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This certified CME activity is designed for retina specialists and general ophthalmologists involved in the management of retinal disease.
Jointly sponsored by The Dulaney Foundation and Retina Today. Supported by an educational grant from Allergan Inc.
This continuing medical educational activity is supported by an unrestricted educational grant from Allergan, Inc.
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This activity has been planned and implemented in accordance with the Essential Areas and Policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint sponsorship of The Dulaney Foundation and Retina Today. The Dulaney Foundation is accredited by the ACCME to provide continuing education for physicians. The Dulaney Foundation designates this enduring material for a maximum of 1 AMA PRA Category 1 Credit.™ Physicians should claim only the credit commensurate with the extent of their participation in the activity.
Although noninfectious intermediate and posterior uveitis are thought to be relatively uncommon, the Northern California Epidemiology of Uveitis Study (n = 731 898), which is the largest population-based uveitis study that has been performed in the United States, showed the incidence of uveitis to be approximately 3 times that of previous estimates.1 This study showed the annual incidence of noninfectious intermediate and posterior uveitis to be 52.4 per 100 000 person-years and a period prevalence of 115.3 per 100 000 persons. The symptoms of noninfectious intermediate uveitis include sudden painless vision loss or vision decrease with appearance of floaters.2 In noninfectious posterior uveitis, the symptoms range from a decrease in visual acuity with floaters to retinal detachment and optic nerve inflammation. 2 Untreated uveitis may result in long-term visionthreatening complications.3 Macular edema is a common problem in patients with uveitis, often limiting visual potential. Optical coherence tomography studies demonstrate that macular edema is more common in these patients than previously thought,even in patients with anterior nongranulomatous uveitis. 4-5 It precludes good vision even after the uveitis is apparently in remission, for reasons that include retinal pigment epithelial (RPE) dysfunction, vitreomacular traction,and epiretinal membrane formation; finally, inflammatory cytokines themselves can lead to increased vascular permeability, leading to macular edema. The treatment options for noninfectious intermediate and posterior uveitis include off-label use of corticosteroids and anti-VEGF agents, but currently, the only 2 US Food and Drug Administration-approved local treatments for noninfectious intermediate and posterior uveitis are the intravitreal fluocinolone acetonide 0.59 mg implant (Retisert, Bausch + Lomb) and the dexamethasone 0.7 mg intravitreal implant (Ozurdex, Allergan Inc). The clinical trial for the fluocinolone acetonide 0.59 mg implant evaluated 278 patients over the course of 34 weeks after implantation with the implant. Patients were randomized to receive either a 0.59 mg implant or a 2.1 mg implant. The implant was shown at all doses to significantly reduce the rate of uveitis recurrence and to stabilize vision in 87% of implanted eyes.6 The most common side effects were increased intraocular pressure (IOP) and cataract progression. The HURON trial7 was to evaluate the safety and efficacy of 2 doses of the dexamethasone intravitreal implant for the treatment of noninfectious intermediate or posterior uveitis. The primary outcome measure in this trial was the proportion of patients with a vitreous haze score of 0 at week 8. Additional outcome measures were vitreous haze through week 26, best corrected visual acuity, adverse events, IOP, and biomicroscopy/ophthalmoscopy. The results of the trial showed that a single dexamethasone intravitreal implant was significantly more effective than sham at eliminating vitreous haze. At the primary endpoint of week 8, approximately 4 times more eyes treated with the dexamethasone implant 0.7 mg had complete resolution of vitreous haze compared with sham. Treatment with the dexamethasone intravitreal implant also led to a significant improvement in BCVA by week 3 that persisted through week 26. In regard to safety, IOP increases were relatively low in the treatment groups. There was no statistically significant difference in rate of cataract surgery between treatment groups and sham at 6 months. Other forms of local therapy include periocular (subconjunctival or sub-Tenon) and intravitreal injections. Sub-Tenon triamcinolone injections are commonly used to treat uveitic cystoid macular edema. Risks include glaucoma, cataract, and rare cases of scleral perforation with or without retinal detachment. A typical regimen is to use triamcinolone acetonide 40 mgs (1 mL) in the sub-Tenon space. Intravitreal injections of triamcinolone acetonide 2 mg to 10 mg can be considered if periocular injections are ineffective. The risk of glaucoma and cataract are greater with intravitreal injections. The use of preservative-free triamcinolone reduces the risk of sterile endophthalmitis. In 2011, the results of the Multicenter Uveitis Steroid Trial were released.8 This study randomized patients with noninfectious intermediate, posterior, and panuveitis to local therapy with the fluocinolone implant or systemic therapy with corticosteroids and/or immunosuppressive drugs. In both treatment groups, vision improved over 2 years, with neither approach showing a statistically significant benefit over the other. Not surprisingly,the risk of glaucoma and cataract was greater in the implant group, and systemic side effects were greater in the systemic therapy group, although these side effects were usually mild and reversible. The results of the study suggested that the choice of therapy should be dictated by the individual patient’s particular circumstances and preferences. Retina specialists who treat noninfectious intermediate and posterior uveitis face a growing number of treatment options, requiring physicians and their staff to identify, learn about, and implement these newer treatments in a seamless manner. As the US population continues to age and the incidence of vascular and metabolic disorders associated with retinal diseases also increases, clinicians will need to recognize the importance of implementing treatment regimens that maximize efficacy, minimize patient burdens, and help patients manage their disease. 1. Gritz DC, Wong IG. Incidence and prevalence of uveitis in Northern California; the Northern California Epidemiology of Uveitis Study. Ophthalmology. 2004;111(3):491-500. 2. The Merck Manuals Online Medical Library website. http://www.merck.com/home/sec20/ ch232/ch232a.html. Acc 3. Antcliff RJ. Comparison between optical coherence tomography and fundus fluorescein angiography for the detection of cystoid macular edema in patients with uveitis. Ophthalmology. 2000;107(3):593-599. 4. Hee MR et al. Quantitative assessment of macular edema with optical coherence tomography. Arch Ophthalmol. 1995;113:1019-1029. 5. Nussenblatt RB, Kaufman SC, Palestine AG et al. Macular thickening and visual acuity: measurement in patients with cystoid macular edema. Ophthalmology. 1987; 94:1134-1139. 6. Jaffe GJ, Martin D, Callanan D, Pearson PA, Levy B, Comstock T; Fluocinolone Acetonide Uveitis Study Group. Fluocinolone acetonide implant (Retisert) for noninfectious posterior uveitis: thirty-four-week results of a multicenter randomized clinical study. Ophthalmology. 2006;113(6):1020-1027. 7. Lowder C, Belfort R Jr, Lightman S, et al; Ozurdex HURON Study Group. Dexamethasone intravitreal implant for noninfectious intermediate or posterior uveitis. Arch Ophthalmol. 2011;129(5):545-553. 8. The Multicenter Uveitis Steroid Treatment (MUST) Trial Research Group, Kempen JH, Altaweel MM, 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;118:1916-1926.
Thomas Albini, MD, is an Associate Professor of Clinical Ophthalmology at the Bascom Palmer Eye Institute in Miami. He specializes in vitreoretinal diseases and surgery and uveitis. He may be reached at firstname.lastname@example.org.
Faculty/Staff Disclosure Declarations Dr. Albini states that he is a consultant for Allergan Inc, Bausch + Lomb, and Eleven Biotherapeutics. All of those involved in the planning, editing, and peer review of this educational activity report no relevant financial relationships.
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