Steroid-induced glaucoma: an avoidable cause of irreversible blindness

Abstract

A man in his 70s on regular follow-up with an ophthalmologist for 10 years presented with blurry vision in his right eye for 4 days. He was diagnosed with elevated intraocular pressure (IOP) bilaterally 18 months earlier and treated with antiglaucoma eye-drops. On direct questioning, he admitted to using fixed combination tobramycin 0.3%/dexamethasone 0.1% eye-drops frequently to relieve ocular redness and discomfort in both eyes for 3.5 years without his ophthalmologist’s knowledge. Examination disclosed markedly elevated IOP, advanced optic disc cupping and tunnel vision due to steroid-induced glaucoma bilaterally. After cessation of the eye-drops and 2 weeks of antiglaucoma therapy, his IOP returned to normal and his visual field remained stable for 4 years.

Our case highlights the danger of habitual self-treatment of prescription medications containing corticosteroids and the importance of taking a detailed medication history in the diagnosis and management of steroid-induced glaucoma.

Background

Topical corticosteroids are a class of anti-inflammatory drugs commonly used to treat various ocular disorders. Individuals who respond to corticosteroids with intraocular pressure (IOP) elevation are called ‘steroid responders’. Elevation of IOP as a result of corticosteroid use is called steroid-induced ocular hypertension.¹ If the IOP elevation is of sufficient magnitude and is not treated, glaucomatous optic neuropathy can develop, resulting in visual loss and blindness (steroid-induced glaucoma).¹

Steroid-induced glaucoma is a form of secondary open-angle glaucoma.¹ Its clinical presentation is like primary open-angle glaucoma (POAG), except perhaps with a higher IOP.¹ There is heavy accumulation of type IV collagen, heparan sulfate proteoglycan, fibronectin and deposits of basement membrane-like material in the outer trabecular meshwork in steroid-induced glaucoma which is not present in POAG.² Corticosteroid inhibits trabecular meshwork cell functions, changes trabecular meshwork cytoskeleton and increases extracellular matrix deposition, resulting in decreased aqueous humour outflow and ultimately causing steroid-induced glaucoma (figure 1).³

Figure 1.

Proposed pathogenesis of steroid-induced glaucoma. (Illustration by BHKT.)

In some countries, topical corticosteroids are often self-administered by persons who are not aware of their potentially catastrophic adverse effects. Its unmonitored use is common when it is readily available over-the-counter (OTC) in some countries, resulting in undesirable side effects such as glaucoma and cataract.

Case presentation

A man in his 70s presented with blurring of vision in his right eye which he first noted while driving 4 days earlier. He also complained of ocular pain and a sensation of a layer covering both his eyes.

The patient had seen and was on regular follow-up with another ophthalmologist for 10 years previously. He was first diagnosed with elevated IOP in both eyes 18 months earlier by his ophthalmologist. He was initially treated with a fixed combination brimonidine tartrate 0.2%/timolol maleate 0.5% eye-drops two times per day in both eyes which was changed 1 year later to fixed combination brinzolamide 1%/brimonidine tartrate 0.2% two times per day in both eyes.

On direct questioning, the patient admitted to using fixed combination tobramycin 0.3%/dexamethasone 0.1% eye-drops frequently to relieve ocular redness and discomfort in both eyes for 3.5 years. His ophthalmologist had previously prescribed the eye-drops to him for ocular redness and discomfort. Without his ophthalmologist’s knowledge, he continued to use the eye-drops by obtaining them at a lower price without a prescription from a neighbouring country which he frequently visited for business.

He had cataract surgery in both eyes 3 years earlier and did not have any history of trauma to his eyes. There was also no family history of glaucoma.

His unaided visual acuity was 6/6–2 in his right eye and 6/6–1 in his left eye. Goldmann applanation tonometry disclosed his IOP was 58.9 and 26.8 mm Hg in his right and left eye, respectively. His pupils were sluggishly reactive to light. He also had dry eyes and blepharitis in both eyes. There were corneal epithelial oedema and punctate epithelial erosions in both eyes. The anterior chamber was quiet and the anterior chamber angles were open in both eyes. The optic cup/disc ratio was 0.8 in both eyes.

Humphrey visual field examination disclosed severely constricted visual field (tunnel vision) in both eyes (figure 2). Optical coherence tomography revealed thinning of the retinal nerve fibre layer in both eyes (figure 3).

Figure 2.

Humphrey visual field 24–2 examination shows tunnel vision in both eyes. OD, right eye; OS, left eye; POS, positive; NEG, negative; SITA, Swedish interactive thresholding algorithm; MD, mean deviation; GHT, glaucoma hemifield test; VFI, visual field index; PSD, pattern standard deviation.

Figure 3.

Optical coherence tomography shows severe thinning of the retinal nerve fibre layer in both eyes. OU, both eyes; OD, right eye; OS, left eye; ONH, optic nerve head; RNFL, retinal nerve fibre layer; TEMP, temporal; SUP, superior; NAS, nasal; INF, inferior.

The patient was diagnosed with steroid-induced glaucoma and treated immediately with a bolus dose of intravenous acetazolamide 500 mg followed by oral acetazolamide 250 mg four times per day and slow-release potassium chloride 600 mg two times per day. He was also given fixed combination preservative-free bimatoprost 0.03%/timolol maleate 0.5% eye-drops once a day in both eyes and brinzolamide 1%/brimonidine tartrate 0.2% two times per day in both eyes. He was advised on the serious and potentially blinding nature of steroid-induced glaucoma and instructed to cease the fixed combination tobramycin 0.3%/dexamethasone 0.1% eye-drops immediately.

His dry eye and blepharitis were treated with a daily eyelid hygiene routine consisting of warm compress with a hot gel pack and eyelid scrub using commercially available eyelid wipes. He was also prescribed copious ocular lubricant (sodium hyaluronate 0.3%) and cyclosporine 0.1% once a day in both eyes.

The patient’s IOP decreased several hours after initiation of treatment and was 8 and 6 mm Hg in the right and left eyes, respectively, the next day. The oral acetazolamide and potassium chloride were reduced gradually and discontinued after 4 days. All antiglaucoma eye-drops were discontinued after 2 weeks.

Over the next 4 years, his IOP remained normal without any antiglaucoma medications and his glaucomatous visual field loss was stable.

Global health problem list

1. Prevalence of steroid-induced glaucoma in the general population.

2. Diagnostic challenges.

3. Self-medication of corticosteroids.

4. Enforcement of prescription of corticosteroids.

Global health problem analysis

Prevalence of steroid-induced glaucoma in the general population

Glaucoma is a heterogeneous group of diseases that can damage the optic nerve and result in loss of vision. It is the leading cause of irreversible blindness in the world.⁴ Steroid-induced glaucoma occurs in steroid responders and can occur at any age.⁵

Although the exact prevalence of steroid-induced glaucoma is not clear, steroid responders form about 30%–40% of the population.⁶ Approximately 61%–63% of the normal population are non-responders to corticosteroid, exhibiting IOP elevations <5 mm Hg, 33% of the normal population exhibits a moderate response of IOP increase (6–15 mm Hg), and 4%–6% of the normal population is highly responsive (IOP elevation >15 mm Hg).⁷ The prolonged use of topical, periocular or intraocular corticosteroids can cause IOP elevation in 3–6 weeks in susceptible individuals.¹ This IOP increase can develop into glaucoma if it is of sufficient magnitude and duration.

Risk factors that compound the effects of steroid-induced glaucoma include genetics, age, severe myopia, type 1 diabetes mellitus and angle recession.^{6 8–10} Individuals with POAG and their first-degree relatives are at a higher risk of developing steroid-induced glaucoma.⁵ Older subjects have a higher risk of elevated IOP after using corticosteroid eye-drops while children have greater ocular hypertensive response as compared with adults due to the functional and structural immaturity of their trabecular meshwork.¹

Diagnostic challenges

Steroid-induced glaucoma develops slowly over time, does not cause pain and presents with few symptoms, making it difficult to detect. As a result, irreversible and significant visual damage can occur before the condition is diagnosed.⁵ A history of systemic or ocular disease, which could require chronic corticosteroid use (eg, uveitis, collagen vascular disease, asthma, dermatitis) should be obtained in patients with raised IOP.¹¹ Use of corticosteroid for a duration of more than a month is considered chronic.¹² The symptoms of each patient vary with age. Infants may present with features of primary congenital glaucoma, teenagers with developmental or juvenile open-angle glaucoma, while adults present with raised IOP, normal and open angles on gonioscopy and visual field defects as seen in our patient.⁵

Steroid-induced glaucoma has an important negative social impact because it is often diagnosed after significant damage has already occurred. A retrospective study by Senthil et al showed the damaging effect of steroid-induced glaucoma, with 78.3% of 157 eyes with steroid-induced glaucoma having glaucomatous disc damage and the remaining 21.6% having ocular hypertension.¹³

Our patient’s chronic unsupervised use of the fixed combination tobramycin 0.3%/dexamethasone 0.1% eye-drops caused his IOP to become elevated. Although this was picked up by his previous ophthalmologist, the prior history of unsupervised topical corticosteroid use was not obtained by or reported to the ophthalmologist. This history was crucial to correctly diagnosing the aetiology of the glaucoma. As a result, the patient was not instructed to cease the corticosteroid use, causing the glaucoma to worsen despite antiglaucoma eye-drops.

Self-medication of corticosteroids

The use of corticosteroid-containing eye-drops to treat irritations to the eye is common practice because of their ease of use and the immediate relief to the patient. Many doctors often use such eye-drops to relieve watering, itching or redness in the eye. In a study on 2160 adults in a rural population in India, close to 1 in 5 reported self-medicating with ophthalmic medication for symptoms such as watering (37.1%), redness (27.7%), itching (19.2%), redness with discharge (13.6%), ocular pain (12.4%), foreign body sensation (10.1%), decreased vision (5.1%) and burning of the eyes (3.8%).¹⁴ In our case, the patient was initially prescribed fixed combination tobramycin 0.3%/dexamethasone 0.1% eye-drops by his ophthalmologist to relieve his ocular redness and irritation. He subsequently obtained the same eye-drops without a prescription in a neighbouring country where law enforcement is poor, and self-medicated on a long-term basis without his ophthalmologist’s knowledge. This ultimately led him to develop steroid-induced glaucoma with severe visual consequences.

Use of such easily available corticosteroids reduces the symptoms for patients, leading to a sense of betterment, which usually results in the unmonitored use of corticosteroids over long periods of time.⁵ In a study of children with glaucoma in a tertiary hospital in India, 4.7% was steroid induced.¹⁵ Some of these children had indiscriminately used corticosteroid eye-drops for 8 years.¹⁵ The children’s unregulated use of these corticosteroids for symptomatic relief of ocular allergies is also enhanced by the cost cap of such drugs by government regulations in India.¹⁵

One reason for self-medication is that people deem themselves to be qualified to choose which medicines to consume when they are ill. When a person falls sick, he has a tendency to self-medicate before seeking professional medical care.¹⁶ Twenty-five per cent of 379 patients in a study in Cordoba, Argentina stated that their main source of recommendations for ophthalmic medication was themselves.¹⁷ This suggests that self-confidence in individuals causes some to self-medicate as they feel capable of making a judgement on their own health and the medicines required to maintain it.

Unfortunately, many who self-medicate are not aware of the medication’s potential side effects. A survey of the Riyadh regional population in Saudi Arabia showed that 37.2% self-medicated with prescription drugs for the eye, with corticosteroid-containing eye-drops being the most frequent (32.6%).¹⁸ Of those who used these eye-drops, 86.6% were not aware of potential steroid-related ocular complications.¹⁸ If not addressed, self-medication with topical corticosteroid may increase the incidence of steroid-induced ocular hypertension and glaucoma.

There are clear dangers of habitual self-administration of topical corticosteroids without monitoring the eye, such as the risk of irreversible blindness from steroid-induced glaucoma. There are many instances where the use of topical corticosteroids can be avoided and replaced with non-steroidal anti-inflammatory alternatives. When this is not possible, monitoring of the IOP is essential, especially when topical corticosteroids are used on a long-term basis. The ocular hypertensive response is fairly reversible and vision-threatening complications can be prevented with timely intervention. The most effective way of treating this ocular hypertensive response appears to be the cessation of the corticosteroid therapy.⁵ However, when managing uveitic glaucoma, successful treatment requires treating both IOP elevation and uveitis which requires corticosteroid usage to prevent damage to the trabecular meshwork.¹⁹

Enforcement of prescription of corticosteroids

OTC drugs are medications that are legally permitted to be sold by a pharmacist without the need for a prescription by a certified medical practitioner. In some countries, topical corticosteroids are readily available without prescription. For example, Lebanon lacks guidelines that prohibit dispensing certain medications without a prescription from a physician, except for narcotics.²⁰ In some other countries such as Saudi Arabia and India where there are rules and restrictions over the dispensing of medication without prescription, its enforcement by the authorities is lax.^{18 21}

In summary, our case illustrates the importance of obtaining a detailed medication history in the management of glaucoma patients. A history of corticosteroid use is critical to the diagnosis of steroid-induced glaucoma and is important for effective treatment and advice for the patient. In addition, our case highlights the need to strictly regulate products containing corticosteroids and for more public health education on the dangers of steroid-induced glaucoma.

Learning points.

• The use of topical, periocular or intraocular corticosteroids can cause intraocular pressure to increase in 3–6 weeks in susceptible individuals leading to blindness.

• A detailed medication history including self-medication with corticosteroids is crucial to the diagnosis of steroid-induced glaucoma.

• Patients on long-term topical corticosteroids should have their intraocular pressure monitored regularly.

• Self-medication with corticosteroid eye-drops should be avoided and discouraged.

• Stricter regulations and enforcement as well as public health education can help to reduce the misuse of corticosteroids.

Ethics statements

Patient consent for publication

Consent obtained directly from patient(s).