STEROID-INDUCED GLAUCOMAS

GUEST AUTHOR

YUSRA TANVEER

Ajmal Khan Tibbiya College
Aligarh Muslim University

Aligarh, India

INTRODUCTION:

Corticosteroids are a double-edged sword. While they are useful in the management of various conditions, they also have multiple ocular and systemic side effects which may even be life threatening at times. 

In certain countries steroids are easily available over-the-counter while online pharmacies are also responsible for the unmonitored accessibility of these agents.

Ocular side effects include: increased susceptibility or reactivation of certain infections, cataract and increase in intra-ocular pressure (IOP).

Prolonged elevation of IOP can cause damage to the optic nerve leading to the development of steroid-induced glaucoma (SIG).  

PATHOGENESIS:

SIG is a form of open angle glaucoma.

The exact mechanism responsible for elevated IOP after steroid intake is not clear.

It is most likely associated with reduced facility of aqueous outflow.

Other theories include:

Stabilization of lysosomal membranes and accumulation of polymerized glycosaminoglycans (GAGs) in the trabecular meshwork (TM). Hydration of GAGs leads to biological edema in the TM and consequently reduced aqueous outflow. Corticosteroids, which stabilize lysosomal membranes, could reduce the release of lysosomal hyaluronidase resulting in a relative inhibition of hyaluronate depolymerization.

Ultra-structurally, accumulation of basement membrane like material staining for type IV collagen is also seen in SIG. Extracellular deposition of extracellular matrix material in the TM shows 2 patterns: Fingerprint-like deposition of material in the uveal meshwork and accumulation of fine fibrillar material in the juxtacanalicular region. 

Corticosteroids cause inhibition of phagocytic properties of endothelial cells lining the TM leading to accumulation of aqueous debris.

Glucocorticoids decrease synthesis of prostaglandins, which regulate aqueous outflow. They also inhibit TM cell arachidonic acid metabolism and reduce phagocytic activity of TM cells. Dexamethasone also causes cross-linked actin network formation. However, the effect of such an alteration of cellular cytoskeleton on TM cell function is not clear. 

There is some genetic influence in the development of SIG, as several genes have been found to be associated with protective as well as damaging glucocorticoid treated TM cells. A number of genes are suspected though not yet proven to have a role in the development of SIG. These include: MYOC (previously called trabecular meshwork induced glucocorticoid response [TIGR]) gene and genes regulating alpha1 chymotrypsin, pigment epithelium derived factor, cornea-derived transcript 6, prostaglandin D2 synthetase, growth arrest specific 1, decorin, insulin like growth factor binding protein 2, ferritin light chain, fibulin-1C and others.

EPIDEMIOLOGY:

Steroid induced IOP elevation can occur at any age.

Children may have a severe ocular hypertensive response to topical steroids.

In a study SIG was responsible for 1/4th of all cases of acquired glaucoma in children.

According to Becker and also Armaly, individuals can be categorized into high, intermediate and low responders to topical steroids. 

HIGH RESPONDERS: Had IOP increase above 31 mmHg or 15 mmHg above baseline.
INTERMEDIATE RESPONDERS: Had IOP increase between 20-31 mmHg or between 6-15 mmHg above baseline.
LOW (NON) RESPONDERS: Had IOP less than 20 mmHg or rise of less than 6 mmHg from baseline.

RISK FACTORS:

Factors which increase the risk of SIG include=

1. Patient related factors: Glaucoma or glaucoma suspects have marked rise in IOP levels after several weeks of topical corticosteroid therapy. First degree relatives of POAG patients have higher risk of being steroid responders. 

2. High myopia, patients with H/O penetrating keratoplasty or refractive surgeries may have a high IOP response which gets masked due to low central corneal thickness, Ocular rigidity changes, Corneal edema and fluid accumulation beneath the LASIK flap.

3. Extremes of age: Children below 10 years of age and elderly individuals show higher steroid responsiveness.

4. Type I Diabetes mellitus and connective tissue disease (specially rheumatoid arthritis).

5. Pigment dispersion syndrome and traumatic angle recession.

6. Systemic disorders such as adrenal adenoma.

ROUTES OF ADMINISTRATION:

Topical: IOP elevation is more common by this route compared to systemic administration.

Periocular therapy: Long-acting repository steroids are most liable to cause rise in IOP. A patient’s previous response to topical steroids does not predict their response to periocular steroids.

Intravitreal injections: Injections of triamcinolone or depot steroids such as ozurdex can cause elevation of IOP within 2-4 weeks of the procedure.

Systemic therapy: Injections, tablets (oral), Skin preparations, Inhalational agents and other systemic steroid use is less commonly associated with rise in IOP. Use of steroids for muscle building is another danger for SIG.

The potency and strength of the steroid used are related to the IOP response which occurs. Often the response does not correlate to the dosage or duration of treatment.

DURATION OF STEROID ADMINISTRATION:

Raised IOP in susceptible individuals usually occurs in a few weeks after commencement (average: 4 weeks). However, it may occur within hours or several years later.

CLINICAL FEATURES:

Signs and symptoms vary with the age of the patients. Infants present with features of congenital glaucoma such as watering and photophobia. Adults show features of open angle glaucoma. SIG may be accompanied with other complications such as mydriasis and ptosis.

DIFFERENTIAL DIAGNOSIS:

Primary open angle glaucoma 

Normal tension glaucoma 

Juvenile open angle glaucoma 

Uveitic glaucoma 

Glaucomatocyclitic crisis

MANAGEMENT:

First line of management is discontinuation of the steroid. Usually IOP returns to normal in a few days or weeks. Patients require pharmacological IOP lowering during this period.

If steroids cannot be stopped in the patient, they can be substituted with non adrenal steroids such as: rimexolone, loteprednol etabonate, fluoromethalone & medrysone.

Depot steroids need to removed by excision and clearing all steroid deposits in the area.

Intravitreal steroids may require vitrectomy to remove them.

Steroids can possibly be replaced with non-steroidal anti-inflammatory agents such as: flurbiprofen, bromfenac, ketorolac and nepafenac.

If IOP does not respond to medical treatment then Argon laser trabeculolasty can be tried. It may control IOP until the steroid-induced hypertensive effect disappears. 

Ultimately glaucoma filtering procedures or even glaucoma drainage devices are required in intractable cases.

CONCLUSION:

SIG is an avoidable condition which is aggravated by factors such as easy accessibility, risk factors for IOP elevation and poor monitoring. Increasing awareness regarding this condition can lead to a reduction in the prevalence of SIG.