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Case Report

Endogenous Fusarium Endophthalmitis after Bone Marrow Transplant: A Case Report and Literature Review

by
Cindy S. Zhao
1,
Karen Wai
1,
Eubee B. Koo
1,
Ehsan Rahimy
1,2,
Prithvi Mruthyunjaya
1,
Vinit B. Mahajan
1,3,4 and
Charles M. T. DeBoer
1,3,4,*
1
Department of Ophthalmology, Byers Eye Institute, Stanford University, Palo Alto, CA 94303, USA
2
Department of Ophthalmology, Palo Alto Medical Foundation, Palo Alto, CA 94301, USA
3
Molecular Surgery Laboratory, Stanford University, Palo Alto, CA 94303, USA
4
Veterans Affairs Palo Alto Health Care System, Palo Alto, CA 94304, USA
*
Author to whom correspondence should be addressed.
Vision 2024, 8(3), 44; https://doi.org/10.3390/vision8030044
Submission received: 5 May 2024 / Revised: 8 July 2024 / Accepted: 16 July 2024 / Published: 21 July 2024

Abstract

:
Purpose: We aim to present a case of disseminated fusariosis that occurred in the setting of immunosuppression and presented with bilateral endogenous endophthalmitis, along with a literature review of Fusarium endophthalmitis, highlighting management strategies. Observation: A 70-year-old male with acute myeloid leukemia who had recently undergone a bone marrow transplant noted bilateral floaters and decreased vision. He was found to have bilateral Fusarium endophthalmitis, with subsequent evidence of fungemia and fusariosis in his skin and joints. Despite aggressive local and systemic treatment, he succumbed to the disease. Endophthalmitis was initially stabilized with pars plana vitrectomy and intravitreal amphotericin and voriconazole until the patient transitioned to comfort measures. A review of 31 cases demonstrates that outcomes are poor and that the disease must be treated aggressively, often both systemically and surgically. Conclusion: This case highlights the recalcitrance of Fusarium bacteremia and Fusarium endophthalmitis.

1. Introduction

Although ubiquitous in the environment as a plant pathogen, Fusarium does not commonly result in systemic fungal infection or enter the eye to cause endophthalmitis [1]. When present, Fusarium endophthalmitis more commonly occurs exogenously after inoculation from trauma, invasion into the eye from keratitis, or after cataract surgery. Often, in these cases, aggressive treatment is required, and prognosis remains poor despite multifaceted local, surgical, and systemic treatment [2,3,4,5]. This report illustrates a case of bilateral endogenous Fusarium endophthalmitis in an immunocompromised patient, highlighting the complex multidisciplinary care these rare cases require.

2. Case Report

A 70-year-old male with acute myeloid leukemia (AML) presented for a mismatched, unrelated donor bone marrow transplant (BMT). He had previously been treated with three cycles of chemotherapy, including two rounds of intrathecal chemotherapy for presumed central nervous system disease. While the central nervous system disease showed improvement, the patient had residual bone marrow involvement.
Despite a hospital course complicated by neutropenic fever, acute pulmonary edema, new-onset atrial fibrillation, and clostridium difficile colonization, his bone marrow transplant team felt optimistic one month after his BMT that his immune system was recovering and that his disease may have been cured. Throughout this first month after BMT, he was on antibacterial, antiviral, and antifungal agents for prophylaxis: oral levofloxacin for neutropenic fever, oral acyclovir for herpes simplex virus (HSV) and varicella-zoster virus (VZV), oral letermovir for cytomegalovirus (CMV), oral trimethoprim/sulfamethoxazole for pneumocystis jiroveci pneumonia, and oral isovuconazole for fungal prophylaxis.
It was at this time, one month following BMT, that the patient noted one week of bilateral floaters and decreased vision. An ophthalmology consult was requested. On exam, his visual acuity was counting fingers from two feet in both eyes with normal intraocular pressures. He had mild temporal conjunctival injection in the left eye but an otherwise normal anterior segment exam. The dilated fundus exam was notable for mild vitreous haze bilaterally, numerous foci of elevated, subretinal lesions, and overlying hemorrhage in the macula of each eye. Ocular ultrasonography (Figure 1) confirmed the presence of subretinal masses and vitreous debris bilaterally, without retinal detachment.
Due to concern for recurrent or widespread malignancy, magnetic resonance imaging (Figure 2) and a lumbar puncture were performed, neither of which showed evidence of neoplasia. The patient received a vitreous tap and intravitreal injection of voriconazole (100 mg/0.1 mL), vancomycin (1 mg/0.1 mL), and ceftazidime (2.25 mg/0.1 mL) in both eyes. After five days, the culture began to grow fungi, which ultimately speciated as Fusarium solani. A blood culture and diagnostic vitrectomy (Figure 3) similarly yielded Fusarium species. His vision remained intact, able to count fingers from two feet in both eyes afterward (Figure 4). Further examination revealed systemic dissemination with the involvement of his skin and several joints, which similarly grew Fusarium species. From the blood sample, amphotericin B was found to have a minimum inhibitory concentration (MIC) of 2 micrograms/mL and voriconazole an MIC of 4 mg/mL.
Systemic coverage was initiated with intravenous amphotericin B and voriconazole and, eventually, a novel experimental antifungal, fosmanogepix. Ocular treatment consisted of ten rounds of intravitreal injections every other day with antifungals, alternating between amphotericin B and voriconazole. Examination findings stabilized during treatment, with similar visual acuity and no extension of the lesions. Given extensive systemic disease, the patient ultimately wished to discontinue local treatments and withdrew care, succumbing to his disease process.

3. Discussion

Even with aggressive systemic and local therapy, fungal endophthalmitis can be a devastating disease with a poor visual prognosis. Fungal endophthalmitis more often occurs exogenously after trauma, keratitis, or intraocular surgery; endogenous endophthalmitis associated with systemic fungal infection represent 2–15% of all cases [6]. The most common organisms found in endogenous fungal endophthalmitis are Candida albicans and Aspergillus species [7]. Here, we present a case of bilateral endogenous fungal endophthalmitis caused by Fusarium solani, which is a rare presentation with isolated case reports in the literature, as summarized below.

4. Literature Review

Twelve species of Fusarium have been reported to be associated with systemic infection, of which the most common are Fusarium solani (~50% of cases), Fusarium oxysporum (~20% of cases), Fusarium verticillioidis (~10% of cases) and Fusarium monoliforme (~10% of cases) [1]. When associated with ocular infection, Fusarium species are more often associated with keratitis and exogenous endophthalmitis [1,6].
A literature review was conducted on April 10, 2024, on PubMed using the keywords “fusarium endophthalmitis” and “endogenous fusarium endophthalmitis.” All cases of endogenous Fusarium endophthalmitis referred to in these articles were also included. Several larger case series reported exogenous Fusarium endophthalmitis, while a limited number of case reports associated with endogenous Fusarium endophthalmitis were found (n = 30, not including the case reported here). Prior to this review, the largest case series included 14 cases [8], so this is the most comprehensive literature review to our knowledge to date. The results are summarized in Table 1.
Most endogenous Fusarium endophthalmitis occurred in the setting of an immunocompromised state. Including our patient, AML (n = 13/31) and acute lymphocytic leukemia (n = 8/31) were the most commonly associated medical comorbidities. Other identified medical risk factors included immunosuppression from Hodgkin lymphoma (n = 1/31) [9], the use of systemic steroids (n = 3/31) [8,10,11], diabetes (n = 2/31) [8,10], Acquired immunodeficiency syndrome (AIDS, n = 1/31) [12], and a history of liver transplantation (n = 1/31) [13]. Aside from the presented case, one other patient (n = 2/31) had undergone a bone marrow transplant [14], while one had undergone a hematopoietic stem cell transplant (n = 1/31) [15]. One case for each was reported where the only identifiable medical history was intravenous drug use [16], preceding kidney infection [17], or a recent thorn prick with a self-limited local inflammatory reaction [18]. When a species was identified, Fusarium solani (n = 17/31) predominated. Two cases were reported for Fusarium dimerum [16,19].
Treatment options for fungal endophthalmitis include topical natamycin (though not often used alone), intravitreal injections of antifungals such as amphotericin B (5–10 µg/0.1 mL) and voriconazole (1 mg/0.1 mL), systemic oral or intravenous antifungal treatment with amphotericin B, and surgical treatment with pars plana vitrectomy (n = 17/31) or the removal of other infected areas (e.g., lensectomy) (n = 4/31) and in recalcitrant cases, evisceration or enucleation (n = 7/31). Almost all authors used systemic amphotericin (n = 24/31) and/or an azole (n = 14/31) such as voriconazole (most common, n = 12), fluconazole (n = 1), or itraconazole (n = 1). Intravitreal injections of amphotericin only (n = 10/31), vorizonacole only (n = 6/31), or an alternating combination of amphotericin and voriconazole (n = 6/31) were given at most, simultaneously and once weekly, up to 6 weeks [20] (aside from the reported case). Seven cases received systemic therapy without intravitreal injections, with one of these patients undergoing pars plana vitrectomy and one requiring enucleation. No well-studied regimen exists to guide treatment selection, and most cases used combination therapy. Vitrectomy provides the advantage of reducing the fungal burden in the vitreous and provides additional samples for establishing the diagnosis, as well as addressing common post-infectious sequelae such as retinal detachment and epiretinal membrane [21]. In one case of fungal endophthalmitis (not specified to be Fusarium), the intralesional injection of voriconazole and povidone-iodine was performed with final vision at 20/25 [22].
Systemic outcome and final vision varied without a consistent pattern. Two cases had patients that ultimately recovered to 20/20 visual acuity; both of these cases involved only the eye and suggested the importance of immune recovery and treatment with vitrectomy, systemic amphotericin B, and intravitreal injections of antifungals [16,20]. Overall, this literature review suggests the need for aggressive treatment and a surgical reduction in disease burden, but no conclusion can be drawn about the most effective treatment nor about systemic and ocular prognosis upon diagnosis. Only three patients had final visual acuities between 20/50 and 20/80, while most patients experienced near or total vision loss of the affected eyes [8,17,23]. Multi-system Fusarium involvement (n = 21/31) resulted in both survival (n = 11 of 24 with reported systemic outcomes) and death (n = 13 of 24 with reported systemic outcomes), likely in part related to factors involved in the course of their systemic disease.
Table 1. Summary of case reports in the literature.
Table 1. Summary of case reports in the literature.
ReferenceNo. of PatientsAge (Years)GenderMedical HistoryAntifungals Prior to Ocular SymptomsInvolved SitesFusarium speciesTreatmentOcular SurgeryOcular OutcomeFinal VisionSystemic Outcome
Tiribelli et al. 2002 [24]1 31MaleAMLItraconazoleSkin, lungs, eye, meningesF. solaniSystemic: AmBVitrectomy
Iridectomy
PK
No responseTotal vision lossDeath from hemorrhagic shock
Intraocular: AmB
Rezai et al. 2005 [25]1 70FemaleAMLNASkin, blood, eyeNASystemic: AmBNoneNo response-Death from multiorgan failure
Intraocular: AmB
Cudillo et al. 2006 [26]1 34MaleALLItraconazoleSkin, blood, lungs, sinuses, eyeNASystemic: AmBNoneResponse-Death from leukemia relapse
Thachil et al. 2010 [15]1 67FemaleAMLNASkin, blood, eyeF. solaniSystemic: Vori, AmBVitrectomyResponseHMSurvival
Intraocular: AmB
Kapp et al. 2011 [27]1 69MaleAML, HSCTPosaconazoleBlood, kidneys, eyeF. solaniSystemic: Vori, AmBVitrectomyNo responseWorse than HMDeath from multiorgan failure
Intraocular: AmB
Kah et al. 2011 [23]1 9MaleALLNASkin, blood, eye, kidney abscess, subcutaneous soft tissueNASystemic: AmB cholesterol dispersionNoneResponseVA 6/24
(20/80)
Survival
Intraocular: Vori
Perini et al. 2013 [28]1 68MaleAMLNASkin, blood, lungs, eyeNASystemic: Vori, AmBEnucleationNo response--
Intraocular: Vori
Malavade et al. 2013 [9]3 62MaleHodgkin lymphomaFluconazoleSkin, eyeNASystemic: itraconazole, AmBVitrectomyNo response-Death from refractory leukemia
Intraocular: AmB
Topical: AmB
66MaleAMLAmB + VoriSkin, bone, eyeNASystemic: AmB, VoriVitrectomyNo response--
Intraocular: AmB, VoriRD repair
Enucleation
46MaleALLVoriSkin, sinus, eyeNASystemic: Vori, AmB, co-trimoxazoleNoneNA--
Jørgensen et al. 2014 [13]1 56FemaleLiver transplant x 2MicafunginEyeF. solaniSystemic: Micafungin, Vori after enucleationEnucleationNA-Death from septic shock
Intraocular: Vori for contralateral eye
Bui & Carvounis 2016 [20]1 14FemaleALLNAEyeNASystemic: Vori, AmBVitrectomyResponseVA 20/20Survival
Intraocular: AmB, Vori
Ocampo-Garza et al. 2016 [29]1 46MaleALLNASkin, lungs, eyeF. solaniSystemic: Vori, AmBNoneNo responseTotal vision lossSurvival, undergoing continued chemotherapy
Topical: AmB
Balamurugan and Khodifad 2016 [10]1 46MaleDiabetes mellitus, topical and oral steroids for uveitis treatmentNAEyeNASystemic: antifungal not specifiedVitrectomyNo responseHM-
Intraocular: Vori
Rizzello et al. 2018 [8]1 59FemaleALL, Diabetes mellitus in setting of prolonged steroid usePosaconazoleSkin, blood, eyeF. solaniSystemic: Vori, AmBVitrectomy
Lensectomy
ResponseVA +0.50 logMAR (20/63)Survival in ALL remission
Intraocular: Vori
Topical: AmB
Glasgow et al. 1996 [12]1 51MaleAIDS, cytomegalovirus retinitisGanciclovirBlood, brain, lung, kidney, thyroid, lymph nodes, eyeF. solaniSystemic: AmB, fluconazoleNoneNo response-Death
Intraocular: AmB
Patel et al. 1994 [30]1 31FemaleALLNASkin, eyeNASystemic: AmB, 5-FCNoneNo responseProgressive vision lossDeath from bronchopneumonia and multiorgan failure
Intraocular: AmB
Topical: AmB
Cho et al. 1973 [31]1 2.5MaleALLNoneSkin, knee, eyeF. solaniSystemic: AmBNoneResponse-Death
Topical: AmB
Simon et al. 2018 [19]1 71FemaleAMLPosaconazoleEyeF. dimerumSystemic: VoriVitrectomyResponseHMSurvival, undergoing continued chemotherapy
Intraocular: AmB, Vori
Topical: Vori
Milligan et al. 2016 [18]1 32FemaleNone; recent thorn prick with self-limited local inflammatoryNoneEyeF. solaniSystemic: VoriVitrectomyNo responseCFSurvival
Intraocular: AmB, VoriRD repair with silicone oil
Yoshida et al. 2018 [32]1 16MaleAMLNALung, spleen, subcutaneous soft tissue, eyeF. solaniSystemic: Vori, AmBVitrectomyResponseVA 20/400Survival
Intraocular: VoriTractional RD repair
Gabriele and Hutchins. 1996 [16]1 30MaleIntravenous drug useNAEyeF. dimerumSystemic: AmBVitrectomyResponseVA 20/20Survival
Intraocular: AmB
Baysal et al. 2018 [33]1 28MaleAMLPosaconazoleEyeNASystemic: Vori, AmBEnucleationNA-Death from pneumosepsis
Voriconazole
Relimpio-López et al. 2018 [34]2 NANANANAEyeF. solaniNALensectomyNo response-NA
PK
Evisceration
NANANANAEyeF. solaniSystemic: VoriVitrectomyResponseHM (aphakic)NA
Intraocular: AmB, VoriPK
Topical: AmB, fortified Vori, Povidone-Iodine
Lieberman et al. 1979 [11]1 45FemaleUveitis treated with oral prednisone 60–120 mg dailyNAEyeF. solaniNoneSector iridectomy
Lensectomy
Enucleation
No response-NA
Comhaire-Poutchinian et al. 1990 [17]1 27FemaleRecent kidney infectionItraconazoleKidney, skin, eyeNASystemic: AmB, 5-FCVitrectomyResponseVA 4/10
(20/50)
Survival
Venditti et al. 1988 [35]1 55MaleAMLNASkin, blood, eyeF. solaniSystemic: AmB, 5-FCNoneNo responseTotal vision lossDeath
Robertson et al. 1991 [14]1 33MaleAML, BMTNASkin, eye, toeF. solaniSystemic: AmBVitrectomyNo response-Survival free of leukemia and fungal disease
Intraocular: AmBEnucleation
Louie et al. 1994 [36]1 67MaleAMLFluconazoleBlood, eyeF. solaniSystemic: AmBVitrectomyResponseVA 4/200 (20/1000)Death from recurrent leukemia
Intraocular: AmB
Topical: None
Present Case1 70MaleAML, BMTisovuconazoleSkin, blood, joints, eyeF. solaniSystemic: AmBVitrectomyNo responseCF at 2-3′Death from complications of treatment
Intraocular: AmB, Vori
TOTAL31
Abbreviations: AML, acute myeloid leukemia; AmB, Amphotericin B; 5-FC, 5-fluorocytosine; ALL, acute lymphocytic leukemia; BMT, bone marrow transplant; HSCT, hematopoietic stem cell transplant; HL, Hodgkin lymphoma; AIDS, Acquired immunodeficiency syndrome; Vori, voriconazole; NA, not available/applicable; RD, retinal detachment; PK, penetrating keratoplasty.

5. Conclusions

Endogenous Fusarium endophthalmitis is rare. When present, it is more likely to occur in the setting of an immunocompromised patient with hematologic malignancy or neutropenia. Aggressive treatment is warranted, and even then, the prognosis for visual recovery remains poor.

Author Contributions

Conceptualization, Investigation, Writing—original draft preparation: C.S.Z., C.M.T.D.; Supervision: K.W., E.B.K., E.R., P.M., C.M.T.D.; Writing—review and editing: K.W., E.B.K., E.R., V.B.M., C.M.T.D. All authors have read and agreed to the published version of the manuscript.

Funding

This work was supported by the P30 Vision Research Core Grant, NEI P30-EY026877, and Research to Prevent Blindness. VBM is supported by R01EY024665; CMD is supported by K12 EY033745, The Robert Machemer Foundation, and E. Matilda Ziegler Foundation for the Blind.

Institutional Review Board Statement

Not applicable, as this is a retrospective case study.

Informed Consent Statement

Written informed consent from the patient’s family was obtained for the publication of this report. This case report does not contain any details or information that could lead to the identification of the patient.

Data Availability Statement

No new data were created or analyzed in this study. Data sharing is not applicable to this article.

Acknowledgments

Additional acknowledgement goes to the Stanford Department of Ophthalmology, Bone Marrow Transplant, and Infectious Disease residents, fellows, and faculty members who assisted in the care of this patient.

Conflicts of Interest

The authors declare no conflicts of interest.

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Figure 1. B-scan ultrasonography of macular lesions in the left eye on initial examination demonstrated vitreous opacities consistent with vitritis, elevated subretinal lesions, and a thickened choroid.
Figure 1. B-scan ultrasonography of macular lesions in the left eye on initial examination demonstrated vitreous opacities consistent with vitritis, elevated subretinal lesions, and a thickened choroid.
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Figure 2. Magnetic resonance imaging of the brain and orbit at the time of initial diagnosis showed abnormal thickening of the left sclera and periorbital soft tissues but no lesions infiltrating the optic nerve to suggest malignancy.
Figure 2. Magnetic resonance imaging of the brain and orbit at the time of initial diagnosis showed abnormal thickening of the left sclera and periorbital soft tissues but no lesions infiltrating the optic nerve to suggest malignancy.
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Figure 3. (a) View of vitritis and subretinal lesions in the right eye during diagnostic vitrectomy and prior to core vitrectomy. (b) View of subretinal lesions in the right eye during diagnostic vitrectomy and after core vitrectomy.
Figure 3. (a) View of vitritis and subretinal lesions in the right eye during diagnostic vitrectomy and prior to core vitrectomy. (b) View of subretinal lesions in the right eye during diagnostic vitrectomy and after core vitrectomy.
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Figure 4. (a) Right eye post-operative day 2 after diagnostic vitrectomy of the right eye. (b) The left eye on the same day.
Figure 4. (a) Right eye post-operative day 2 after diagnostic vitrectomy of the right eye. (b) The left eye on the same day.
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MDPI and ACS Style

Zhao, C.S.; Wai, K.; Koo, E.B.; Rahimy, E.; Mruthyunjaya, P.; Mahajan, V.B.; DeBoer, C.M.T. Endogenous Fusarium Endophthalmitis after Bone Marrow Transplant: A Case Report and Literature Review. Vision 2024, 8, 44. https://doi.org/10.3390/vision8030044

AMA Style

Zhao CS, Wai K, Koo EB, Rahimy E, Mruthyunjaya P, Mahajan VB, DeBoer CMT. Endogenous Fusarium Endophthalmitis after Bone Marrow Transplant: A Case Report and Literature Review. Vision. 2024; 8(3):44. https://doi.org/10.3390/vision8030044

Chicago/Turabian Style

Zhao, Cindy S., Karen Wai, Eubee B. Koo, Ehsan Rahimy, Prithvi Mruthyunjaya, Vinit B. Mahajan, and Charles M. T. DeBoer. 2024. "Endogenous Fusarium Endophthalmitis after Bone Marrow Transplant: A Case Report and Literature Review" Vision 8, no. 3: 44. https://doi.org/10.3390/vision8030044

APA Style

Zhao, C. S., Wai, K., Koo, E. B., Rahimy, E., Mruthyunjaya, P., Mahajan, V. B., & DeBoer, C. M. T. (2024). Endogenous Fusarium Endophthalmitis after Bone Marrow Transplant: A Case Report and Literature Review. Vision, 8(3), 44. https://doi.org/10.3390/vision8030044

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