Intracameral Voriconazole Research Articles

To compare the safety and efficacy of intrastromal voriconazole alone and in combination with intracameral voriconazole in intractable cases of fungal keratitis

Background: Mycotic keratitis is a potential sight-threatening infection and a leading cause of ocular morbidity worldwide. It is inherently difficult to treat due to the delayed diagnosis and fungistatic nature of available topical medications. Aims and Objectives: The aim is to compare the safety and efficacy of intrastromal voriconazole alone and in combination with intracameral voriconazole in recalcitrant fungal keratitis cases. Materials and Methods: A prospective, hospital-based, interventional study was conducted in 40 cases of fungal keratitis involving >50% stromal thickness and not showing a good response to conventional antifungal treatment even after 4 weeks. Cases were randomly divided into two groups: group A and group B of 20 each; group A patients received intrastromal voriconazole, while group B patients were given intrastromal+intracameral voriconazole combination in 50 mg/0.1 mL dose. Cases were examined daily for 1 week and then every week for 4 weeks to monitor progression. Results: Out of 20 cases in group A, 14 (70%) patients got improved, while 18 (90%) patients in group B showed significant improvement after 4 weeks, and the difference was statistically significant (P=0.02). In group A, the average number of injections given to the patients was 3.65±1.56 for 15.2±8.79 days, while in group B, the average number of injections given to the patients was 2.65±1.44 for 13.2±7.768 days, with a statistically significant difference (P=0.033). Conclusion: Intrastromal and intracameral voriconazole combination is a cost-effective and highly efficacious modality in managing recalcitrant cases of fungal keratitis. It should be recommended in cases with thick hypopyon and Aspergillus as the causative fungi that do not respond to conventional treatment.

Toxicity of simultaneous intrastromal and intracameral injection of voriconazole on corneal endothelium in a rabbit model

Purpose To investigate the toxicity of repeated simultaneous intrastromal and intracameral injections of voriconazole in corneal endothelial cells in a rabbit model. Methods Thirty-six eyes of 18 New Zealand white rabbits (six eyes per group) were divided into 6 groups according to the concentration of voriconazole (Group A, 0%; Group B, 0.05%; Group C, 0.1%; Group D, 0.25%; Group E, 0.5%; Group F, 1%). A combination of intrastromal and intracameral voriconazole injections were administrated to the eyes of each group three times on days 0, 3, and 7. Corneal clouding grades and central corneal thickness (CCT) were examined on days 0, 3, 7, 10, and 14. The endothelial cell counts (ECC) were measured on days 0 and 14. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) were performed on day 14. Results Group F (1%) showed more severe corneal clouding than the other groups (Groups A–E) from day 7 (p < 0.05, respectively). There were no significant differences in CCT and ECC among the six groups at any time point (p > 0.05, respectively). SEM revealed blurring of the cell border and loss of microvilli at concentrations ≥0.25% (Groups D–F). TEM revealed microstructural changes in endothelial cells at concentrations ≥0.1% (Groups C–F), and multiple vacuoles were observed at a concentration of 1% voriconazole (Group F). Conclusions Repeated simultaneous intrastromal and intracameral voriconazole injections at a concentration of 0.1% or higher induced microstructural endothelial damage in rabbit corneal endothelial cells.

Intrastromal and intracameral voriconazole combination: An adjuvant therapy in intractable mycotic keratitis

: To study role of intrastromal and intracameral voriconazole combination in recalcitrant fungal Keratitis.: 20 cases of recalcitrant fungal keratitis involving &amp;#62;50% stromal thickness and not showing good response to oral fluconazole, topical natamycin (5%) and topical voriconazole (1%) eye drops after 4 weeks of treatment were included in the study after taking informed written consent. Patients with impending or frank perforation, scleral involvement and endophthalmitis were excluded from the study. 30 min before the procedure, patient was given Tab acetazolamide 250mg stat to lower the intraocular pressure (IOP). Then under all aseptic conditions, 50 microgram/0.1 ml dose of intrastromal and intracameral voriconazole was given with 30G needle. Cases were examined daily for 1 week and then every week for 4 weeks for monitoring progression of fungal keratitis. Out of 20 cases, 18 (90%) patients showed significant improvement after 4 weeks. Depending on the response after 1 week, patients were planned for repeat injection and only 1 patient required &amp;#62;3 injections in whom Lasiodiplodia theobromae was the causative organism. Only 1 patient got worsened and was ultimately managed with therapeutic keratoplasty. Intrastromal and intracameral voriconazole combination is an easy procedure with short learning curve which is highly efficacious and cost effective in recalcitrant fungal keratitis.

P166 Traumatic implantation keratitis with Schizophyllum commune in Central India

Poster session 2, September 22, 2022, 12:30 PM - 1:30 PMObjectivesDocumentation and dissemination of findings of difficult-to-treat fungal isolate in cases of Keratitis.MethodsBoth the cases received in 2019 and 2021 were followed and consent from the patient was obtained for documentation.Case 1: A 30-year-old farmer from Raisen, Madhya Pradesh was admitted to AIIMS, Bhopal on December 16, 2019. He presented with eye ache, watering of eyes, and diminution of vision for 15 days. On day0 (D0) December 2, 2019 trauma to the eye by husk, diminution of vision and other symptoms and consulted nearby hospital, and started medication on D06. With symptoms worsening on D14 he was admitted to AIIMS Bhopal. Same day corneal scrapping on KOH mount showed branched septate hyaline hyphae. Culture showed on D20 whitish wooly growth with central pale to pinkish growth. On LBCB mount hyaline septate hyphae with no sporulation and clamp connections observed. Based on whitish growth with raised fanning hairy structures and on microscopy some spicules tear drop like structures and resemblance as clamp connections no other sporulation provisional diagnosis of Schizophyllum species was given. Patient's condition worsened with no response to azoles and therapeutic keratoplasty was done.Case 2: A 56-year-old female sufffered trauma with a leaf. Around D10 was admitted in ophthalmology department of AIIMS, Bhopal with left corneal ulcer and hypopyon. Corneal scrapping was sent but no fungal elements were seen. After 15 days white fluffy growth was observed on SDA with chloramphenicol. On LPCB mount it showed no sporulation and parallel hyphae with clamp connections were observed. Therapeutic keratoplasty was done. Graft failed and condition worsened. No response to intracameral voriconazole. Patient lost vision in both eyes. Case was identified as fungal keratitis with suspected Basidiomycetes Schizophyllum species.Both the isolates were confirmed from PGIMER Reference Center at Chandigarh.ResultIn both cases surgical intervention was essential but therapeutic keratoplasty failed.ConclusionRecently surge in cases with Schizophyllum commune is observed with difficult management, Failure of therapeutic keratoplasty and infection of graft is a challenge.

A hospital-based observational comparative study of efficacy of intracameral voriconazole and oral ketoconazole in deep keratomycosis

Background: Fungal keratitis, one of the most common causes of ocular mycosis, is the second most common cause of blindness in the world, after cataracts. The aim of the study was to compare the efficacy of conventional topical, systemic medications and intracameral voriconazole injection in visual and structural outcomes in keratomycosis. Material and methods: We conducted a hospital-based observational study of 45 patients of 45 eyes with smear-positive fungal keratitis. Patients were categorized into three groups: Group I received systemic topical with oral ketoconazole 200 mg, Group II — topical medications with intracameral voriconazole 50 μgm/0.1 mL, Group III — topical medications with both oral ketoconazole 200 mg and intracameral voriconazole 50 μgm/0.1 mL. Results: The common fungal organism is identified as Fusarium. The mean final visual acuity (VA) was 1.25 ± 0.32, 1.47 ± 1.05, and 1.22 ± 0.37 logMAR in Group I, group II, and Group III, respectively. The mean improvement in VA was 0.33 ± 0.07, 0.01 ± 0.71, and –0.19 ± 0.02 logMAR without significant change (p = 0.9). There was a significant difference in VA between the final postoperative follow-up period and baseline in Group I cases (p = 0.0019). Whereas no difference in VA between the final postoperative follow-up period and baseline in either Group II (p = 0.0671) or Group III (p = 0.1505) cases. The difference in time between the disappearance of hypopyon and the mean time to infection healing was not statistically significant (p = 0.1). Three cases in each group were perforated, and keratoplasty was performed. These perforated cases did not show culture positive. Histopathology identified the isolated organisms as Aspergillus species (n = 3) and Fusarium species (n = 2) in the corneal buttons. Conclusion: The differences in VA between the three methods were not statistically significant, indicating no treatment method superior to others (inter-group). However, in Group I, there was a significant difference in VA between the final postoperative follow-up period and baseline (p = 0.0019). There was no difference in VA between these time intervals in either Group II (p = 0.0671) or Group III (p = 0.1505). Within-group or intra-group analysis reveals that the Group I method is more effective for VA. The success rate of the method depended cumulatively on the duration of intracameral voriconazole in the anterior chamber, non-drainage of hypopyon, and individual clinical response.

Candida keratitis and endopthalmitis after corneal transplantation; two case reports, a novel regimen and literature overview of therapeutic options.

To evaluate treatment options for candida keratitis and endopthalmitis after corneal transplantation. Case reports and literature review. Two patients with keratitis due to Candida glabrata/parapsilosis after corneal transplantation were successfully treated with a combination of topical voriconazole, intracameral voriconazole and amphotericin B, and systemic treatment with flucytosine. Natamycine and voriconazole topically are preferred therapeutic options for the treatment of fungal keratitis. Systemic flucytosine is a useful alternative additive, particularly for countries where natamycine is not registered as a pharmaceutical agent.

Fungal keratitis due to Rhodotorula glutinis: A Case Report

We describe a case of mycotic keratitis involving a rare fungus and review the literature on Rhodotorula keratitis. A 40-year-old man was struck in the right eye with a tree branch and developed a corneal ulcer involving the anterior portion of the cornea. Cultures grew Rhodotorula glutinis. The patient was initially treated with topical amphotericin, but only improved with topical and intracameral voriconazole administration. The corneal infiltrate resolved, leaving an anterior stromal scar, and the patient’s best-corrected visual acuity was 20/60 in the involved eye. Cases of Rhodotorula keratitis can pose a challenge to the ophthalmologist, with the diagnosis and the treatment regimen, as this yeast may not respond well to commercially available drugs. We report a case of Rhodotorula keratitis that was only resolved with voriconazole. Our case rein- forces the importance of the early diagnosis and correct management of fungal keratitis involving this rare, but potentially damaging yeast.

Efficacy of adjuvant intrastromal and combination of intrastromal and intracameral voriconazole in &lt;em&gt;Aspergillus fumigatus&lt;/em&gt;-induced moderate fungal keratitis in rabbits

BACKGROUND There is no in vivo evidence for the effectiveness of adjuvant intrastromal and combination of intrastromal and intracameral voriconazole (VCZ) for treating Aspergillus fumigatus keratitis. This study aimed to compare the efficacy of both agents against it. &#x0D; METHODS A randomized, masked, controlled experimental study was conducted on 11 albino New Zealand white rabbits in which moderate fungal keratitis was induced by inoculating spores of A. fumigatus to the cornea. The rabbits were allocated into 3 groups: 50 μg/0.1 ml intrastromal VCZ injection, 50 μg/0.1 ml intrastromal VCZ and intracameral VCZ injections, and topical VCZ (control). The treatment was given 5 days after inoculation. Epithelial defect, infiltrate size, corneal ulcer depth, and hypopyon were evaluated clinically. Histopathological and mycological examinations were also done 14 days after treatment. &#x0D; RESULTS All rabbits in the adjuvant treatment groups demonstrated a tendency of a better clinical response with decreasing size of epithelial defect (p = 0.679) and infiltrate (p = 0.755) than in the control group. Direct microscopy, corneal culture, and chop corneal tissue culture were still positive in most of the rabbits from all groups. Histopathological examination showed an increase of inflammatory cells after treatment in all groups, especially in rabbits which were inoculated with A. fumigatus spores in both eyes. &#x0D; CONCLUSIONS An adjuvant combination of intrastromal and intracameral VCZ showed a tendency of better clinical response for A. fumigatus-induced moderate fungal keratitis in rabbits.

To Study the Comparison of Therapeutic Effect of Topical Intrastromal and Intracameral Voriconazole in Patients of Fungal Corneal Ulcer

To Study the Comparison of Therapeutic Effect of Topical Intrastromal and Intracameral Voriconazole in Patients of Fungal Corneal Ulcer

The use of miltefosine in the management of refractory Acanthamoeba keratitis.

Acanthamoeba keratitis (AK) is a sight threatening infection most commonly affecting contact lens wearers. The authors report a case of intractable A.polyphaga and A.castellanii, with extensive intraocular spread, managed using oral miltefosine. A 59-year old male contact lens wearer was referred to the tertiary corneal service at Bristol Eye Hospital. Vision was hand movements on the left and 6/6 on the right. Clinical examination was consistent with left AK (confirmed by corneal scrape). Management included biguanide (polyhexamethylene biguanide (PHMB) 0.02%, later 0.06%) and diamidine (hexamidine 0.1%). Further treatment included imidazole (guttae voriconazole, oral posaconazole) and fortified biguanide (chlorhexidine 0.2%). Therapeutic PKP was performed. Microscopy revealed Acanthamoeba throughout host stroma. Corneal scrape and anterior chamber tap revealed persistent infection with Acanthamoeba. Intracameral voriconazole was administered twice. Clinically there was scleritis, with concerns regarding posterior segment involvement. There was a severe necrotic keratitis with almost complete corneal melt, requiring enucleation. Oral miltefosine was commenced to reduce the risk of transmission of Acanthamoeba beyond ocular structures at the time of the enucleation. Histopathological analysis detected A.polyphaga and A.castellanii in vitreous but not retina, choroid or optic nerve suggesting that infection had not progressed posteriorly through the ocular structures and the central nervous system was not involved. The use of miltefosine as a component of combination anti-parasitic therapy is associated with long-term survival in cases of Acanthamoeba infection of the central nervous system. This case reports its first systemic use in the United Kingdom in a case of severe intractable AK with intraocular spread.

Candida dubliniensis: A novel cause of fungal keratitis.

A 45-year-old female with history of contact lens wear presented with a persistent corneal ulcer that was unresponsive to topical moxifloxacin. The patient’s exam was concerning for fungal keratitis. Cultures were obtained, and the patient was started on fortified amphotericin B drops and oral voriconazole. The cultures identified Candida dubliniensis as the causative organism. The patient’s exam worsened despite treatment, and the decision was made for surgery. At the time of surgery, her cornea was found to have unexpectedly perforated. She underwent cryotherapy; tectonic penetrating keratoplasty; anterior chamber tap; intracameral voriconazole, amphotericin B, and cefuroxime; and a partial conjunctival flap. Pathology from the cornea showed GMS and PAS stains positive for fungal forms.C. dubliniensis is a yeast closely related to Candida albicans that was first described in 1995 as a cause of oral candidiasis in patients with AIDS. There are a few published cases of endophthalmitis due to C. dubliniensis in the ophthalmology literature, but to our knowledge, no cases of fungal keratitis due to this organism have been reported. C. dubliniensis is a novel cause of fungal keratitis that can be difficult to identify and treat but is felt to be less virulent than C. albicans and generally susceptible to available anti-fungal therapies.

Purpureocillium lilacinum keratitis: a case series and review of the literature

ObjectiveTo describe the clinical features and risk factors of and optimal antifungal therapy for Purpureocillium lilacinum keratitis. DesignRetrospective case series in a quaternary referral hospital setting. MethodsComprehensive chart review of patients diagnosed with P. lilacinum keratitis in the past 10 years. ParticipantsFour patients were identified. All were aged 60 years or greater, with none having prior ocular trauma. Two had significant potential environmental exposure risks, and 3 were using systemic immunosuppressants for scleritis. ResultsAll cases received empirical treatment that included topical corticosteroids. Three were treated with combined oral, topical, and intracameral voriconazole, but developed endophthalmitis necessitating surgery with poor outcomes, including enucleation in 2. One case received combined oral and topical voriconazole with terbinafine, and maintained visual acuity without the need for surgery. All P. lilacinum isolates were susceptible to voriconazole. ConclusionsP. lilacinum keratitis is rare, with the major risk factor being immunosuppression. There may be no history of ocular trauma. Microbiological diagnosis and antifungal susceptibility testing is essential. Combination synergistic antifungal therapy with topical voriconazole and oral terbinafine, with addition of systemic voriconazole if needed, results in the best outcome.

Ineffectiveness of intrastromal voriconazole for filamentous fungal keratitis.

PurposeThe purpose of this study is to describe the ineffectiveness of intrastromal voriconazole injection for filamentous fungal keratitis by contrasting the effectiveness for yeast keratitis.MethodsWe examined seven fungal keratitis patients prospectively. All yeast was identified by molecular phylogenetic analyses of the chromosomal regions coding for the D1/D2 domain of the large-subunit 26S ribosomal RNA gene. All filamentous fungi were identified by the sequencing of internal transcribed spacers of the ribosomal DNA gene regions. Approximately 0.1 mL of voriconazole diluted with saline to 1.0% was injected with a 30-gauge needle inserted obliquely into the three to five clear cornea sites around the abscess. All subjects were administered natamycin ointment and oral itraconazole. When needed, intravenous micafungin, voriconazole, and/or intracameral voriconazole were added. Clinical courses were observed by the slit lamp microscope. Histopathology was examined when the corneas were removed.ResultsAll cases that were caused by yeast healed quickly after injections. Two cases of keratitis caused by Fusarium, and one case caused by Aspergillus, did not heal completely. In the Fusarium cases, additional antifungal medications (3.0% topical voriconazole and intravenous injection of micafungin) were needed. After optical penetrating keratoplasty in one of the cases, fungi were found in the deep stroma of the removed cornea. In the case of Aspergillus keratitis, pathological findings also showed fungi deep in the stroma of the removed cornea and the keratitis recurred after therapeutic penetrating keratoplasty.ConclusionIntrastromal voriconazole injection is successful in treating yeast keratitis. However this is not the case for filamentous fungal keratitis.

Management of Fusarium keratitis and its associated fungal iris nodule with intracameral voriconazole and amphotericin B

A retrospective case report on the management of a 56‐year‐old man who was diagnosed with Fusarium keratitis with an associated iris fungal nodule. He presented with persistent right ocular pain, redness, photophobia and reduced vision following an injury six weeks earlier. Conservative management with topical antibiotics and intracameral injections was successfully used to treat a rare case of Fusarium keratitis with an associated fungal iris nodule. The patient had complete resolution of his vision. Therefore, conservative management of the fungal nodule is a successful therapy without the risk of anterior chamber dissemination, which may occur with surgical resection.

Management of recurrent Paecilomyces lilacinus keratitis

A 72‐year‐old man presented with Paecilomyces keratitis subsequent to immunosuppressive treatment. Despite medical therapy with voriconazole, perforation occurred requiring a tectonic keratoplasty of 10-mm. Despite oral, topical and intracameral voriconazole, there was recurrent stromal infiltration. A corneoscleral graft of 15-mm was undertaken. Two weeks later, hyphae were seen on the anterior lens capsule with hypopyon requiring phacoemulsification and anterior chamber washout. Six weeks later, there was evidence of endophthalmitis. Pars plana vitrectomy, capsulectomy and intravitreal injection of voriconazole were performed. Voriconazole treatment was continued for a further 10-months and then ceased. At 16-months following the last recurrence of Paecilomyces, there was no evidence of infection. After 20-months, the patient had a sutured intraocular lens with an artificial iris. Vision is 6/36 unaided and 6/24 pinhole.

Clinical Effects of Intracameral Voriconazole Injection in Patients with Fungal Keratitis Refractory to Conventional Treatment

Clinical Effects of Intracameral Voriconazole Injection in Patients with Fungal Keratitis Refractory to Conventional Treatment

Intracameral and Topical Voriconazole for Fungal Corneal Endoexudates

To evaluate the role of intracameral and topical voriconazole as treatment for fungal keratitis presenting with endothelial exudates. Five eyes of 5 patients with fungal keratitis presenting with endoexudates with or without infiltrates in the corneal stroma were included in the study. Intracameral voriconazole 50 mcg/0.1 mL was given followed by topical voriconazole 1% hourly. Main outcome measure was Resolution of endoexudates and corneal stromal infiltrates. On presentation, all 5 eyes had endoexudates. Diagnosis of fungal keratitis was based on microbiological analysis of endoexudates (3 eyes) and corneal scrapings (2 eyes). After the intervention, the reduction in the size and density of endoexudates were documented and a complete resolution of the infection was seen in all cases within 3 weeks to 3 months. Two patients experienced burning sensations with topical voriconazole. Best-corrected visual acuity (BCVA) at presentation was hand motions in 3 patients and less than 20/125 in the remaining 2 patients. Final BCVA varied from 20/2000 to 20/40 depending on location of corneal scar. Intracameral and topical voriconazole may be effective against deep fungal keratitis presenting with endoexudates.

Combination of intracameral and intrastromal voriconazole in the treatment of recalcitrant Acremonium fungal keratitis

We present a report of a 28-year-old female with fungal keratitis due to Acremonium that was unresponsive to full medical therapy over 3 weeks. The patient was treated with superficial keratectomy, intrastromal and intracameral voriconazole injections. There was a marked clinical improvement beginning on day 3 post-therapy that was sustained until the last follow-up at 6 months. This is the first case of fungal keratitis due to Acremonium treated by a combination of intrastromal and intracameral voriconazole. This cost-effective treatment modality proved to be significant in impeding the progression of this potentially blinding disease and improving visual prognosis.

Cytotoxicity of Voriconazole on Cultured Human Corneal Endothelial Cells

The purpose of the present study was to evaluate the toxicity of voriconazole on cultured human corneal endothelial cells (HCECs). HCECs were cultured and exposed to various concentrations of voriconazole (5.0 to 1,000 μg/ml). Cell viability was measured using a Cell Counting Kit-8 (CCK-8) and live/dead viability/cytotoxicity assays. Cell damage was assessed using phase-contrast microscopy after 24 h of exposure to voriconazole. To analyze the effect of voriconazole on the intercellular barrier, immunolocalization of zonula occludens 1 (ZO1) was performed. A flow cytometric assay was performed to evaluate the apoptotic and necrotic effects of voriconazole on HCECs. Cytotoxicity tests demonstrated the dose-dependent toxic effect of voriconazole on HCECs. Voriconazole concentrations of ≥100 μg/ml led to a significant reduction in cell viability. The morphological characteristics of HCECs also changed in a dose-dependent manner. Increasing concentrations of voriconazole resulted in fading staining for ZO1. Higher concentrations of voriconazole resulted in an increased number of propidium iodide (PI)-positive cells, indicating activation of the proapoptotic pathway. In conclusion, voriconazole may have a dose-dependent toxic effect on cultured HCECs. The results of this study suggest that although voriconazole concentrations of up to 50 μg/ml do not decrease cell viability, intracameral voriconazole concentrations of ≥100 μg/ml may increase the risk of corneal endothelial damage.

Severe Arthrographis kalrae Keratomycosis in an Immunocompetent Patient

To describe a severe case of keratomycosis caused by Arthrographis kalrae requiring repeated keratoplasty. A 42-year-old otherwise healthy soft contact lens wearer developed a unilateral central corneal ulcer. Treatment with topical and systemic voriconazole is described. Repeated microbiological testing of ocular swabs (culture) initially yielded Candida albicans. Under treatment with topical clotrimazole, the ulcer progressed, and a corneal perforation required a keratoplasty à chaud. For prophylaxis, the patient received fluconazole systemically and continuous topical clotrimazole. However, in 2 weeks time, the mycotic infiltrates penetrated the corneal transplant and led to a second keratoplasty only 1 month after the first one. In the meantime, the microbiological analysis of the first keratoplasty revealed A. kalrae, which was sensitive to voriconazole. High-dose serum level-controlled systemic voriconazole and topical voriconazole were able to stabilize, but not eliminate the infection. About 1 year after the start of the voriconazole therapy, treatment had to be discontinued because of side effects. Mycotic infiltrates increased, and even an intracameral voriconazole injection could not prevent a third and a fourth keratoplasty. Ocular infection with A. kalrae is very rare. The microbiological differentiation of A. kalrae can be difficult. Because a broad spectrum of fungi is sensitive to voriconazole, the early topical and possibly systemic treatment is a reasonable therapeutic option when a mycotic infection of the eye is suspected, even before the causative fungus is identified.