Abstract
Cryptococcal endophthalmitis is a rare manifestation of cryptococcal infection, typically occurring in immunocompromised patients. In this case report, we present a 50-year-old female with advanced-stage lung cancer with multiple metastases presenting with blurred vision for 10 days. A diagnostic pars plana vitrectomy revealed Cryptococcus neoformans in the vitreous. She was treated with systemic amphotericin B and flucytosine, followed by fluconazole for consolidation and maintenance, along with intravitreal amphotericin B and voriconazole injections. Her visual acuity improved from counting fingers at 2 feet to 3/60, with a pinhole correction of 6/18 after 10 months of treatment.
1. Introduction
Cryptococcus neoformans is a fungal pathogen that primarily infects individuals with compromised immune systems [1]. The most common clinical manifestation is cryptococcal meningitis, particularly in patients with advanced HIV infection [2]. However, the spectrum of cryptococcal disease is broad [1,[3], [4], [5]], and ocular involvement, though rare, can lead to significant morbidity. In particular, cryptococcal endophthalmitis, characterized by inflammation of the intraocular cavities, is an unusual presentation with limited cases reported in the literature.
Endophthalmitis caused by C. neoformans typically occurs in the setting of disseminated infection, and is most often associated with severely immunocompromised individuals, such as those with HIV, organ transplantation, or malignancies [[6], [7], [8]]. The condition may present with non-specific symptoms, including visual impairment [[9], [10], [11], [12], [13], [14], [15]], which can lead to delayed diagnosis and treatment. Early detection and prompt initiation of antifungal therapy are critical to preventing irreversible vision loss.
Although cryptococcal infection is well described in the context of HIV and organ transplantation, its occurrence in non-HIV, non-transplant patients [3,7], particularly those undergoing chemotherapy, is rarely documented. This case report details cryptococcal endophthalmitis in a 50-year-old patient with metastatic lung adenocarcinoma and includes a literature review.
2. Case presentation
A 50-year-old woman with an 8-month history of adenocarcinoma of the lung with pleural, liver, bone, and leptomeningeal metastases presented with acute blurred vision in her left eye for 10 days. She had been undergoing chemotherapy with a carboplatin/gemcitabine regimen and had previously received whole-brain radiotherapy (WBRT) with a total dose of 3000 Gy delivered in 10 fractions.
On examination, her visual acuity was 6/60 in the right eye, improving to 6/18 with pinhole correction, and finger counting at 2 feet in the left eye (Table 1). A fundoscopic examination revealed anterior uveitis, vitreous clumping, and areas of retinitis along the artery (Fig. 1). She was admitted to the hospital for further management. A serum cryptococcal antigen test was weakly positive, and a lumbar puncture was performed, with the cerebrospinal fluid (CSF) cryptococcal antigen test returning negative results. A diagnostic pars plana vitrectomy (PPV) was performed, and vitreous fluid was sent for cytology, flow cytometry, Gram staining, culture, KOH preparation, and PCR for bacteria, viruses, and fungi. The vitreous culture grew C. neoformans (Fig. 2), confirming the diagnosis of cryptococcal endophthalmitis in the left eye. Neither blood nor CSF cultures showed any growth.
Table 1.
Initial eye examination of the present case.
| Right eye | Left eye | |
|---|---|---|
| VA | 6/60, with PH 6/18 | FC 2 feet |
| Intraocular pressure | 14 mmHg | 8 mmHg |
| Lid and lashes | Normal | Normal |
| Lacrimal system | Normal | Normal |
| Conjunctiva | Not injected | Not injected |
| Cornea | Normal | Few Descemet's membrane fold, iris nodule, fine keratic precipitates |
| Anterior chamber | Deep, no cell | Deep, no cell |
| Iris | Normal | Normal |
| Pupil | 8 mm dilated | 8 mm dilated |
| Lens | Nuclear sclerosis 1+ | Nuclear sclerosis 1+ |
| Vitreous | Anterior vitreous clear | Anterior vitreous cell 2+ |
| Fundus | C/D 0.3, normal background and macula | Haze grade 1, vitreous clumping |
Abbreviations: VA, visual acuity; PH, pinhole; FC, finger count; C/D, cup-to-disc ratio.
Fig. 1.
Fundus photograph on left eye demonstrates yellowish chorioretinitis at major retinal vascular arcades in various size.
Fig. 2.
Vitreous culture grew Cryptococcus neoformans.
She initially started on amphotericin B at a dose of 0.5 mg/kg/day and flucytosine at 100 mg/kg/day. However, due to rising creatinine levels, amphotericin B was replaced with liposomal amphotericin B at 3.7 mg/kg/day. For intravitreal treatment, she received intravitreal injections of amphotericin B, vancomycin, and ceftazidime on Day 1 (August 23rd, 2023), a second intravitreal amphotericin B injection on Day 5 (August 27th, 2023), and an intravitreal voriconazole injection on Day 10 (August 31st, 2023). The drug susceptibility test results for C. neoformans in this patient are presented in Table 2.
Table 2.
Drug susceptibility testing for Cryptococcal neoformans from the vitreous of the left eye.
| Susceptibility | MIC (ug/mL) |
|---|---|
| 5-Flucytosine | 4 |
| Amphotericin B | 1 |
| Anidulafungin | >8 |
| Caspofungin | >8 |
| Fluconazole | 16 |
| Itraconazole | 0.06 |
| Micafungin | >8 |
| Posaconazole | 0.12 |
| Voriconazole | 0.12 |
After 5 weeks of induction therapy, her vision in the left eye improved from counting fingers at 2 feet to 6/96+2, with a pinhole correction of 6/19-2. The treatment was then transitioned to the consolidation phase with fluconazole at 800 mg/day plus flucytosine at 100 mg/kg/day for 15 weeks. Subsequently, flucytosine was discontinued, and fluconazole was reduced to 200 mg/day for the maintenance phase, planned to continue for 1 year. After 10 months of treatment, her visual acuity in the left eye improved to 3/60, with a pinhole correction of 6/18, as noted at the most recent follow-up.
3. Discussion
Cryptococcal endophthalmitis is a rare but serious ocular complication of Cryptococcus neoformans infection, typically occurring in severely immunocompromised individuals, such as those with HIV/AIDS, organ transplants, or other causes of immunosuppression [4,6,8,[16], [17]]. In the present case, the patient had a history of metastatic adenocarcinoma of the lung, complicated by pleural, liver, bone, and leptomeningeal metastases, and was undergoing chemotherapy and radiotherapy, which likely contributed to her immunocompromised state. Although cryptococcal infections are more commonly associated with disseminated disease in people who live with HIV, this case demonstrates that malignancy-related immunosuppression can also increase the risk for opportunistic fungal infections, including those involving the eye.
The patient's presentation with acute blurred vision and the subsequent diagnosis of cryptococcal endophthalmitis is unusual, especially given the absence of central nervous system (CNS) involvement, as confirmed by the negative CSF cryptococcal antigen test and culture. Ocular cryptococcosis without CNS involvement is rare, and the mechanism by which C. neoformans reached the eye in this case remains unclear. Possible routes of infection include hematogenous spread from a subclinical pulmonary or disseminated infection, facilitated by the patient's compromised immune defenses.
Management of cryptococcal endophthalmitis requires urgent and aggressive antifungal therapy to reduce risk of irreversible vision loss. In this case, the patient was initially treated with amphotericin B and flucytosine. However, due to nephrotoxicity, the patient was switched to liposomal amphotericin B, which has a better safety profile while maintaining antifungal efficacy. The recommended dose of liposomal amphotericin B typically ranges from 3 to 5 mg/kg/day. In this patient, a dose of 3.7 mg/kg/day was administered, determined by the hospital's drug supply format, which provides liposomal amphotericin B in 50 mg vials. To optimize drug utilization and minimize wastage, a total of 200 mg (four vials) was administered, corresponding to 3.7 mg/kg/day based on the patient's body weight. Empiric intravitreal administration of amphotericin B, vancomycin, and ceftazidime was initiated to cover both bacterial and fungal pathogens prior to confirmation of C. neoformans from vitreous culture. After the diagnosed with C. neoformans endophthalmitis was established, ophthalmologist prescribed intravitreal amphotericin B and voriconazole to achieve higher localized drug concentrations within the eye, a strategy supported by previous case reports of fungal endophthalmitis treatment [14,16,18].
The patient responded well to the treatment, with significant improvement in visual acuity from finger counting at 2 feet to 6/96+2 in her left eye after 5 weeks of induction therapy. This outcome highlights the importance of early diagnosis and the use of both systemic and intravitreal antifungal therapies in managing cryptococcal endophthalmitis. Following induction therapy, the transition to consolidation and maintenance phases with fluconazole is standard practice to prevent relapse, as C. neoformans is known for its potential to cause recurrent infection. The maintenance phase, planned for 1 year, aims to ensure long-term eradication of the fungus and minimize the risk of recurrence, which is especially crucial in immunocompromised patients. At the most recent follow-up, after 10 months of treatment, her visual acuity (VA) in the left eye improved to 3/60, with a pinhole correction of 6/18.
Table 3 presents case reports of cryptococcal endophthalmitis in non-HIV/non-transplant patients. The cases highlight the diverse underlying conditions (cancer, autoimmune diseases) that can predispose individuals to this infection. Despite varying treatment regimens, the outcomes were generally positive, with improvements in visual acuity observed in most patients. However, some patients experienced persistent visual impairment and unfavorable outcomes [[9], [10], [11], [12], [13], [14], [15]].
Table 3.
Reports of cryptococcal endophthalmitis cases in non-HIV/non-transplant patients.
| Author | Year | Age | Sex | Clinical presentation | Underlying disease | Diagnostic method | Systemic treatment | Intravitreal treatment | Outcome |
|---|---|---|---|---|---|---|---|---|---|
| Present study | 2025 | 50 | F | Blurred vision, LE | Lung adenocarcinoma with pleural, liver, bone, and leptomeningeal metastases | Vitreous culture: C. neoformans | IV amphotericin B → liposomal amphotericin B and flucytosine (total 5 weeks) → flucytosine and fluconazole → fluconazole | IVT amphotericin B → IVT voriconazole | VA: LE 6/96 + 2 (after induction phase) |
| VA: FC | Serum cryptococcal antigen positive | LE 3/60 (10 months after treatment) | |||||||
| Hiss et al. [9] | 1988 | 63 | M | Clouding of vision, RE | Polyarteritis nodosa, treated with oral prednisone therapy, tapered over a 10-month period from 60 mg to 12.5 mg daily | Fine-needle aspiration biopsy of a solitary fluffy retinovitreal mass: C. neoformans | IV amphotericin B 40 mg/day and flucytosine 2.5 g every 6 hours | IVT amphotericin-B | VA: RE 6/6 |
| VA: 6/18 | |||||||||
| Crump et al. [10] | 1992 | 87 | F | Blurred vision, RE | Hypertension, angina pectoris, and congestive heart failure | Vitreous cytology: encapsulated, budding yeasts | Fluconazole for 5 months | – (vitrectomy) |
VA: RE FC |
| VA: FC | Blood, CSF, and vitreous cultures: C. neoformans | Deceased (due to cryptococcal meningitis after fluconazole discontinuation) | |||||||
| Shwu-Jiuan et al. [11] | 1998 | 45 | F | Progressive painless visual loss, LE | SLE with lupus nephritis | Retina biopsy | IV amphotericin B 20 mg/day for 20 days and fluconazole 400 mg/d for 6 weeks | IVT amphotericin B | – |
| History of long-term use of systemic corticosteroid | |||||||||
| Vela et al. [12] | 2009 | 84 | F | Progressive painless visual loss, LE | Repeated urinary infections treated with systemic antibiotics | Vitreoretinal biopsy | IV amphotericin B 20 mg/day, flucytosine 2.5 g every 6 hours, and voriconazole therapy | IVT amphotericin B | VA: LE HM |
| VA: HM | Retinal lesion remained unchanged | ||||||||
| Amphornphruet et al. [13] | 2018 | 45 | F | Hypopyon with severe vitritis, LE | Unremarkable, except for a previous craniotomy with ventriculoperitoneal shunt for an unidentified brain tumor more than 10 years prior | Vitreous culture: C. neoformans | IV amphotericin B | Bilateral IVT of amphotericin B (5 μg), twice a week for 1 month | VA: LE HM |
| Multifocal chorioretinitis at macula, RE | CSF culture: C. neoformans | RE 20/800 | |||||||
| Serum cryptococcal antigen: positive | |||||||||
| Peck et al. [14] | 2020 | 66 | M | Blurred vision | Myasthenia gravis treated with chronic prednisolone therapy of 20 mg/day and metastatic thymic carcinoma, which was treated with carboplatin and paclitaxel (last 9 days prior to presentation) | Vitreous Gram stain: yeast | Voriconazole therapy → | IVT voriconazole → | VA: RE 20/60 |
| VA: RE 20/400 -1 | Vitreous and CSF cultures: C. neoformans | IV amphotericin B 5 mg/kg every 24 hours, and flucytosine 1750 mg every 6 hours | IVT amphotericin 5 mg/0.1 mL, twice a week for 3 weeks | ||||||
| LE 20/50 | CSF and serum cryptococcal antigen: positive | ||||||||
| Tang et al. [15] | 2024 | 57 | F | Progressive visual loss, RE VA: 20/40 |
Immunocompetent woman | CSF cryptococcal antigen: positive | IV amphotericin B, fluconazole, and flucytosine | IVT amphotericin B (vitrectomy, trans-scleral cryotherapy) | VA: RE 20/30 |
Abbreviations: M, male; F, female; LE, left eye; RE, right eye; VA, visual acuity; FC, finger count; IV, intravenous; IVT, intravitreal injection therapy; HM, hand motion; SLE, systemic lupus erythematosus.
This case highlights the importance of clinicians maintaining a high index of suspicion for fungal endophthalmitis in patients with malignancy-related immunosuppression, even in the absence of HIV infection or a history of transplantation. The cryptococcal endophthalmitis in non-HIV, non-transplant patients can lead to diagnostic delays, which may result in worse visual outcomes. Thus, timely diagnostic interventions, such as pars plana vitrectomy and vitreous fluid analysis, are essential for confirming the diagnosis and guiding appropriate therapy.
In conclusion, this case highlights the successful management of cryptococcal endophthalmitis in a patient with metastatic lung cancer, emphasizing the importance of early intervention, tailored antifungal therapy, and close monitoring to achieve favorable visual outcomes in such complex cases.
CRediT authorship contribution statement
Kamonchanok Phaopraphat: Writing – original draft, Investigation, Data curation, Conceptualization. Rujipas Sirijatuphat: Writing – review & editing, Writing – original draft, Investigation, Funding acquisition, Data curation, Conceptualization.
Ethical statement
The authors confirm adherence to the journal's ethical policies, as outlined in the author guidelines. Ethical approval was not necessary for this study. The patient provided consent for the publication of anonymous case information.
Declaration of cometing interest
The authors declare no conflicts of interest related to this case report.
Acknowledgements
The authors thank the ophthalmologists, laboratory team, and microbiology staff of the Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand, especially Dr. Piriyaporn Chongtrakool, for their invaluable contributions to this case.
Handling Editor: Prof Adilia Warris
Contributor Information
Kamonchanok Phaopraphat, Email: imkamonchanok@gmail.com.
Rujipas Sirijatuphat, Email: rujipas.sir@mahidol.ac.th.
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