Audina M. Berrocal

Off-label use of intravitreal bevacizumab (Avastin) for salvage treatment in progressive threshold retinopathy of prematurity.

Purpose: To report the short term anatomic response of intravitreal bevacizumab (Avastin, Genentech) as salvage treatment in progressive retinopathy of prematurity (ROP) in a small series of patients. Methods: The study included five eyes of three patients with progressive ROP despite peripheral laser ablation. Patients received intravitreal injections of bevacizumab (Avastin, Genentech). RetCam (Clarity Medical Systems, Inc., Pleasanton, CA) photography and ultrasonography were used to document effect. Results: Three patients were transferred to the Bascom Palmer Eye Institute/Jackson Memorial Hospital for management of progressive ROP despite laser therapy at an outside facility. RetCam fundus photography and ultrasonography were used to document all cases. After informed consent was obtained from the parents, the patients received off-label intravitreal bevacizumab as salvage treatment. Repeat intravitreal injections of bevacizumab were utilized in several cases. The ROP stabilized allowing laser supplementation. There was varying development of tractional retinal detachments in several of the eyes but the ROP component quieted in all cases. Conclusions: Off-label use of bevacizumab appears to be useful as a salvage treatment for ROP when laser treatment is precluded. It improves dilation, quiets the disease when visibility is difficult, and temporizes the disease until laser can be supplemented.

Endophthalmitis after intravitreal anti-vascular endothelial growth factor antagonists: A six-year experience at a university referral center

Purpose: To assess the rate of infectious endophthalmitis and to describe the clinical and microbiological features of eyes that develop clinically suspected endophthalmitis after an intravitreal injection of vascular endothelial growth factor antagonists. Methods: The medical records of patients undergoing intravitreal injections of anti-vascular endothelial growth factor agents from January 1, 2005, through December 31, 2010, at a single university referral center and associated satellite clinics were retrospectively analyzed to determine the rate of infectious endophthalmitis after intravitreal anti-vascular endothelial growth factor injections. Results: Twelve cases (11 patients) of clinically suspected endophthalmitis were identified after a total of 60,322 injections (0.02%; 95% confidence interval, 0.0114%-0.0348%). Of the 12 cases, 11 presented within 3 days of the injection. Of the 7 culture-positive cases, 5 were because of Streptococcus species. In 4 of the 5 Streptococcus cases, final visual acuity was hand motions or worse. The rate of clinically suspected endophthalmitis was 0.018% after bevacizumab and 0.027% after ranibizumab injections. Conclusion: A very low rate of endophthalmitis after intravitreal injections of anti-vascular endothelial growth factor agents was observed. Patients typically presented within 3 days of injection. Streptococcus species was the most common bacteria isolated, and it was generally associated with poor visual outcomes.

One-year Safety And Efficacy Of Intravitreal Triamcinolone Acetonide For The Management Of Macular Edema Secondary To Central Retinal Vein Occlusion

Purpose: To evaluate the safety and efficacy of intravitreal triamcinolone acetonide (IVTA) as treatment for macular edema associated with central retinal vein occlusion (CRVO). Methods: A retrospective review was performed of data for 40 consecutive patients (40 eyes) with CRVO and macular edema treated with IVTA at the Bascom Palmer Eye Institute (Miami, FL). Results: Median duration of symptoms before the first injection was 3 months (range, 1 day to 8 years). Median Snellen visual acuity was 20/400 at baseline (range, 20/60 to light perception; n = 40), 20/300 at 1 month (P = 0.010; n = 37), 20/300 at 3 months (P = 0.007; n = 33), 20/400 at 6 months (P = 0.726; n = 28), and 8/200 at 1 year (P = 0.569; n = 17). Vision improved by ≥3 lines in 21% of eyes at 1 month, 27% at 3 months, 14% at 6 months, and 12% at 1 year. Visual acuity was unchanged from baseline in 71% of eyes at 6 months and 1 year. By 1 year, 50% of eyes received more than one injection (mean = 1.6 injections; range 1–4 injections). Overall, intraocular pressure increased by ≥10 mmHg in 24% of eyes at 1 year. Trabeculectomy was performed on 2 of 12 eyes with preexisting open-angle glaucoma. Conclusion: IVTA can substantially improve vision in some patients, but most patients have stable visual acuity compared with baseline at 1 year despite repeated injections.

Retinopathy of Prematurity in the Time of Bevacizumab: Incorporating the BEAT-ROP Results into Clinical Practice

t z a 3 W t c 2 a h 2 o t o a Recently, the results of the Bevacizumab Eliminates the Angiogenic Threat of Retinopathy of Prematurity (BEAT-ROP) trial were published in the New England Journal of Medicine and careful review is important since the authors advocate for a change in the standard of care in the treatment of ROP. The BEAT-ROP trial design was a prospective, multicenter, randomized, unmasked Phase II trial of intravitreal bevacizumab (0.625 mg in 0.025 ml) vs. conventional diode laser photocoagulation. Eligible patients were 1500 g or less and 30 weeks gestational age or less with Stage 3 ROP in Zone I or Zone II posterior disease in both eyes. The primary outcome of the trial was modified from an absence of recurrence of Stage 3 ROP in Zone I or Zone II posterior by 54 weeks to recurrence of retinal neovascularization requiring retreatment by 54 weeks. Bevacizumab was injected 2.5 mm posterior to the limbus using a 31-gauge needle. Based upon a pre-study analysis of the predicted efficacy of bevacizumab, the trial targeted 50 patients with Zone I disease and 100 patients with Zone II posterior disease, with a 1:1 randomization of bevacizumab: diode laser photocoagulation. The authors elected to randomize based upon infants, not eyes, because of the threat of amblyopia induced by 1 eye receiving laser photocoagulation and potential exuberant inflammation and the other eye receiving an injection; each infant received the same therapy in both eyes. At the time of full enrollment, 150 patients had been enrolled, 67 in Zone I (33 bevacizumab, 34 laser), and 83 in Zone II posterior (42 bevacizumab, 41 laser). Of these, 143 were considered eligible for analysis, with 7 deaths before the 54 week primary outcome endpoint. There was 1 protocol violation, a patient who inadvertently received bevacizumab when they should have received laser photocoagulation, and they were included in the laser group by virtue of the intentto-treat analysis plan. The BEAT-ROP demonstrated a beneficial effect for bevacizumab vs. laser in the treatment of Zone I, Stage 3 ROP. In the bevacizumab group, recurrence of retinal neovascularization requiring treatment was 6% at 54 weeks vs. 42% in the laser group, for an odds ratio of 0.09 favoring bevacizumab (95% confidence interval of 0.02–0.43). No statistical difference was noted for Zone II posterior, Stage 3 ROP between bevacizumab and laser. Recurrence rates were 5% vs. 12%, bevacizumab and laser, respectively. Of the 7 deaths, 5 were in the bevacizumab group, 2 in the laser group, and this did not reach statistical significance. The authors offered the following conclusions: (1) bevacizumab is superior to laser for treatment of Zone I, Stage 3 ROP; (2) peripheral retinal vascularization continued as normal in the bevacizumab group, but not the laser group; and (3)“Bevacizumab is an inexpensive drug that can be rapidly administered at the bedside by any ophthalmologist.” g

Initial outcomes following intravitreal ocriplasmin for treatment of symptomatic vitreomacular adhesion

BACKGROUND AND OBJECTIVE When delivered via a single intravitreal injection, ocriplasmin can effect proteolytic resolution of symptomatic vitreomacular adhesion (VMA). The authors describe their initial clinical experience with ocriplasmin at a large academic center. PATIENTS AND METHODS Retrospective review of all patients with symptomatic VMA treated with ocriplasmin from January 2013 through May 2013 at a single center. RESULTS Nineteen patients with symptomatic VMA received intravitreal ocriplasmin. Eight patients (42%) exhibited resolution of VMA. Macular holes in three of six patients (50%) closed after injection. A higher proportion of VMA resolution was observed in patients with the following baseline characteristics: age less than 65 years, focal adhesions less than or equal to 1,500 μm, presence of macular hole, phakic status, and absence of epiretinal membrane. CONCLUSION Initial clinical outcomes using ocriplasmin in this study are consistent with those reported in the phase 3 clinical trials. Improved clinical results can be achieved with careful case selection based on specific baseline characteristics.

Macular spectral-domain optical coherence tomography in patients with X linked retinoschisis

Aim: To evaluate macular anatomy in patients with X linked retinoschisis (XLRS) using spectral-domain optical coherence tomography (SD-OCT). Methods: Consecutive observational case series. Clinical features were obtained through retrospective chart review. Only eyes without prior surgical interventions and those scanned with SD-OCT were included. The OCT images were analysed. Results: Fourteen eyes of seven males with XLRS scanned with SD-OCT, age 5 to 45 years, were identified. On clinical examination, stellate spoke-like cystic maculopathy was present in nine eyes, and an atrophic foveal lesion in five eyes. SD-OCT revealed cystoid spaces accounting for retinal splitting in the inner nuclear layer in 12 eyes, and outer plexiform layer in two eyes of one patient. A few small cysts, not accounting for the foveal splitting, were seen in the outer nuclear layer in four eyes and in the ganglion cell layer and/or nerve fibre layer in six eyes. Conclusions: SD-OCT localised the foveomacular retinoschisis in XLRS to the retinal layers deeper than the nerve fibre layer. In the present study, the foveomacular schisis was seen most frequently in the inner nuclear layer.

Comparison of intravitreal bevacizumab followed by ranibizumab for the treatment of neovascular age-related macular degeneration

Purpose: To compare outcomes after switching from intravitreal bevacizumab (Avastin) to ranibizumab (Lucentis) in patients with neovascular age-related macular degeneration (AMD). Methods: A retrospective review was performed of patients with neovascular AMD who were switched from treatment with intravitreal bevacizumab to intravitreal ranibizumab once ranibizumab became commercially available. All reviewed patients had at least three bevacizumab injections before being switched to ranibizumab. The treatment outcomes included comparisons of visual acuity and dosing frequency while receiving both drugs. Results: Eighty-four eyes met the inclusion criteria. Mean baseline visual acuity was 20/100+1. Mean duration of bevacizumab treatment was 7.1 months followed by 7.3 months with ranibizumab (P = 0.68). Best-obtained visual acuity during treatment was 20/63+1 with bevacizumab and 20/63+2 with ranibizumab (P = 0.5). Last mean visual acuity after receiving bevacizumab at the time of the first ranibizumab injection was 20/80. Mean visual acuity at the last ranibizumab follow-up visit was 20/80+1 (P = 0.49). Mean injection rates per month while receiving bevacizumab and ranibizumab were 0.66 (P = 0.98). Conclusion: In this subset of patients with neovascular AMD switched from bevacizumab to ranibizumab therapy, there were no apparent differences in visual acuity outcomes or injection rates. Larger prospective studies are under way to directly compare these drugs for the treatment of neovascular AMD.

Endophthalmitis Caused by Bacillus Species

PURPOSE To investigate clinical settings, management, and visual outcomes of endophthalmitis caused by Bacillus species and to review in vitro effectiveness of antibiotics commonly used against Bacillus species. DESIGN Retrospective, consecutive case series. METHODS Record review of all patients with endophthalmitis caused by Bacillus species treated at Bascom Palmer Eye Institute between January 1, 1990 and July 1, 2007. Antibiotic sensitivities were conducted on 21 of 22 isolates. RESULTS Twenty-two eyes of 22 patients met study inclusion criteria. Median follow-up was 18 months. Clinical settings included open globe injury (18 eyes), endogenous (two eyes), delayed-onset bleb-associated (one eye), and acute-onset postoperative (one eye). Twelve (67%) of 18 patients with open globe injuries had intraocular foreign bodies. Presenting visual acuity (VA) was hand movements or better in 13 (59%) patients. Initial treatment included pars plana vitrectomy and injection of antibiotics in 14 eyes (64%), vitreous tap and injection of antibiotics in seven eyes (32%), and evisceration in one eye (5%). Four (18%) patients received additional doses of intravitreal antibiotics; 16 (73%) underwent secondary surgical procedures. Eight (36%) patients achieved a final VA of 20/400 or better and four (18%) achieved a final VA of 20/60 or better. All patients received intraocular vancomycin and a cephalosporin or aminoglycoside. Systemic antibiotics were used in 18 (82%) patients. Fifteen (68%) isolates were Bacillus cereus. All isolates tested were sensitive to vancomycin, gentamicin, and five fluoroquinolones. Only three of 21 isolates were susceptible to penicillin and cephalosporins. CONCLUSIONS Endophthalmitis caused by Bacillus species often results in poor visual outcomes. In vitro antibiotic sensitivities indicate that vancomycin, aminoglycosides, and fluoroquinolones were effective against Bacillus isolates, whereas cephalosporins were relatively ineffective.

Safety and efficacy of intravitreal bevacizumab (Avastin) for the management of branch and hemiretinal vein occlusion

Purpose: To evaluate the safety and efficacy of intravitreal bevacizumab (Avastin, Genentech) for the treatment of macular edema (ME) secondary to branch retinal vein occlusion (BRVO) and hemiretinal vein occlusion (HRVO). Methods: A retrospective review was performed of consecutive patients treated with intravitreal bevacizumab (1.25 mg) for ME secondary to BRVO/HRVO from May 2005 to August 2006 with follow-up through February 2007. Re-treatment was performed at monthly or longer intervals at the discretion of the treating physician. Results: Fifty-two eyes with a BRVO and 13 eyes with an HRVO received intravitreal bevacizumab at baseline. Visual acuity improved by a mean of 12 letters at 1 month (n = 51; P < 0.001), 13 letters at 3 months (n = 61; P < 0.001), 13 letters at 6 months (n = 42; P < 0.001), 14 letters at 9 months (n = 27; P < 0.001), and 15 letters at 12 months (n = 17; P = 0.015). The mean optical coherence tomography (OCT) thickness decreased by 184 &mgr;m (P < 0.001), 131 &mgr;m (P < 0.001), 161 &mgr;m (P < 0.001), 158 &mgr;m (P = 0.002), and 205 &mgr;m (P = 0.002) at 1 month, 3 months, 6 months, 9 months, and 12 months, respectively. The mean number of injections was 1.4, 2.1, 2.7, and 3.1, and 3.3 at 1 month, 3 months, 6 months, 9 months, and 12 months, respectively. No ocular or systemic adverse events were observed. Conclusion: Improvements in visual acuity and OCT outcomes were observed during the first year after intravitreal bevacizumab in patients with ME secondary to BRVO and HRVO.

Bilateral choroidal effusions associated with dengue fever.

related to the application of scatter photocoagulation for retinal nonperfusion and neovascularization. Subsequent tears may have been related to laser photocoagulation to “wall off” the original rhegmatogenous retinal detachment. It is possible that thermal energy had been transmitted via fibrous or fibrocellular vitreous adhesions to areas of ischemic retina, causing contraction and tearing in the thinned, atrophic retina. The outcome in these cases was favorable. Visual acuity was 20/25 in Case 1 nearly 3 years after the last retinal tear was treated with laser photocoagulation. In Case 2, the visual acuity was 20/30 3 years after treatment. No additional retinal tears or detachment was present in either patient during the follow-up period. As in the case of retinopathy of prematurity, adults with IP have long-lasting effects of their neonatal retinopathy and are subject to rhegmatogenous retinal detachment decades after the acute processes of their retinal disease have completely subsided. Lifelong follow-up is therefore indicated for all such patients.