Choriocapillaris Flow Voids in Cryptococcal Choroiditis using Optical Coherence Tomography Angiography

Abstract

Purpose

To report an unusual case of cryptococcal choroiditis and highlight the multimodal imaging findings, particularly the choriocapillaris flow voids using optical coherence tomography angiography (OCTA)

Method

Retrospective review of the clinical course of a single patient with cryptococcal choroiditis

Results

A 69-year-old man undergoing chemotherapy for T-cell prolymphocytic leukemia developed disseminated crytococcal neoformans infection. He developed bilateral cyrotococcal choroidits with multiple yellow-white choroidal lesion on fundoscopy in both eyes. Multimodal imaging of the choroidal lesions revealed flow voids at the level of the choriocapillaris on OCT-A that corresponded to hypocyanescent areas on indocyanine green angiography (ICGA) when registered and overlaid on the ICGA images. The superficial and deep capillary plexus were spared.

Conclusion

This case illustrates that that OCT-A was useful in demonstrating that the cryptococcal choroidal lesions impaired choriocapillaris perfusion, but spared the superficial and deep retinal plexus

Introduction

Cryptococcal choroiditis and chorioretinitis are typically caused by endogenous spread of Cryptococcus neoformans in immunocompromised individuals. Although rare, the infection is presumed to spread hematogenously to the choroid, before secondarily affecting the retina. This has been suggested by a limited number of histologic and imaging case reports.^1–4 Herein we report that optical coherence tomography angiography (OCT-A) was able to demonstrate choriocapillaris vascular compromise with intact superficial and deep retinal vasculature in a patient with cryptococcal choroiditis.

Case Report

A 69-year-old man undergoing chemotherapy for T-cell prolymphocytic leukemia was admitted to the hospital for febrile neutropenia and diagnosed with fungemia. Ophthalmology was consulted to evaluate for ocular involvement. He reported no ophthalmic complaints and his visual acuity was 20/20 in both eyes. Anterior segment examination was unremarkable. Fundus exam revealed multiple yellow/white choroidal lesions and few dot-blot hemorrhages involving the macula and mid-periphery in both eyes with no vitreous inflammation (Figure 1A). Enhanced depth imaging-optical coherence tomography (EDI-OCT) showed that these lesions corresponded to multiple bilateral foci of mild choroidal elevation with overlying disruption of the outer retina layers and there was a thickened choroid (Figure 1B). Fundus autofluorescence revealed multiple discrete areas of hyperautofluoresence corresponding to these lesions. Fluorescein angiography (FA) was unremarkable and indocyanine green angiography (ICGA) showed multiple hypocyanescent spots corresponding to the choroidal lesions (Figure 2A). OCT-A (Spectralis OCT2 device, Heidelberg Engineering, Heidelberg, Germany, 15×10°area (4.3 × 2.9 mm) composed of 261 B-scans at a distance of 11 μm each) demonstrated an intact superficial and deep retinal plexus (Figure 2B, C) and there were choriocapillaris flow voids on structural and en face OCTA (Figure 2D and E). These flow voids when registered and overlaid on the ICGA images, corresponded to the hypocyanescent areas on ICGA (Figure E, F). Blood cultures and lumbar puncture revealed the fungal element was Cryptococcus neoformans and the CSF cryptococcal antigen titres were > 1:2560. The patient was treated with intravenous flucytosine and amphotericin B for disseminated cryptococcal infection. While there was consolidation of the lesions seen on ophthalmoscopy, OCTA findings were unchanged at the 3 month follow up and he was continued on oral fluconazole planned for a total of a year following diagnosis.

Figure 1.

Color photograph of the left eye shows multiple yellow depigmented choroidal lesions throughout the posterior pole in the left eye (A). Fluorescein angiogram (B) is unremarkable. Near infrared Image (C) shows a hyperreflective center with hyporeflective rim corresponding to the lesions. Corresponding OCT B scan with enhanced depth imaging (D) shows a thickened choroid and loss of outer retinal layers in the area of the lesion. The right eye had very similar findings.

Figure 2.

Mid phase Indocyanine Green Angiography (ICGA) of the left eye shows multiple hypocyanescent spots corresponding to the lesions. En face Optical Coherence Tomography Angiography (OCT-A) shows an intact superficial (A) and deep capillary plexus (C). Structural OCT B scan with flow overlay (D) at the level corresponding to the white horizontal line on the ICGA image shows a flow void (white arrow) which in turn corresponded to the hypocyanescent area on ICGA. En Face OCTA at the level of the choriocapillaris (50-micron thick slab) overlaid on the ICGA shows multiple dark flow voids which when registered and overlaid on the ICGA image correspond to the hypocyanescent spots showing agreement between the perfusion abnormality on OCTA and ICGA (F). The right eye had very similar findings.

Discussion

We present a case in which an immunosuppressed individual was discovered to have disseminated cryptococcal infection with bilateral choroidal involvement. Cryptococcal choroiditis is a rare opportunistic infection, usually occurring with cryptococcal meningitis.^1–4

Multimodal imaging of the choroidal lesions revealed flow voids at the level of the choriocapillaris on OCT-A that corresponded to hypocyanescent areas on ICG angiography when registered and overlaid on the ICG images. In our patient, OCT-A was instrumental in demonstrating that the cryptococcal choroidal lesions impaired choriocapillaris perfusion, but spared the superficial and deep retinal plexus, an OCT-A finding that has not been previously described. On histological examination, Shields et al. have previously described that the cryptococcal yeast were primarily located in the choroid and the subretinal space.¹ It has been suggested that the disease spreads hematogenously to the choriocapillaris. This is consistent with our multimodal imaging and prior dye-based angiographic case reports that show impaired choroidal blood flow at the location of the choroidal lesions.^2–3

In conclusion, Cryptococcal choroiditis is a rare manifestation of disseminated cryptococcal infection that appears to primarily impair choriocapillaris perfusion. This case with its unique imaging findings supports the theory that cryptococcal choroiditis initially involves the choriocapillaris with secondary retinal effects. Few other case reports have reported the OCT-A findings of different infectious chorioretinopathies^5,6 and further studies are needed to fully characterize changes on OCT-A with disease progression and their potential for improvement with treatment.

Summary Statement.

We describe the multimodal imaging findings in an immunosuppressed patient with cryptococcal choroiditis. OCT-Angiography showed choriocapillaris flow voids corresponding to hypocyanescent areas on Indocyanine Green Angiography with sparing of the superficial and deep retinal plexuses, a finding which has not been previously described. This provides further evidence that the infection likely spreads hematogenously to the choroid, before secondarily affecting the retina.