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      Peripheral retinal ischaemia, as evaluated by ultra-widefield fluorescein angiography, is associated with diabetic macular oedema

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          Abstract

          Purpose

          To determine the relationship between retinal ischaemia and the presence of macular oedema (DMO) in patients with diabetic retinopathy (DR) using ultra-widefield fluorescein angiography (UWFA) imaging.

          Methods

          A retrospective review of 122 eyes of 70 treatment-naïve diabetic patients who underwent diagnostic UWFA using the Optos 200Tx imaging system. Two independent, masked graders quantified the area of retinal ischaemia. Based on clinical examination and optical coherence tomography (OCT), each patient was given a binary classification as either having DMO or no DMO. McNemar's test (with Yates' correction as indicated) and a two-sample test of proportions were used to determine the relationship between DMO and ischaemia for binary and proportional data, respectively. Linear and logistic models were constructed using generalised estimating equations to test relationships between independent variables, covariates and outcomes while controlling for inter-eye correlation, age, gender, haemoglobin A1c, mean arterial pressure and dependence on insulin.

          Results

          Seventy-six eyes (62%) exhibited areas of retinal ischaemia. There was a significant direct correlation between DMO and peripheral retinal ischaemia as seen on UWFA (p<0.001). In addition, patients with retinal ischaemia had 3.75 times increased odds of having DMO compared with those without retinal ischaemia (CI 1.26 to 11.13, p<0.02).

          Conclusion

          Retinal ischaemia is significantly correlated with DMO in treatment-naïve patients with DR. UWFA is a useful tool for detecting peripheral retinal ischaemia, which may have direct implications in the diagnosis, follow-up and treatment such as targeted peripheral photocoagulation.

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          Most cited references9

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          Photocoagulation for diabetic macular edema. Early Treatment Diabetic Retinopathy Study report number 1. Early Treatment Diabetic Retinopathy Study research group.

          (1985)
          Data from the Early Treatment Diabetic Retinopathy Study (ETDRS) show that focal photocoagulation of "clinically significant" diabetic macular edema substantially reduces the risk of visual loss. Focal treatment also increases the chance of visual improvement, decreases the frequency of persistent macular edema, and causes only minor visual field losses. In this randomized clinical trial, which was supported by the National Eye Institute, 754 eyes that had macular edema and mild to moderate diabetic retinopathy were randomly assigned to focal argon laser photocoagulation, while 1,490 such eyes were randomly assigned to deferral of photocoagulation. The beneficial effects of treatment demonstrated in this trial suggest that all eyes with clinically significant diabetic macular edema should be considered for focal photocoagulation. Clinically significant macular edema is defined as retinal thickening that involves or threatens the center of the macula (even if visual acuity is not yet reduced) and is assessed by stereo contact lens biomicroscopy or stereo photography. Follow-up of all ETDRS patients continues without other modifications in the study protocol.
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            Increased vascular endothelial growth factor levels in the vitreous of eyes with proliferative diabetic retinopathy.

            The vitreous levels of the angiogenic polypeptide vascular endothelial growth factor (also known as vascular permeability factor) were measured and compared in eyes with and without proliferative diabetic retinopathy. Undiluted vitreous samples from 20 eyes were collected at the time of vitrectomy, and vascular endothelial growth factor levels were determined by using a time-resolved immunofluorometric assay. Vitreous vascular endothelial growth factor levels were significantly higher in eyes with proliferative diabetic retinopathy than in eyes without proliferative diabetic retinopathy (P = .006; Wilcoxon Rank Sum Test). The median vitreous concentration in the eyes with proliferative diabetic retinopathy was 29.1 pM and exceeded the known concentration required for the maximal proliferation of vascular endothelial cells in vitro. These data are consistent with vascular endothelial growth factor serving as a physiologically relevant angiogenic factor in proliferative diabetic retinopathy.
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              Intravitreal bevacizumab (Avastin) therapy for persistent diffuse diabetic macular edema.

              To evaluate the efficacy of bevacizumab (Avastin; Genentech, Inc., South San Francisco, CA) for the treatment of diabetic macular edema. This prospective, consecutive, noncomparative case series included 51 consecutive patients (26 females and 25 males; mean age, 64 years) with diffuse diabetic macular edema. Inclusion criteria were determined independently of the size of edema, retinal thickness, visual acuity, age, metabolic control, type of diabetes, or previous treatments beyond a 6-month period. At each visit, patients underwent complete eye examination, including determination of best-corrected visual acuity, slit-lamp examination, intraocular pressure measurement, stereoscopic biomicroscopy of the macula, retinal thickness measurement by optical coherence tomography, fluorescein angiography, and fundus photography. After written informed consent was obtained, all patients were treated with a 0.05-mL injection containing 1.25 mg of bevacizumab. All patients completed 6 weeks of follow-up; 23 (45%) completed 12 weeks of follow-up. Sixteen patients (70%) had received at least two intravitreal injections. All patients had undergone previous treatments, such as focal laser therapy (35%), full-scatter panretinal laser therapy (37%), vitrectomy (12%), and intravitreal injection of triamcinolone (33%). The mean diameter of the foveal avascular zone was 503 micro m, with 49% with values of >500 micro m. At baseline, mean visual acuity +/- SD was 25.88 +/- 14.43 ETDRS letters (0.86 +/- 0.38 logMAR of Snellen letters). Mean central retinal thickness by optical coherence tomography +/- SD was 501 +/- 163 micro m (range, 252-1,031 micro m). Mean visual acuity +/- SD increased to 0.75 +/- 0.37 logMAR of Snellen letters at 6 weeks after injection (P = 0.001), with some regression to 0.84 +/- 0.41 logMAR of Snellen letters after 12 weeks. Changes in ETDRS letters were not significant throughout follow-up. Mean retinal thickness +/- SD decreased to 425 +/- 180 micro m at 2 weeks (P = 0.002), 416 +/- 180 micro m at 6 weeks (P = 0.001), and 377 +/- 117 micro m at 12 weeks (P = 0.001). Changes of retinal thickness and visual acuity correlated weakly (r = -0.480 and P = 0.03 at 6 weeks; r = -0.462 and P = 0.07 at 12 weeks). The increase of visual acuity after 6 weeks as measured by ETDRS charts could be predicted best by baseline visual acuity. No other factors investigated, such as age, thickness by optical coherence tomography, or previous treatments, were predictive for the increase in visual acuity. Even in cases of diffuse diabetic macular edema not responding to previous treatments such as photocoagulation, intravitreal injection of triamcinolone, or vitrectomy, improvement of visual acuity and decrease of retinal thickness could be observed after intravitreal injection of bevacizumab. Although our follow-up period was too short to provide specific treatment recommendations, the short-term results encourage further prospective studies with different treatment groups and longer follow-up.
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                Author and article information

                Journal
                Br J Ophthalmol
                Br J Ophthalmol
                bjo
                bjophthalmol
                The British Journal of Ophthalmology
                BMJ Group (BMA House, Tavistock Square, London, WC1H 9JR )
                0007-1161
                1468-2079
                15 March 2012
                May 2012
                15 March 2012
                : 96
                : 5
                : 694-698
                Affiliations
                Department of Ophthalmology, Weill Cornell Medical College. 1305 York Avenue, 11th Floor, New York, New York, USA
                Author notes
                Correspondence to Dr Szilárd Kiss, Department of Ophthalmology, Weill Cornell Medical College, 1305 York Avenue, 11th Floor, New York, NY 10021; szk7001@ 123456med.cornell.edu
                Article
                bjophthalmol-2011-300774
                10.1136/bjophthalmol-2011-300774
                3329634
                22423055
                9b17fe31-6346-4233-8789-c4935ce70ffb
                © 2012, Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

                This is an open-access article distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits use, distribution, and reproduction in any medium, provided the original work is properly cited, the use is non commercial and is otherwise in compliance with the license. See: http://creativecommons.org/licenses/by-nc/2.0/ and http://creativecommons.org/licenses/by-nc/2.0/legalcode.

                History
                : 12 November 2011
                Categories
                Clinical Science
                1506
                Original article

                Ophthalmology & Optometry
                diabetes,diabetic macular oedema,retina,fluorescein angiography,diabetic retinopathy,ultra-wide field imaging,epidemiology

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