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
Figure 1A: Fundus photo of the right eye demonstrates few peripapillary punctate yellow intraretinal lesions and a white fluffy intraretinal lesion superonasal to the optic nerve.Figure 1B: Fundus photo of the left eye demonstrates several peripapillary punctate yellow intraretinal lesions and subretinal fluid involving the fovea.
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.
Figure 2A: Optos fundus photo of the right eye demonstrates resolution of the white intraretinal lesion with irregular borders. There are a few residual yellow punctate lesions.Figure 2B: Optos fundus photo of the left eye demonstrates resolving peripapillary punctate yellow intraretinal lesions and trace subretinal fluid involving the fovea.
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.
