Effects of Acute Intracranial Pressure Changes on Optic Nerve Head Morphology in Humans and Pig Model

ABSTRACT

Purpose

The lamina cribrosa (LC) is a layer of fenestrated connective tissue tethered to the posterior sclera across the scleral canal in the optic nerve head (ONH). It is located at the interface of intracranial and intraocular compartments and is exposed to intraocular pressure (IOP) anteriorly and intracranial pressure (ICP) or Cerebrospinal fluid (CSF) pressure (CSFP) posteriorly. We hypothesize that the pressure difference across LC will determine LC position and meridional diameter of scleral canal (also called Bruch’s membrane opening diameter; BMOD).

Methods

We enrolled 19 human subjects undergoing a medically necessary lumbar puncture (LP) to lower CSFP and 6 anesthetized pigs, whose ICP was increased in 5 mm Hg increments using a lumbar catheter. We imaged ONH using optical coherence tomography and measured IOP and CSFP/ICP at baseline and after each intervention. Radial tomographic ONH scans were analyzed by two independent graders using ImageJ, an open-source software. The following ONH morphological parameters were obtained: BMOD, anterior LC depth and retinal thickness. We modeled effects of acute CSFP/ICP changes on ONH morphological parameters using ANOVA (human study) and generalized linear model (pig study).

Results

For 19 human subjects, CSFP ranged from 5 to 42 mm Hg before LP and 2 to 19.4 mm Hg after LP. For the six pigs, baseline ICP ranged from 1.5 to 9 mm Hg and maximum stable ICP ranged from 18 to 40 mm Hg. Our models showed that acute CSFP/ICP changes had no significant effect on ONH morphological parameters in both humans and pigs.

Conclusion

We conclude that ONH does not show measurable morphological changes in response to acute changes of CSFP/ICP. Proposed mechanisms include compensatory and opposing changes in IOP and CSFP/ICP and nonlinear or nonmonotonic effects of IOP and CSFP/ICP across LC.

KEYWORDS:

• Optic nerve head morphology
• intracranial pressure
• intraocular pressure
• lamina cribrosa
• optical coherence tomography

Disclosure statement

No potential conflict of interest was reported by the author(s).

Study support

Lisa Reid and Toni Goeser (Department of Ophthalmology UNMC), Marsha Morien, Nathan Bills and Crystal Krause (Center for Advanced Surgical Techniques, UNMC), Neil Jouvenat (Department of Neurological Sciences).

Commercial relationships

Deepta Ghate MBBS, MD: Licensed technology with EON Reality Inc.

Sachin Kedar MBBS, MD: Licensed technology with EON Reality Inc.

Shane Havens MD: None

Shan Fan MD: None

William Thorell MD: None

Carl Nelson PhD: None

Linxia Gu PhD: None

Junfei Tong PhD: None

Vikas Gulati MD: None

Robin High: None

John Bader: None

Additional information

Funding

This study was supported by grant funding through Nebraska University Collaboration grant (Nebraska Research Initiative), Department of Neurological Sciences, Fremont Area Alzheimer’s Committee grant, Nebraska Tobacco Settlement Biomedical Research Development Fund 307 (NTSBRDF), the National Eye Institute, K23EY023266, and the National Institute of General Medical Sciences, 1 U54 GM115458, which funds the Great Plains IDeA-CTR Network. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.