Uveitis Complicated by Cystoid Macular Edema
Title: Uveitis Complicated by Cystoid Macular Edema
Authors: Brandon K. Winward; Marissa B. Larochelle, MD
Keywords: Uveitis; Cystoid Macular Edema; Uveitic Macular Edema; Intraocular Inflammation
Diagnosis: Anterior and Intermediate Uveitis of Both Eyes Complicated by Cystoid Macular Edema of the Right Eye
Description of Case:
An 18-year-old female with no past medical history presented with blurry vision, pain, and light sensitivity of the right eye. She was treated for “pink eye” by her primary care provider without improvement prior to being referred to an outside ophthalmologist. Visual acuity at that time was 20/40 in the right eye and 20/25 in the left eye. Slit lamp examination revealed posterior synechiae and inflammatory cells in the anterior chambers and vitreous of both eyes. Optical coherence tomography revealed central cystoid intraretinal fluid pockets of the right macula. The patient was started on topical corticosteroids to both eyes and received a right-sided sub-Tenon’s triamcinolone injection. This resulted in resolution of macular edema and improvement of inflammatory cell grade of both anterior and vitreous chambers but also increased intraocular pressure (IOP) in the right eye (up to 30 mmHg). She was started on brimonidine, timolol, and latanoprost eyedrops in the right eye before being referred to a tertiary care center for further management.
Upon arrival at the tertiary care center, the patient’s visual acuity was 20/30 in each eye. IOP was 24 and 21 mmHg in the right and left eyes, respectively. Examination revealed mild ptosis of the right eye, quiet anterior chambers, moderate vitreous cell of the left eye, and snowbanks in the inferior vitreous of both eyes. No macular edema was detected on repeat optical coherence tomography at the time. Fluorescein angiography demonstrated mild peripheral fernlike leakage of both eyes. Laboratory testing (including complete blood count, complete metabolic panel, erythrocyte sedimentation rate, rheumatoid factor, angiotensin converting enzyme, lysozyme, tuberculosis, syphilis, and viral hepatitis panel) was negative.
The patient was started on a 6-week taper of oral prednisone which resulted in initial improvement, but with recurrence shortly after taper completion. Subcutaneous methotrexate (with another oral steroid taper) was started with mild improvement. Subcutaneous adalimumab was later added. In the setting of posterior subcapsular cataract formation, posterior synechiae, steroid-response ocular hypertension (peak IOP of 46 mmHg), and uveitis with inferior snowbanks, a combined phacoemulsification with intraocular lens implantation, synechiolysis, gonioscopy assisted transluminal trabeculotomy, and pars plana vitrectomy with endolaser to the inferior retina was performed in the right eye. Two repeat episodes of cystoid macular edema (Figure 1), each about one year apart, were successfully treated with intravitreal anti-VEGF therapy. The patient reported persistent gastrointestinal upset from methotrexate despite decreasing dosage, so methotrexate was replaced with mycophenolate mofetil. Additionally, the patient’s right upper eyelid ptosis which developed following initial sub-Tenon’s injection has yet to improve after three years. Last recorded visual acuity was 20/25 in each eye.
Uveitic macular edema (UME) is the most common cause of permanent vision loss in uveitis. The incidence of UME is roughly 9-11, 40-60, 28-34, and 53-64 percent for anterior, intermediate, posterior and panuveitis, respectively. UME is largely due to breakdown of the blood-retinal barrier in the setting of inflammation.
The most common symptom of UME is decreased central vision. UME may also cause micropsia and metamorphopsia. A decreased central reflex with a thin hyperreflective edge may be appreciated on fundus exam. Optical coherence tomography, the gold standard for detecting UME, classically demonstrates cystoid intraretinal fluid with or without subretinal fluid (Figure 1). Fluorescein angiography often reveals petaloid leakage or dye pooling in the cystoid spaces.
Noninfectious UME Treatment:
Treatment of noninfectious UME is aimed at controlling inflammation.
Local corticosteroids are the mainstay of treatment for UME. A trial of topical corticosteroids may prove effective for mild cases of UME. Periocular (such as sub-Tenon) or intravitreal corticosteroids are typically used as first line therapy for moderate to severe cases. In the POINT trial, intravitreal triamcinolone acetonide (ITA) and intravitreal dexamethasone implant (IDI) were superior in treating UME and improving visual acuity compared to periocular triamcinolone acetonide (PTA). However, ITA and IDI carried a higher risk for steroid-response ocular hypertension compared to PTA. Systemic corticosteroids have high efficacy, but prolonged use is avoided due to significant adverse effects.
Topical indomethacin was demonstrated to be superior to placebo, but NSAID monotherapy is rarely sufficient.
Several nonbiologic immunomodulators including systemic azathioprine, methotrexate, mycophenolate mofetil, and cyclosporine have demonstrated efficacy in UME. Providers prescribing these systemic therapies should be familiar with the contraindications and routinely monitor for adverse effects (eg, hepatotoxicity, nephrotoxicity, cytopenias, alopecia). Intravitreal methotrexate has shown promising results in some studies. The MERIT trial comparing intravitreal methotrexate, intravitreal ranibizumab, and intravitreal dexamethasone implant for treatment of UME is currently in phase 3 with an estimated study completion date in July 2022.
Intravitreal anti-VEGF therapy has shown suboptimal or transient response in most studies but may be considered as an alternative or adjunct in certain cases.
The TNF-alpha inhibitors adalimumab and infliximab are the most commonly used systemic biologics and are generally reserved for recalcitrant cases of UME. Adverse effects include the potential for malignancy and infections (most notably tuberculosis). Studies investigating intravitreal administration of TNF-alpha inhibitors has yielded mixed results and this modality is not routinely used.
Pars plana vitrectomy (PPV) can be diagnostic and therapeutic in certain recalcitrant cases. The therapeutic benefit of PPV (seen in 33-58 percent of patients) is hypothesized to be due to removal of inflammatory mediators and media opacities. PPV may have additional utility in cases with comorbid epiretinal membrane or vitreoretinal traction.
Infectious UME Treatment:
UME from infectious uveitis must target the underlying infection.
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Faculty Approval by: Marrissa B. Larochelle, MD
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