Can steroid intravitreal injection or the use of intravitreal devices cause ocular hypertension and/or glaucoma?
Angela Carneiro, MD, PhD
In the literature, steroid use has long been associated with development of ocular hypertension (OHT)1,2. The most commonly suggested mechanism for pressure increase caused by steroids is reduced aqueous humour drainage at both trabecular and uveoscleral level. There are multiple explanatory theories, ranging from a reduction in the phagocytic activity of trabecular endothelial cells to the inhibition of extracellular matrix degradation, etc3,4.
There are currently several types of corticoids for intraocular administration: there is triamcinolone and dexamethasone in off-label use and dexamethasone and fluocinolone slow-release devices (Ozurdex®, Iluvien® and Retisert®).
It is important to stress that adverse effects in off-label uses are typically reported irregularly and randomly, so the OHT and glaucoma rates are probably underestimated in the literature.
For triamcinolone, of which multiple formulations are available and in a wide range of intravitreal doses, case series reported in the literature suggest highly variable OHT rates (between 28% and 83%) in treated patients. Pressure can rise at once, in the first week after drug administration, and be sustained for up to 60 weeks. Pressure increase is typically dose-dependent. Pre-treatment OHT, young age, male gender and previous uveitis have all been identified as risk factors. Glaucoma surgery is required in approximately 0.01-5% of the cases to control OHT5,6,7.
There are too few reports for off-label dexamethasone intravitreal injection in the literature to give a definite idea of the actual OHT or glaucoma rates.
Randomized multicentre studies on slow-release devices, with published results, are available in the literature and provide some information on the rates of OHT and surgery required to treat high pressure.
Ozurdex®, a device providing the slow release of 0.7 mg of dexamethasone in a biodegradable Novadur® polymer administered by intravitreal injection has been approved by the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) to treat macular oedema associated with retinal venous occlusion or chronic non-infectious posterior uveitis. Twelve-month results in patients with macular oedema secondary to retinal venous occlusion show a rate of intraocular pressure increase ³ 10 mmHg from baseline of 12.6% of the eyes 60 days after application of the first implant and of 15.4% of the eyes 60 days after application of the second implant. Overall, 32.8% of the eyes undergoing a second implant showed an increase at some point during the 12 months of the study. In most cases, high pressure responded to topical medication and resolved 180 days after Ozurdex® implantation. Laser treatment or surgery was required in only 14 of the 756 implanted eyes to control the pressure increase8.
Retisert®, a surgically implanted, non-biodegradable device for the slow release of 0.59 mg fluocinolone approved by the FDA for the treatment of chronic, non-infectious posterior uveitis provides 4-year results in a patient group with diabetic macular oedema. An increase of intraocular pressure (IOP) to ³ 30 mmHg was recorded in 61.4% of the eyes at some point in the 4 years of follow-up and 33.8% of the patients required filtration or laser surgery for pressure control9.
Iluvien® is a non-biodegradable device for the slow release of 190 mg fluocinolone by intravitreal injection. It is approved in some countries, including Portugal, to treat chronic diabetic macular oedema. Results of FAME 1 and 2 studies, which used implants with a daily release of 0.2 or 0.5 mg fluocinolone, showed OHT in 37.1% of the patients with low dose implants and in 45.5% of the patients with high dose implants. Laser trabeculoplasty or filtration surgery was required respectively in 1.3% and 4.8% of the patients with low dose implants, and in 2.5% and 8.1%, respectively, of the patients with high dose implants10,11.
Therefore, steroid intravitreal administration shows a range of OHT rates that vary from drug to drug, and even between different presentations of the same drug and in groups of risk patients. However, given the high percentage of patients with pressure increase, its use should be avoided in risk groups and careful monitoring of intraocular pressure from the very first week after use should not be overlooked in any of these patients.