**1. Introduction**

Glaucoma represents a heterogeneous group of chronically progressive neurodegenerative bilateral diseases of the optic nerve, clinically characterized by optical neuropathy, resulting in retinal ganglion cell death, optic nerve head cupping, and associated specific loss of the visual field [1–3]. The aetiology of the disease is considered to be multifactorial [4], while the clinical picture can differ, with a substantial risk of associated blindness, especially in adults over the age of 60 [5].

Studies have shown that in Europe glaucoma occurs in 2.93% of people aged 40 to 80, reaching 10% at the age of over 90 [6]. Several types of glaucoma are described, which form a group of eye diseases and are the main cause of permanent blindness worldwide. [7,8].

**Citation:** Ciobanu, A.M.; Dionisie, V.; Neagu, C.; Bolog, O.M.; Riga, S.; Popa-Velea, O. Psychopharmacological Treatment, Intraocular Pressure and the Risk of Glaucoma: A Review of Literature. *J. Clin. Med.* **2021**, *10*, 2947. https://doi.org/10.3390/ jcm10132947

Academic Editor: Emmanuel Andrès

Received: 2 June 2021 Accepted: 29 June 2021 Published: 30 June 2021

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Based on the mechanism by which aqueous outflow is impaired with respect to the anterior chamber configuration, the disease is typically divided into 2 basic subtypes: open angle and angle closure [9,10]. Clinical presentation of open-angle glaucoma (OAG) includes mainly chronic, slow and irreversible loss of peripheral vision, ultimately leading to blindness. Because of the gradual and insidious development, more than 50% of patients are unaware of their condition (known as 'the sneak thief of sight'), especially due to the pattern of visual field loss that spares the central vision until advanced stages [9]; therefore, periodic ophthalmologic evaluation is important [11,12]. On the other hand, acute angleclosure glaucoma (AACG) represents a dramatic urgent event that is caused by the sudden increase in the intraocular pressure (IOP) due to occlusion of the trabecular meshwork by the peripheral iris (in predisposed eyes with a narrow iridocorneal angle), obstructing aqueous outflow, that can lead to a potential risk of rapid blinding. ACG patients usually present more acute symptoms such as hyperaemia, teary, and painful eyes, sudden blurring of vision, or halos around lights secondary to corneal oedema from a sudden rise in IOP. Increased IOP is responsible for additional symptoms such as headache, nausea, and vomiting [9]. It must also be kept in mind that a narrow angle can be asymptomatic in the absence of a predisposing factor for angle-closure (e.g., pupillary dilatation) or that there are cited cases of insidious angle-closure glaucoma, which tends to be more visually destructive subtypes [9].

Above all, we have to make a firm distinction between acute angle-closure and angleclosure glaucoma. The major difference between the two entities is the absence and presence of optic nerve damage and visual field defects, respectively, especially when a specific treatment is rapidly received by the patient. The notion of glaucoma is under discussion when an optic neuropathy with elements specific to glaucoma damage occurs.

The scientific literature identifies several local and systemic risk factors associated with the development and progression of glaucoma [13]. In the case of OAG the local risk factors are represented by IOP (the key modifiable factor), family history of primary OAG, intraocular anti-VEGF (vascular endothelial growth factor) therapy, decreased thickness of the central region of the cornea, pre-existing myopia (low–moderate and high), low intraocular vascular pressure, optic nerve pathology, visual field changes, disc haemorrhage, and pseudo-exfoliation. Systemic risk factors include cardiovascular diseases, diabetes mellitus, dyslipidaemia, cerebral stroke, steroid treatment, arterial hypertension, with old age and male gender acting as additional risks [8,10,14]. Concerning the rapid progression of glaucoma, the most important favouring factors are considered to be high IOP and cardiovascular diseases [15].

On the other hand, the risk factors for developing ACG mentioned in the literature are the following: age (62 years being the average age at presentation), gender (more commonly female), race (Asian descent), family history, hyperopic eyes, short eyes. Those at risk for ACG with packed angle configuration can develop an attack exacerbated by mydriasis either spontaneously (primary) or pharmacologically (secondary) [9,10].

Medication represents a distinct risk for glaucoma. Corticosteroids are the most common cause of open-angle glaucoma (OAG), but several non-steroidal anti-inflammatory agents can also lead to OAG [16]. Regarding ACG, the list of potentially risky drugs includes antidepressants, such as selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants and monoamine oxidase inhibitors, antipsychotic drugs, antihistaminic medication, antiparkinsonian agents, anticonvulsants (e.g., topiramate), mydriatic agents, sympathomimetic drops, antispasmodic drugs, and botulinum toxin.

Among the two types of glaucoma, ACG represents a pathology of interest concerning psychiatric treatment. Medications with anticholinergic effects could induce a precipitation of iridocorneal angle closure in patients with predisposition via mydriasis which is the primary pathogenic mechanism in the appearance of glaucoma in psychiatric patients [17,18] This rapid onset of the angle obstruction produces an imbalance between the production and drainage of aqueous humour in the anterior chamber, thus an accumulation of liquid and the increase of IOP. Other presumed involved mechanisms in the

development of glaucoma are the anterior dislocation of the iris and lens or the inflammation of the ciliary body [7].

The challenges presented by glaucoma in psychiatry are bidirectional: on the one hand, patients with risk factor for angle-closure may develop clinical symptoms (eye pain, visual changes, headache) as a direct side effect of the psychiatric treatment. In case of patients with non-diagnosed OAG the raise in IOP can lead to severe aggravation of the disease, which can pass unnoticed until advanced stages [19]. On the other hand, glaucoma patients may exhibit a wide array of psychiatric symptoms, as a consequence of progression of vision loss, such as depression [20], anxiety [21] and insomnia [22].

Therefore, a minimal and specific screening before initiating a psychiatric treatment should be kept in mind, at least for the patients who have risk factors to develop OAG (IOP measure, fundus examination, +/− optic coherence tomography—OCT of the optic nerve head) or ACG (IOP measure, gonioscopy, +/− OCT of the optic nerve head) depending on the mechanism of action of the class of drugs used. Nevertheless, a good multidisciplinary collaboration between the psychiatrist and the ophthalmologist is strongly recommended, especially in complex cases.

Given the importance of glaucoma in influencing the choice of psychiatric drugs, we propose to review the main psychiatric therapeutic agents and their potential effects on glaucoma occurrence. Secondly, our aim is to provide a useful review of current data for clinicians facing dilemmas regarding the pharmacology treatment of psychiatric disorders in patients with glaucoma or glaucoma risk factors.
