Steven R. Sanislo

A Prospective Randomized Evaluation of Topical Gatifloxacin on Conjunctival Flora in Patients Undergoing Intravitreal Injections

PURPOSE We sought to assess the efficacy of 3-day topical gatifloxacin use in combination with povidone-iodine (PVI) versus PVI alone in eliminating conjunctival bacterial flora in patients scheduled to undergo intravitreal (IVT) injection. DESIGN Prospective, randomized single-blind clinical trial. PARTICIPANTS We included 129 patients scheduled to undergo 273 IVT injections at California Vitreoretinal Center at Stanford University. METHODS Study patients were randomized to self-administration of gatifloxacin drops for 3 days before injection, or no pretreatment antibiotics. Cultures were collected from the bulbar conjunctiva at the injection site and at the corresponding location in the fellow eye before PVI preparation. After topical PVI treatment and immediately before injection, a third culture was obtained at the injection site. Additionally, the injection needle was also cultured after the procedure. MAIN OUTCOME MEASURES Incidence of positive bacterial samples collected from injection site conjunctiva and injection needles. RESULTS Three-day gatifloxacin use resulted in a significantly lower rate of SeptiChek (Becton Dickinson, Franklin Lakes, NJ) positive cultures compared with untreated controls (21% vs 48% respectively, P = 0.005). After topical PVI, the rate of positive bacterial cultures in gatifloxacin-treated and control eyes were similar (8% and 4%, respectively; P = 0.324). CONCLUSIONS Although 3-day topical gatifloxacin use is effective in reducing the frequency of conjunctival bacterial growth relative to untreated eyes, antibiotic use confers no additional benefit in combination with PVI than eyes receiving PVI alone. This supports that topical PVI is an effective preinjection monotherapy for infection prophylaxis in the setting of IVT injections.

Surveillance for potential adverse events associated with the use of intravitreal bevacizumab for retinal and choroidal vascular disease.

Purpose: To systematically study potential adverse events associated with the use of intraocular bevacizumab at a single medical center. Methods: Retrospective study of all consecutive patients receiving intraocular bevacizumab injections at the Stanford University Department of Ophthalmology between November 15, 2005 and July 14, 2006. Bevacizumab was given for exudative age-related macular degeneration, retinal vascular occlusion, diabetic macular edema, neovascular glaucoma, and five other indications. Results: We analyzed medical records of 186 subjects (203 eyes) who received a total of 578 injections of 1.25 mg of bevacizumab. The average follow-up was approximately 6 months. Five eyes with exudative age-related macular degeneration developed retinal pigment epithelial (RPE) tears, all with preexisting RPE detachments. These five eyes represented 2.9% of all age-related macular degeneration eyes treated and 7% of the age-related macular degeneration eyes with preexisting RPE detachments at initiation of treatment. Other adverse events were rare and included retinal ischemia, subretinal hemorrhage, vitreous hemorrhage, ocular irritation or pain, worsened hypertension, and headache. No death or thromboembolic events were observed. Conclusion: Intraocular bevacizumab appears to be well tolerated for the treatment of a variety of retinal and choroidal vascular diseases. RPE tears may occur when treating choroidal neovascularization, particularly in patients with preexisting RPE detachment.

Retinal pigment epithelium tears after intravitreal injection of bevacizumab (avastin) for neovascular age-related macular degeneration.

Background: Intravitreal bevacizumab (Avastin, Genentech, Inc., South San Francisco, CA) treatment of neovascular age-related macular degeneration (AMD) has become an important part of clinical retinal practice. We describe retinal pigment epithelium (RPE) tears that were noted after intravitreal injection of bevacizumab. Methods: In this multimember, retrospective case series, data on eyes that developed RPE tears after intravitreal bevacizumab injection were collected and analyzed. Previous treatments, type of lesion, time to tear, and preinjection and final visual acuities were all compared. The total numbers of bevacizumab injections were available from all four institutions and compiled to estimate the incidence rate. Results: Four retina centers administered a total of 1,455 intravitreal 1.25-mg bevacizumab injections for neovascular AMD during the 9-month study period. Twelve patients presented with RPE tears within 4 days to 8 weeks of injection (mean ± SD, 24.3 ± 15.2 days from injection to tear). In each case, the RPE tear was preceded by an RPE detachment, and all had a component of serous sub-RPE fluid. On the basis of our collective data, we estimate an incidence rate of ≈0.8%. Conclusions: RPE tears can occur after intravitreal injection of bevacizumab. The low incidence of this adverse event should not preclude anti–vascular endothelial growth factor therapy counseling for patients with neovascular AMD, but eyes with serous RPE detachments appear to be most vulnerable to this adverse event.

Bacterial contamination of ocular surface and needles in patients undergoing intravitreal injections.

Purpose: To evaluate potential sources of bacterial contamination during intravitreal (IVT) injection procedures. Methods: Patients scheduled for IVT injection were asked to enroll in the study at the California Vitreoretinal Center (Menlo Park, CA) and the Vantage Eye Center (Salinas, CA) between October 2004 and April 2005. A total of 104 patients participated in the study, with a total of 118 IVT injection procedures performed on 107 eyes. Standard microbiological techniques were used to culture, identify, and quantify bacterial contamination of injection needles and the bulbar conjunctiva at the injection site in patients undergoing IVT injections. The main outcomes measured were type and quantity of bacterial isolates. Results: Two (2%) of 114 needles collected were contaminated with bacteria. The prevalence of bacterial contamination of the injection site on the bulbar conjunctiva was 43% before prophylaxis on the day of the injection with topical antibiotics and povidone–iodine, with a statistically significant reduction to 13% after prophylaxis (P < 0.0001). Coagulase-negative Staphylococcus, the most common bacterium isolated from the ocular surface, was isolated from both culture-positive needles. Conclusions: IVT injection needles became contaminated with bacteria during the injection procedure. Although the contamination rate was low, this supports a mechanism of postinjection endophthalmitis in which there is direct inoculation of ocular surface flora into the vitreous cavity by the injection needle.

Antibiotic Susceptibility Patterns of Ocular Bacterial Flora in Patients Undergoing Intravitreal Injections

PURPOSE To determine the antibiotic susceptibility patterns of conjunctival flora in patients undergoing intravitreal (IVT) injection. DESIGN Prospective, observational study. PARTICIPANTS Patients (n = 85) scheduled to undergo 136 IVT injections at California Vitreoretinal Center at Stanford University. METHODS Conjunctival cultures were obtained on the day of the IVT injection from the injection site bulbar conjunctiva before the application of povidone-iodine or antibiotics. MAIN OUTCOME MEASURES Bacterial isolates were identified and tested for antibiotic susceptibility using either the Kirby-Bauer disc-diffusion technique or MicroScan-WalkAway system. RESULTS Our analysis included 136 samples collected from 90 eyes of 85 patients. Of those with positive cultures (n = 65), the most common bacterial isolates were coagulase-negative staphylococci (CNS), comprising 59 (83%) of the 71 bacterial strains. Among the CNS, all were susceptible to vancomycin and >80% were susceptible to gentamicin, chloramphenicol, tetracycline, and imipenem. Between 60% and 80% of the CNS were susceptible to the cephalosporins and newer generation fluoroquinolones. Fewer than 60% were susceptible to the penicillin analogs, erythromycin, and the earlier generation fluoroquinolones. Nearly half of the CNS (47%) were resistant to oxacillin/methicillin. CONCLUSIONS Bacteria isolated from the injection site of patients undergoing IVT injections were mostly CNS. Most are sensitive to vancomycin, gentamicin, and chloramphenicol. FINANCIAL DISCLOSURE(S) Proprietary or commercial disclosure may be found after the references.

Triamcinolone Acetonide Preparations: Impact of Crystal Size on In Vitro Behavior

Purpose: To characterize the in vitro behavior of three preparations of triamcinolone acetonide (TA). Methods: Three preparations of TA were mixed with Balanced Salt Solution Plus: commercially available TA (Kenalog 40, Bristol-Myers Squibb, Princeton, NJ), compounded preservative-free triamcinolone acetonide (PFTA, New England Compounding Center, Framingham, MA), and triamcinolone acetonide injectable suspension (TAIS, TRIESENCE, Alcon, Inc., Fort Worth, TX). We determined the mean number of crystalline aggregates per high-power deconvolution microscopy field, largest aggregate area, and spectroscopic photometric absorption. Results: Preservative-free triamcinolone acetonide had larger mean number of aggregates compared with TA (time 0 P = 0.002, 10 minutes P < 0.001) and TAIS (time 0 P < 0.001, 10 minutes P = 0.003). Aggregate size varied at both 0 and 10 minutes: TAIS > TA > PFTA. Spectroscopic photometric absorption decreased in direct correlation to aggregate size over time for all three preparations. Conclusion: In vitro, PFTA in Balanced Salt Solution Plus had more aggregates of smaller size than either TA or TAIS. By contrast, TAIS had much larger aggregate size than both PFTA and TA, and this increased over time. These findings correlate with the clinical observations that PFTA and TA tend to disperse throughout the vitreous, whereas TAIS tends to conglomerate and gravitate toward the most dependent portion of the eye in a globular fashion.

Barriers to Follow-Up and Strategies to Improve Adherence to Appointments for Care of Chronic Eye Diseases.

PURPOSE To understand factors associated with poor attendance of follow-up appointments for care of glaucoma (GL), AMD, and diabetic retinopathy (DR) in a tertiary referral center, and to identify strategies to improve adherence. METHODS Cross-sectional study of 240 adults attending follow-up appointments for GL, AMD, or DR. Cases (N = 102) were patients with poor follow-up who missed and failed to reschedule an appointment within 1 month of the recommended follow-up date during the preceding year. Controls (N = 138) were patients who completed the assigned follow-up. Data regarding the factors impacting adherence to appointments were collected via an orally administered questionnaire. Multivariate logistic regression was performed to determine factors associated with poor follow-up. RESULTS In a multivariate logistic regression model, independent factors significantly associated with poor follow-up included incorrectly answering more than 50% of questions about eye disease (adjusted odds ratio [OR] = 3.24, P = 0.001), legal blindness (adjusted OR 2.64, P = 0.013), the presence of glaucomatous versus retinal disease (adjusted OR 2.06, P = 0.013), and difficulty for the study subject and/or escort taking time away from work for the appointments (adjusted OR 1.80, P = 0.049). Subjects identified the following strategies to improve follow-up: contact with others having the same eye condition (41.3%), greater education regarding eye disease (40.8%), and improved transportation services to the clinic (44.6%). CONCLUSIONS Low disease knowledge scores, legal blindness, and difficulty getting time away from work for appointments adversely impacted follow-up independent of eye disease diagnosis. Improvements in patient education, transportation services, and clinic efficiency may increase adherence to recommended appointment intervals.

16-Gy low-voltage x-ray irradiation with ranibizumab therapy for AMD: 6-month safety and functional outcomes.

BACKGROUND AND OBJECTIVE To describe the 6-month safety and preliminary efficacy outcomes of the use of 16-Gy radiation with intravitreal ranibizumab for patients with neovascular age-related macular degeneration (AMD). PATIENTS AND METHODS A single treatment of a non-invasive, externally delivered low-voltage 16-Gy x-ray irradiation was administered in one session through three locations in the inferior pars plana. Optical coherence tomography (OCT) and Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity (VA) examinations were performed at 1 week, 1 month, and monthly thereafter, with quarterly fluorescein angiography (FA). After the two initial ranibizumab injections, subsequent injections were administered according to the following criteria: VA decline of 10 ETDRS letters compared with baseline, increase of 100-μm central foveal thickness on OCT compared with baseline, the development of new submacular hemorrhage, and the development of a new area of classic choroidal neovascularization on FA. RESULTS Twenty-six patients completed a 6-month follow-up. There was no evidence of radiation retinopathy, optic neuropathy, or cataract. The mean baseline ETDRS score was 46.6 letters (range: 5 to 80; standard deviation [SD]: 21.5). At 6 months, the corresponding ETDRS score was 55.6 letters (range: 25 to 80; SD: 18.9) and the mean change in VA was 9.5 ETDRS letters (SD: 10.3). On responder analysis, 96% lost 15 or fewer ETDRS letters, 81% gained 0 or more ETDRS letters, and 50% gained 15 or more ETDRS letters. Patients received a total of 13 ranibizumab injections following two initial injections. At 6 months, patients received an average of 0.5 additional injections following the initial two mandated injections. CONCLUSION A single treatment of externally applied, non-invasive 16-Gy low-voltage x-ray therapy in conjunction with ranibizumab demonstrated an overall improvement of VA in patients with neovascular AMD at 6 months with no radiation-related adverse effects.

24-Gy Low-Voltage X-Ray Irradiation With Ranibizumab Therapy for Neovascular AMD: 6-Month Safety and Functional Outcomes

BACKGROUND AND OBJECTIVE To describe the 6-month safety and preliminary efficacy outcomes of the use of 24-Gy radiation with intravitreal ranibizumab for patients with neovascular age-related macular degeneration (AMD). PATIENTS AND METHODS A single treatment of a non-invasive, externally delivered low-voltage x-ray irradiation at a dose of 24 Gy was administered in one session through three locations in the inferior pars plana in a consecutive series of patients with neo-vascular AMD (treatment naïve and previously treated). Optical coherence tomography (OCT) and Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity examinations were performed at 1 week, 1 month, and monthly thereafter with quarterly fluorescein angiography. RESULTS Nineteen patients completed 6 months of follow-up. There was no evidence of radiation retinopathy, optic neuropathy, or cataract. The mean baseline ETDRS score was 38.3 ± 19.5 letters. At 6 months, the corresponding ETDRS score was 44.7 ± 16.8 letters. At 6 months, the mean change in visual acuity was 6.4 ± 9.8 ETDRS letters. Patients received an average of 0.4 additional ranibizumab injections following the initial two mandated injections. CONCLUSION A single treatment of external 24-Gy low-voltage x-ray therapy in conjunction with ranibizumab demonstrated an overall improvement in visual acuity in patients with neovascular AMD at 6 months, with no radiation-related adverse effects.

16 Gy low-voltage x-ray irradiation followed by as needed ranibizumab therapy for age-related macular degeneration: 12 month outcomes of a ‘radiation-first’ strategy

Background and objective To describe ‘radiation-first’ combination treatment with a non-invasive, low-voltage x-ray irradiation system followed by as needed ranibizumab for neovascular age-related macular degeneration (AMD). Study design and methods Phase I study of non-invasive, low-voltage 16 Gy x-ray irradiation delivered in three beams via the inferior pars plana in patients with active neovascular AMD. Ranibizumab was administered as needed per protocol. Patients were followed monthly for safety and efficacy over 12 months. Results 13 patients were enrolled and completed 12 months follow-up. Safety was good with no serious ocular/non-ocular adverse events or radiation-related ocular complications. 11 patients lost <15 Early Treatment of Diabetic Retinopathy Study (ETDRS) letters, seven gained ≥0 ETDRS letters and 0 gained ≥15 ETDRS letters. Patients received a total of 31 subsequent ranibizumab injections (of possible 156) over the 12 months following x-ray irradiation. Mean time to first injection was 3.9 months. One patient received no ranibizumab injections, three patients received one injection, four patients received two injections, and five patients received three or more injections. Conclusions After 12 months, non-invasive, low-voltage x-ray irradiation with as needed ranibizumab rescue therapy demonstrated good safety with a visual acuity stabilising effect and reduction in retinal thickness in patients with neovascular AMD.