Post-coronavirus disease bilateral endogenous fungal endophthalmitis with full visual acuity recovery: a case report

Abstract

Background

Increasing reports and case series describe cases of endogenous endophthalmitis (EE) following severe acute respiratory syndrome coronavirus 2 infection. Endogenous endophthalmitis is a severe ophthalmologic pathology caused by bacteremic or fungemic seeding of the eye, often in immunocompromised patients. Delayed treatment can lead to permanent visual impairment. We report the diagnosis and management of a case of fungal endogenous endophthalmitis with voriconazole and surgery that led to complete visual acuity recovery.

Case presentation

We present a case of post-coronavirus disease 2019 bilateral fungal endogenous endophthalmitis due to Candida albicans in a 64-year-old Caucasian male patient. Upon arrival, he had a visual acuity of 6/200 and slow pupillary light reflex. Ocular examination revealed conjunctival hyperemia, keratic precipitates, moderate vitritis with cotton wool spots, intraretinal hemorrhages, and foci of chorioretinitis.

Conclusion

Treatment for endogenous endophthalmitis is often delayed because cultures frequently yield negative results. Early diagnosis is key for better outcomes in endogenous endophthalmitis. This case highlights the need for a high index of suspicion for endogenous endophthalmitis in patients with coronavirus disease 2019 to ensure early diagnosis and timely intervention.

Background

Opportunistic infections have been widely reported in patients who have required hospitalization and prolonged corticosteroid use during and after coronavirus disease 2019 (COVID-19) infection [1]. Ocular involvement is not uncommon and several infectious complications have been described, including fungal endogenous endophthalmitis (EE) [2, 3], although diagnosis can be challenging. Fungal EE is an ophthalmologic pathology associated with various fungi such as Candida spp. or Aspergillus spp., and has been reported recently in patients post-COVID diagnosis, often leading to permanent visual acuity (VA) impairment [4–6]. We describe the first case of endogenous endophthalmitis due to Candida albicans reported in Venezuela, which was successfully treated with intraocular and systemic voriconazole and vitrectomy with successful recovery of visual acuity (20/25).

Case presentation

A 64-year-old Caucasian male patient with a history of hypertension presented with a 7-day history of progressive reduction in visual acuity (VA) on the day of admission; 2 months prior he had been hospitalized in the intensive care unit for severe COVID-19 and received intravenous antibiotics and systemic corticosteroids. He continued a tapering course of oral corticosteroids, beginning with dexamethasone 8 mg a day for 1 month followed by 4 mg daily for 2 weeks, and finally 2 mg daily for 1 week.

Upon admission, his VA was 20/200 in both eyes (OU). Pupillary reflexes were sluggish to light (1/4+). Intraocular pressure (IOP) was 2 mmHg OU. Ocular examination revealed moderate mixed conjunctival hyperemia, keratic precipitates (KP), and anterior chamber cell grade 1+ . Fundoscopy showed moderate vitritis with cotton wool spots in a “string of pearls” appearance, intraretinal hemorrhages, and foci of chorioretinitis in the posterior and peripheral retina (Fig. 1).

Fig. 1.

Fundoscopy of endogenous fungal endophthalmitis at first evaluation. A Right eye showing opacity and subretinal exudate in “fluff balls” and “string of pearls” pattern; B left eye showing opacity and subretinal exudate

Vitreous culture was obtained, and a dose of intravitreal voriconazole 100 mcg was administered in both eyes. The patient was also given outpatient treatment: topical voriconazole 10 mg/ml every 4 hours, prednisolone 1% every 6 hours, and cyclopentolate 1% twice a day, for 3 months, along with intravenous voriconazole 200 mg twice a day. Prognosis was assessed 10 days later, and a second dose of intravitreal voriconazole was administered (Fig. 2).

Fig. 2.

Fundoscopy of endogenous fungal endophthalmitis, 2 weeks of treatment with voriconazole. A Right eye showing less opacity and visualization of optic disc, along with subretinal exudate lateral to the fovea extending beyond inferior arcade B Left eye with less opacity

Culture showed no growth after 2 weeks, but an eye ultrasound was performed and demonstrated retinal detachment in both eyes (Fig. 3). The patient then underwent pars plana vitrectomy, silicone oil tamponade, endolaser photocoagulation, and a scleral buckle, with 1-week interval between each eye’s surgery. During the surgery, another dose of intravitreal voriconazole 100 mcg was applied, and the vitreous samples were sent for a second culture, which ultimately tested positive for Candida albicans, confirmed by direct microscopy of the vitreous (Fig. 4). Topic and intravitreal voriconazole were continued for 1 week until silicone oil removal and phacoemulsification were performed. VA was assessed at Snellen 20/25 1 week post-surgery, and follow-up fundoscopy was performed 1 month after treatment (Fig. 5).

Fig. 3.

Eye ultrasound with posterior retinal detachment. A Left eye B right eye

Fig. 4.

Microbiology of vitreous culture. A Spread microscopy stained with Giemsa showing abundant polymorphonuclear neutrophils B Direct microscopy with potassium hydroxide showing yeast and pseudohyphae suggesting Candida. C Culture of isolated colonies of Candida albicans

Fig. 5.

Fundoscopy of endogenous fungal endophthalmitis after 1 month of treatment with voriconazole and surgery, A (right eye) and B (left eye); totally reattached retina with scar tissue in the chorioretinal place where Candida infection started

Discussion and conclusion

The use of high and/or prolonged doses of corticosteroids in patients with severe COVID-19, along with prolonged hospitalization and use of immunosuppressive drugs, can lead to impaired immunologic response. Moreover, COVID-19 viremia itself can cause a decrease in overall peripheral lymphocytes, collectively predisposing patients to infection of opportunistic microorganisms [5, 7]. Similar to our case, most reports involve patients who required hospitalization, received high doses of corticosteroids, and had ocular symptoms starting after acute COVID-19. The use of corticosteroids during the COVID-19 pandemic was neither standardized nor guided by clear clinical protocols, which resulted in significant variability, and at times, overuse. In the absence of definitive guidelines, treatment strategies were often tailored by individual physicians, as in this case report.

It is rare to obtain positive cultures in EE. In a case series of patients with fungal EE post-COVID-19 in India, no patient obtained an exact microbiological diagnosis, even with vitreous biopsy [8]. Another case series in India also reported negative cultures [6]. Furthermore, a long-term study from a center in India over 15 years found that only half of the patients with EE resulted positive for fungus in direct fluorescent microscopy and culture [9]. Large-scale studies have reported positive cultures from ocular fluids in EE in 14–43% of cases [8]. Therefore, regardless of blood cultures not showing any signs of fungal growth, Candidemia in these patients is frequent, especially C. albicans [8, 10]. Ocular manifestations can be the first sign of candidemia and initiating treatment early significantly reduces complications and sequelae [11].

Visual outcomes in EE are generally reported to be poor [12, 13]. In previous studies among 64 cases of EE, VA ranged from Snell 6/6 to no perception of light (NPL) at evaluation, resulting in final VA from 6/6 to NPL [12]. Bacterial EE, particularly caused by Klebsiella species, often has worse outcomes than endogenous fungal endophthalmitis (EFE), and authors suggest vitrectomy only for those bacterial-confirmed cases [12]. Regarding EFE, in a review of several published reports that included seven patients who had Candida endophthalmitis treated with voriconazole, VA in the six survivors ranged from 20/20 to 20/100 [11]. Aspergillus has also been identified in previous studies with a worse prognosis than reported C. albicans cases [6, 14]. While Aspergillus is the predominant cause of fungal EE in South India, an equal incidence was found in North India [5]. Despite the poor visual prognosis typically associated with fungal endophthalmitis, other case reports show that good visual outcomes are achievable when timely diagnosis and treatment are initiated [5, 15].

The best therapeutic strategy appears to be vitrectomy (especially in severe vitritis scenarios) [16], intravitreal injection of an antifungal agent (amphotericin B 5–10 mcg in 0.1 mL sterile water, or voriconazole 100 mcg in 0.1 mL sterile water or normal saline), and systemic antifungal therapy. In Venezuela, access to amphotericin B—particularly for intravitreal use—is extremely limited, and its supply is inconsistent, especially in the region where the patient was treated. In contrast, voriconazole was more readily available and offered a practical alternative with proven efficacy [17, 18]. Treatment with oral fluconazole 100–200 mg daily, or intravitreal 5–10 µg/ml is safe and has shown effectiveness in EFE on immunosuppression/immunocompetent patients and can be combined with other antifungal therapies [17].

EFE can significantly impact vision outcomes. Although this is a single case report, our case underscores the critical need for a high index of suspicion for EE in patients with COVID-19 presenting with new-onset visual symptoms regardless negative cultures (particularly in those with comorbidities such as diabetes mellitus and recent corticosteroid use). It is imperative to emphasize the importance of prompt ophthalmic cross-consultation that can facilitate early diagnosis and timely intervention, potentially preventing further vision-related complications.

Abbreviations

COVID-19

Coronavirus disease 2019

EE

Endogenous endophthalmitis

EFE

Endogenous fungal endophthalmitis

VA

Visual acuity

Author contributions

RTC, GG, DAFP, and JLL carried out the literature search and drafted the first version of the manuscript. AV and RJC supervised and revised the manuscript. JLL and DAFP supervised the completion of this case series and substantively revised it. All authors read and approved the final manuscript.

Funding

The authors received no specific funding for this work.

Data availability

All data and materials in this article are included in the manuscript.

Declarations

Ethics approval and consent to participate

Not applicable.

Consent for publication

Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.

Competing interests

The authors declare no competing interests.