Endogenous
Route of infection: Hematogenous dissemination from fungemia
Main causative organism: Candida albicans (most common)
Frequency: More than half of all endogenous endophthalmitis cases
Bilaterality: Seen in approximately 30% of cases
Fungal Endophthalmitis
Key Points at a Glance
Section titled “Key Points at a Glance”1. What is fungal endophthalmitis?
Section titled “1. What is fungal endophthalmitis?”Fungal endophthalmitis is a severe eye disease in which fungi infect and proliferate in the intraocular fluids (vitreous humor and aqueous humor). It is classified into two types based on the route of infection: endogenous (hematogenous dissemination) and exogenous (spread from surgery, trauma, or keratitis).
More than half of endogenous endophthalmitis cases are fungal, and 30% are bilateral. Exogenous cases are subdivided into three categories: postoperative, post-traumatic, and keratitis-related 7). Compared to bacterial endophthalmitis, progression is slower, with symptoms worsening over days to weeks.
Exogenous
Route of infection: Spread from surgery, trauma, or keratitis
Main causative organism: Aspergillus species (most common)
Frequency: Mostly unilateral
Classification: Three categories: postoperative, post-traumatic, and keratitis-related
The causative organisms are typically Candida and Aspergillus species, but reports of rare species are increasing. Trichosporon species (naturally resistant to echinocandins) 6), C. rugosa (less than 0.1% of non-albicans Candida) 3), Arthrographis kalrae 5), and Neoscytalidium dimidiatum 7) have been reported.
After the COVID-19 pandemic, cases of fungal endophthalmitis triggered by immunosuppression due to steroid use have been reported in succession 1, 9).
2. Main Symptoms and Clinical Findings
Section titled “2. Main Symptoms and Clinical Findings”
Nianjia Wang; Jiayi Wu; Xintong Xiang; Qian Zhao; Liang Yao. Endogenous Fungal Endophthalmitis Following Eyebrow Tattooing: A Case Report. Cureus.; 17(9):e93246. Published 2025. Figure 2. PMCID: PMC12553984. License: CC BY.
Baseline ophthalmic examination findings of the right eye. (A) Marked ciliary congestion. (B) Slit-lamp examination revealed abundant inflammatory cells and a significant aqueous flare in the anterior chamber. (C) Dense vitreous opacity precluding view of the fundus. (D) Ocular B-scan ultrasound showed extensive vitreous opacities.
Subjective Symptoms
Section titled “Subjective Symptoms”Floaters, blurred vision, and decreased visual acuity are common early symptoms. In advanced cases, eye pain and redness may occur.
The rate of disease progression varies depending on the causative organism.
- Candida endophthalmitis: Indolent, with vision declining over days to weeks.
- Aspergillus endophthalmitis: More acute course, with rapid vision loss accompanied by dense vitreous opacities.
- Exogenous (post-surgical/post-traumatic): Subacute to chronic, with an incubation period that can range from weeks to months.
Clinical Findings
Section titled “Clinical Findings”Yellow-white fluffy chorioretinal infiltrates with indistinct borders, predominantly in the posterior pole. May be accompanied by intraretinal hemorrhages.
- Fungus ball: Feathery characteristic vitreous opacity. Seen in Candida endophthalmitis.
- “String of pearls” appearance: Beaded opacities due to aggregation of focal vitreous inflammation. Also confirmed in cases with concurrent Klebsiella infection 8).
- Risk of misdiagnosis: Fungal infection is easily overlooked as postoperative recurrent vitritis. Cases exacerbated by steroid administration have been reported4).
- Similarity to sarcoidosis: The morphology of vitreous opacities is similar, and up to 50% may be misdiagnosed in the early stage2).
Q
Are the symptoms of fungal endophthalmitis difficult to distinguish from other eye diseases?
A
The appearance of vitreous opacities is similar to non-infectious uveitis such as sarcoidosis, and it has been reported that up to 50% are misdiagnosed in the early stage2). Additionally, fungal infection may be overlooked as postoperative recurrent vitritis4). For details, see the “Diagnosis and Examination Methods” section.
3. Causes and Risk Factors
Section titled “3. Causes and Risk Factors”Risk factors differ between endogenous and exogenous types. The main risk factors are shown below.
| Classification | Main Risk Factors |
|---|---|
| Endogenous | Central venous nutrition, immunosuppressants, steroids |
| Endogenous | Organ transplantation, neutropenia, malignancy |
| Endogenous | Diabetes, prolonged ICU stay |
| Exogenous | Intraoperative complications, advanced age, steroid eye drops |
| Exogenous | Corneal ulcer, improper contact lens use |
COVID-19-related cases have been reported where prolonged hospitalization and systemic steroid administration led to immunosuppression and triggered fungal endophthalmitis 1, 9). Other reported causes include breast cancer chemotherapy (docetaxel-induced leukopenia) 3), immunosuppressive therapy (methotrexate + steroids) 2), keratitis spreading from poor hygiene during contact lens use 5), fungal biofilm colonization on IOL 6), infection by phytopathogenic fungi due to plant trauma 7), and poor diabetes control 4, 8).
Q
Is there a risk of fungal endophthalmitis after COVID-19?
A
Yes. Systemic steroids used for COVID-19 treatment and prolonged ICU stay can cause immunosuppression and trigger endogenous fungal endophthalmitis 1, 9). If vision changes occur, prompt ophthalmologic evaluation is necessary.
4. Diagnosis and testing methods
Section titled “4. Diagnosis and testing methods”Culture and microbiological tests
Section titled “Culture and microbiological tests”Intraocular fluid culture is the gold standard. Vitreous samples have a higher diagnostic yield than aqueous humor. Sabouraud agar is used, and cultures are incubated at both 37°C and room temperature for at least 2 weeks.
Blood cultures are positive in only one-third to one-half of endogenous cases, so a negative result does not rule out endophthalmitis.
Enrichment culture: Inoculating vitreous fluid into blood culture bottles has been reported to yield positivity in an average of 1.23 days 6).
Ancillary Diagnosis
Section titled “Ancillary Diagnosis”- β-D-glucan: Used for ancillary diagnosis, but negative cases exist. In a case of C. rugosa, serum ≤3.2 pg/mL and vitreous ≤3.0 pg/mL were reported 3).
- PCR (panfungal primer/ITS gene): Enables species identification even when culture is negative. Its utility has been reported in COVID-19-associated cases and C. rugosa cases 1, 3).
- MALDI-TOF MS: Enables rapid and accurate species identification 6).
Antifungal Susceptibility Testing
Section titled “Antifungal Susceptibility Testing”Once the causative organism is identified, antifungal susceptibility testing should always be performed. Aspergillus terreus shows high resistance (98%) to amphotericin B (MIC 2 μg/mL) 2). In a case where fluconazole susceptibility (MIC 2.0 μg/mL) of Trichosporon inkin was confirmed, fluconazole monotherapy was successful 6).
Q
Is it possible to have fungal endophthalmitis even if blood tests are negative?
A
Yes. Even in endogenous endophthalmitis, blood cultures are positive in only one-third to one-half of cases. β-D-glucan can also be negative 3). Direct culture and PCR of intraocular fluid are essential for definitive diagnosis.
5. Standard Treatment
Section titled “5. Standard Treatment”Systemic Administration
Section titled “Systemic Administration”The characteristics of major antifungal agents are shown below.
| Drug | Route | Characteristics |
|---|---|---|
| Fluconazole | IV/Oral | First-line for Candida |
| Voriconazole | Intravenous / Oral | Effective against filamentous fungi and resistant Candida |
| Amphotericin B | Intravenous / Intravitreal | Broad spectrum, limited intraocular penetration |
- Fluconazole: 100 mg IV or 200–400 mg/day orally. First-line for Candida chorioretinitis.
- Voriconazole: Effective against filamentous fungi and fluconazole-resistant Candida. 200 mg/day orally. Good intravitreal penetration.
- Amphotericin B: Broad spectrum but limited intraocular penetration. Nephrotoxicity is a concern 2).
- Isavuconazole: Reported as an alternative when voriconazole blood levels are low 1, 2).
- Micafungin: Reported at 300 mg/day in A. terreus cases 2). However, it should not be used for Trichosporon species due to natural resistance 6).
Treatment duration is usually 4–6 weeks. Successful control of Trichosporon inkin with 16 weeks of fluconazole has been reported 6).
Intravitreal Injection
Section titled “Intravitreal Injection”- Amphotericin B: 5 μg/0.1 mL 2).
- Voriconazole: 100 μg. Half-life in vitrectomized eyes is approximately 8 hours (amphotericin B is over 24 hours) 2).
Pars Plana Vitrectomy (PPV)
Section titled “Pars Plana Vitrectomy (PPV)”It is performed for physical removal (debulking) of the infection source, enhancement of drug diffusion, and specimen collection. It is indicated in the following cases.
- When vitreous opacity is severe and drug therapy alone is insufficient
- When specimen collection is needed for definitive diagnosis
- Refractory or recurrent cases
In IOL-related cases, removal of the IOL and the lens capsule including biofilm is important 5, 6).
Treatment Strategies by Causative Organism
Section titled “Treatment Strategies by Causative Organism”Candida
Chorioretinitis only: Oral azoles (fluconazole, voriconazole)
Vitreous involvement: Add vitrectomy + intravitreal antifungal injection
Treatment duration: Generally 4–6 weeks
Aspergillus
First-line: Voriconazole (A. terreus has 98% amphotericin B resistance rate)
Local therapy: Vitrectomy + intravitreal voriconazole injection
Susceptibility testing: Mandatory (to confirm resistance)
Rare fungal species
Trichosporon: Echinocandins are ineffective. Use after confirming fluconazole susceptibility.
Others: After identification by MALDI-TOF MS, select based on drug susceptibility testing.
Q
Should steroids not be used for fungal endophthalmitis?
A
In principle, they should be avoided. Steroids promote fungal growth and risk rapid worsening of the condition. There are reports of rapid exacerbation after steroid (intravitreal dexamethasone) administration in A. terreus endophthalmitis2). It is important to rule out fungal infection before using steroid eye drops or intravitreal injections.
6. Pathophysiology and detailed pathogenesis
Section titled “6. Pathophysiology and detailed pathogenesis”Progression of endogenous endophthalmitis
Section titled “Progression of endogenous endophthalmitis”Fungemia → colonization of choroid and retina → formation of infectious foci → vitreous seeding → endophthalmitis → panuveitis → panophthalmitis, a stepwise progression.
- Angioinvasive entry of Aspergillus: Invades from around blood vessels, forming vascular occlusion and hemorrhagic lesions.
- IOL biofilm: Fungi adhere to and proliferate on the intraocular lens (IOL), functioning as an immune evasion mechanism. This causes chronic and recurrent infection6).
Special pathogenic mechanisms of rare fungal species
Section titled “Special pathogenic mechanisms of rare fungal species”Koide et al. (2023) reported a case of C. rugosa endophthalmitis and suggested an invasion route into the vitreous cavity via the Virchow-Robin space 3). C. rugosa is a rare species, accounting for less than 0.1% of non-albicans Candida, but can cause invasive infection in immunocompromised states.
Kaderli Tamer et al. (2022) reported that in a case of endophthalmitis that developed during COVID-19 treatment, steroids enhanced the disruption of the blood-retinal barrier and promoted fungal intraocular invasion 9).
Trichosporon species produce a capsular polysaccharide (glucuronoxylomannan; GXM) antigen, which inhibits phagocytosis by phagocytic cells, thereby establishing invasive infection 6). This mechanism, together with natural resistance to echinocandins, is the main cause of treatment-refractory disease.
7. Latest Research and Future Perspectives (Investigational Reports)
Section titled “7. Latest Research and Future Perspectives (Investigational Reports)”Povidone-Iodine Perfusion Vitrectomy
Section titled “Povidone-Iodine Perfusion Vitrectomy”As a novel treatment for refractory fungal endophthalmitis, a technique using 0.025% povidone-iodine as an irrigating solution during vitrectomy has been reported.
Huang et al. (2024) performed 0.025% povidone-iodine perfusion vitrectomy in a case of severe endophthalmitis caused by Arthrographis kalrae 5). The infection, which was difficult to control with conventional antifungal drugs, was controlled by this surgery. Povidone-iodine has no resistance mechanisms and is expected as a countermeasure against multidrug-resistant fungi.
Advances in Rapid Diagnostic Techniques
Section titled “Advances in Rapid Diagnostic Techniques”- MALDI-TOF MS: Enables faster and more accurate species identification than conventional morphological or biochemical identification 6). It is particularly useful for identifying rare species such as Trichosporon inkin.
- PCR + Sequencing: Even in culture-negative cases, panfungal PCR targeting the ITS gene region can identify the fungal species 1, 3). Since the COVID-19 pandemic, it has contributed to the diagnosis of endogenous endophthalmitis cases with negative blood cultures.
Unresolved Issues
Section titled “Unresolved Issues”Breakpoints (clinical thresholds) for antifungal drugs against Trichosporon species have not yet been established 6). Currently, individual treatment based on drug susceptibility test results at each facility is the norm, and the development of evidence-based treatment guidelines is a future challenge.
8. References
Section titled “8. References”- Mohan S, Kandle K, Ganesan S, Prakash VJ, Mistry S, Anand AR, et al. Endogenous fungal endophthalmitis following COVID-19 infection with microbiological and molecular biological correlation — A report of two cases. Indian J Ophthalmol. 2023;71(5):2272-2275.
- Awh CC, Mammo DA, Bergstrom R, Baynes K, Srivastava SK. Fungal endophthalmitis secondary to Aspergillus terreus exacerbated by intravitreal dexamethasone in a patient with sarcoidosis. J VitreoRetinal Dis. 2023;7(5):448-454.
- Koide R, Yamamoto S, Kobayashi Y, Irie J, Enaida H. Atypical endogenous fungal endophthalmitis caused by Candida rugosa. Retinal Cases Brief Rep. 2023;17(6):672-675.
- Narnaware SH, Bawankule PK, Sontakke S. Misdiagnosed case of fungal endophthalmitis. Eye. 2024;38(1):76-77.
- Huang D, Tran L, Li JYH, Lee W, Kim E, Moussa K. Povidone iodine-infused pars plana vitrectomy for severe Arthrographis kalrae fungal endophthalmitis. Am J Ophthalmol Case Rep. 2024;36:102207.
- Fan N, Duan X, Liu X, Fan P, Chen N, Sun J. First documented successful treatment of chronic postoperative fungal endophthalmitis induced by Trichosporon inkin with fluconazole. Infect Drug Resist. 2024;17:5803-5813.
- Qi C, Mo B, Jiang C, Li J, Bo X, Xiao X, et al. Clinical characteristics and treatment outcomes of fungal endophthalmitis caused by Neoscytalidium dimidiatum. Infect Drug Resist. 2025;18:3671-3675.
- Sugantheran J, Zunaina E, Md Kasim WM, Talib N. Invasive Klebsiella syndrome with coexisting fungal endophthalmitis. Malays Fam Physician. 2021;16(2):94-97.
- Tamer Kaderli S, Karalezli A, Citil BE, Saatci AO. Endogenous fungal endophthalmitis in a patient admitted to intensive care and treated with systemic steroid for COVID-19. Turk J Ophthalmol. 2022;52(2):139-141.
- Durand ML. Bacterial and Fungal Endophthalmitis. Clin Microbiol Rev. 2017;30(3):597-613.
- Haseeb AA et al. Fungal Endophthalmitis: A Comprehensive Review. J Fungi (Basel). 2021;7(11).