Intrastromal Voriconazole Research Articles

Efficacy of corneal debridement combined with intrastromal voriconazole injection as adjunctive therapy for recalcitrant fungal keratitis

Background Fungal keratitis is a serious cause of blindness worldwide, especially in developing countries. Many trial were done to accelerate healing and improve outcome of recalcitrant fungal keratitis unresponsive to standard clinical treatment. Aim To evaluate the efficacy of corneal debridement combined with intrastromal voriconazole injection as an adjunctive treatment for recalcitrant mycotic keratitis. Patients and methods This prospective randomized interventional study was carried out on 40 eyes of 40 patients with resistant fungal corneal ulcers. Patients were equally divided into two groups: in one group, corneal debridement combined with intrastromal voriconazole in the same setting (group A) was done as adjunctive therapy to topical treatment, and in the other group, only topical antifungal therapy was used guided with culture and sensitivity results (group B). All patients were subjected to ophthalmic examination and were followed-up daily for the first week then weekly till complete healing. Results Healing was achieved in 95% of cases of group A at the fourth week while healing was achieved in group B in only 55% of cases at the same duration with a statistically significant difference between both groups (X2=14.983, P = 0.002). No cases required amniotic membrane transplantation (AMT) in group A while 4 cases in group B required AMT due to thinning. Conclusions Corneal debridement combined with intrastromal injection of voriconazole may offer a good option as adjunctive therapy to traditional topical therapy for recalcitrant fungal keratitis and may shorten the duration of the treatment with faster recovery of vision.

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.

Fungal Keratitis Associated with Curvularia lunata: First Case Report from Türkiye

Fungal keratitis is a medical emergency that is among the most common causes of blindness in developing countries. The type of the agent may vary depending on the geographical conditions under which the patient lives, trauma exposure, the use of contact lenses and profession. Curvularia spp. is a saprophytic genus that rarely causes systemic disease in humans and has 250 species identified to date. They proliferate in soil and plants and spread to the environment with their spores and the formation of blackish and fluffy colonies is its most well-known morphological feature. There may be difficulties in cultivating brown (dematiaceous) fungi. Due to the similarity between the genera, conventional methods remain inadequate for diagnosis. In this report, a case of fungal keratitis associated with C.lunata was presented. Seventy-five years-old female patient admitted to the hospital with the symptoms of stinging pain, blurred vision, and swelling in the right eye. Her symptoms had begun four days ago after her eye was hit by a plant. The patient who had a history of peripheral neuropathy due to diabetes mellitus (DM) was hospitalized with a preliminary diagnosis of keratitis, and in the cultures of the patient's corneal scraping samples, the filamentous, black pigment-forming colonies of the pathogen growing on 5% sheep blood agar and potato dextrose agar showing an aerial hyphal structure, were stained with lactophenol cotton blue and examined under the microscope. The microscopic examination revealed geniculate conidiophores with brown pigmentation. On top of these structures were tetralocular macroconidia, one of which appeared to be larger than the main axis. The fungus was subjected to molecular identification with the prediagnosis of Curvularia/Bipolaris. DNA extraction of the ITS region polymerase chain reaction amplification and Sanger sequencing were performed for molecular identification. Sanger sequencing identified the agent to be Curvularia lunata with a similarity rate of 99.79% (NCBI-GenBank Nucleotide ID: OR365075). In vitro antifungal susceptibility of C.lunata was evaluated by microdilution method. Itraconazole and amphotericin B showed higher activity against C.lunata compared to other antifungals while fluconazole was the least active antifungal. Intrastromal and subconjunctival voriconazole injection was applied to the patient who was unresponsive to empirically initiated oral moxifloxacin and different topical treatments (vancomycin, ceftazidime, flucanozole, ganciclovir, cyclopentolate hydrochloride, hyaluronic acid and trehalose). After injection, right penetrating keratoplasty was applied due to increased thinning of the ulcerated area. No pathogen was detected in cultures taken after keratoplasty. Rare fungi should be considered in cases of keratitis that are difficult to treat. Fungal keratitis caused by brown fungi are clinically similar to each other and effective treatment protocols cannot be implemented without a species identification. Identification of the pathogen will enable genus-specific treatment. This will also help prevent complications that may occur. This article aims to present a case of fungal keratitis associated with C.lunata.

Intrastromal voriconazole as successful adjunctive approach for recalcitrant deep fungal keratitis.

Aim: To assess efficacy of intrastromal voriconazole (ISV) in the treatment of fungal keratitis non-responding to conventional antifungals. Methods: Eighteen patients with smear positive fungal keratitis, not responding to conventional topical/ systemic antifungal therapy up to 2 weeks, were included in the study. Afterwards, they were given ISV (50 µg in 0.1 ml) around the ulcer and continued to receive conventional antifungal therapy. Responses to treatment (decrease in size of the ulcer and infiltrates) were recorded daily for 3-days, at 1-week and every 2 weeks for 3-months, or until the ulcer had healed completely. Results: The mean age at presentation was 51 ± 17.83 years. The most common organism isolated was Fusarium (17/ 18), followed by Aspergillus (1/ 18). All the patients were successfully treated in terms of corneal healing, but one case did not improve in vision due to the existence of diabetic macular oedema. 6 patients improved after a single injection, 7 had to receive 2 and 5 improved after 3 injections. The mean number of injections in 17 treated patients was 1.94 ± 0.78. Moreover, the mean resolution time was 18.50 ± 6.25 days. The size of ulcer and height of hypopyon at presentation were noteworthy risk-factors linked to management outcomes. Deeper ulcers required a greater number of injections when compared to superficial ulcers. The mean best-corrected visual acuity improved from 0.94 to 0.25 at 3 months follow-up in all the patients. Conclusion: Intrastromal Voriconazole (50 µg/ 0.1 mL) appears to be an effective adjunct therapy in cases of recalcitrant deep fungal keratitis non-responding to conventional antifungals. Though, some may require repeated injections, timely ISV administration certainly reducing the need for tectonic/ therapeutic keratoplasty. Abbreviations: ISV = Intrastromal Voriconazole, AS-OCT = anterior-segment optical coherence topography, KOH = potassium hydroxide, BCVA = best-corrected visual acuity.

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.

Amniotic membrane transplantation with intra-stromal Voriconazole versus amniotic membrane transplantation with argon laser photocoagulation for treatment of resistant fungal keratitis

Background Fungal keratitis is a serious problem that may affect vision. Many procedures like argon laser, voriconazole injection, and amniotic membrane transplantation (AMT) may be used to control infection. Aim To compare between intrastromal voriconazole injection with AMT and argon laser photocoagulation with AMT as treatment for fungal keratitis. Patients and methods Mycotic keratitis cases were divided in two groups, with 15 cases each. In one group, intrastromal voriconazole injection and AMT in the same setting was done, and in the other group, argon laser photocoagulation and AMT in the same setting was done. The studied cases included 21 cases with mixed infection and nine cases were pure fungal keratitis according to culture results. In the voriconazole group, intrastromal injection followed by AMT was done, whereas in the argon group, the corneal ulcer was irradiated with argon after fluorescein staining followed by AMT in the same settings. Results Healing was achieved in both groups in 2–6 weeks in all cases. Less than 50% of cases of the voriconazole group healed by the third week, whereas 80% of cases of the argon laser group healed by the third week. Vision was increased in four (26.7%) patients in the voriconazole group, whereas in six (40%) cases in the argon laser group. Conclusions Argon laser with AMT gives better results than intrastromal voriconazole injection with AMT for the treatment of resistant mycotic keratitis.

Effectiveness of intrastromal voriconazole injection in the management of deep non healing fungal corneal ulcer

One of the most difficult conditions to cure is often corneal fungus infections. Due to low stromal penetration, current topical antifungal medications are not very successful in the treatment of fungal keratitis, which makes it challenging to treat cases of deep fungal corneal ulcers. To assess the efficiency of voriconazole intra stromal injection in the treatment of deep fungal corneal ulcers that donot heal. In this prospective interventional study of thirty patients, deep non-healing fungal corneal ulcers were successfully treated by combining intrastromal voriconazole with topical therapy. Voriconazole 50 gm/0.1 ml was injected intrastromally into the corneas of 30 patients with deep stromal non-healing fungal corneal ulcers who had not responded to topical antifungal medication. Patients were monitored for six to ten weeks following the operation. The size of the corneal infiltration was noted to decrease more quickly, and in the majority of cases, ulcers completely disappeared between 6 to 10 weeks. As an additional therapy, intrastromal voriconazole injection may be a safe and efficient strategy to treat cases of deeply seated fungal corneal ulcers that refuse to heal.

Amphotericin B versus Voriconazole in the treatment of fungal keratitis

Purpose Evaluate the efficiency and safety of Voriconazole compared with Amphotericin B in the treatment of fungal keratitis. Background Fungal keratitis in Egypt is considered the second prevalent corneal infection after bacterial keratitis. It is one of the main causes of corneal blindness in Egypt. Many recalcitrant cases are frequently met with. Delay in the diagnosis and management usually leads to complications. Patients and methods During the period from July 2016 to October 2019, 106 patients who were clinically diagnosed in one eye as fungal keratitis, followed by culture and histopathological proof were recruited. They were divided into groups A and B. One hundred and six eyes of 106 patients whose age ranged from 10 to 74 years of both sexes were recruited, 53 eyes in each group. Group A received Amphotericin B while group B received Voriconazole. Adjuvant measures were used in deteriorating progressive cases in the form of cyanoacrylate glue with a high oxygen permeability contact lens in impending perforation, intrastromal Voriconazole injection, and lastly therapeutic penetrating keratoplasty. Follow-up was done on days 1, 3, 7, then weekly until cure. Size, depth, deep vascularization, presence of satellites, intraocular pressure monitoring, hypopyon, and any complication were recorded. Visual acuity and healing outcome and duration to achieve were also recorded. Results In all, 80 cases (39 of group A and 41 of group B) were healed, 21 cases (11 of group A and 10 of group B) progressed and needed adjuvant treatment to heal, five cases (three of group A and two of group B) needed urgent therapeutic penetrating keratoplasty. Voriconazole group showed a shorter time for healing and less complications. Discussion Voriconazole was slightly better than Amphotericin B as regards the duration for healing, progression of keratitis, extent of deep vascularization, density of the healed scar, and visual acuity. Conclusion Both Amphotericin B and Voriconazole were successful in treating fungal keratitis. Voriconazole showed statistically significant better results.

Comparison of Safety and Efficacy of Intrastromal Injections of Voriconazole, Amphotericin B and Natamycin in Cases of Recalcitrant Fungal Keratitis: A Randomized Controlled Trial.

ObjectiveTo compare the safety and efficacy of intrastromal voriconazole (IS-VCZ), amphotericin B (IS-AMB) and natamycin (IS-NTM) as an adjunct to topical natamycin (NTM) in cases of recalcitrant fungal keratitis.DesignProspective randomized trial.SettingTertiary eye centre.ParticipantsSixty eyes of 60 patients with microbiologically proven recalcitrant fungal keratitis (ulcer size >2 mm, depth >50% of stroma, and not responding to topical NTM therapy for two weeks) were recruited.Methodspatients were randomized into three groups of 20 eyes, each receiving ISVCZ 50ug/0.1 mL, ISAMB, 5ug/0.1 mL and ISNTM 10ug/0.1 mL (prepared aseptically in ocular pharmacology). The patients in all three groups continued topical NTM 5% every four hours until the ulcer healed. Primary outcome measure was time taken till complete clinical resolution of infection, and secondary outcome measure was best corrected visual acuity (BCVA) at six months.ResultsAll three groups had comparable baseline parameters. The mean duration of healing was significantly better (p=0.02) in the ISNTM group (34±5.2 days) as compared to the ISVCZ group (36.1±4.8 days) and the ISAMB group (39.2±7.2 days). About 95%, 90% and 95% patients healed successfully in the ISVCZ, ISAMB and ISNTM groups, respectively. In terms of healing, deep vascularization was significantly greater in the ISAMB group (55%, p=0.02) when compared to the ISVCZ and ISNTM groups (31% and 26%, respectively). There were fewer repeat injections in the ISNTM group (7/20 vs 8/20 and 9/20 in the ISVCZ and ISNTM groups, respectively).ConclusionIntrastromal injections are a safe and effective adjunct to conventional therapy in the management of recalcitrant fungal keratitis. ISNTM had a similar visual outcome with faster healing while ISAMB had a higher rate of deep vascularization after healing.

Comparison of modified corneal cross-linking with intrastromal voriconazole for the treatment of fungal corneal ulcer.

The present study aimed to evaluate the efficacy of modified corneal cross-linking (CXL) for the treatment of fungal corneal ulcers compared with that following intrastromal voriconazole injection. In total, 31 patients with fungal corneal ulcers treated at The General Hospital of Northern Theater Command between October 2017 and October 2019 were enrolled. Among them, 10 eyes were treated with ultraviolet A (UV-A)/riboflavin CXL (CXL group), whilst 21 eyes were treated with debridement combined with intrastromal voriconazole (stromal injection group). Preoperative microbiological examination was performed in both groups, and evaluated using Fisher's exact test. Postoperatively, infection control and total efficacy rates, localized lesion, ulcer healing rate 1 week after surgery, visual acuity and complications were evaluated using Fisher's exact test, however visual acuity was analyzed by mixed-model ANOVA. The results showed that the pre-operative species distribution between the CXL and stromal injection groups did not significantly differ. The infection control rate in the CXL group was notably higher compared with that in the stromal injection group (P=0.04). Furthermore, the total efficacy rate in the CXL group was also markedly higher compared with that in the stromal injection group, though no statistically significant differences were observed. Localized lesions were observed in nine eyes (90.0%) in the CXL group and nine eyes (42.9%) in the stromal injection group (P=0.02). However, the rate of ulcer healing at 1 week postoperatively and the logarithm of the minimum angle of resolution (logMAR) of visual acuity were not found to be significantly different between the two groups. In terms of complications, with the exception of one patient in the CXL group exhibiting loss of corneal transparency and one patient in the stromal injection group presenting with partial corneal thinning, no other forms of complications were observed. In conclusion, the present study suggested that CXL could have a beneficial impact for treating fungal corneal ulcers in the aspects of infection control, localized lesions and accelerated epithelialization. In addition, except the loss of corneal transparency, this treatment approach could be applied with reduced risks of adverse events.

English

BACKGROUND Treatment of fungal ulcers is one of the most challenging tasks. Various topical antifungal drugs have poor corneal stromal penetration. Voriconazole is a broad spectrum drug and is an effective agent for the treatment of fungal keratitis as a topical preparation. It is potent against a broad range of clinically significant fungal infections both in the eye as well systemically. In tropical climatic conditions filamentous fungi commonly cause eye infections and are associated with poor visual outcomes. The treatment options for mycotic ulcers are limited, therefore direct intrastromal injections are helpful in the management of these deep mycotic keratitis. We wanted to evaluate the role of intrastromal injection of voriconazole in the management of deep fungal keratitis not responding to conventional therapy. METHODS This an interventional case series study done at a tertiary care centre in south India from the year April 2019 to August 2020. Eight eyes of eight patients with microbiologically proven deep stromal recalcitrant mycotic keratitis not responding to topical antifungal medications were evaluated. Voriconazole 50 microgram / 0.1 ml was injected around the infiltrate in the corneal stroma as an adjunctive to the topical antifungal treatment. Main outcome measure was a reduction of the size of the infiltrate and ulcer and decrease in infection on regular follow ups. RESULTS Before injecting voriconazole, all the cases were of either gradually worsening of lesions on topical treatment, or not responding to topical treatment. After the injection a rapid decrease in the size of corneal ulcer, hypopyon, and infiltration was seen within 3 weeks. CONCLUSIONS Targeted delivery of intrastromal voriconazole may be a safe and effective way in the management of deep seated fungal ulcers which respond poorly to conventional treatment procedures, thus reducing the need for further surgical treatment. KEYWORDS Intrastromal Injection, Voriconazole, Fungal Keratitis, Deep Mycotic Keratitis

TO EVALUATE THE EFFICACY OF INTRASTROMAL INJECTION OF VORICONAZOLE IN RESISTANT CASES OF FUNGAL CORNEAL ULCER

Purpose: To evaluate the efficacy of intrastromal injection of voriconazole in resistant cases of fungal corneal ulcer. Methods: 25 cases of fungal corneal ulcer were diagnosed on the basis of clinical findings and KOH staining between July 2019 to July 2020 in NMCH, Sasaram, Bihar. They were treated with topical natamycin (5%) and voriconazole (1%). 6 cases that did not improve; judged clinically by increasing size of ulcer and clinical signs; were subjected to intrastromal voriconazole (50mcg/0.1ml) around ulcer in 4 meridians. Observation and result: 3 cases improved clinically and rest 3 cases which did not improve were referred for therapeutic keratoplasty. Conclusion: In resistant cases of fungal corneal ulcer intrastromal injection of voriconazole can be tried.

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.

Therapeutic response time of topical voriconazole 1% and intrastromal voriconazole 0.05% versus topical natamycin 5% monotherapy in Fusarium keratitis in rabbit.

Fungal keratitis can be more difficult to treat than bacterial keratitis with worse outcomes. To evaluate the therapeutic response time of topical voriconazole combined with intrastromal voriconazole, and topical natamycin on Fusarium keratitis. The stroma of corneas of twelve New Zealand White rabbits was inoculated with Fusarium sp spores. Seven days after inoculation, they were divided into 2 groups randomly. Group A was treated with topical natamycin 5% for 21days. Group B was treated with intrastromal voriconazole 0.05% single injection at the beginning of treatment, continued with topical voriconazole 1% for 21days. Clinical evaluations for epithelial defect size and clinical scores in each group were performed on 1st, 3rd, 7th, 10th, 14th and 21st days after treatment. Mycological examinations were performed before and after the treatment. After treatment, there was no statistically significant difference between natamycin and voriconazole in reducing epithelial defect size at first, second or third week after treatment (P=.15; P=.39; and P=.90). The clinical scores on both groups also showed no statistically significant differences at first, second and third weeks after treatment (P=.24; P=.09; and P=.32). Qualitative mycological evaluation before and after the treatment showed no statistically significant difference in KOH examination (P=1; P=1) and culture in Sabouraud dextrose agar (P=1; P=1). Intrastromal voriconazole injection combined with topical voriconazole seems to give similar response time but not earlier in improving clinical presentation of Fusarium keratitis as topical natamycin.

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

Voriconazole in Treatment of Resistant Fungal Keratitis

Purpose: To study the effect of intrastromal Voriconazole for treatment of resistant fungal keratitis in a tertiary care eye hospital in Lahore, Pakistan.&#x0D; Study Design: Experimental interventional study.&#x0D; Place and Duration of Study: Avicenna Medical College Hospital, Lahore, from July 2017 to July 2019.&#x0D; Methods: Sixty four patients were selected. All patients with fugal keratitis were included. The patients with previous corneal scar, mature cataract, endophthalmitis, Panophthalmitis, scleral involvement, impending or frank corneal perforation and uncontrolled diabetic patientswere excluded.Corneal scrapings of all patients were sent for 10% KOH staining. All patients were given intrastromal Voriconazole at 3 to 4 sites in divided doses in one ml syringe with 27-guage needle. Injection was repeated on 4th and 8th day. It was combined by topical antifungal and antibiotic eye drops six hourly. Patients were followed at day two, five, nine, three weeks and at 3 months.&#x0D; Results: There were 55 males and 9 females. Average size of ulcer was 6.4mm ranging from 5.5mm ± 1.8mm. Fifty six (88%) patient showed improvement while eight (12%) patients ended up in melting of cornea which was managed with tectonic corneal graft. In three (5%) patients penetrating Keratoplasty was done. Conjunctival congestion and ocular pain improved significantly one week after third dose but final visual acuity was not significantly improved due to scarring.&#x0D; Conclusion: The intrastromal corneal voriconazole is an effective treatment for fungal keratitis in term of healing corneal ulcer, control of infection and saving of eye from corneal perforation and permanent blindness.&#x0D; Key Words: Voriconazole, Fungal keratitis, Penetrating Keratoplasty.

Combined Intrastromal Voriconazole and Amphotericin B Treatment for Persistent Fungal Keratitis.

To evaluate the clinical outcomes of combined intrastromal voriconazole and intrastromal amphotericin B for the treatment of persistent fungal keratitis. Patients who received combined corneal intrastromal voriconazole (0.05 mg/0.1 mL) and intrastromal liposomal amphotericin B (0.01 mg/0.1 mL) injections in addition to topical therapy for treatment of persistent fungal keratitis were included in the study. Persistence was described as no improvement or progression in the clinical findings despite treatment with combined topical voriconazole (1 mg/0.1 mL) and topical amphotericin B drops (0.15 mg/0.1 mL) hourly for at least 10 days. The healing of keratitis was considered as the complete closure of epithelial defect with complete resolution of a corneal infiltrate. Thirty-two eyes of 32 patients who met the inclusion criteria were included in this study. Predominant organisms in fungal isolates were Aspergillus species. Combination therapy of intrastromal amphotericin B and intrastromal voriconazole in addition to topical therapy resulted in complete resolution of persistent fungal keratitis in 28 (87.5%) patients. The mean number of intrastromal injections was 9.3±6.4 and ranged from 1 to 18. The mean best-corrected visual acuity values improved from 2.17±0.43 to 1.76±0.77 logarithm of the minimum angle of resolution units (P=0.003). The mean duration of complete epithelial closure was 45.3±16.3 days. Four patients required therapeutic penetrating keratoplasty because of persistence of fungal keratitis (3 patients) and progression of keratitis (1 patient). There was no need for evisceration. Combination therapy with intrastromal voriconazole and intrastromal amphotericin B may be an effective adjunct treatment for persistent fungal keratitis.

Intrastromal voriconazole: An adjuvant approach for recalcitrant mycotic keratitis.

Purpose:To evaluate the efficacy of intrastromal voriconazole for the management of fungal keratitis not responding to conventional therapy.Methods:Patients having microbiologically proven fungal keratitis with poor response to 2 weeks of conventional topical therapy were included in the study. After obtaining informed consent, an intrastromal injection of voriconazole was administered around the ulcer. Response to treatment in the form reduction in the size of the ulcer and infiltration was recorded on regular follow-ups.Results:Out of a total of 20 patients, 14 responded to intrastromal treatment and resolved, whereas six patients progressed to perforation. Mean resolution time was 35.5 ± 9.2 days. The most common organism isolated was Fusarium in six patients while Aspergillus and Mucor were isolated in two each. The causative organism could not be isolated in eight patients. The size of the ulcer at presentation and height of hypopyon were found to be significant risk factors associated with treatment outcomes.Conclusion:Intrastromal voriconazole as an adjuvant therapy appeared to be effective in treatment of fungal keratomycosis not responding to conventional therapy, thus, reducing the need for therapeutic or tectonic keratoplasty.

Role of intrastromal voriconazole in recalcitrant fungal keratitis

Objectives: To study role of intrastromal voriconazole in recalcitrant fungal Keratitis.Material and Methods: 30 cases of fungal keratitis who were having >50% stromal thickness involvement and not showing good response to topical Natamycin (5%) and topical Voriconazole (1%) eye drops were included in the study. Cases with impending or frank perforation, involvement of sclera or endophthalmitis were excluded from the study. 50 microgram/0.1 ml of Voriconazole was injected with a 30G needle in midstoma, divided equally in all four quadrants. 1% voriconazole eye drops were also continued. Cases were examined daily for 1 week and then every week for 4 weeks.Results: Out of 30 patients, 24 patients (80%) showed significant improvement after 4 week, 3 patients (10%) did not show any improvement and 3 patients (10%) got worsened and ultimately managed with therapeutic keratoplasty.Conclusion: Intrastromal voriconazole is highly efficacious in recalcitrant fungal keratitis. It is just an OPD procedure. It may not only save the eye but less number of patients will require therapeutic keratoplasty.