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 Table of Contents  
Year : 2021  |  Volume : 1  |  Issue : 2  |  Page : 251-252

Double trouble - Fungal keratitis with concomitant presumed herpes simplex virus keratouveitis

1 Cornea and Anterior Segment Service, The Cornea Institute, LV Prasad Eye Institute, GMR Varalakshmi Campus, Visakhapatnam, Andhra Pradesh, India
2 Ocular Microbiology Service, LV Prasad Eye Institute, GMR Varalakshmi Campus, Visakhapatnam, Andhra Pradesh, India

Date of Submission06-Aug-2020
Date of Acceptance09-Oct-2020
Date of Web Publication01-Apr-2021

Correspondence Address:
Dr. Merle Fernandes
Cornea and Anterior Segment Service, The Cornea Institute, L V Prasad Eye Institute, GMR Varalakshmi Campus, Hanumanthawaka Jn, Visakhapatnam - 530 040, Andhra Pradesh
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijo.IJO_2493_20

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A gentleman with microbiological proven fungal keratitis developed pigmented keratic precipitates with increased anterior chamber reaction on antifungals. Presumed HSV iritis was suspected. Topical steroids were contraindicated. Complete resolution was observed with oral Acyclovir and anti-fungal therapy. A year later acute granulomatous anterior uveitis occurred which responded to topical steroids but progressed to corneal melt with perforation. Following penetrating keratoplasty, he has a clear graft and 20/80 vision. Concomitant HSV iritis with active fungal keratitis is extremely rare. This management dilemma necessitated only oral Acyclovir while continuing anti-fungal therapy while avoiding steroids for HSV kerato-uveitis.

Keywords: Corneal perforation, fungal keratitis, herpes simplex virus, HSV iritis, HSV necrotizing stromal keratitis

How to cite this article:
Kanhere MD, Madduri B, Mohan N, Fernandes M. Double trouble - Fungal keratitis with concomitant presumed herpes simplex virus keratouveitis. Indian J Ophthalmol Case Rep 2021;1:251-2

How to cite this URL:
Kanhere MD, Madduri B, Mohan N, Fernandes M. Double trouble - Fungal keratitis with concomitant presumed herpes simplex virus keratouveitis. Indian J Ophthalmol Case Rep [serial online] 2021 [cited 2021 Sep 24];1:251-2. Available from: https://www.ijoreports.in/text.asp?2021/1/2/251/312381

Microbial keratitis is a sight-threatening condition that requires prompt diagnosis and treatment to prevent unfavorable outcomes. Proper identification of the causative organism is crucial for successful treatment.[1] Mixed infections with more than one bacteria or bacteria and fungus or protozoa, are not common, ranging from 1.9% to 15.8%,[2] and occur as a co-infection or a secondary infection superimposed with the existing microorganism.[3] However, there is sparse literature on mixed infections with herpes simplex virus (HSV) and bacteria or fungus. We would like to report our experience of a case of active fungal keratitis which was complicated by HSV iritis with subsequent recurrence of HSV kerato-uveitis.

  Case Report Top

A 52-year-old male reported with pain and redness in the left eye since 10 days. He denied any history of trauma. Best-corrected vision in the right and left eyes was 20/30 and 20/40 respectively. Examination revealed conjunctival congestion and a peripheral corneal infiltrate with irregular feathery margins adjacent to the limbus with an overlying epithelial defect and diffuse endothelial exudates [Figure 1]a and [Figure 1]b. Fungal filaments were noted on microbiological workup [Figure 1]c and [Figure 1]d. He was started on topical and systemic anti-fungals. On day 12, multiple endothelial keratic precipitates (KP) were noted [Figure 2]a. Suspecting concomitant HSV iritis and since diagnostic tests for HSV (RTPCR) were not available, oral Acyclovir 400 mg 5 times daily was started. Subsequently, progressive thinning developed, and cyanoacrylate glue was applied on day 19.
Figure 1: (a) Peripheral corneal infiltrate with feathery borders, adjacent to the temporal limbus with diffuse endothelial exudates and (b) large overlying epithelial defect seen in cobalt blue filter after fluorescein staining. (c) Thin, septate, hyaline branching fungal filaments on Gram's stain (oil immersion, 1000x). (d) Multiple septate branching fungal filaments seen with 10% Potassium Hydroxide (KOH) - Calcofluor white mount using a fluorescence microscope (400x)

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Figure 2: (a) Whitish corneal infiltrate, with multiple endothelial keratic precipitates, surrounding stromal edeme and cellular reaction, radiating Descemet's membrane folds and a streak hypopyon. (b) Vascularized corneal scar with multiple keratic precipitates on the endothelium with no corneal edema and absence of cellular reaction in the stroma. (c) Vascularized corneal scar with central corneal melt and 4 mm perforation with pseudocornea formation and a flat anterior chamber. (d) Clear graft with well apposed graft host junction, intact sutures and vascularized host bed post therapeutic penetrating keratoplasty

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Apparent resolution was noted in 2 months, with thinning, scarring, vascularization, and endothelial pigments. Anti-fungals were stopped. However, 2 weeks later, these were restarted due to thinning, keratic precipitates, radiating DM folds, vascularization, diffuse stromal edema, and a 2.7 mm hypopyon. Gradual improvement was seen over 2 months, and tissue adhesive was removed. By 6 months, the fungal keratitis completely resolved and a vascularized adherent leucoma along with overlying spheroidal degeneration was seen. A year later, he presented with multiple granulomatous KPs along with 3+ cells in the anterior chamber [Figure 2]b. In the absence of diagnostic tests for HSV, a differential diagnosis of presumed HSV iritis or acute granulomatous anterior uveitis was considered. Tapering doses of topical steroids were prescribed.

A month later, his vision dropped to hand movements with a perforation and pseudocornea formation [Figure 2]c. This was diagnosed as HSV necrotizing stromal keratitis, for which a therapeutic penetrating keratoplasty was done [Figure 2]d. Histopathology of the half corneal button was inconclusive. He recovered well with vision improving to 20/80 with a clear graft. He is on prophylactic oral Acyclovir with topical steroids.

  Discussion Top

Fungal keratitis comprises almost 40% of microbial keratitis in the tropics with cure rates of close to 65%,[4] however fungal polymicrobial infections had a poorer outcome compared to fungal keratitis.[2] We encountered a case of fungal keratitis which developed co-existent HSV iritis posing a significant challenge in management.

HSV keratitis is usually a clinical diagnosis.[5] Laboratory investigations include viral cultures, immunofluorescence assay for HSV antigen, and polymerase chain reaction for HSV DNA.[6] These tests were not available in our city and hence could not be done for our patient. The onset of large endothelial keratic precipitates while responding to anti-fungal treatment led to a diagnosis of concomitant HSV iritis. Following complete resolution, a year later, recurrence of the keratic precipitates in the absence of corneal infiltrate followed by corneal melt, confirmed the suspected HSV etiology. The literature on HSV keratitis and fungal keratitis is sparse and mainly on healed HSV keratitis followed by fungal keratitis.[7],[8],[9] One report of fungal keratitis in a setting of prior healed HSV keratitis was managed by multiple transplants.[7] Another was of presumed HSV keratitis with fungal keratitis, though no HSV recurrences were documented.[9] Toriyama et al.[8] described a case of healed HSV keratitis which developed Candida keratitis which resolved completely. Subsequent recurrence was Candida culture negative with Acyclovir resistant HSV necrotizing keratitis proven by a polymerase chain reaction and managed with Triflurothymidine.[8] Our patient developed fungal keratitis and concomitant HSV iritis which subsequently recurred and resulted in a corneal melt with perforation. Management of this condition was challenging since steroids play an important role in reducing inflammation in HSV keratitis[10] and are detrimental if used in fungal keratitis. During co-existing active fungal infection with HSV keratitis or any other form, oral acyclovir should be used and steroids, for managing the immune component, are deferred until complete resolution of fungal infection. It is unclear what triggered HSV reactivation in this setting however it is likely that the inflammatory cytokines (ex Interleukin 6) released by macrophages and polymorphonuclear neutrophils in fungal keratitis[11] could have reactivated the latent HSV virus in the cornea or ganglion cells.[12]

  Conclusion Top

In conclusion, the inflammatory milieu in fungal keratitis may trigger reactivation of HSV keratitis, and may be suspected if pigmented granulomatous keratic precipitates develop in a fungal keratitis responding to therapy. Steroids are withheld until the complete resolution of fungal keratitis.

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.

Financial support and sponsorship

This work was supported by Hyderabad Eye Research Foundation.

Conflicts of interest

There are no conflicts of interest.

  References Top

Alkatan HM, Al-Essa RS. Challenges in the diagnosis of microbial keratitis: A detailed review with update and general guidelines. Saudi J Ophthalmol 2019;33:268-76.  Back to cited text no. 1
Fernandes M, Vira D, Dey M, Tanzin T, Kumar N, Sharma S. Comparison between polymicrobial and fungal keratitis: Clinical features, risk factors and outcome. Am J Ophthalmol 2015;160:873-81.  Back to cited text no. 2
Ahn M, Yoon KC, Ryu SK, Cho NC, You IC. Clinical aspects and prognosis of mixed microbial (bacterial and fungal) keratitis. Cornea 2011;30:409-13.  Back to cited text no. 3
Gopinathan U, Sharma S, Garg P, Rao GN. Review of epidemiological features, microbiological diagnosis and outcome of microbial keratitis: Experience of over a decade. Ind J Ophthalmol 2009;57:273-9.  Back to cited text no. 4
Yamamoto S, Shimomura Y, Kinoshita S, Nishida K, Yamamoto R, Tano Y. Detection of herpes simplex virus DNA in human tear film by the polymerase chain reaction. Am J Ophthalmol 1994;117:160-3.  Back to cited text no. 5
Farhatullah S, Kaza S, Athmanathan S, Garg P, Reddy SB, Sharma S. Diagnosis of herpes simplex virus-1 keratitis using Giemsa stain, immunofluorescence assay, and polymerase chain reaction assay on corneal scrapings. Br J Ophthalmol 2004;88:142-4.  Back to cited text no. 6
Malecha MA, Tarigopula S, Malecha MJ. Successful treatment of Paecilomyces lilacinus keratitis in a patient with a history of herpes simplex virus keratitis. Cornea 2006;25:1240-2.  Back to cited text no. 7
Toriyama K, Inoue T, Suzuki T, Kobayashi T, Ohashi Y. Necrotizing keratitis caused by acyclovir-resistant herpes simplex virus. Case Rep Ophthalmol 2014;5:325-8.  Back to cited text no. 8
Lin TT, Wei RH, Yang RB, Huang Y, Zhang C, Ning YX, et al. Fungal keratitis associated with viral keratitis. Chin Med J (Engl). 2015;128:2823-5.  Back to cited text no. 9
Austin A, Lietman T, Rose-Nussbaumer J. Update on the management of infectious keratitis. Ophthalmology 2017;124:1678-89.  Back to cited text no. 10
Zhong W, Yin H, Xie L. Expression and potential role of inflammatory cytokines in experimental keratomycosis. Mol Vis 2009;15:1303-11.  Back to cited text no. 11
Al-Dujaili LK, Clerkin PP, Clement C, McFerrin HE, Bhattacharjee PS, Varnell ED, et al. Ocular simplex virus: how are latency, reactivation, recurrent disease and therapy interrelated? Future Microbiol 2011;6: 877-907.  Back to cited text no. 12


  [Figure 1], [Figure 2]


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