Editors Selection IGR 21-3

Medical Treatment: Oral Acetazolamide affects both IOP and ICP

John Berdahl
Brian M. Shafer

Comment by John Berdahl & Brian M. Shafer on:

90013 Intraocular and intracranial pressure in glaucoma patients taking acetazolamide, Loiselle AR; de Kleine E; van Dijk P et al., PLoS ONE, 2020; 15: e0234690

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A theory of the pathogenesis of glaucoma involves the pressure differential of intraocular pressure (IOP) and intracranial pressure (ICP) across the lamina cribrosa (LC) ‐ this differential is known as the trans-lamina cribrosa pressure differential (TLCPD).1 While IOP is typically higher than ICP, significantly elevated IOP may lead to axoplasmic stasis and subsequent programmed cell death of ganglion cells.2 Although patients with mildly elevated IOPs can be managed with topical medications, there are occasions in which significant IOP reduction is necessary ‐ in these situations oral acetazolamide is often employed as a bridge to surgery.

Acetazolamide is a carbonic anhydrase inhibitor that decreases the production of aqueous fluid in the eye as well as reduces production of cerebrospinal fluid (CSF) in the choroid plexus of the brain. Since both IOP and ICP are affected by acetazolamide, it is important to determine the effect on the TLCPD in patients. Loiselle et al. recently set out to evaluate this question.

The authors do an admirable job attempting to answer the difficult question of acetazolamide's effect on IOP and ICP. In a cohort of glaucoma subjects compared to normal subjects at specified time-points 125 mg of acetazolamide was orally administered. IOP was measured using iCare tonometry, and ICP was estimated using distortion product otoacoustic emissions (DPOAEs). In this method of non-invasively measuring ICP, sound emissions are used to estimate the change in ICP over time or in different conditions.

Generally, DPOAEs best detect changes in ICP when there are large fluctuations in pressure ‐ a good example of this is before and after a lumbar puncture in a patient with idiopathic intracranial hypertension. Minimal changes in ICP are undetected and moderate changes are not reliably detected.3 Unfortunately, absolute values of ICP are not obtained. Therefore, given these constraints, the data may not be representative of true values of ICP at ear level.

While the authors conclude that there is a reduction in ICP after administration of acetazolamide, there is no appreciable change in IOP. This result is inconsistent with our clinical practice as acetazolamide is widely experienced to be an effective method of rapid IOP reduction. Additionally, acetazolamide is typically initiated at higher doses in patients with elevated IOPs, and furthermore the mean IOPs in the glaucoma and control group were 16.6 and 16.1 mmHg, respectively. Therefore, these results may not be generalizable to the most relevant population of glaucoma patients who are prescribed acetazolamide.

Given the inherent challenge of non-invasively measuring ICP, studying the role of acetazolamide on the TLCPD remains an important but difficult task. We applaud the authors for their attempt and appreciate the contribution to the literature. We look forward to future studies with even more robust methods to measure ICP following acetazolamide.


  1. Price DA, Harris A, Siesky B, Mathew S. The Influence of Translaminar Pressure Gradient and Intracranial Pressure in Glaucoma: A Review. J Glaucoma. 2020;29(2):141-146. doi: 10.1097/IJG.0000000000001421. PMID: 31809396.
  2. Quigley HA. Ganglion cell death in glaucoma: pathology recapitulates ontogeny. Aust N Z J Ophthalmol. 1995;23(2):85-91. doi: 10.1111/j.1442-9071.1995.tb00135.x. PMID: 7546696.
  3. Bershad EM, Urfy MZ, Pechacek A, et al. Intracranial pressure modulates distortion product otoacoustic emissions: a proof-of-principle study. Neurosurgery. 2014;75(4):445-454; discussion 454-5. doi: 10.1227/NEU.0000000000000449. PMID: 24871147.

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