Manju L. Subramanian

Bevacizumab vs Ranibizumab for Age-Related Macular Degeneration: Early Results of a Prospective Double-Masked, Randomized Clinical Trial

PURPOSE To report early outcomes of a prospective, double-masked, controlled trial comparing bevacizumab (Avastin; Genentech Inc, South San Francisco, California, USA) to ranibizumab (Lucentis; Genentech Inc) for the treatment of age-related macular degeneration. DESIGN Prospective, double-masked, randomized clinical trial. METHODS This is a single-center, randomized clinical trial at the Boston Veterans Affairs Healthcare System. Patients who met inclusion criteria were randomized 2:1 to bevacizumab or ranibizumab. Each patient contributed 1 eye to the study. All subjects and investigators (except for the pharmacist responsible for study assignments) were masked to treatment arms. Visual acuity (VA) was checked on Early Treatment Diabetic Retinopathy Study (ETDRS) chart. Patients were given either bevacizumab or ranibizumab every month for the first 3 months, followed by optical coherence tomography-guided, variable-dosing schedule. Main outcomes measured were VA and foveal thickness. RESULTS Twenty patients completed the 6-month follow up. Thirteen patients received bevacizumab and 7 patients received ranibizumab. No subjects in either group lost more than 15 letters on ETDRS chart. The average preoperative VA was 31.6 letters in the bevacizumab group and 30.4 letters in the ranibizumab group. At 6 months follow-up, mean vision was 46.4 letters in the bevacizumab group and 37.4 letters in the ranibizumab group. Two-tailed ttest failed to show statistical significance between the two groups. Patients in the bevacizumab group underwent an average of 5 injections, while patients in the ranibizumab group underwent a mean of 4 injections. CONCLUSION Early results of a head-to-head, randomized, double-masked, prospective, single-center controlled trial between bevacizumab and ranibizumab show no difference in efficacy between the two treatments for choroidal neovascularizaton in the treatment of age-related macular degeneration. As this study conveys results of a small number of patients, further studies with larger sample sizes are needed in order to establish statistical significance.

Bevacizumab vs ranibizumab for age-related macular degeneration: 1-year outcomes of a prospective, double-masked randomised clinical trial

PurposeTo report 1-year visual and anatomic outcomes of a prospective, double-masked randomised clinical trial comparing bevacizumab with ranibizumab for the treatment of age-related macular degeneration (AMD).MethodsPatients who met inclusion criteria were randomised 2 : 1 to bevacizumab or ranibizumab. All subjects and investigators (except for the pharmacist responsible for study assignments) were masked to treatment arms. Visual acuity was taken on Early Treatment Diabetic Retinopathy Study chart. Patients were given either bevacizumab or ranibizumab every month for the first 3 months, followed by an optical coherence tomography-guided, variable-dosing treatment schedule. Main outcomes measured included visual acuity, foveal thickness, and total number of injections over the 1-year treatment period.ResultsIn total, 15 patients received bevacizumab and 7 patients received ranibizumab. The average pre-operative visual acuity was 34.9 letters in the bevacizumab group, and 32.7 letters in the ranibizumab group. At 1-year follow-up, mean vision was 42.5 letters in the bevacizumab group, and 39.0 letters in the ranibizumab group. Two-tailed t-test failed to showed statistical significance between the two groups (P=0.5). Patients in the bevacizumab group underwent an average of eight injections, whereas patients in the ranibizumab group underwent a mean of four injections (P=0.001).ConclusionThe 1-year outcomes of a prospective, double-masked, randomised clinical trial comparing bevacizumab with ranibizumab failed to show a difference in visual and anatomic outcomes between the two treatments for choroidal neovascularisation in AMD. Total injections given over the treatment period were significantly different between the two groups. Further studies with larger sample sizes are warranted.

Controversies in the management of primary retinal detachments.

Rhegmatogenous retinal detachments occur when a retinal break provides access for synergetic vitreous fluid to enter the subretinal space. It is a serious disorder that can lead to permanent blindness without intervention. The age-adjusted incidence of idiopathic retinal detachments is approximately 12.5 cases per 100,000 population per year. By extrapolation, the number of phakic idiopathic retinal detachments per year in the United States is 22,000. The number of cases increases to 28,000 when including aphakic and pseudophakic cases. The repair of retinal detachments has been investigated and studied for over a century. Visualization of retinal breaks was not possible until Helmholtz introduced the ophthalmoscope in 1851. A few years later, Coccius and his colleagues observed that retinal breaks were involved in the pathogenesis of retinal detachments. But it was not until 1921 when the first, somewhat successful, intervention for retinal detachment was described. Jules Gonin changed the landscape of retinal detachment repair by developing a treatment to close retinal breaks through transscleral cautery, a procedure termed ignipuncture. Although his success rates were modest by modern standards, he was the first to realize that the key to treatment of retinal detachments is closure of the retinal break. Notable ophthalmologists such as Schepens have revolutionized the repair of retinal detachments by perfecting scleral buckling techniques, leading to success rates of primary repair of detachments currently as high as 80% to 90%. Over the last 2 to 3 decades, surgical management of primary retinal detachments has evolved dramatically, with the emergence of alternative techniques to scleral buckling such as pars plana vitrectomy JOBNAME: ioc 44#4 2004 PAGE: 1 OUTPUT: Mon September 13 11:15:47 2004

Risk factors for progression of subclinical diabetic macular oedema

Backgroud/aims The purpose of this study was to determine the incidence of, and risk factors dictating, progression of subclinical macular oedema (SCME) to clinically significant macular oedema (CSME) in patients with diabetes. Methods This was a retrospective, observational case-controlled study at the Veterans Administration (VA) Boston Healthcare System. The study group included subjects with central subfield macular thickness (CSMT) of 200–300 μm, measured by optical coherence tomography, compared with a control group with foveal thickness of <200 μm, matched for age, sex and duration of diabetes. Main outcomes measured were progression to CSME by clinical examination. Results A total 124 eyes of 73 diabetic patients from the greater Boston area were included in this retrospective study. The study group comprised 52 eyes of 37 diabetic patients with SCME in one or both eyes. The control group included 72 eyes of 36 patients without macular oedema. Sixteen eyes of 13 subjects (35%) progressed to CSME in the study group, compared with six eyes of four subjects (11%) in the control group. Stepwise logistic regression analysis confirmed that prior history of CSME increased the risk of progression (OR 3.69, CI 1.10 to 12.31, p=0.03). Logistic regression analysis also depicted a 15% increase in odds of progression with each 10 μm increase in CSMT (OR 1.15, CI 1.03 to 1.28, p=0.01). Conclusions The results and statistical analyses of this retrospective study suggest that a significant number of patients with SCME ultimately progress to CSME compared with controls. A significant association with prior history of CSME, advancing age and graded increases in CSMT was found.

Intravitreal Foscarnet Therapy for Acyclovir-Resistant Acute Retinal Necrosis After Herpes Simplex Encephalitis.

The development of acute retinal necrosis (ARN) is not uncommon among individuals with a history of herpes simplex encephalitis, as the virus may be capable of transport via axonal cells to the neuroretina. Though it is known that ARN severely threatens vision, timely initiation of effective therapy can help save a patients vision and retina. In this case report, clinical resistance to acyclovir was found. Subsequent treatment with intravitreal foscarnet resulted in immediate clinical improvement. This case suggests that patients with acute retinal necrosis can be considered for treatment with intravitreal foscarnet in the setting of systemic acyclovir resistance.

Preoperative Visual Acuity as a Prognostic Indicator for Laser Treatment of Macular Edema Due to Branch Retinal Vein Occlusion

The authors report a case of acute development of an extensive retrobulbar abscess 3 weeks after an orbital floor fracture. Urgent drainage of the abscess was performed by an anterior transconjunctival approach. A dramatic recovery was observed a few days following the operation. The visual acuity increased from hand motions to 0.7 to 0.8 in the early postoperative period and to 1.0 shortly thereafter. The severity of infection, the importance of antibiotic prophylaxis for blowout fractures, and the efficacy of the transconjunctival approach on the final visual and functional outcome are described.A 38-year-old man with human immunodeficiency virus was referred for evaluation of retinal lesions in both eyes. Optical coherence tomography was performed after dilating the pupils. Biomicroscopy of the retina showed an atypical, solitary, yellowish-white lesion in the macula of both eyes with no inflammation of the vitreous. Optical coherence tomography of the lesions showed an area of extremely low reflectivity with well-defined but irregular borders in the outer retina. The surrounding retina showed normal reflectivity and was of normal thickness. Optical coherence tomography showed selective necrosis of the outer layers due to progressive outer retinal necrosis. Optical coherence tomography may serve as a useful tool for the early diagnosis of progressive outer retinal necrosis.

A New Variant of Polypoidal Choroidal Vasculopathy With Annular Pigmentary Changes in Haitian Males

The authors report a new variant of idiopathic polypoidal choroidal vasculopathy (IPCV) in middle-aged Haitian men characterized by extramacular polypoidal lesions and bilateral extensive pigmentary alterations in the posterior pole in an annular wreath-like pattern surrounding the optic nerve and macular area. Two patients were seen at Massachusetts Eye and Ear Infirmary and one at Boston University Medical Center between 2010 and 2015. All three patients were middle-aged Haitian men who exhibited bilateral features of IPCV, including subretinal hemorrhages and serosanguinous pigment epithelial detachments. Indocyanine green angiography revealed extramacular polypoidal lesions located mostly along the major vascular arcades. Extensive pigmentary alterations were evident in the posterior pole surrounding the macula and optic nerve in an annular wreath-like pattern. These cases further expand the clinical spectrum of IPCV.

Transitioning from Stratus OCT to Cirrus OCT using Lin's concordance coefficient.

Dear Editor, We thank Drs. Tan and Li for their valuable comments on our original paper [1]. The purpose of our paper was to study the differences between central subfield macular thickness (CSMT) measurements obtained by time-domain Stratus optical coherence tomography (OCT) and Cirrus spectral-domain OCT (Carl Zeiss Meditec, Dublin, CA, USA) and to propose a method for deriving an equation to convert CSMT values from one to the other. Our method proposes to derive a linear transformation by maximizing the Lin’s concordance coefficient [2] between the CSMT measurements obtained by time-domain Stratus OCT and Cirrus spectral domain OCT rather then using simple regression. Lin’s concordance correlation coefficient evaluates the degree to which pairs of observations fall on the 45° line through the origin, and thus a transformation that maximizes this concordance measure is more appropriate for our purpose. We obtained the linear transformation 0.76 × −0.51, which proved to work very well for our practice. Unfortunately, our study was retrospective, and at the time of our study we had a limited number of eyes on both machines. Since the data was very limited, we decided to use all data points to estimate our formula more accurately. We did not have the option to get more data, as one of the machines had been retired. We thank the authors for highlighting this shortcoming with our method. We agree with the authors that using an independent sample for validation will more likely lead to a more robust equation. In their letter [3], the authors use regression to derive a linear transformation and then point out that the intra-class correlation (ICC) between the two measures is higher on the data used for deriving the equation (fit data) than on the independent data (validation data). This is expected, as the equation was estimated on the fit data. If we were aware of the differences between the two machines we would have designed the study in a more optimal way. One method that might avoid the problem mentioned by Drs. Tan and Li would be to create several splits of the data and estimate a separate equation for each split, and then average over the equations. Note that this method does require more data, which we did not have. We do hope that our paper will contribute to raising awareness of this problem in the ophthalmology community, so that physicians can use the methods discussed in [1, 3] G. Abedi (*) Vitreoretinal Disease and Surgery, University of Texas Health Science Center, San Antonio, 7703 Floyd Curl Drive, MC 6230, San Antonio, TX 78229-3900, USA e-mail: abedig@uthscsa.edu

Diabetic Macular Edema

Diabetic macular edema represents one of the most important causes of visual morbidity in diabetes mellitus. The National Diabetes Information Clearinghouse estimates the prevalence of diabetes mellitus types 1 and 2 at 11.3% of the population above the age of 20, with an annual incidence of 1.9 million cases in the United States alone. In this population, the prevalence of diabetic macular edema is estimated at 30% of patients inflicted by the disease for 20 years or more. Diabetes mellitus is the leading cause of preventable blindness owing to both diabetic macular edema and complications of proliferative diabetic retinopathy (NDIC 2011). Thus once can expect that diabetic macular edema is a common entity in any Retina specialty practice with serious implications for vision loss if not treated in a timely and appropriate manner. Based on the critical findings of the Early Treatment in Diabetic Retinopathy Study, the standard of care has been focal laser photocoagulation therapy along with strong recommendations for strict blood glucose and blood pressure control. However since then, the spectrum of therapies for diabetic macular edema has expanded and continues to evolve. The use of steroid therapy and anti-vascular endothelial growth factor biologics have been compared to focal laser photocoagulation in order to establish more treatment options with equivalent efficacy and safety.

The role of intravenous immunoglobulin in treatment of acute retinal necrosis.

PURPOSE To describe a case of successful treatment of acute retinal necrosis with a combination of antivirals and intravenous immunoglobulin. METHODS This is a case report of a 77-year-old white man diagnosed with unilateral acute retinal necrosis. RESULTS Combination therapy with systemic antivirals, prophylactic laser retinopexy, and intravenous immunoglobulin halted progression of retinitis and preserved visual acuity. CONCLUSION Acute retinal necrosis is an aggressive disease with significant risk of vision loss even when treated with appropriate therapy. In this report, the authors describe a case of successful treatment with a combination of systemic antivirals and intravenous immunoglobulin. Intraocular antiviral injection plus systemic treatment remain to be a more cost-effective option.