Why does intraocular pressure increase at night?
Entering edit mode
5 months ago

My question is, why does IOP increase during sleep even with normal eyes? Is there a natural mechanism here that hasn't been documented? I'm not a doctor or a biology expert by any means, my background is in engineering, but presumably the fluid inside the eye needs to be refreshed periodically to remove toxins, refresh nutrients etc.

glaucoma iop:intraocular-pressure nocturnal-iop • 303 views
Entering edit mode
5 months ago
david 4.2k

I'm going to start with one concrete answer, and then I will finish with some reasons why the full understanding of the importance of (and consequences of) elevated nocturnal intraocular pressure in glaucoma is a very complex topic.

The short answer is that both the rate of production of aqueous humor and the rate of outflow are altered during the night due to a number of different physiological changes associated with sleep.

One of those physiological changes, as this 2022 paper suggests, is suppression of trabecular meshwork phagocytosis, which will be explained below. (Posture has an effect as well, as we already know, and that's just one of the other contributing factors.)

Suppression of trabecular meshwork phagocytosis by norepinephrine is associated with nocturnal increase in intraocular pressure in mice - PubMed

[These results] suggest that trabecular meshwork phagocytosis suppression by norepinephrine can regulate IOP rhythm through aqueous humor outflow. This discovery may aid glaucoma management.

Trabecular meshwork  phagocytosis can decrease particulate material and debris from aqueous humor, [reducing] outflow resistance, and contributing to IOP reduction. 

Conversely,  suppression of trabecular meshwork phagocytosis (e.g., by norepinephrine) can contribute to IOP elevation.

Phagocytosis is thought to play an important role in the normal functioning of the outflow pathway by keeping the drainage channels free of debris.

Rho-kinase (ROCK) inhibitors lower IOP, not only by relaxation of the trabecular meshwork by disruption of actin stress fibers, but also by the activation of phagocytosis.

Surprisingly, timolol and betaxolol tended to reverse the norepinephrine-suppressed phagocytosis according to this research. That surprises me because beta blockers are not known for being highly efficacious at reducing nocturnal IOP.

Here are some other tidbits from the paper: 

Norepinephrine (noradrenaline, NE) released from ... the sympathetic nervous system transmits circadian timing signals to the ciliary body of the eye to regulate pupil size, among other functions. 

In humans, nocturnal IOP increases irrespective of posture [6]. Nocturnal IOP is elevated in patients with glaucoma (obviously).

I'm still reading the paper. I may have more to say on this particular paper later. However, I'd like to now discuss why the topic of elevated nocturnal intraocular pressure in glaucoma is complex.

Intraocular pressure is only part of the equation. It stands in relation to cerebral spinal fluid pressure (CSFP). The two generate a pressure gradient across the lamina cribrosa (back of eye) that is thought to contribute to the glaucoma pathology.

The other important pressure is blood pressure (BP) because the difference in IOP and BP determines (in part) the blood flow to the retina. This falls under the discussion of ocular perfusion pressure (OPP).

presumably the fluid inside the eye needs to be refreshed periodically to remove toxins, refresh nutrients etc.

Yes. That fluid is called aqueous humor. It is filtered blood, made clear so light can enter the eye. It carries oxygen and nutrients. It is continually produced in the ciliary body and it flows through the eye, driven by the ocular pulse (which is derived from the heart beat). See Dr. Murray Johnstone's groundbreaking 2013 paper for more on this. The paper is available here:

New Concepts in Our Understanding of Glaucoma: How dynamic pulsatile mechanisms determine aqueous outflow. | FitEyes.com

The ultimate question for me is whether my nocturnal elevated IOPs are doing damage while I sleep (or whether this is perfectly natural).

Yes, that's the important question. The answer is, it depends.

If your OPP shifts in the wrong direction, your BP dips, your IOP increases and your CSFP does not increase as much as your IOP (i.e., the trans-laminar pressure gradient goes up), you have multiple factors that have all moved in the wrong direction during sleep. For many people, this is indeed the situation each night. Sometimes the only solution is glaucoma surgery. Sometimes even that is not enough, unfortunately.

But I suppose there are people who have an IOP increase where OPP and the trans-laminar pressure gradient have not become less favorable than daytime values. (That's speculation.)

Also, keep in mind that elevated IOP alone (disregarding all these dynamic relationships) is potentially problematic. An absolute value of elevated IOP puts metabolic stress (and probably oxidative stress) on the retinal ganglion cells. Some neurons are strong enough to handle this stress without dying. Others are not. It's very individual.


Login before adding your answer.

Traffic: 17 users visited in the last hour

Use of this site constitutes acceptance of our User Agreement and Privacy Policy.