Endogenous Fungal Endophthalmitis following COVID-19 Hospitalization: Evidence from a Year-Long Observational Study.

PURPOSE: To describe cases of endogenous fungal endophthalmitis (EFE) post-recovery from or hospitalization for coronavirus disease 2019 (COVID-19). METHODS: This prospective audit involved patients with suspected endophthalmitis referred to a tertiary eye care center over a one-year period. Comprehensive ocular examinations, laboratory studies, and imaging were performed. Confirmed cases of EFE with a recent history of COVID-19 hospitalization±intensive care unit admission were identified, documented, managed, followed up, and described. RESULTS: Seven eyes of six patients were reported; 5/6 were male, and the mean age was 55. The mean duration of hospitalization for COVID-19 was approximately 28 days (14-45); the mean time from discharge to onset of visual symptoms was 22 days (0-35). All patients had underlying conditions (5/6 hypertension; 3/6 diabetes mellitus; 2/6 asthma) and had received dexamethasone and remdesivir during their COVID-related hospitalization. All presented with decreased vision, and 4/6 complained of floaters. Baseline visual acuity ranged from light perception (LP) to counting fingers (CF). The fundus was not visible in 3 out of 7 eyes; the other 4 had "creamy-white fluffy lesions" at the posterior pole as well as significant vitritis. Vitreous taps were positive for Candida species in six and Aspergillus species in one eye. Anti-fungal treatment included intravenous amphotericin B followed by oral voriconazole and intravitreal amphotericin B. Three eyes underwent vitrectomy; the systemic health of two patients precluded surgery. One patient (with aspergillosis) died; the others were followed for 7-10 months - the final visual outcome improved from CF to 20/200-20/50 in 4 eyes and worsened (hand motion to LP) or did not change (LP), in two others. CONCLUSION: Ophthalmologists should maintain a high index of clinical suspicion for EFE in cases with visual symptoms and a history of recent COVID-19 hospitalization and/or systemic corticosteroid use - even without other well-known risk factors.

Clinical differentiation of keratitis due to fungus and Pythium: A photographic survey.

Purpose: To evaluate the knowledge and skills of clinicians in differentiating cases of Pythium from fungal keratitis based on their clinical appearance. Methods: Thirty slit-lamp photographs from culture-proven cases of Pythium and fungal keratitis were selected for conducting a prospective online-based photographic survey. The participants were asked to identify the causative organism and enlist the specific clinical features which helped in reaching the diagnosis. Both cornea specialists and clinical fellows/trainees participated in the survey. Sensitivity, specificity, and predictive values were estimated, and the factors associated with these, including the identification rates of clinical signs, were evaluated using bivariate and multivariate linear regression analyses. The identification rates between the consultants and fellows were compared. Results: A total of 42 cornea specialists (28 consultants and 14 clinical fellows) participated in the survey. Clinicians were able to differentiate Pythium from fungal etiology in only 56% of cases. The differentiating ability between the consultants and fellows was statistically insignificant. Average sensitivity, specificity, and positive and negative predictive values for differentiating Pythium from fungus were 56%, 65%, 56%, and 66%, respectively. The specific clinical features enlisted by the participants to differentiate Pythium from fungus were the presence of tentacles, peripheral guttering, dot-like infiltrates, and elevated plaques. Conclusion: Clinical knowledge regarding the signs and symptoms and the microbiological identification of features for Pythium are still lacking among clinicians. As the treatment protocols are distinctly different for both, it is imperative to enhance the knowledge and diagnosing ability to tackle this emerging microorganism which causes high morbidity.

Is mucormycosis the end? A comprehensive management of orbit in COVID associated rhino-orbital-cerebral mucormycosis: preserving the salvageable.

BACKGROUND: Rhino-orbital-cerebral mucor mycosis (ROCM) is a relatively rare opportunistic infection caused by the Mucorales species. While ROCM suggests involvement of the paranasal sinuses, orbit and brain ROM (rhino-orbital-Mucormycosis) stands for the fungal invasion in sinuses and orbit sans cerebral involvement. In India with the outbreak of the second COVID wave and the delta variant of the virus, there has been a steep increase in this opportunistic fulminant fungal infection, named COVID-associated Mucor mycosis (CAM). The most critical question in orbital management is when to go ahead with an exenteration. Our study aims to design a pertinent minimal invasive surgical protocol for surgeons to manage such cases based on our surgical experience and mitigate the need for exenteration and save the eyes wherever possible. METHODS: The study is a retrospective analysis of patients of ROM with and without brain involvement, who underwent minimal surgical management between March 2021 to March 2022 along with their follow-up. RESULTS: There were 184 eyes of 148 patients diagnosed with CAM. The mean age was 51.7 years with a male predominance of 103 (70%). All patients developed ROM following the COVID-19 infection and the duration between diagnosis of COVID-19 and ROM was 36 ± 23 days. 18 cases (12%) were bilateral. 76 eyes (41%) had no vision at the presentation. Imaging revealed paranasal sinus involvement (100%), orbital apex involvement (61%), cavernous sinus involvement (53%), and central nervous system (CNS) involvement (47%). All the patients (100%) were treated with systemic Liposomal amphotericin-B and sinus debridement. Endoscopic debridement of the orbital disease was performed in 45 (30.4%) cases, 15(8.1%) eyes underwent exenteration and were later rehabilitated with a customized ocular prosthesis, 103 (56%) eyes underwent transcutaneous retrobulbar amphotericin-B. At a mean follow-up of 13.1 months; the complete resolution was seen in 25 (17%) cases, the residual stable lesion was seen in 77(52%) of the cases and new lesions were developed in 13(9%) of the cases. Mortality was seen in 33 (22%) patients and all of them had CNS involvement. CONCLUSIONS: Systemic and protocol-based management can save the life and salvage the eyes.

Acremonium keratitis: Risk factors, clinical characteristics, management, and outcome in 65 cases.

Purpose: To study the risk factors, clinical presentation, management options, and outcomes in cases of culture-proven Acremonium keratitis. Methods: Medical and microbiology records of culture-proven Acremonium keratitis from Jan 2007 to Dec 2019 at a tertiary eye care center were reviewed. Details of clinical findings on each visit and operating notes were reviewed from the medical records. All cases were subjected to corneal scraping at the first visit for microbiological investigation consisting of direct smear examination and culture. Topical natamycin 5% was the mainstay of medical treatment. Surgical treatment was considered for nonresponding patients. Results: During the 13-year study period, 65 cases of culture-proven Acremonium keratitis were identified out of 1605 cases of fungal keratitis. Trauma was the most common predisposing factor in 32 cases (49.2%). The average area of the corneal stromal infiltrate was 24.8 mm2 at the initial presentation. Hypopyon at the time of presentation was evident in 28 (43.1%) cases. Staphylococcus spp. was the most common (n = 22, 33.8%) organism coexistent with Acremonium. Direct microscopy of corneal scraping was positive for fungal filaments in 57/65 (87.6%) cases. Medical management alone was given in 44 patients (67.6%). Age (>50 years) and treatment delay (>15 days) were found to be independent risk factors for the poor final visual outcome (VA <20/60). Conclusion: When treated early, Acremonium keratitis responds well to medical therapy with currently available topical antifungals. However, advanced and nonresponding cases require surgical intervention for resolution of the infection.

[Ophthalmopathologic Aspects of Endophthalmitis]. / Endophthalmitis aus ophthalmopathologischer Sicht.

Endophthalmitis is one of the most severe ophthalmic emergencies. Most patients experience a permanent decrease in visual acuity after the event, but the eye can be preserved in most cases. However, when the eye is enucleated after endophthalmitis, ophthalmopathologic investigation of the globe with respect to the clinical history can provide valuable information regarding the ultimately frustrating course of the disease that can be helpful for the treatment of future patients. Often, valuable aspects also emerge with regard to the therapeutic approach. For example, in therapy-resistant fungal endophthalmitis the necessity of penetrating keratoplasty with a large graft diameter and possibly even removal of the lens including the capsular bag should be stressed. In the following, five enucleated eyes with a different spectrum of endophthalmitis, as well as different potential pathways of exogenous and endogenous endophthalmitis, are illustrated clinically and ophthalmopathologically. In summary, endophthalmitis requires urgent intervention; however, various differential diagnoses must be excluded. Histopathologic examination of enucleated eyes is helpful for understanding the course of the disease and may also have forensic significance.

Clinical profile of keratitis treated within 3 months of acute COVID-19 illness at a tertiary care eye centre.

PURPOSE: To report the spectrum of keratitis treated within 3 months of acute COVID-19 infection. METHODS: Retrospective, descriptive case series study of 19 eyes of 16 patients who presented at tertiary eye care centre in Southern India. RESULTS: Median age of the patients was 43(IQR 35-55.5) years. Majority (15/16, 93.75%) were males. Unilateral affliction was predominant (13/16, 81.25% patients). Nine had a history of hospitalization, five had received oxygen supplementation and five had been treated with steroids during COVID-19 illness. The median duration between COVID-19 diagnosis and the ocular symptoms in the eye was 29 (IQR 22-57) days. Microbiological diagnosis consisted of microsporidia in nine eyes of seven patients, fungus in six patients, Pythium in one patient, and herpes zoster ophthalmicus in one patient. One patient had neurotrophic keratitis. Therapeutic penetrating keratoplasty was performed in five patients, glue application in two patients and three were managed with tarsorrhaphy with/without amniotic membrane grafting or tenonplasty. There was medical and surgical cure in all patients. CONCLUSIONS: Microsporidia was the commonest cause of keratitis, followed by fungal infection. Majority of the microsporidia infections were keratoconjunctivitis. The fungal isolates identified were Aspergillus and Mucor species. All patients responded to conventional management guidelines with favourable outcomes.

Total Anterior Staphyloma Secondary to Acanthamoeba Keratitis.

ABSTRACT: There are very few published cases of total anterior staphyloma, all of which have been reported as secondary to fungal keratitis. This study reports the clinical and histopathological findings and subsequent management of a 27-year-old healthy female patient who developed total anterior staphyloma after poor compliance with treatment for clinically diagnosed acanthamoeba keratitis. She underwent a successful evisceration with good long-term results. This case highlights that total anterior staphyloma may also result from untreated keratitis which is not fungal in origin. In cases of fungal and acanthamoeba keratitis, patient compliance with both treatment and follow-up is paramount to avoid vision-threatening sequelae that present significant challenges in their management.

Epidemiology, clinical profile and treatment outcomes of bacterial and fungal keratitis.

PURPOSE: The purpose of the study is to determine the microbiological etiology, epidemiological factors, and clinical profile and treatment outcomes of infective keratitis in Ophthalmology department, Minia University, Egypt. METHODS: Prospective, nonrandomized, observational clinical series of cases, including 150 patients with mean age 30 (range 12 to 85 years), 90 patients (60%) were males and 60 (40%) were females, clinically diagnosed as infective corneal ulcer, attending the Ophthalmology Department-Faculty of Medicine. Minia University, Minia, Egypt. From December 2018 to December 2020. Detailed history taking and all clinical findings were collected. Corneal scrapings were obtained from patients and subjected to staining and culture for bacterial and fungal pathogens; Bacterial and fungal growth were identified by standard laboratory procedures. RESULTS: Corneal trauma by a vegetative matter was the commonest risk factor associated with infective keratitis in 92 cases (61.3%). Smear and culture was positive in 83 cases (58.4%) of 142 corneal scrapings obtained, of which 60 cases were fungal (72.3%), 21 cases were bacterial (25.3%) and two cases were mixed bacterial and fungal (2.4%), Aspergillus species was the commonest fungal species isolated in fungal keratitis. One hundred forty-two cases (94.67%) healed completely with scar. Only six cases (4%) required evisceration due to aggressive presentation from the start and keratoplasty was performed for two cases (1.33%). CONCLUSIONS: Fungal keratitis was the commonest type in cases attending to our department. Adequate diagnosis, management and follow-up helped in achieving high successful curative outcomes. CLINICAL TRIAL NUMBER: Clinical Trials.gov ID: NCT04894630. Time of registration 1 December 2018.

Fungal keratitis: Mechanisms of infection and management strategies.

Fungal corneal ulcers are an uncommon, yet challenging, cause of vision loss. In the United States, geographic location appears to dictate not only the incidence of fungal ulcers, but also the fungal genera most encountered. These patterns of infection can be linked to environmental factors and individual characteristics of fungal organisms. Successful management of fungal ulcers is dependent on an early diagnosis. New diagnostic modalities like confocal microscopy and polymerase chain reaction are being increasingly used to detect and identify infectious organisms. Several novel therapies, including crosslinking and light therapy, are currently being tested as alternatives to conventional antifungal medications. We explore the biology of Candida, Fusarium, and Aspergillus, the three most common genera of fungi causing corneal ulcers in the United States and discuss current treatment regimens for the management of fungal keratitis.

Clinical Presentations and Management Outcomes of Culture-Proven Mixed Bacterial and Fungal Endophthalmitis.

OBJECTIVE: To report the clinical features and management outcomes of mixed fungal and bacterial endophthalmitis. METHODS: Retrospective, consecutive non-comparative case series. Fifteen eyes of 15 patients were included from January 2009 to December 2019 with culture proven mixed fungal and bacterial endophthalmitis. Demography, clinical presentations, interventions received, and final visual and anatomical outcomes were noted. A favorable anatomic outcome was defined as preservation of the globe, absence of hypotony, attached retina, and absence of active inflammation at the last visit. RESULTS: The mean age of patients in this series was 34.2 ± 19.6 years (range: 5-61 years). Male preponderance was found in 14 (93.3%). Eight (53.3%) eyes had open globe injury, 5(33.3%) had postoperative endophthalmitis and one (6.6%) each with endogenous endophthalmitis and post-keratitis. Pars plana vitrectomy was done in eight (53.3%) eyes whereas vitreous tap alone was done in seven (46.7%) eyes. Gram positive cocci (n = 11, 73.3%) were the commonest bacterial isolates (n = 7, 46.6%). Staphylococcus aureus (n = 3, 20%) was the most common bacterial isolate. The commonest fungi were filamentous hyaline fungi (n = 5, 33.3%). An unfavorable visual outcome (VA<20/400) was seen in all the eyes. The mean duration of follow-up was 13 ± 18.3 months. Globe salvage was possible only in five (33.3%) eyes. The bacterial isolates were highly sensitive to all of the tested antibiotics. CONCLUSION: Mixed fungal and bacterial endophthalmitis occur commonly in a setting of open-globe trauma. The presence of fungus concurrently leads to a very poor management outcome even if the bacterial isolate sensitivity is good.

Impact of COVID-19 Pandemic on Infectious Keratitis Outcomes: A Retrospective Multicenter Study in Tertiary Eye Hospitals of South India.

PURPOSE: The purpose of this study was to report the adverse effects of the COVID-19 pandemic on the clinical outcomes of infectious keratitis in South India. METHODS: Two hundred fifty-eight patients presented with infectious keratitis at 6 tertiary care centers when strict travel restrictions were in place from March 24 to May 31, 2020. Case records were collected retrospectively and analyzed for demographics, type of initial treatment, length of delay in presentation, microbiological diagnosis, clinical course, and final treatment outcome. RESULTS: The mean age of the patients was 49.2 years, with most of them (61.2%) being male. Forty-one patients (15.9%) did not receive any treatment for at least a week after the onset of symptoms. One hundred eight patients (41.9%) presented with severe ulcer (32 had a frank perforation). Resolution of the infection was achieved only in 103 patients (45.6%). A total of 90 patients (39.8%) with ulcers had a perforation, yet only 29 patients (32.2%) could receive keratoplasty because of the unavailability of donor tissues. At the end of 6-month follow-up, 47 patients had anatomical failure (loss of globe) and 12 additional patients had functional failure (total permanent vision loss). CONCLUSIONS: Delay in presentation and acute shortage of donor corneal tissues for emergency keratoplasty because of the COVID-19 pandemic had a grave impact, resulting in irreversible blindness in a significant number of patients.

Epidemiology, clinical profile, management, and outcome of COVID-19-associated rhino-orbital-cerebral mucormycosis in 2826 patients in India - Collaborative OPAI-IJO Study on Mucormycosis in COVID-19 (COSMIC), Report 1.

Purpose: COVID-19-associated rhino-orbital-cerebral mucormycosis (ROCM) has reached epidemic proportion during India's second wave of COVID-19 pandemic, with several risk factors being implicated in its pathogenesis. This study aimed to determine the patient demographics, risk factors including comorbidities, and medications used to treat COVID-19, presenting symptoms and signs, and the outcome of management. Methods: This was a retrospective, observational study of patients with COVID-19-associated ROCM managed or co-managed by ophthalmologists in India from January 1, 2020 to May 26, 2021. Results: Of the 2826 patients, the states of Gujarat (22%) and Maharashtra (21%) reported the highest number of ROCM. The mean age of patients was 51.9 years with a male preponderance (71%). While 57% of the patients needed oxygen support for COVID-19 infection, 87% of the patients were treated with corticosteroids, (21% for > 10 days). Diabetes mellitus (DM) was present in 78% of all patients. Most of the cases showed onset of symptoms of ROCM between day 10 and day 15 from the diagnosis of COVID-19, 56% developed within 14 days after COVID-19 diagnosis, while 44% had delayed onset beyond 14 days. Orbit was involved in 72% of patients, with stage 3c forming the bulk (27%). Overall treatment included intravenous amphotericin B in 73%, functional endoscopic sinus surgery (FESS)/paranasal sinus (PNS) debridement in 56%, orbital exenteration in 15%, and both FESS/PNS debridement and orbital exenteration in 17%. Intraorbital injection of amphotericin B was administered in 22%. At final follow-up, mortality was 14%. Disease stage >3b had poorer prognosis. Paranasal sinus debridement and orbital exenteration reduced the mortality rate from 52% to 39% in patients with stage 4 disease with intracranial extension (p < 0.05). Conclusion: : Corticosteroids and DM are the most important predisposing factors in the development of COVID-19-associated ROCM. COVID-19 patients must be followed up beyond recovery. Awareness of red flag symptoms and signs, high index of clinical suspicion, prompt diagnosis, and early initiation of treatment with amphotericin B, aggressive surgical debridement of the PNS, and orbital exenteration, where indicated, are essential for successful outcome.

Chronic endogenous fungal endophthalmitis: diagnostic and treatment challenges: A case report.

RATIONALE: Endogenous fungal endophthalmitis (EFE) is a sight-threatening complication of systemic fungemia. As the prevalence rises, treatment remains a challenge especially when there is a failure in first-line treatment or drug-resistant fungus. This case report studies a case of chronic EFE, focusing on the diagnostic procedures, treatment options, monitoring parameters and the treatment outcome. PATIENT CONCERNS: A 64-year-old man with underlying well controlled diabetes mellitus was treated with 2 weeks' course of intravenous antifungal fluconazole for pyelonephritis as his blood culture grew Candida albicans. Concurrently, he complained of 3 months of bilateral painless progressive blurring of vision. At presentation, his visual acuity (VA) was light perception both eyes. Ocular examination revealed non granulomatous inflammation with dense vitritis of both eyes. DIAGNOSIS: He was diagnosed with EFE but the condition responded poorly with the medications. INTERVENTIONS: He was treated with intravitreal (IVT) amphotericin B and fluconazole was continued. Vitrectomy was performed and intraoperative findings included bilateral fungal balls in the vitreous and retina with foveal traction in the left eye. Postoperatively, vision acuity was 6/24, N8 right eye and 2/60, N unable for left eye with extensive left macular scar and hole. Vitreous cultures were negative. He received multiple IVT amphotericin B and was started on topical steroid eye drops for persistent panuveitis with systemic fluconazole. Ocular improvement was seen after switching to IVT and topical voriconazole. Despite this, his ocular condition deteriorated and he developed neovascular glaucoma requiring 3 topical antiglaucoma agents. Panretinal photocoagulation was subsequently performed. OUTCOMES: At 3 months' follow-up, his vision acuity remained at 6/24 for right eye and 2/60 for the left eye. There was no recurrence of inflammation or infection in both eyes. LESSONS: Voriconazole could serve as a promising broad spectrum tri-azole agent in cases of failure in first-line treatment or drug-resistant fungus.

Microsporidial Stromal Keratitis: Epidemiological Features, Slit-Lamp Biomicroscopic Characteristics, and Therapy.

PURPOSE: Microsporidial stromal keratitis is a rare form of infectious keratitis, with only 7 cases reported in the United States to date. This study was performed to evaluate risk factors, clinical features, and response to therapy. METHODS: A retrospective review of the medical records of all patients diagnosed with microsporidial stromal keratitis seen in the practices of the authors between 1999 and 2020 was performed. Diagnosis was determined by cytology or histopathology in corneal specimens. Risk factors, presence or absence of distinctive clinical features, and response to medical and surgical therapies were recorded. RESULTS: Nine patients-7M:2F, aged 7 to 99 years-with microsporidial stromal keratitis were identified. Exposures to recreational water and hymenopteran insect bites, both epidemiologically linked risk factors for systemic microsporidial infection, were identified in our patients. Presence of stromal edema with features of disciform keratitis and a distinctive granular keratitis were observed in 6 of 9 and 5 of 9 patients, respectively. Poor response to medical therapy was noted. Penetrating keratoplasty was effective in curing the infection. Final visual acuity was 20/40 or better in 6 of 9 patients. CONCLUSIONS: In patients with slowly progressive keratitis, history of exposure to recreational water or hymenopteran insects should be sought. In patients with corneal edema consistent with disciform keratitis, with evolution to a granular keratitis, microsporidia should be considered in the differential diagnosis. In cases of established microsporidial stromal keratitis, penetrating keratoplasty should be considered if prompt response to medical therapy is not noted.

[Fungal keratitis associated with the use of contact lenses (clinical case)]. / Gribkovyi keratit, assotsiirovannyi s kontaktnoi korrektsiei (klinicheskoe nablyudenie).

Currently, the number of keratomycoses and the interest of ophthalmologists to this type of keratitis have significantly increased due to the severity of the disease and non-satisfactory outcomes in some cases. According to published data, perforation of the cornea develops 6 times more often after keratomycosis than after keratitis of another etiology. The outcomes of keratoplasty in these patients are also not always satisfactory. The article presents a relatively rare clinical case of keratomycosis in a teenager caused by Arthrographis kalrae. The description of diseases caused by this microorganism is rarely found in literature. We have found only 4 cases describing keratomycosis caused by A. kalrae. The case presented here is associated with the use of contact lenses. The microorganism was identified from a container with contact lenses. Fungicidal drugs such as Anidulafungin, Voriconazole, as well as topical and systemical Amphotericin B were used in the treatment. The patient was discharged with a good functional result (best-corrected visual acuity of 0.7). This case indicates the possibility of a positive functional outcome in treating keratomycosis with present-day means.

Unusual presentation of mucormycosis mimicking a localised sino-orbital pathology.

Mucormycosis is an aggressive and deadly fungal infection, which is invariably associated with an immunocompromised patient. Mucormycosis in the head and neck region presents as skeletal necrosis, with or without soft tissue involvement. Early identification and treatment with combination of surgical debridement and parenteral antifungal therapy is critical for a favourable outcome. This paper reports an unusual presentation of mucormycosis, mimicking a localised sino-orbital pathology involving the infraorbital subcutaneous tissue and the maxillary sinus, in a 35 years old immunocompetent man. Despite aggressive antifungal therapy and surgical management, the course of disease was fatal, reiterating the high mortality associated with mucormycosis.