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A CME-certified supplement to Release date: August 15, 2014 Expiration date: August 15, 2015 Estimated time to complete activity: 30 minutes Target Audience: This educational activity is designed for physicians who treat patients with diabetes at risk for diabetic macular edema. Statement of Need: Diabetes is the leading cause of blindness among adults in the United States. Diabetic retinopathy (DR), a consequence of long-term exposure to excess blood glucose in the microvasculature of the eye, is a significant contributor to impaired vision and blindness in patients with diabetes. Diabetic macular edema (DME), which involves retinal thickening, can develop at any stage of retinopathy and is a principal cause of vision loss in diabetes. Although the American Diabetes Association recommends an annual dilated eye examination in patients with diabetes, 30% to 40% of patients do not receive this preventive measure. Adequate control of hyperglycemia and hypertension are also paramount to decreasing risks for DR and DME. In the last decade, improved understanding of the multifactorial pathophysiology of DME has resulted in novel approaches to suppress angiogenesis and edema, such as anti-VEGF therapies. This activity will review strategies for recognizing and managing DME. Learning Objectives: Upon completion of this activity, participants will be able to: •Outline data supporting primary prevention strategies for DR and DME in patients with diabetes •Identify patients with DR and DME who require treatment early in disease progression to minimize vision loss •Discuss therapies for DME, including laser photocoagulation, anti-VEGF therapies, and corticosteroids •Evaluate data on combination therapies and dosing paradigms in DME management to improve outcomes and reduce treatment burden for patients. Accreditation Statement: Indiana University School of Medicine is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. Credit Designation: Indiana University School of Medicine designates this enduring material for a maximum of 0.5 AMA PRA Category 1 Credit™. Physicians should claim only the credit commensurate with the extent of their participation in the activity. While it offers CME/CE credits, this activity is not intended to provide extensive training or certification in the field. How to Receive Credit: To receive credit, participants are required to review the supplement, relate the content material to the learning objectives, achieve at least 70% on the self-assessment, and complete an evaluation form online. These forms can be completed online at www.ACHLcme.org. Click on “Get Certificate”; Enter the Certificate Code 2881331. A certificate will be immediately available. Inquiries may be directed to ACHL at (877) 444-8435, ext. 203. Recognizing Eye Complications in Diabetes: Diabetic Retinopathy and Diabetic Macular Edema Jennifer I. Lim, MD, FARVO Professor of Ophthalmology Marion H. Schenk, Esq., Chair in Ophthalmology for Research of the Aging Eye Director of the Retina Service Illinois Eye and Ear Infirmary UIC Department of Ophthalmology and Visual Sciences University of Illinois at Chicago Chicago, Illinois Prevention of Diabetic Retinopathy Visual loss from diabetes remains a major cause of blindness in the world. Untreated, diabetes affects not only the lens (cataracts), but more importantly, the retina. Fortunately, there are treatments available to mitigate, and sometimes reverse, visual loss from diabetic retinopathy (DR). Diabetes is a growing health problem in the United States; its prevalence is expected to rise to 21% of adults in 2050 from the estimated 11.3% of the US population in 2010.1,2 In the United States, it is the seventh leading cause of death.2 In the prevention and treatment of DR, systemic factors are very important. Numerous epidemiologic studies and trials have documented the importance of glycemic and blood pressure control in patients with diabetes. The Diabetes Control and Complications Trial (DCCT, 1982-1993) compared intensive with conventional control for onset and progression of DR in type 1 diabetics.3 The Epidemiology of Diabetes Interventions and Complications study (1994-present) followed the DCCT cohort. At baseline in the DCCT, 726 of the 1,441 participants had no DR (primary prevention cohort) while 715 had mild DR (secondary intervention cohort). Participants were followed for a mean of 6.5 years. The median HbA1c was 7% for the intensive control group compared with 9% for the conventional control group. The intensive control showed a 76% reduction in the adjusted mean risk for the development of DR compared with the conventional control group. In addition, intensive control slowed progression of DR by 54% compared with conventional control. Although subsequent HbA1c levels in the original intensive and conventional groups converged to approximately 8% for both groups by year 8, initial assignment to intensive therapy continued to significantly lower the incidence of further DR progression (hazard reduction 53%-56%).3 Thus, earlier optimization of glycemic levels continues to have effects many years later on the progression of DR. Other studies, such as the United Kingdom Prospective Diabetes Study, which studied type 2 diabetics, the Wisconsin Epidemiology Study of Diabetic Retinopathy,4 and the Early Treatment of Diabetic Retinopathy Study (ETDRS),5 also support the importance of glucose control in reducing the incidence and progression of DR. In addition, these studies also showed the importance of control of blood pressure, lipids, renal function, and body weight on the incidence and progression of DR. Thus, systemic diabetes control significantly impacts patients’ eyes. Approximately one third of patients with diabetes has DR.6 The American Academy of Ophthalmology and the American Diabetes Association recommend that a dilated eye exam be performed within 3 to 5 years for type 1 diabetics and at the time of diagnosis for type 2 diabetics.7,8 Yearly dilated eye exams are recommended thereafter for both types. Unfortunately, studies have shown that patients do not get regular eye exams and they are unaware of the existence of sight-threat- This activity is co-provided by: Our acknowledgement to Regeneron Pharmaceuticals, Inc. for an educational grant in support of this activity. Claim your credits at www.ACHLcme.org • www.globalacademycme.com Disclosure of Conflicts of Interest: Indiana University School of Medicine requires that the faculty participating in a CME/CE activity disclose all affiliations or other financial relationships (1) with the manufacturers of any commercial product(s) and/or provider(s) of commercial services discussed in an educational presentation and (2) with any commercial supporters of the activity. All conflicts of interest have been resolved prior to this CME/CE activity. Indiana University School of Medicine also requires participating faculty to disclose when unapproved/unlabeled uses of a product are discussed in a CME/CE activity. This CME/CE activity might describe the off-label, investigational, or experimental use of medications that may exceed their FDA-approved labeling. Physicians should consult the current manufacturers’ prescribing information for these products. Indiana University School of Medicine requires the speaker to disclose that a product is not labeled for the use under discussion. The following disclosure information has been provided: Jennifer I. Lim, MD, FARVO Sources of Funding Research: Genentech and Regeneron Consulting Agreements, Speaker’s Bureau, and Honorarium Agreements: Genentech, Regeneron, and Santen Discussion of Off-Label, Investigational, or Experimental Drug/Device Use: Use of aflibercept for diabetic macular edema All Indiana University School of Medicine and Academy for Continued Healthcare Learning staff members and others involved with the planning, development, and review of the content for this activity have no relevant affiliations or financial relationships to disclose. Disclaimer: The content for this activity was developed independently of the commercial supporter. All materials are included with permission. The opinions expressed are those of the faculty and are not to be construed as those of the publisher or grantor. This educational activity was planned and produced in accordance with the ACCME Essential Areas and Elements, Updated Criteria, Policies, and Standards for Commercial Support. Recommendations involving clinical medicine in a continuing medical education (CME/CE) activity must be based on evidence that is accepted within the profession of medicine as adequate justification for their indications and contraindications in the care of patients. All scientific research referred to, reported, or used in CME/CE in support or justification of a patient care recommendation must conform to the generally accepted standards of experimental design, data collection, and analysis. This supplement was produced by the Academy for Continued Healthcare Learning. Neither the editors of Clinical Endocrinology News, nor the Editorial Advisory Board, nor the reporting staff contributed to its content. The opinions expressed in this supplement are those of the faculty and do not necessarily reflect the views of the supporters, the joint providers, or of the Publisher. Copyright © 2014 Global Academy for Medical Education, LLC and Frontline Medical Communications Inc. All rights reserved. No part of this publication may be reproduced or transmitted in any form, by any means, without prior written permission of the Publisher. The Publisher will not assume responsibility for damages, loss, or claims of any kind arising from or related to the information contained in this publication, including any claims related to the products, drugs, or services mentioned herein. ening retinopathy. In a study of 2,798 patients at the Joslin Diabetes Center, 83% of those with DR and 78% with advanced DR were unaware of their disease at their first visit (personal communication, Lloyd Paul Aiello, MD, PhD). Patients should also be followed more closely during onset of tight glucose control as acceleration of DR is frequently seen, although it is transient. During puberty and pregnancy, more frequent exams are also warranted as DR can rapidly accelerate. Diagnosis and Treatment of Diabetic Retinopathy Levels of Diabetic Retinopathy Diabetic retinopathy can be classified by the level of DR and also by the presence or absence of diabetic macular edema (DME), swelling in the area within the vascular arcades, temporal edge of the optic nerve head, and the equivalent area temporal to the foveal center. Diabetic retinopathy is generally divided into non-proliferative (NPDR) and proliferative (PDR) DR. NPDR has three stages: mild, moderate, and severe. These levels, defined by ETDRS, refer to the severity of the disease and have associated prognostic implications for acceleration of disease. A patient with mild NPDR may be seen yearly, whereas a patient with severe NPDR may need to be seen as often as every 3 months. In NPDR, microaneurysms are present. Depending upon the severity of the disease, retinal hemorrhages, cotton wool spots, venous beading, and intraretinal microvascular anomalies may be seen. There is typically none to minimal visual loss. However, if there is concomitant DME, there may be significant visual acuity loss. In eyes with PDR, neovascular vessels sprout from the retinal venous circulation. These vessels are immature and prone to bleeding, which can result not only in preretinal hemorrhages but also vitreous hemorrhages with significant loss of vision. Depending on the location of the neovascularization and presence/type of hemorrhage, the PDR may be graded as high risk for visual acuity loss. PDR on the nerve head or within 1 disc diameter of the nerve head is termed neovascularization of the disc (NVD); neovascularization elsewhere is termed NVE. NVD and NVE will continue to progress over time. Fibrosis and scarring can occur, and these can result in retinal detachment. Fortunately, panretinal laser photocoagulation (PRP) is highly effective in curbing the growth of these blood vessels and can help prevent visual loss. In fact, in the Diabetic Retinopathy Study, 2 panretinal laser photocoagulation resulted in a 50% reduction of severe visual loss.9 In the ETDRS, prompt laser was again associated with reduction in progression and visual loss even in less severe levels of retinopathy.10 It is thus important for the patient to receive prompt care. Fibrosis and scarring associated with progressive neovascularization can lead to tractional retinal detachments. Continued traction on the retina may result in retinal holes, which may cause elevation of the retina and hence a rhegmatogenous retinal detachment. When the detachment threatens the macula or involves the macular areas, pars plana vitrectomy surgery (PPV) is needed. During PPV, the vitreous is removed, the membranes and vitreous attachment are carefully dissected off the retinal surface, and laser is applied. An injection of intraocular gas (or sometimes a longer tamponade such as silicone oil, which requires a second surgical procedure for removal) is needed if there are associated retinal holes. In some eyes with significant ischemia, neovascular vessels may develop on the iris (rubeosis). These fragile vessels can result in a hyphema (anterior chamber bleed) as well as glaucoma (neovascular or rubeotic glaucoma). Unmitigated growth will cause the anterior chamber angle to scar. These patients will present with painful eyes and elevated eye pressure. Glaucoma eyedrops and treatment to cause regression of the neovascularization is urgently needed. Depending upon the view to the retina, PRP may be performed. An anti-vascular endothelial growth factor (VEGF) drug is also frequently injected into the eye to help cause regression of the neovascular vessels. In cases in which no view of the retina is possible, vitrectomy surgery with PRP is urgently needed to prevent blindness. Diabetic Macular Edema DME occurs in 13% of DR eyes. The presence of DME has been found to be associated with higher risks of myocardial infarction (2.5X) and stroke/cerebral vascular accident (2X) than in patients without DME. If the central foveal area is involved, visual acuity loss may be severe. The term clinically significant macular edema (CSDME) is used specifically to refer to the subtype of DME with high risk for severe, and perhaps permanent, visual acuity loss, if not treated. There are three types of CSDME as defined in the ETDRS: 1. Edema involving the foveal center or within 500 microns of the fovea; 2. Edema www.globalacademycme.com • Recognizing Eye Complications in Diabetes within 1 disc diameter of the fovea and at least 1 disc diameter in size; and 3. Edema associated with any exudate that is within 500 microns of the foveal center.11 CSDME is typically detected through the use of clinical examination with either a contact lens on the patient’s eye or through a non-contact lens. Ancillary tests are helpful to document the presence and extent of DR or CSDME. Objective measurements of the degree of thickening are made with the use of optical coherence tomography (OCT), a quick, noninvasive, in-office procedure. Using OCT, the amount of thickening in various regions of the macula is measured (microns) (see Figure). These measurements are very helpful in following a patient’s response to therapy. OCT is frequently repeated during treatment of CSDME. At the time of CSDME diagnosis, a fluorescein angiogram (FA), in which a vegetable-based dye is injected through a peripheral vein and special filters are used that allow the retinal vasculature to be imaged, is helpful to determine the presence and extent of ischemia. Sometimes, edema may result from ischemia in the absence of active vascular leakage and this affects the treatment plan. A FA is also helpful to detect areas of retinal neovascularization (leaks profusely). However, a good clinical exam alone is often all that is needed to make a diagnosis of CSDME or PDR. Treatment options for CSDME include laser, intravitreal steroid, and intravitreal injection of anti-VEGF drugs. The ETDRS showed that focal or grid laser of CSDME reduced the risk of moderate visual loss (3 lines) by approximately 50%.12 Focal laser treatment may need to be repeated at 4-month intervals until a response or complete treatment is achieved. Recent Clinical Trial Results: Advancements in Therapy for DME Most recently, treatments other than laser or in combination with laser have been shown to be efficacious for treatment of DMEassociated edema. These include corticosteroids and anti-VEGF therapies. Corticosteroids stabilize the blood-retinal barrier. The use of VEGF as a target was predicated by findings that increased levels of VEGF have been well documented in eyes with DME or DR.13,14 In general, the more severe the DME and the higher the level of DR, the higher the VEGF level.15 The efficacy of intravitreal injections of anti-VEGF has been well documented in numerous clinical trials. Most noteworthy are the DRCR Protocol I results16 and the RIDE/RISE17 and VISTA/VIVID18 studies. These phase 3 clinical trials led to the approval of the anti-VEGF drugs ranibizumab and aflibercept. The DRCR presented an alternative dosing regimen to the monthly injections used in RISE and RIDE for ranibizumab. The VISTA and VIVID studies showed that aflibercept was superior to laser treatment but was not compared directly to ranibizumab.18 The use of bevacizumab is off-label for DME, but is often used due to its lower cost and evidence of efficacy.19 At present, a large, randomized DRCR study is comparing the effects of ranibizumab, ters (RIDE control) and 2.9 letters (RISE control) at 24 months. After 24 months, the sham group was allowed to receive ranibizumab 0.5 mg monthly. At the end of 3 years, the visual acuity improved 10.5 to 11.4 letters (RIDE) and 11 to 14.2 letters (RISE) versus 4.7 (RIDE/ sham/ranibizumab) and 4.3 (RIDE sham/ranibizumab).17 In the eyes that received 0.3 mg ranibizumab monthly, 39% to 36% received rescue laser by 24 months in the RIDE/ RISE studies.17 In contrast, 70% (RIDE) or 74% (RISE) of the sham group received laser treatment. Furthermore, it was rare (1.6% RIDE and 0% RISE) for ranibizumab 0.3 mg treated eyes to require PRP as compared with the sham-treated eyes (12.3% RIDE and Image courtesy of Dr. Jennifer Lim 11% RISE). In fact, OCT image of the left eye of a patient with marked macular the overall retinopedema. The dark circular spaces represent macular edema cyst athy severity of the within the retina. The bright white dots represent lipids. The an-ti-VEGFtreated dome-shaped area centrally represents subretinal fluid. eyes improved in aflibercept, and bevacizumab in the treat- over one third of the ranibizumab-treated ment of CSDME eyes. eyes versus only 4% (RIDE) to 7% (RISE) of Adverse events associated with anti-VEGF sham-treated eyes.17 It is unclear at this time therapies include local adverse events and whether the effects will persist or wane over potential systemic risks in patients with di- time after frequent therapy is decreased or abetes, such as the ocular potential for infec- stopped. tion or damage to ocular structures during In the DRCR study, anti-VEGF was given the intravitreal injection itself. The risk of at baseline and monthly for a total of 3 indamage to ocular structures is extremely jections. If the visual acuity was not 20/20, low in trained hands, and the risk of en- or if the OCT still showed edema, 2 more dophthalmitis is about 1 in 1000. Potential injections spaced monthly were given.16 A systemic adverse events include Antiplate- computerized algorithm was used to deterlet Trialists’ Collaboration (APTC)-defined mine the need for further treatments. Using arterial thromboembolic events. There was this method, a total of approximately 9 to 10 a trend for the higher dose of ranibizumab injections were given in the first year, 3 to 4 (0.5 mg) to be associated with more APTC in the second year, and 1 to 2 in the third year events than the lower dose of ranibizum- of the study. Thus, it appears that continuous ab (0.3 mg).17 Because of this potential, therapy is not required to achieve sustained the lower (0.3 mg) dose was approved for visual acuity improvement. The timing of use in diabetes instead of the 0.5 mg dose. laser therapy immediately with the first anHowever, one should remember that these ti-VEGF treatment was compared to deferred studies were not powered to detect a differ- laser therapy (6 months) in the DRCR study. ence in systemic risks between anti-VEGF– The results were similar. In fact, it was found treated eyes and control (laser-treated) eyes. that 70% of the deferred eyes never required The dosing regimen used in RIDE and laser. Many questions about the timing of RISE was monthly intravitreal injections of laser therapy remain to be answered: whetheither 0.3 mg or 0.5 mg ranibizumab versus er to add, when to add, and what long-term a sham injection.17 Patients were followed benefit occurs with combined anti-VEGF and monthly, and OCT was performed at each laser in the treatment of DME. visit. Laser photocoagulation was allowed Most recently, the VISTA and VIVID beginning at month 3, and could be given results have been reported. In these multievery 3 months. Using this regimen, the vi- center, randomized studies, eyes with CSDsual acuity improved 11 to 12 letters (RIDE) ME were randomized to laser therapy (as and 12 to 13 letters (RISE) versus 2.3 let- needed every 12 weeks) versus aflibercept Recognizing Eye Complications in Diabetes • www.globalacademycme.com 3 2 mg monthly versus aflibercept 2 mg monthly for 3 doses and then every 8 weeks.18 In VIVID, aflibercept eyes improved 10.5 letters (2 mg monthly) and 10.7 letters (2 mg q 8) versus laser eyes, which improved 1.2 letters. In VISTA, aflibercept eyes improved 12.5 letters (2 mg monthly) and 10.7 letters (2 mg q 8) versus laser eyes, which improved 0.2 letters. More aflibercept-treated eyes improved 2 steps in the severity of DR than sham-treated eyes (33 to 27% vs 7.5% VIVID; 33.8%-29% vs 14.3% VISTA). Results were maintained at 100 weeks. The use of corticosteroids is usually restricted to pseudophakic or phakic eyes, due to risk of cataract formation. In fact, in the DRCR studies, corticosteroids given every 4 months decreased macular edema, but visual acuity decreased later due to cataract formation.16 When a subgroup of pseudophakic eyes was studied, no subsequent secondary drop in visual acuity occurred. In fact, the visual acuity improvement in these eyes receiving laser with corticosteroid injected intravitreally was similar to that seen in eyes given anti-VEGF intravitreally with or without prompt laser. Sustained release implants have been studied in the treatment of DME. In the dexamethasone implant study, eyes with DME of at least 90 days duration were randomized to either 350 µg or 700 µg dexamethasone implant.20 The primary endpoint, a 10 or more letter increase at day 90, was seen in 33.3% of the 700 µg and 21.1% of the 350 µg group versus 12.3% in the observation group (P=0.007 for 700 µg). At day 180, a 10 or more letter increase was seen in 30% of the 700 µg and 19% of the 350 µg group, and 23% in the observation group (P>0.4 for treated vs observed eyes). Greater improvements in central retinal thickness and fluorescein leakage were found in treated eyes than observed eyes (P=0.03; day 90). The dexamethasone implant was well tolerated. Another steroid, fluocinolone, has also been studied in eyes with DME. In the FAME study, more eyes gained visual acuity in either the 0.2 µg/day (28.7%) or the 0.5 µg/day (27.8%) fluocinolone implant groups compared with control (18.9%) (P=0.018).21 In a preplanned subgroup analysis, there was a doubling of benefit compared with sham injections in patients who reported a duration of DME for ≥3 years at baseline; ≥15 gain at month 36 was 34.0% (low dose; P<0.001) or 28.8% (high dose; P=0.002) compared with 13.4% (sham). In addition, an improvement ≥2 steps in the ETDRS retinopathy scale occurred in 13.7% (low dose) and 10.1% (high dose) compared with 8.9% in the sham group. Complications included cataract in almost all phakic patients, but their visual benefit after cataract surgery was similar to that in pseudophakic patients.22 One must remember that intraocular infection is a real risk with all intravitreal treatments. Therefore, if the edema does not involve the center and the visual acuity is better than 20/40, one should consider focal laser treatment. The timing of focal laser with anti-VEGF therapies and the treatment of chronic DME is not yet established. For eyes with chronic edema, intraocular steroids may be more beneficial than anti-VEGF drugs. References 9. The Diabetic Retinopathy Study (DRS) Research Group: Preliminary report on the effects of photocoagulation therapy: DRS Report No. 1. Am J Ophthalmol. 1976;81:383-396. 10. Early Treatment of Diabetic Retinopathy Study Group. Early Photocoagulation Study Group. Techniques for scatter and local photocoagulation treatment of diabetic retinopathy: The Early Treatment of Diabetic Retinopathy Study report no. 3. Int Ophthalmol Clin. 1987;27:254-264. 11. T reatment techniques and clinical guidelines for photocoagulation of diabetic macular edema. Early Treatment Diabetic Retinopathy Study Report Number 2. Early Treatment Diabetic Retinopathy Study Research Group. Ophthalmology. 1987;94(7):761-774. 12. Photocoagulation for diabetic macular edema. Early Treatment Diabetic Retinopathy Study report number 1. Early Treatment Diabetic Retinopathy Study research group. Arch Ophthalmol. 1985;103(12):1796-1806. 13. Aiello LP, Avery RL, Arrigg PG, et al. Vascular endothelial growth factor in ocular fluid of patients with diabetic retinopathy and other retinal disorders. N Engl J Med. 1994;331(22):1480-1487. 14. Funatsu H, Yamashita H, Noma H, Mimura T, Yamashita T, Hori S. Increased levels of vascular endothelial growth factor and interleukin-6 in the aqueous humor of diabetics with macular edema. Am J Ophthalmol. 2002;133(1):70-77. 15. Funatsu H, Yamashita H, Ikeda T, et al. Vitreous levels of interleukin-6 and vascular endothelial growth factor are related to diabetic macular edema. Ophthalmology. 2003;110(9):1690-1696. 16. Diabetic Retinopathy Clinical Research Network, Elman MJ, Aiello LP, et al. Randomized trial evaluating ranibizumab plus prompt or deferred laser or triamcinolone plus prompt laser for diabetic macular edema. Ophthalmology. 2010;117(6):1064-1077. 17. B rown DM, Nguyen QD, Marcus DM, et al. Longterm outcomes of ranibizumab therapy for diabetic macular edema: The 36-month results from two phase III trials: RISE and RIDE. Ophthalmology. 2013;120(10):2013-2022. 18. D o DV. Intravitreal afliberept injection (IAI) for diabetic macular edema (DME): 12-month results of VISTA-DME and VIVID-DME. Paper presented at: the 2013 Annual Meeting of the American Academy of Ophthalmology; November 16-19, 2013; New Orleans, LA. 19. Michaelides M, Kaines A, Hamilton RD, et al. A prospective randomized trial of intravitreal bevacizumab or laser therapy in the management of diabetic macular edema (BOLT study) 12-month data: Report 2. Ophthalmology. 2010;117(6):1078-1086. 20. H aller JA, Kuppermann BD, Blumenkranz MS, et al. Randomized controlled trial of an intravitreous dexamethasone drug delivery system in patients with diabetic macular edema. Arch Ophthalmol. 2010;128(3):289-296. 21. C ampochiaro PA, Brown DM, Pearson A, et al. Long-term benefit of sustained-delivery fluocinolone acetonide vitreous inserts for diabetic macular edema. Ophthalmology. 2011;118(4):626-635. 22. Campochiaro PA, Brown DM, Pearson A, et al. Sustained delivery fluocinolone acetonide vitreous inserts provide benefit for at least 3 years in patients with diabetic macular edema. Ophthalmology. 2012;119(10):2125-2132. 1. Boyle JP, Thompson TJ, Gregg EW, Barker LE, Williamson DF. Projection of the year 2050 burden of diabetes in the US adult population: Dynamic modeling of incidence, mortality, and prediabetes prevalence. Popul Health Metr. 2010;8:29. 2. Centers for Disease Control and Prevention Website. National Diabetes Fact Sheet, 2011. http://www.cdc. gov/diabetes/pubs/factsheet11.htm. Accessed May 16, 2014. 3. Aiello LP. Diabetic retinopathy and other ocular findings in the diabetes control and complications trial/ epidemiology of diabetes interventions and complications study. Diabetes Care. 2014;37(1):17-23. 4. Klein R, Knudtson MD, Lee KE, Gangnon R, Klein BE. The Wisconsin Epidemiologic Study of Diabetic Retinopathy: XXII the twenty-five-year progression of retinopathy in persons with type 1 diabetes. Ophthalmology. 2008;115(11):1859-1868. 5. Fong DS, Ferris FL 3rd, Davis MD, Chew EY. Causes of severe visual loss in the early treatment diabetic retinopathy study: ETDRS report no. 24. Early Treatment Diabetic Retinopathy Study Research Group. Am J Ophthalmol. 1999;127(2):137-141. 6. Zhang X, Saaddine JB, Chou CF, et al. Prevalence of diabetic retinopathy in the United States, 20052008. JAMA. 2010;304(6):649-656. 7. American Academy of Ophthalmology Retina Panel. Preferred Practice Pattern Guidelines. http://one. aao.org/preferred-practice-pattern/diabetic-retinopathy-ppp--september-2008-4th-print. Accessed May 16, 2014. 8. American Diabetes Association. Standards of medical care in diabetes--2013. Diabetes Care. 2013;36 (suppl 1):S11-S66. 4 Summary Novel treatments in development include drugs that inhibit pericytes and those that affect non-VEGF pathways. At present, we are fortunate that there are several drugs that can reduce the edema and cause regression of DR. For eyes in which DME does not involve the center of the fovea, laser remains an important treatment. Laser is also the main treatment for eyes with PDR. Studies are ongoing to determine the benefit of anti-VEGF and laser combination therapy in eyes with CSDME as well as eyes with PDR. However, with all of these treatments, one needs to remember that earlier stages of disease are more readily treated and have better potential outcome. Prompt diagnosis and treatment of retinopathy combined with concomitant systemic glycemic, blood pressure, lipid, and weight control will result in lower rates of morbidity from DR. www.globalacademycme.com • Recognizing Eye Complications in Diabetes