There is evidence that increasing aqueous humour outflow is the superior strategy.
There is evidence that aggregation of proteins and different biochemical processes in the cerebrospinal fluid as well as in the aqueous humour is likely to be involved in the pathogenesis of glaucoma. Therefore, a treatment option that facilitates the outflow of aqueous humour from the anterior chamber might not only be beneficial for reducing IOP but also for the washout of potentially noxious proteins. If we consider glaucomatous damage something more as just a mechanical damage to ganglion cells and retinal axons we hypothesize that interventions focusing on the aqueous humour outflow might be preferable to interventions that focus on the reduction of aqueous humour production.
Citation: Killer, H.E., Pircher, A. What is the optimal glaucoma treatment: reducing aqueous humour production or facilitating its outflow?. Eye 34, 1719–1721 (2020). https://doi.org/10.1038/s41433-020-0862-8
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As you mentioned, glaucoma medications can reduce IOP by these two different mechanisms. Different surgical methods can work either way as well. Cyclodestructive (cyclophotocoagulation) procedures such as Endocyclophotocoagulation (ECP), Micropulse transscleral cyclophotocoagulation (MP-TSCPC) and any other cyclophotocoagulation, reduce aqueous humour production. If the theory proposed in the paper above is correct, these surgeries would be less desirable than some others.
Laser surgeries such as ALT and SLT increases the outflow by focusing on the trabecular meshwork. Incisional surgery (trabeculectomy, deep sclerectomy, viscocanalostomy, canaloplasty and aqueous shunt devices (including many MIGS) allow the aqueous humour to bypass the trabecular meshwork through an artificially created canal or an installed tube.
The article is an interesting read. Some of its points are:
- Glaucoma = high IOP is incorrect. The equation is not that simple.
- Elevated IOP alone does not explain the pathogenesis of glaucoma.
- The complete pathogenesis of glaucoma is not yet elucidated.
- NTG comprises up to 30% of glaucoma in the western hemisphere and up to 90% in the far east.
- Reduced turnover of the cerebrospinal fluid with accumulation of toxic proteins is considered to be one of the risk factors in Alzheimer’s disease.
- In glaucoma an abnormal accumulation of potentially toxic proteins was found not only in the subarachnoid space of the optic nerve but also in the aqueous humour of the anterior chamber. The protein content measured in the aqueous humour of glaucoma versus non-glaucoma patients has demonstrated significant differences.
- The source of aqueous humour is the ciliary body. Aqueous humour consists of water and an impressive proteome of at least 2851 proteins.
- If the turnover of aqueous humour is compromised because of a partially blocked outflow path, the pressure in the eye increases, and so does the concentration of proteins, some of them toxic.
- Glaucoma patients have a higher concentration of betatrace protein in the aqueous humour.
Increasing aqueous humor outflow as the more superior strategy seems to make physiological sense. Aqueous humor has important positive roles of providing nutrients to eye as well as “washing away” toxins, so if its natural production is reduced, that may compromise eye health. Also, there’s been research suggesting that aqueous humor may drain through lymphatics, so improving lymphatic circulation (even by benign means such as acupressure massage surrounding eyes, acupuncture, etc.) may also improve aqueous outflow.