DISCLOSURE: Dr. Emami- Naeini has no relevant financial disclosures.
Uveitis is one of the major causes of vision loss among young, working- age people.1 Visual impairment is noted in 70 percent of patients with noninfectious uveitis, with macular edema the most common etiology.1,2 In these patients, inflammation leads to impairment of the blood-retinal barrier and increased permeability of chorioretinal vasculature, which will result in accumulation of fluid and uveitic macular edema (UME).3 Macular edema can be seen in any type of noninfectious uveitis, but it’s most commonly seen in association with intermediate, posterior or panuveitis.
Fluorescein angiography and optical coherence tomography are used to confirm the presence of vascular leakage and macular edema. Based on the location of fluid on OCT, UME can be classified into cystoid macular edema, diffuse macular edema and serous retinal detachment. Of these, diffuse edema is the most common, and cystoid macular edema has the most impact on patient’s vision.4,5
Chronic, untreated UME may result in damage to photoreceptors and permanent vision loss. Moreover, UME can be seen even in the setting of controlled uveitis as well as a result of previous inflammation and permanent damage to the blood-retinal barrier.6 Several systemic and local treatment options are available for UME, which we’ll review here.
|Figure 1. A) A 68-year-old woman with a history of sarcoidosis presented with leakage and uveitic macular edema (UME) in the left eye. B) After treatment with intravitreal triamcinolone acetonide, the UME resolved six weeks later.|
Local treatments fall into two subcategories: topical eye drops, and peri- and intraocular steroids.
Eye drops have been used extensively to control anterior uveitis. Recent studies have shown favorable intraocular penetration and effectiveness of various topical drops in the control of UME. Non-steroidal drops, including bromfenac, nepafenac and ketorolac, and steroidal drops, including prednisolone acetate and difluprednate, have been successfully used to treat UME. Corticosteroid drops have been associated with an increase in intraocular pressure and cataract formation. However, they seem to have fewer side effects than other treatment modalities.7,8
A number of peri- and intraocular steroids are available. They include:
- Triamcinolone acetonide 40 mg/ml. Preservative-free triamcinolone acetonide (Triesence, Novartis) is injected intravitreally and has shown to be effective for six to eight weeks, less in vitrectomized eyes. Sub-Tenon’s or transseptal injection of preserved triamcinolone acetonide (Kenalog, Bristol-Myers Squibb) provides a depot of slowly releasing steroids for two to three months. However, the duration is less predictable because of triamcinolone’s variable particle size.
- Dexamethasone 0.7-mg implant. It’s approved for intravitreal use in patents with uveitis and the effect lasts for three to six months. The POINT trial of Ozurdex (Allergan/AbbVie), a prospective randomized clinical study with intravitreal and periocular triamcinolone, showed that both intravitreal steroids are more potent than the periocular steroid in controlling UME and improving visual acuity, with a modest increase in intraocular pressure. No statistically significant difference was found between the two intraocular steroids9 (Figure 1).
- Fluocinolone acetonide 0.18-mg injectable implant. This implant (Yutiq, EyePoint Pharmaceuticals) has shown effectiveness in controlling intraocular inflammation, decreasing flares and preventing vision loss in patients with posterior uveitis.10 The fluocinolone acetonide 0.19-mg implant (Iluvien, Alimera Sciences) is a similar steroid with slightly different dosing. It’s approved for use in diabetic macular edema in the United States and Europe, and for noninfectious uveitis in Europe.11 Studies have demonstrated its effectiveness in managing UME.12
Figure 2. A) A 24-year-old woman with a history of ulcerative colitis and panuveitis was diagnosed with uveitic macular edema (UME), which failed to respond to systemic immunosuppressives. B) The fluocinolone acetonide 0.59-mg surgical implant (Retisert, Bausch + Lomb) resulted in resolution of the UME within two months after surgery.
- Suprachoroidal triamcinolone acetonide injectable suspension. This implant (Xipere, Clearside Biomedical and Bausch + Lomb) recently received Food and Drug Administration approval for use in patients with UME.14 The efficacy and safety of this platform in UME have been studied in the Phase III PEACHTREE trial.15 In this study, 47 percent of patients who received the suprachoroidal steroid gained >15 letters compared to only 16 percent in the sham group (p<0.001). The drug was well-tolerated with comparable rates of cataract and elevated intraocular pressure between the treatment and control arms.
- Anti-VEGF. Recent studies have shown that these medications can be effective in UME, as well. Ranibizumab (Lucentis, Genentech) and aflibercept (Eylea, Regeneron Pharmaceuticals) have been used successfully in treating refractory UME.16
Corticosteroids are effective in controlling ocular inflammation, retinal vasculitis and UME. Their use is associated with a lower risk of local side effects, such as glaucoma and cataract. However, high rates of systemic side effects, including hypertension, diabetes, osteoporosis, mood changes, increased risk of infections and more limits their long-term use. Systemic corticosteroids are generally used for a short period of time and to control acute or breakthrough inflammation.
So, steroid-sparing immunosuppressives are an option for longer-term therapy. They include:
Figure 3. A) A 9-year-old boy had panuveitis and macular edema in both eyes despite topical drops. B) The macular edema resolved three months after the patient started systemic therapy with methotrexate and adalimumab (Humira, AbbVie).
- Adalimumab. This tumor necrosis factor (TNF) inhibitor (Humira, AbbVie) is a fully human monoclonal antibody FDA-approved for systemic use in patients with noninfectious intermediate, posterior or panuveitis (Figure 3).19 This medication can reduce the rate of treatment failure by 43 to 87 percent in patients with inactive and active uveitis, respectively.
Moreover, adalimumab decreased the risk of UME formation by 67 percent and resulted in resolution of edema in up to 70 percent of cases.20 Off-label intravitreal use of adalimumab has also shown effectiveness in reducing UME in a small retrospective series.21 Side effects include increased risk of infection, lymphoma, heart failure and demyelinating disease.
- Tocilizumab. This monoclonal antibody (Actemra, Genentech) targets interleukin 6, and is used to control inflammation and refractory uveitis. A multicenter retrospective study compared the efficacy of tocilizumab with an anti-TNF agent, infliximab (Remicade, Janssen Biotech).22 This study found tocilizumab to be more effective for controlling and achieving complete resolution of UME (Figure 4). Side effects included infections, elevated liver enzymes and hypertension.
|Figure 4. A 16-year-old girl had pars planitis and macular edema in both eyes. The edema (A) didn’t respond well to infliximab (Remicade, Janssen Biotech) and adalimumab (Humira, AbbVie). The patient was switched to tocilizumab (Actemra, Genentech) and the macular edema resolved after two months (B).|
Various systemic and local treatment options are available to manage uveitic macular edema, the most common cause of vision loss in these patients. RS
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