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Ahead of print publication  

Exogenous cryptococcal endophthalmitis in an immunocompetent patient

 Department of Ophthalmology, Northwell Health Eye Institute, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Great Neck, New York, USA

Date of Submission21-Jul-2022
Date of Acceptance25-Sep-2022
Date of Web Publication11-Jan-2023

Correspondence Address:
Daniel Zhu,
Department of Ophthalmology, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Northwell Health Center for Adult Ophthalmology, 600 Northern Blvd, Suite 214, Great Neck, New York 11021
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/tjo.TJO-D-22-00095


We describe a case of exogenous cryptococcal endophthalmitis without central nervous system (CNS) involvement or systemic infection in an immunocompetent patient. An 82-year-old male with hypertension, hyperlipidemia, type 2 diabetes mellitus, and primary open-angle glaucoma with a history of left eye trabeculectomy presented with 3 months of worsening left eye pain and redness. Vitreous cultures resulted as Cryptococcus, prompting treatment with intravitreal amphotericin and further investigation. Systemic workup was unrevealing for an endogenous source, CNS involvement, or immunocompromising conditions. He was treated with an aggressive regimen of systemic antifungals, leading to subjective improvements in clinical exam and in vision.

Keywords: Bleb-related endophthalmitis, Cryptococcus, endophthalmitis, fungal, glaucoma

How to cite this URL:
Zhu D, Rai R, Mechel E, Shah PP, Hymowitz M, Rohring V, Cheela I, Samson C M. Exogenous cryptococcal endophthalmitis in an immunocompetent patient. Taiwan J Ophthalmol [Epub ahead of print] [cited 2023 Jan 28]. Available from: https://www.e-tjo.org/preprintarticle.asp?id=367590

  Introduction Top

Cryptococcus neoformans is an encapsulated yeast with a polysaccharide capsule that is often found in soil and bird droppings. Infection in humans commonly occurs secondary to inhalation of spores and can manifest with a variety of symptoms. Patients can range from being completely asymptomatic to having severe meningoencephalitis that can progress to coma or death.[1] Rarely, C. neoformans can lead to infection of the eye, resulting in ocular manifestations such as choroiditis and endophthalmitis.[2],[3],[4],[5] Prior reports of cryptococcal endophthalmitis have typically described patients with systemic disease that subsequently seeded the eye. Instances of C. neoformans infection localized to the eye are much more limited.[3],[4],[5],[6] We report a case of a patient with cryptococcal endophthalmitis confined to the eye without an endogenous source. The patient information collected and evaluated in this report was HIPAA compliant and adhered to ethical principles in the Declaration of Helsinki.

  Case Report Top

An 82-year-old male with a history of hypertension, hyperlipidemia, diet-controlled type 2 diabetes mellitus, bilateral cataracts, and severe bilateral primary open-angle glaucoma presented due to a 3-month course of left eye pain, redness, and discharge. The patient had a history of left eye trabeculectomy with adjunctive mitomycin C 3 years prior. On initial ophthalmological evaluation, visual acuity (VA) was 20/50 in the right eye and hand motion (HM) in the left eye along with minimally reactive pupils bilaterally with no afferent pupillary defect. Intraocular pressures were normal. Slit lamp examination was remarkable for 4+ injection in the left eye with scleral thinning superiorly of approximately 6 mm × 3 mm [Figure 1]. There was a corneal epithelial defect adjacent to the area of scleral thinning, measuring 1.8 mm × 1 mm in the left eye with limbal areas of neovascularization. Corneal thinning was present, but there was no evidence of perforation. The Seidel test was negative. A 0.5 mm hypopyon was present in the anterior chamber, along with 3+ cellular reaction. There was a limited view on dilated fundus exam, but B-scan ultrasonography demonstrated vitreous debris [Figure 2]. The patient underwent needle vitreous aspiration with samples sent for gram stain and cultures. He was given an intravitreal injection of vancomycin and ceftazidime on the day of aspiration. He was subsequently started on fortified vancomycin and voriconazole 1% drops four times daily to the left eye, erythromycin ointment twice daily, topical moxifloxacin 0.5% solution, 1 g valacyclovir daily, Vitamin C 1 g daily, and oral doxycycline 100 mg twice daily. Vitamin C and oral doxycycline were included in the regimen to as preventative measures to mitigate the risk of dehiscence and corneal melting. Despite this treatment, the patient continued to develop progressive scleral thinning. Gram stain of the vitreous sample was negative. Preliminary vitreous cultures returned positive for cryptococcal infection, which was later confirmed as C. neoformans. The patient denied any known contact history associated with Cryptococcus. He received intravitreal injections of amphotericin and voriconazole and was sent to the emergency department (ED) for further evaluation.
Figure 1: Anterior segment photograph of the left eye on presentation showing conjunctival injection and scleral thinning at the trabeculectomy site

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Figure 2: B-scan of the left eye on presentation showing hyperechoic vitreous debris

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In the ED, a computed tomography scan of the head was unremarkable and cerebrospinal fluid (CSF) gram stain was negative. Human immunodeficiency virus testing was negative and complete blood count with differential was unremarkable. CSF and serum were negative for cryptococcal antigen. Magnetic resonance imaging of the orbits with and without contrast was performed, which revealed abnormal T2 prolongation associated enhancement involving the intraorbital segment of the left optic nerve, compatible with optic neuritis secondary to infectious etiology, given the patient's history [Figure 3]. The patient was admitted and continued on intravenous (IV) liposomal amphotericin B 250 mg every 24 h.
Figure 3: Magnetic resonance imaging showing T2 prolongation involving the intraorbital segment of the left optic nerve which is compatible with optic neuritis secondary to infection

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Over the course of the admission, the patient's VA in the left eye remained HM, but he reported subjective improvement and diminishing pain. His scleral thinning improved and his corneal epithelial defect and hypopyon resolved. A full workup remained negative, thereby excluding an endogenous source. It was therefore suspected that the source of the infection was exogenous, likely bleb-related endophthalmitis (BRE) occurring years after trabeculectomy. The amphotericin was discontinued after 1 week due to a lack of central nervous system (CNS) infection or an endogenous source. The patient was started on IV fluconazole 600 mg daily. The patient was then discharged on 600 mg oral fluconazole daily, a daily vitamin C tablet, fortified vancomycin eye drops four times daily, moxifloxacin 0.5% eye drops four times daily, voriconazole 1% eye drops four times daily, atropine sulfate 1% eye drops three times daily, and prednisolone acetate 1% eye drops twice daily. The patient was followed up outpatient, and 2 weeks after discharge, his endophthalmitis appeared to have resolved, with no evidence of posterior segment involvement and the patient reported no pain. However, the patient's vision remained HM in the left eye.

  Discussion Top

Exogenous endophthalmitis is most commonly secondary to bacterial infection with fungal etiologies being much rarer.[7] For example, the incidence of fungal endophthalmitis following cataract surgery in a cohort study in the United States was only 0.002%–0.005%.[8] The most prevalent causative agent of exogenous fungal endophthalmitis is typically mold, usually Fusarium and Aspergillus.[9]

Cryptococcal endophthalmitis is an extremely unique source of fungal endophthalmitis, with one review reporting only 27 cases in the English literature over a span of 24 years.[10] Eleven of these 27 patients had an underlying illness predisposing them to cryptococcosis, while another two patients had direct inoculation of the organism into the eye. Two cases of cryptococcal endophthalmitis were believed to be postoperative following cataract surgery, with a very long latency period, the time between exposure and development of symptoms, ranging from 3 months to 2 years.[11] One case occurred following a corneal transplant from an infected host. The most common finding was choroiditis with or without associated retinitis, whereas anterior uveitis was less commonly seen. Most patients, 25 of 27 (93%) had extraocular manifestations of infection, with CNS involvement in 22 of 27 (81%) of patients. Furthermore, eye involvement preceded CNS involvement in six of these patients, highlighting the importance of prompt recognition and systemic treatment of infection. Given the propensity of systemic involvement in these patients, bilateral ocular involvement was common as well.[10]

As the patient did not report any known contact history associated with Cryptococcus, our proposed mechanism is BRE occurring years after trabeculectomy. Some estimates of BRE suggest a risk of up to 7.8% per patient-year, depending on the location of the bleb.[12] It is postulated that bleb immersion within the tear lake with concentrated organisms could be the mechanism of infection. The use of antimetabolites has been shown to increase the risk of BRE, and our patient had a history of trabeculectomy with mitomycin C 3 years prior to his presentation, thus increasing the odds of this complication.[13] The prognosis of BRE is also strongly correlated with initial VA.[13] Our patient presented with a VA of HM and even following resolution of his infection at his last documented follow-up 2 months after discharge, his VA remained HM. Unfortunately, even eyes that are treated successfully for BRE are at risk of recurrent infections, thus it is important to manage any recurrent infections aggressively to prevent further visual deterioration.[13]

Exogenous fungal endophthalmitis management depends on the patient's condition and has evolved over time with advancements in vitreoretinal techniques, with intravitreal antifungal agents becoming a common treatment modality.[7] In the aforementioned patients, 24 of the 27 received antifungal therapy; 13 patients received amphotericin B and voriconazole, nine patients received amphotericin B only, one patient received flucytosine only, and one patient received fluconazole only. Regardless, the prognosis of endophthalmitis secondary to Cryptococcus remains guarded. The majority of previously reported patients developed significant visual loss and the return of VA to baseline prior to endophthalmitis was unusual, only happening in four cases. A total of five patients required enucleation of the eye.[10] It should be noted that in the management of endophthalmitis, vitrectomy is most effective in eyes with visual acuities of light perception or worse.[7],[14] Since the patient in this case presented with a VA of HM, we did not perform a vitrectomy, but instead proceeded with medical management. The patient in this study showed subjective improvement in visual brightness and objective improvement in ocular examination over the course of his treatment with the use of various antifungals, including voriconazole, fluconazole, and amphotericin B. The authors postulate that timely diagnosis and management was pivotal in his outcome.

A previous review reported that the leading predisposing factors associated with cryptococcal endophthalmitis were immunosuppression, hematologic malignancy, and acquired immunodeficiency syndrome.[10] Our patient did not have any of these underlying conditions and did not have CNS involvement, making this case especially rare.[15] The patient in this report demonstrates that exogenous cryptococcal endophthalmitis can be encountered in patients without immunosuppression or malignancy, in the absence of CNS disease, and can occur after a long latency period.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understands that his name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.

Financial support and sponsorship


Conflicts of interest

The authors declare that there are no conflicts of interests of this paper.

  References Top

Lewis JL, Rabinovich S. The wide spectrum of cryptococcal infections. Am J Med 1972;53:315-22.  Back to cited text no. 1
Aderman CM, Gorovoy IR, Chao DL, Bloomer MM, Obeid A, Stewart JM. Cryptococcal choroiditis in advanced AIDS with clinicopathologic correlation. Am J Ophthalmol Case Rep 2018;10:51-4.  Back to cited text no. 2
Amphornphruet A, Silpa-Archa S, Preble JM, Foster CS. Endogenous cryptococcal endophthalmitis in immunocompetent host: Case report and review of multimodal imaging findings and treatment. Ocul Immunol Inflamm 2018;26:518-22.  Back to cited text no. 3
Sheu SJ, Chen YC, Kuo NW, Wang JH, Chen CJ. Endogenous cryptococcal endophthalmitis. Ophthalmology 1998;105:377-81.  Back to cited text no. 4
Haider AA, Gallagher JR, Johnson JS, Benevento JD. Intravitreal voriconazole for the treatment of Cryptococcus neoformans endogenous endophthalmitis. Ochsner J 2020;20:319-22.  Back to cited text no. 5
Okun E, Butler WT. Ophthalmologic complications of cryptococcal meningitis. Arch Ophthalmol 1964;71:52-7.  Back to cited text no. 6
Sheu SJ. Endophthalmitis. Korean J Ophthalmol 2017;31:283-9.  Back to cited text no. 7
Du DT, Wagoner A, Barone SB, Zinderman CE, Kelman JA, MaCurdy TE, et al. Incidence of endophthalmitis after corneal transplant or cataract surgery in a medicare population. Ophthalmology 2014;121:290-8.  Back to cited text no. 8
Wykoff CC, Flynn HW, Miller D, Scott IU, Alfonso EC. Exogenous fungal endophthalmitis: Microbiology and clinical outcomes. Ophthalmology 2008;115:1501-7.e2.  Back to cited text no. 9
Crump JR, Elner SG, Elner VM, Kauffman CA. Cryptococcal endophthalmitis: Case report and review. Clin Infect Dis 1992;14:1069-73.  Back to cited text no. 10
Hiles DA, Font RL. Bilateral intraocular cryptococcosis with unilateral spontaneous regression. Report of a case and review of the literature. Am J Ophthalmol 1968;65:98-108.  Back to cited text no. 11
Greenfield DS, Suñer IJ, Miller MP, Kangas TA, Palmberg PF, Flynn HW Jr. Endophthalmitis after filtering surgery with mitomycin. Arch Ophthalmol 1996;114:943-9.  Back to cited text no. 12
Yassin SA. Bleb-related infection revisited: A literature review. Acta Ophthalmol 2016;94:122-34.  Back to cited text no. 13
Microbiologic factors and visual outcome in the endophthalmitis vitrectomy study. Am J Ophthalmol 1996;122:830-46.  Back to cited text no. 14
Weis RF, Everett ED, Sprouse R, Elfervig JL. Endogenous cryptococcal endophthalmitis. South Med J 1981;74:482-3.  Back to cited text no. 15


  [Figure 1], [Figure 2], [Figure 3]


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