Naomi S. Falk

Adverse events after intravitreal infliximab (Remicade).

Purpose: To determine the tolerability of intravitreal infliximab (Remicade) in patients with refractory diabetic macular edema or choroidal neovascularization secondary to age-related macular degeneration. Methods: This is a prospective, interventional, noncomparative, open-label, 12-week pilot study of intravitreal infliximab in four patients who failed conventional therapies. Two had diabetic macular edema and two had choroidal neovascularization secondary to age-related macular degeneration. All patients received 0.5 mg/0.05 mL intravitreal infliximab and were eligible for a second injection at 6 weeks if reinjection criteria were met. Outcome measures were best-corrected visual acuity using standard Early Treatment Diabetic Retinopathy Study refraction, central retinal thickness on optical coherence tomography, fluorescein angiography, standard electroretinography, and microperimetry. Patients were evaluated at Days 0 and 1 and Weeks 2, 6, and 12. Six months after study completion, all patients were tested for human antimouse and human antichimeric antibodies. Results: At Week 12, visual acuity scores had declined in three patients. All patients had persistence of cystoid macular edema on optical coherence tomography, although two had a decrease in central retinal thickness. Three patients had an overall worsened appearance on angiography. On the final electroretinography, all patients had a decrease in maximal combined responses, from 7% to 24% from baseline, which may have been within expected variability of electroretinography data. To photopic flicker stimulus, three patients had slower latency of response, and all had decreased amplitudes. All patients declined on microperimetry. The first patient entered in the study met the criteria for a second injection because of improved standard electroretinography and microperimetry at Week 6. However, 2 weeks after the second injection, he developed panuveitis. Two other patients, after one injection only, had evidence of inflammation (vitritis or panuveitis) on examination at Week 6. Three patients developed systemic antibodies against infliximab (human antichimeric antibodies). Conclusion: Low-dose intravitreal infliximab was not well tolerated in this small group of patients and was both immunogenic and probably retinotoxic.

Vitreous Penetration Of Topical Moxifloxacin And Gatifloxacin In Humans

Purpose: To determine the vitreous penetration of the new fourth-generation topical fluoroquinolones moxifloxacin 0.5% and gatifloxacin 0.3%. Methods: A prospective randomized clinical trial comprising 12 eyes of 12 patients scheduled for pars plana vitrectomy between August 2003 and September 2003 was performed in a clinical practice. The patients were randomly assigned to receive topical moxifloxacin 0.5% (n = 6) or gatifloxacin 0.3% (n = 6). One half the patients in each antibiotic group received 1 drop every 15 minutes for a total of 3 doses starting 1 hour before surgery, and the other one half self-administered the antibiotic drop 4 times daily for 3 days before surgery and at 7 am on the day of surgery. Undiluted vitreous samples were obtained and analyzed using high-performance liquid chromatography. Results: Either moxifloxacin 0.5% or gatifloxacin 0.3% was detected in the vitreous in all 12 patients in the study. There was no significant difference between the mean vitreous concentration of moxifloxacin 0.5% given over 1 hour preoperatively (0.012 ± 0.011 &mgr;g/mL) and that given in the 3-day regimen (0.011 ± 0.008 &mgr;g/mL) (P = 0.93). There was also no significant difference between the mean vitreous concentration of gatifloxacin 0.3% given over 1 hour preoperatively (0.001 ± 0.0003&mgr;g/mL) and that given over 3 days (0.008 ± 0.006 &mgr;g/mL) (P = 0.11). Vitreous concentrations of moxifloxacin 0.5% and gatifloxacin 0.3% in each eye were all lower than the 90% minimum inhibitory concentration for the commonest bacterial isolates causing endophthalmitis. With both dosing regimens, the mean vitreous concentration of moxifloxacin 0.5% was higher than that of gatifloxacin 0.3% administered at the same regimen, but this was not statistically significant. Conclusion: Both topical moxifloxacin 0.5% and gatifloxacin 0.3% penetrated the vitreous in the uninflamed eye, but the vitreous concentrations attained were all lower than the 90% minimum inhibitory concentration for the commonest bacterial pathogens causing acute postoperative endophthalmitis.

Role of intravitreal triamcinolone acetonide in the treatment of postoperative endophthalmitis.

Purpose: To report the use of commercially available triamcinolone acetonide as adjunct treatment for acute-onset endophthalmitis after intraocular procedures. Methods: Charts of 14 patients who received intravitreal triamcinolone in combination with intravitreal antibiotics for treatment of acute endophthalmitis were reviewed. Patients were included if they presented with pain, vision loss, and severe anterior chamber reaction or hypopyon. Visual acuities, intraocular pressures, anterior chamber reaction, and view of fundus details were recorded at baseline, 1 day, 1 week, 1 month, and 3 months to 5 months. Results: Culture-positive results were found for 57% (8/14) of patients. Isolated species included Staphylococcus epidermidis, viridans streptococcus, group D Streptococcus (nonenterococcus), Propionibacterium acnes, and diphtheroid bacilli. Visual acuities improved an average of 7.5 Snellen lines. Preendophthalmitis level visual acuities were recovered in 78.6% patients (11/14), with 64% (9/14) of patients achieving visual acuity of 20/40 or better regardless of presenting vision. Resolution of anterior chamber reaction and view of fundus details were consistent with visual acuities. Conclusions: Intravitreal triamcinolone combined with intravitreal antibiotics appears to have a safety profile similar to current modalities with a favorable effect on visual recovery and function in the setting of acute postoperative endophthalmitis.

Infliximab stability after reconstitution, dilution, and storage under refrigeration.

Purpose: The purpose of this study was to investigate the stability of reconstituted infliximab solutions and determine whether infliximab is suitable for compounding for potential intravitreal use. Methods: Infliximab was reconstituted, and the solution was aliquoted and stored refrigerated. On each day of testing, an aliquot was serially diluted to concentrations ranging from 50,000 pg/mL to 69 pg/mL. Each dilution was assayed by microsphere immunoassay daily for 5 days and weekly for a total of 6 weeks. The outcome measure was median fluorescence intensity measured by dual laser flow analysis of fluorochrome-labeled secondary antibodies to infliximab bound to tumor necrosis factor-α–coated microspheres. Results: There was an increasing median fluorescence intensity for increasing infliximab concentration in a sigmoidal dose–response curve with a variable slope that was equivalent for each time point. Each respective concentration of infliximab showed nearly equivalent median fluorescence intensity for every time point over the 6-week period. Conclusion: The authors found that the immunoreactivity of 2 different concentrations of infliximab stored at 4°C over a 6-week period remained stable. Infliximab is suitable for compounding and could be a cost-effective intravitreal medication for use in clinical practice if further study supports its safety and efficacy.

Analysis of the molecular biologic milieu of the vitreous in proliferative vitreoretinopathy.

Purpose: Previous investigations have explored molecular differences between proliferative vitreoretinopathy and primary retinal detachment. An exploration of a greater number of molecules might provide novel insight into the biology of this disorder and identify potential therapeutic targets. Methods: Vitreous specimens were obtained from patients with epiretinal membranes or macular puckers (n = 15), patients with a primary retinal detachment without proliferative vitreoretinopathy (n = 15), and patients with retinal detachments and proliferative vitreoretinopathy (n = 15). A multiplex assay was performed to calculate the concentrations of 48 different cytokines and chemokines, and statistical analyses were performed to identify differences between the groups. Results: Of the 48 molecules that were studied, we identified 10 that were statistically significantly different in cases of proliferative vitreoretinopathy, including interleukins 4, 5, 6, and 15; granulocyte–macrophage colony-stimulating factors; stem cell factor; stem cell growth factor; macrophage inflammatory protein 1&agr;; and interferon &ggr;–induced protein 10. Conclusion: Proliferative vitreoretinopathy represents a highly ordered molecular process that involves discrete changes in the concentrations of specific cytokines and chemokines. These molecules may represent novel therapeutic targets.

Silicone oil migration into the orbit

ABSTRACT Purpose: To report a case in of intravitreal silicone oil migration into the inferior orbit. Silicone oil tamponade is commonly used in retinal detachment repair and extrusion into the orbital tissues is very rare. Methods: A 70-year-old male with a remote history of repair of a right ruptured globe and retinal detachment surgery presented with progressive right lower eyelid edema. There was a known history of intravitreal silicone oil instillation and removal. An elective right inferior orbitotomy with excisional biopsy was performed. Results: Histopathology confirmed the presence of silicone oil intermixed with necrotic fat. The patient had excellent cosmetic and functional outcome. Conclusion: The presence of silicone oil within the orbital fat may be a result of increased intraocular pressure and extrusion through presumably water-tight sclerotomy sites.