Woman presents with cloudy vision with halos

Elevated IOP and anterior chamber and vitreous inflammation were seen in both eyes.

Priti Batta

Namrata Nandakumar

A 51-year-old woman presented to our clinic complaining of intermittent cloudy vision for the past few weeks. She noted redness of her eyes during these episodes and halos in her vision. She denied any pain, foreign body sensation or discharge.

The patient’s ocular history included chronic floaters and soft contact lens use with good hygiene. Her medical history included rheumatoid arthritis diagnosed 8 years prior, for which she had been taking etanercept for the past 3 years. On review of systems, she reported a dry cough for the past 2 months, but no upper respiratory infections or fevers. She had no known drug allergies. She worked as a systems analyst and denied any tobacco or alcohol use.

Examination

On examination, the patient’s best corrected visual acuity was 20/20 in the right eye and 20/30 in the left eye. Pupils were equally reactive with no afferent pupillary defect. Extraocular movements and confrontation visual fields were full in both eyes. Anterior segment exam showed bilateral trace conjunctival injection, microcystic corneal edema, as well as a Salzmann’s nodule and 10% inferior corneal thinning in the left eye. Other findings included 1+ anterior chamber cell in the right eye and trace to 1+ anterior chamber cell in the left eye, 1+ nuclear sclerotic cataracts in both eyes, as well as 1+ anterior vitritis in both eyes. IOP by Goldmann applanation was 68 mm Hg in the right eye and 69 mm Hg in the left eye. Gonioscopy revealed open angles with 2+ pigmented trabecular meshwork and no peripheral anterior synechiae. Dilated fundus exam showed faint, multifocal, creamy-white to yellowish subretinal infiltrates in both eyes. There was no surrounding edema or hemorrhage. Optic nerves appeared healthy with no significant increase in cup-to-disc ratio in both eyes (Figure 1).

Figure 1. Both optic nerves appear healthy with no significant increase in cup-to-disc ratio. Images: Cox CA, Krishnan D, Reichel E

What is your diagnosis?

Panuveitis with subretinal infiltrates

Bilateral elevated IOP, anterior chamber and vitreous inflammation, and subretinal infiltrates together suggest an underlying inflammatory or infectious process.

Our patient’s subretinal infiltrates were multifocal and numerous, thus bringing white dot syndromes associated with anterior chamber or vitreous cell into consideration. Possible white dot syndromes include multiple evanescent white dot syndrome (MEWDS), acute posterior multifocal placoid pigment epitheliopathy (APMPPE), birdshot retinochoroidopathy, and multifocal choroiditis and panuveitis (MCP).

MEWDS is typically unilateral but can, in rare cases, be bilateral. It may be preceded by an upper respiratory infection, and it can present with mild vitritis along with subtle small lesions in the mid-peripheral retina. The hallmark of MEWDS is a pattern of early hyperfluorescence on fluorescein angiogram. APMPPE presents bilaterally, can be preceded by a viral prodrome, and is also associated with vitritis but exhibits more prominent placoid lesions of the posterior pole. In contrast to MEWDS, APMPPE shows a pattern of late hyperfluorescence on fluorescein angiogram. Birdshot retinochoroidopathy is a chronic, bilateral inflammatory disorder of which more than 90% of cases are positive for human leukocyte antigen (HLA) A29. MCP is a relatively common bilateral condition presenting with significant intraocular inflammation and mid-peripheral lesions. These lesions may eventually appear as atrophic retinal scars containing a punched-out dark center.

Several systemic conditions can present with intraocular inflammation (or pseudo-inflammation) along with subretinal lesions. These include sarcoidosis, syphilis, tuberculosis and lymphoma. Sarcoidosis is perhaps the most likely etiology given the patient’s symptoms, history and eye examination. It is important to remember that all of these conditions can present in a protean fashion due to potential involvement of both the anterior and posterior segments.

Of these possibilities, MEWDS was highest on our differential for a white dot syndrome, and sarcoidosis was highest on our differential for an immune etiology. Although a bilateral presentation would be rare, our patient’s faint-appearing multifocal subretinal lesions suggested the possibility of MEWDS. On the other hand, she also reported a history of rheumatoid arthritis and a recent dry cough, both of which can be correlated with sarcoidosis. She denied any additional symptoms (fever, weight loss) or risk factors (sexual promiscuity, foreign travel) that would point to an alternative systemic diagnosis.

Clinical course

Initial management focused on decreasing IOP. The patient was given oral acetazolamide and multiple rounds of pressure-lowering eye drops, including dorzolamide, travoprost, brimonidine and timolol. IOP was reduced to 34 mm Hg in the right eye and 36 mm Hg in the left eye within a few hours, and the patient was sent home on a combination of brimonidine and dorzolamide-timolol eye drops. At a 1-day follow-up, IOP was 15 mm Hg in the right eye and 17 mm Hg in the left eye. Anterior chamber inflammation was still present; therefore, she was also started on a regimen of prednisolone eye drops.

Additional testing was obtained, including fluorescein angiogram, indocyanine green angiography and optical coherence tomography. The fluorescein angiogram showed patchy hyperfluorescence along the superior and inferior arcades (Figure 2), slightly suggestive of a MEWDS etiology. Indocyanine green angiography showed no abnormal hyperfluorescence in the choroid, and OCT of the macula was found to be within normal limits. Further testing was needed for diagnosis; therefore, serological testing was performed. HLA-A29 was found to be negative, but an ACE level was found to be elevated. As a result, a chest CT was obtained. This showed enlarged hilar lymph nodes, supporting a diagnosis of systemic sarcoidosis.

Figure 2. Fluorescein angiogram staining is most suggestive of multiple evanescent white dot syndrome.

The patient’s primary care physician recommended observation due to the absence of significant systemic disease. She was continued on brimonidine, dorzolamide-timolol and prednisolone eye drops. Over 6 to 7 months, attempts were made to discontinue the eye drops, but rebound inflammation led to pressure spikes into the 40 mm Hg range. Follow-up visual fields and nerve fiber layer testing were within normal limits.

Discussion

Sarcoidosis is a multisystem inflammatory disorder that can affect any part of the body, although the eyes, lacrimal glands, lungs, lymph nodes and salivary glands are the most commonly affected. It is histologically characterized by non-caseating granulomas, has a peak incidence between the ages of 30 to 39 years, and is three times more likely in African-Americans as compared with whites.

Of patients diagnosed with sarcoidosis, ocular manifestations are present in 50% to 78%. Anterior uveitis is the most common presentation. Nodular infiltration and neovascularization of the angle can occur, both leading to significant elevations in IOP. Other anterior segment findings may include Koeppe iris nodules and mutton-fat keratic precipitates. Posterior segment disease can include perivascular exudation (“candle-wax drippings”) and vitritis, although these findings are present in only 30% of patients. Rarely, venous occlusions, neovascularization and optic nerve infiltration may be seen.

Although a diagnostic biopsy is the gold standard, most clinicians feel an elevated ACE and/or lysozyme level plus evidence of bilateral hilar adenopathy is adequate for presumptive diagnosis and initiation of treatment. It is important to note that ACE levels are only elevated in 60% of patients with sarcoidosis and can also be elevated in patients with diabetes mellitus, leprosy, histoplasmosis and tuberculosis, as well as in healthy children.

Treatment typically consists of topical steroids for anterior uveitis, plus systemic treatment as needed. Some groups have reported use of periocular, intravitreal or systemic steroids for posterior segment disease. Pulsed intravenous or retrobulbar steroid injections have also been reported in the treatment of optic nerve infiltration. As an alternative to steroids, other immunomodulatory therapies include hydroxychloroquine, thalidomide, methotrexate, azathioprine, pentoxifylline, cyclophosphamide, chlorambucil, cyclosporin, infliximab, etanercept and radiation therapy.

Interestingly, several reports have linked the use of etanercept, for treatment of autoimmune disorders such as rheumatoid arthritis, with a paradoxical incidence of sarcoidosis. Because our patient was taking etanercept at the time of diagnosis, this raises the question of whether it played a role in her development of sarcoidosis.

References:

• Gaskin BJ, Danesh-Meyer HV. Neovascular glaucoma and sarcoidosis. Eye (Lond). 2005;19(5):599-601.
• Massara A, Cavazzini L, La Corte R, Trotta F. Sarcoidosis appearing during anti-tumor necrosis factor alpha therapy: a new “class effect” paradoxical phenomenon. Two case reports and literature review. Semin Arthritis Rheum. 2010;39(4)313-319.
• Skoie IM, Wildhagen K, Omdal R. Development of sarcoidosis following etanercept treatment: a report of three cases [published online ahead of print Jan. 9, 2010]. Rheumatol Int. doi:10.1007/s00296-009-1349-x.
• Takahashi H, Kaneta K, Honma M, et al. Sarcoidosis during infliximab therapy for Crohn’s disease. J Dermatol. 2010;37(5):471-474.
• Takahashi T, Ohtani S, Miyata K, Miyata N, Shirato S, Mochizuki M. A clinical evaluation of uveitis-associated secondary glaucoma. Jpn J Ophthalmol. 2002;46(5):556-562.
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• Catherine A. Cox, MD, Dru Krishnan, MD, and Elias Reichel, MD, can be reached at New England Eye Center, Tufts University School of Medicine, 750 Washington St., Box 450, Boston, MA 02111; 617-636-4219; fax: 617-636-4866; website: www.neec.com.
• Edited by Priti Batta, MD, and Namrata Nandakumar, MD. Drs. Batta and Nandakumar can be reached at New England Eye Center, Tufts University School of Medicine, 750 Washington St., Box 450, Boston, MA 02111; 617-636-4219; fax: 617-636-4866; website: www.neec.com.