Abstract
Purpose
Acanthamoeba and fungal infections can be recalcitrant to therapy – more so when the deeper layers of the corneas are involved. We describe the diagnosis and successful management strategies employed in a case of deep keratitis due to co-infection with Acanthamoeba and Cladosporium sp.
Observations
Once the diagnosis of co-infection with both Acanthamoeba and Cladosporium was made, treatment was initiated with a combination of PHMB, chlorhexidine, natamycin, and voriconazole; to which the response was favorable. Signs of relapse with spread of the infection to the deeper plane and the presence of endothelial exudates were noted at 5 weeks. This was attributed to poor compliance. Though the response to re-initiation of therapy under direct supervision was once again favorable; it was only after the introduction of intrastromal voriconazole repeated at timely intervals that rapid and complete resolution was obtained.
Conclusions
Severe keratitis due to fungi or Acanthamoeba very often requires surgical intervention. Complete resolution with medical therapy was obtained only after the introduction of intrastromal voriconazole; thereby avoiding a therapeutic keratoplasty. The addition of voriconzole both topically and particularly intrastromally facilitated faster resolution as well as restricted the duration of therapy with more toxic drugs such as phmb and chlorhexidine.
1
Introduction
The management of fungal keratitis can be challenging, with size and depth of the lesion being important predictors of successful medical management. Superficial keratomycosis responds fairly well (albeit with some exceptions) to topical antifungal therapy; natamycin 5% suspension being the drug of choice for most filamentous fungal keratitis. This approach works in most circumstances considering that Fusarium species is the most commonly identified fungus in South India. Treatment of deep fungal keratitis however remains challenging, irrespective of the causative organism. The uses of broad spectrum antifungal agents such as voriconazole, as well as alternate routes of administration such as intracorneal injections, have been used to treat deep or resistant fungal keratitis. , ,
Cladosporium spp are rare causes of fungal keratitis. They are Ascomycota fungi that are commonly found on plants. Indoors, they can be found on moist surfaces. Cladosporium is a fairly uncommon cause of keratitis with the incidence being variably reported from 1.3% to 3%. , Guidelines for the management of Cladosporium keratitis are scarce. Although this fungus is known to be refractory to topical natamycin and systemic antifungals, it has been reported that voriconazole could be effective in the treatment of Cladosporium keratitis.
Acanthamoeba keratitis is also a difficult to treat infection, especially when the deeper layers of the cornea are involved. Although Acanthamoeba and fungi share similar environments, and are widely distributed in nature, coexistent Acanthamoeba and fungal infections in non-contact lens users are considered scarce, with documentation of a case each by Gupta and Lin, respectively. , However, it is increasingly evident that co-infections with Acanthamoeba and fungi can occur, and more importantly, can also present with features traditionally considered exclusive to bacterial, fungal, or Acanthamoeba keratitis.
This case report discusses the successful management of an advanced case of combined Cladosporium and Acanthamoeba keratitis. To the best of our knowledge, only 2 cases of successful medical therapy of co-infection involving Acanthamoeba and fungi in non-contact lens users have been described. ,
1.1
Case report
A 36-year old male in apparently good health was seen 3 weeks after exposure to cement particles in the right eye. He reported vigorous washing of the eye with tap water and subsequent consultation with an ophthalmologist who treated him for suspected viral keratitis with a combination of topical ganciclovir eye ointment and topical steroids. Since there was no symptomatic relief over a period of 8 days, the patient discontinued his medications; he then presented to us 2 weeks later with complaints of increasing redness, pain and defective vision in his right eye.
On examination, his best corrected visual acuity in the right eye was 6/60 and 6/6 in the left eye. Slit-lamp examination of the right eye was significant for circumcorneal congestion, and the presence of a central corneal ring infiltrate 5mm × 7.6mm in diameter with an overlying epithelial defect 8.3mm × 8mm in size. The infiltrate extended up to the mid-stroma and was associated with deep stromal edema and Descemet’s membrane folds. The anterior chamber was devoid of any hypopyon, had 2+ cells, and was of normal depth. The lens was clear. Digitally, the intra-ocular pressure was normal in the right eye. Slit-lamp evaluation of the left eye was within normal limits. Given the combination of a ring infiltrate with stromal edema, the differential diagnosis included Acanthamoeba keratitis, viral keratitis, and co-infection with Acanthamoeba and fungus.
Confocal microscopy using Heidelberg Retinal Tomograph 3 (with Rostock Cornea Module) was carried out – which showed multiple cysts. The corneal infiltrate was then scraped and inoculated onto blood agar, non-nutrient agar, and potato dextrose agar. Additional scrapings were taken for smears for direct microscopy. The Gram stain as well as the potassium hydroxide mount were positive for hyphae. Accordingly, therapy was initiated with polyhexamethylene biguanide (PHMB) 0.04%, chlorhexidine 0.04%, and natamycin 5% eye drops on an hourly basis, along with homatropine hydrobromide eye drops twice daily. Given the presence of two organisms as well as the prior history of treatment with steroids, he was advised to undergo treatment as an in-patient. Four days later, Acanthamoeba trophozoites were identified on the non-nutrient agar. A day later fungal colonies were detected on the agar plates; subsequently identified as Cladosporium species. Topical voriconazole drops (Vozole 1%, Aurolab, Madurai, India) was added to the treatment regimen once cultures were positive for fungi. The initial response to the therapy was good with peripheral scarring and resolution of the epithelial defect. The patient was discharged with recommendations to continue the same medications, i.e. hourly PHMB, chlorhexidine, natamycin, and voriconazole. When seen on follow-up over the next few weeks the infiltrate continued to reduce in size. However, when reviewed 5 weeks from the onset of treatment, and due to poor compliance (the patient had discontinued his hourly drops since he claimed to have felt much better), his vision had deteriorated to hand movements and his condition had worsened with involvement of the deep stroma and recurrence of the epithelial defect. The peripheral region remained scarred, and pigmented keratic precipitates were noted on the back of cornea. Endothelial exudates were also noted. The patient was re-admitted and therapy continued with hourly PHMB (0.04%), natamycin 5%, and voriconazole 1% eye drops. Chlorhexidine was withheld due to concerns regarding toxicity. Oral ketoconazole 200mg twice-a-day was added.
Approximately 10 days after re-admission, there was an anterior-to-deep stromal infiltrate measuring 4.4mm × 3.9mm with an overlying epithelial defect; peripheral scarring was also noted. Given the recalcitrance of the central lesion to therapy, intrastromal voriconazole 50 μg/0.1ml. (Vozole PF, Aurolab, Madurai, India) was administered under topical anesthesia. There was significant improvement in a week’s time with the infiltrate reducing to 2.8mm X X 3.3mm. An increase in intraocular pressure necessitated the addition of topical anti-glaucoma medication. He was once again discharged. The second intrastromal injection was repeated 10 days later with subsequent injections spaced approximately a week apart. Approximately 50 days after presentation, medications were tapered to 8 times a day. When the 5th injection was administered, the surface had healed with a small residual infiltrate in the anterior stroma. All-in-all he received 6 injections of intrastromal voriconazole. Rapid taper of topical medications was instituted after the last dose of intrastromal voriconazole (13weeks after starting therapy). Natamycin was stopped a month later, followed by PHMB 2 months later. Topical voriconazole eye drops was discontinued after another month. Uncorrected visual acuity had improved to 6/36 ( Fig. 1 a, b, 1c).
