Andrew A. Moshfeghi

Optical coherence tomography findings after an intravitreal injection of bevacizumab (avastin) for neovascular age-related macular degeneration.

To determine whether intravitreal bevacizumab could improve optical coherence tomography and visual acuity outcomes in a patient with neovascular age-related macular degeneration who was responding poorly to pegaptanib therapy, an intravitreal injection of bevacizumab (1.0 mg) was given. Within 1 week, optical coherence tomography revealed resolution of the subretinal fluid, resulting in a normal-appearing macular contour. The improved macular appearance was maintained for at least 4 weeks, and visual acuity remained stable. No inflammation was observed. An intravitreal injection of bevacizumab may provide an effective, safe, and inexpensive option for patients with age-related macular degeneration who are losing vision secondary to macular neovascularization.

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.

Systemic Complement Inhibition with Eculizumab for Geographic Atrophy in Age-Related Macular Degeneration: The COMPLETE Study

PURPOSE To evaluate the effect of eculizumab, a systemic inhibitor of complement component (C5), on the growth of geographic atrophy (GA) in patients with age-related macular degeneration (AMD). DESIGN Prospective, double-masked, randomized clinical trial. PARTICIPANTS Patients with GA measuring from 1.25 to 18 mm(2) based on spectral-domain optical coherence tomography imaging. METHODS Patients were randomized 2:1 to receive intravenous eculizumab or placebo over 6 months. In the eculizumab treatment arm, the first 10 patients received a low-dose regimen of 600 mg weekly for 4 weeks followed by 900 mg every 2 weeks until week 24, and the next 10 patients received a high-dose regimen of 900 mg weekly for 4 weeks followed by 1200 mg every 2 weeks until week 24. The placebo group was infused with saline. Patients were observed off treatment for an additional 26 weeks. Both normal-luminance and low-luminance visual acuities were measured throughout the study, and the low-luminance deficits were calculated as the difference between the letter scores. MAIN OUTCOME MEASURES Change in area of GA at 26 weeks. RESULTS Thirty eyes of 30 patients were enrolled. Eighteen fellow eyes also met inclusion criteria and were analyzed as a secondary endpoint. For the 30 study eyes, mean square root of GA area measurements ± standard deviation at baseline were 2.55 ± 0.94 and 2.02 ± 0.74 mm in the eculizumab and placebo groups, respectively (P = 0.13). At 26 weeks, GA enlarged by a mean of 0.19 ± 0.12 and 0.18 ± 0.15 mm in the eculizumab and placebo groups, respectively (P = 0.96). At 52 weeks of follow-up, GA enlarged by a mean of 0.37 ± 0.22 mm in the eculizumab-treated eyes and by a mean of 0.37 ± 0.21 mm in the placebo group (P = 0.93, 2 sample t test). None of the eyes converted to wet AMD. No drug-related adverse events were identified. CONCLUSIONS Systemic complement inhibition with eculizumab was well tolerated through 6 months but did not decrease the growth rate of GA significantly. However, there was a statistically significant correlation between the low-luminance deficit at baseline and the progression of GA over 6 months.

Postoperative Hemorrhagic Occlusive Retinal Vasculitis: Expanding the Clinical Spectrum and Possible Association with Vancomycin.

PURPOSE To describe a syndrome of hemorrhagic occlusive retinal vasculitis (HORV) that developed after seemingly uncomplicated cataract surgery. DESIGN Retrospective case series. SUBJECTS Eleven eyes of 6 patients from 6 different institutions. METHODS Cases were identified after discussion among retina specialists. The findings on presentation, clinical course, and outcome of a series of 7 eyes of 4 patients were compared with a previous report of 4 eyes of 2 patients, and data from both series were combined for a comprehensive analysis. MAIN OUTCOME MEASURES Historical data, examination findings, imaging results, systemic evaluation findings, treatment regimens, and visual outcomes. RESULTS Eleven eyes of 6 patients underwent otherwise uncomplicated cataract surgery, receiving viscoelastic and prophylactic intracameral vancomycin during the procedure. Despite good initial vision on postoperative day 1, between 1 to 14 days after surgery, all eyes demonstrated painless vision loss resulting from HORV. Extensive ocular and systemic evaluations were unrevealing in all patients. All patients were treated with aggressive systemic and topical corticosteroids. Additional treatments included systemic antiviral medication in 4 patients, intravitreal antibiotics in 4 eyes, and pars plana vitrectomy in 4 eyes. Skin testing for vancomycin sensitivity showed negative results in 3 patients and was not performed in the others. Neovascular glaucoma developed in 7 eyes, and all eyes received intravitreal anti-vascular endothelial growth factor (VEGF) injection, panretinal photocoagulation, or both for retinal ischemia. Final visual acuity was less than 20/100 in 8 of 11 eyes. CONCLUSIONS Postoperative HORV is an exceedingly rare and potentially devastating condition that can occur after otherwise uncomplicated cataract surgery. Although the precise cause remains unknown, this disease may represent a delayed immune reaction similar to vancomycin-induced leukocytoclastic vasculitis. Despite treatment with high-dose corticosteroids, antiviral medication, and early vitrectomy in many patients, visual outcomes typically were poor in this series. Early intervention with intravitreal anti-VEGF medication and panretinal photocoagulation may help to prevent additional vision loss resulting from neovascular glaucoma.

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.

Predicting the progression of geographic atrophy in age-related macular degeneration with SD-OCT en face imaging of the outer retina.

BACKGROUND AND OBJECTIVE Spectral-domain optical coherence tomography (SD-OCT) en face imaging was used to measure the growth of geographic atrophy (GA) and identify baseline anatomic changes in the outer retina in eyes with nonexudative age-related macular degeneration (AMD). PATIENTS AND METHODS In this prospective study, eyes were imaged using 200 × 200 and 512 × 128 A-scan raster patterns. Outer retinal anatomy was visualized using en face imaging of a 20-μm thick slab encompassing the inner segment/outer segment (IS/OS) band. RESULTS En face SD-OCT imaging of the IS/OS region revealed a bilaterally symmetrical pattern of outer retinal disruption extending beyond the borders of GA that accurately predicted the progression of GA over 1 year in 13 of 30 eyes (43.3%). In the remaining cases, the area of disruption was much larger than the area of progression. CONCLUSION En face imaging of the outer retina can predict the growth of GA in some eyes. Due to the bilateral symmetry of these findings, this imaging strategy may identify a genetic subset of patients in whom photoreceptor loss precedes the progression of GA. These areas with outer retinal disruption should be followed in clinical trials designed to test treatments for dry AMD.

Pegaptanib sodium for the treatment of neovascular age- related macular degeneration

This article reviews pegaptanib sodium, a compound developed by Eyetech Pharmaceuticals Inc. and Pfizer Inc., for the treatment of neovascular age-related macular degeneration (AMD). Traditional treatment approaches to neovascular AMD have included destructive therapies such as thermal laser photocoagulation and photodynamic therapy; the use of pegaptanib sodium heralds a new treatment approach that is a non-destructive therapy based on the inhibition of vascular endothelial growth factor activity in the eye. This diminishes the neovascular drive in the pathologically hyperpermeable state of the diseased eye. Pegaptanib sodium is one of the first therapeutics belonging to the class of compounds known as aptamers. The chemistry, mechanism of action, pharmacokinetics and rationale for the clinical use of the drug are reviewed. The article highlights and summarises the results of the multi-centre, randomised, sham-controlled clinical trials with pegaptanib sodium to treat subfoveal choroidal neovascularisation in AMD. In addition, the safety profile is reviewed.

OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY OF RETINAL VENOUS OCCLUSION.

Purpose: To noninvasively evaluate the retinal microvasculature in human subjects with retinal venous occlusions using optical coherence tomography angiography and assess potential clinical applications. Methods: This was a prospective, observational study of adult human subjects with clinical and imaging findings demonstrating retinal venous occlusion. Subjects underwent complete ophthalmic examination and fluorescein angiography as appropriate for their standard of care. Optical coherence tomography angiography was performed on a prototype spectral domain-OCTA system in 3 mm × 3 mm and 6 mm × 6 mm regions centered on the fovea and parafoveal areas. Retinal vasculature was assessed within three horizontal slabs consisting of the superficial, middle, and deep retina. The vasculature within each slab was reconstructed using intensity contrast-based algorithms and visualized as en-face images. Optical coherence tomography angiograms were manually segmented to verify the accuracy of the automated segmentation algorithms. Results: Optical coherence tomography angiography was able to demonstrate almost all of the clinically relevant findings in 25 subjects with acute and chronic retinal venous occlusion. These findings were consistent with clinical, anatomic, and fluorescein angiographic findings including areas of impaired vascular perfusion, retinal atrophy, vascular dilation, shunt vessels, and some forms of intraretinal edema. Conclusion: Optical coherence tomography angiography is an investigational method that generates high-resolution, noninvasive angiograms that qualitatively illustrate most of clinically relevant findings in retinal venous occlusion. Optical coherence tomography angiography corresponds well with fluorescein angiograms and in many cases provides more detailed anatomic and blood flow information. Optical coherence tomography angiography, in conjunction with standard spectral domain-OCT, is at least equally as effective as fluorescein angiography for evaluation and management of the macular complications of retinal venous occlusions.

Photodynamic Therapy for Choriocapillaris Using Tin Ethyl Etiopurpurin (SnET2)

BACKGROUND AND OBJECTIVE To investigate the use of photodynamic therapy (PDT) using tin ethyl etiopurpurin (SnET2) for occluding the choriocapillaris in the eyes of pigmented rabbits. MATERIALS AND METHODS Following intravenous injection of SnET2 (0.5 and 1 mg/kg) or lipid emulsion alone, the fundus of pigmented rabbits (n = 21) was irradiated starting 15 to 45 minutes after photosensitizer injection using 664-nm light at a fluence of 300 mW/cm2 and light doses of 5 to 20 J/cm2. Funduscopy, fluorescein angiography, and light and electron microscopy were performed at 1, 14, and 28 days after PDT. RESULTS Following SnET2 and PDT, closure of the choriocapillaris was achieved with light doses as low as 5 J/cm2 (17 seconds) and a drug dose of 0.5 mg/kg of SnET2. Vascular occlusion was documented by fluorescein angiography and histology. Photodynamic damage was noted in the choriocapillary endothelial cells. Retinal pigment epithelial damage and outer retinal damage were also observed. No funduscopic, angiographic, or histologic findings were present in the eyes of pigmented control rabbits. CONCLUSIONS PDT with SnET2 was effective in this animal model, using low levels of activating light for the occlusion of the choriocapillaris. This has clinical implications for the treatment of choroidal neovascularization and could be a more selective therapy than thermal laser photocoagulation.

Intravitreal injection analysis at the Bascom Palmer Eye Institute: evaluation of clinical indications for the treatment and incidence rates of endophthalmitis

Objective To report the incidence of endophthalmitis, in addition to its clinical and microbiological aspects, after intravitreal injection of vascular-targeting agents. Methods A retrospective review of a consecutive series of 10,142 intravitreal injections of vascular targeting agents (bevacizumab, ranibizumab, triamcinolone acetonide, and preservative-free triamcinolone acetonide) between June 1, 2007 and January 31, 2010, performed by a single service (TGM) at the Bascom Palmer Eye Institute. Results One case of clinically-suspected endophthalmitis was identified out of a total of 10,142 injections (0.009%), presenting within three days of injection of bevacizumab. The case was culture-positive for Staphylococcus epidermidis. Final visual acuity was 20/40 after pars plana vitrectomy surgery. Conclusions In this series, the incidence of culture-positive endophthalmitis after intravitreal injection of vascular agents in an outpatient setting was very low. We believe that following a standardized injection protocol, adherence to sterile techniques and proper patient follow-up are determining factors for low incidence rates.