Michael J. Cooney

Intravitreal bevacizumab treatment of choroidal neovascularization secondary to age-related macular degeneration.

Purpose: To describe the short-term anatomical and visual acuity responses after intravitreal injection of bevacizumab (Avastin, Genentech) in patients with choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD). Methods: We conducted a retrospective study of patients with CNV secondary to AMD who were treated with intravitreal injection of bevacizumab (1.25 mg) during a 3-month period. Patients underwent best-corrected Snellen visual acuity testing, optical coherence tomography, and ophthalmoscopic examination at baseline and follow-up visits. Results: There were 266 consecutive eyes of 266 patients who received injections, and follow-up information was available for 251 (94.4%). The mean age of the patients was 80.3 years, the mean baseline visual acuity was 20/184, and 175 (69.7%) had inadequate response to alternate methods of treatment. At the 1-month follow-up (data available for 244 patients), the mean visual acuity was 20/137 (P < 0.001 as compared with baseline), and 74 (30.3%) of patients had improvement in visual acuity as defined by a halving of the visual angle. At the 2-month follow-up (data available for 222 patients), the mean visual acuity was 20/122 (P < 0.001), and 78 (31.1%) of patients had visual improvement. At the 3-month follow-up (data available for 141 patients), the mean visual acuity was 20/109 (P < 0.001), and 54 (38.3%) of patients had visual acuity improvement. The mean central macular thickness at baseline was 340 &mgr;m and decreased to a mean of 247 &mgr;m at month 1 (P < 0.001) and 213 &mgr;m at month 3 (P < 0.001). At 1 month, two patients had mild vitritis, as did one patient at 2 months, who had a history of recurrent uveitis. No endophthalmitis, increased intraocular pressure, retinal tear, or retinal detachment occurred. The risk for thromboembolic disorders did not seem to be different than reported previously in studies concerning macular degeneration. Conclusion: There were no apparent short-term safety concerns for intravitreal bevacizumab injection for CNV. Treated eyes had a significant decrease in macular thickness and improvement in visual acuity. The follow-up was too short to make any specific treatment recommendations, but the favorable short-term results suggest further study is needed.

Retinal Vascular Layers Imaged by Fluorescein Angiography and Optical Coherence Tomography Angiography

IMPORTANCE The retinal vasculature is involved in many ocular diseases that cause visual loss. Although fluorescein angiography is the criterion standard for evaluating the retina vasculature, it has risks of adverse effects and known defects in imaging all the layers of the retinal vasculature. Optical coherence tomography (OCT) angiography can image vessels based on flow characteristics and may provide improved information. OBJECTIVE To investigate the ability of OCT angiography to image the vascular layers within the retina compared with conventional fluorescein angiography. DESIGN, SETTING, AND PARTICIPANTS In this study, performed from March 14, 2014, through June 24, 2014, a total of 5 consecutive, overlapping B-scan OCT angiography images composed of 216 A-scans were obtained at 216 discrete positions within a region of interest, typically a 2 × 2-mm area of the retina. The flow imaging was based on split-spectrum amplitude decorrelation angiography (SSADA), which can dissect layers of vessels in the retina. These distinct layers were compared with the fluorescein angiograms in 12 healthy eyes from patients at a private practice retina clinic to evaluate the ability to visualize the radial peripapillary capillary network. The proportion of the inner vs outer retinal vascular layers was estimated by 3 masked readers and compared with conventional fluorescein angiograms of the same eyes. MAIN OUTCOMES AND MEASURES Outcome measures were visualization of the radial peripapillary capillary network in the fluorescein and SSADA scans and the proportion of the inner retinal vascular plexus vs the outer retinal capillary plexus as seen in SSADA scans that would match the fluorescein angiogram. RESULTS In none of the 12 eyes could the radial peripapillary capillary network be visualized completely around the nerve head by fluorescein angiography, whereas the network was readily visualized in the SSADA scans. The fluorescein angiograms were matched, with a mean proportion of the inner vascular plexus being 95.3% (95% CI, 92.2%-97.8%) vs 4.7% (95% CI, 2.6%-5.7%) for the outer capillary plexus from the SSADA scans. CONCLUSIONS AND RELEVANCE Fluorescein angiography does not image the radial peripapillary or the deep capillary networks well. However, OCT angiography can image all layers of the retinal vasculature without dye injection. Therefore, OCT angiography, and the findings generated, have the potential to affect clinical evaluation of the retina in healthy patients and patients with disease.

Intravitreal bevacizumab (Avastin) treatment of macular edema in central retinal vein occlusion: a short-term study.

Purpose: To report the short term anatomic and visual acuity response after intravitreal injection of bevacizumab (Avastin, Genentech) in patients with macular edema due to central retinal vein occlusion (CRVO). Methods: The authors conducted a retrospective study of patients with macular edema due to CRVO who were treated with at least one intravitreal injection of bevacizumab 1.25 mg in 0.05 mL. Patients underwent Snellen visual acuity testing, optical coherence tomography (OCT) imaging, and ophthalmoscopic examination at baseline and follow-up visits. Results: There were 16 eyes of 15 consecutive patients with a mean age of 76.1 years (SD 9.8 years). Intravitreal triamcinolone had been previously administered to 9 patients, but all of these patients either had no improvement or had excessive intraocular pressure caused by the triamcinolone. The patients received a mean of 2.8 injections of bevacizumab per eye. No adverse events were observed, including endophthalmitis, clinically evident inflammation, increased intraocular pressure, retinal tears, retinal detachment, or thromboembolic events in any patient. The mean central macular thickness at baseline was 887 &mgr;m and decreased to a mean of 372 &mgr;m at month 1 (P < 0.001). The mean baseline acuity was 20/600 (logMAR = 1.48) and the mean acuity at month 1 was 20/200 (logMAR = 1.05), a difference that was highly significant (P = 0.001). At last follow-up, a mean of 3 months after the first injection, the mean visual acuity was 20/138 (logMAR = 0.84), which was significantly better than baseline (P < 0.001). Visual acuity improvement, defined as a halving of the visual angle, was seen in 14 of the 16 eyes. Conclusion: Initial treatment results of patients with macular edema secondary to CRVO did not reveal any short-term safety concerns. Intravitreal bevacizumab resulted in a significant decrease in macular edema and improvement in visual acuity. The number of patients in this pilot study was limited and the follow-up is too short to make any specific treatment recommendations, but the favorable short-term results suggest further study is needed.

Endophthalmitis Associated with Intravitreal Anti-Vascular Endothelial Growth Factor Therapy Injections in An Office Setting

PURPOSE To determine the incidence of endophthalmitis following intravitreal injection of anti-vascular endothelial growth factor (VEGF) agents. DESIGN A retrospective interventional case series. METHODS A total of 10,254 intravitreal anti-VEGF injections (406 pegaptanib, 3,501 bevacizumab, and 6,347 ranibizumab) were performed from January 5, 2005 to October 18, 2007. The number of the injections was determined from the injection log books and billing records. The injections were performed as an office based procedure with use of povidone-iodine as a part of preinjection preparation. Preinjection antibiotics, eye drape, or surgical attire were not used. The main outcome measures were the incidence of suspected and proven endophthalmitis. RESULTS There were three cases of suspected endophthalmitis, one case following bevacizumab injection and two cases following ranibizumab injection. There was no case of culture-proven endophthalmitis. All three patients regained their preinjection visual acuity. The incidence of suspected endophthalmitis was 0.029% (95% confidence interval, 0.006% to 0.085%). There was no difference in the incidence of endophthalmitis between ranibizumab and bevacizumab injections (P = .6). CONCLUSIONS Although there is no consensus regarding the intravitreal injection procedure technique, the incidence of suspected endophthalmitis was very low in a large series of injected patients in a community setting and the incidence compares favorably with that reported in clinical trials where much more extensive preinjection preparation was mandated. We found no difference in the endophthalmitis risk of patients receiving bevacizumab as compared with ranibizumab.

Retinal Vascular Layers in Macular Telangiectasia Type 2 Imaged by Optical Coherence Tomographic Angiography

IMPORTANCE Macular telangiectasia type 2 (MacTel 2) is a rare disease in which abnormalities of the retinal vasculature play a key role. The vascular abnormalities are typically evaluated using fluorescein angiography, a modality with known defects in imaging the deeper layers of the retinal vasculature. Angiography based on optical coherence tomography can image vessels based on flow characteristics without dye injection and may provide improved information concerning the pathophysiology of MacTel 2. OBJECTIVE To investigate MacTel 2 using optical coherence tomographic angiography. DESIGN, SETTING, AND PARTICIPANTS Fourteen eyes of 7 patients with MacTel 2 were analyzed in a community-based retina practice. The flow imaging was based on split-spectrum amplitude decorrelation angiography, which can dissect layers of vessels in the retina. The inner retinal vascular plexus, the outer plexus, and deeper vascular invasion into the outer and subretinal spaces were optically dissected in en face images based on flow. MAIN OUTCOMES AND MEASURES Visualization and qualitative evaluation of the vascular layers of the retina as they may be affected by MacTel 2, both in terms of depth and topographic characteristics. RESULTS A consistent set of retinal vascular changes were seen in the eyes with MacTel 2. There was some loss of capillary density in the inner retinal vascular plexus but many more prominent alterations in the deep retinal vascular plexus. In milder forms of the disease, the deep plexus showed dilation and telangiectasis and, in more advanced cases, thinning and loss. The remaining vessels were elongated and widely spaced capillary segments. Invasion by new vessels into the outer and subretinal spaces occurred subjacent to the regions showing greatest flow imaging abnormalities in the inner and deep retinal vascular layers. CONCLUSIONS AND RELEVANCE As evidenced by the patients in this study, important retinal vascular changes in MacTel 2 occur in the deep capillary plexus of the retina, a layer poorly visualized by fluorescein angiography and, to a lesser extent, in the inner vascular plexus. The proliferation of vessels in the outer and subretinal spaces may be in part compensatory for poor retinal perfusion by established vascular layers in the retina.

Rebound macular edema following bevacizumab (Avastin) therapy for retinal venous occlusive disease.

Background: Bevacizumab, a humanized monoclonal antibody to vascular endothelial growth factor (VEGF), has been given via intravitreal injection as an off-label therapy for both neovascular age-related macular degeneration and for macular edema secondary to retinal vascular disease. The authors describe three patients with macular edema secondary to retinal venous occlusion whose edema initially responded to intravitreal bevacizumab but subsequently recurred in excess of that observed before treatment. Methods: This is a retrospective case series of three patients with macular edema secondary to retinal vein occlusion treated with intravitreal bevacizumab. Results: In all three patients, the rebound retinal edema observed was more pronounced than that present before treatment. Conclusion: These cases suggest a potential limitation of using relatively short-acting VEGF antagonists in retinal vascular disease of a chronic nature. Frequent repeated injections may be required to prevent a rebound effect with no clearly defined endpoint. Until the long-term safety of multiple injections of these agents is established, the authors recommend caution in using this treatment strategy.

Intravitreal Bevacizumab (avastin) For Retinal Angiomatous Proliferation

Objective: To evaluate the short-term visual acuity and anatomic responses after intravitreal bevacizumab (Avastin, Genentech) treatment in patients with retinal angiomatous proliferation (RAP). Methods: The authors conducted a retrospective review of consecutive patients with newly diagnosed or recurrent RAP treated with intravitreal bevacizumab (1.25 mg) during a 3-month period. Complete ocular examination was performed at baseline and follow-up visits. Interval data were analyzed statistically at 1 and 3 months follow-up. Results: Twenty-three eyes of 23 patients underwent intravitreal bevacizumab treatment. The mean age of patients was 81.1 years, median baseline visual acuity of treated eyes was 20/80 (range 20/25–20/800), and mean baseline central macular thickness was 335 &mgr;m (optical coherence tomography was available for 22 eyes). Nine eyes had retinal pigment epithelial detachments (PEDs) at baseline. At 1-month follow-up, the median acuity improved to 20/60 (range 20/30–20/400) (P < 0.001), mean central macular thickness decreased to 202 &mgr;m (P < 0.001), and PED was present in only 2 eyes (P = 0.016). Seven of 23 eyes at 1 month (30.4%) had improved visual acuity, defined as halving of the visual angle, and no eyes had worse acuity, defined as doubling of the visual angle. Of the 17 eyes available for 3-month follow-up, 5 eyes (29.4%) had better visual acuity, 1 eye (5.9%) had worse acuity, and the remaining 11 (64.7%) had the same acuity. The median visual acuity at month 3 was 20/60 (range 20/25–20/400). There were no thromboembolic phenomena, endophthalmitis cases, retinal detachments, or any other adverse events. Conclusion: Treatment of RAP with intravitreal bevacizumab during this retrospective review resulted in a significant decrease in macular thickness and improvement or stabilization of visual acuity. Further long-term investigation is warranted given the promising short-term results.

Intravitreal bevacizumab for the management of choroidal neovascularization in pseudoxanthoma elasticum.

Purpose: To determine the results of intravitreal bevacizumab injections for the management of choroidal neovascularization (CNV) in patients with pseudoxanthoma elasticum (PXE)–associated angioid streaks. Methods: A consecutive series of patients with PXE and CNV were managed with intravitreal bevacizumab injection (1.25 mg per 0.05 cc). The main outcome measures were visual acuity and greatest lesion height as measured by optical coherence tomography (OCT). Results: Nine eyes of nine consecutive patients received intravitreal bevacizumab (1.25 mg/0.05 mL) injections. The mean follow-up time was 6 months, during which eyes received an average of 1.8 injections. The baseline visual acuity was a mean of 20/368 and improved to 20/289 at the last visit (P = 0.056). Visual acuity either improved or stabilized in all 9 eyes (100%). Serial OCT measurements in 8 eyes showed a mean of 353 &mgr;m at baseline, which decreased to 201 &mgr;m at the last visit (P = 0.012). No complications were noted. Conclusions: These short-term results support the use of intravitreal bevacizumab for the management of CNV in patients with PXE. Continued experience with intravitreal bevacizumab in this population will help establish its longer-term efficacy and better define the potential need for serial injections to maintain these results.

Ruboxistaurin, a Protein Kinase C β Inhibitor, as an Emerging Treatment for Diabetes Microvascular Complications

OBJECTIVE: To review current clinical data regarding the pharmacologic actions of ruboxistaurin (LY333531) mesylate, an inhibitor of protein kinase C (PKC) β, and its role to potentially reduce the development and/or the progression of diabetic microvascular complications. DATA SOURCES: Primary literature was obtained via a MEDLINE search (1966–August 2004) and through review of pertinent abstracts and presentations at major medical meetings. STUDY SELECTION AND DATA EXTRACTION: Literature relevant to PKC physiology, the pharmacokinetics of ruboxistaurin, and data evaluating the use of ruboxistaurin in treating diabetic microvascular complications in human and relevant animal models was reviewed. DATA SYNTHESIS: PKC is part of a group of intracellular signaling molecules activated in response to various specific hormonal, neuronal, and growth factor stimuli. Hyperglycemia leads to PKC β 1 and 2 isoform activation, which experimentally has been shown to contribute to the development and progression of diabetic microvascular complications (retinopathy, nephropathy, neuropathy) through various biochemical mechanisms. Animal and/or human studies using ruboxistaurin mesylate, a novel, highly selective inhibitor of PKC β, have shown delay in the progression and, in some cases, reversal of diabetic retinopathy, nephropathy, and neuropathy. CONCLUSIONS: Ruboxistaurin mesylate, by inhibiting excessive activation of certain PKC isoforms, has the potential to reduce the burden of microvascular complications for patients with diabetes.

Evaluation Of Safety For Bilateral Same-day Intravitreal Injections Of Antivascular Endothelial Growth Factor Therapy

Purpose: To explore the incidence of complications after bilateral same-day intravitreal injections of antivascular endothelial growth factor pharmacotherapies in this retrospective interventional case series. Methods: An electronic review of billing records was performed to identify all bilateral same-day intravitreal antivascular endothelial growth factor injections performed within a single group retina practice between January 6, 2006 and June 1, 2009. The charts were reviewed to identify the complications of endophthalmitis, intraocular inflammation, retinal tear, and retinal detachment. Results: A total of 1,534 bilateral intravitreal injections (326 bevacizumab and 1,208 ranibizumab: 3,068 injections total) were performed in 367 patients. Three complications were identified. Two cases of unilateral culture-proven endophthalmitis occurred after bilateral intravitreal ranibizumab, and one case of unilateral acute intraocular inflammation occurred after bilateral intravitreal bevacizumab. In all three of these eyes, visual acuity returned to its preinjection level. No cases of retinal tear or retinal detachment were identified. The incidence of culture-proven endophthalmitis was 0.065%, and the incidence of acute intraocular inflammation was 0.033%. Conclusion: The complication rates after bilateral same-day intravitreal antivascular endothelial growth factor injections seem to be similar to those after unilateral injections. Severe acute intraocular inflammation can occur unilaterally after same-day bilateral injections of bevacizumab.