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Middle-aged woman experiences refractory uveitis
The right eye featured pigmented keratic precipitates in Arlt's triangle, anterior chamber cell and flare, and a focal posterior synechia.
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A 46-year-old Indian woman was referred by her optometrist for uveitis in the right eye. She initially presented to the optometrist’s office 1 month before the referral with a 1-day history of blurred vision, tearing and photophobia. The optometrist prescribed prednisolone acetate 1% four times per day.
On review of systems, she reported dysphagia and odynophagia for the past several months. Ocular history was significant for three to four prior episodes of anterior uveitis beginning 3 to 4 years before presentation, always in the right eye, as well as a choroidal nevus in the right eye with no thickening or adjacent inflammation. No prior laboratory workup was performed to investigate the etiology of the uveitis. There was no significant medical or surgical history. She denied any history of cold sores. Family history was significant for her two children who were diagnosed and treated for latent tuberculosis upon starting grade school in the United States. She did not use any medications, tobacco or alcohol and did not have known drug allergies.
Examination
On exam, uncorrected distance visual acuity was 20/30 in the right eye and 20/20 in the left eye. The right pupil was irregular and larger than the left pupil, but both were reactive with no afferent pupillary defect. IOP was 15 mm Hg on the right and 17 mm Hg on the left. Extraocular motility and confrontational visual fields were full. Anterior segment exam of the right eye was significant for ciliary injection, diffuse fine and medium pigmented keratic precipitates in Arlt’s triangle, 1+ cell and flare, a focal posterior synechia at 5 o’clock and 1+ nuclear sclerosis. Posterior segment exam revealed trace vitreous cell and a flat choroidal nevus but no other chorioretinal lesions. Exam of the left eye showed trace nuclear sclerosis but was otherwise unremarkable.
Images: Liu E, Rao NK
What is your diagnosis?
Refractory uveitis
The differential diagnosis for a patient with recurrent unilateral granulomatous anterior uveitis included infectious causes such as herpes simplex virus, varicella zoster virus, tuberculosis, Lyme disease and syphilis. HLA-B27-associated anterior uveitis and Posner-Schlossman syndrome were also considerations. Sarcoid uveitis, while typically bilateral, must still be considered and can present years before systemic manifestations.
Her history was inconsistent with other common causes of anterior granulomatous uveitis such as postoperative, drug-induced, traumatic and sympathetic ophthalmia because she did not have any surgeries or injuries and was not taking any medications. Vogt-Koyanagi-Harada syndrome is often bilateral with posterior and systemic involvement. Fuchs’ heterochromic iridocyclitis usually has a less dramatic presentation with less cell, no synechiae-formation and more diffuse depositions of keratic precipitates.
Diagnosis and management
Uveitis labs were ordered, specifically Lyme serology, QuantiFERON-TB Gold, ACE, lysozyme, anti-CCP, CRP, ANA and HLA-B27. The patient was initially treated with prednisolone acetate 1% every hour and cyclopentolate 1% three times per day. After 2 weeks her symptoms improved, but she still had persistent 2+ cell (mostly pigment) and flare and her IOP rose to 25 mm Hg. Her QuantiFERON-TB Gold test returned positive, and all other workup was negative. She was referred to the infectious disease service for evaluation due to concern for scrofula given her sore throat. She was also started on dorzolamide-timolol two times per day for elevated IOP (max: 25 mm Hg).
Due to the mixed diagnostic picture with the possibility of infectious uveitis secondary to TB or viral causes, the infectious disease service requested that aqueous humor be sent for viral and TB PCR studies before initiating any systemic empiric antimicrobial therapy. Anterior chamber tap was performed, and the aqueous fluid was sent for HSV, VZV, CMV and TB PCR testing. Chest X-ray and CT of the neck were normal. One month after initial presentation, the aqueous HSV PCR came back strongly positive, and all other aqueous studies were negative. Oral valacyclovir 500 mg three times per day was started. Soon after, the infectious disease specialist also prescribed rifampin 300 mg two times per day for latent TB but felt the four-drug treatment was not necessary because there was no evidence of disseminated TB.
After valacyclovir was started, the patient began to improve within a week, with significantly less pigment and fewer white blood cells in the anterior chamber. After 1 month of every hour prednisolone, she was decreased to four times daily and eventually to one time daily over another month. Two months after initial presentation, valacyclovir was decreased to prophylactic dosing of 500 mg daily. However, she developed persistent mydriasis and inferior sectoral iris atrophy in the right eye. At 5 months, her visual acuity was 20/20 with trace anterior chamber pigment, and she took prednisolone once daily.
Discussion
HSV uveitis is rare, causing 5% of uveitis overall. Presentation typically includes unilateral anterior uveitis with photophobia, blurred vision and pain. Unlike most other causes of uveitis, herpetic uveitis tends to increase IOP and can occur with or without epithelial involvement. VZV can cause similar symptoms but tends to present in an older age group. Diagnosis of a herpetic infection (HSV or VZV) can be made by history and key exam findings such as elevated IOP and iris atrophy.
Given the relatively low-risk profile of acyclovir and valacyclovir, a trial of empiric systemic antiviral treatment in cases suspicious for herpetic uveitis can be considered. Refractory cases may warrant an anterior chamber tap with fluid sent for HSV, VZV and CMV PCR, as CMV also presents similarly but requires different antiviral medication for treatment. Further management consists of cycloplegic drops to prevent or break posterior synechiae and topical steroids for inflammation when epithelial disease has resolved. IOP-lowering drops should be started if necessary, but prostaglandin analogues should be avoided due to studies showing correlation with activation of herpes virus. The prognosis is good: Vision often returns to baseline with proper management, although residual iris atrophy and mydriasis often remain.
For patients with recurrent herpetic uveitis, long-term prophylactic antiviral therapy should be strongly considered, as this can reduce the recurrence rate by 50%. Prophylactic dosing of acyclovir and valacyclovir does not require blood draws for monitoring.
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- For more information:
- Erica Liu, MD, and Naveen K. Rao, MD, can be reached at New England Eye Center, Tufts University School of Medicine, 750 Washington St., Box 450, Boston MA 02111; website: www.neec.com.
- Edited by Kristen E. Dunbar, MD, and Kendra Klein, MD. They can be reached at New England Eye Center, Tufts University School of Medicine, 750 Washington St., Box 450, Boston MA 02111; website: www.neec.com.