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Young woman presents with unilateral decreased vision
On anterior segment examination, the left eye showed limbal injection, diffuse stromal haze, trace folds/striae, deep stromal vascularization inferiorly and two large keratic precipitates centrally.
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A 16-year-old active young woman was referred to the New England Eye Center for evaluation of a stromal opacity of the left eye. She noticed decreased vision approximately 2 weeks earlier, upon awakening one morning.
At that time, she noted no pain, headache, tinnitus, hearing loss, vertigo, fever, upper respiratory symptoms or injection. Over the following weeks, she noted no progression of symptoms, no fluctuation throughout the day and no associated symptoms. There was no recent illness or history of oral ulcers. She was not sexually active. She noted a history of Lyme synovitis that required surgical drainage of her knee. There was no history of contact lens wear or other ocular history.
Examination
The patient’s best corrected visual acuity was 20/20 in the right eye and 20/200 in the left with no improvement with pinhole. Pupillary examination was normal without afferent defect or anisocoria in light and dark. Extraocular movements were full with no pain or diplopia, and IOPs and confrontational visual fields were normal.
Anterior segment exam of the right eye was normal; however, the left eye showed 2+ limbal injection, diffuse stromal haze, moderate corneal thickening, trace folds/striae, deep stromal vascularization inferiorly and two large keratic precipitates centrally (Figure 1). The anterior chamber was difficult to visualize; however, no inflammation was appreciated. The rest of the anterior segment exam was grossly normal.
Figure 1. Anterior segment photo of the left eye showing limbal injection, diffuse stromal haze, trace folds/striae, deep stromal vascularization inferiorly, mild edema, and two large keratic precipitates centrally.
Images: Dunbar K, Raizman MB
Figure 2. A normal posteroanterior view of the chest showing no infiltrates or granulomas.
Laboratory testing showed Lyme C6 positive, Lyme C6 titer 1.46 high, Lyme WB IgM negative and Lyme WB IgG positive. Chest X-ray (Figure 2), RPR, ACE level, PPD, EBV, muramidase, ANA, rheumatoid factor and ANCA level all were unremarkable.
What is your diagnosis?
Unilateral decreased vision
The diagnosis of herpetic stromal keratitis in some ways is a diagnosis of exclusion. Nonnecrotizing interstitial keratitis is characterized by a unifocal or multifocal interstitial haze without overlying ulceration. It can be associated with mild iritis, localized granulomatous precipitates and sometimes increased IOP. Associated corneal edema is common. Other causes of stromal haze include varicella zoster, syphilis, Acanthamoeba, Epstein-Barr virus, mumps, sarcoidosis, Cogan’s syndrome, Lyme disease and tuberculosis.
In this case, the differential diagnosis was broad, and diagnosis was not straightforward. After evaluating the results of the above laboratory studies, Cogan’s syndrome, Lyme disease and herpetic stromal keratitis remained considerations. Cogan’s was eliminated because of the absence of hearing loss and vertigo. Considering the patient’s history, Lyme disease was possible; however, given the rarity of this diagnosis, the absence of other features of the disease and the history of treatment with antibiotics, the decision was made to treat for herpes stromal keratitis.
Discussion
Herpes simplex virus type 1 (HSV-1) is a double-stranded DNA herpes virus that is found only in humans. HSV-1 has a seroprevalence of greater than 90% in the general adult population in the United States, with a mean age of first occurrence of 37.4 years. In fact, of those older than 60 years, close to 100% have HSV in their trigeminal ganglia at autopsy.
New ocular herpetic infections comprise 11.8 per 100,000 people in the United States, and it is the most common cause of corneal blindness in the world. There are three major types of herpetic eye infections: epithelial dendritic lesions (56.3%), herpetic stromal keratitis (29.5%) and geographic corneal ulcers (9.8%).
What makes the herpes virus particularly threatening is its ability to remain dormant in the body for many years after initial infection. On primary infection, the virus gains access to termini of sensory neurons within the infected tissue. The HSV-1 capsid is then transported to the neuronal nucleus, where it attaches to nuclear pores and inserts its DNA into the host nucleus. There it lies dormant in a latent state for months to decades.
The stromal component of ophthalmic infection is thought to be caused by virus reactivation and shedding. While stromal keratitis can be found on initial infection, it is seen more frequently with reactivation of the virus. The morbidity of the tissue is a result of CD4+ cell destruction in an inflammatory response to virus reactivation. These immune responses from viral proteins trigger ingrowth of blood vessels and infiltration of leukocytes, and cause damage to the corneal stromal and endothelium, thus creating a corneal opacity. With each episode, the immune response grows stronger, increasing the damage done to the tissue.
There has been controversy as to whether to use topical or oral antiviral medications and the utility of topical steroids in the treatment of herpetic eye disease. The Herpetic Eye Disease Study (HEDS), a large prospective, randomized, double-masked, placebo-controlled, multicenter study divided into six trials, further elucidated how to effectively treat stromal keratitis. The first branch was a prospective study of 106 patients with stromal keratitis with two treatment arms: topical corticosteroids and topical trifluridine vs. placebo and topical trifluridine for 10 days. Results showed corticosteroids shortened the duration and decreased inflammation of keratitis. The second branch of HEDS showed no significant benefit using oral acyclovir and prednisolone and trifluorothymidine in a trial of 104 patients randomized to oral acyclovir (400 mg five times per day) vs. placebo for a 10-week course. Both groups received prednisolone acetate drops and trifluridine drops. Based on these hallmark studies, stromal keratitis is routinely treated with an antiviral and topical steroid.
Given the significant risk of decreased vision with herpes simplex keratitis, one must always consider this disease in an eye with stromal disease. Prompt treatment with oral or topical antiviral medication is necessary to prevent permanent scarring and decrease the need for further more invasive surgical treatment in the future.
Follow-up
Figure 3. Anterior segment photo of the left eye showing resolution of the stromal haze.
The decision was made to start the patient on oral acyclovir 400 mg five times per day and prednisolone acetate one drop six times per day in the left eye. She was brought back for daily follow-up initially, then weekly follow-up and finally monthly follow-up. At her follow-up exam 3 months after initial presentation, her vision was 20/20 in both eyes (Figure 3).