The effect of corticosteroids on IOP is well known to all clinicians. Whether the agents are dosed systemically, topically, or intraocularly, even the short-term use of steroids can significantly raise the IOP to levels that threaten the health of the optic nerve. The occurrence of steroid-related ocular hypertension (OHT) is unpredictable and can be unnerving, because the problem is entirely iatrogenic and often requires additional intervention for IOP management. For patients who need an immediate decrease in pressure, selective laser trabeculoplasty (SLT) may be an effective alternative to more invasive intervention.
THE NEW REALITY OF
STEROID-RELATED OHT
Changes in practice patterns over the past decade or
so have increased the frequency—and the severity—of
steroid-related OHT. The intravitreal injection of triamcinolone
acetonide has become commonplace in the management
of a variety of ocular conditions, ranging from
macular degeneration to diabetic macular edema to posterior
uveitis. In recent clinical trials, up to one in three
eyes receiving intravitreal triamcinolone therapy required
IOP-lowering treatment, depending on the steroid dose
received.1-3 The popularity of steroid-eluting implants has
also grown during the past several years. Retisert (Bausch
+ Lomb, Rochester, NY) is a posterior segment intraocular
implant that slowly releases fluocinolone acetonide
into the vitreous cavity over a 2- to 3-year period. It is
labeled for the treatment of noninfectious posterior
uveitis. Three-quarters of eyes implanted with the
Retisert will require IOP-lowering medications, and one
in three will require trabeculectomy.4
The management of steroid-related OHT remains problematic. The effect of steroids on IOP is temporary upon discontinuation, so physicians' first choice is to consider stopping the steroids. This is easy to do with systemic or topical steroid therapy. There will be a lag, however, before the IOP returns to normal. The clinical conundrum occurs when a patient has an unacceptably high IOP on maximal medical therapy and does not have the luxury of waiting for the steroid's effect to wear off. A filtering procedure seems like overkill in this situation—a potentially permanent solution to a temporary problem.
Removing a steroid depot from the sub-Tenon's space or the vitreous cavity or explanting a device requires a surgical intervention. It is worth remembering that the steroids were administered for a reason and removing them might have worse consequences than would an IOP-lowering procedure. For example, posterior uveitis has a horrible prognosis, and most eyes require constant steroid therapy to maintain vision. In this case, a trabeculectomy might be preferable to explantation of the Retisert device.
Clearly, safe and effective IOP-lowering intervention is needed for eyes with medically uncontrolled steroidrelated OHT, whether the elevation in IOP lingers after the discontinuation of steroid therapy or ceasing steroid treatment is impractical or imprudent.
THE EVIDENCE FOR SLT
The literature on the use of SLT in eyes with steroidrelated
OHT is limited but growing. In the first case
report, published in 2006, a 63-year-old white man presented
with an IOP of 45 mm Hg in one eye 3 months
after receiving an intravitreal injection of triamcinolone
in that eye. On maximal tolerated medical therapy, his
IOP remained 38 mm Hg. After SLT, the IOP dropped
substantially. His IOP was 16 mm Hg on no medications
2 months after SLT, and it was 15 mm Hg with no medications
6 months after the procedure.5 Unfortunately,
this report provides no information on the patient's IOP
immediately after SLT.
According to a similar report published in 2009, a 44-year-old man with medically uncontrolled IOP (36 mm Hg) 4 months after an intravitreal injection of triamcinolone underwent two 180° SLT sessions 1 month apart. His IOP had dropped to 20 mm Hg by 1 month and to 12 mm Hg by 2 months after the second 180° treatment. All medications were discontinued, and the eye maintained an IOP of 12 mm Hg.6
Case reports are an effective means of announcing novel therapeutic options, but they lack evidentiary gravitas. The summarized reports do not exclude the possibility that the steroid response ran its course during the 1 to 2 months after treatment and that SLT had little or no real effect on IOP.
Rubin and colleagues reported a retrospective series of seven eyes undergoing SLT for medically uncontrolled IOP after intravitreal injections of triamcinolone. The mean baseline IOP of all seven eyes was 38.4 mm Hg. All were re-examined within 3 weeks of SLT, at a mean of 9 days after the procedure. At this first post-SLT visit, the IOP was 25.6 mm Hg, a reduction of nearly 14 mm Hg. One, 3, and 6 months after SLT, the mean IOP was approximately 26, 24, and 16 mm Hg, respectively. Five of these eyes had preexisting open-angle glaucoma or OHT, four of the seven eyes required a second SLT procedure, and five of the seven were deemed therapeutic successes (the other two underwent surgery). The rapid decrease in IOP in these eyes provides compelling evidence that SLT was directly related to the observed reduction in pressure.7
It is worth mentioning that the IOP benefit in steroidrelated OHT may not be unique to the selective laser system. Two groups have reported similarly significant reductions in IOP among eyes with steroid-related OHT that were treated with argon laser trabeculoplasty (ALT). Decreases of 10 to 20 mm Hg were measured in as few as 3 days after treatment.8,9
MECHANISM OF ACTION
Why would trabeculoplasty be so effective in eyes
with steroid-induced OHT? The mechanism by which
trabeculoplasty lowers IOP in eyes with primary openangle
glaucoma remains poorly understood. Mechanical,
cellular, and biochemical mechanisms have been proposed
for ALT,10 and it has been suggested—based on
their similar efficacy and safety profiles—that ALT and
SLT likely work by the same mechanism.11
One intriguing biological theory involves the recruitment of macrophages into the trabecular meshwork after trabeculoplasty. There, they mediate remodeling of the extracellular matrix and clearing of the debris responsible for obstructing aqueous outflow, resulting in improved outflow facility and thus a reduction in IOP.12,13 If the material clogging the meshwork in steroid-related OHT is particularly amendable to macrophage-mediated removal, this might explain the magnitude of trabeculoplasty's observed effect. Indirectly supporting this theory is that unilateral SLT significantly reduces the IOP in untreated fellow eyes.14,15 These findings could be due to patients' improved compliance with medical therapy. It might also occur, however, if macrophages recruited to the treated eye gain access to the systemic circulation and find their way to the trabecular meshwork in the fellow eye.
The author and colleagues recently probed this theory in a trial in which subjects undergoing bilateral SLT received topical steroids for 1 week in one randomly selected eye.16 The hypothesis was that, if macrophages mediated the IOP-lowering effect of SLT, then steroid therapy to suppress macrophage activity might reduce the effectiveness of the procedure. The study found no significant difference in IOP reduction among eyes that did and did not receive steroids after SLT. The mechanism by which SLT lowers IOP in steroid-related OHT remains unclear.
CLINICAL APPLICATION
For some eyes with steroid-related OHT, SLT (and
probably ALT) appears to provide a rapid and dramatic
reduction in IOP. When faced with a patient who has
medically uncontrolled IOP after steroid therapy, it is
reasonable for physicians to consider SLT before proceeding
with incisional surgery. More than one SLT treatment may be necessary. Based on the limited data
available, at least some SLT-treated eyes will avoid incisional
surgery. Given that there are no significant downsides
to SLT, the potential benefit more than justifies
the small risk.
Tony Realini, MD, is an associate professor of ophthalmology at West Virginia University Eye Institute in Morgantown. Dr. Realini may be reached at (304) 598-6884; realinia@wvuh.com.
