History

• 51-year-old female with Systemic Lupus Erythematosus (SLE) treated with cellcept 1g BID and prednisone 3mg daily
• Three-day history of acute shortness of breath
• No changes in vision
• Past medical history: SLE, Chronic kidney disease stage V, anemia of chronic disease, hypertension, diabetes
• Past ocular history: Negative
• Started on pulse steroids of IV solumedrol and dexamethasone for a presumed lupus flare
• She then developed pancytopenia with neutropenic fever
• Blood cultures were positive for cryptococcus neoformans
• Ophthalmology consulted to r/o ocular involvement

Exam Findings

• VA: OD: 20/40; OS: 20/40
• Pupils: Round and reactive OU, no RAPD
• IOP: 15; 17
• EOM: Full OU
• Slit lamp exam: Significant for 1+ NS OU

Differential Diagnosis

• Fungal endophthalmitis
• Syphilis, Tuberculosis
• ARN/PORN
• Non-infectious uveitis
• Sarcoidosis, Behcet, sympathetic ophthalmia, VKH
• Malignancy
• Intraocular lymphoma, leukemic infiltrates

Additional Investigations

• Lumbar puncture performed which was positive for cryptococcal neoformans antigen

Diagnosis

• Cryptococcal chorioretinitis

Pathophysiology

• Crypotococcus neoformans initially inoculates the pulmonary system. The organism then spreads hematogenously overcoming the blood brain barrier and reaching the choroid where the organism multiplies and subsequently invades the retina followed by vitreous cavity.

Treatment

• The patient was treated for cryptococcal meningitis:
• Induction therapy: AmphoB IV (5mg/Kg) + flucytosine for 14 days.
• Consolidation therapy: Fluconazole 400mg PO daily for eight weeks.
• At four weeks follow up the patient denies any changes in VA and she was still receiving treatment with fluconazole 400mg PO daily.

Prognosis and Future Directions

• There has been a 10-fold increase in fungemia in inpatients over the past 20 years.
• Related to increased patient risk factors: IV drug use, indwelling catheters, trauma, hyperalimentation, GI surgery, diabetes, immunosuppression, HIV/AIDS
• Ocular prognosis for fungal endogenous endophthalmitis has improved over the recent years. Historically the rates of fungal endophthalmitis was 9-45% but more recent reports demonstrate a rate of 2-9%.
• Newer agents such as fluconazole and especially voriconazole have good intraocular penetration with broad spectrum activity against organisms. Chorioretinitis without vitreous involvement can be treated with systemic treatment alone.
• Patients with vitritis or active macular disease require a vitreous tap and injection of antimicrobials, and rarely in patients with progressive disease, a pars plana vitrectomy may be necessary.

References

• Shah CP, McKey J, Spirn MJ, Maguire J. Ocular candidiasis: a review. Br J Ophthalmol 2008;92:466-468.
• Essman TF, Flynn HW Jr, Smiddy WE, et al. Treatment outcomes in a 10-year study of endogenous fungal endophthalmitis. Ophthalmic Surg Lasers 1996;28:185-94.
• Donahue SP, Greven CM, Zuravleff JJ, et al. Intraocular candidiasis in patients with candidemia. Ophthalmology 1994;101:1302-9.
• Hariprasad SM, Mieler WF, Holz ER, et al. Determination of vitreous, aqueous, and plasma concentration of orally administered voriconazole in humans. Arch Ophthalmol 2004;122:42-7.
• Zhange YQ, Wang WJ. Treatment outcomes after pars plana vitrectomy for endogenous endophthalmitis. Retina 2005;25:746-50.
• Ghodasra DH, Eftekhari K, Shah AR, VanderBeek BL. Outcomes, impact on management, and costs of fungal eye disease consults in a tertiary care setting. Ophthalmology 2014; 121(12):2334-2339.
• Henderly DE, Liggett PE, Rao NA. Cryptococcal chorioretinitis and endophthalmitis. Retina. 1987;7:75-9.

Contact

• Brian Toy, MD, Assistant Professor of Clinical Ophthalmology, brian.toy@med.usc.edu
• Nadim Rayess, MD, PGY-4 Ophthalmology Resident, nadim.rayess@med.usc.edu