Dexamethasone Intravitreal Implant: Pharmacology and Clinical Update

By Yoshihiro Yonekawa, MD; and Jeremy D. Wolfe, MD

The dexamethasone intravitreal implant (Ozurdex, Allergan) is approved by the US Food and Drug Administration (FDA) for the treatment of diabetic macular edema (DME),1 macular edema associated with retinal vein occlusion (RVO),2 and noninfectious posterior uveitis.3 It delivers a potent corticosteroid via a biodegradable polymer that gradually disintegrates into water and carbon dioxide while the medication is released in a sustained and safe dose over several months.4

Corticosteroids have a broad spectrum of biologic action, including down-regulation of inflammatory cytokines, endothelial adhesion molecules, and growth factors such as VEGF, giving this class of drug antiinflammatory, anti–vascular permeability, and antiangiogenic effects, respectively.4 These molecular mechanisms are dysregulated in many vitreoretinal diseases to varying degrees, making corticosteroids effective treatment options for a number of disease states. However, not all corticosteroids are the same, and their varying chemical structures result in different clinical properties.


Triamcinolone is minimally water-soluble and becomes a depot of crystals that release steroid, resulting in a long half-life.5 Conversely, dexamethasone has two additional hydroxyl groups in the acetonide functional group, making it significantly more hydrophilic compared with triamcinolone and fluocinolone.6 Water solubility has two benefits: a shorter half-life, which makes it amenable as a sustained-release medication by allowing controlled and steady release6; and less aggregation onto ocular structures such as the trabecular meshwork,7 which appears to result in lower rates of intraocular pressure (IOP) elevation.


When using intravitreal corticosteroids in our practice, we ensure that patients have a clear understanding of the risk for cataract progression and possible ocular hypertension. We find that patients are less concerned about cataract, viewing cataract surgery as a matter of when rather than if. Most patients are accepting of drops for ocular hypertension, but glaucoma surgery is always an undesirable course. Among the various intravitreal steroid options, the dexamethasone intravitreal implant has a favorable IOP profile.

In the MEAD trial, incisional glaucoma surgery was required in 0.6% of patients with DME treated with the 700-μg dose of the dexamethasone intravitreal implant.1 By comparison, 33.8% of patients treated with the 0.59-mg fluocinolone acetonide implant (Retisert, Bausch + Lomb),8 4.8% of patients treated with the 0.19-mg fluocinolone acetonide implant (Iluvien, Alimera Sciences),9 and 1.2% treated with 4.0 mg of intravitreal triamcinolone10,11 required incisional glaucoma surgery in the respective large clinical trials evaluating these therapies in patients with DME.

As reflected in the MEAD study results, we find that IOP elevation with the dexamethasone intravitreal implant is mild and predictable. These elevations peak at 6 to 8 weeks after injection and then return to close to baseline by 3 or 4 months.1 In our practice, we have not experienced the so-called staircase progressive IOP elevation with repeated injections as is sometimes seen with triamcinolone. IOP elevation with triamcinolone also appears to be less predictable in terms of timing (several days to many months)12 and severity (between 70-80 mm Hg).13-15 On the other hand, 89% of patients who developed ocular hypertension at any point during the MEAD trial did so within the first three injections, and 99% of patients who developed ocular hypertension did so within the first four injections.16 This means that if a patient has not demonstrated an IOP spike by the third or fourth injection, it is unlikely that he or she will do so after future injections.


Clinical application of the dexamethasone intravitreal implant is broad, and many studies have reported on usages beyond FDA-approved indications. Its efficacy has been demonstrated in use for macular edema after cataract surgery,17-19 retinal detachment repair,19,20 epiretinal membrane peeling,19,21 radiation maculopathy,22,23 retinitis pigmentosa,24,25 and in combination with anti-VEGF agents for neovascular age-related macular degeneration.26 Pediatric uses have also been described.27,28

In our practice, we most commonly use the dexamethasone intravitreal implant in patients with DME and RVO who respond poorly to anti-VEGF agents. The literature supports the efficacy of the dexamethasone intravitreal implant as rescue treatment for recalcitrant DME29-31 as well as branch and central RVO.31,32 The controversial question is when to switch to the dexamethasone intravitreal implant—in other words, after how many ineffective anti-VEGF injections do you consider a patient to be a poor anti-VEGF responder?


It has been demonstrated that if central retinal thickness does not decrease by at least 25% after the first anti-VEGF injection in patients with RVO, the patient is likely to be a poor responder regardless of the number of injections.33 Similar findings have been reported in DME patients (Shah AR, et al, unpublished data). We are therefore comfortable switching to the dexamethasone intravitreal implant relatively early, and these patients often respond well (Figure).


There is controversy over the faster clearance of anti-VEGF agents34,35 and triamcinolone36 in eyes that have undergone vitrectomy. The dexamethasone intravitreal implant, as well as other sustained-release products, have theoretical advantages in vitrectomized eyes because cleared corticosteroid is immediately replaced by more elution of medication.37 Studies have shown the efficacy of the dexamethasone intravitreal implant in vitrectomized eyes with uveitic cystoid macular edema,38 DME,39 and RVO.40

Figure. The efficacy of the dexamethasone intravitreal implant for DME with poor response to anti-VEGF agents is illustrated. The patient’s eye had previously undergone vitrectomy for nonclearing vitreous hemorrhage (A). DME was treated with ranibizumab 0.3 mg (Lucentis, Genentech; A). There was a subtle response seen 5 weeks after injection (B). The patient returned after 11 weeks with worsening intraretinal fluid (C). Aflibercept (Eylea, Regeneron) was administered. There was minimal response seen after 6 weeks, and another aflibercept injection was used (D). There was worsening of edema 8 weeks subsequently, and the patient was switched to the dexamethasone intravitreal implant (E). The edema acutely resolved for the first time, seen 7 weeks after injection of the dexamethasone intravitreal implant (F). There was mild intraretinal fluid on follow-up examination 8 weeks later, and aflibercept was administered (G). The edema worsened 8 weeks later, and it was decided to resume treatment with the dexamethasone intravitreal implant (H). The edema resolved 8 weeks subsequently (I). The patient remains on the dexamethasone intravitreal implant every 3 to 4 months on an as-needed basis, demonstrating excellent control of edema for more than a year.




The dexamethasone intravitreal implant and the two fluocinolone acetonide implants are all sustained-release devices, but they differ in their durations of action. The fluocinolone implants were designed to last for 3 years. Significantly fewer injections are required, but, once the implant is placed, the eye is committed to potentially 3 years of steroid exposure and accompanying IOP complications. On the other hand, the dexamethasone intravitreal implant, while initially designed to last for 6 months, usually provides clinically meaningful effects for 3 to 4 months based on our experience with refractory edema. The drawback of requiring more injections becomes an advantage when managing IOP issues, because the steroid effects subside sooner.


The dexamethasone intravitreal implant is an efficacious steroid delivery system that provides sustained release of a safe and potent steroid in a controlled and predictable manner. It has played an important role in our practice’s treatment paradigms for retinovascular disorders and posterior uveitis. n

Yoshihiro Yonekawa, MD, is a second-year vitreoretinal surgery fellow at Associated Retinal Consultants/William Beaumont Hospital in Royal Oak, Mich. He reports no conflicts of interest. Dr. Yonekawa may be reached at


Jeremy D. Wolfe, MD, is a partner at Associated Retinal Consultants, Royal Oak, Mich., and assistant professor of Ophthalmology at Oakland University William Beaumont School of Medicine. He is a consultant for Allergan, Alimera, and Genentech. Dr. Wolfe may be reached at

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About Retina Today

Retina Today is a publication that delivers the latest research and clinical developments from areas such as medical retina, retinal surgery, vitreous, diabetes, retinal imaging, posterior segment oncology and ocular trauma. Each issue provides insight from well-respected specialists on cutting-edge therapies and surgical techniques that are currently in use and on the horizon.