Evaluating Factors That Influence Optic Nerve Head Morphology

Purpose: The optic nerve head (ONH) is a relative weak point and is susceptible to the pressure differential across the lamina cribrosa (i.e., intraocular pressure [IOP] – intracranial pressure [ICP]). Assessment of ONH morphology using optical coherence tomography (OCT) has the potential to detect early disease resulting from a loss of IOP/ICP homeostasis, however clinical use of ONH parameters is not well established. The purpose of this dissertation was to use ONH OCT parameters to assess normal variations in ONH morphology, changes with alterations in IOP and/or ICP, and changes in disease. Methods: (1) In healthy human subjects, ONH OCT scans, IOP, and optic nerve sheath diameter (ONSD, a surrogate measure for ICP) were acquired over a 12-hour period in both seated (n = 30) and 6-degree head-down tilt (HDT, n = 10) positions. Changes in ONH morphology were assessed and compared between postures. (2) In 8 healthy non-human primates, the ONH neuroretinal rim change was assessed over two-hour periods of mild-to-moderate IOP elevation. (3) ONH OCT scans were acquired from 21 papilledema (15 mild), 27 pseudopapilledema, and 42 control subjects, and the ability to differentiate papilledema (individuals with elevated ICP) from non-papilledema eyes was compared between ONH and adjacent measures and conventional 6-degree radius retinal nerve fiber layer thickness (RNFLT). Results: (1) The ONH minimum rim width (BMO-MRW) thinned an average of 9.55 μm over 12 hours in a seated position, with modest thinning also observed for adjacent peripapillary measures. Thinning did not occur in HDT, suggesting a role of the translaminar pressure difference. (2) The BMO-MRW thinned over an extended duration of time in response to IOP elevation and exhibited residual thinning following IOP reduction. In both (1) and (2), there was considerable inter-individual variability in ONH morphological change. (3) RNFLT adjacent to the ONH, BMO-MRW, and BMO height detected more cases of mild papilledema than conventional RNFLT. Conclusions: The ONH is a dynamic structure that exhibits morphological changes throughout the day and in response to alterations in IOP and/or ICP. Understanding factors that influence variability in morphology will help improve repeatability of clinical measures and may provide insight regarding risk of disease.