Evaluation of Intrastromal Injection of Voriconazole as a Therapeutic Adjunctive for the Management of Deep Recalcitrant Fungal Keratitis

Prakash, Gaurav; Sharma, Namrata; Goel, Manik; Titiyal, Jeewan S; Vajpayee, Rasik B

doi:10.1016/j.ajo.2008.02.023

Cited by 135 publications

(115 citation statements)

References 11 publications

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“…Penetrating keratoplasty (PK) is the most common surgical treatment used to excise lesions of the cornea and replaced with a donor corneal graft in case of refractory or severe cases of fungal keratitis [150]. In addition, it is an effective way to treat corneal perforations as a result of fungal infections [212].…”

Section: Treatmentmentioning

confidence: 99%

Pathogenesis of microbial keratitis

Lakhundi

Siddiqui

Khan

2017

Microbial Pathogenesis

156

113

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Microbial keratitis is a sight-threatening ocular infection caused by bacteria, fungi, and protist pathogens. Epithelial defects and injuries are key predisposing factors making the eye susceptible to corneal pathogens. Among bacterial pathogens, the most common agents responsible for keratitis include Staphylococcus aureus, Pseudomonas aeruginosa, Streptococcus pneumonia and Serratia species. Fungal agents of corneal infections include both filamentous as well as yeast, including Fusarium, Aspergillus, Phaeohyphomycetes, Curvularia, Paecilomyces, Scedosporium and Candida species, while in protists, Acanthamoeba spp. are responsible for causing ocular disease. Clinical features include redness, pain, tearing, blur vision and inflammation but symptoms vary depending on the causative agent. The underlying molecular mechanisms associated with microbial pathogenesis include virulence factors as well as the host factors that aid in the progression of keratitis, resulting in damage to the ocular tissue. The treatment therefore should focus not only on the elimination of the culprit but also on the neutralization of virulence factors to minimize the damage, in addition to repairing the damaged tissue. A complete understanding of the pathogenesis of microbial keratitis will lead to the rational development of therapeutic interventions. This is a timely review of our current understanding of the advances made in this field in a comprehensible manner. Coupled with the recently available genome sequence information and high throughput genomics technology, and the availability of innovative approaches, this will stimulate interest in this field.

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Section: Treatmentmentioning

confidence: 99%

Pathogenesis of microbial keratitis

Lakhundi

Siddiqui

Khan

2017

Microbial Pathogenesis

156

113

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“…No other antifungal agent was used concurrently to detect the response to voriconazole as a single antifungal medication. However, in other studies [6,12] the other antifungal eye drops were not stopped and were maintained after intrastromal injections of voriconazole for their patients with deep and/or resistant fungal keratitis. Thus, evaluation of the efficacy of intrastromal voriconazole as a single treatment modality in their cases was doubted.…”

Section: Discussionmentioning

confidence: 99%

“…So, each voriconazole vial of (Vfend 200 mg) can be used to prepare about 800 injections. Prakash et al [6] and Sharma et al [12] on the other hand, used a different method of reconstitution that was sufficient for only one injection and was very costly.…”

Section: Discussionmentioning

confidence: 99%

“…After topical and local anesthesia, the preloaded voriconazole was injected into cornea under the operating microscope according to the technique described by Prakash et al [6]. With the bevel down, the needle was inserted obliquely from the uninvolved, clear cornea to reach just flush to the ulcer at the mid-stromal level (as the intended level for drug deposit).…”

Section: Preparation and Injection Of Intrastromal Voriconazolementioning

confidence: 99%

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Topical Voriconazole Drops With and Without Intrastromal Voriconazole Injection for Treatment of Deep or Resistant Fungal Keratitis

Solaiman¹,

Alkawas²,

Ibrahim³

2015

J Clin Exp Ophthalmol

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Purpose: To compare the safety and efficacy of topical voriconazole drops with and without intrastromal voriconazole injection for treatment of deep and/or resistant fungal keratitis. Patients and methods:A prospective, randomized and comparative study performed on eyes with deep and/or resistant fungal keratitis. Eyes were randomly allocated into two groups according to their order of presentation. Group (A) included eyes treated with intrastromal injection(s) of voriconazole (50 μg/0.1 ml) plus voriconazole eye drops 1% and group (B) included eyes treated with topical voriconazole eye drops 1% alone. Healing of the fungal keratitis was considered as the primary outcome measure. Secondary outcome measures included any reported complication as well as the visual outcome.Results: Each group included 20 eyes with deep and/or resistant fungal keratitis. Complete healing of fungal keratitis was higher in group A (85%) than in group B (55%) and the difference was statistically significant (P<0.05). The duration of healing ranged between 2-4 weeks in group A and between 2-6 weeks in group B (P>0.05). Laboratory studies showed increased prevalence of filamentous fungi (70% in group A and 65% in group B) more than yeasts (30% in group A and 35% in group B), and the difference between both groups was statistically not significant (P>0.05). Conclusion:Voriconazole eye drops might be effective for treatment of deep and/or resistant fungal keratitis. Adding intrastromal injection to topical drops could significantly raise the healing rate and hasten the resolution period without significant complications related to injection.

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“…The use of intrastromal voriconazole was reported in a series of patients (n = 3) who were not responding to topical therapies [50]. However, in a separate study of persistent cases of FK that were not responding to NMN, VCN was added to the regimen in either the topical or intrastromal form, and healing times revealed no statistical difference [51].…”

Section: Intrastromal/intracameral Anti-fungal Treatmentmentioning

confidence: 99%

Fungal Keratitis: Update for 2014

Stone

Tan

2014

Curr Ophthalmol Rep

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Fungal keratitis is a challenging problem worldwide, and many obstacles remain to the effective prevention, diagnosis, and therapy of this vision-threatening condition. Recent research has highlighted progress in each of these facets of the clinical approach to keratomycosis. Increased awareness of contact lens-associated fungal keratitis has prompted regulators to pay greater attention to testing of contact lens solutions under realworld conditions. Related research has also delved into the mechanisms of fungal biofilm formation and related therapeutic targets. Advances in polymerase chain reaction methodologies promise to increase the rapidity and accuracy of diagnosis, thereby decreasing the delay in instituting appropriate therapy. Antifungal pharmacologic agents remain the first line of therapy, with the newer azole antifungal voriconazole being utilized in innovative ways, such as via intrastromal injection. Large prospective studies such as the Mycotic Ulcer Treatment Trial have helped delineate optimal treatment algorithms, and variations in surgical techniques and postoperative regimens continue to be refined. Natamycin may still be more effective than other recently utilized antifungals for the treatment of Fusarium infections, but treatment failure is still a concern. Post-keratoplasty immunosuppression may benefit from the use of topical calcineurin inhibitors such as cyclosporine and tacrolimus, given their intrinsic antifungal properties. It can be argued that the prevention, diagnosis, and treatment of fungal keratitis lag behind the state of the art for bacterial keratitis, but dramatic improvements are undoubtedly on the horizon.

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Evaluation of Intrastromal Injection of Voriconazole as a Therapeutic Adjunctive for the Management of Deep Recalcitrant Fungal Keratitis

Cited by 135 publications

References 11 publications

Pathogenesis of microbial keratitis

Pathogenesis of microbial keratitis

Topical Voriconazole Drops With and Without Intrastromal Voriconazole Injection for Treatment of Deep or Resistant Fungal Keratitis

Fungal Keratitis: Update for 2014

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