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 Table of Contents  
REVIEW ARTICLE
Year : 2020  |  Volume : 58  |  Issue : 4  |  Page : 262-267

Dexamethasone implant – An update


Department of Uvea, Medical and Vision Research Foundations, Sankara Nethralaya, Chennai, Tamil Nadu, India

Date of Submission21-Jun-2020
Date of Decision12-Jul-2020
Date of Acceptance07-Aug-2020
Date of Web Publication16-Dec-2020

Correspondence Address:
Dr Jyotirmay Biswas
Department of Uvea, Sankara Nethralaya 18, College Road, Nungambakkam, Chennai - 600 006, Tamil Nadu
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/tjosr.tjosr_75_20

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  Abstract 


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

How to cite this URL:
Pyare R, Biswas J. Dexamethasone implant – An update. TNOA J Ophthalmic Sci Res [serial online] 2020 [cited 2021 Jan 19];58:262-7. Available from: https://www.tnoajosr.com/text.asp?2020/58/4/262/303657




  Introduction Top


Uveitis may be infectious or noninfectious in etiology. The major bulk of uveitis is noninfectious in nature.[1] Options for the treatment of noninfectious intermediate, posterior, and panuveitis include steroids given systemically (oral or intravenous) or locally, immunosuppressive agents, and biologics.[2] 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 Top


Corticosteroids are often the first-line therapy used against noninfectious uveitis.[2] 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.[3] 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.[4] 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 Top


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.[5] 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.[6],[7]

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.[8]


  History of Intravitreal Injections Top


Intravitreal injections have a long history of use in ophthalmology. [Table 1] traces the history of use of intravitreal injections and sustained release implants.
Table 1: History of intravitreal injections

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  Intravitreal Steroid Implants Top


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.
Figure 1: Ozurdex implant in the vitreous cavity

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Figure 2: Degrading Ozurdex implant in the vitreous cavity

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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.[16]


  Technique for Ozurdex Insertion Top


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 Top


There are various studies evaluating the efficacy of Ozurdex implants. [Table 2] summarizes a number of such studies.
Table 2: Results of Ozurdex implantation: Review of various studies

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  Complications of Ozurdex Top


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.
Table 3: Complications of Ozurdex: Review of various studies

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  Pearls for Practice Top


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 Top


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

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Hsu YR, Huang JC, Tao Y, Kaburaki T, Lee CS, Lin TC, et al. Noninfectious uveitis in the Asia-Pacific region. Eye (Lond) 2019;33:66-77.  Back to cited text no. 1
    
2.
Dick AD, Rosenbaum JT, Al-Dhibi HA, Belfort R, Jr., Brezin AP, et al. Guidance on noncorticosteroid systemic immunomodulatory therapy in noninfectious uveitis: Fundamentals of care for uveitis (FOCUS) initiative. Ophthalmology 2018;125:757-73  Back to cited text no. 2
    
3.
Ericson-Neilsen W, Kaye AD. Steroids: Pharmacology, complications, and practice delivery issues. Ochsner J 2014;14:203-7.  Back to cited text no. 3
    
4.
Yoshikawa K, Kotake S, Ichiishi A, Sasamoto Y, Kosaka S, Matsuda H. Posterior sub-Tenon injections of repository corticosteroids in uveitis patients with cystoid macular edema. Jpn J Ophthalmol 1995;39:71-6.  Back to cited text no. 4
    
5.
Steeples LR, Anand N, Moraji J, Jones NP. Clinical outcomes of intravitreal preservative-free triamcinolone preparation (Triesence®) for cystoid macular oedema and inflammation in patients with uveitis. Ocul Immunol Inflamm 2018;26:997-1004.  Back to cited text no. 5
    
6.
Renfro L, Snow JS. Ocular effects of topical and systemic steroids. Dermatol Clin 1992;10:505-12.  Back to cited text no. 6
    
7.
Armaly MF. Effect of corticosteroids on intraocular pressure and fluid dynamics. I. The effect of dexamethasone in the normal eye. Arch Ophthalmol 1963;70:482-91.  Back to cited text no. 7
    
8.
James ER. The etiology of steroid cataract. J Ocul Pharmacol Ther 2007;23:403-20.  Back to cited text no. 8
    
9.
Peyman GA, Lad EM, Moshfeghi DM. Intravitreal injection of therapeutic agents. Retina 2009;29:875-912.  Back to cited text no. 9
    
10.
Schneider J, Frankel SS. Treatment of late postoperative intraocular infections with intraocular injection of penicillin. Arch Ophthal 1947;37:304-7.  Back to cited text no. 10
    
11.
Peyman GA, Vastine DW, Raichand M. Experimental aspects and their clinical application. Ophthalmology 1978;85:374-85.  Back to cited text no. 11
    
12.
Graham RO, Peyman GA. Intravitreal injection of dexamethasone. Treatment of experimentally induced endophthalmitis. Arch Ophthalmol 1974;92:149-54.  Back to cited text no. 12
    
13.
Blumenkranz M, Hernandez E, Ophir A, Norton EW. 5-fluorouracil: New applications in complicated retinal detachment for an established antimetabolite. Ophthalmology 1984;91:122-30.  Back to cited text no. 13
    
14.
Henry K, Cantrill H, Fletcher C, Chinnock BJ, Balfour HH Jr. Use of intravitreal ganciclovir (dihydroxy propoxymethyl guanine) for cytomegalovirus retinitis in a patient with AIDS. Am J Ophthalmol 1987;103:17-23.  Back to cited text no. 14
    
15.
Penfold PL, Gyory JF, Hunyor AB, Billson FA. Exudative macular degeneration and intravitreal triamcinolone. A pilot study. Aust N Z J Ophthalmol 1995;23:293-8.  Back to cited text no. 15
    
16.
Multicenter Uveitis Steroid Treatment (MUST) Trial Research Group, Kempen JH, Altaweel MM, Holbrook JT, Jabs DA, Louis TA, et al. Randomized comparison of systemic anti-inflammatory therapy versus fluocinolone acetonide implant for intermediate, posterior, and panuveitis: The multicenter uveitis steroid treatment trial. Ophthalmology 2011;118:1916-26.  Back to cited text no. 16
    
17.
Kuppermann BD, Blumenkranz MS, Haller JA, Williams GA, Weinberg DV, Chou C, et al. Randomized controlled study of an intravitreous dexamethasone drug delivery system in patients with persistent macular edema. Arch Ophthalmol 2007;125:309-17.  Back to cited text no. 17
    
18.
Lowder C, Belfort R Jr., Lightman S, Foster CS, Robinson MR, Schiffman RM, et al. Dexamethasone intravitreal implant for noninfectious intermediate or posterior uveitis. Arch Ophthalmol 2011;129:545-53.  Back to cited text no. 18
    
19.
Zarranz-Ventura J, Carreño E, Johnston RL, Mohammed Q, Ross AH, Barker C, et al. Multicenter study of intravitreal dexamethasone implant in noninfectious uveitis: Indications, outcomes, and reinjection frequency. Am J Ophthalmol 2014;158:1145.e5.  Back to cited text no. 19
    
20.
Arcinue CA, Cerón OM, Foster CS. A comparison between the fluocinolone acetonide (Retisert) and dexamethasone (Ozurdex) intravitreal implants in uveitis. J Ocul Pharmacol Ther 2013;29:501-7.  Back to cited text no. 20
    
21.
Palla S, Biswas J, Nagesha CK. Efficacy of Ozurdex implant in treatment of noninfectious intermediate uveitis. Indian J Ophthalmol 2015;63:767-70.  Back to cited text no. 21
[PUBMED]  [Full text]  
22.
Sella R, Oray M, Friling R, Umar L, Tugal-Tutkun I, Kramer M. Dexamethasone intravitreal implant (Ozurdex®) for pediatric uveitis. Graefes Arch Clin Exp Ophthalmol 2015;253:1777-82.  Back to cited text no. 22
    
23.
Rajesh B, Zarranz-Ventura J, Fung AT, Busch C, Sahoo NK, Rodriguez-Valdes PJ, et al. Safety of 6000 intravitreal dexamethasone implants. Br J Ophthalmol 2020;104:39-46.  Back to cited text no. 23
    
24.
Pohlmann D, Vom Brocke GA, Winterhalter S, Steurer T, Thees S, Pleyer U. Dexamethasone inserts in noninfectious uveitis: A single-center experience. Ophthalmology 2018;125:1088-99.  Back to cited text no. 24
    
25.
Alba-Linero C, Sala-Puigdollers A, Romero B, Llorenç V, Adan A, Zarranz-Ventura J. Long-term intravitreal dexamethasone implant outcomes in uveitis. Ocul Immunol Inflamm 2020;28:228-37.  Back to cited text no. 25
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]
 
 
    Tables

  [Table 1], [Table 2], [Table 3]



 

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Abstract
Introduction
Use of Corticost...
Intravitreal Inj...
History of Intra...
Intravitreal Ste...
Technique for Oz...
Studies Evaluati...
Complications of...
Pearls for Practice
Conclusion
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