Uveitis patient referred after not responding to therapy

Mark E. Patron

Andre J. Witkin

A 55-year-old woman initially presented to her primary ophthalmologist with decreased visual acuity in her left eye. The day before presentation she noted floaters that coalesced into “cobwebs,” with abrupt visual loss. The patient was diagnosed with anterior uveitis in the left eye and was started on topical prednisolone and cyclopentolate. She did not improve on topical therapy and was subsequently started on oral prednisone. She was referred to the uveitis specialist at the Lahey Clinic for further evaluation 1 week later.

On review of systems, the patient described having been unwell for 10 to 14 days before presentation. She had been experiencing fevers up to 102°F associated with flu-like symptoms, night sweats, headache and generalized weakness. She saw her primary care physician roughly 10 days before presentation and was prescribed azithromycin for a presumed sinus infection vs. walking pneumonia. She did not improve and re-presented to her primary care physician for further evaluation.

Basic labs demonstrated a neutrophil predominant leukocytosis, and chest X-ray showed a patchy right lower lobe infiltrate. The patient was presumed to have bacterial pneumonia and was started on high-dose levofloxacin. The patient had never had previous intraocular surgery or trauma. Otherwise, the patient’s medical history was remarkable for osteopenia, fibrocystic breast changes, remote C-section and question of a heart murmur in childhood.

Examination

On examination, the patient’s best corrected visual acuity was 20/25 in the right eye and hand motion in the left. There was no improvement with pinhole in either eye. IOPs were 10 mm Hg in the right eye and 9 mm Hg in the left. The right pupil was reactive without an afferent pupillary defect. Extraocular movements were full in both eyes and produced no significant pain. On slit lamp exam, the left eye demonstrated a 1-mm layering hypopyon with 3+ anterior chamber cell and flare. There were broken posterior synechiae on the anterior lens capsule in the left eye (Figures 1a and 1b). Both lenses showed trace nuclear sclerosis. The right eye had a normal fundus with no vitreous cells. There was dense 3 to 4+ vitritis with a hazy view in the left eye. A B-scan ultrasound demonstrated vitritis without evidence of a retinal detachment (Figure 2).

Figure 1a. Less than 1-mm layering hypopyon.

Figure 1b. Broken posterior synechiae on the anterior lens capsule with 3+ anterior chamber reaction. Images: Goren JF, Soukiasian SH and Marx JL

Figure 2. B-scan ultrasound demonstrating dense vitritis without retinal detachment.

What is your diagnosis?

Unilateral panuveitis

The differential diagnosis of a patient with unilateral panuveitis includes endophthalmitis, sarcoidosis, tuberculosis, syphilis, toxoplasmosis, toxocariasis, sympathetic ophthalmia and Vogt-Koyanagi-Harada syndrome.

Endophthalmitis can present with panuveitis and would be high on the differential diagnosis given the patient’s systemic symptoms and hypopyon. Sarcoidosis typically produces both anterior and posterior inflammation and may include other findings such as iris nodules, mutton-fat keratic precipitates, retinal vascular sheathing and peripheral retinal neovascularization. Systemic findings in sarcoidosis may include shortness of breath, parotid gland enlargement and arthralgias.

Tuberculosis produces many varied clinical manifestations including anterior uveitis (granulomatous or nongranulomatous) and multifocal yellow-white choroidal lesions. Syphilis can present with either anterior or posterior uveitis, and the pathognomonic finding is patchy hyperemia of the iris with fleshy pink nodules near the iris sphincter. Toxoplasmosis typically causes moderate to severe focal vitreous inflammatory reaction over a white-yellow retinal lesion, often associated with an old pigmented chorioretinal scar.

Toxocariasis is typically seen in children and can present unilaterally with macular granuloma, pars planitis, peripheral granuloma or endophthalmitis. Sympathetic ophthalmia occurs in patients who have had previous ocular trauma or surgery in the contralateral eye.

Vogt-Koyanagi-Harada syndrome can present with a significant anterior chamber reaction, granulomatous keratic precipitates, vitiligo, serous retinal detachment often associated with underlying choroidal thickening, vitreous cells and opacities, and optic disc edema. The ocular findings in Vogt-Koyanagi-Harada syndrome are typically associated with headache, stiff neck, nausea, vomiting, fever and malaise.

Labs on admission were significant for WBC 17.8 with 73% neutrophils, a mild transaminitis (AST 57, ALT 75) and an albumin of 2.4. ACE and lysozyme levels were normal. PPD was negative. RPR was non-reactive, and FTA-Abs was negative. Toxoplasma IgM was negative. ESR was 130. Blood cultures were positive for gram-positive cocci, which were eventually speciated as alpha-hemolytic Streptococcus. Chest X-ray demonstrated a right lower lobe infiltrate, and CT scan of the abdomen demonstrated a large, complex hepatic mass. The infectious disease service was consulted, and the patient was admitted to the hospital for further workup.

Endogenous endophthalmitis was considered the most likely diagnosis due to the constellation of systemic constitutional symptoms including fever, elevated white count and hypopyon panuveitis unresponsive to systemic prednisone.

Discussion

Endophthalmitis is an inflammation of the internal coats of the eye, which is typically categorized into endogenous vs. exogenous. Exogenous endophthalmitis occurs after ocular surgery or trauma to the eye. The pathophysiology involves direct seeding of the eye with bacteria. Endogenous endophthalmitis, on the other hand, occurs via hematogenous spread from the bloodstream with a remote primary site of infection.

The typical clinical presentation of endophthalmitis includes ocular pain, blurred vision, chemosis, and injection of the conjunctiva and underlying episclera. There is inflammation of the anterior chamber and vitreous cavity that typically produces a diminished red reflex. Endophthalmitis may also be associated with elevated IOP and hypopyon.

Endogenous endophthalmitis can occur at any age with equal predilection for men and women. The most common cause of endogenous endophthalmitis is fungal infection, and risk factors include intravenous drug use, malignancy, intravenous nutrition such as total parenteral nutrition, endovascular lines, diabetes, neutropenia, and the use of broad-spectrum antibiotics or immunosuppressive medications. Bacterial infection is another important cause of endogenous endophthalmitis, with gram-positive bacteria being the most common organism causing disease in the United States and Europe and gram-negative bacteria being more common in Asia. The gram-positive organisms that are implicated commonly include Staphylococcus aureus, group B Streptococcus, Streptococcus pneumoniae and Listeria monocytogenes. Gram-negative organisms that frequently cause infection include Klebsiella, Escherichia coli, Pseudomonas and Neisseria. The most common sites of primary infection are liver abscess, pneumonia, meningitis, endocarditis, and renal and urinary tract infection.

The diagnosis of endogenous endophthalmitis is typically made by a combination of vitreous tap with culture as well as blood cultures. Some also advocate for tapping the anterior chamber in addition to the vitreous, although this is not required for diagnosis. Blood cultures are more likely to be positive than vitreous cultures, which are typically positive only 50% to 60% of the time. An alternative to vitreous tap and injection for diagnosis and treatment is vitrectomy with intraoperative injection of antibiotics. Although the data from the Endophthalmitis Vitrectomy Study included patients with exogenous endophthalmitis, many physicians use the guidelines set forth in that study to advocate for vitrectomy over vitreous tap and injection for patients with vision worse than light perception on presentation.

Figure 3. Intraoperative photograph during 23-gauge pars plana vitrectomy demonstrating two subretinal lesions, the presumed initial site of bacterial seeding.

Despite improved understanding of the pathophysiology of endophthalmitis, the outcomes have not improved over the past 50 years. In a 17-year prospective study of 267 cases of endogenous bacterial endophthalmitis by Jackson et al, 69% of the patients had count fingers vision or worse despite treatment, 25% required enucleation, and there was an associated mortality of 5%. Endophthalmitis is a particularly challenging infection to treat due to the immunosuppressive environment of the eye that limits bacterial clearance.

Treatment

In our patient’s case, she underwent vitrectomy with intraoperative injection of vancomycin and ceftazidime (Figure 3). She was started on intravenous vancomycin by the infectious disease team. Imaging was significant for both a liver abscess and lung pneumonia vs. abscess. The liver abscess was percutaneously drained with cultures that grew Streptococcus viridans. She was switched from intravenous vancomycin to ceftriaxone, and was discharged home with a PICC line to complete a prolonged course of IV antibiotic therapy. The patient’s vision improved dramatically 1 week postoperatively to 20/70, and her systemic symptoms resolved. The etiology of the liver abscess, lung pneumonia and bacteremia was believed to be due to bacterial seeding during a dental procedure 6 weeks before presentation.

References:

• Callegan MC, Gilmore MS, Gregory M, et al. Bacterial endophthalmitis: therapeutic challenges and host-pathogen interactions. Prog Retin Eye Res. 2007;26(2):189-203.
• Durand ML. Bacterial endophthalmitis. Curr Inf Disease Resp. 2009;11(4):283-288.
• Endophthalmitis Vitrectomy Study Group. Results of the Endophthalmitis Vitrectomy Study. A randomized trial of immediate vitrectomy and of intravitreous antibiotics for the treatment of postoperative bacterial endophthalmitis. Arch Ophthalmol. 1995;113(12):1479-1496.
• Jackson TL, Eykyn SJ, Graham EM, Stanford MR. Endogenous bacterial endophthalmitis: a 17-year prospective series and review of 267 reported cases. Surv Ophthalmol. 2003;48(4):403-423.
• Romero CF, Rai MK, Lowder CY, Adal KA. Endogenous endophthalmitis: case report and brief review. Am Fam Physician. 1999;60(2):510-514.
• Tan YM, Chee SP, Soo KC, Chow P. Ocular manifestations and complications of pyogenic liver abscess. World J Surg. 2004;28(1):38-42.
• Yanoff M, Duker JS. Ophthalmology. Elsevier; 2009.

• Jordana Firestone Goren, MD, MS, Sarkis H. Soukiasian, MD, and Jeffrey L. Marx, MD, can be reached at Lahey Clinic Department of Ophthalmology, 1 Essex Center Drive, Peabody, MA 01960; 978-538-4400; fax: 978-538-4724; Web site: www.lahey.org.

• Edited by Mark E. Patron, MD, and Andre J. Witkin, MD. Drs. Patron and Witkin 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; Web site: www.neec.com.