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Do D.V.,Wilmer Eye Institute | Pieramici D.J.,California Retina Consultants and Research Foundation | Van Lookeren Campagne M.,Genentech | Beres T.,Genentech | And 3 more authors.
Retina | Year: 2014

PURPOSE: Multicenter, open-label, single-dose, dose-escalation Phase Ia study to determine the safety, tolerability, maximum tolerated dose, and immunogenicity of FCFD4514S, an antigen-binding fragment from a humanized monoclonal antibody directed against complement factor D, in patients with geographic atrophy. METHODS: Eighteen patients with geographic atrophy (lesion size: ≥0.75 disk areas; best-corrected visual acuity: 20/125-20/400 Snellen equivalent) were sequentially enrolled and received 1 of 6 escalating doses of intravitreal FCFD4514S subject to dose-limiting toxicity criteria. Follow-up assessments (clinical examination, best-corrected visual acuity, intraocular pressure) were conducted at postadministration Days 1, 3, 7, 14, 30, 60, and 90. Serum pharmacokinetics, immunogenicity, and complement activity were also evaluated. RESULTS: All patients completed the study with no reported FCFD4514S-related dose-limiting toxicities or ocular or systemic adverse events. The maximum tolerated dose for this study was 10 mg, the highest dose tested. No antitherapeutic antibody response or adverse effects on systemic complement activity were observed. Time to maximum serum concentration was 1 day to 3 days postdosing; serum terminal half-life was 5.9 days. CONCLUSION: Single-dose intravitreal FCFD4514S administrations were safe and well tolerated and not associated with any study drug-related ocular or systemic adverse events. These data support a multidose safety and tolerability assessment of FCFD4514S in geographic atrophy. Copyright © by Ophthalmic Communications Society, Inc.


Williams P.D.,Texas Retina Associates | Callanan D.,Texas Retina Associates | Solley W.,Texas Retina Associates | Avery R.L.,California Retina Consultants and Research Foundation | And 2 more authors.
Clinical Ophthalmology | Year: 2012

Purpose: This prospective multi-center pilot study compares the use of half-fluence photodynamic therapy combined with ranibizumab with ranibizumab monotherapy for the treatment of neovascular age-related macular degeneration. Methods: All patients presenting with untreated subfoveal neovascular age-related macular degeneration were considered for inclusion. Patients were randomized to receive either ranibizumab with half-fluence photodynamic therapy or ranibizumab alone. Patients in the ranibizumab alone group were given three consecutive monthly ranibizumab injections and were followed monthly. They were treated with ranibizumab as needed, based on clinical discretion, using vision and optical coherence tomography. Patients in the combined group were given one same-day combined ranibizumab and half-fluence (25 j/cm 2) photodynamic therapy treatment and were treated monthly as needed. Outcomes included changes in standardized visual acuity, optical coherence tomography foveal thickness, and percentage of as-needed injections to maintenance examinations. Results: Fifty-six out of 60 enrolled patients completed the twelve month primary outcome visit; this consisted of 27 patients receiving ranibizumab alone and 29 receiving combined treatment. The average age was 79.1 for the ranibizumab alone group and 79.3 for the combined group. The mean visual acuity in the ranibizumab alone group improved from 52.9 Early Treatment of Diabetic Retinopathy letters initially to 62.8 letters at twelve months. The mean visual acuity in the combined group improved from 49.2 letters to 51.8 letters at twelve months. The differences in visual acuity improvements were not statistically significant based on a two-tailed t-test (P = 0.2). Due to the presence of outliers in each group, a Mann-Whitney U test was performed to confirm the results (U = 325; P = 0.28). The mean optical coherence tomography foveal thickness improved 92.5 microns and 106.7 microns in the ranibizumab alone and the combined group, respectively. The difference was not significant based on a two-tailed t-test (P = 0.6). The ranibizumab alone group received an average of 6.8 injections, while the combined group received an average of three injections. This difference was not significant based on a chi-square test (P = 0.11). Conclusion: The groups appeared similar based on statistical analysis, but larger studies are needed to determine possible small differences between combination therapy and monotherapy. © 2012 Williams et al, publisher and licensee Dove Medical Press Ltd.


Dhoot D.S.,California Retina Consultants and Research Foundation | Avery R.L.,California Retina Consultants and Research Foundation
Current Diabetes Reports | Year: 2016

The prevalence of diabetes is growing at epidemic rates in the USA. Diabetic retinopathy develops in a large proportion of patients and is a leading cause of blindness worldwide. Systemic management of diabetic retinopathy has included glycemic, hypertension, and lipid control. Local ophthalmic treatment in the form of focal/grid or panretinal laser photocoagulation has been shown to prevent vision loss in diabetic edema and proliferative diabetic retinopathy, respectively. The introduction of anti-vascular endothelial growth factor for diabetic macular edema and retinopathy has provided clinicians with improved clinical outcomes with potentially less damaging effects than laser. © 2016, Springer Science+Business Media New York.


Song J.,Long Beach Memorial Medical Center | Castellarin A.,Long Beach Memorial Medical Center | Song M.,California Retina Consultants and Research Foundation | Song A.,Long Beach Memorial Medical Center
Journal of Medical Case Reports | Year: 2013

Introduction. Malignant glaucoma occurs when the intraocular pressure elevates in the setting of a shallow anterior chamber and patent iridectomy. We describe a case in which malignant glaucoma that was refractory to conventional treatment and complete vitrectomy was successfully managed by rerouting the glaucoma tubes into the pars plana. Case presentation. A 47-year-old Latino man had a history of neovascular glaucoma and subsequent peripheral anterior synechiae. He was status post-two glaucoma drainage devices. He developed pupillary block. Laser iridotomy was performed without complications. He subsequently developed malignant glaucoma that was refractory to yttrium aluminum garnet capsulohyaloidotomy of the anterior hyaloid. He underwent pars plana vitrectomy with successful control of his intraocular pressure. After 2 weeks, the malignant glaucoma recurred. He underwent repositioning of the tubes into the pars plana with successful control of his intraocular pressure. Conclusion: In rare cases of malignant glaucoma refractive to yttrium aluminum garnet hyaloidotomy and vitrectomy, placement of glaucoma drainage devices is a reasonable alternative. © 2013 Song et al.; licensee BioMed Central Ltd.


Quezada-Ruiz C.,California Retina Consultants and Research Foundation | Pieramici D.J.,California Retina Consultants and Research Foundation | Nasir M.,California Retina Consultants and Research Foundation | Rabena M.,California Retina Consultants and Research Foundation | And 6 more authors.
Retina | Year: 2015

Purpose: To report initial experience with intravitreal ocriplasmin (IVO) and to describe outer retina reflectivity changes observed on spectral domain optical coherence tomography (SD-OCT) after IVO injection in patients with vitreomacular traction (VMT) with or without macular holes (MHs). Methods: A consecutive retrospective review of patients with VMT and MH who were treated with IVO was performed. Patients underwent complete ophthalmic evaluation, including nonstandardized Snellen visual acuity testing, and SD-OCT at baseline and follow-up visits. Results: A total of 23 patients who received IVO for VMT and/or MH were included for analysis. Patient age ranged from 53 years to 93 years with a mean of 74 years. The mean follow-up was 174 days (range: 20-291 days). Vitreomacular traction release at Day 30 after IVO was achieved in 11 of 23 patients (47.82%), at an average of 14.54 days (range: 1-30 days) after treatment. The mean visual acuity improved from 0.50 to 0.38. At presentation, eight patients had MH associated with VMT. Closure of the MH with ocriplasmin was achieved in two patients, and six patients underwent pars plana vitrectomy for MH repair. Ten of 23 patients (43.47%) presented with changes in the outer retina reflectivity on SD-OCT after IVO, 4 patients of this group experienced a decrease in visual acuity. In 7 of these 10 patients (70%), VMT release was documented on OCT by Day 30 postinjection compared with 4 of 13 patients (30.76%) without outer retina changes post-IVO. Normalization of the outer retina reflectivity was achieved in all cases. Conclusion: In this case series of VMT/MH patients treated with ocriplasmin, changes in the SD-OCT outer retina reflectivity were relatively common. Within weeks, the outer retinal reflectivity on SD-OCT improved, as did the visual acuity. Further studies to investigate the association between outer retina reflectivity changes with the use of IVO and long-term visual acuity outcomes are warranted. Copyright © by Ophthaimac Communications Society, Inc.unauthorized Reproduction Of This Article Is Prohibited.


Avery R.L.,California Retina Consultants and Research Foundation | Gordon G.M.,California Retina Consultants and Research Foundation
JAMA Ophthalmology | Year: 2016

IMPORTANCE Anti-vascular endothelial growth factor (VEGF) therapy is commonly used to treat numerous retinal conditions and appears safe, yet controversy remains regarding systemic safety. OBJECTIVE To evaluate the systemic safety of intravitreous anti-VEGF injections in high-risk patients with diabetic macular edema (DME) and to investigate separately the subgroup of these patients with the highest level of exposure to anti-VEGF monthly treatment for 2 years. DATA SOURCES A search of MEDLINE, Cochrane Central Register of Controlled Trials, clincaltrials.gov, and ophthalmology congress abstracts January 1, 1947, to May 19, 2015. STUDY SELECTION Randomized clinical trials were selected that evaluated monthly anti-VEGF injections for DME for 2 years and reported the outcome measures of cerebrovascular accidents,myocardial infarctions, arteriothrombotic events, and mortality. DATA EXTRACTION AND SYNTHESIS Two reviewers collected data independently from each study for the meta-analysis. Data were pooled using a fixed-effects model and analyzed from November 6, 2014, to June 28, 2015. Peto odds ratios with 95%CIs were calculated. MAIN OUTCOMES AND MEASURES Primary end points included cerebrovascular accidents and all-cause mortality in the highest-dose arms. Secondary outcomes includedmyocardial infarctions, arteriothrombotic events, and vascular-related death. RESULTS Of 1126 articles reviewed, 598 were removed as duplicate studies and 524, for lack of monthly treatment data for 2 years, leaving 4 studies for the meta-analysis that met the search criteria: 2 trials using monthly aflibercept and 2 using monthly ranibizumab, representing 1328 patients. The primary evaluation (1078 patients) combined the monthly aflibercept and the 0.5-mg ranibizumab arms and yielded an increased risk for death compared with sham and laser treatments (odds ratio [OR], 2.98; 95%CI, 1.44-6.14; P = .003). Analysis including monthly aflibercept and 0.5-mg ranibizumab yielded an increased risk for cerebrovascular accidents (OR, 2.33; 95%CI, 1.04-5.22; P = .04) and vascular death (OR, 2.51; 95%CI, 1.08-5.82; P = .03). No definitive increased risk for myocardial infarctions and arteriothrombotic events was seen with all dose combinations. CONCLUSIONS AND RELEVANCE In this meta-analysis of anti-VEGF agents for patients with DME, assessment of the highest-level exposure group (those high-risk patients with DME who received 2 years of monthly treatment) revealed a possible increased risk for death and potentially for cerebrovascular accidents. Consideration of total exposure to anti-VEGF agents when treating those at high risk for vascular disease may be important. Copyright © 2016 American Medical Association. All rights reserved.


Dhoot D.S.,California Retina Consultants and Research Foundation | Pieramici D.J.,California Retina Consultants and Research Foundation | Nasir M.,California Retina Consultants and Research Foundation | Castellarin A.A.,California Retina Consultants and Research Foundation | And 6 more authors.
Eye (Basingstoke) | Year: 2015

PurposeTo compare the efficacy of ranibizumab 0.5-mg and 2.0-mg intravitreal injections for persistent diabetic macular edema (DME) previously treated with bevacizumab.MethodsIn all, 43 patients with residual center-involved DME following intravitreal bevacizumab were included in this 12-month prospective, nonrandomized, multicenter study. Enrolled patients received three monthly ranibizumab 0.5-mg injections. At month 3, patients with residual macular edema switched to three monthly injections of ranibizumab 2.0-mg. Assessments included monthly visual acuity and spectral-domain optical coherence tomography.ResultsMean visual acuity improved by +6.4 letters at month 3 and +8.8 letters at month 6. Mean central subfield thickness (CST) decreased by -113 μm at month 3 and -165 μm at month 6. Before enrollment, 29/43 (67.4%) patients showed <10% CST reduction following monthly bevacizumab treatment. After three monthly ranibizumab 0.5-mg injections, 22/29 (75.9%) patients showed >10% reduction in CST, whereas 6 showed <10% reduction. Of these six, three (50%) showed >10% reduction in CST after switching to three monthly ranibizumab 2.0-mg doses. No serious adverse events were observed to month 6.ConclusionRanibizumab 0.5-mg or 2.0-mg may improve visual and anatomic outcomes in patients with DME who demonstrated minimal or no response to bevacizumab therapy. Moreover, increased dosage of ranibizumab (2.0-mg) may provide additional benefit over ranibizumab 0.5-mg in some patients. However, 2.0-mg ranibizumab is not currently commercially licensed or available. © 2015 Macmillan Publishers Limited All rights reserved.


Quezada Ruiz C.,California Retina Consultants and Research Foundation | Pieramici D.J.,California Retina Consultants and Research Foundation | Nasir M.,California Retina Consultants and Research Foundation | Rabena M.,California Retina Consultants and Research Foundation | Avery R.L.,California Retina Consultants and Research Foundation
Retinal Cases and Brief Reports | Year: 2015

Purpose: To present the long-term follow-up of a patient injected with intravitreal ocriplasmin who experienced severe acute post-intravitreal ocriplasmin complications. Methods: Case report. Results: A 68-year-old man with vitreomacular traction was treated with intravitreal ocriplasmin. He experienced dyschromatopsia, severe acute visual acuity, and field loss 4 hours after the injection. This was accompanied by decreased reflectivity on spectral domain optical coherence tomography in the ellipsoid zone of the outer retina. These changes were transient, and 3 years after the injection, the patient is asymptomatic and no outer reflectivity changes are noted on his spectral domain optical coherence tomography images. Conclusion: Acute visual changes and spectral domain optical coherence tomography hyporeflectivity in the ellipsoid zone after intravitreal ocriplasmin can occur in some individuals, but in this case, these changes were reversible, and there have been no longterm implications. Copyright © by Ophthalmic Communications Society, Inc.


Steinle N.C.,California Retina Consultants and Research Foundation
Retina | Year: 2016

PURPOSE:: To assess the posterior vitreous release rates following a single, office-based intravitreal injection of expansile gas in treating vitreomacular traction. METHODS:: Thirty eyes of 29 consecutive patients with symptomatic vitreomacular traction received a single, office-based intravitreal injection of up to 0.3 mL of 100% perfluoropropane (C3F8). RESULTS:: Overall, vitreomacular traction release occurred in 25 of 30 eyes by the final follow-up visit (83% final release rate); furthermore, 90% (9 of 10 eyes) with diabetes mellitus released, 83% (5 of 6 eyes) with concurrent epiretinal membrane released, and 83% (5 of 6 eyes) previously treated with ocriplasmin released. Vitreomacular traction release occurred overnight in some patients and was documented on spectral domain optical coherence tomography at an average of 13 days (range, 1–62 days). The phakic release rate was 89% (16 of 18 eyes) versus a 75% pseudophakic release rate (9 of 12 eyes) (P = 0.3173). Ellipsoid zone changes on spectral domain optical coherence tomography occurred in 1 of 30 gas-treated eyes. One patient developed pupillary block. CONCLUSION:: Office-based intravitreal injection of C3F8 offers an inexpensive and effective treatment for vitreomacular traction, including for patients who underwent previous ocriplasmin administration and in patients with diabetes mellitus or epiretinal membrane. © 2016 by Ophthalmic Communications Society, Inc.


PubMed | California Retina Consultants and Research Foundation
Type: Journal Article | Journal: JAMA ophthalmology | Year: 2016

Anti-vascular endothelial growth factor (VEGF) therapy is commonly used to treat numerous retinal conditions and appears safe, yet controversy remains regarding systemic safety.To evaluate the systemic safety of intravitreous anti-VEGF injections in high-risk patients with diabetic macular edema (DME) and to investigate separately the subgroup of these patients with the highest level of exposure to anti-VEGF monthly treatment for 2 years.A search of MEDLINE, Cochrane Central Register of Controlled Trials, clincaltrials.gov, and ophthalmology congress abstracts January 1, 1947, to May 19, 2015.Randomized clinical trials were selected that evaluated monthly anti-VEGF injections for DME for 2 years and reported the outcome measures of cerebrovascular accidents, myocardial infarctions, arteriothrombotic events, and mortality.Two reviewers collected data independently from each study for the meta-analysis. Data were pooled using a fixed-effects model and analyzed from November 6, 2014, to June 28, 2015. Peto odds ratios with 95% CIs were calculated.Primary end points included cerebrovascular accidents and all-cause mortality in the highest-dose arms. Secondary outcomes included myocardial infarctions, arteriothrombotic events, and vascular-related death.Of 1126 articles reviewed, 598 were removed as duplicate studies and 524, for lack of monthly treatment data for 2 years, leaving 4 studies for the meta-analysis that met the search criteria: 2 trials using monthly aflibercept and 2 using monthly ranibizumab, representing 1328 patients. The primary evaluation (1078 patients) combined the monthly aflibercept and the 0.5-mg ranibizumab arms and yielded an increased risk for death compared with sham and laser treatments (odds ratio [OR], 2.98; 95% CI, 1.44-6.14; P = .003). Analysis including monthly aflibercept and 0.5-mg ranibizumab yielded an increased risk for cerebrovascular accidents (OR, 2.33; 95% CI, 1.04-5.22; P = .04) and vascular death (OR, 2.51; 95% CI, 1.08-5.82; P = .03). No definitive increased risk for myocardial infarctions and arteriothrombotic events was seen with all dose combinations.In this meta-analysis of anti-VEGF agents for patients with DME, assessment of the highest-level exposure group (those high-risk patients with DME who received 2 years of monthly treatment) revealed a possible increased risk for death and potentially for cerebrovascular accidents. Consideration of total exposure to anti-VEGF agents when treating those at high risk for vascular disease may be important.

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