Steroid-Induced Glaucoma: A Literature Review

Arslan Khaliq Raja

Abstract

Corticosteroids can induce ocular hypertension and a type of secondary open-angle glaucoma, referred to as steroid-induced glaucoma. The use of corticosteroids is widespread and readily prescribed in clinical practice, and they have adverse effects on ocular health when used for long periods or in high doses; thus, it is important for clinicians to understand how to prevent vision-threatening complications in patients on corticosteroid therapy. This article will discuss the pathophysiology of steroid-induced glaucoma, associated risk factors, methods of diagnosing, and management, so that the clinician is somewhat familiar with the condition before diagnosing, managing, or even preventing it in patients.

Introduction

While corticosteroids are used in a number of medical conditions, they are associated with an increase in intraocular pressure (IOP) and may induce steroid-induced glaucoma (SIG) in susceptible patients. Glaucoma is a progressive optic neuropathy of the eye that is chronic in nature, characterized by elevated IOP and damage to the optic nerve. SIG is a type of secondary glaucoma, which is related to the use of corticosteroids. There is little to no published epidemiological research available in the UK to assist with monitoring the incidence of SIG; however, studies conducted internationally suggest that 4-6% of patients on systemic corticosteroids will experience a significant rise in IOP while greater than 30% will have at least a moderate rise in IOP (4,5). While systemic steroids exhibit a lower incidence than ocular routes and formulations, the risk is still present in patients utilizing oral or parenteral steroids, especially for those receiving high doses and long durations of therapy (7). Given that health care practitioners routinely prescribe corticosteroids within their practice, it is important for all relevant healthcare workers to recognize, diagnose, and manage SIG adequately in order to prevent irreversible visual loss (1,5).

Pathophysiology

Steroid-induced glaucoma is primarily caused from anatomical changes at the site of aqueous drainage in the eye. The trabecular meshwork is the primary aqueous outflow pathway, and corticosteroids can alter its anatomy and function by increasing the extracellular matrix whilst decreasing aqueous outflow. The decrease in aqueous outflow increases resistance to drainage pathway and results in elevated IOP.

Although most patients with SIG demonstrate some increase in IOP, steroid response shows considerable variability. Some patients may have a very high increase in IOP, while some may demonstrate only minute increases. The limited understanding of the genetic basis for individual variability regarding the response to corticosteroid has resulted in some findings. The role of the gene myocilin, which encodes a protein associated with aqueous humor drainage, has been implicated in steroid responsiveness (9). It has also been demonstrated that corticosteroids elevate expression of other proteins in the trabecular meshwork that contribute to resistance to outflow or visually recognized as elevated IOP (3).

Epidemiology and Risk Factors

Prevalence is difficult to accurately estimate, but it is believed that 4-6% of patients on corticosteroids experience a significant rise in IOP; the risk is higher if there is a family history of glaucoma, existing ocular hypertension, presence of high myopia, and presence of diabetes mellitus (4). The paediatric and elderly population also appear to be more vulnerable to developing IOP elevation. In one study, children on systemic or periocular steroids developed elevated IOP more acutely than adults in response to their medication (4).

The route of corticosteroid administration also appears to impact the risk of developing elevated IOP, with the highest risk associated to topical ophthalmic formulations, especially when using long-term or potent preparation, such as dexamethasone (5). Moreover, the risk is slightly reduced with use of systemic and periocular steroids, and it’s even lower with inhaled and dermatologic steroids (7).

Clinical Presentation and Diagnosis

Patients are often missing apparent symptoms of elevated IOP, such as blurred vision or eye discomfort, making an early diagnosis of SIG extremely challenging. Symptoms tend to occur only once significant damage has already occurred. Therefore, routine monitoring of IOP is essential, particularly for patients receiving corticosteroid therapy.

The diagnostic approach involves a comprehensive ophthalmologic examination. Tonometry is the primary tool for diagnosing steroid-induced glaucoma. It is recommended to measure IOP before starting steroid therapy and regularly thereafter, particularly in patients planned on long term steroid therapy. Gonioscopy is another diagnostic tool used to assess the angle of the anterior chamber, which is relevant in open angle glaucoma. The optic disc should also be examined for signs of glaucomatous damage, namely cupping. Visual field testing enables assessment of functional loss due to optic nerve damage. Lastly, Optical Coherence Tomography (OCT) is an excellent method of identifying structural damage to the retinal nerve fiber layer and optic disc, which may indicate glaucomatous changes (6).

Early detection of elevated IOP and associated optic disc changes is pivotal for prompt management, as chronically elevated IOP may lead to optic nerve damage and permanent vision loss.

Management and Treatment

Discontinuation or Substitution of Steroids
Initial management of SIG involved discontinuing or tapering the dose of the corticosteroid in question, which is especially important to avoid exacerbation of the underlying inflammatory condition. If steroid therapy cannot be stopped due to risk of flare-up, then replacement with a lower-potency steroid such as loteprednol or fluorometholone, may help minimise ocular damage (2).

IOP-Lowering Medications
If IOP remains elevated after adjusting steroid therapy, topical drugs can be used to effectively lower IOP. Common medications include beta-blockers (e.g., timolol), prostaglandin analogs (e.g., latanoprost), carbonic anhydrase inhibitors (e.g., dorzolamide), alpha agonists (e.g., brimonidine). In cases of severe or resistant IOP elevation, oral carbonic anhydrase inhibitors, such as acetazolamide, may prove useful in further reducing the IOP (8).

Surgical Intervention
When medical management has failed, a few surgical options can be considered, including laser trabeculoplasty, which can increase the outflow of aqueous humor and reduce IOP, or, trabeculectomy, which is a more invasive procedure often used as a last resort.

Prevention

Preventing SIG typically involves risk stratification and aggressive monitoring. This can be achieved by performing baseline IOP measurement followed by regular monitoring in patients receiving corticosteroids, with increased frequency of testing in those on long-term or high-dose steroid therapy (11).

Conclusion

SIG remains an important issue to both clinicians and patients due to the widespread application of corticosteroids in medical practice. Appreciation of the underlying pathophysiology, risk factors, and diagnostic methods of SIG is crucial for effective and timely management and avoidance of irreversible loss of vision. With the prevalence of corticosteroid usage on the rise, research into genetic risk factors, emerging treatments, and less harmful forms of steroids is imperative in a bid to minimize the impact of this disease on public health.

References

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  9. Tripathi BJ, Li J, Chan WF, Tripathi RC. Aqueous humor in glaucomatous eyes contains an increased level of TGF-beta 2. Exp Eye Res. 2009;89(5):840–5.
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  11. American Academy of Ophthalmology. Guidelines for the management of ocular hypertension. San Francisco: American Academy of Ophthalmology; 2020.

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