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Clinical Pearls for Uveitis: Five Dos and Five Don’ts
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Uveitis can be challenging to treat for comprehensive ophthalmologists as well as retina and uveitis specialists. This heterogeneous group of ocular inflammatory conditions presents in all age groups and is often seen in patients with no family history or who are otherwise healthy. While steroids are frequently successful in treating uveitis, ophthalmologists must attempt to identify a specific cause, particularly since the inappropriate use of corticosteroids in patients with infectious uveitis can lead to sight-threatening complications and visual loss. When in doubt regarding the diagnostic workup or optimal treatment plan for a complex patient, you should always consider referral to a subspecialist. 

Listed below are five dos and don’ts to properly identify the etiology of uveitis and avoid exacerbating the inflammation.

DO

1. Rule out infectious causes in all patients. Tests for rapid plasma reagin and microhemagglutination assay with treponemal pallidum antigen should be ordered to rule out syphilis. Since syphilis can present as an isolated anterior uveitis, it is important to ask about sexual history. For patients with an endemic-area/high-exposure risk for TB (e.g., history of incarceration or HIV), consider purified protein derivative (PPD) testing and a posteroanterior/lateral chest x-ray. Quantiferon-TB testing or an appropriate interferon-gamma release assay should be considered in patients who may be anergic to PPD-testing (e.g., patients with HIV or systemic immunosuppression from chemotherapy and patients with sarcoidosis).

2. Think about herpetic uveitis in a patient with high IOP and uveitis.
Patients with herpes simplex virus (HSV)-, varicella zoster virus (VZV)- and cytomegalovirus-associated uveitis often have elevated IOP in conjunction with their inflammation. You may also find iris atrophy, iris transillumination defects or a history of oral ulcers or shingles lesions. Polymerase chain reaction testing can be obtained for anterior or posterior uveitis, in which herpes virus is a consideration.

3. Perform gonioscopy or a scleral depressed exam in a patient with persistent postoperative inflammation. Always look for retained lens material or foreign body in the angle or in the pars plana as a cause for persistent inflammation after cataract surgery — even if uncomplicated. Consider referring to a vitreoretinal or uveitis specialist to rule out chronic endophthalmitis caused by Propionibacterium acnes or exacerbated HSV/VZV infection after surgery. Remember that P. acnes can be associated with white plaques on the posterior capsule or IOL.

4. Tailor a uveitis workup based on the anatomical location of the inflammation. Patients with human leucocyte antigen-B27 (HLA-B27) uveitis develop anterior segment inflammation with occasional spillover into the anterior vitreous. Consider HLA-B27 testing, particularly if a patient complains of chronic lower back pain (i.e., ankylosing spondylitis) or plantar heel pain. This type of uveitis can be recurrent, severe and extremely symptomatic in nature. HLA-A29+ birdshot chorioretinopathy may present with vitreous cells in conjunction with creamy, mid-peripheral retinal lesions, retinal vasculitis and optic disc edema. Sarcoidosis may present with anterior, intermediate, posterior or panuveitic findings. Besides characteristic granulomatous keratic precipitates, sarcoidosis patients may develop choroidal and retinal granulomata and warrant angiotensin-converting enzyme, serum lysozyme, and ionized calcium testing and imaging (i.e., posteroanterior/lateral chest x-ray and/or chest computed tomography scan).

5. Monitor the patient closely while tapering any steroid. Common causes for rebound or recurrent inflammation are inadequate treatment (starting prednisone dosage lower than the appropriate treatment dose [0.5–1 mg/kg] or initiation of infrequent topical corticosteroid dosing) or tapering too quickly. Medication tapers should be considered when disease inactivity is observed. A judicious taper is recommended with follow-up visits to monitor for inflammation recurrence. Closely monitor systemic side effects of prednisone (i.e., hypertension, weight gain and mood swings) and local side effects (i.e., ocular hypertension and cataract formation).


DON’T …

6. Operate on an inflamed eye. Patients with uncontrolled uveitis who undergo intraocular surgery are at greater risk of increased and recalcitrant inflammation, delayed healing, pupillary membranes, ciliary body shut down, cystoid macular edema and other complications related to inflammation. Uveitis should be inactive for a minimum of three to six months before undergoing surgery.

7. Give a periocular steroid injection in patients who may have acute retinal necrosis or toxoplasmosis. This can exacerbate or accelerate their condition. A thorough dilated exam with attention to the peripheral retina can help lead to these diagnoses. Systemic steroids can still be appropriate if used in conjunction with antivirals or antiparasitics.

8. Forget the dilated exam in patients with recalcitrant anterior uveitis. While anterior uveitis seems straightforward to treat, one of the causes of recalcitrant disease is subtle posterior segment disease. Specific findings could lead to the correct diagnosis. Re-examine the anterior vitreous and dilate the eye, specifically looking for retinal whitening, vessel sheathing or optic nerve swelling. Review the previous diagnostic testing or consider repeating labs, particularly if there are changes in the patient’s medical history or review of systems.

9. Check antinuclear antibodies (ANA) in an isolated anterior uveitis. ANA testing is valuable in patients with autoimmune disease suggestive of systemic lupus erythematosus (e.g., glomerulonephritis and malar rash) and specific anatomic subtypes of ocular inflammation, including scleritis, choroiditis/choroidopathy, retinal vasculitis or juvenile idiopathic arthritis-associated uveitis. However, because the likelihood of systemic lupus erythematosus is extremely low in isolated anterior uveitis, positive ANA testing can often be misleading and lead to additional unnecessary testing and treatment.

10. Forget about intraocular lymphoma in an elderly patient with chronic intermediate uveitis. Patients who don’t respond to local corticosteroids should be worked up for lymphoma. Work with the patient’s primary care provider to get an MRI of the brain and lumbar puncture, and positron emission tomography scans. A diagnostic vitrectomy with appropriate testing (e.g., cytopathology, flow cytometry and gene rearrangement studies) can help to clinch the diagnosis and avoid diagnostic delay.


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About the authors: Janice Law, MD, is an assistant professor in vitreoretinal diseases and surgery at Vanderbilt Eye Institute in Nashville, Tenn., where she completed a two-year medical and surgical retina fellowship. Dr. Law is also the associate program director for Residency Education in Ophthalmology and plays a very active role in developing curricula and assessing teaching and learning within ophthalmic education. Steven Yeh, MD, is an assistant professor in vitreoretinal diseases and surgery at the Emory Eye Center at Emory University School of Medicine. After medical school and a residency at Baylor College of Medicine, he completed an oncular oncology fellowship at NEI and a retina/vitreous surgery fellowship at Oregon Health and Science University's Casey Eye Institute.

 
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