Severe Fungal Keratitis Research Articles

A double-masked, sham-controlled trial of rose bengal photodynamic therapy for the treatment of fungal and acanthamoeba keratitis: Rose Bengal Electromagnetic Activation with Green Light for Infection Reduction (REAGIR) study

BackgroundInfectious keratitis secondary to fungus or acanthamoeba often has a poor outcome despite receiving the best available medical therapy. In vitro rose bengal photodynamic therapy (RB-PDT) appears to be effective against fungal and acanthamoeba isolates (Atalay HT et al., Curr Eye Res 43:1322–5, 2018, Arboleda A et al. Am J Ophthalmol 158:64-70, 2014). In one published series, RB-PDT reduced the need for therapeutic penetrating keratoplasty in severe bacterial, fungal, and acanthamoeba keratitis not responsive to medical therapy.MethodsThis international, randomized, sham and placebo controlled 2-arm clinical trial randomizes patients with smear positive fungal and acanthamoeba and smear negative corneal ulcers in a 1:1 fashion to one of two treatment arms: 1) topical antimicrobial plus sham RB-PDT or 2) topical antimicrobial plus RB-PDT.DiscussionWe anticipate that RB-PDT will improve best spectacle-corrected visual acuity and also reduce complications such as corneal perforation and the need for therapeutic penetrating keratoplasty. This study will comply with the NIH Data Sharing Policy and Policy on the Dissemination of NIH-Funded Clinical Trial Information and the Clinical Trials Registration and Results Information Submission rule. Our results will be disseminated via ClinicalTrials.gov website, meetings, and journal publications. Our data will also be available upon reasonable request.Trial registrationNCT, NCT05110001, Registered on November 5, 2021.

Temporary Conjunctival Flap Plus Medical Treatment Versus Medical Treatment Only for High-Risk Fungal Keratitis: A Randomized Controlled Trial.

The purpose of this study was to evaluate the efficacy of temporary conjunctival flap with topical natamycin and oral voriconazole compared with medical treatment only in reducing the rate of perforation in high-risk fungal keratitis. Sixty-two eyes of 62 patients with severe fungal keratitis were examined; only 54 patients were enrolled and divided randomly into 2 groups. The first group received medical treatment only in the form of topical natamycin 5% together with oral voriconazole 200 mg, while the second group received the same medical treatment plus a temporary conjunctival flap that was removed after 2 weeks. Five patients were lost during the follow-up, and only 49 patients were statistically analyzed. All patients were examined frequently until reepithelialization or the development of perforation. Fifteen perforations were reported, with a higher rate among the medical group (48%) compared with the conjunctival flap group (12.5%), with P value <0.05. A significant delay was noted in reepithelialization time in the medical group compared with the conjunctival flap group (mean time was 21.69 ± 5.41 and 15.36 ± 2.2 days, respectively), with P value = 0.001. Significant improvement in visual acuity was reported over time when comparing baseline versus 3-month visual acuity in the same group using paired t sample test (P value was 0.003 and <0.001 in the first and second group, respectively). Temporary conjunctival flap is associated with a lower perforation rate compared with medical treatment only in severe fungal keratitis, which can provide a cheap and available alternative to therapeutic penetrating keratoplasty.

Favorable outcome of Lasiodiplodia theobromae keratomycosis : a clinical case and systematic review

BackroudKeratitis caused by Lasiodiplodia theobromae is rare and typically associated with a poor prognosis. Current literature lacks sufficient evidence on effective management of patients with this condition.Case presentationA 74-year-old former agricultural worker presented with a red right eye, discomfort, and decreased visual acuity, progressing over three days without treatment. Examination revealed type 2 diabetes and a non-perforating, spiculated corneal abscess with a hypopyon in the right eye. Initial treatment included a triple antibiotic therapy and supportive care. Direct mycological examination identified numerous septate mycelial filaments. Antifungal treatment with natamycin and voriconazole, both topically and orally, was initiated. Cultures confirmed Lasiodiplodia theobromae. The patient showed significant improvement. Treatment continued for eight weeks, with a final visual acuity of 20/50 due to a stromal scar.ConclusionAn extensive literature review conducted in November 2023, using databases such as PubMed and Google Scholar with the keywords “lasiodiplodia” and “keratitis” yielded no previous cases of this specific condition being managed solely with the combined use of natamycin and voriconazole. This antifungal combination is commonly included in most management protocols for fungal keratitis. Factors such as the use of corticosteroids and delayed diagnosis were noted to adversely affect the prognosis. This case and this systematic review underscores the potential for non-surgical management options in severe fungal keratitis.

A double-masked, sham-controlled trial of rose bengal photodynamic therapy for the treatment of fungal and acanthameoba keratitis: Rose Bengal Electromagnetic Activation with Green Light for Infection Reduction (REAGIR) Study.

Infectious keratitis secondary to fungus or acanthamoeba often has a poor outcome despite receiving the best available medical therapy. In vitro Rose Bengal Photodynamic therapy (RB-PDT) appears to be effective against fungal and acanthamoeba isolates.22,23 In one published series RB-PDT reduced the need for therapeutic penetrating keratoplasty in severe bacterial, fungal, and acanthameoba keratitis not responsive to medical therapy. This international, randomized, sham and placebo controlled 2-arm clinical trial, randomizes patients with smear positive fungal and acanthameoba and smear negative corneal ulcers in a 1:1 fashion to one of two treatment arms: 1) Topical antimicrobial plus sham RB-PDT or 2) Topical antimicrobial plus RB-PDT. We anticipate that RB-PDT will improve best spectacle corrected visual acuity and also reduce complications such as corneal perforation and the need for therapeutic penetrating keratoplasty. This study will comply with the NIH Data Sharing Policy and Policy on the Dissemination of NIH-Funded Clinical Trial Information and the Clinical Trials Registration and Results Information Submission rule. Our results will be disseminated via clinicaltrials.gov website, meetings, and journal publications. Our data will also be available upon reasonable request. NCT, NCT05110001, Registered November 5, 2021. https://www.clinicaltrials.gov/study/NCT05110001.

Fungal Keratitis: Diagnosis, Management, and Recent Advances.

Fungal keratitis is one of the major causes of microbial keratitis that may lead to corneal blindness. Many problems related to diagnosis and therapy are encountered in fungal keratitis, including difficulty in obtaining laboratory diagnoses and the availability and efficacy of antifungal medications. Intensive and prolonged use of antifungal topical preparations may not be enough. The use of antifungal medications is considered the main treatment for fungal keratitis. It is recommended to start antifungal therapy after confirmation of the clinical diagnosis with a smear or positive cultures. Topical application of antifungal medications is a mainstay for the treatment of fungal keratitis; however, systemic, intra-stromal, or intra-cameral routes may be used. Therapeutic keratoplasty is the main surgical procedure approved for the management of fungal keratitis with good success rate. Intrastromal corneal injection of antifungal medications may result in steady-state drug levels within the corneal tissue and prevent intervals of decreased antifungal drug concentration below its therapeutic level. In cases of severe fungal keratitis with deep stromal infiltration not responding to treatment, intracameral injection of antifungal agents may be effective. Collagen cross-linking has been proposed to be beneficial for cases of fungal keratitis as a stand-alone therapy or as an adjunct to antifungal medications. Although collagen cross-linking has been extensively studied in the past few years, its protocol still needs many modifications to optimize UV fluence levels, irradiation time, and concentration of riboflavin to achieve 100% microbial killing.

Therapeutic Penetrating Keratoplasty for Severe Fungal Keratitis in a Thai Tertiary Care Center

Objective: To evaluate the outcomes of therapeutic penetrating keratoplasty (TPK) performed for severe fungal keratitis. Materials and Methods: Medical records of all patients who underwent TPK in Siriraj Medical Center between April 2010 and July 2020 were culled, and those in which fungal pathogens were definitively identified were studied. Patient records with follow up less than three months were excluded. Patient demographic data, outcome measures and complications following TPK were recorded. The primary outcome was eradication of the fungal infection. Secondary outcomes were preservation of anatomical integrity, graft survival and achievement of visual acuity (VA) greater than or equal to 3/60. Results: Sixty patients met the study criteria and were included in the analysis. The mean patient age was 56 (range: 23-79) years, and most patients were men (46, 77%). The mean follows up time was 30.87 months (range1.61-122.71). Fifteen eyes (25%) sustained corneal perforation before undergoing TPK. Graft survival was 30% at 1 year, 18% at 5 years, and 11% at 10 years. The most common organism was fusarium (23 patients, 38%). The median duration from presentation to surgery was 14 (8-21) days. Disease eradication was achieved in 44 patients (73%) and VA better than 3/60 was achieved in 14 (23%). Anatomical integrity was maintained in 46 (76%) eyes. Repeat PKP was performed in 15 patients (25%), most commonly for recurrent infection. Conclusion: TPK offers a good chance of disease eradication and maintenance of anatomical globe integrity and is a reasonable therapeutic option in patients with severe fungal infection.

Modified Corneal Collagen Cross-linking (M-CXL) Combined With Intrastromal Injection Of Voriconazole For The Treatment Of Severe Fungal Keratitis With Ongoing Corneal Melting

Objective The aim of this work is to evaluate the safety and efficacy of repeated sessions of modified corneal collagen cross linking (M-CXL) combined with intrastromal injection of voriconazole for the treatment of severe fungal keratitis with ongoing corneal melting and compare the outcome with intrastromal injection of voriconazole alone. Patients and Methods This is a retrospective comparative clinical cohort study. Thirty eyes with clinically suspected and lab-confirmed severe fungal keratitis with ongoing corneal melting were included. These eyes were classified randomly into two groups each of 15 eyes. In group (A), all the eyes underwent repeated sessions of M-CXL with frequent instillations (FI) of topical voriconazole each week till the reversal of corneal melting, then intrastromal injections of voriconazole were added each week till complete corneal healing together with negative culture on lab examination. In group (B), all the eyes underwent repeated intrastromal injections of voriconazole each week together with frequent instillations (FI) of topical voriconazole till complete corneal healing with negative culture on lab examination. Identification of organisms was done by lab study before and after treatment. Corneal healing was evaluated by corneal examination and anterior segment OCT (AS-OCT). Results Successful treatment was reported in 13 eyes (86.7%) of group (A), while in group (B), successful treatment was reported in 9 eyes (60%), while failure of treatment with complications was reported in 2 eyes (13.3%) in group (A) , however, in group (B), failure of treatment with complications was reported in 6 eyes (40%), with statistically significant difference (p &lt;0.05) between the two groups. Visual improvement was observed in group (A) more than group (B). Conclusion M-CXL followed by intrastromal injection of voriconazole was found to be effective in treating severe fungal keratitis with ongoing corneal melting due to the known action of CXL for reversal of corneal melting and anti-infective properties. Our results revealed that combined M-CXL and intrastromal injection of voriconazole was safer than intrastromal injection of voriconazole alone for treating severe fungal keratitis with corneal melting with better visual outcomes.

Effect of Corneal Collagen Cross-Linking on Subsequent Corneal Fungal Infection in Rats.

The purpose of this study was to determine whether corneal collagen cross-linking (CXL) alters fungal susceptibility and increases the severity of keratitis through macrophage activation in rats. Four weeks following CXL pretreatment, the corneal epithelium of adult rats was removed and inoculated with Candida albicans (C. albicans; CXL+inoculation group). The non-CXL-pretreated corneas were also inoculated with C. albicans (inoculation group). Clinical scoring and histopathological examination were performed to determine the severity of fungal keratitis. Immunofluorescence and confocal microscopy imaging were applied to determine the effects of CXL treatment on corneal local macrophage content. Real-time polymerase chain reaction (RT-PCR) and Western blots were used to evaluate mRNA and protein expression. Flow cytometry assays were performed to detect M1- and M2-type macrophages. CXL pretreatment (CXL+inoculation) resulted in higher infection success rate and more severe fungal keratitis than inoculation alone (inoculation group). On days 1, 3, and 7 following fungal infection, the increase in macrophage infiltration and IL-1β, MMP-9, and VEGFA expression was greater in the CXL+inoculation group than in the inoculation group. Number of M1- and M2-type macrophages, M1 to M2 ratio, M1-type macrophage genes, inducible nitric oxide synthase (iNOS), and tumor necrosis factor (TNFα) expression were higher in the CXL+inoculation group compared with the inoculation group. Our data demonstrate that CXL may increase the colonization of macrophages and activate more M1-type macrophages to increase fungal susceptibility and severity of keratitis. This study may aid long-term risk assessment and treatment of the complications of CXL.

The Outcome of Concurrent Intracameral Fluconazole Injection with Amniotic Membrane Transplantation for Fungal Keratitis in Dr. M. Djamil General Hospital: A Case Series

Background: Fungal keratitis is often difficult to eradicate and requires long treatment. Antifungal agents have lower efficacy because of low tissue penetration and the indolent nature of the infection. Fluconazole has effective ocular penetration ability, reaching aqueous concentration as same as plasm concentration. Multilayer amniotic membrane transplantation (MLAMT) has been shown to be a promising surgical procedure to reconstruct the ocular surface by supporting the epithelialization of the cornea and having protective antimicrobial properties. This study aims to report the outcome of concurrent intracameral fluconazole injection with amniotic membrane transplantation for fungal keratitis in Dr. M. Djamil General Hospital.&#x0D; Case presentation: Four inpatients in the ophthalmology ward of Dr. M. Djamil General Hospital with moderate to severe fungal keratitis. All patients were first treated with medications. Because the patients did not show clinical improvement after getting maximum therapy, they underwent intracameral fluconazole injection concurrent with MLAMT. MLAMT was performed with multilayered amniotic membranes to fill and cover the defect. The bandage contact lens was placed to protect and keep the MLAMT in place and for patients’ comfort. Patients were then observed for signs of inflammatory reaction and epithelialization. All patients showed reduced inflammation and improved epithelization after surgery.&#x0D; Conclusion: Concurrent intracameral fluconazole injection with MLAMT can be considered an alternative treatment for refractory fungal keratitis as it decreases the rate of inflammation and improves epithelization.

Clinical Outcome of Fungal Keratitis after Topical use of Injectable Fluconazole

Objectives: To evaluate the clinical outcome of fungal keratitis after topical use of injectable Fluconazole. Materials and Methods: This cross sectional study was conducted in the Department of ophthalmology in Nishtar Medical University, Multan and the duration of this study were from January 2022 to June 2022. Totally 100 patients who were suffering from fungal keratitis were enrolled. The enrolled patients were given topical 2% Fluconazole using Injectable fluconazole 2mg/ml and making it to 2% topical solution. They were also added topical 1% Atropine, lubricant and Cyclosporin A 0.05% was used for corneal melting. Patients were followed after 1 week and 1 month. A predesign questionnaire was used to collect data. Results: Out of total 100 patients, 79 were male and 21 were female with mean age of 38.70 ±9.41 years. The most common age group was 20-35 years and 36-50 years, followed by &gt;50 years of age group. Out of total patients, 69 (69.0%) patients had full recovery of appreciable vision, quality of life and pain related complaints. 30 (30%) patients had no improvement in vision. 1 (1%) patient had worsening of keratitis. Practical implication: This study suggest that topical use of injectable fluconazole is a safe and effective antifungal drug for the treatment of fungal keratitis. So this study will help the ophthalmologist to select better treatment option in order to recover the patients at time. Conclusion: It is concluded that Fluconazole in the form of injection can be a very useful treatment for severe fungal keratitis. Keywords: Fluconazole, Fungal Keratitis, Topical, Injectable, Ophthalmology, Sight-Threatening,

Outcomes of Severe Fungal Keratitis Using in vivo Confocal Microscopy and Early Therapeutic Penetrating Keratoplasty.

PurposeThe purpose of this study was to assess the impact of early diagnosis using in vivo confocal microscopy and early therapeutic penetrating keratoplasty (TPK) on the outcomes of severe cases of fungal keratitis.MethodsThis retrospective single-center study included 38 patients (40 eyes) with fungal keratitis who presented between December 2013 and February 2020. Preoperative, intraoperative, and postoperative parameters were recorded to assess the role of early correct diagnosis and early surgical therapy on visual acuity outcome and enucleation rate during follow-up.ResultsThe mean patient age was 51 years (71% females). The initial external diagnosis was correct in 20 cases (50%). The mean time from symptom onset until admission to our department was 46.8 ± 68.0 (median 28.5) days. The mean time to correct diagnosis after admission to our department was 1 day with in vivo confocal microscopy (IVCM). IVCM was performed in 38 cases, of which 36 (sensitivity: 94.7%) were positive for fungal infection. Twenty-seven out of 40 (67.5%) eyes received a TPK 4.2 ± 3.9 days after admission, with a mean graft size of 8.9 ± 1.9 mm. Three eyes (7.5%) were enucleated. The corrected distance visual acuity of the entire study population increased from 2.0 ± 1.2 LogMAR to 0.96 ± 1.17 LogMAR.ConclusionIn vivo confocal microscopy is a powerful tool for the early detection of fungal organisms in infectious keratitis. An early TPK with a large graft helps to eradicate the infection timely and results in a favorable visual acuity outcome and lower enucleation rate, especially when treating filamentous fungi.

A Case of Iris Neovascularization in Severe Fungal Keratitis Treated with Intracameral Bevacizumab

Purpose: We report a case in which iris neovascularization (NVI) improved after intracameral bevacizumab injection in a patient who exhibited fungal keratitis with NVI.Case summary: A 47-year-old man experienced a tree branch-induced injury to his right eye and was treated for keratitis for 1 month. However, his condition deteriorated and he was referred to our hospital. Initial slit lamp biomicroscopy findings showed a large, thick central deep stromal infiltration with a concentric circle shaped feathery-like margin, epithelial defect, satellite lesion, fungal ball, hypopyon, and NVI. Aspergíllus fumigatus was isolated in the corneal scraping culture. Amphotericin B, voriconazole, and natamycin were administered as topical treatment along with systemic amphotericin B. After treatment, the corneal lesions gradually improved, but NVI worsened. After the 5th week, total hyphema occurred; anterior chamber irrigation and intracameral bevacizumab injection were performed. Two weeks postoperatively, the NVI exhibited complete regression; corneal stromal melting with descemetocele appeared after 8 weeks. Penetrating keratoplasty was performed and NVI was no longer observed at 6 months after surgery.Conclusions: For the treatment of iris neovascularization in patients with infectious keratitis, intracameral bevacizumab injection at an appropriate time may be effective.

Combined topical and intracameral injection of Amphotericin B versus topical Amphotericin B in management of fungal keratitis in MOC, Egypt

Abstract: Fungal keratitis is one of the leading causes of blindness in developing countries in this study we evaluated the efficacy of a combination of topical and intracameral injections of amphotericin B in the treatment of severe fungal keratitis. Patients and methods: This prospective, comparative interventional randomized study included 40 patients of fungal keratitis attended outpatient clinic of MOC, faculty of medicine Mansoura University ,Egypt, in the period from January 2017 to December 2018.The patients were randomly divided into 2 groups: Group A: underwent only topical amphotrcine B. Group B: underwent combined topical & intracameral injection of antimicrobials. Patients were followed up at 1 day, 1 week, 2W, first month ,then monthly till the 6th month. Results: Both groups were sex and age matched .Trauma was the most common risk factor recorded .Asperigulus was the commonest causative agent (85%).in group A ,the size of corneal ulcer improved from 32.44±19.37to 29.71±17.16 at 1st week to 18.81±10.04 in the 1st month, in group B the ulcer size decreased from 30.24±16.09 to 21.81 ±11.04(p <0.001)in the 1st week the ulcer achieved complete healing within 3 months. The mean duration for the complete healing in group A ,was 48.82 ± 5.31 days while the mean duration in group B, that was 29.59 ± 3.24 days (p < 0.001). Conculsions: intrcameral Amphotrecine B injection is safe and effective technique in treatment of fungal keratitis.

Combined topical and intracameral injection of Amphotericin B versus topical Amphotericin B in management of fungal keratitis in MOC, Egypt

Fungal keratitis is a sight threatening condition which is widespread in tropical and subtropical countries. This study aimed to evaluate the efficacy of a combination of topical and intracameral injections of amphotericin B in the treatment of severe fungal keratitis. Patients and methods. This prospective, comparative study included 40 patients of culture proved fungal keratitis recruited from outpatient clinic of Mansoura ophthalmic center, faculty of medicine Mansoura University, Egypt, in the period from January 2017 to December 2018. Pregnant and lactating women, Children &lt; 12 years of age, One-eyed patients, Patients with concurrent sclera involvement and Patients with impending perforations, elevated intraocular pressure were excluded from the study. The patients were randomly divided into 2 groups: Group A: underwent only topical amphotericin B. Group B: underwent combined topical &amp; intracameral injection of antimicrobials. Patients were followed up at 1 day, 1 week, weekly till the end of the first month after injection then every 2 weeks for another month after then monthly till the 6th month. Results. Both groups were sex and age matched. Trauma was the most common risk factor recorded. Aspergillus was the commonest causative agent (85%) in group A, the size of corneal ulcer improved from 32.44 ± 19.37 to 29.71 ± 17.16 at 1st week to 18.81 ± 10.04 in the 1st month, in group B the ulcer size decreased from 30.24 ± 16.09 to 21.81 ± 11.04 (p&lt;0.001) in the 1st week the ulcer achieved complete healing within 3 months. In group A the hypopyon level was 2.46 ± 1.23 mm which was fixed at the same value at 2nd day then decreased to 1.36 ± 0.43 ml at 1st month then to 0.90 ± 0.31 mm and 0.37 ± 0.17 mm at 2nd and 3rd months. In group B, the base line of hypopyon level was 3.22 ± 2.09 mm decreased to 1.45 ± 0.62 mm (at 1st week) decreased from 1.02 ± 0.61 mm at 2nd weeks to 0.33 ± 0.19 mm at 6th weeks. In group A, the reported complications were staphyloma (2 cases), thinning (6 cases), hyphema (2 cases) and Atrophia Bulbi (1 case). In group B the complications showed mild variations in distribution as follows; staphyloma (1 case), thinning (3 cases), hyphema (3 cases) and Atrophia Bulbi (1 case). The mean duration for the complete healing in group A, was 48.82 ± 5.31 days while the mean duration in group B, that was 29.59 ± 3.24 days (p&lt; 0.001). Conclusions. Intracameral Amphotericin B injection is safe and effective technique in treatment of fungal keratitis.

Treatment of Severe Recalcitrant Fungal Keratitis Using Subconjunctival Fluconazole as an Adjunctive Therapy

Purpose: To evaluate the safety and effectiveness of 2% subconjunctival injection of Fluconazole as an adjunctive treatment in severe recalcitrant fungal keratitis.&#x0D; Study Design: Interventional case series.&#x0D; Place and Duration of Study: Ophthalmology department of Holy family hospital, Rawalpindi medical university, from January 2019 to August 2019.&#x0D; Methods: The study included 18 eyes of 18 patients with severe resistant fungal corneal ulcer.We excluded those cases who had known hypersensitivities to Fluconazole. These ulcers were refractory toprimary conventional antifungal therapy with topical Natamycin, topical and systemic Fluconazole. Sample for culture was taken with sterile cotton bud and scraping was taken with kimura spatula. All resistant cases were given1.0 ml of 2% subconjunctival Fluconazole injection once a day for at least one week. After that depending upon the condition, the injections were givenonalternate days for 2 weeks.&#x0D; Results: Average age of the patients was 35.22 years (SD ± 10.42). Among total 18 patients, six (33.33%) were females and 12 (66.67%) were males. Thirteen (72.22%) cases showed absolute response after one week and 5 (27.77%) cases needed more injections. Four (22.22%) of these 5 cases partiallyimproved andone case failed to show improvement. Final vision varied in different cases according to the position of the residual scar. Five cases ended up in keratoplasty. Local or systemic toxicity was not seen in any case.&#x0D; Conclusion: Subconjunctival injection of 2% Fluconazole can be used as an adjunctive therapy for severe fungal keratitis without any toxic complications.&#x0D; Key Words: Keratomycosis, Evisceration, Keratoplasty.

Clinical outcome after air-assisted manual deep anterior lamellar keratoplasty for fungal keratitis poorly responsive to medical treatment.

PurposeFungal keratitis remains an important disorder because of difficulty in its diagnosis, and some patients do not respond to medical treatment using antifungal local and systemic agents. This study was carried out to determine the therapeutic value of air-assisted manual therapeutic deep anterior lamellar keratoplasty (TDALK) in the treatment of fungal keratitis not curable by antifungal chemotherapy.MethodsSeventeen patients (18 eyes) who were referred to Fukuoka University Hospital and treated surgically from January 2006 to April 2018, in whom a diagnosis of fungal keratitis was confirmed by typical clinical findings and microbiological or histological analysis of corneal specimens, and who were poorly responsive to topical and systemic antifungal medication, whereas the lesion had not resulted in corneal perforation, were enrolled in this study and were treated by air-assisted manual TDALK. Clinical outcomes including treatment course, therapeutic success rate, visual acuity outcomes and graft clarity rate were analyzed.ResultsThe most common pathogen was Fusarium, followed by Candida and Aspergillus. Beneficial therapeutic results (a clear or translucent graft) were achieved in 15 of 18 eyes (83%). There was no recurrence of infection and resulting visual acuity ≤0.15 logarithm of minimal angle of resolution unit was achieved in 15 eyes (83%). Intraoperative microperforation of Descemet’s membrane (DM) was not observed in any patients.ConclusionAir-assisted manual TDALK can be effective for treating severe fungal keratitis. In addition, air-assisted manual TDALK might be an alternative procedure to big-bubble DALK, because it can provide ambulatory vision and can preserve potentiality of vision with less risk of intraoperative perforation of DM.

Epidemiology, risk factors, and clinical outcomes in severe microbial keratitis in South India

ABSTRACTPurpose: Here, we report risk factors associated with outcome in severe bacterial keratitis (BK), fungal keratitis (FK), and Acanthamoeba keratitis (AK) in India.Methods: Prospective observational cohort study conducted in Aravind Eye Hospital, India. Adults presenting with severe microbial keratitis (MK) were enrolled (size ≥3 mm) and followed to 21 days post-enrolment. Ulcer clinical features were recorded at presentation. Outcomes by final visit were classified as good (completely healed or reduced infiltrate size) or poor (enlarged infiltrate size, perforated, or surgery performed).Results: Of 252 participants with severe MK, 191 had FK, 18 had AK, 19 had BK, 4 had mixed BK/FK, and 20 were microbiologically negative. Median age was 50 years (interquartile range [IQR]: 37–60 years), 64% were male, 63% were agriculturalists, and 45% had no formal education. Corneal trauma occurred in 72%, and median symptom duration before presentation was 7 days (IQR: 5–15 days). Clinical features associated with FK were feathery margins (p < 0.001), raised profile (p = 0.039), or dry surface (p = 0.007). Hypopyon was more likely in BK (p = 0.001) and ring infiltrate in AK (p < 0.001). Ulcers with poor outcome (n = 106/214) were more likely to be larger (odds ratio [OR]: 1.63, 95% confidence interval [CI]: 1.30–2.05, p < 0.001), involve the posterior cornea at presentation (OR: 2.31, 95% CI: 1.16–4.59, p = 0.017), involve Aspergillus sp. (OR: 3.23, 95% CI: 1.26–8.25, p = 0.014), or occur in females (OR: 2.04, 95% CI: 1.03–4.04, p = 0.04). Even after treatment, 34% (n = 76/221) had severe visual impairment by the final visit.Conclusions: Severe MK occurred predominantly in agriculturalists post-corneal trauma and often had poor outcomes. Provision of community-based eyecare may allow earlier treatment and improve outcomes.

The Significance of Repeat Cultures in the Treatment of Severe Fungal Keratitis

To identify fungal keratitis patients who are at risk of a poor outcome and may benefit from closer follow-up or more aggressive treatment. Secondary analysis of randomized clinical trial data. We compared the clinical outcomes of patients who had positive 6-day fungal cultures with those who did not, using backward stepwise regression with covariates for all baseline clinical characteristics. Patients presenting with a smear-positive filamentous fungal ulcer and visual acuity of 20/400 or worse, and who subsequently had a 6-day fungal culture performed at the Aravind Eye Care system (India), Lumbini Eye Hospital (Nepal), or Bharatpur Eye Hospital (Nepal). The primary outcome is rate of corneal perforation and/or the need for therapeutic penetrating keratoplasty. Secondary outcomes include 3-month best spectacle-corrected visual acuity (BSCVA), 3-month infiltrate and/or scar size, and rate of re-epithelialization. Patients who tested positive at their 6-day culture had twice the hazard of experiencing a corneal perforation or the need for therapeutic penetrating keratoplasty (P= .002) than those who tested negative, even after controlling for baseline ulcer characteristics. These patients also had on average 0.26 logMAR lines worse BSCVA at 3months (P= .001). Culture positivity at day 6 was not a statistically significant predictor of 3-month infiltrate/scar-size (-0.24mm1; P= .45) or time to re-epithelialization (hazard ratio= .81; P= .31). Here we identify a uniquely valuable clinical tool, day 6 culture results, for the treatment of severe fungal keratitis. Risk stratification based on repeat culture positivity is an objective way to assess response to medical therapy and identify patients who are at high risk of a poor clinical outcome. This establishes a new standard of care for severe fungal keratitis management.

Full-thickness conjunctival flap covering surgery combined with amniotic membrane transplantation for severe fungal keratitis.

Fungal keratitis is a severe and common ocular infectious disease. The present study evaluated the efficiency of full-thickness conjunctival flap covering surgery with amniotic membrane transplantation (FCCS + AMT) as a transitional surgery for severe fungal keratitis. A total of 17 patients with severe fungal keratitis without corneal perforation underwent FCCS + AMT between January 2010 and December 2015. The pathogenic factors, preoperative diagnosis and postoperative prognosis of FCCS + AMT at 3 months were evaluated. Subsequently, 7 patients received sclerokeratoplasty, and the best-corrected visual acuity (BCVA) and recurrence ratio were analyzed at 1 month postoperatively. The primary risk factor was agricultural trauma (7 cases), followed by a non-agricultural object entering the eye (3 cases). Preoperatively, there were 10 cases of fungal keratitis positively identified using confocal microscopy and 9 cases positively identified by corneal scrapings. A total of 3 months following FCCS + AMT, the percentage of cases resulting in preservation of the eyeball was 88.24%, with 15/17 patients demonstrating complete conjunctival re-epithelization and a smooth conjunctival surface without any complications. A total of 2 (11.76%) patients experienced melting of the conjunctival flap and development of endophthalmitis, and subsequently underwent ocular evisceration surgery. A total of 7 patients underwent sclerokeratoplasty and the mean logarithm of the minimum angle of resolution BCVA at 1 month was significantly improved (0.689±0.121; P<0.001) compared with preoperative values (2.459±0.037) and BCVA values following FCCS + AMT (2.529±0.066). No recurrence was observed in any of the cases during the follow-up period. Conclusively, FCCS + AMT may be a preferable treatment for severe fungal keratitis of the entire corneal ulcer without perforation, and may save the eyeball and provide a greater opportunity for corneal transplantation.

Comparison of Oral Voriconazole Versus Oral Ketoconazole as an Adjunct to Topical Natamycin in Severe Fungal Keratitis: A Randomized Controlled Trial.

To compare the efficacy of oral voriconazole (VCZ) with oral ketoconazole (KCZ) as an adjunct to topical natamycin in severe fungal keratitis. Fifty eyes of 50 patients with proven severe fungal keratitis, (>5 mm size, involving >4 mm central cornea and >50% stromal depth), smear, and/or culture positive were randomized to receive either oral VCZ (n = 25) or oral KCZ (n = 25) 200 mg twice a day. Both groups received topical natamycin along with oral medication. The primary outcome measure was best spectacle-corrected visual acuity (BSCVA) at 3 months of follow-up. Secondary outcomes were the percentage of healed cases and scar size. The mean BSCVA after treatment was 1.3 ± 0.35 logarithm of minimum angle of resolution units in the VCZ group and 1.6 ± 0.39 logarithm of minimum angle of resolution units in the KCZ group [P = 0.004, 95% confidence interval (CI), -0.10 to 0.54]. The final mean scar size was smaller for oral VCZ than for oral KCZ (P = 0.04, 95% CI, -0.01 to 0.93 mm). The percentage of cases healed were 80% and 72% in VCZ and KCZ groups, respectively (P = 0.51, 95% CI, -0.15 to 0.31). The ratio of tear film to serum concentration of oral VCZ was better than oral KCZ at days 14 (P = 0.002) and 21 (P = 0.006). Although the duration and percentage of healing was similar in both groups, oral VCZ attained a significantly better tear film concentration with a smaller scar size and better BSCVA compared with oral KCZ. Thus, oral VCZ may be preferred over oral KCZ in severe fungal keratitis.