|Year : 2020 | Volume
| Issue : 4 | Page : 262-267
Dexamethasone implant – An update
Richa Pyare, Jyotirmay Biswas
Department of Uvea, Medical and Vision Research Foundations, Sankara Nethralaya, Chennai, Tamil Nadu, India
|Date of Submission||21-Jun-2020|
|Date of Decision||12-Jul-2020|
|Date of Acceptance||07-Aug-2020|
|Date of Web Publication||16-Dec-2020|
Dr Jyotirmay Biswas
Department of Uvea, Sankara Nethralaya 18, College Road, Nungambakkam, Chennai - 600 006, Tamil Nadu
Source of Support: None, Conflict of Interest: None
Uveitic entities may be infectious or noninfectious in etiology. Corticosteroids remain the first-line treatment for noninfectious posterior uveitis. Intravitreal injections of steroids have been useful in targeted therapy of the posterior segment. However, a host of systemic and local adverse effects limits the usefulness of steroids. Intravitreal implants of dexamethasone with sustained release of the drug over months are a more effective and safer option. Various formulations with varying dosage and lifespan such as retisert, ozurdex, and yutiq are available. Ozurdex has a very successful track record over numerous studies in treating posterior uveitis in adults and children. It is important to rule out infectious causes of uveitis before administering ozurdex. We can achieve optimal control of ocular inflammation with minimal systemic side effects when used judiciously.
Keywords: Corticosteroids, dexamethasone, intravitreal implants, intravitreal injections, management of uveitis, noninfectious posterior uveitis, ozurdex
|How to cite this article:|
Pyare R, Biswas J. Dexamethasone implant – An update. TNOA J Ophthalmic Sci Res 2020;58:262-7
| Introduction|| |
Uveitis may be infectious or noninfectious in etiology. The major bulk of uveitis is noninfectious in nature. Options for the treatment of noninfectious intermediate, posterior, and panuveitis include steroids given systemically (oral or intravenous) or locally, immunosuppressive agents, and biologics. Here, we present a review of dexamethasone implant available for the treatment of noninfectious posterior uveitic entities.
We searched PubMed for all published articles regarding intravitreal injections of dexamethasone in uveitis. Keywords used were treatment of non-infectious posterior uveitis, corticosteroids in non-infectious posterior uveitis, intravitreal injections, intravitreal corticosteroids and uveitis, dexamethasone and uveitis, ozurdex, and uveitis. To ensure that this review is up to date as possible, PubMed was regularly reviewed during the preparation of the manuscript.
| Use of Corticosteroids in Noninfectious Uveitis|| |
Corticosteroids are often the first-line therapy used against noninfectious uveitis. They act by suppressing the constant release of inflammatory mediators, decreasing vascular permeability, strengthening the epithelial tight junctions, and maintaining the blood ocular barriers. However, systemic use of steroids carries multiple adverse effects, affecting almost all parts of our body. Besides, the physiological blood–retinal barrier prevents effective penetration and action of steroids in the posterior segment. Local steroid administration helps to limit disease severity with minimal systemic side effects. Topical steroid therapy is effective for anterior uveitis, but due to limited penetration into the posterior segment is less useful in the intermediate or posterior uveitis.
Injection of repository steroids such as triamcinolone acetonide into the posterior subtenon space is of value in the treatment of cystoid macular edema secondary to uveitis. However, the efficacy is limited, with one study indicating only 56% patients showing improvement. Besides the side effects associated with steroid use like cataract and glaucoma, blepharoptosis is a limiting adverse effect associated with multiple repository injections.
| Intravitreal Injection of Steroids|| |
Intravitreal preservative-free triamcinolone is an additional option for uveitis-related macular edema, particularly in unilateral cases, with favorable visual and anatomical outcomes. However, repeat injections are often necessary, as the period of efficacy varies between eyes. The rates of ocular adverse effects of cataract and intraocular pressure (IOP) rise are very high, with one study showing raised IOP of >21 mmHg in 45.4% eyes and cataract progression in 47% of phakic eyes. The adverse effects most commonly observed with all forms of steroid use are IOP rise and cataract progression. The mechanism of IOP rise is postulated to include corticosteroids decreasing the outflow by inhibiting degradation of extracellular matrix material in the trabecular meshwork (TM) by altering the metabolism of mucopolysaccharides, leading to aggregation of an excessive amount of the material within the outflow channels and a subsequent increase in outflow resistance.,
For steroid-induced cataracts, there is proof for the key role of involvement of aberrant migrating lens epithelial cells. Glucocorticoids may be capable of inducing changes to the transcription of genes in lens epithelial cells that are related to many cellular processes such as proliferation, suppressed differentiation, a reduced susceptibility to apoptosis, altered transmembrane transport, and enhancement of reactive oxygen species activity. These altered cellular processes are postulated to lead to cataract formation.
| History of Intravitreal Injections|| |
Intravitreal injections have a long history of use in ophthalmology. [Table 1] traces the history of use of intravitreal injections and sustained release implants.
| Intravitreal Steroid Implants|| |
Intravitreal implants cause sustained release of the steroid slowly over the course of months to years. These implants can be biodegradable or nonbiodegradable. The types of steroid implants available are as follows: Ozurdex™, a dexamethasone 0.7 mg carrying implant made of biodegradable poly DL-lactide-co-glycolide (PLGA), Retisert™, fluocinolone acetonide 0.59 mg carrying implant, and Yutiq™ fluocinolone acetonide 0.18 mg carrying implant both of which are nonbioerodible and require removal of the reservoir after depletion. Of these, Retisert gained approval of the Food and Drug Administration in 2005 to treat uveitic macular edema, Ozurdex gained the approval in 2010, and Yutiq in 2018.
Ozurdex implant has 0.7 mg dexamethasone, contained in a bioerodible implant [Figure 1]. The implant is a mix of polylactic and polyglycolic acid polymers (PLGA). PLGA is slowly hydrated and converted into the inert compounds, lactic acid and glycolic acid which are then converted to CO2 and water through the Krebs cycle releasing dexamethasone over months [Figure 2]. It is possible to manipulate the polymer composition during manufacturing to produce a desired rate of degradation that can vary from weeks to years. Ozurdex was designed and manufactured to release the drug over a period of 6 months.
Retisert 0.59 mg fluocinolone acetonide carrying implant is nonbioerodible and requires removal after depletion of steroid drug. Studies have shown its efficacy in various noninfectious uveitic diseases. The efficacy is, however, counterbalanced by its high rate of adverse reactions, including a nearly 4 times greater risk of cataract progression and 77.9% of implant group requiring IOP-lowering medications.
| Technique for Ozurdex Insertion|| |
The technique of insertion of Ozurdex implant is fairly simple. It may be done as an office procedure, although in India, it is done in the operation theater complex under aseptic precautions. The foil pouch is removed from the carton and the implant is examined to see that there is no damage to the implant. The cap is then removed from the applicator. The surgeon holds the applicator in one hand and pulls the safety tab from the applicator by the other hand. The long axis of the applicator is held parallel to the limbus and the sclera should be engaged in an oblique way with the bevel of the needle looking up. The tip of the needle is advanced within the sclera for about 1 mm and then redirected to the center of the eye and then re-advanced until the sclera is penetrated and vitreous is entered. The surgeon presses the activator button, until an audible click is heard. The applicator is then removed in the same manner as it was advanced.
| Studies Evaluating the Role of Ozurdex|| |
There are various studies evaluating the efficacy of Ozurdex implants. [Table 2] summarizes a number of such studies.
| Complications of Ozurdex|| |
Various studies have also documented the complications associated with the use of Ozurdex implant [Table 3]. The most common adverse events associated are IOP rise, which can usually be controlled with topical medications and visually significant cataract.
| Pearls for Practice|| |
Ozurdex implant is an appropriate treatment option in noninfectious uveitic eyes with macular edema, with or without vitritis [Figure 3] and [Figure 4]. It is essential to rule out infectious causes of uveitis, especially viral and toxoplasma-related uveitis before considering Ozurdex. It should also be avoided in patients who are aphakic or have had a posterior capsular rent during cataract surgery due to the risk of anterior migration of implant. Ozurdex can be considered in patients of glaucoma, unlike posterior subtenon or intravitreal triamcinolone as it has a lower IOP raising potential than these modalities. It is effective in cases where standard therapy has failed. Ozurdex can also be considered in pediatric uveitis cases.
|Figure 3: Cystoid macular edema secondary to intermediate uveitis: Foveal thickness: 619 microns|
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|Figure 4: Postozurdex injection: Cystoid macular edema in the same patient as figure 3 has resolved, foveal thickness: 171 microns|
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| Conclusion|| |
Dexamethasone implant Ozurdex is an extremely useful tool in the uveitis specialist's armamentarium. Appropriate use in noninfectious uveitic conditions helps achieve optimal inflammatory control and visual results with minimal systemic side effects.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4]
[Table 1], [Table 2], [Table 3]