Bibhuti Thapa, MBBS, MD; Glaucoma specialist; Nepal Eye Hospital
Glaucoma is a chronic, progressive, degenerative disorder of the optic nerve that leads to
characteristic visual field loss. It is associated frequently but not always with raised intraocular
pressure.
Glaucoma is the second leading cause of blindness worldwide, and importantly, the vision loss
it causes is irreversible.
Globally , approximately 80 million people are affected by glaucoma and nearly half of the
individuals are unaware that they have the disease, and this number may be even higher in
under developed countries. This is largely due to absence of symptoms in the early stages. If
untreated, glaucoma may progress to permanent blindness.
Classification:
Broadly categorized into:
1.Open angle Glaucoma 2. Angle closure Glaucoma 3. Congenital Glaucoma
Risk factors:
Several factors increase the risk of glaucoma , including:
Family History
Age above 60 years
Certain ethnic backgrounds(e.g. African or Hispanic descent)
Diabetes Mellitus
Hypertension
Ocular Trauma
Use of Steroids
Among these risk factors, steroid induced glaucoma is particularly important because it is
largely preventable with timely ocular examinations and monitoring for prompt diagnosis and
early intervention.
Steroids and their Ocular Effects
Steroids are commonly prescribed for various autoimmune and inflammatory conditions and
are routinely used after intraocular surgery. Despite their benefits, steroids can have adverse
systemic and ocular side effects, including cataracts, increased intraocular pressure, and
glaucoma.
Steroid-induced glaucoma is defined as elevated IOP with glaucomatous optic neuropathy
resulting from of corticosteroid use. Approximately, one-third of individuals may develop
elevated IOP, a condition known as steroid responder. Steroid-induced ocular hypertension
would be a more accurate designation in most cases.
Management of this iatrogenic disease can be challenging, especially when steroid therapy
cannot be discontinued due to patients underlying conditions.
Steroid-induced IOP elevation is dependent on the route of administration, potency, dose,
treatment duration, and type of steroid, in addition to patient-related risk factors.
Therefore, physicians/ ophthalmologist must be mindful of the association between steroids
and secondary glaucoma. 2
Epidemiology
The classic tudies by Armaly and Becker indicate that 5–6% of normals develop marked IOP
rises after 4–6 weeks of topical dexamethasone or betamethasone administration. However, an
even higher percentage of normal individuals develop substantially increased IOPs if the
glucocorticoid is administered in greater frequency, at higher doses or for a longer period . 3
In the general population exposed to topical ocular steroids, 5% to 6% are high steroid
responders (IOP elevation >15 mm Hg), 29% to 36% are moderate responders (IOP elevation
between 6 mm Hg and 15 mm Hg), and 58% to 66% do not experience significant IOP elevation.
A study in a tertiary eye hospital in eastern Nepal found that steroid –induced glaucoma
accounted for 16.3%of all secondary glaucoma cases. 1
High Risk Groups:
These groups include patients with POAG, their first-degree relatives, diabetic patients, highly
myopic individuals , angle-recession glaucoma, very young (<6 years old) or elderly individuals,
and patients with connective tissue disorders. 5
In case of post refractive surgery like (LASIK and DSEK)IOP measurement can be falsely masked
as low due to thin central corneal thickness, corneal opacity or fluid accumulation beneath the
flap. 3
Pathogenesis:
Steroid-induced glaucoma is a secondary open-angle glaucoma. Although the exact mechanism
is unknown, the main cause of the disease is increased aqueous outflow resistance at the level
of the trabecular meshwork (TM), leading to IOP elevation. 5
Trabecular meshwork morphological and biochemical changes:
Glycosaminoglycans (GAG) theory- Corticosteroids inhibit the release of hydrolases due
to which the GAGs present in the trabecular meshwork cannot depolymerize and they
retain water in the extracellular space. This leads to narrowing of trabecular spaces and
decrease in aqueous outflow.
Endothelial cell theory- Corticosteroids are known to suppress the phagocytic activity of
endothelial cells leading to collection of debris in the trabecular meshwork and
decreasing the aqueous outflow.
Prostaglandin theory -Corticosteroids can inhibit the synthesis of PGE and PGF, which
normally facilitate aqueous outflow, resulting in increase in IOP.
Genetic factors:
Several genes are associated with steroid-induced glaucoma, including those encoding for
myocilin. 5 Increased expression of myocilin in response to steroids may contribute to elevated
IOP. Further research into the genetics associated with steroid-induced glaucoma would be
beneficial to identify patients at risk.
Route of Steroid Administration
Steroid-induced ocular hypertension and glaucoma can occur after topical, periocular,
intraocular, inhaled, nasal, systemic, or transcutaneous administration. In most of the cases,
steroid induced glaucoma is due to topical, periocular, and intravitreal administration, with the
topical route being the most frequently involved.
Topical steroids.
The effect of topical ocular steroids on IOP depends on the potency of the drug formulation.
Dexamethasone and prednisolone are more potent steroids. In one study, 0.1%
dexamethasone was associated with an average increase of 22 mm Hg from baseline IOP, while
prednisolone acetate, showed IOP elevation of 10 mm Hg in patients who were previously
identified as steroid responders. 6 Difluprednate is one of the most potent topical steroids which
showed approximately 10 mmHg elevation of IOP in 3% of cases, compared with 1% in the
placebo group. 7
Less potent topical ocular steroids include medrysone 1.0%, tetrahydrotriamcinolone 0.25%,
hydrocortisone 0.5%, and fluorometholone 0.1%. On average, these drugs raise the IOP by 1.0,
1.8, 3.2, and 6.1 mm Hg, respectively. 5 Newer medications such as loteprednol etabonate and
rimexolone have less effect on IOP.
Periocular and intravitreal steroids.
Periocular and intravitreal steroids include triamcinolone
acetonide (TA), fluocinolone acetonide (FA), and dexamethasone (DEX). These medications
have a longer duration of action compared with topical steroids. Among the periocular steroid
routes of administration, sub-Tenon has the highest risk of IOP elevation.
The most used intravitreal steroids are Dexamethasone and Triamcinolone acetonide(TA).
Intravitreal TA has been shown to cause ocular hypertension in 30% to 45% of patients for up to
nine months. 8 Intravitreal Dexamethasone is considered to have a lower risk of steroid response
(11%-17%), with a shorter duration (lasting about one month) due to its water-soluble
properties.
Sustained-release implants. The need for repeated intravitreal steroid injections has led to the
development of sustained-release steroid implants. These devices include the
nonbiodegradable FA implants Retisert, Iluvien, and Yutiq and the biodegradable DEX implant
Ozurdex.
The risk of steroid response is higher with intravitreal FA implants. Most patients with ocular
hypertension following a DEX implant can be managed medically, with only a small percentage
(0.2%-3.2%) requiring glaucoma surgery. 5
Sometimes, the IOP rise occurs months after the injection; if not monitored, optic nerve damage
could occur. If IOP elevation persists and/or optic nerve damage does occur following a
periocular injection of depot corticosteroid, removal of the repository of periocular steroid often
allows the IOP to return to non dangerous levels.
There have been several case reports of increased IOP following use of a corticosteroid inhaler
for asthma. Corticosteroids used in nasal sprays get into the bloodstream in sufficient quantities
over the long term . In rare cases, glaucoma is produced by endogenous glucocorticoids
associated with adrenal hyperplasia or adenoma.
Clinical Course
Steroid-induced ocular hypertension typically occurs after several weeks of continued steroid
therapy; but, an acute rise in IOP within hours has been reported. IOP elevation can occur
within weeks with potent steroids or after several months with less potent forms. Those with
glaucoma have an increased risk of steroid response, as illustrated by Becker and Mills’ study, in
which the mean IOP elevation in those with glaucoma was 17 mm Hg compared with 4 mm Hg
in the control group. 4 Upon cessation of steroids, IOP usually normalizes within one to four
weeks.
Steroid-induced glaucoma develops if ocular hypertension persists and leads to progressive
optic nerve damage. Clinically, steroid-induced glaucoma is very similar to POAG in
presentation, aside from the significant history of steroid use. Patients present with elevated
IOP, open angle on gonioscopy, optic nerve damage, and characteristic visual field changes.
Adults and older children are usually asymptomatic, while young children may present with
symptoms similar to primary infantile glaucoma (tearing, photophobia, blepharospasm). Steroid
response can be more aggressive in infants and young children, with earlier onset of response
and greater severity of glaucoma on presentation with signs of megalocornea and
buphthalmos.
The rise in IOP from corticosteroids may occur within a week of initiating treatment or may be
delayed for years.
Management
The best way to manage steroid-induced glaucoma is to prevent its occurrence, if possible.
Medical history should be properly taken to assess the risk of steroid response. Steroids should
be used judiciously in patients who have glaucoma or are glaucoma suspects. If prescribed, it
should be at the lowest efficacious dose and should be administered by the safest route.
Monitoring
Baseline IOP should be assessed before starting steroids and then measured every few weeks
after initiation of treatment, as glaucoma can develop at any time.
Medical management: Ocular hypertension usually resolves within four weeks. Unfortunately,
in about 3% of cases, the steroid response is irreversible.
If a patient develops steroid response, steroids should be discontinued or minimized as soon as
possible. If necessary, less potent steroid such as fluorometholone 0.1% or rimexolone 1%.
NSAIDs can also be substituted in certain situations. If ocular hypertension occurs in response
to systemically administered steroids, steroid-sparing agents should be considered. Excision of
the steroid depot or vitrectomy for intravitreal steroids may be needed.
If steroids cannot be discontinued, topical glaucoma medications, specifically aqueous
suppressants, are used as the first-line agents. Prostaglandin analogues are another option for
decreasing IOP, but they are relatively contraindicated in certain inflammatory conditions. If
needed, oral acetazolamide can be used for short term control.
Laser therapy: Apart from medical management, there is growing evidence that laser
trabeculoplasty may be an effective alternative therapy. Selective laser trabeculoplasty can
provide a rapid and substantial reduction in IOP. In one study, 50% IOP reduction has been
shown at one year. 9
Surgical treatment: Incisional surgery may be indicated if the IOP is markedly elevated, if there
is progressive optic nerve damage or visual field loss, or if a patient requires long-term steroid
treatment. Most patients receive either a glaucoma drainage device or trabeculectomy for
medically uncontrolled glaucoma. Cyclodestructive procedures are reserved for refractory
cases.
Global Awareness:
This condition is a major public health issue, frequently resulting from over the counter access to
or lack of proper monitoring of steroid medications.
Patients undergoing long-term steroid treatment must be examined periodically
because no time limit exists for this problem.
Judicious use of potent steroids should be used with precaution and proper IOP
monitoring.
Over the counter selling of steroid should be stopped. Inappropriately allowing to refill
steroid drops for an extended period of time should be banned. These patients are at
significant risk of developing a dangerous elevation of IOP.
If IOP is elevated because of a periocular glucocorticoid injection and medical therapy is
unsuccessful in controlling the pressure and protecting the optic nerve, the repository
material should be excised.
In the cases that require topical ocular corticosteroid therapy, the patient should be
treated if possible with less potent steroids such as medrysone or fluorometholone
because these drugs have less of a tendency to raise IOP.
Patients undergoing long-term glucocorticoid treatment must be examined periodically
because no time limit exists for this problem. Tragically, many cases of corticosteroid
glaucoma are produced by treatment for trivial conditions such as contact lens
discomfort or red eyes such as VKC or allergic conjunctivitis.
1. World glaucoma association.www.worldglaucomaweek.org[Internet]
2. Characteristics and Management of Steroid-Induced Glaucoma by Teresa Horan,MD,and Sarwat Salim, MD,
FACS)
3. Robert L.Beckers and Shaffers.18 th edition.UK.Mosby Elsevier.2009.
4. Becker B, Mills DW. JAMA. 1963;185(11):884-886.
5. Kersey JP, Broadway DC. Eye (Lond). 2006;20(4):407-416.
6. 6.Cantrill HL et al. Am J Ophthalmol. 1975;79(6):1012-1017
7. Korenfeld MS et al. J Cataract Refract Surg. 2009;35(1):26-34.
8. 8.Kiddee W et al. Surv Ophthalmol. 2013;58(4):291-310.
9. 9.Maleki A et al. Ophthalmology. 2016;123(12):2630-2632.
10. Iwao K et al. Am J Ophthalmol. 2011;151(6):1047-1056.e1.
11. Eksioglu U et al. Int Ophthalmol. 2018;38(5):1833-1838.
12. Malone PE et al. Am J Ophthalmol. 2010;149(5):800-806.e1.
13. Jamuna G et al.profile of secondary glaucoma in a tertiary eye hospital of Eastern Nepal, NEPJOPH.2021;
13(1):98-103