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 Table of Contents  
Year : 2021  |  Volume : 33  |  Issue : 2  |  Page : 205-208

Challenges in the diagnosis of early endogenous fungal endophthalmitis

Department of Uvea and Viteoretinal Services, Dr. Tony Fernandez Eye Hospital, Aluva, Kerala, India

Date of Submission24-Jun-2020
Date of Decision06-Jul-2020
Date of Acceptance10-Jul-2020
Date of Web Publication21-Aug-2021

Correspondence Address:
Dr. Nusrath Parambil
Dr. Tony Fernandez Eye Hospital, Aluva - 683 101, Kerala
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/kjo.kjo_87_20

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Endogenous fungal endophthalmitis (EFE) is an uncommon disease caused by the dissemination of fungal infection to posterior segments of the eye and has a high rate of visual loss. Most patients have associated predisposing risk factors, including immunocompromised conditions, and the condition is less likely to occur in healthy individuals. Here, we report two patients who presented like uveitis and deteriorated after starting standard treatment for uveitis, which included steroids. They were later diagnosed with EFE. Fungal endophthalmitis should be suspected even in ambulatory individuals with immunocompromised states, when they present with uveitis like features, before starting steroid treatment. Polymerase chain reaction based diagnosis is extremely useful and should be considered in diagnosing EFE.

Keywords: Endogenous fungal endophthalmitis, molecular diagnosis, uveitis

How to cite this article:
Parambil N, Mani SL, Shahi A, Ramesh R. Challenges in the diagnosis of early endogenous fungal endophthalmitis. Kerala J Ophthalmol 2021;33:205-8

How to cite this URL:
Parambil N, Mani SL, Shahi A, Ramesh R. Challenges in the diagnosis of early endogenous fungal endophthalmitis. Kerala J Ophthalmol [serial online] 2021 [cited 2021 Nov 30];33:205-8. Available from: http://www.kjophthal.com/text.asp?2021/33/2/205/324204

  Introduction Top

The morbidity and mortality rates associated with fungal infections are high, and prevention, diagnosis, and treatment of these infections remain a challenge. Most of the fungal pathogens are opportunistic, and infection becomes invasive only when predisposing factors such as immune deficiency or other underlying severe disease are concomitantly present.[1] Endogenous fungal endophthalmitis (EFE) is most commonly caused by Candida albicans, followed by Aspergillus species, and have a high chance of visual loss and poor visual outcome.[1]

Candida is a commensal but can cause problems when body's defense mechanisms are abridged or when patients undergo certain procedures, such as bladder catheterization or urologic surgery, which increases colonization of mucosal surfaces. The biofilm formation gives protection to the organism from host defense and in developing antifungal drug resistance.[2] Aspergillus species are filamentous fungi commonly found in the natural environment, but when the patient's immunity is weak, the inhaled spores can reach the bloodstream. Through blood, these microbes can get dispersed to other organs,[3] including eye, causing infection.

We report herein two cases of unilateral EFE; first case: candida tropicalis and second case: aspergillus species presented as uveitis in patients with predisposing factors but were otherwise ambulatory and came as outpatients in a standalone tertiary eye hospital. Treatment with systemic steroids worsened the condition, and traditional microbial culture was negative for fungal infection. This report emphasizes the need for encouraging molecular diagnostics in patients having predisposing factors, and not to solely rely on less sensitive traditional diagnostics.[4]

  Case Report Top

Case 1

A 62-year-old male came to our eye hospital with pain, redness, photophobia for 5 days, and decreased vision for 2 days in the left eye. He had a history of portal hypertension and liver cirrhosis and a known diabetic under control. His history was significant for recent hospitalization for urinary tract infection. On examination, the patient's best-corrected visual acuity was 6/6, N6 in the right eye, and 6/12, N8 in the left eye. His left eye was congested, pseudophakic with anterior chamber inflammation with anterior vitreous cells. Fundus view was hazy but within the normal limits barring a few exudates in the inferior anterior vitreous. The fellow eye was completely normal. Diagnosed with intermediate uveitis with anterior spillover, he was treated with topical 1% prednisolone acetate and cycloplegics. Diagnostic workup for uveitis did not reveal any infection or immune-mediated etiology. Hence, he was started on systemic steroids after physician's clearance. However, his vision rapidly dropped to hand movements with the development of hypopyon [Figure 1] and coarse vitreous opacities. B scan ultrasonography showed thickened choroid with hyperechoic vitreous echoes [Figure 2]. A vitreous sample was sent for culture and polymerase chain reaction (PCR) and were positive for Candida tropicalis. Urine culture revealed Candida species, while blood culture was negative. He was treated with intravitreal voriconazole (0.1 mg/0.1 ml), topical 1% voriconazole, and systemic fluconazole 400 mg per day, with no improvement. Core vitrectomy was then performed with intravitreal voriconazole. Systemic fluconazole was continued for 6 weeks, which helped to resolve the infection completely, with no visual improvement.
Figure 1: Pseudophakic left eye showing hypopyon

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Figure 2: B scan ultrasonography showing nasal choroidal detachment and thickened choroid

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Case 2

A 53-year-old male complained of severe pain and loss of vision in his right eye for one month. He was treated as uveitis with topical prednisolone acetate and systemic steroids elsewhere with no improvement and gradual worsening. He had a history of recently detected carcinoma prostate with vertebral metastasis, for which chemotherapy had been deferred because of ocular problems. On examination, his visual acuity was no perception of light in the right eye and 6/6, N6 in the left eye. The eye had a severe fibrinous reaction in the anterior chamber with hypopyon and no view of the fundus. B-scan ultrasonography showed pronounced vitreous opacities and choroidal thickening [Figure 3]. Lensectomy with vitrectomy was performed. The vitreous sample sent for diagnostic microbiology showed fungal hyphae in gram stain and KOH [Figure 4], but the vitreous culture was negative. PCR revealed aspergillus species. The patient was treated with topical, systemic, and intravitreal voriconazole. However, due to persisting pain and insignificant clinical improvement, evisceration was performed and sent for histopathology, which showed fungal granuloma with inflammatory cells.
Figure 3: B scan ultrasonograph of right eye showing vitreous opacities and choroidal thickening

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Figure 4: Cytology preparation from vitreous specimen demonstrating fungal hyphae in (a) gram staining and (b) KOH test

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  Discussion Top

Endophthalmitis is one of the most devastating eye infections and may lead to irreversible blindness in the infected eye within hours or days of symptom onset. The risk factors for EFE include systemic diseases such as diabetes, liver cirrhosis, malignancy, acquired immunodeficiency syndrome, and immunocompromised states.[5] Among all cases of EFE, endogenous C. albicans endophthalmitis is the most common causative organism, representing 75%–80% of the cases, followed closely by Aspergillus species.[6] Classically EFE is suspected in patients who are either febrile or hospitalized. The presentation is commonly bilateral, can be asymmetric, although unilateral cases have been reported.

The patients reported here had risk factors of liver cirrhosis, diabetes mellitus, or malignancy, but they were otherwise ambulatory and were seen as outpatients in a standalone tertiary eye hospital. The examination did not show typical EFE features like posterior pole chorioretinitis lesions.[7] They were treated as idiopathic intermediate uveitis, a differential for EFE.[7] Oral steroids increased inflammation. As ophthalmologists, it is imperative that we investigate risk factors such as recent hospitalization or surgery. Patients, too, may not attach much significance to a recent hospitalization. The ophthalmic signs may be minimal and subtle at presentation.[8] Consequently, a high index of suspicion of fungal endophthalmitis is required in patients with predisposing factors where blood cultures are frequently negative.[4] The rate of misdiagnosis of EFE is as much as 50%.[7] It is, therefore, critical to improve awareness of this condition and to reduce the incidence of its misdiagnosis. Another challenge in treating EFE is the delay in presentation.

By using a PCR-based technique, we were able to rapidly diagnose EFE. PCR-based methods offer the possibility of establishing an etiologic diagnosis in less time than standard cultures[9] and because they can detect very low numbers of DNA copies, they have the potential to be extremely sensitive.[10] In addition, in intraocular infections, the relatively small volume of sample that can be obtained at any one time and the broad range of infectious pathogens make a PCR-based technique very useful.

  Conclusion Top

The subacute nature of early infection in EFE makes early diagnosis challenging. It is, therefore, critical to improving awareness of this condition among ophthalmologists to reduce the incidence of its misdiagnosis. When patients with predisposing factors, hospitalized or ambulatory, present with uveitis, EFE should be considered as a probable differential, especially if the progression of signs and symptoms are seen despite treatment. A PCR based diagnosis of the vitreous specimen is extremely useful, as it can establish a rapid etiologic diagnosis, even in culture-negative patients. This technique could allow the institution of prompt appropriate therapy to improve patient's outcome.

Declaration of patient consent

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


The authors acknowledge Dr. Anil Kumar, Department of Microbiology, Amrita Institute of Medical Science for the help in microbial diagnosis.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Sridhar J, Flynn HW Jr., Kuriyan AE, Miller D, Albini T. Endogenous fungal endophthalmitis: Risk factors, clinical features, and treatment outcomes in mold and yeast infections. J Ophthalmic Inflamm Infect 2013;3:60.  Back to cited text no. 1
Fisher JF, Kavanagh K, Sobel JD, Kauffman CA, Newman CA. Candida urinary tract infection: Pathogenesis. Clin Infect Dis 2011;52 Suppl 6:S437-51.  Back to cited text no. 2
Zhou L, Zhao H, Chen Z, Zhu L. Urinary tract aspergillosis in a patient with chronic kidney disease. BMJ Case Rep 2017;2017:1-3.  Back to cited text no. 3
Liu K, Fang F, Li H. Reliability of vitreous histological detection of pathogenic fungi in the diagnosis of fungal endophthalmitis. Eye (Lond) 2015;29:424-7.  Back to cited text no. 4
Connell PP, O'Neill EC, Fabinyi D, Islam FM, Buttery R, McCombe M, et al. Endogenous endophthalmitis: 10-year experience at a tertiary referral centre. Eye (Lond) 2011;25:66-72.  Back to cited text no. 5
Safneck JR. Endophthalmitis: A review of recent trends. Saudi J Ophthalmol 2012;26:181-9.  Back to cited text no. 6
Ajay EK, Stephen GS, Janet LD, Harry WF. Endogenous endopththalmitis: Bacterial and Fungal. In: Sadda S, editor. Ryan's Retina. 2. 6th ed. London: Elsevier; 2016:1700-1.  Back to cited text no. 7
Oude Lashof AM, Rothova A, Sobel JD, Ruhnke M, Pappas PG, Viscoli C, et al. Ocular manifestations of candidemia. Clin Infect Dis 2011;53:262-8.  Back to cited text no. 8
Hong BK, Lee CS, Van Gelder RN, Garg SJ. Emerging techniques for pathogen discovery in endophthalmitis. Curr Opin Ophthalmol 2015;26:221-5.  Back to cited text no. 9
Sugita S, Kamoi K, Ogawa M, Watanabe K, Shimizu N, Mochizuki M. Detection of Candida and Aspergillus species DNA using broad-range real-time PCR for fungal endophthalmitis. Graefes Arch Clin Exp Ophthalmol 2012;250:391-8.  Back to cited text no. 10


  [Figure 1], [Figure 2], [Figure 3], [Figure 4]


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