The “Eye Movement Test” in the Clinical Management of Chronic Open-Angle Glaucoma

Fabrizio Magonio^1*

¹Department of Ophthalmology, Igea Private Hospital, Milan, Italy

*Correspondence author: Fabrizio Magonio, Department of Ophthalmology Igea Private Hospital, via Marcona, 69 20129 Milan, Italy; Email: [email protected]

Citation: Magonio F. The “Eye Movement Test” in the Clinical Management of Chronic Open-Angle Glaucoma. J Ophthalmol Adv Res. 2025;6(1):1-5.

Copyright^© 2025 by Magonio F, et al. All rights reserved. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Table 1: Mean IOP.

Discussion

Glaucoma is a neurodegenerative disease characterised by increased IOP, progressive apoptosis of retinal ganglion cells, increased optic nerve head excavation, reduced visual field and visual acuity. COAG represents the most common form of glaucoma and has a multifactorial aetiology. Several risk factors have been highlighted as contributing to the damage and progression of the disease, such as elevated IOP, ageing, gender, familiarity, oxidative stress, mitochondrial damage, excitotoxicity, sleep disturbances, vascular and glymphatic system alterations [1,10,11]. In COAG, increased IOP is currently the only modifiable risk factor. The eyeball is filled with two fluids, the vitreous Humour and Aqueous humour (HA) which, among other functions, also regulate IOP. HA is secreted by the ciliary bodies and through the pupil, passes from the posterior chamber to the anterior chamber where it encounters two pathways for its outflow. The first pathway (conventional) consists of the Trabecular meshwork (TR), a highly contractile tissue similar to smooth muscle, Schlemm’s Canal (SC), collector canals and the episcleral venous system until it reaches the systemic circulation [1,2,5]. The filtering portion of the TR is composed of three different structures: the inner uveal reticulum, the deep sclerocorneal reticulum and the iuxtacanalicular tissue consisting of a fenestrated endothelial layer in contact with the inner wall of the SC [1,2,4]. HA passes through the two reticular layers passively along a pressure gradient, whereas the endothelial layer also appears to utilise an active transport system [4]. In the second pathway (unconventional), HA passes through the interstitium of the ciliary muscle adjacent to the TR, then reaches the suprachoroidal space, the episcleral vessels (uveo-scleral pathway), the vortical veins (uveo- vortex pathway) or the lymphatic vessels (uveo-lymphatic pathway) and finally flows into the systemic circulation [3]. In humans, approximately 90% of HA outflow occurs via the trabecular pathway [1]. Probably, during the REM phase of sleep, the uveo-scleral outflow increases due to the combined action of the glymphatic system and rapid eye movements, which may be at the origin of nocturnal IOP fluctuations [10]. The mechanical stress of these rapid eye movements, which is useful for the homeostasis of a healthy eye, interacting with an altered trabecular network, might result in morphogenic changes in the structure of the TR, affecting its elasticity, ECM activity, cytoskeleton rearrangement, increased outflow resistance and IOP, ultimately giving rise to proinflammatory and neurodegenerative factors [10,11]. There is growing evidence that external mechanical factors can influence the configuration of biomacromolecules, cell fate and tissue structure [6]. Mechanistic evidence indicates that experimental ocular hypertension can increase cell contractility by activating Rho GTPases, which cause increased resistance to AH drainage [7,8]. Within the eye, the balance between HA production and outflow contributes to maintaining an IOP of about 12-20 mmHg. In COAG, the main cause of ocular hypertension is the increased resistance to trabecular outflow at the level of the iuxtacanalicular tissue due to remodelling of the Extracellular Matrix (ECM), which would lead to its stiffening and reduced porosity as is usually the case in atrophic or aged tissues [1]. The same changes also appear to occur in the endothelial cells of the SC [1]. The ECM is a crucial component of the ocular microenvironment, playing an essential role in every part of the eye, both by maintaining the transparency and hydration of the cornea and vitreous and by modulating angiogenesis, IOP maintenance and vascular signalling [6]. The ECM is a three-dimensional non-cellular macromolecular network composed of water, glycosaminoglycans, proteoglycans, hyaluronic acid, collagen, fibrin, elastin, fibronectin and several other glycoproteins. It continuously undergoes remodelling mediated by various matrix-degrading enzymes such as metalloproteinases and glycosidases. Environmental stimulation, such as mechanical stretching or a variety of growth factors, cytokines and drugs (such as dexamethasone), can alter the expression of ECM components and its mechanical properties, triggering the continuous increase in trabecular outflow resistance, leading to an increase in IOP [6,7]. In conclusion, in COAG, the pump that allows HA drainage fails due to the loss of elasticity of the trabecular tissue and ciliary muscle fibres [4,5]. Due to its elasticity, the TR stretches and contracts in response to physiological changes in IOP caused by ocular and extraocular factors. The vitreous moves within the eyeballs through head movements, the voluntary action of extraocular muscles and the accommodation of the lens, directly or indirectly exerting positive and negative pressure on the structures contained within the eyeball [9,10]. This “vitreal pump” contributes to the maintenance of tissue elasticity and the movement of fluids entering and leaving the eyeballs [10]; it also increases blood flow, shear stress, nitric oxide release and indirectly stimulates the contraction of the trabecular meshwork [10,11]. COAG is more frequent in elderly people in whom, in addition to reduced tissue elasticity, atherosclerosis, cardiovascular disease and diabetes may contribute to impaired fluid circulation and elimination from the eyeball. The “heart pump” also acts on the trabecular meshwork. Indeed, during systole the left ventricle contracts giving rise to a wave that causes the choroid to expand, thus increasing IOP [4]. The increase in IOP causes the trabecular meshwork to move into the lumen of the SC, constricting it and increasing its internal pressure, which will favour the outflow of HA into the collecting ducts, aqueous and episcleral veins [4]. However, during diastole the choroidal volume and IOP decrease. The recoil of the TR creates a negative pressure in the SC while the valves of the collector canals and veins prevent the retrograde flow of HA and blood [4]. In daily life, the eyes are never at rest, even while we sleep and can generate voluntary and involuntary movements [10]. Saccadic (rapid) eye movements are the most common, produced by both eyes simultaneously and in the same direction when we stare at an object. Tracking (slow) eye movements, on the other hand, are used to follow the object. Finally, involuntary movements are due to the contraction of the ciliary muscle (accommodation), which favours near vision. The blinking of the eyelids, which helps keep the ocular surface hydrated and pumps tears into the tear ducts, also indirectly exerts a mechanical action on the trabecular meshwork. In addition to contributing to image capture, eye movements therefore perform biomechanical actions that are useful to the physiology of the eye [10,12]. Many of the drugs that lower IOP act by reducing HA production (β-blockers, carbonic anhydrase inhibitors, alpha2-agonists) or by increasing its outflow through the uveo-scleral pathway (prostaglandins, prostanoids, alpha2-agonists). On the other hand, drugs that act on the conventional pathway are the muscarinic cholinergic agonists (pilocarpine) which, by contracting the ciliary muscle, increase HA outflow by widening the trabecular meshwork and the SC [1,2]. Indeed, contraction (pilocarpine) or relaxation of the ciliary muscle (atropine) respectively abolish or increase the presence of muscle fissures to increase or reduce uveoscleral outflow [1,2]. However, these drugs have seen a reduction in clinical use in recent years, mainly due to the side effects (headache, myopia, blurred vision especially at night, frequency of instillation) resulting in poor patient compliance. A new class of drugs (RHO- kinase inhibitors) has recently been introduced into clinical practice. By acting on the cytoskeleton of trabecular cells, they weaken their intercellular bonds and promote the formation of new vacuolar spaces and the dilation of episcleral veins, facilitating HA outflow [8]. EMT, through IOP changes induced by eye movement, investigates the degree of elasticity of the TR and thus the efficiency of conventional outflow. It is known that cataract surgery can lower IOP. This study shows that in pseudophakic eyes with COAG, EMT detected pressure drops < 1 mmHg: the reduction in IOP would therefore be attributable not so much to the increase in trabecular outflow as to the reduction in intraocular mass. In healthy, even pseudophakic eyes, EMT showed a mean IOP drop of 2 mmHg with peaks of 3 mmHg while in glaucomatous eyes the mean drop was < 1 mmhg. Finally, in 16 eyes (10 with pseudoexfoliation glaucoma in group A and 6 in group B2), we had a rise in IOP of 2-3 mmHg after EMT, a phenomenon that can be explained by the recall of fluid at the level of the TR, which is not compensated by an efficient outflow. This result would demonstrate a severe impairment of trabecular outflow and, in the case of pseudoexfoliative glaucoma, the presence of frequent and unpredictable increases in IOP caused by transient obstruction of the trabecular network.

Conclusion

The clinical management of COAG includes numerous diagnostic examinations such as biomicroscopy of the optic papilla, tonometry, corneal pachymetry, gonioscopy, coherent light optical tomography and perimetry. It was explained how the regulation of trabecular HA outflow is a biomechanical action supported by a series of pumps (cardiac, palpebral, muscular and vitreal) that act on the contractility of the TR. EMT is a new diagnostic technique that, by exploiting ocular motility and thus the muscular-vitreal-palpebral pump, has proved useful in assessing the efficiency of trabecular outflow, the effectiveness of therapies acting on the TR and above all in identifying subjects with borderline IOP, at risk of developing the disease. Finally, perhaps we are not realising that nowadays our lifestyle forces us to use our eyes, much of the time, for near vision due to the excessive use of electronic devices that could represent a further risk factor. In fact, in addition to the damage we already know about (photo-oxidation, dry eye, conjunctival hyperemia, asthenopia, headache, sleep disturbances), these devices restrict the movement of our eyes in a narrow range of action and consequently could reduce the elasticity of ocular tissues including the trabecular meshwork. If this statement were correct, we would see the incidence of glaucoma increase in the coming years.

Conflict of Interest

The author declares no potential conflicts of interest with respect to the research, authorship and/or publication of this article.

Funding Details

No funding was received for this review.

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