Mechanisms leading to open-angle glaucoma
Disturbance of intraocular fluid secretion
When inflammation of the ciliary body usually decreases the production of intraocular fluid. While maintaining a normal outflow, the intraocular pressure decreases, which is often observed with acute urine. However, with simultaneous violation of the outflow and reduced production of intraocular fluid, the intraocular pressure may remain normal or even elevated. It is not known whether there is an increase in the production of intraocular fluid and intraocular pressure in uveitis, where there is a violation of the “blood-watery moisture” barrier. Nevertheless, the most plausible explanation for the increase in intraocular pressure in uveitis is a violation of the outflow of intraocular fluid with its unchanged secretion.
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Intraocular fluid proteins
One of the first assumptions about the reason for the increase in intraocular pressure in uveitis was a violation of the composition of the intraocular fluid. At the initial stage, when the “blood-watery moisture” barrier is broken, proteins from the blood enter the intraocular fluid, which leads to disruption of the biochemical balance of intraocular fluid and an increase in intraocular pressure. Normally, intraocular fluid contains 100 times less protein than blood serum, and if the blood-to-moisture moisture barrier is broken, the concentration of proteins in the fluid may be the same as in undiluted blood serum. Thus, due to the increased concentration of proteins in the intraocular fluid, there is a violation of its outflow by mechanical obstruction of the trabecular meshwork and dysfunction of the endothelial cells lining the trabeculae. In addition, with a high content of proteins, the formation of posterior and peripheral anterior synechia occurs. With the normalization of the barrier, the outflow of intraocular fluid and intraocular pressure are restored. However, with an irreversible violation of the permeability of the blood-to-moisture moisture barrier, the flow of proteins into the anterior chamber of the eye can continue even after the resolution of the inflammatory process.
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Soon after the proteins, inflammatory cells that produce inflammatory mediators begin to flow into the intraocular fluid: prostaglandins and cytokines. Inflammation cells are considered to have a more pronounced effect on intraocular pressure than proteins. The increase in intraocular pressure occurs due to infiltration of inflammatory cells of the trabecular network and Schlemm's canal, which leads to the formation of a mechanical obstacle to the outflow of intraocular fluid. Due to severe macrophage and lymphocytic infiltration, the likelihood of an increase in intraocular pressure during granulomatous is higher than with a non-granulomatous one, in which the infiltrate contains mainly polymorphonuclear cells. In chronic, severe, or recurrent damage due to damage to the endothelial cells or the formation of hyaloid membranes lining the trabeculae, irreversible damage to the trabecular network and scarring of the trabeculae and Schlemm's canal occurs. Inflammation cells and their fragments in the area of the anterior chamber angle can also lead to the formation of peripheral anterior and posterior synechiae.
It is known that prostaglandins are involved in the formation of many symptoms of intraocular inflammation (vasodilation, miosis and increase in the permeability of the vascular wall), which in a complex can affect the level of intraocular pressure. Whether prostaglandins are able to directly increase intraocular pressure is unknown. By affecting the blood-to-aqueous moisture barrier, they can increase the flow of proteins, cytokines, and inflammatory cells into the intraocular fluid, indirectly affecting the increase in intraocular pressure. On the other hand, they can lower intraocular pressure by increasing uveoscleral outflow.
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The diagnosis of "trabeculitis" is made in cases of localization of the inflammatory response in the area of the trabecular network. Clinically, trabeculitis is manifested by deposition of inflammatory precipitates in the trabecular network in the absence of other signs of active intraocular inflammation (precipitates on the cornea, opalescence, or the presence of inflammatory cells in the intraocular fluid). As a result of the sedimentation of inflammatory cells, swelling of the trabeculae and reduction of the phagocytic activity of the endothelium cells of the trabeculae, mechanical obstruction of the trabecular network is formed and the outflow of intraocular fluid worsens. Since the production of intraocular fluid during trabeculitis, as a rule, does not decrease, due to the violation of its outflow, a significant increase in intraocular pressure occurs.
Steroid Induced Intraocular Hypertension
Glucocorticoids are considered the first choice drugs for treating patients with uveitis. It is known that with local and systemic use, as well as with periocular administration and introduction into the sub-tone space, glucocorticoids accelerate the formation of cataracts and increase intraocular pressure. Glucocorticoids inhibit the enzymes and phagocytic activity of trabecular endothelial cells, as a result of which glycosaminoglycans and inflammation products accumulate in the trabecular network, resulting in impaired outflow of intraocular fluid through the trabecular network. Glucocorticoids also inhibit prostaglandin synthesis, leading to impaired outflow of intraocular fluid.
The term “steroid-induced intraocular hypertension” and “steroid responder” are used to refer to patients in whom intraocular pressure has increased in response to treatment with glucocorticoids. It is estimated that about 5% of the population are "steroid responders", and in 20-30% of patients receiving long-term treatment with glucocorticoids, we can expect a "steroid response." The likelihood of an increase in intraocular pressure in response to glucocorticoid administration depends on the duration of treatment and dosage. In patients with glaucoma, diabetes, high myopia, and in children under the age of 10, the risk of developing a “steroid response” is higher. Steroid-induced intraocular hypertension may develop at any time after the start of taking these drugs, but more often it is detected 2-8 weeks after the start of treatment. When applied topically, the "steroid response" develops more frequently. Patients suffering from ocular hypertension should avoid periocular administration of the drug, as a sharp rise in intraocular pressure may develop. In most cases, after the cancellation of glucocorticoids, the intraocular pressure normalizes; nevertheless, in some cases, especially with the introduction of a depot of glucocorticoids, an increase in intraocular pressure can be observed for 18 months or more. In these cases, if it is impossible to control the intraocular pressure with drug, it may be necessary to remove the depots or conduct an operation to improve the outflow.
When treating glucocorticoid patients with uveitis, it is often difficult to identify the cause of the increase in intraocular pressure: a change in the secretion of intraocular fluid, or a deterioration in its outflow due to intraocular inflammation, or a result of the development of a “steroid response”, or a combination of all three causes. Similarly, a decrease in intraocular pressure during the cancellation of glucocorticoids can either prove the steroid nature of intraocular hypertension, or result from an improvement in the outflow of intraocular fluid through the trabecular meshwork or a decrease in its secretion due to the resolution of the inflammatory process. Suspicion of the development of a “steroid response” in a patient with active intraocular inflammation, requiring systemic administration of glucocorticoids, may be an indication for the prescription of steroid replacement drugs. If a steroid-induced intraocular hypertension is suspected in a patient with controlled or inactive uveitis, the concentration, dose or frequency of glucocorticoid administration should be reduced.
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Mechanisms leading to angular glaucoma
The morphological changes in the structures of the anterior chamber of the eye that develop in uveitis are often irreversible, leading to a significant increase in intraocular pressure, disrupting or blocking the flow of intraocular fluid from the posterior chamber of the eye to the trabecular network. The structural changes that most often lead to the secondary closure of the anterior chamber angle include peripheral anterior synechiae, posterior synechiae and pupillary membranes leading to the development of the pupillary block and, rarely, rotation of the processes of the ciliary body anteriorly.
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Peripheral Anterior Synechia
Peripheral anterior synechia - fusion of the iris with the trabecular network or cornea, which can disrupt or completely block the flow of intraocular fluid into the trabecular network. Best of all, the peripheral anterior synechiae are seen with gonioscopy. They are a frequent complication of anterior uveitis, more often develop with granulomatous than with non-granulomatous uveite. Peripheral anterior synechia are formed by organizing the products of inflammation, as a result of which the iris is pulled towards the anterior chamber angle. They often develop in the eyes with an initially narrow angle of the anterior chamber or when the angle is narrowed due to the bombardment of the iris. The adhesions are usually extensive and cover large segments of the anterior chamber angle, but they can also be in the form of a plaque or cord and involve only a small fragment of the trabecular meshwork or the cornea. During the formation of peripheral anterior synechias as a result of uveitis, despite the fact that most of the angle remains open, the patient may increase intraocular pressure due to the functionally inferior preserved part of the angle (due to the previous inflammatory process), which may not be revealed during gonioscopy.
Prolonged formation of peripheral anterior synechia with recurrent and chronic uveitis may lead to full cover of the anterior chamber angle. When closing the anterior chamber angle or the formation of pronounced peripheral anterior synechia with uveitis, one should always pay attention to possible neovascularization of the iris or anterior chamber angle. Reduction of fibrovascular tissue in the area of the anterior chamber angle or the anterior surface of the iris can quickly lead to its complete closure. Usually, with neovascular glaucoma that has developed as a result of uveitis, drug and surgical treatment is ineffective, the prognosis is poor.
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The formation of posterior synechia occurs due to the presence of inflammatory cells, proteins and fibrin in the intraocular fluid. Posterior synechia - adhesions of the posterior surface of the iris with the anterior capsule of the lens, the vitreous surface with aphakia or with the intraocular lens with arthifakia. The likelihood of developing back synechiae depends on the type, duration and severity of uveitis. With granulomatous, posterior synechiae form more often than with non-granulomatous. The greater the length of the posterior synechia, the worse the dilation of the pupil occurs and the greater the risk of the subsequent formation of posterior synechia with recurrences of uveitis.
The term "pupillary block" is used to refer to a violation as a result of the formation of the posterior synechias of intraocular fluid from the back to the anterior chamber of the eye through the pupil. The formation of a seclusio pupillae, posterior synechia over a 360 ° circumference of the pupil and pupillary membranes can lead to the development of a full pupillary block. In this case, the current of intraocular fluid from the back of the camera to the front completely stopped. Excess intraocular fluid in the posterior chamber can lead to bombardment of the iris or to a significant increase in intraocular pressure. As a result, the iris bends towards the anterior chamber. Iris bombing with continued inflammation leads to rapid closure of the angle due to the formation of peripheral anterior synechia, even if the anterior chamber angle was initially open. In some cases, when uveitis with the pupillary block, wide adhesions form between the iris and the anterior capsule of the lens, then only the peripheral part of the iris bends anteriorly. In this situation, it is quite difficult to detect the bombardment of the iris without the help of gonioscopy.
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Rotation of the ciliary body anteriorly
In acute intraocular inflammation, edema of the ciliary body with supraciliary or suprahoroidal effusion may develop, resulting in rotation of the ciliary body anteriorly and closure of the anterior chamber angle, which is not associated with the pupillary block. An increase in intraocular pressure due to such a closure of the anterior chamber angle often develops with iridocyclitis, circular detachment of chorus, posterior sclerite and in the acute stage of Vogt-Koyanagi-Harada syndrome.
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