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Frame Portals on Steroids
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In this subset of patients, IOPs should be monitored regularly. Care should be taken to avoid corticosteroids If possible. If corticosteroids are indicated, the judicious use of an adequate potency and duration should be considered.
Intraocular pressure rise may occur with corticosteroid drops or ointment applied to the eye or with steroid preparations applied to the skin of the eyelids. In general, the potency of the steroid as well as the frequency and duration of use, appears to correlate with the risk of elevating the IOP.[24] For example, dexamethasone and prednisolone are more potent steroids and similarly increase the IOP more frequently than less potent steroids such as fluoromethalone, hydrocortisone, and rimexolone.[25]
Difluprednate (Durezol) is one of the most potent topical steroids, and one of the most likely to cause an increase in IOP. An estimated 3% of patients treated with difluprednate experience a significant increase in IOP. This estimate is based on a study of patients who had recently undergone ocular surgery and were treated with difluprednate two or four times daily in the post-operative period. Amongst the difluprednate group, 3% exhibited an increase in IOP 10 mm Hg or greater above their baseline to an IOP of 21 mm Hg or greater, compared to 1% in the placebo (vehicle only) group.[26] These findings were supported by another study of patients who underwent cataract surgery, which showed that 3.7% of those treated with difluprednate twice daily exhibited an IOP increase greater than 10 mm Hg or more from baseline to greater than 21 mm Hg, compared to 0% in the placebo group.[27]
Dexamethasone, prednisolone, and fluoromethalone are all early generation topical ocular corticosteroids. Because of their introduction prior to strict regulatory research requirements, placebo-controlled clinical trials are lacking.[28] The broadest comparative data comes from a small study which investigated the effect of multiple early generation topical corticosteroids on the IOP in ten known steroid responders. These patients underwent sequential testing with a number of topical steroids, including dexamethasone 0.005%, hydrocortisone 0.5%, fluoromethalone 0.1%, prednisolone acetate 1%, and dexamethasone 0.1%. Hydrocortisone 0.5% elicited the smallest IOP rise (average 3.2 mm Hg), followed by fluoromethalone 0.1% (average 6.1 mm Hg), dexamethasone 0.005% (average 8.2 mm Hg), and prednisolone 1.0% (average 10 mm Hg). Patients treated with dexamethasone 0.1% exhibited the greatest rise in IOP (average 22 mm Hg).[24]
As newer topical steroids have been released, comparative studies against earlier generation preparations have provided greater insight into their efficacy and effect on IOP. In a study comparing the postoperative management of uneventful cataract surgery, the proportion of patients who displayed a significant increase in IOP (defined as a 6 mm Hg greater than preoperative IOP) was twice that in the difluprednate group compared to the prednisolone group (8% compared to 4.14%, respectively).[29] A study comparing the efficacy and safety of loteprednol with prednisolone acetate (each administered four times daily) found that the mean IOP and mean change in IOP was higher in patients treated with prednisolone, though this finding did not reach statistical significance.[30]
As displayed in the aforementioned studies, the potency of topical ophthalmic steroids tends to correlate with the severity of IOP rise. Ultimately, difluprednate is the most likely to elevate IOP, followed by dexamethasone, prednisolone, loteprednol, and fluoromethalone. However, the proportion of patients who will experience an IOP rise is not as well defined. As mentioned, it is likely strongly correlated with patient risk factors for developing glaucoma regardless of steroid use; however, comparisons and incidence estimates in studies are confounded by non-modifiable glaucoma risk factors within the patient population as well as varying definitions of categorical IOP elevation.
Given the differing ocular pathology they are best used for, there are not many studies which offer direct comparison between periocular mechanisms of steroid delivery. Of the studies which compare routes of periocular steroid delivery, it appears that while all periocular steroids may increase IOP, the delivery route likely plays an important role in the timing to the peak effect, as well as how long this effect lasts. In one study on subconjunctival injection of repository corticosteroid, the mean peak in IOP occurred at 7.1 weeks, and lasted for a mean duration of 3 months.[33]
Several studies offer comparisons between intravitreal and periocular delivery of corticosteroids. A study examining the efficacy of intravitreal and retrobulbar triamcinolone in patients with macular edema associated with branch retinal vein occlusion found an IOP increase in both therapy groups. However, the incidence of an IOP rise 20 mm Hg or greater was significantly higher in the intravitreal group (33.3%), compared to the retrobulbar group (7.4%). Although no significant difference in mean IOP throughout the follow-up period was appreciated, patients were only followed to three months before being re-treated.[34] Another study investigating the IOP elevation after intravitreal or sub-Tenons injection of triamcinolone found a statistically significant mean IOP elevation above baseline at all follow-up periods, though likely became clinically insignificant beyond 6 months. However, the mean IOP of eyes receiving sub-Tenon injection increased significantly at all follow-ups (1, 2, 3, 6 months), whereas the mean IOP of eyes receiving intravitreal injection was only significantly increased at the 1 month time point.[32]
The most common corticosteroids administered intravitreally include triamcinolone, fluocinolone, and dexamethasone. Dexamethasone, often used at 0.4-mg or 0.8-mg dosing, is the more potent steroid, with a shorter duration of action. Triamcinolone is often dosed at 4 mg and has a duration of action extending to three months.[35] Most ocular pathology requiring treatment with intravitreal corticosteroids requires multiple treatments to maintain therapeutic effect, raising the risk of adverse events, such as endophthalmitis, as well as patient discomfort with multiple injections. For this reason, sustained release corticosteroid implants have an important role in the treatment of many ocular microvascular and inflammatory pathologies. Ozurdex is the shortest acting and only biodegradable, sustained-release implant, which is inserted into the vitreous where it releases dexamethasone at a controlled rate for up to 6 months. Retisert and Iluvien are non-biodegradable implants that release fluocinolone at a controlled rate for 30 and 36 months, respectively. Retisert is inserted via the pars plana and sutured to the sclera, whereas Iluvien is inserted via the pars plana into the vitreous.[35]
The timing and incidence rate of IOP elevation that develops after intravitreal administration of corticosteroids varies depending on the molecule and the dose. In about half of patients that received intravitreal triamcinolone, IOP elevation developed between two to four weeks after the injection. In eyes that are pseudophakic or have undergone vitrectomy, the rise can happen more rapidly.[36] [37] [38] In a systemic review of patients who had been treated with triamcinolone 4 mg, the onset of IOP elevation (defined as IOP of or greater than 21 mm Hg, or IOP of or greater than 10 mm Hg from baseline) was 2-4 weeks in randomized controlled trials and 1-8 weeks in non-randomized controlled trials.[39]
As indicated above, the incidence of IOP elevation associated with intravitreal corticosteroids appears to be directly correlated with the molecule and dose administered. Between the two fluocinolone implants, Retisert, which is inserted pars plana and sutured to sclera may carry a greater risk of IOP elevation.
Close IOP monitoring of these patients is essential and consideration of a non-steroidal topical medication, such as tacrolimus and pimecrolimus, should be considered as an alternative in patients with glaucoma. Elevation in IOP has also been noted with application of steroids on skin that was not periocular, either from ocular contamination or systemic absorption. [44] Patients should be advised to wash their hands after applying dermatologic steroids or to use gloves.
There is a relative paucity of large studies on the IOP effects of non-ocular targeted localized corticosteroids. In one cohort study based out of an orthopedic clinic, the IOP of patients receiving intraarticular knee injections of triamcinolone were compared to those receiving hyaluronic acid. This study showed a difference in the mean increase in IOP between the groups as well as a significant difference in the number of patients who developed an IOP increase > 7 mm Hg (29% in the triamcinolone group, 0% in the hyaluronic acid group)[52]. 041b061a72