Glaucomas: Uveitic Glaucoma

Core Messages

››Making a correct diagnosis of the etiology of intraocular inflammation is the first and most important step in the management of uveitic glaucoma.

››Glaucoma is seen in approximately 10% of patients with uveitis.

››Glaucoma is more common with certain types of uveitis.

››Careful history and follow-up help distinguish steroid-induced IOP rise from uveitis-induced IOP rise.

››Uveitic glaucoma initially should be managed medically – to decrease inflammation and IOP. However, glaucoma medications can often have unpredictable effects on IOP in the setting of uveitis.

››Laser trabeculoplasty has no role in uveitic glaucoma, but may be tried in steroid-induced glaucoma.

››Glaucoma surgery should be considered in patients on maximum tolerated medical treatment when there is (1) significant optic nerve damage from chronic/intermittent IOP elevation, or (2) significant elevation of IOP causing high risk of optic nerve damage, irrespective of the present degree of optic neuropathy.

L.Shuba ( )

Department of Ophthalmology and Visual Sciences, Dalhousie University, 2 West, 1278 Tower Road, Halifax, Nova Scotia, Canada B3H 2Y9

e-mail: lesya.shuba@dal.ca

››Inflammation must be controlled preoperatively for optimum outcomes.

››There is no significant difference in the outcomes between Baerveldt and Ahmed shunts in uveitic glaucoma.

48.1  How Often Does One See

Glaucoma as a Consequence

of Uveitis?

Secondary glaucoma occurs in about 10% of patients with uveitis and management is often challenging [21, 27]. Identifying the etiology of inflammation is an important step in managing a patient who presents with intraocular inflammation and increased intraocular pressure (IOP). A number of conditions that cause ocular inflammation may lead to blindness or even death if misdiagnosed; these include infectious endophthalmitis (endogenous or exogenous), intraocular foreign body, and tumors (lymphoma, melanoma).

Uveitis can be classified as acute or chronic (more than 3 months in duration). Anatomically, it can be divided into anterior (iridocyclitis), intermediate (e.g., pars planitis), posterior, and panuveitis categories. All patients presenting with uveitis need a detailed ocular and medical history with review of systems and a thorough eye examination, including dilated fundus examination. Patients presenting with a first episode of acute unilateral iridocyclitis or in the setting of a known systemic or ocular disease do not require laboratory investigations. However, if uveitis is bilateral, chronic, recurrent, granulomatous, or intermediate/posterior, a systemic work-up is indicated. This includes screening

Fig. 48.1  Patient with Fuchs’ heterochromic iridocyclitis in the right eye

for ankylosing spondylitis (HLA-B27, sacroiliac joints X-ray), sarcoidosis (chest X-ray/CT, angiotensin converting enzyme level), syphilis (rapid plasma reactant or Venereal Disease Research Laboratory, and micro- hemagglutination-Treponema pallidum or fluorescent treponema antibody, absorbed) and tuberculosis (chest X-ray, PPD and anergy panel). If a specific diagnosis is suspected based on history and examination, a more directed work-up should be performed.

Glaucoma occurs more commonly in anterior uveitis than in intermediate or posterior uveitis, and more commonly in chronic than in acute uveitis [21]. Some forms of chronic anterior uveitis have a particularly high rate of glaucoma, including Fuchs’ heterochromic iridocyclitis (Fig. 48.1), Posner-Schlossman syndrome, herpetic keratouveitis, and juvenile rheumatoid arthritis associated uveitis.

Establishing a target IOP is an important step in the management of uveitic glaucoma. Often these patients do not have severe glaucomatous optic neuropathy and IOP elevations may be transient. In the setting of minimal or no optic nerve damage, a target IOP in the low 20s (mmHg) may be adequate (assuming average corneal thickness).

Summary for the Clinician

››Approximately 10% of uveitis patients will develop secondary glaucoma.

››Glaucoma is more commonly seen in anterior uveitis and in chronic uveitis.

››Often uveitis patients have high IOP but healthy nerves, and in these settings target IOPs in the low 20s may be adequate.

48.2  Is There a Way to Distinguish Between Elevated IOP Due to a Steroid Response vs. Uveitis?

Steroid-induced IOP elevation has been shown to occur with various routes of corticosteroid administration. However, most commonly it is caused by topical, periocular, intraocular or systemic steroid administration. Recently intravitreal and subtenon’s injections of triamcinolone have become popular for the treatment of macular edema of different etiologies. These treatments can cause significant IOP elevations, at times requiring surgical intervention. A recent study found that the presence of uveitis was the strongest risk factor for IOP elevation after intravitreal injections of triamcinolone (odds ratio, 2.5; 95% confidence interval 1.0–6.1) [13].

In general, the higher the anti-inflammatory potency of corticosteroid medications, the stronger the association with IOP elevation [5, 20]. Table 48.1 shows steroid potency relative to Hydrocortisone 0.5% and the IOPinducing effect of commonly used ophthalmic steroid medications. Risk factors for steroid-induced IOP elevation are listed in Table 48.2 [18, 20]. In steroid-respon- sive patients, IOP elevation usually develops within the first few weeks of steroid administration [2, 3, 20]; however, IOP can elevate within hours of initial administration (this is rarely seen) [45] or many years after chronic steroid use [4]. After steroids are discontinued IOP usually normalizes within 1–4 weeks.

Table 48.1  Comparison of IOP-elevating effect of various glucocorticoids and anti-inflammatory potency relative to hydrocortisone 0.5%

Table 48.2  Risk factors for steroid-induced IOP elevation

History of glaucoma, glaucoma suspect

First-degree relatives of glaucoma

Older age and children

High myopia

Type I diabetes

Connective tissue disease

Confusion can arise when an acute IOP elevation occurs after steroid treatment is initiated in the setting of uveitis. The IOP elevation may not be a true steroidinduced one, but rather secondary to decreased inflammation and improved ciliary body function, which in turn can lead to increased aqueous production overwhelming a dysfunctional trabecular meshwork (TM). It should be kept in mind that a true steroid-induced IOP elevation is rarely an acute elevation (i.e., IOP will not increase from 10 to 30 mmHg within a 24 h period but rather will occur more gradually). Steroid-induced glaucoma should also be on the differential diagnosis of normal tension glaucoma, as a resolved steroid-induced IOP elevation may have caused optic nerve damage that is apparent with currently low IOP measurements.

Some types of uveitis (e.g., herpetic keratouveitis, Posner-Schlossman) frequently cause IOP elevation. In these situations treatment with steroids will decrease inflammation and in turn the IOP.

Summary for the Clinician

››Uveitis is a strong risk factor for IOP elevation after intravitreal injection of triamcinolone.

››In steroid-responsive patients, IOP elevation usually develops within the first few weeks following steroid administration; acute elevation of IOP secondary to steroids is very rare.

››After discontinuation of steroids, the IOP usually normalizes within 1–4 weeks.

››After initiation of steroids, inflammation may decrease and ciliary body function may improve, which together can cause a sudden increase in aqueous humor production and elevation of IOP (not a true steroid-response).

››Steroid-induced glaucoma should be on the differential diagnosis of normal tension glaucoma.

48.3  How Do Inflammation and Steroids Cause an Increase in IOP?

The etiology of elevated IOP in uveitis is multifactorial. Intraocular inflammation affects IOP by altering aqueous production and/or outflow [27]. Low IOP can result from inflammation that usually causes the ciliary body to decrease aqueous production. However, in

Posner-Schlossman syndrome, for example, it is believed that aqueous production is actually increased, possibly due to elevated levels of aqueous prostaglandins [29]. High IOP can result when inflammation leads to a decrease in aqueous outflow. This reduction can be either acute, which is often reversible, or chronic. In acute uveitis, TM outflow is decreased by either (1) inflammatory cells and/or fibrin, (2) swelling and dysfunction of the lamellar and endothelial cells (trabeculitis), or (3) uveal effusion or serous retinal detachment leading to angle-closure. In chronic uveitis, aqueous outflow is usually affected irreversibly by either (1) scarring or obliteration of the TM, (2) overgrowth of a fibro vascular membrane, or (3) synechial angle-closure. IOP can also be affected by central posterior synechiae leading to pupillary seclusion or inflammatory pupillary membranes that can lead to acute angle-closure.

It is generally believed that IOP elevation in steroidinduced glaucoma is secondary to a reduction in aqueous outflow facility [20, 46]. The precise mechanism by which this occurs is unknown, but several theories exist. Corticosteroids suppress phagocytosis of the trabecular endothelium that may lead to accumulation of aqueous debris in the meshwork and a decrease in the outflow facility. In perfusion-cultured human eyes, a dexamethasone-induced IOP increase was associated with thickening of trabecular beams and juxtacanalicular tissue, decrease in intertrabecular spaces, and an increase in the amorphous granular extracellular material [9, 21]. Several genes are up regulated in glucocor- ticoid-treated TM cells. The myocilin gene is the best studied and has been induced in human cultured TM cells exposed to dexamethasone [1, 26, 40]. It is also associated with the onset of juvenile and adult primary open angle glaucoma. However, in monkeys, there was no statistically significant link between myocilin mutations and steroid-induced ocular hypertension [11].

Summary for the Clinician

››Inflammatory glaucoma is usually secondary to a reduction in aqueous outflow that is either acute (blockage by cells, swelling, uveal effusion) or chronic (peripheral anterior synechiae, fibro vascular membrane).

››IOP elevation in steroid-induced glaucoma is secondary to the reduction of the aqueous outflow through incompletely understood mechanisms.

48.4  When Should I Operate

on Uveitic Glaucoma?

Uveitic glaucoma is initially managed medically to decrease inflammation and IOP. A pearl of medical management is that the IOP reduction normally seen with glaucoma medications may be unpredictable in the inflamed eye. Beta blockers are effective in uveitis and usually are our first line drug; however, IOP reduction may be less than the expected 30% [21]. Topical and systemic carbonic anhydrase inhibitors (CAI) and selective a-adrenergic agonists can also be used. However, a-adrenergic agonists, similar to prostaglandin analogues (see the discussion below), may exacerbate ocular inflammation. Topical CAI may also inhibit corneal endothelial carbonic anhydrase and should be used with caution in patients with corneal edema (see Chap. 47 for further explanation) [10, 22]. Miotic agents should be avoided in uveitis because of proinflammatory effects and the possibility of developing synechiae.

If acute angle-closure occurs due to a secluded pupil and pupillary block, laser peripheral iridotomy should be performed alongside dilation and antiinflammatory medication. However, in a patient with active ongoing inflammation, an iridotomy may not remain patent [39]. In such cases, surgical iridectomy, possibly combined with synechiolysis of the secluded pupil, should be considered. Alternatively, more than one peripheral iridotomy can be performed to reduce the chance of recurrent pupillary block. In patients with less than 360° central posterior synechiae, it is reasonable to avoid iridotomy. Iridotomy will alter aqueous dynamics and may cause the remainder of the iris to scar down to the lens. In cases where there is significant inflammation, fibrin formation and impending pupillary block from a secluded pupil, one can inject tissue plasminogen activator (TPA) (12.5 mm) in the anterior chamber [37, 40]. Such injection alone may be successful in breaking central posterior synechiae and avoiding surgical interventions [37].

In uveitic open angle or chronic angle-closure glaucoma, where there is chronically poorly controlled IOP on maximally tolerated medical treatment, surgery should be considered. There are two scenarios in which we recommend surgical intervention:

1)Significant optic nerve damage from chronic/intermittent IOP elevation requiring maximum medical management (e.g., Posner-Schlossman syndrome,

herpetic keratouveitis, juvenile rheumatoid arthritis associated uveitis, steroid-response glaucoma).

2)Significant elevation of IOP despite maximum med­ ical treatment, when there is a high risk of optic nerve damage, irrespective of the present degree of optic neuropathy.

Active intraocular inflammation will decrease the success rate of any surgical procedure. Therefore, if the IOP does not require immediate control, it is advisable to wait for approximately a 3-month inflammation-free period to pass before proceeding with surgery.

Summary for the Clinician

››Use topical glaucoma medications to control IOP when possible. However, glaucoma medications can have unpredictable effects on IOP with the setting of uveitis.

››Correctly diagnose and treat pupillary block glaucoma in the setting of pupillary seclusion.

››Proceed to surgery with caution and a plan.

48.5  Is There a Preferred Surgery for Uveitic Glaucoma (Trabeculectomy vs. Tube vs. Laser)?

The currently accepted surgical options for treatment of glaucoma include trabeculectomy, tube shunt, or cyclophotocoagulation procedure. Laser trabeculoplasty is contraindicated in uveitic glaucoma, but may be tried in steroid-induced glaucoma [33]. Before proceeding with surgery, reversible causes, such as pupillary block, need to be ruled out.

In patients with uveitic glaucoma requiring surgery we often start with trabeculectomy with mitomycin C (MMC) or 5-fluorouracil (5-FU) (Fig. 48.2). There are situations, however, when the best surgical option is a tube shunt (see the discussion below), e.g. previous trabeculectomy or other conjunctival surgery, aphakia, scleromalacia, severe active inflammation.

Trabeculectomy with antiproliferative agents (either 5-FU or MMC) can be effective in the management of uveitic glaucoma. The long-term (7 months to 5 years) qualified success rate ranges from 50 to 85% [6, 17, 31, 40, 42]. Most of these studies are retrospective