SD-OCT measures had high intereye agreement (intraclass correlation, 0.83-0.93) and high intragrader and intergrader agreement (intraclass correlation ≥0.94). Conventional clinical signs had low sensitivity (11%-42%) for detecting intracranial hypertension. CONCLUSIONS AND RELEVANCE: Noninvasive quantitative measures of the peripapillary retinal structure by SD-OCT were correlated with invasively measured intracranial pressure. Optical coherence tomographic parameters showed promise as surrogate, noninvasive measures of intracranial pressure, outperforming other conventional clinical measures. Spectral-domain OCT of the peripapillary region has the potential to advance current treatment paradigms for elevated intracranial pressure in children.
IMPORTANCE: Detecting elevated intracranial pressure in children with subacute conditions, such as craniosynostosis or tumor, may enable timely intervention and prevent neurocognitive impairment, but conventional techniques are invasive and often equivocal. Elevated intracranial pressure leads to structural changes in the peripapillary retina. Spectral-domain (SD) optical coherence tomography (OCT) can noninvasively quantify retinal layers to a micron-level resolution. OBJECTIVE: To evaluate whether retinal measurements from OCT can serve as an effective surrogate for invasive intracranial pressure measurement. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study included patients undergoing procedures at the Children's Hospital of Philadelphia from September 2014 to June 2015. Three groups of patients (n = 79) were prospectively enrolled from the Craniofacial Surgery clinic including patients with craniosynostosis (n = 40). The positive control cohort consisted of patients with hydrocephalus and suspected intracranial hypertension (n = 5), and the negative control cohort consisted of otherwise healthy patients undergoing a minor procedure (n = 34). MAIN OUTCOMES AND MEASURES: Spectral-domain OCT was performed preoperatively in all cohorts. Children with cranial pathology, but not negative control patients, underwent direct intraoperative intracranial pressure measurement. The primary outcome was the association between peripapillary retinal OCT parameters and directly measured elevated intracranial pressure. RESULTS: The mean (SD) age was 34.6 (45.2) months in the craniosynostosis cohort (33% female), 48.9 (83.8) months in the hydrocephalus and suspected intracranial hypertension cohort (60% female), and 59.7 (64.4) months in the healthy cohort (47% female). Intracranial pressure correlated with maximal retinal nerve fiber layer thickness (r = 0.60, P ≤ .001), maximal retinal thickness (r = 0.53, P ≤ .001), and maximal anterior retinal projection (r = 0.53, P = .003). Using cut points derived from the negative control patients, OCT parameters yielded 89% sensitivity (95% CI, 69%-97%) and 62% specificity (95% CI, 41%-79%) for detecting elevated intracranial pressure. The SD-OCT measures had high intereye agreement (intraclass correlation, 0.83-0.93) and high intragrader and intergrader agreement (intraclass correlation ≥0.94). Conventional clinical signs had low sensitivity (11%-42%) for detecting intracranial hypertension. CONCLUSIONS AND RELEVANCE: Noninvasive quantitative measures of the peripapillary retinal structure by SD-OCT were correlated with invasively measured intracranial pressure. Optical coherence tomographic parameters showed promise as surrogate, noninvasive measures of intracranial pressure, outperforming other conventional clinical measures. Spectral-domain OCT of the peripapillary region has the potential to advance current treatment paradigms for elevated intracranial pressure in children.
Authors: Chieh-Li Chen; Karine D Bojikian; Chen Xin; Joanne C Wen; Divakar Gupta; Qinqin Zhang; Raghu C Mudumbai; Murray A Johnstone; Philip P Chen; Ruikang K Wang Journal: J Biomed Opt Date: 2016-06-01 Impact factor: 3.170
Authors: Karen A Eley; David Johnson; Andrew O M Wilkie; Jayaratnam Jayamohan; Peter Richards; Steven A Wall Journal: Plast Reconstr Surg Date: 2012-11 Impact factor: 4.730
Authors: Linda R Dagi; Laura M Tiedemann; Gena Heidary; Caroline D Robson; Amber M Hall; David Zurakowski Journal: J AAPOS Date: 2014-12 Impact factor: 1.220
Authors: Susan E Yanni; Jingyun Wang; Christina S Cheng; Kelly I Locke; Yuquan Wen; David G Birch; Eileen E Birch Journal: Am J Ophthalmol Date: 2012-11-03 Impact factor: 5.258
Authors: Jordan W Swanson; Wen Xu; Gui-Shuang Ying; Wei Pan; Shih-Shan Lang; Gregory G Heuer; Scott P Bartlett; Jesse A Taylor Journal: Childs Nerv Syst Date: 2019-12-17 Impact factor: 1.475
Authors: Vivek Vijay; Susan P Mollan; James L Mitchell; Edward Bilton; Zerin Alimajstorovic; Keira A Markey; Anthony Fong; Jessica K Walker; Hannah S Lyons; Andreas Yiangou; Georgios Tsermoulas; Kristian Brock; Alexandra J Sinclair Journal: JAMA Ophthalmol Date: 2020-12-01 Impact factor: 7.389
Authors: Tracy M Flanders; Shih-Shan Lang; Tiffany S Ko; Kristen N Andersen; Jharna Jahnavi; John J Flibotte; Daniel J Licht; Gregory E Tasian; Susan T Sotardi; Arjun G Yodh; Jennifer M Lynch; Benjamin C Kennedy; Phillip B Storm; Brian R White; Gregory G Heuer; Wesley B Baker Journal: J Pediatr Date: 2021-05-15 Impact factor: 6.314
Authors: Jui-Kai Wang; Randy H Kardon; Johannes Ledolter; Patrick A Sibony; Mark J Kupersmith; Mona K Garvin Journal: Invest Ophthalmol Vis Sci Date: 2017-05-01 Impact factor: 4.799