Clearance of intravitreal moxifloxacin

PURPOSE: To study the clearance of moxifloxacin after intravitreal injection in rabbits. METHODS: Intravitreal injections of 200 microg/0.1 mL of moxifloxacin were administered to rabbits. Four eyes per time point after injection (1 hour and 6, 12, 24, and 36 hours) and three eyes at 48 hours, respectively, were enucleated and immediately frozen and stored at -80 degrees C. Ocular dissection and isolation of frozen vitreous was performed. Vitreous samples were acquired at the various time intervals after injection. Antibiotic assays were performed with high performance liquid chromatography. RESULTS: The concentration of intravitreal moxifloxacin showed an exponential decay with a half-life of 1.72 hours. The mean vitreous concentration was 120.49 +/- 49.23 microg/mL 1 hour after injection, and declined to 20.23 +/- 5.85 microg/mL at 6 hours and 1.06 +/- 0.81 microg/mL at 12 hours, respectively. CONCLUSIONS: The vitreous concentrations achieved were several orders of magnitude greater than the MIC90 of organisms commonly involved in bacterial endophthalmitis, and therapeutic levels were maintained at 12 hours in uninflamed, phakic rabbit eyes. The pharmacokinetic data suggest that intravitreal moxifloxacin may have a role in the treatment of bacterial endophthalmitis.     

Liposome-bound cyclosporine: Clearance after intravitreal injection

The concentration of cyclosporine in the vitreous after intravitreal injection of 100 micrograms of either free or liposome-bound cyclosporine was studied in albino rabbits. We found that the half-life of free cyclosporine was about 6 hours and that of liposome-bound cyclosporine was about 3 days. The finding indicates that liposome-bound cyclosporine prolongs the availability of the drug.     

Successful treatment of postoperative fungal endophthalmitis using intravitreal and intracameral voriconazole

AIM: The aim of this study was to describe 3 cases of postoperative fungal endophthalmitis successfully treated with anterior chamber washout, pars plana vitrectomy, and intracameral and intravitreal voriconazole injection. RESULTS: Three (3) patients from a single retina center in India developed culture-proven fungal endophthalmitis after cataract surgery in 1 eye. All patients underwent anterior chamber washout, pars plana vitrectomy, and intracameral and intravitreal voriconazole injections intraoperatively. All cases demonstrated substantial improvement in vision and intraocular inflammation after surgery. CONCLUSIONS: The combination of anterior chamber washout, pars plana vitrectomy, and intracameral and intravitreal voriconazole injection is a viable therapeutic option in cases of fungal endophthalmitis.     

Clearance of intravitreal fluorouracil. Normal and aphakic vitrectomized eyes

The ocular pharmacokinetics of 5-fluorouracil (5-FU) after intravitreal administration in the rabbit are described for the first time. Following a 1 mg intravitreal injection of C-14 labeled 5-FU in the phakic nonvitrectomized eye, a peak level of 664 micrograms/ml is achieved which declines to 7.8 micrograms/ml at 24 hours. For the aphakic vitrectomized eye comparable values are 669 micrograms/ml at 0.1 hour and 0.21 micrograms/ml at 24 hours. 5-FU is cleared more than two times more rapidly in aphakic vitrectomized eyes than normal eyes during the first 12 hours following injection. Following this, when the actual concentrations are relatively low, the rate of clearance appears relatively similar for both groups of eyes. Although it is difficult to extrapolate from previous in vitro results, potentially therapeutic vitreous concentrations are present in normal rabbit eyes for up to 72 hours following a single intravitreal injection.     

Clearance and localization of intravitreal liposomes in the aphakic vitrectomized eye

The authors have examined the fate of intravitreally injected liposomes in the aphakic, vitrectomized eye of the rabbit. Liposomes labelled with 125[I]-p-hydroxybenzimidylphosphatidylethanolamine were eliminated rapidly from the intraocular fluid. Nonetheless, a significant fraction of these liposomes were found to bind to various ocular tissues including the retina, iris, sclera, and cornea. Ultrastructural studies with gold colloid-loaded liposomes revealed that retinal bound liposomes were attached to the inner limiting lamina but did not penetrate to the internal cells of the retina. Epiretinal cells bound and internalized gold colloid-loaded liposomes suggesting that these cells may be very sensitive to liposome mediated drug delivery.     

Unusual pharmacokinetics of intravitreal and systemic voriconazole in a patient with Scedosporium apiospermum endophthalmitis.

In this paper, we report a case of a post-traumatic Scedosporium endophthalmitis treated with a posterior vitrectomy, followed by intravitreal injections and systemic voriconazole. This is the second documented case of S. apiospermum endophthalmitis treated with voriconazole and the first case with intravitreal injections of voriconazole. A 29-year-old man developed endophthalmitis after being struck in the left eye by a chip from a swimming pool pump. Despite 3 weeks of prophylactic antibiotherapy, his visual acuity remained only for the perception of light and vitreous inflammation increased. A creamy-white fungal mass grew at the inferior peripheral retina and pars plana. The fungus was identified as S. apiospermum. Oral voriconazole, at 200 mg twice-daily, did not bring the infection under control, considering the low plasma and intravitreal concentrations. Before steady-state plasma voriconazole concentrations reached an efficacy level greater than minimum inhibitory concentration of Scedosporium, intravitreal injections of 64 ug/0.1 mL of voriconazole were initiated twice-weekly for 3 weeks. Administration of higher intravenous voriconazole doses (6 mg/kg b.i.d.) for 6 weeks was needed to achieve an antifungal effect without systemic dissemination.     

Successful treatment of Fusarium endophthalmitis with voriconazole and Aspergillus endophthalmitis with voriconazole plus caspofungin

PURPOSE: To report successful treatment of exogenous Fusarium and Aspergillus endophthalmitis with new antifungal agents. DESIGN: Interventional case report. METHODS: Treatment of two cases is reviewed. RESULTS: A 64-year-old man developed post-cataract Fusarium moniliforme endophthalmitis. Infection persisted despite removal of the intraocular lens, three vitrectomies, and five intravitreal injections of amphotericin. Inflammation resolved and vision improved from 20/80 to 20/40 on 6 months of oral voriconazole. A 55-year-old man developed post-cataract intraocular inflammation. After three vitrectomies and removal of the intraocular lens, Aspergillus fumigatus endophthalmitis was diagnosed. Intravitreal amphotericin and systemic voriconazole were given, but one week later there were early signs of recurrence. Intravenous caspofungin was added and the eye improved. Caspofungin was continued for 6 weeks and voriconazole for 6 months. Vision improved from counting fingers to 20/80 at 6 months and 20/25 at 23 months. CONCLUSION: Voriconazole is a promising new therapy for Fusarium and Aspergillus endophthalmitis. Caspofungin may act synergistically with voriconazole in treating Aspergillus endophthalmitis.     

Efficacy of intravitreal bevacizumab after unresponsive treatment with intravitreal ranibizumab

Objective: To evaluate visual outcomes of eyes with choroidal neovascular membrane secondary to age-related macular degeneration that were initially treated with intravitreal ranibizumab then switched to intravitreal bevacizumab due to treatment failure.Design: Retrospective chart review.Participants: Fifty eyes of 50 patients presenting to the Barnes Retina Institute.Methods: Patients unresponsive to treatment with intravitreal ranibizumab were switched to intravitreal bevacizumab. Main outcome measures included number of intravitreal injections, visual acuity (VA), and resolution of leakage. Mean follow-up was 6 months after the final intravitreal bevacizumab injection. On average, each patient received 3.5 ranibizumab injections and 2.5 bevacizumab injections. Each patient received an average of 6 injections.Results: Resolution of leakage on fluorescein angiography and optical coherence tomography was achieved in 44 eyes (88%). Initial VA ranged from 20/30 to counting fingers (CF) (median VA 20/125). Final VA ranged from 20/20 to CF (median VA 20/100). Change in VA varied from loss of 2 lines to gain of 4 lines, but overall, remained stable (average gain 0.3 lines). Eighteen eyes (36%) had afinal VA of ≥ 20/50 and 18 eyes (36%) had a final VA of ≤ 20/200.Conclusions: Treatment with intravitreal bevacizumab may be effective, as measured by visual and anatomic criteria, in patients who are unresponsive to treatment with intravitreal ranibizumab.     

Evaluation of pain during intravitreal Ozurdex injections vs intravitreal bevacizumab injections

Purpose

The purpose was to evaluate the pain associated with intravitreal Ozurdex injections, and to compare it with that associated with intravitreal bevacizumab injections.

Methods

The study included 57 eyes of 57 patients who received an intravitreal Ozurdex injection at our institution. Pain was measured by the visual analog scale (VAS). Additional parameters recorded included age, sex, indication for the injection, number of previous Ozurdex injections in the study eye, presence of diabetes mellitus, and lens status. Data were compared with a 2 : 1 sex- and age-matched control group of 114 patients who received intravitreal bevacizumab injections.

Results

Indications for injection included diabetic macular edema (40.4%) and macular edema secondary to central and branch retinal vein occlusion (28% and 31.6%, respectively). Pain scores on the VAS ranged from 0 to 90, with a mean of 20.8±20.3. There was no significant difference in pain between Ozurdex and bevacizumab injections. Pseudophakia was correlated with increased pain in Ozurdex injections.

Conclusions

This is the first series evaluating the pain associated with intravitreal Ozurdex injections. Despite a larger needle gauge and tunneled injection technique, intravitreal injection of Ozurdex is not associated with increased pain compared with bevacizumab. This finding may be a potential advantage for Ozurdex, and may serve to improve patient compliance with future long-term treatment protocols.     

Treatment of candida chorioretinitis with voriconazole

A 63-year-old female with candidemia following necrotizing pancreatitis developed clinical signs of chorioretinitis and underwent the systemic administration of voriconazole, after which anterior chamber inflammation and multiple, white, fluffy, chorioretinal lesions, under 1mm in diameter, were gradually resolved and visual acuity improved. We report the first Korean case of candida chorioretinitis successfully treated with the systemic administration of voriconazole.     

Toxicity of intravitreal oxiconazole

Oxiconazole, a new imidazole derivative, has a broad antifungal spectrum in vitro and in vivo. Adult New Zealand white rabbits were injected intravitreally with doses ranging from 10 to 100 micrograms of this drug. Eyes were evaluated with preoperative and postoperative biomicroscopy and indirect ophthalmoscopy, electroretinography, and light microscopy. From these data, it was determined that an intravitreal injection containing a concentration of up to 100 micrograms per 0.1 milliliter of oxiconazole was nontoxic to the rabbit eye.     

The efficacy of intravitreal levofloxacin and intravitreal dexamethasone in experimental Staphylococcus epidermidis endophthalmitis

This study was designed to investigate the efficacy of intravitreal levofloxacin, and intravitreal levofloxacin and dexamethasone combined in Staphylococcus epidermidis endophthalmitis. Albino rabbits (n = 25), infected with an intravitreal inoculum of S. epidermidis (1.0 x 10(5) colony forming units/0.1 ml), were divided into five groups (n = 5). Groups 1 and 2 received treatment 24 h after the inoculation, and groups 3 and 4 48 h after the inoculation. No treatment was given to the control group. Treatment efficacy was assessed by vitreous culture, clinical examination and histopathology. Five days after treatment, groups 1 and 2 had significantly lower clinical scores than the control group (p = 0.004, p = 0.007). The culture results of the treatment groups were sterile. The histopathological scores of the treatment groups were lower than the control group (p = 0.007). Studies on retinal toxicity and dose-response relation are needed to prove the efficacy of levofloxacin in S. epidermidis endophthalmitis.     

Use of topical voriconazole in Alternaria keratitis

CLINICAL CASE: A 38-year-old man with fungal Alternaria keratitis was referred from another hospital 25 days after post-traumatic penetrating keratoplastia surgery on his right eye. We commenced treatment with topical voriconazole and the condition resolved. DISCUSSION: Fungal Alternaria keratitis is rare, and treatment is difficult because the clinical response does not correlate well with the antibiotic in vitro sensitivity of the fungus. Clinical cases need to be diagnosed and treated quickly if visual loss is to be avoided. The combination of topical and systemic voriconazole has been shown to be an effective treatment for this condition     

Management of tunnel fungal infection with voriconazole

A 59-year-old woman presented 1 month after cataract surgery in the right eye with a stromal infiltrate at the site of the cataract surgery wound. The visual acuity was perception of light with accurate projection. Corneal scraping of the infiltrate revealed septate hyphae. There was no response to 6 weeks of therapy with topical fortified antibiotic agents and topical antifungal therapy in the form of natamycin 5%, amphotericin B 0.15%, and intracameral amphotericin B. The patient was started on oral voriconazole 200 mg twice daily and topical voriconazole 1% every hour, and resolution of the ulcer was noted within 3 days. At the 4-month follow-up, a visual acuity of 20/60 was achieved, with the formation of a vascularized corneal opacity superiorly. This case illustrates that topical and oral voriconazole may be used in the treatment of recalcitrant cases of fungal tunnel infections not responding to conventional antifungal therapy.