Refractory keratitis – A microbial cocktail or infectious enigma?

Ritika Mukhija; Abhijeet Beniwal; Kumar Kartikay Rajaura; Seema Kashyap; Radhika Tandon

doi:10.4103/IJO.IJO_3151_22

CASE REPORT

Year : 2023 | Volume : 3 | Issue : 2 | Page : 283-284

Refractory keratitis – A microbial cocktail or infectious enigma?

Ritika Mukhija¹, Abhijeet Beniwal², Kumar Kartikay Rajaura², Seema Kashyap³, Radhika Tandon²
¹ Cornea and Anterior Segment Fellow, Sussex Eye Hospital, United Kingdom
² Department of Ophthalmology, RP Centre for Ophthalmic Sciences, AIIMS, New Delhi, India
³ Department of Pathology, Ocular Pathology Section, RP Centre for Ophthalmic Sciences, AIIMS, New Delhi, India

Date of Submission	01-Dec-2022
Date of Acceptance	09-Feb-2023
Date of Web Publication	28-Apr-2023

Correspondence Address:
Radhika Tandon
Department of Ophthalmology, RP Centre for Ophthalmic Sciences, AIIMS, New Delhi
India

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/IJO.IJO_3151_22

Abstract

A 39-year-old adult male presented to the outpatient department of a tertiary care eye hospital with keratouveitis and responded to treatment for viral keratouveitis. On a follow-up, the clinically ulcer suggested fungal keratitis, which was supported by in vivo confocal scan. The episode was managed with antifungal therapy. Tear film polymerase chain reaction (PCR) found cytomegalovirus DNA. Repeated episodes were likewise managed, but ultimately there was stromal scarring which required penetrating keratoplasty. Surprisingly, histopathology of specimen showed microsporidia. Till last follow-up, the graft was clear and the patient had 20/40 vision. Microsporidia should be a differential in refractory stromal keratitis.

Keywords: Histopathology, microsporidia, penetrating keratoplasty

How to cite this article:
Mukhija R, Beniwal A, Rajaura KK, Kashyap S, Tandon R. Refractory keratitis – A microbial cocktail or infectious enigma?. Indian J Ophthalmol Case Rep 2023;3:283-4

How to cite this URL:
Mukhija R, Beniwal A, Rajaura KK, Kashyap S, Tandon R. Refractory keratitis – A microbial cocktail or infectious enigma?. Indian J Ophthalmol Case Rep [serial online] 2023 [cited 2023 Jun 2];3:283-4. Available from: https://www.ijoreports.in/text.asp?2023/3/2/283/375026

Microsporidia are obligate intracellular spore-forming parasites related to fungi. Immunocompromised people are at greater risk, but it infects immunocompetent too. In cornea, it causes keratoconjunctivitis and rarely stromal keratitis. The organism can be cultured in tissue media only, is easily missed on routine scrapings, and in vivo confoscan can be misleading due to its small size.

Case Report

A 39-year-old male patient presented to the eye department with sudden onset painful blurring of vision in his right eye of 5 days duration. On examination, the right eye had visual acuity of 20/30 with normal intraocular pressure and clinical appearance in keeping with herpetic disciform keratitis. The left eye was exotropic with hand movement vision, relative afferent pupillary defect, and optic atrophy, likely nutritional. He was managed with oral acyclovir and topical steroids, which resulted in the resolution of symptoms and recovery of visual acuity. Subsequent recurrences were managed with the same regimen.

On follow-up, based on the clinical appearance of dry infiltrates with feathery margins on a background of prolonged use of topical steroids, fungal keratitis was suspected, and in-vivo confocal microscopy was requested, which was suggestive of dendritic cells [Figure 1]a and [Figure 1]b. The patient was thereafter treated with topical natamycin 5%, which resulted in the resolution of keratitis over the next few weeks.

Figure 1: (a) Active keratitis phase with an epithelial defect. (b) In vivo confocal microscopy suggestive of fungal hyphae. (c) Stromal scarring, before the patient was taken for penetrating keratoplasty for visual rehabilitation. (d) Postoperative clinical picture showing clear graft

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The waxing and waning course continued with a further few recurrences, which were treated using antifungal and antivirals as per the clinical scenario. A tear film sample was sent for viral PCR testing, which was interestingly found to be positive for cytomegalovirus DNA and negative for herpes simplex and herpes zoster virus. Baseline blood tests were also requested and revealed normal full blood count, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), urea, and electrolytes, and fasting blood sugar and HIV 1 and 2 and venereal disease research laboratory (VDRL) serology were negative. Patient's vision invariably improved after every episode; however, with multiple episodes, the extent of corneal scarring increased, and visual acuity reduced from a baseline of 20/30 to finger counting at 2–3 m. The patient finally underwent penetrating keratoplasty for visual rehabilitation [Figure 1]c and [Figure 1]d, and histopathology of his cornea revealed numerous tiny oval organisms positive for acid-fast stain, consistent with a diagnosis of microsporidial stromal keratitis [Figure 2]. He had no further recurrence with best-corrected visual acuity of 20/40 till the last follow-up visit 6 months after surgery.

Figure 2: (a) Microphotograph showing numerous oval spores of microsporidia in the mid and deep corneal stroma (H and E stain × 20). (b) Corneal button showing oval spores of microsporidia which appear red in color, some having darkly stained bands within them (1% acid-fast stain ×1000)

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Discussion

Ashton et al.^[1] in 1973 reported refractile structures in the host corneal button with prominent polar vacuole and central banded nucleus.

Font et al.^[2] reported a case of persistent stromal keratitis, treated with various agents. Finally, a corneal punch biopsy led to the diagnosis of microsporidia.

Another patient was reported by the same author^[3] with 4-month-old history. Scrapings were inconclusive. The patient was not responsive to treatment and cornea perforated, requiring penetrating keratoplasty. Only in histopathology of the corneal button diagnosis of microsporidia could be made.

A retrospective case series^[4] of 34 cases of microsporidial keratitis revealed that 38.2% cases were initially diagnosed as viral keratitis and 35.3% cases were initially diagnosed as fungal keratitis, with only 14.7% cases correctly diagnosed as microsporidial etiology.

Confocal imaging further added to the enigma as it was suggestive of fungal keratitis. Intracellular dots were not seen in confoscan, but hyphae-like structures were seen. The pathologist may also miss it since it is a tiny organism, unless there is a high index of suspicion. Another problem in diagnosis is that the organism needs tissue cultures to grow.

It is interesting that our patient responded very well to treatment with antiviral and antifungal for almost 1 year since the first episode. Authors believe that early on the disease course, topical steroids provided symptomatic relief and reduced inflammation, and during the later course, antifuingals may have played a role as they may be effective against microsporidia.

Few case reports of successful medical treatment of microsporidia exist, using topical voriconazole and oral albendazole^[5] and using 0.02% polyhexamethylene biguanide,^[6] but ultimately significant scarring will require penetrating keratoplasty. Hence, it is important to suspect microsporidia early on in refractory keratitis cases. For instance, Coca et al. reported a case of corneal ulcer in a construction worker, which worsened on cefazolin despite cultures reporting Streptococcus pneumoniae sensitive to the drug. Fortunately, multiple punch biopsies were taken, and one with a deeper stroma revealed microsporidial spores. The patient responded to topical voriconazole and oral itraconazole.^[7]

In the recalcitrant keratitis case described by Font et al.,^[2] oral albendazole 400 mg thrice daily and topical fumagillin 3 mg/ml hourly, then tapering dose was started, but there was no response keratoplasty needed to control infection. Another refractory stromal keratitis by the same author also underwent penetrating keratoplasty, and only then, the infection was cured.^[3]

Interestingly, in our case, the penetrating keratoplasty was done in quiescent phase, and accidently microsporidia were revealed. This is probably the first such case where optical penetrating keratoplasty revealed microsporidia. This case highlights an atypical presentation of microsporidial keratitis, which is a relatively rare cause of microbial keratitis. It is important to consider these organisms as a possible differential in stromal keratitis.

Conclusion

Microsporidia should be considered a differential in refractory stromal keratitis not responding to conventional treatment. Microsporidia are an important cause of disease in both HIV and non-HIV patients with or without immunosuppression. In healthy persons, they can mimic herpetic keratitis with a history of recurrent redness, pain, photophobia, watering, and decreased vision. A high index of suspicion is needed for prompt diagnosis and treatment.

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

Nil.

Conflicts of interest

There are no conflicts of interest.

References

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