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1. Dr Shylesh B Dabke
Glaucoma Fellow
Aravind Eye Hospital
Steroid Induced Glaucoma
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2.  Steroid-induced glaucoma is a form of open-angle glaucoma
occurring as an adverse effect of corticosteroid therapy.
 Corticosteroids use has gained popularity in ophthalmology as anti-
inflammatory and anti-allergic agents.
 Iatrogenic open-angle glaucoma in susceptible individuals.
Overview

3. History
1949 1950 1950 1963 1963
Kendall and Hench – Cortisol - Rheumatoid Arthritis
Woods – corticosteroids - ocular inflammatory diseases
Woods AC: Clinical and experiental observation on the use of ACTH and cortisone in ocular inflammatory disease.
Am J Ophthal 1950;33:1325
Publications of Armaly and Becker
At the same time - long-term topical steroid users developing increased IOP - other findings
resembling open angle glaucoma with optic nerve head cupping and visual field loss.
Elevated IOP with corticosteroid use was reported

4.  Working separately, Armaly and Becker published benchmark studies on corticosteroid
glaucoma, which documented the rise of intraocular pressure in formal studies.
 Armaly and Becker developed a classification of “low, intermediate, and high” steroid
responders.
 Their studies showed that patients with POAG and their first degree relatives were
more likely to be steroid responders than normal individuals.

5. Classification
Armaly
Low - <6mmHg
Intermediate – 6-15mmHg
High - >15mmHg
Becker
Low - <20mmHg
Intermediate – 20-30mmHg
High - >31mmHg

6. Low(%) Intermediate(%) High(%)
Normal Population
Armaly 66 29 5
Becker 58 36 6
Patients with primary open angle
glaucoma
Armaly 6 48 46
Becker 0 8 92

7.  any age group
 either gender
 any ocular or systemic disease
 Any Route of administration
 Normal individuals who are steroid responders are at higher risk for
subsequently developing primary open angle glaucoma.
 Steroid responsiveness appears to be heritable.
It can occur in

9.  Most cases of steroid-induced glaucoma occurs from exogenous steroids
 However, endogenous steroids can also cause this condition
- Adrenal hyperplasia
- Adrenal adenoma or carcinoma
- Ectopic ACTH syndrome
Route of Administration
Haas JS, Nootens RH. Glaucoma secondary to benign adrenal adenoma. Am J Ophthalmol 1974;78:497

10.  Ocular drops and ointments.
 Of various routes - topical therapy most commonly induces elevated IOP and
correlates with the duration and frequency of administration.
 The potency of topical steroids is directly correlated with the propensity to
elevate intraocular pressure.
Topical

11.  Before the advent of anti VEGF, intravitreal steroid injections have been used largely.
 IOP may rise in 30-50 % of patients as soon as 1 -4 weeks after intravitreal injection of
triamcinolone acetonide and often returns to baseline several months after injection.
 It is advisable to perform a trial of topical prednisolone acetate.
Intraocular route

12.  Subconjunctival, sub-Tenon and retrobulbar injections of triamcinolone acetonide
may cause dangerous and prolonged elevation of IOP because of their long duration
of action.
Periocular route

13.  Systemic administration of corticosteroids is least likely to induce glaucoma.
However, the IOP elevation may occur as long as weeks to years after treatment
 .
Systemic route
Intraviteal Parenteral Inhalation
 Steroids when administered systemically and topically, IOP elevation induced is
additive.

14.  In general the pressure inducing effect of a topical steroid is proportional to its
anti-inflammatory potency.
 The concentration or dose of a steroid is also related to the likelihood of
producing an intraocular pressure elevation.
Steroid Formulation

15.  Patients who receive corticosteroid therapy may develop IOP elevations in
days, weeks, months or years after initiating treatment.
 Topical corticosteroids - Within 2 to 6 weeks.
 Systemically administered steroids, however, may take longer duration to
elicit an IOP rise.
Duration of Steroid Administration

16.  Corticosteroids raise intraocular pressure by reducing the facility of outflow.
– The most widely accepted theory
Pathophysiology
Inhibit catabolism of
GAG
GAGs then accumulate in the trabecular
meshwork obstructing outflow.
Steroids stabilize
lysosomal membranes, inhibiting release of
enzymes which breakdown GAGs.

17. Other theories
Inhibiting phagocytosis of foreign
material by
trabecular endothelial cells,
clogging outflow
channels
Inhibiting the synthesis of
Prostaglandin E2 and F2
alpha which are proposed to
control intraocular
pressure
Increasing the expression of TM
cellular tight
junction protein

18.  These theories do not explain why some people are more likely to be steroid
responders than others.
Armaly suggested that POAG patients may have preexisting changes in
trabecular meshwork which makes them susceptible to small changes in
GAGs.

19.  In an experiment involving exposure of cultured trabecular meshwork cells to
dexamethasone, delayed increase in expression of a gene product was observed(1).
 This protein was termed “trabecular meshwork inducible glucocorticoid reponse” protein,
which is subsequently linked to the myocilin gene (MYOC).
 Normal myocilin expression may have a protective role in the outflow pathway
 Myocilin gene mutations result in the formation of abnormal gene products which when
produced in larger concentrations may lead to trabecular meshwork clogging and
increased IOP
 However, a recent study conducted in steroid responders failed to identify a statistically
significant association between myocilin variations and steroid response.
Genetic Influence
Shepard AR, Jacobson N, Fingert JH, et al. Delayed secondary glucocorticoid responsiveness of MYOC in human trabecular
meshwork cells 2001;42:1769.

20.  The main finding in steroid-induced glaucoma is an accumulation of basement
membrane-like material staining for type IV collagen. These accumulations are
found throughout all layers of the TM
 Steroids affect TM cell morphology by increasing synthesis of endoplasmic
reticulum, golgi complexes, secretory vesicles, and increased cell and nuclear size.
 There is an increased deposition of extracellular matrix, thickened trabecular
beams and increased expression of fibronectin and laminin.
ULTRASTRUCTURAL CHANGES IN THE TRABECULAR
MESHWORK

21.  Very few symptoms exist.
 Infants may present with features of congenital glaucoma Unlike congenital
glaucoma, however, the anterior chamber angle is normal.
 Teenagers and adults usually present with features of primary open angle
glaucoma. Clinical evaluation reveals an elevated IOP, open and normal
appearing angles on gonioscopy, painless white eye, optic disk cupping and
visual field defects.
Clinical Features

22.  Mydriasis
 Increased corneal thickness
 Corneal ulcer
 Posterior subcapsular cataracts
 Delayed wound healing
 Ptosis
 Skin atrophy of eyelids.

23.  POAG
 Uveitic glaucoma
 Glaucomatocyclitic crisis
 Normal pressure glaucoma
 Traumatic glaucoma (esp. unilateral cases)
 Juvenile glaucoma
DIFFERENTIAL DIAGNOSIS

24.  Monitoring of IOP
- Obtain baseline IOP before starting steroid.
- IOP should then be measured after 2 weeks after initiation of treatment
- Every 4 weeks for 2–3 months
- 6-monthly if therapy is to continue.
 Patients undergoing intravitreal triamcinolone should be monitored for several
months following the steroid injection.
Management

25.  Cessation of corticosteroid treatment
- The chronic steroid response resolves in 1–4 weeks, whereas the rare acute
response may resolve within a few days of steroid cessation.
- In the case of repository corticosteroids, the steroid may have to be surgically
removed.
- If cessation of steroid therapy is not possible, then methods of reducing the
effects of the corticosteroid need to be considered.

26.  Alternative corticosteroid formulations
- Topical treatments can be changed to preparations such as fluoromethalone
0.1% or rimexolone 1%, which are claimed to have less effect on IOP or in
situations to NSAIDs.
- For patients prescribed systemic corticosteroids, introducing or increasing
steroid-sparing agents such as cyclophosphamide or methotrexate may allow
the corticosteroid dosage to be reduced.

27.  Irreversible steroid-induced ocular hypertension/glaucoma
- In about 3% of cases, and in particular when there is a family history of
glaucoma and/or chronic use of steroid (at least 4 years), the ocular
hypertensive response has been shown to be irreversible.
- The management of such cases is no different from that for POAG.

28.  Medical antiglaucomatous therapy
- Beta-blockers :
Popular first-line agent for the condition.
- Prostaglandin analogues :
Concomitant latanoprost is as effective as cessation of therapy in controlling the
rise, so can be useful if steroid treatment must be continued.
However, latanoprost has been reported to induce uveitis and is relatively
contraindicated in eyes with uveitic glaucoma
- Alpha agonists :
Brimonidine can be useful in many patients with steroid-induced glaucoma
- Carbonic anhydrase inhibitors :
Oral acetazolamide is an effective short-term treatment for the IOP control
Topical CAI’s (dorzolamide and brinzolamide)

29.  Argon laser trabeculoplasty (ALT)
- This treatment has been tried both before and after commencing corticosteroid
therapy and has not been shown to be effective in preventing corticosteroid
pressure rises.(1)
 Filtration surgery
- Trabeculectomy remains an effective treatment for patients who have a persistently
raised IOP following cessation of therapy and are refractory to medical therapy
Galin MA, Hirschman H, Gould H, Hofmann I. Does laser trabeculoplasty prevent steroid glaucoma?
Ophthalmic Surg Lasers 2000; 31(2): 107–110.

30.  Anecortave acetate injection into the anterior sub-Tenon space in eye with
uncontrolled steroid-related ocular hypertension following intravitreal or sub-
Tenon injections of triamcinolone acetonide.
 The mechanism by which anecortave acetate lowers intraocular pressure in
eyes with steroid-related ocular hypertension is unknown.
 Recent studies have shown that anecortave acetate blocks glucocorticoid
induction of plasminogen activator inhibitor–1, which may be partially
responsible for anecortave acetate's intraocular pressure lowering activity.
New Treatment under investigation

31. Steroid Induced Glaucoma
Refractory
Surgery
Uveitic
Glaucoma
NTG

32.  Steroid-induced glaucoma is known to be masked following refractive
surgery as IOP recordings are erroneous
- Central corneal thinning
- Ocular rigidity changes
- Corneal edema/fluid accumulation beneath the LASIK flap.
 Early onset steroid induced elevation of IOP after LASIK may cause corneal
edema and a sudden decrease in visual acuity.
 Rapid diagnosis and treatment can control IOP and recover the visual loss.
Refractory surgery

33.  Corticosteroids remain the mainstay of therapy for uveitis in controlling
inflammation, but monitoring of IOP is critical.
 IOP often falls in an acutely inflamed eye
Uveitic glaucoma
Aqueous production
Uveo-scleral outflow
 However rise may occur if this effect is exceeded by obstruction of the TM
outflow pathway.

34.  An increase in outflow resistance can be due to
- Increase in aqueous protein content
- Accumulation of cellular debris in the TM
- Angle closure through anterior synechiae formation
- Iatrogenic corticosteroid response.
 In such a situation it is impossible to determine whether an elevation in IOP is
due to the steroid therapy or the uveitic disease process itself.

35.  The principles of management, therefore, are to minimise the use of steroid
appropriately and apply standard antiglaucomatous therapy.
 First-line therapy for lowering IOP in eyes with uveitis is usually with a beta-
blocker, carbonic anhydrase inhibitors or adrenergic agonists being used as
second-line agents

36.  Steroid-induced glaucoma may mimic low tension glaucoma when the steroid-
induced pressure elevation has damaged the optic nerve head and visual field
in the past, but the IOP has subsequently returned to normal with cessation of
the steroid.
NTG

37.  Careful monitoring of all patients on corticosteroids (especially those with a
family history of glaucoma) is warranted.
 Self medication and injudicious use of steroids should be avoided.
 If necessary, steroid therapy must be used with intermittent drug holidays and
never on a continuous basis.
Conclusion