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Original Investigation | Clinical Sciences

Underuse of the Health Care System by Persons With Diabetes Mellitus and Diabetic Macular Edema in the United States FREE

Neil M. Bressler, MD1; Rohit Varma, MD2; Quan V. Doan, PharmD3; Michelle Gleeson, PhD3; Mark Danese, PhD3; Julie K. Bower, PhD4; Elizabeth Selvin, PhD4; Chantal Dolan, PhD5; Jennifer Fine, ScD5; Shoshana Colman, PhD5; Adam Turpcu, PhD5
[+] Author Affiliations
1Wilmer Eye Institute, Johns Hopkins University School of Medicine and Hospital, Baltimore, Maryland
2Department of Ophthalmology and Visual Sciences, Illinois Eye and Ear Infirmary, University of Illinois College of Medicine, Chicago
3Outcomes Insights, Inc, Westlake Village, California
4Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
5Genentech, Inc, South San Francisco, California
JAMA Ophthalmol. 2014;132(2):168-173. doi:10.1001/jamaophthalmol.2013.6426.
Text Size: A A A
Published online

Importance  Thickening of the center of the retina, diabetic macular edema (DME), is the most common cause of visual loss due to diabetes mellitus. Treatment of DME has improved dramatically, and the prompt diagnosis of DME and referral of these patients have become more critical. Nonetheless, awareness of and care for DME in the US population is uncharacterized.

Objective  To characterize eye care and awareness of eye disease among persons with DME in the general US population.

Design, Setting, and Participants  Cross-sectional analysis of data from participants in the 2005 to 2008 National Health and Nutrition Examination Survey 40 years or older with diabetes mellitus and fundus photographs.

Main Outcomes and Measures  Among persons with DME, (1) awareness that diabetes has affected their eyes; (2) report on the last time they visited a diabetes specialist; (3) report on their last eye examination with pupil dilation; and (4) prevalence of visual impairment.

Results  In 2010, only 44.7% (95% CI, 27.0%-62.4%) of US adults 40 years or older with DME reported being told by a physician that diabetes had affected their eyes or that they had retinopathy; 46.7% (95% CI, 27.5%-66.0%), that they had visited a diabetes nurse educator, dietician, or nutritionist for their diabetes mellitus more than 1 year ago or never; and 59.7% (95% CI, 43.5%-75.9%), that they had received an eye examination with pupil dilation in the last year. Among persons with DME, 28.7% (95% CI, 12.7%-44.7%) were visually impaired (defined as visual acuity worse than 20/40 in the eye with DME) based on visual acuity at the initial examination and 16.0% (95% CI, 2.5%-29.4%) based on best-corrected visual acuity.

Conclusions and Relevance  Many persons with diabetes mellitus in the United States are not getting care that can prevent visual impairment and blindness. Strategies to increase awareness are warranted, especially given the recent availability of improved therapies for DME.

Figures in this Article

Diabetic retinopathy is the most common cause of new cases of blindness in working-age Americans,1 usually as a result of proliferative diabetic retinopathy or diabetic macular edema (DME). Diabetic retinopathy is also the most common cause of less severe levels of visual impairment in this age group,24 most often due to DME.5 Because DME can lead to substantial visual loss if left untreated for 1 year or longer,6,7 health care providers need to ensure that individuals with diabetes mellitus are aware that the condition can affect their eyes, especially those with DME. According to the American Diabetes Association8 and the American Academy of Ophthalmology,6 an eye examination with pupil dilation is needed at least annually to identify the presence of diabetic retinopathy, including DME, even in the absence of visual loss.

Treatment of DME has improved dramatically during the past few years. Recent government- and industry-sponsored trials914 have shown that injections of anti–vascular endothelial growth factor drugs, sometimes in combination with laser photocoagulation, safely provide superior visual outcomes compared with the previous standard of care of laser photocoagulation alone in eyes in which DME is causing visual impairment. For example, the National Institutes of Health–funded Diabetic Retinopathy Clinical Research Network reported in 2012 that ranibizumab therapy with prompt or deferred laser photocoagulation in eyes with DME causing visual loss resulted in approximately 50% of treated eyes gaining substantial vision and less than 5% losing substantial vision through at least 3 years of follow-up compared with laser photocoagulation alone.9 However, prompt diagnosis of DME and referral of patients with these complications are critical to initiate treatment before substantial visual loss has occurred. Despite these recent advances, awareness and care of DME in the US population, to our knowledge, is uncharacterized. We undertook this study to characterize the prevalence of eye care and the awareness of eye disease and visual impairment among persons with DME in the general US population.

Study Population

The National Health and Nutrition Examination Survey (NHANES) is a series of cross-sectional surveys conducted by the National Center for Health Statistics, a part of the Centers for Disease Control and Prevention.15 Participants are selected from the noninstitutionalized civilian population in the United States by using a stratified, multistage, probability sampling design. This study analyzed data from the 2005 to 2008 NHANES cycles, when retinal photographs were obtained among participants 40 years or older. Persons were excluded from the retinal imaging examination for blindness, eye infections, or eye patches on both eyes.16 The present analysis includes persons who completed a mobile examination visit (n = 6797), those with complete retinal imaging data (n = 5351), and those who had self-reported diabetes mellitus (defined below) (n = 798). The NHANES protocol was approved by a human subjects review board, and written informed consent was obtained from all participants.17

Assessment of Diabetes Mellitus and Diabetic Retinopathy

Persons were classified as having diagnosed diabetes mellitus if they answered yes to the question: “Have you ever been told by a doctor or health professional that you have diabetes or sugar diabetes?” Diagnosis of diabetic retinopathy, including DME, was based on the grading of fundus photographs by masked graders at the University of Wisconsin Ocular Epidemiologic Reading Center, Madison, using a single nonmydriatic image of the optic nerve and macula in each eye from an ophthalmic digital imaging system (CR6-45NM; Canon, Inc) and a digital camera (EOS 10D; Canon, Inc).

Assessment of Eye Care and Visual Acuity

Persons who reported a diagnosis of diabetes mellitus were asked the following questions during the interview: (1) “Have you been told by a doctor that diabetes has affected your eyes or that you had retinopathy?” (2) “When was the last time you saw a diabetes nurse educator or dietitian or nutritionist for your diabetes?” and (3) “When was the last time you had an eye examination in which the pupils were dilated?” For the question regarding a visit to a diabetes specialist, the response options of “13 to 24 months,” “greater than 2 years,” and “never” were aggregated in this analysis to improve the precision of the estimate for a combined group response of longer than 1 year or never. Likewise, responses were aggregated for question 3 (the last time the individual had an eye examination in which the pupils were dilated). In addition, presenting and best-corrected visual acuity (VA) of eyes diagnosed with diabetic retinopathy and DME were determined. Presenting VA was measured using a digital lensometer (model LM-990A; Nidek), allowing individuals to use any necessary usual correction, including eyeglasses, contact lenses, or both. For eyes with usual correction of 20/30 or worse, best-corrected VA was determined after refraction of these eyes using a commercially available autorefractor (model ARK-760; Nidek). For eyes with usual correction better than 20/30, the usual correction was considered the best-corrected VA. If both eyes had diabetic retinopathy and DME, the VA of the worse-seeing eye was used in the analysis.

Statistical Analysis

All analyses were performed incorporating the sampling weights to account for the complex NHANES sampling design. The standard errors for all estimates were obtained using the Taylor series (linearization) method following recommended procedures.18 Any estimate with an associated relative standard error greater than 30% of the estimate may be unreliable and should be interpreted with caution.19 Statistical analyses were conducted using commercially available software (SAS, version 9.2; SAS Institute, Inc).

Characteristics of the population 40 years or older with diabetes mellitus are summarized in the Table. Among 798 persons with self-reported diabetes mellitus in the analytic sample, 238 had diabetic retinopathy without DME and 48 had DME. Persons with DME had higher glycated hemoglobin A1c levels and longer duration of diabetes mellitus compared with persons with diabetes mellitus without macular edema. Among those with diabetes mellitus and DME, only 44.7% (95% CI, 27.0%-62.4%) reported being told by a physician that diabetes mellitus had affected their eyes or that they had retinopathy (Figure 1) compared with 26.1% (95% CI, 19.8%-32.3%) with diabetic retinopathy but no macular edema and 15.3% (95% CI, 12.3%-18.3%) with diabetes mellitus but no retinopathy. Only 49.2% (95% CI, 29.4%-69.0%) with DME reported seeing a diabetes nurse educator, a dietician, or a nutritionist for their diabetes mellitus within the past year compared with 33.5% (95% CI, 23.8%-43.3%) with diabetic retinopathy but no macular edema and 30.5% (95% CI, 26.1%-34.9%) with diabetes mellitus but no retinopathy. In contrast, 46.7% (95% CI, 27.5%-66.0%) with DME reported seeing a diabetes specialist more than 1 year ago or never (Figure 2) compared with 64.7% (95% CI, 55.5%-74.0%) with diabetic retinopathy but no macular edema and 69.5% (95% CI, 65.1%-73.9%) with diabetes mellitus but no retinopathy. Furthermore, only 59.7% (95% CI, 43.5%-75.9%) of persons with DME reported having had an eye examination within the past year at which the pupils were dilated (Figure 3) compared with 67.5% (95% CI, 59.6%-75.4%) with diabetic retinopathy but no macular edema and 61.8% (95% CI, 54.7%-68.9%) with diabetes mellitus but no retinopathy.

Table Graphic Jump LocationTable.  Demographics and Clinical Characteristics of Study Participants With Self-reported Diabetes Mellitus Stratified by DR and DME Statusa
Place holder to copy figure label and caption
Figure 1.
Awareness of Eye Diseases Among Study Participants With Self-reported Diabetes Mellitus

Participants 40 years or older were asked, “Have you been told by a doctor that diabetes has affected your eyes or that you had retinopathy?” Unknown responses were not reported. Error bars represent 95% confidence intervals. DME indicates diabetic macular edema; DR, diabetic retinopathy.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 2.
Self-reported Last Visit to a Diabetes Mellitus Specialist Among Study Participants With Diabetes

Participants 40 years or older were asked, “When was the last time you saw a diabetes nurse educator or dietitian or nutritionist for your diabetes?” The total for each cohort equals 100%. If not, the difference represents participants who responded “don't know” to this question (not shown). Error bars represent 95% confidence intervals. DME indicates diabetic macular edema; DR, diabetic retinopathy.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 3.
Self-reported Last Examination With Pupil Dilation Among Study Participants With Diabetes Mellitus

Participants 40 years or older were asked, “When was the last time you had an eye examination in which the pupils were dilated?” The total for each cohort equals 100%. If not, the difference represents participants who responded “don't know” to this question (not shown). Error bars represent 95% confidence intervals. DME indicates diabetic macular edema; DR, diabetic retinopathy.

Graphic Jump Location

Among persons with DME, the presenting VA of the eye with disease was 20/40 or better in 69.4% (95% CI, 52.9%-86.0%) compared with 76.6% (95% CI, 71.4%-81.8%) with diabetic retinopathy but no macular edema and 75.1% (95% CI, 70.8%-79.4%) with diabetes mellitus but no retinopathy, whereas the best-corrected VA was 20/40 or better in 81.4% (95% CI, 66.6%-96.1%) compared with 87.3% (95% CI, 83.2%- 91.5%) and 88.0% (95% CI, 84.5%- 91.5%), respectively. Figure 4 displays the percentage of persons with DME with presenting or best-corrected VA worse than 20/40 (ie, visual impairment; 28.7% vs 16.0%, respectively).

Place holder to copy figure label and caption
Figure 4.
Percentage of Study Participants With Presenting or Best-Corrected Visual Acuity (VA) Worse Than 20/40

Participants 40 years or older included those with diabetes mellitus, diabetes mellitus and diabetic retinopathy (DR) but no diabetic macular edema (DME), and diabetes mellitus with DME. Responses of “unknown” were not reported. Error bars represent 95% confidence intervals.aStandard error is more than 30% of the estimate; estimate may be unreliable.

Graphic Jump Location

Diabetic macular edema is a major cause of visual impairment among US adults 40 years or older with diabetes mellitus.1,20,21 A recent report suggests that approximately 745 000 persons with diabetes mellitus in the US population have swelling of the center of the retina (ie, DME).22 Treatment of DME has improved dramatically during the past few years so that prompt diagnosis and referral of patients with these complications has become more critical. Because, to our knowledge, the awareness and care of DME in the US population is uncharacterized, this study aimed to characterize eye care and awareness of eye disease among persons with DME in the general US population. Our results suggest that many individuals with DME report not receiving prompt diabetes-related or eye-related care, although many of these individuals are at risk of substantial visual loss that could be lessened or eliminated with appropriate care. Furthermore, many people 40 years or older in the United States have DME with best-corrected VA of 20/40 or better when they may not be seeking visual correction services, including many who are unaware that diabetes mellitus has affected their eyes. This study indicates that, even though DME is a major cause of visual impairment among people with diabetes mellitus, many individuals with DME report not receiving diabetes-related or eye-related care for at least 1 year.

Limitations of this study include the relatively small number of NHANES participants with DME, fundus photographs were not stereoscopic pairs, and the lack of optical coherence tomography measurements to determine the proportion of cases with central macular thickening among those in whom DME was or was not suggested by retinal photographs. Furthermore, the answers to the eye care questions were based on self-report (as opposed to actual recorded use of health care resources), precluding the ability to eliminate recall bias. The possibility of underreporting cannot be excluded, and its magnitude, if present, cannot be determined. However, with respect to pupil dilation, self-reported use of eye examinations with dilation within the past year was comparable to that of the National Committee for Quality Assurance indicators report,23 suggesting that the self-reported data, at least for this variable, is likely not affected substantially by recall bias. Also, persons who are severely ill may be less likely to participate in the NHANES. Although the NHANES design should account for this differential nonresponse by health status, severely ill people might still be underrepresented in this data set.

In summary, our results suggest that despite recent successes in the ability to treat visual loss due to diabetes mellitus, one of the most frequent and most feared complications of the disease, hundreds of thousands of people in the United States report that they are not getting care that can prevent visual impairment and blindness. These findings from the NHANES, which provide nationally representative estimates of the burden of diabetic eye disease and awareness of having the condition in the general US population, emphasize the need to strengthen our efforts in educating patients with diabetes mellitus concerning the eye complications of the disease. These efforts include getting patients to health care providers, including diabetes nurse educators, dieticians, nutritionists, primary care physicians, or endocrinologists, for treatment of their diabetes mellitus; getting appropriate eye examinations to detect and treat diabetic retinopathy, including DME; and identifying strategies that might result in greater awareness and appropriate eye care24 to reduce the magnitude of visual impairment and blindness due to this common complication of diabetes mellitus.

Submitted for Publication: May 16, 2013; final revision received July 10, 2013; accepted July 26, 2013.

Corresponding Author: Neil M. Bressler, MD, Maumenee 752, Wilmer Eye Institute, Johns Hopkins University School of Medicine and Hospital, 600 N Wolfe St, Baltimore, MD 21287 (nmboffice@jhmi.edu).

Published Online: December 19, 2013. doi:10.1001/jamaophthalmol.2013.6426.

Author Contributions: Drs Bressler and Selvin had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: Bressler, Varma, Doan, Danese, Selvin, Dolan, Fine, Colman, Turpcu.

Acquisition of data: Doan, Danese, Selvin, Turpcu.

Analysis and interpretation of data: Bressler, Varma, Doan, Gleeson, Danese, Bower, Selvin, Dolan, Colman, Turpcu.

Drafting of the manuscript: Bressler, Doan, Selvin, Dolan, Fine.

Critical revision of the manuscript for important intellectual content: Bressler, Varma, Doan, Gleeson, Danese, Bower, Selvin, Dolan, Colman, Turpcu.

Statistical analysis: Doan, Gleeson, Danese, Bower, Selvin.

Obtained funding: Bressler, Doan, Danese.

Administrative, technical, and material support: Varma, Doan, Danese, Dolan, Colman.

Study supervision: Bressler, Varma, Selvin, Fine, Colman, Turpcu.

Conflict of Interest Disclosures: Dr Bressler is principal investigator of grants at The Johns Hopkins University sponsored by Bausch & Lomb Incorporated, ForSight Labs, LLC, Genentech, Inc, Genzyme Corporation, Lumenis Inc, Notal Vision, Novartis Pharma AG, Optovue, Inc, and Regeneron Pharmaceuticals, Inc, and not including the National Institutes of Health. Dr Varma is a consultant for Allergan, Aquesys, Genentech, Inc, Merck, and Replenish and has received research funding from Genentech, Inc, and Replenish. Drs Doan, Gleeson, and Danese are employees of Outcomes Insights, Inc, and paid consultants for Genentech, Inc. Drs Bower and Selvin are coinvestigators supported by Dr Bressler’s grant at The Johns Hopkins University sponsored by Genentech, Inc. Dr Dolan is a paid consultant for Genentech, Inc. Drs Fine, Colman, and Turpcu are employees of Genentech, Inc.

Funding/Support: This study was supported by a grant from Genentech, Inc, and Roche to The Johns Hopkins University through the Office of Research Administration of the Johns Hopkins University School of Medicine. Support for third-party writing assistance for this manuscript, provided by Rebecca Jarvis, PhD, CMPP, of Envision Scientific Solutions, was provided by Genentech Inc.

Role of the Sponsors: Genentech, Inc, and Roche employees participated in the design of the study, in the revision of the manuscript, and had access to the data before the completion of data analysis but did not participate in the statistical analysis. The Johns Hopkins University School of Public Health investigators independently replicated and verified all analyses.

Disclaimer: Dr Bressler is the Editor of JAMA Ophthalmology. He was not involved in the editorial evaluation or decision to accept this article for publication.

Previous Presentations: Portions of these data were presented at the Retina Society Annual Meeting; September 28, 2012; Washington, DC; at the Macula Society Annual Meeting; March 1, 2013; Dana Point, California; and at the American Academy of Optometry Annual Meeting; October 24, 2012; Phoenix, Arizona.

Additional Contributions: An independent statistical analysis, used for all data provided in the report, was conducted by the Johns Hopkins University Bloomberg School of Public Health faculty (Drs Bower and Selvin). Additional statistical analysis was performed by Outcomes Insights, Inc (Drs Doan and Gleeson). Rebecca Jarvis, PhD, CMPP, of Envision Scientific Solutions, provided editorial assistance and was compensated by Genentech, Inc.

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Roy  MS, Klein  R, O’Colmain  BJ, Klein  BE, Moss  SE, Kempen  JH.  The prevalence of diabetic retinopathy among adult type 1 diabetic persons in the United States. Arch Ophthalmol. 2004;122(4):546-551.
PubMed   |  Link to Article
Congdon  N, O’Colmain  B, Klaver  CC,  et al; Eye Diseases Prevalence Research Group.  Causes and prevalence of visual impairment among adults in the United States. Arch Ophthalmol. 2004;122(4):477-485.
PubMed   |  Link to Article
Prevent Blindness America. Vision problems in the US: prevalence of adult vision impairment and age-related eye disease in America: 2008 update to the fourth edition. 2008. http://www.preventblindness.net/site/DocServer/VPUS_2008_update.pdf. Accessed April 30, 2013.
Klein  R, Lee  KE, Gangnon  RE, Klein  BE.  The 25-year incidence of visual impairment in type 1 diabetes mellitus: the Wisconsin Epidemiologic Study of Diabetic Retinopathy. Ophthalmology. 2010;117(1):63-70.
PubMed   |  Link to Article
American Academy of Ophthalmology Retina/Vitreous Panel. Preferred Practice Pattern® guidelines: diabetic retinopathy. San Francisco, CA: American Academy of Ophthalmology; 2008. http://www.aao.org/ppp. Accessed April 30, 2013.
Ferris  FL  III.  How effective are treatments for diabetic retinopathy? JAMA. 1993;269(10):1290-1291.
PubMed   |  Link to Article
American Diabetes Association.  Standards of medical care in diabetes: 2013. Diabetes Care. 2013;36(suppl 1):S11-S66.
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Elman  MJ, Qin  H, Aiello  LP,  et al; Diabetic Retinopathy Clinical Research Network.  Intravitreal ranibizumab for diabetic macular edema with prompt versus deferred laser treatment: three-year randomized trial results. Ophthalmology. 2012;119(11):2312-2318.
PubMed   |  Link to Article
Rajendram  R, Fraser-Bell  S, Kaines  A,  et al.  A 2-year prospective randomized controlled trial of intravitreal bevacizumab or laser therapy (BOLT) in the management of diabetic macular edema: 24-month data: report 3. Arch Ophthalmol. 2012;130(8):972-979.
PubMed   |  Link to Article
Nguyen  QD, Brown  DM, Marcus  DM,  et al; RISE and RIDE Research Group.  Ranibizumab for diabetic macular edema: results from 2 phase III randomized trials: RISE and RIDE. Ophthalmology. 2012;119(4):789-801.
PubMed   |  Link to Article
Mitchell  P, Bandello  F, Schmidt-Erfurth  U,  et al; RESTORE Study Group.  The RESTORE study: ranibizumab monotherapy or combined with laser versus laser monotherapy for diabetic macular edema. Ophthalmology. 2011;118(4):615-625.
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Do  DV, Nguyen  QD, Boyer  D,  et al; da VINCI Study Group.  One-year outcomes of the da Vinci Study of VEGF Trap-Eye in eyes with diabetic macular edema. Ophthalmology. 2012;119(8):1658-1665.
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Figures

Place holder to copy figure label and caption
Figure 1.
Awareness of Eye Diseases Among Study Participants With Self-reported Diabetes Mellitus

Participants 40 years or older were asked, “Have you been told by a doctor that diabetes has affected your eyes or that you had retinopathy?” Unknown responses were not reported. Error bars represent 95% confidence intervals. DME indicates diabetic macular edema; DR, diabetic retinopathy.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 2.
Self-reported Last Visit to a Diabetes Mellitus Specialist Among Study Participants With Diabetes

Participants 40 years or older were asked, “When was the last time you saw a diabetes nurse educator or dietitian or nutritionist for your diabetes?” The total for each cohort equals 100%. If not, the difference represents participants who responded “don't know” to this question (not shown). Error bars represent 95% confidence intervals. DME indicates diabetic macular edema; DR, diabetic retinopathy.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 3.
Self-reported Last Examination With Pupil Dilation Among Study Participants With Diabetes Mellitus

Participants 40 years or older were asked, “When was the last time you had an eye examination in which the pupils were dilated?” The total for each cohort equals 100%. If not, the difference represents participants who responded “don't know” to this question (not shown). Error bars represent 95% confidence intervals. DME indicates diabetic macular edema; DR, diabetic retinopathy.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 4.
Percentage of Study Participants With Presenting or Best-Corrected Visual Acuity (VA) Worse Than 20/40

Participants 40 years or older included those with diabetes mellitus, diabetes mellitus and diabetic retinopathy (DR) but no diabetic macular edema (DME), and diabetes mellitus with DME. Responses of “unknown” were not reported. Error bars represent 95% confidence intervals.aStandard error is more than 30% of the estimate; estimate may be unreliable.

Graphic Jump Location

Tables

Table Graphic Jump LocationTable.  Demographics and Clinical Characteristics of Study Participants With Self-reported Diabetes Mellitus Stratified by DR and DME Statusa

References

Centers for Disease Control and Prevention. National diabetes fact sheet, 2011. http://www.cdc.gov/diabetes/pubs/pdf/ndfs_2011.pdf. Accessed April 30, 2013.
Roy  MS, Klein  R, O’Colmain  BJ, Klein  BE, Moss  SE, Kempen  JH.  The prevalence of diabetic retinopathy among adult type 1 diabetic persons in the United States. Arch Ophthalmol. 2004;122(4):546-551.
PubMed   |  Link to Article
Congdon  N, O’Colmain  B, Klaver  CC,  et al; Eye Diseases Prevalence Research Group.  Causes and prevalence of visual impairment among adults in the United States. Arch Ophthalmol. 2004;122(4):477-485.
PubMed   |  Link to Article
Prevent Blindness America. Vision problems in the US: prevalence of adult vision impairment and age-related eye disease in America: 2008 update to the fourth edition. 2008. http://www.preventblindness.net/site/DocServer/VPUS_2008_update.pdf. Accessed April 30, 2013.
Klein  R, Lee  KE, Gangnon  RE, Klein  BE.  The 25-year incidence of visual impairment in type 1 diabetes mellitus: the Wisconsin Epidemiologic Study of Diabetic Retinopathy. Ophthalmology. 2010;117(1):63-70.
PubMed   |  Link to Article
American Academy of Ophthalmology Retina/Vitreous Panel. Preferred Practice Pattern® guidelines: diabetic retinopathy. San Francisco, CA: American Academy of Ophthalmology; 2008. http://www.aao.org/ppp. Accessed April 30, 2013.
Ferris  FL  III.  How effective are treatments for diabetic retinopathy? JAMA. 1993;269(10):1290-1291.
PubMed   |  Link to Article
American Diabetes Association.  Standards of medical care in diabetes: 2013. Diabetes Care. 2013;36(suppl 1):S11-S66.
PubMed   |  Link to Article
Elman  MJ, Qin  H, Aiello  LP,  et al; Diabetic Retinopathy Clinical Research Network.  Intravitreal ranibizumab for diabetic macular edema with prompt versus deferred laser treatment: three-year randomized trial results. Ophthalmology. 2012;119(11):2312-2318.
PubMed   |  Link to Article
Rajendram  R, Fraser-Bell  S, Kaines  A,  et al.  A 2-year prospective randomized controlled trial of intravitreal bevacizumab or laser therapy (BOLT) in the management of diabetic macular edema: 24-month data: report 3. Arch Ophthalmol. 2012;130(8):972-979.
PubMed   |  Link to Article
Nguyen  QD, Brown  DM, Marcus  DM,  et al; RISE and RIDE Research Group.  Ranibizumab for diabetic macular edema: results from 2 phase III randomized trials: RISE and RIDE. Ophthalmology. 2012;119(4):789-801.
PubMed   |  Link to Article
Mitchell  P, Bandello  F, Schmidt-Erfurth  U,  et al; RESTORE Study Group.  The RESTORE study: ranibizumab monotherapy or combined with laser versus laser monotherapy for diabetic macular edema. Ophthalmology. 2011;118(4):615-625.
PubMed   |  Link to Article
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