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   Table of Contents      
Year : 2020  |  Volume : 68  |  Issue : 7  |  Page : 1461-1463

Conidiobolus, a hitherto unidentified pathogen in microbial keratitis

1 Cornea and Refractive Surgery, Aravind Eye Hospital and Post-Graduate Institute of Ophthalmology, Coimbatore, Tamil Nadu, India
2 Cornea and Refractive Surgery, Sri Venkateswara Aravind Eye Hospital, Tirupati, Andhra Pradesh, India
3 Aravind Eye Hospital and Post-Graduate Institute of Ophthalmology, Coimbatore, Tamil Nadu, India
4 Division of Laboratory Services, Aravind Eye Hospital and Post-Graduate Institute of Ophthalmology, Coimbatore, Tamil Nadu, India

Date of Submission11-Aug-2019
Date of Acceptance31-Jan-2020
Date of Web Publication25-Jun-2020

Correspondence Address:
Dr. Anita Raghavan
Aravind Eye Hospital and Post-Graduate Institute of Ophthalmology, Coimbatore - 641 014, Tamil Nadu
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijo.IJO_1436_19

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Fungal infections are a significantly increasing cause of ocular and systemic morbidity; the vast majority of cases being ascribed to a handful of species. Fungal keratitis, unlike systemic infections, usually occur in immunocompetent individuals. Rarely, systemic infections can be associated with ocular involvement (e.g., Candida, Mucor, Pythium), or a fungus that predominantly causes systemic disease can affect the eye. One such fungus is Conidiobolus which is known to cause muco-cutaneous infections. We report the identification and successful treatment of a case of Conidiobolus corneal ulcer in an immunocompetent individual, who had no co-existing muco-cutaneous disease. Identification of this particular fungus and awareness of its potential to cause systemic disease is especially relevant, given its potential for chronic indolent infection of the subcutaneous tissues. To the best of our knowledge, this is the first reported case of a Conidiobolus corneal ulcer.

Keywords: Conidiobolus, diagnosis, keratitis, treatment

How to cite this article:
Raghavan A, Balaka B, Venkatapathy N, Rammohan R. Conidiobolus, a hitherto unidentified pathogen in microbial keratitis. Indian J Ophthalmol 2020;68:1461-3

How to cite this URL:
Raghavan A, Balaka B, Venkatapathy N, Rammohan R. Conidiobolus, a hitherto unidentified pathogen in microbial keratitis. Indian J Ophthalmol [serial online] 2020 [cited 2023 May 29];68:1461-3. Available from: https://journals.lww.com/ijo/pages/default.aspx/text.asp?2020/68/7/1461/287484

Conidiobolus spp. are ubiquitous, cosmopolitan fungi, which occasionally cause human naso-facial mucocutaneous or subcutaneous infections.[1],[2] In the immunocompetent host, it causes a progressive mass lesion over the nasal submucosa, nose, eyelids, and over the malar and frontal regions of the face. Occasionally, it can involve the nasolacrimal duct and orbit.[3],[4] Although many facial and maxillary sinus cases have involved the lower eyelid, or abut the orbital rim, direct ocular involvement of Conidiobolus has not been reported (except for one case of lacrimal sac tumor [5]). Reported infections have mainly been from West Africa, India, Central and South America.[1],[6]

Stages of the disease may be classified into:[7]

  • Atypical - infection of the facial region (e.g., orbit) other than the nose and maxillary sinus, or in non facial cutaneous sites, diagnosed within 11 months after suspected onset;
  • Early Disease – diagnosed before the occurrence of characteristic nodule at the nostril;
  • Intermediate Disease; or
  • Late Disease

  Case Report Top

We report the first case, worldwide, of a Conidiobolus infection, presenting only as a keratitis. A 61-year-old male presented with complaints of pain, watering, and redness of the left eye of 5 days' duration. Diagnosed elsewhere as a fungal corneal infiltrate, he was using Natamycin 5% and Moxifloxacin 0.5% eye drops hourly, Homatropine 2% eye drops twice daily, and Tobramycin eye ointment. He had no prior history of ocular disease, was in apparently good health, albeit with well-controlled hypertension. There was no history of trauma, exposure to foreign body, or upper respiratory tract infections; no recent history of nasal blockage, sinusitis; and no evidence of skin infections or peri-ocular lesions.

His uncorrected visual acuity was 6/24 in the right eye and 5/60 in the left eye. Slit lamp biomicroscopy of the right eye was within normal limits, while that of the left eye revealed normal lid contour, with conjunctival congestion. An anterior stromal greyish-white infiltrate with ulceration (4.5 mm × 3.5 mm) and Descemet's membrane folds, was seen in the inferonasal quadrant of the cornea. [Figure 1]a There was 1+ AC flare, and the lens was cataractous. The initial diagnosis was 'mixed infection' (the ulcer had features of bacterial as well fungal keratitis).In vivo confocal microscopy (IVCM) evaluation revealed mid-stromal hyper-reflective, branched, linear structures suggestive of fungal hyphae [Figure 1]b.
Figure 1: (a) Para-central corneal infiltrate with Descemet's folds. (b) Confocal biomicroscopy showing mid-stromal hyper-reflective, branched, hyphae (Heidelberg Retinal Tomography 3, with Rostock Cornea Module). (c): Gram stain showing irregularly wide, sparsely septate hyphae (100 × Oil Immersion). (d) Dry glabrous colony (Sabouraud Dextrose Agar; 25°C). (e) Blue-stained globose sporangioles (Lacto-Phenol Cotton-Blue; 20×). (f) Blue-stained globose sporangioles with typical papillae (Lacto-Phenol Cotton-Blue; 40×)

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Corneal scrapings from the infiltrate were inoculated onto Blood Agar (BA), Sabouraud Dextrose Agar (SDA), and Non Nutrient Agar with E. coli overlay. Additional scrapings were taken for smears. The 10% potassium hydroxide (KOH) mount was positive for wide, hyaline, sparsely septate hyphae, and the Gram staining showed poorly staining wide, non septate, branching hyphae [Figure 1]c.

Based on smears and pending cultures, the patient was started on hourly Natamycin 5% and Voriconazole 1% eye drops. Only fungal growth was noted (rapid growth on BA, 24-48 hrs @ 37°C; slower growth on SDA @ 25°C) - starting as dry glabrous, powdery-white with sparse aerial mycelium, becoming light brown with a pale reverse [Figure 1]d. Lactophenol blue mounts revealed broad irregular hyaline hyphae with rare septation, and large blue-stained globose sporangioles (conidia) with typical basal papilla [Figure 1]e and [Figure 1]f; rare thick-walled zygospores (without conjugation beaks) were also seen. There were no villose or multiplicative secondary conidia. Based on these macro- and micro-morphological criteria, the isolate was identified as Conidiobolus incongruus.

Since this uncommon fungus is usually associated with morbid infections of the subcutaneous tissue or sinuses, the patient was referred to a physician for systemic evaluation, and to an oto-rhino-laryngologist. Clinical evaluation was normal; computerized tomography showed no sinus abnormalities, except for a right concha bullosa with focal paradoxical curve of right middle turbinate. White blood cell count was 5200/mm 3 (51% neutrophils); ESR was 07 mm; serology was negative for Hepatitis B surface antigen, HCV, and Human Immunodeficiency Virus (HIV).

Most cases reported from India have been Atypical disease, where Amphotericin-B has been used (in combination with other anti-fungals).[7],[8],[9] Therefore, Natamycin was replaced with Amphotericin-B, 0.15% hourly. Itraconazole eye ointment 1% t.i.d. and tablet Ketoconazole were added, while Voriconazole was continued. Over the next 2 weeks, the infiltrate healed slowly, and 30 days after institution of tapered therapy it had resolved completely. Corrected visual acuity improved to 6/9 N8.

  Discussion Top

Conidiobolus spp. and Basidiobolus sp. belong to Class Zygomycetes.[1] Conidiobolomycosis or rhino-facial entomophthoramycosis invariably involves the mucosa and subcutaneous tissues of the nose. They are more predominantly observed as a sinusitis in adult males, spreading into subcutaneous fat. Sources are contaminated water, soil, leaf litter, or via insect vectors.[1] Rare cases of disseminated infection in immunocompromised hosts have been reported.[1] As of 2015, only 198 well-documented cases of Conidiobolomycosis have been reported.[7] Except for one case of lacrimal sac tumor (secondary to traumatic entry of soil into the eye),[5] no cases of purely ocular involvement have been reported. A rare occurrence in India, about 40 cases of Conidiobolomycosis have been reported.[10]

Conidiobolomycosis is very difficult to treat, and Itraconazole or potassium iodide has usually been first-line choices. Combination of anti-fungals (potassium iodide, Miconazole, Co-trimoxazole, Ketoconazole, Itraconazole, Amphotericin-B, Terbinafine) have been used successfully.[2],[6],[7],[8],[9] In our case, the Conidiobolus infection was restricted to the cornea, the ulcer healed slowly but completely within a month (with Amphotericin-B, Voriconazole, and Ketoconazole), with no signs or symptoms of extraocular spread.

This may be the first reported incident of Conidiobolus keratitis. Morphologically, in smears, Conidiobolus looks similar to Mucor or Rhizopus, exhibiting wide, ribbon-like aseptate hyaline hyphae. Although, in culture the colony grows rapidly, there is absence of aerial mycelia and most often remains flattish, waxy or glabrous. The presence of unique globose conidia with characteristic prominent papillae, were confirmatory for Conidiobolus sp.

Given the potential for serious sinus and maxillo-facial infections, and the need for systemic anti-fungal therapy, identification of the fungus is particularly relevant. More importantly, the drug of choice is probably Amphotericin-B, and not the more commonly administered Natamycin. Our patient did not respond to the administration of Natamycin and Voriconazole, but did so only after the addition of Amphotericin-B.

  Conclusion Top

To the best of our knowledge, this is the first reported case of a Conidiobolus corneal ulcer.

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.

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Conflicts of interest

There are no conflicts of interest.

  References Top

Mendoza L, Vilela R, Voelz K, Ibrahim AS, Voigt K, Lee SC. Human fungal pathogens of mucorales and entomophthorales. Cold Spring Harb Perspect Med 2015;5. pii: a019562. doi: 10.1101/cshperspect.a019562.  Back to cited text no. 1
Prabhu RM, and Patel R. Mucormycosis and entomophthoramycosis: A review of the clinical manifestations, diagnosis and treatment. Clin Microbiol Infect 2004;10:31-47.  Back to cited text no. 2
Ramesh A, Deka RC, Vijayaraghavan M, Ray R, Kabra SK, Rakesh K, et al. Entomophthoromycosis of the nose and paranasal sinus. Indian J Pediatr 2000;67:307-10.  Back to cited text no. 3
Michael RC, Michael JS, Mathews MS, Rupa V. Unusual presentation of entomophthoromycosis. Indian J Med Microbiol 2009;27:156-8.  Back to cited text no. 4
[PUBMED]  [Full text]  
Bittencourt AL, Marback R, Nossa LMB. Mucocutaneous entomoptharomycosis acquired by conjunctival inoculation of the fungus. Am J Trop Med Hyg 2006;75:936-8.  Back to cited text no. 5
Spellberg B, Edwards J Jr, Ibrahim A. Novel perspectives on mucormycosis: Pathophysiology, presentation, and management. Clin Microbiol Rev 2005;18:556-69.  Back to cited text no. 6
Blumentrath CG, Grobusch MP, Matsiégui PB, Pahlke F, Zoleko-Manego R, Nzenze-Aféne S, et al. Classification of rhinoentomophthoromycosis into atypical, early, intermediate, and late disease: A proposal. PLoS Negl Trop Dis 2015;9:e0003984.  Back to cited text no. 7
Gugnani HC. Entomophthoromycosis due to conidiobolus. Eur J Epidemiol 1992;8:391-6.  Back to cited text no. 8
Foss NT, Rocha MR, Lima VT, Velludo MA, Roselino AM. Entomophthoramycosis: Therapeutic success by using amphotericin B and terbinafine. Dermatology 1996;193:258-60.  Back to cited text no. 9
Chowdary A, Randhawa HS, Khan ZU, Ahmad S, Khanna G, Gupta R, et al. Rhinoentomophthoromycosis due to Conidiobolus coronatus. A case report and an overview of the disease in India. Med Mycol 2010;48:870-9.  Back to cited text no. 10


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