Intravitreal voriconazole for the treatment of endogenous endophthalmitis caused by Scedosporium apiospermum

Scedosporium apiospermum is an increasingly recognized cause of endogenous fungal endophthalmitis in immunocompromised patients. The authors describe two patients with endogenous S. apiospermum endophthalmitis treated with intravitreal and systemic voriconazole. Despite a prolonged course of systemic antifungal treatment, both patients subsequently required enucleation for intractable ocular pain due to secondary scleritis. Histological examination of the globes demonstrated the presence of fungal hyphae. Endogenous S. apiospermum endophthalmitis need to be considered in the differential diagnosis of necrotizing retinitis. Despite its efficacy in suppressing disseminated S. apiospermum infection, voriconazole may be ineffective in the treatment of endogenous S. apiospermum endophthalmitis especially if treatment is delayed.     

Bilateral endogenous Scedosporium prolificans endophthalmitis after lung transplantation

PURPOSE: To report a case of bilateral endogenous fungal endophthalmitis resulting from disseminated Scedosporium prolificans. DESIGN: Observational case report. METHODS: A 56-year-old woman with cystic fibrosis status post dual lung transplantation on chronic immunosuppressive therapy presented with acute graft rejection. Cultures of bronchial brushings revealed S. prolificans. Three weeks after admission, the patient noted increased blurriness and a central scotoma in her right eye. Dilated fundus examination revealed profound vitritis in the right eye with hemorrhagic retinitis involving the macula. A peripheral, yellow choroidal infiltrate with overlying retinitis and localized vitritis was present in the left eye. RESULTS: Intravitreal antibiotics were initiated, and vitreous cultures revealed S. prolificans. The patient ultimately succumbed to her disseminated disease. Pathologic examination of the eyes confirmed bilateral endogenous fungal endophthalmitis. CONCLUSION: S. prolificans is an opportunistic infection resistant to standard antifungal therapy that can result in endogenous endophthalmitis in immunocompromised individuals.     

Scedosporium prolificans corneoscleritis: A successful outcome

Background: A case of Scedosporium prolificans corneoscleritis is reported in a patient who had developed scleral necrosis following pterygium surgery, with adjunctive β-irradiation. This fungus has been reported to be the causative organism in only two previous cases of corneoscleritis. Methods: The patient presented with signs and symptoms typical of corneoscleritis. When the fungus was isolated from a biopsy specimen, aggressive scleral debridement was carried out and intensive antifungal therapy was instigated. Results: After a prolonged course, the eye was rendered sterile. Conclusion: Early conjunctival recession and aggressive scleral debridement combined with intensive instillation of antifungals are crucial to the successful management of fungal corneoscleritis.     

Cryptococcal chorioretinitis and endophthalmitis

The diagnosis of endogenous ophthalmic fungal infection may be difficult. A patient initially presented with hydrocephalus and later developed a progressive bilateral intraocular inflammation unresponsive to corticosteroids or antituberculous therapy. Further evaluation with vitreous biopsy study and lumbar puncture led to the diagnosis of cryptococcal chorioretinitis, endophthalmitis, and meningitis. Initial treatment with intravenous amphotericin failed to control the intraocular infections. Vitrectomy and intravitreal injections of amphotericin combined with the systemic intravenous amphotericin halted progression of the intraocular disease. This case demonstrates the difficulty in making the diagnosis of an endogenous fungal endophthalmitis and the value of diagnostic vitreous biopsy study in cases of increasing intraocular inflammation unresponsive to medical therapy. It also suggests the usefulness of vitrectomy combined with intravitreal amphotericin in cases of fungal endophthalmitis that are unresponsive to systemic antifungal agents.     

Endogenous Candida endophthalmitis. Management without intravenous amphotericin B

Eight consecutive cases of culture-proven endogenous Candida endophthalmitis (ECE) were managed between 1980 and 1988. All patients were treated with vitrectomy and injection of intravitreal amphotericin B. Blood cultures were negative in all patients, although Candida albicans was cultured from a foot ulcer in one patient. No systemic therapy was used in three patients, three patients received oral ketoconazole, and two patients received oral flucytosine postoperatively. Intravenous amphotericin B was not used because of lack of evidence of disseminated candidiasis and the systemic toxicity associated with its use. The ECE responded favorably to treatment in all cases. Final vision was better in patients with a shorter interval between onset of symptoms and initiation of antifungal therapy. Posttreatment visual acuities were: four eyes greater than or equal to 20/50, two eyes at 20/80 to 20/200, and two eyes less than 5/200. This series showed that ECE without evidence of disseminated disease can be treated successfully with vitrectomy and intravitreal amphotericin B.     

Efficacy of intracameral amphotericin B injection in the management of refractory keratomycosis and endophthalmitis

PURPOSE: To evaluate the efficacy of intracameral amphotericin B injection in the adjunctive management of keratomycosis with probable intraocular extension not responding to conventional antifungal therapy. METHODS: Fourteen eyes of 12 patients with fungal keratitis that did not respond to initial treatment with topical and intravenous fluconazole and oral itraconazole were treated with up to 5 intracameral injections of 5 microg of amphotericin B. Six eyes received one injection, and 8 required subsequent injections. RESULTS: Twelve eyes responded to amphotericin B therapy, including 5 that healed with a central corneal scar and 8 that healed with a peripheral opacity. Two eyes progressed to evisceration. Four eyes developed anterior subcapsular cataract after intracameral amphotericin B. CONCLUSIONS: Intracameral amphotericin B may be an effective adjunctive treatment of fungal keratitis unresponsive to conventional antifungal therapy, although cataract may occur.     

Fungal endophthalmitis complicating subconjunctival injection of triamcinolone acetonide in anterior scleritis

Fungal endophthalmitis following subconjunctival triamacinolone acetonide in anterior scleritis is a rare complication. Two patients with aneterior scleritis, who received subconjunctival injection of triamcinolone developed fungal endophthalamitis. Both patients were positive by smear and polymerase chain reaction for 28S ribosmal RNA gene for fungus. Colletotrichum dematium was identified in one patient. Both patients responded well to pars plana vitrectomy and antifungal therapy.     

Post-traumatic Scedosporium inflatum endophthalmitis

This is the first documented case of post-traumatic Scedosporium inflatum endophthalmitis and only the second of S. inflatum endophthalmitis occurring in a non-immunocompromised individual, to the authors' knowledge. A case is reported of a 57-year-old woman who, while chopping wood, had a wood chip hit her in the right eye. This caused a penetrating corneal injury with uveal prolapse and damage to the crystalline lens. There were also vitreous and suprachoroidal haemorrhages. No detectable intraocular foreign material was retained. The clinical manifestation of infection was delayed, but once established, it was very destructive. The initially indolent endophthalmitis eventually led to loss of all light perception and panophthalmitis which required enucleation. The responsible strain of S. inflatum was found to be resistant to all antifungal medication in vitro.     

经玻璃体腔内注射药物联合玻璃体切割术治疗真菌性眼内炎

目的：研究经玻璃体腔内注射伏立康唑及两性霉素B脂质体联合玻璃体切割术治疗真菌性眼内炎的效果。

方法：选取2014-09/2016-09本院眼科接受治疗的感染烟曲霉菌的真菌性眼内炎患者27例54眼为研究对象,随机分为对照组、研究1组、研究2组三组,每组9例。在行玻璃体切割术后,对三组患者进行药物敏感度实验,检测药物为两性霉素B脂质体和伏立康唑。之后对三组患者都应用伏立康唑口服,用阿托品膏散瞳,并且每天换药,另外对研究1组和研究2组患者的玻璃体腔内分别注入伏立康唑溶液和两性霉素B脂质体溶液。术后观察前房炎症情况、角膜混浊程度、玻璃体混浊情况和视力恢复情况。

结果：烟曲霉菌对两性霉素B脂质体和伏立康唑均敏感。三组患者术后不同时间角膜混浊情况的比较：除术后1d对照组分别与研究1组和研究2组差异无统计学意义外(P>0.05),其余术后时间比较差异均有统计学意义(P<0.05)。术后不同时间研究1组和研究2组角膜混浊情况比较差异无统计学意义(P>0.05)。三组患者术后不同时间房水闪辉情况的比较：除术后1d对照组分别与研究1组和研究2组差异无统计学意义(P>0.05),其余术后时间比较差异均有统计学意义(P<0.05)。研究1组和研究2组房水闪辉情况除术后9d和15d 差异有统计学意义(P<0.05),其余术后时间比较差异均无统计学意义(P>0.05)。三组患者术后不同时间玻璃体混浊情况的比较：对照组与研究1组除术后1d比较无统计学意义外,其余术后时间均有统计学意义(P<0.05)。对照组与研究2组比较除术后1、4、6d比较无统计学意义外,其余术后时间均有统计学意义(P<0.05)。研究1组和研究2组比较除术后6d有统计学意义(P<0.05),其余术后时间比较差异均无统计学意义(P>0.05)。

结论：经玻璃体内注射伏立康唑和两性霉素B脂质体联合玻璃体切割术可以有效地治疗真菌性眼内炎,与两性霉素B脂质体相比,伏立康唑对治疗早期和中期的真菌性眼内炎效果较好。     

Intravitreal corticosteroids in the treatment of exogenous fungal endophthalmitis.

A rabbit model of exogenous Candida albicans endophthalmitis was used to determine if intravitreal corticosteroids combined with an efficacious antifungal agent enhanced fungal proliferation and ocular destruction, or if the combination can suppress the inflammatory and immunogenic response that causes retinal and uveal destruction. Exogenous Candida albicans endophthalmitis was experimentally induced in 20 rabbit eyes. Eight eyes received intravitreal amphotericin B alone; eight eyes received amphotericin B plus dexamethasone. Four eyes served as controls. By clinical grading on the fourth day after infection, the vitreous of the eyes in the two drug-treated groups was significantly clearer in comparison to that of eyes in the control group. By the seventh day after infection, the eyes treated with amphotericin B plus dexamethasone had significantly clearer vitreous in comparison to the eyes receiving only amphotericin B (P = 0.0017). Quantitative culture results were negative in both treatment groups, and histopathologic examination confirmed the clinical grading. Contrary to current beliefs, there was no evidence that the addition of corticosteroids impaired antifungal activity or enhanced fungal proliferation.     

Involvement of intraocular structures in disseminated histoplasmosis

Purpose: To describe ocular involvement and response to treatment in a patient with human immunodeficiency virus (HIV) infection with severe progressive disseminated histoplasmosis (PDH). Methods: We report a 35‐year‐old HIV‐infected patient seen in our clinics over a period of 4 years. During antiretroviral treatment (ART), the HIV load became undetectable at 3 months; however, CD4 T‐cell count increased slowly and rose to 100 cells/μl. Histoplasma capsulatum was cultured from skin pustules, cerebrospinal fluid (CF) and aqueous humour. Results: The patient developed central nervous system (CNS) involvement 2 months and panuveitis in both eyes 4 months after the initiation of ART. With intravenous liposomal amphotericin B followed by oral voricanozole, the chorioretinal lesions of the right eye (RE) became inactivated and magnetic resonance imaging (MRI) lesions of CNS disappeared. Relapse of the inflammation in the anterior segment of the left eye (LE) resulted in a total closure of the chamber angle and severe glaucoma. Despite medical therapy, two cyclophotocoagulations, total vitrectomy and repeated intravitreal amphotericin B injections, LE became blind. Histoplasma capsulatum was cultured from the aqueous humour after antifungal therapy of 16 months’ duration. Conclusion: PDH with intraocular and CNS manifestations was probably manifested by an enhanced immune response against a previous subclinical disseminated infection. It seems difficult to eradicate H. capsulatum from the anterior segment of the eye in an immunocompromised patient.     

Microsphaeropsis olivacea keratitis and consecutive endophthalmitis

PURPOSE: To report a case of fungal keratitis with consecutive endophthalmitis caused by Microsphaeropsis olivacea. METHODS: Case report. RESULTS: A 51-year-old man developed fungal keratitis and consecutive endophthalmitis after sustaining a penetrating injury to the right eye. Cultures of the aqueous humor yielded M. olivacea. Infection resolved after intraocular fungal debridement, intravitreous amphotericin B, and aggressive topical natamycin and oral fluconazole. Persistent, low-grade smoldering corneal and intraocular inflammation required topical corticosteroid therapy. CONCLUSION: M. olivacea is an exceedingly rare ocular pathogen. The intraocular portion of the infection responded quickly to intravitreal antifungal treatment; however, the course was prolonged by smoldering corneal inflammation. Prompt recognition of intraocular spread and aggressive treatment may be beneficial in fungal infections caused by unusual organisms with uncertain virulence.     

Endogenous fungal endophthalmitis following intensive corticosteroid therapy in severe COVID-19 disease

Purpose:To report endogenous fungal endophthalmitis, postrecovery from severe COVID-19 infection in otherwise immunocompetent individuals, treated with prolonged systemic steroids.Methods:Retrospective chart review of cases with confirmed and presumed fungal endogenous endophthalmitis, following severe COVID-19 disease, treated at two tertiary care referral eye institutes in North India.Results:Seven eyes of five cases of endogenous fungal endophthalmitis were studied. All cases had been hospitalized for severe COVID-19 pneumonia and had received systemic steroid therapy for an average duration of 42 ± 25.1 days (range 18–80 days). All the cases initially complained of floaters with blurred vision after an average of 6 days (range 1–14 days) following discharge from hospital. They had all been misdiagnosed as noninfectious uveitis by their primary ophthalmologists. All eyes underwent pars plana vitrectomy (PPV) with intravitreal antifungal therapy. Five of the seven eyes grew fungus as the causative organism (Candida sp. in four eyes, Aspergillus sp. in one eye). Postoperatively, all eyes showed control of the infection with a marked reduction in vitreous exudates and improvement in vision.Conclusion:Floaters and blurred vision developed in patients after they recovered from severe COVID-19 infection. They had received prolonged corticosteroid treatment for COVID-19 as well as for suspected noninfectious uveitis. We diagnosed and treated them for endogenous fungal endophthalmitis. All eyes showed anatomical and functional improvement after PPV with antifungal therapy. It is important for ophthalmologists and physicians to be aware of this as prompt treatment could control the infection and salvage vision.     

Aspergillus endophthalmitis.

A case is reported of bilateral aspergillus endophthalmitis in an infant without any detectable systemic predisposition or focus of infection. The patient is the youngest recorded case of endogenous aspergillus endophthalmitis so far, with an onset of symptoms at the age of 15 days. After histopathological confirmation of the aetiology by enucleation of the atrophic eye, systemic amphotericin B therapy was instituted with excellent results in the fellow eye. This is the first recorded instance of a complete clinical cure in aspergillus ocular disease on systemic amphotericin B therapy alone.     

The impact of amphotericin B-fortified preservation media on donor rim cultures and posttransplant infection

Purpose:To determine the impact of amphotericin B supplementation to donor cornea preservation solutions on the rates of positive donor rim fungal cultures and postkeratoplasty fungal infections.Methods:This was a retrospective analysis of cases undergoing corneal transplantations at a single tertiary referral center from 2016 to 2021. Patients undergoing corneal transplantations with and without amphotericin B supplementation to the storage media were reviewed for donor rim culture results and postoperative infection. The primary outcome measures were positive donor rim fungal culture results and postkeratoplasty fungal infection.Results:A total of 1238 corneal transplants were analyzed. Of these, 849 were stored in preservation solution without amphotericin B, while 389 had amphotericin B included. There was a lower incidence of positive donor rim fungal cultures in cases with amphotericin B supplementation (1.8%) compared to the cases without amphotericin B (2.9%), although this difference was not statistically significant (P = 0.24). Of the 389 cases with amphotericin B supplementation, one (0.25%) went on to develop clinically significant infection, while three of 849 (0.35%) cases without amphotericin B developed infection. The sample size was too small to determine the effect of amphotericin B on the incidence of postkeratoplasty fungal infection.Conclusion:The addition of amphotericin B to donor cornea preservation solution resulted in a downward trend of positive donor rim fungal cultures and postkeratoplasty fungal infections, although these differences did not reach statistical significance. Further studies with larger sample sizes are necessary to appropriately determine the impact of amphotericin B supplementation in the storage solution on positive donor rims and postkeratoplasty fungal infections.     

Advanced fusarium keratitis progressing to endophthalmitis

PURPOSE: To review the clinical course, treatment, and visual outcomes of keratitis with endophthalmitis caused by the filamentary fungus Fusarium. METHOD: One hundred fifty-nine cases of Fusarium keratitis at Bascom Palmer Eye Institute between January 1, 1987 and August 21, 2000 were reviewed. Ten patients with culture-proven Fusarium keratitis progressed to endophthalmitis. All 10 underwent standard diagnostic microbiologic evaluation, and topical and oral antifungal therapy was instituted. Surgical therapy was applied when necessary. Main outcome measures included the incidence of intraocular invasion of fungal keratitis and response to treatment. RESULTS: Ten cases of 159 Fusarium keratitis patients had intraocular involvement that was culture proven. The isolated species were Fusarium oxysporum in seven cases and Fusarium solani in two cases, and in one case, the species could not be identified. Cultures of aqueous and intraocular tissues grew Fusarium in eight cases, whereas vitreous cultures were positive in two. Nine cases had preexisting risk factors. All patients received oral ketoconazole or fluconazole and topical natamycin 5%. In two cases, intravitreal amphotericin B injections were also given. Four patients required a penetrating keratoplasty, enucleation was performed in two patients, two patients required a combination of a penetrating keratoplasty and pars plana vitrectomy, and one patient developed phthisis. CONCLUSION: The combination therapy with oral imidazoles (fluconazole or ketoconazole) and topical natamycin is inadequate in severe Fusarium keratitis with intraocular spread. Early diagnosis and suspicion of endophthalmitis in patients with keratomycosis not responding to aggressive topical antifungal are important.     

Case Report: Bilateral Granulomatous Anterior Uveitis in HIV-patient with Disseminated Talaromycosis (penicilliosis) Marneffei Infection

ABSTRACT

We report on a 22-years-old Thai male patient with congenital HIV infection. Due to his non-adherence to antiretroviral treatment he developed disseminated Talaromyces marneffei infection and was treated with intravenous amphotericin B. Despite this treatment, he presented with bilateral granulomatous anterior uveitis. Uveitis improved only after intracameral injection of amphotericin B.     

Activity of voriconazole against corneal isolates of Scedosporium apiospermum

PURPOSE: To determine the in vitro antifungal activity of voriconazole, a new triazole, compared with other polyene and imidazole antifungal agents against corneal isolates of Scedosporium apiospermum. METHODS: Macro-broth dilution susceptibility testing was performed on five isolates of S. apiospermum obtained from patients with keratomycosis to determine the minimal inhibitory concentrations (MICs) for amphotericin B, natamycin, ketoconazole, itraconazole, and voriconazole. The use of oral voriconazole in the management of a patient with posttraumatic S. apiospermum keratitis is described. RESULTS: S. apiospermum is generally resistant to commonly used topical ophthalmic antifungal agents. The MIC of voriconazole was 0.5 microg/mL, a concentration lower than that of other imidazoles. CONCLUSION: Voriconazole has promising activity against and may prove useful in the management of fungal keratitis.     

Candida dubliniensis endophthalmitis: first case in North America

To report an unusual case of endogenous fungal endophthalmitis due to Candida dubliniensis. Interventional case report of a 27-year-old immunocompetent male with loss of vision, dense vitritis, and chorioretinal infiltrates, who underwent a diagnostic pars plana vitrectomy. Microbiology cultures obtained by a diagnostic vitrectomy were positive for the growth of C. dubliniensis. This infectious process was then appropriately treated with intravitreal amphotericin B and systemic fluconazole with resolution of the endophthalmitis. Endogenous fungal endophthalmitis is a condition that can masquerade other more common causes of endophthalmitis. Atypical cases of endophthalmitis may benefit from diagnostic pars plana vitrectomy for prompt diagnosis and treatment.     

<Emphasis Type="Italic">Nocardia</Emphasis> Keratitis in a Human Immunodeficiency Virus Patient

Background The development of Nocardia keratitis in a patient with human immunodeficiency virus infection is rare, and we could find no cases reported in the literature.Case A 48-year-old woman who had human immunodeficiency virus infection presented with decreased visual acuity, redness, and irritation in the right eye.Observations Initially, the diagnosis was fungal keratitis, and she was treated with 0.3% amphotericin B eye drops and oral fluconazole for 1 month without improvement. Then, all former drugs were discontinued, and a corneal scraping was carried out. The culture result disclosed Nocardia asteroides, and after treatment with 10% sulfacetamide eye drops and oral trimethoprim-sulfamethoxazole, the keratitis subsided dramatically.Conclusions The treatment result for Nocardia keratitis in a human immunodeficiency virus patient was favorable after intensive use of 10% sulfacetamide eyedrops. Nocardia keratitis should be kept in mind as a possible causative organism when antifungal therapy fails in a keratitis case. Jpn J Ophthalmol 2004;48:272–275 © Japanese Ophthalmological Society 2004