Advances in the Treatment of Intermediate and Posterior Uveitis

Samantha Fraser-Bell; Carlos Pavesio


Expert Rev Ophthalmol. 2008;3(4):449-456. 

In This Article

Local Therapy

In unilateral or asymmetric cases, the use of periocular injections (orbital floor and posterior sub-Tenon's) of corticosteroid can be attempted as first-line therapy, as long as the formal contraindications have been observed (especially infective causes such as toxoplasmosis and acute retinal necrosis). It is also useful if systemic therapy is contradicted.[74] Local therapy allows the delivery of the drug in close proximity to the eye, with penetration occurring through the sclera and reducing the risk of systemic side effects. More recently, intraocular delivery has become another alternative, overcoming all barriers and placing the drug where it is needed. Steroid response is a contraindication for local corticosteroid deposition.

Intravitreal triamcinolone acetonide (IVTA) in doses from 2 to 25 mg has been used for the treatment of inflammatory CME, vitritis and choroidal neovascularization.[75,76,77,78,79,80,81,82] This treatment is an off-label use of the drug. CME is the most common cause of vision loss in uveitis and can persist even after other signs of inflammation have resolved. It usually responds rapidly to intravitreal injection of corticosteroid, at least anatomically. The duration of the effect is 2-6 months. Complications include elevated intraocular pressure in 41% of eyes from a meta analysis of 112 eyes,[83] which usually occurs between 1 week and 3 months[84] and is more common in younger people with uveitis. Infective endophthalmitis occurs in approximately 0.5% and cataract in most.[84]

The problem with IVTA is the short duration of the effect and the need for retreatment. Multiple injections increase the risk of complications including cataract, glaucoma and endophthalmitis.

A more desirable modality is sustained delivery over a prolonged period of time. One such device, the Retisert™ (Bausch & Lomb), has received US FDA approval for the management of noninfectious posterior uveitis, while others are being investigated. The Retisert uses the same delivery technology previously used for the treatment of CMV retinitis with ganciclovir, and delivers fluocinolone acetonide for a period of 2.5 years. The implantation procedure involves a small incision over the pars plana and suturing of the device to the sclera using prolene suture. Studies have shown that the 0.59-mg device significantly reduces the rate of disease reactivation and compares favorably to standard of care with systemic therapy [Bausch & Lomb-Sponsored Trial; Unpublished Data]. The most frequently seen complications are cataract, in over 90% of the implanted eyes, and glaucoma, with approximately 30% of eyes requiring filtering procedures.[85]

Another device is Posurdex® (Allergan), which uses dexamethasone, and is composed of biodegradable copolymer of lactic acid and glycolic acid. As dexamethasone is released, the polymer slowly biodegrades into carbon dioxide and water over 6 months. Since the implant eventually dissolves completely, sequential implants can be placed into the eye over time without the need for surgical removal. A randomized, controlled trial of 315 eyes with macular edema from any cause (randomized to 700 µg, 350 µg or sham), showed improved visual acuity at 90 days after implantation, with better results seen in the 700-µg arm.[86]

Bevacizumab is a humanized, full-length monoclonal antibody to VEGFα. It has been effective in reducing CME from vascular causes and has recently been studied as a treatment in eyes with CME secondary to uveitis in ten patients.[87] There was a significant reduction in macula thickness, but not all eyes improved vision (four out of eleven), which the authors postulated was due to the chronicity of the edema and secondary structural changes present. The effect was transient and repeated injections are necessary.

In summary, the past few years have witnessed the appearance of new options for the management of noninfective posterior uveitis, including biological agents, which still require well conducted randomized clinical trials to confirm their benefit. Local options have become increasingly appealing owing to the reduction of significant systemic side effects, but are still confronted with problems related to the form of delivery and drug-related local side effects.


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