Treatment Patterns for Diabetic Macular Edema: An Intelligent Research in Sight (IRIS®) Registry Analysis
Authors: Ronald A. Cantrell, Flora Lum, Yifeng Chia, Lawrence S. Morse, William L. Rich, Craig A. Salman, Jeffrey R. Willis
Journal: Ophthalmology (2019)

Diabetic macular edema (DME) is a leading cause of vision impairment among working-age adults, and the public health burden it imposes will only increase as the global prevalence of diabetes continues to rise.1Cho N.H. Shaw J.E. Karuranga S. et al.IDF Diabetes Atlas: global estimates of diabetes prevalence for 2017 and projections for 2045.Diabetes Res Clin Pract. 2018; 138: 271-281Abstract Full Text Full Text PDF PubMed Scopus (2366) Google Scholar To improve future outcomes for patients, caregivers, and health care systems, it is important to understand the current state of DME management in clinical practice. The American Academy of Ophthalmology Intelligent Research in Sight (IRIS®) Registry, containing data from the electronic health records of participating ophthalmologists, optometrists, and other eye care providers, was developed to improve the quality of ophthalmic care in the United States.2Chiang M.F. Sommer A. Rich W.L. et al.The 2016 American Academy of Ophthalmology IRIS® Registry (Intelligent Research in Sight) database: characteristics and methods.Ophthalmology. 2018; 125: 1143-1148Abstract Full Text Full Text PDF PubMed Scopus (40) Google Scholar With this in mind, we examined the utility of the IRIS Registry to characterize real-world treatment patterns and visual outcomes among treatment-naive patients newly diagnosed with DME. Our retrospective analysis of the IRIS Registry identified treatment-naive adults with a first International Classification of Diseases 9th or 10th Revision Clinical Modification diagnostic code indicating DME between July 1, 2013, and March 31, 2016 (index date). Follow-up data were collected for 365 days or more after the index date until March 31, 2017. Data stored within the IRIS Registry are deidentified and compliant with the Health Insurance Portability and Accountability Act; as such, institutional review board approval and written informed consent were not required for this study. We assessed the first treatment administered to study eyes within 28 days of initial DME diagnosis and over 1 year of follow-up. Treatments were identified using Healthcare Common Procedure Coding System and Current Procedural Terminology codes and were categorized as follows: observation (i.e., no treatment), intravitreal anti–vascular endothelial growth factor (VEGF) injection (i.e., ranibizumab, aflibercept, or off-label bevacizumab), laser photocoagulation, corticosteroid therapy, or combination treatment (i.e., any combination of anti-VEGF, corticosteroid, or laser photocoagulation administered within a 2-week period). In the subset of patients who received prompt anti-VEGF therapy within 28 days of initial DME diagnosis, the number of anti-VEGF injections administered over 1 year was evaluated. Among patients who had valid visual acuity (VA) data at the index date and within ±30 days of 1 year after the index date, additional analyses measured 1-year VA change in patients who received anti-VEGF therapy within 28 days of diagnosis and those who received no treatment (i.e., observation) during follow-up. To further explore the effect of anti-VEGF injection frequency on vision outcomes, 1-year VA change was assessed in patients who received 1 to 5 versus 6 or more anti-VEGF injections during follow-up. Of 197 220 eligible patients amassed in the IRIS Registry, 13 410 treatment-naive patients with a diagnostic code indicating DME were included in our analyses. Figure S1 (available at www.aaojournal.org) presents patient attrition and the geographic distribution of eye care providers for the eligible DME cohort; baseline patient characteristics are summarized in Table S1 (available at www.aaojournal.org). We observed that the majority of patients included in this study (n = 9990 [74.5%]) received no treatment within 28 days of diagnosis (Fig 1). In patients who first received anti-VEGF therapy within 28 days of diagnosis (n = 2086 [15.6%]), 71.3% were treated with bevacizumab, 17.1% were treated with aflibercept, and 11.6% were treated with ranibizumab, and the median number of injections received during the first year of treatment was 4 (interquartile range, 2–6). Patients who received no treatment during follow-up had moderate VA impairment at the index date (mean VA, 0.37 logarithm of the minimum angle of resolution units; Snellen equivalent <20/40) that remained stable over 1 year (mean VA improvement, –0.02 logarithm of the minimum angle of resolution units). In comparison, patients who initiated anti-VEGF therapy within 28 days of diagnosis had greater visual impairment at the index date and achieved greater levels of 1-year VA improvement, particularly in those who received 6 or more injections during follow-up (Fig S2, available at www.aaojournal.org). The IRIS Registry represents the nation's first comprehensive electronic health record–based ophthalmology database and offers a unique opportunity to characterize DME management in current clinical practice. We demonstrated the value of the IRIS Registry to identify a large DME population, elucidate real-world treatment patterns, and evaluate associated vision outcomes. The majority of patients with DME identified in this study received no treatment in the year after initial diagnosis. Observation may have been an appropriate course of action in these patients, given that baseline vision impairment was moderate on average and mean VA remained stable over 1 year of follow-up. In comparison, patients who received prompt anti-VEGF therapy within 28 days of diagnosis had lower mean VA at the index date, which improved over 1 year of treatment. Among those who received prompt anti-VEGF therapy, we additionally found that patients who received 6 or more anti-VEGF injections over 1 year achieved greater 1-year VA gains than those who received 1 to 5 injections over the same period. However, it is important to note that the average number of anti-VEGF injections received by patients who received prompt treatment was consistent with recent analyses that reported lower real-world injection frequencies than landmark anti-VEGF trials.3Ciulla T.A. Bracha P. Pollack J. et al.Real-world outcomes of anti–vascular endothelial growth factor therapy in diabetic macular edema in the United States.Ophthalmol Retina. 2018; 2: 1179-1187Abstract Full Text Full Text PDF PubMed Scopus (49) Google Scholar, 4Dugel P.U. Layton A. Varma R.B. Diabetic macular edema diagnosis and treatment in the real world: an analysis of Medicare claims data (2008 to 2010).Ophthalmic Surg Lasers Imaging Retina. 2016; 47: 258-267Crossref PubMed Scopus (29) Google Scholar, 5Kiss S. Liu Y. Brown J. et al.Clinical utilization of anti-vascular endothelial growth-factor agents and patient monitoring in retinal vein occlusion and diabetic macular edema.Clin Ophthalmol. 2014; 8: 1611-1621Crossref PubMed Scopus (77) Google Scholar Although our results may suggest that DME is undertreated in clinical practice, it is important to consider the limitations associated with this study. Specifically, International Classification of Diseases diagnostic codes used to identify eligible patients may not reflect confirmed diagnoses and may have been used by clinicians to monitor patients for possible DME. At present, the International Classification of Diseases lacks specific coding to indicate clinically significant or center-involving edema, and the IRIS Registry lacks imaging data to verify the presence and severity of DME. Taken together, these factors limited our ability to differentiate between patients indicated for prompt intervention6American Academy of Ophthalmology Retina/Vitreous PanelPreferred Practice Pattern® Guidelines. Diabetic retinopathy.https://www.aao.org/preferred-practice-pattern/diabetic-retinopathy-ppp-updated-2017Date accessed: October 25, 2018Google Scholar and those who may be appropriately managed with observation only.7Baker C.W. Glassman A.R. Beaulieu W.T. et al.Effect of initial management with aflibercept vs laser photocoagulation vs observation on vision loss among patients with diabetic macular edema involving the center of the macula and good visual acuity: a randomized clinical trial.JAMA. 2019; 321: 1880-1894Crossref PubMed Scopus (74) Google Scholar Finally, vision data captured in the IRIS Registry are based on Snellen VA collected in routine clinical practice and should be interpreted with appropriate caution. This study demonstrated the value of the IRIS Registry to characterize the current state of DME management in US clinical practice. Improved coding processes and integrated retinal imaging data will further enhance the potential of the IRIS Registry to provide insight and drive quality improvement in ophthalmic care. Download .pdf (1.78 MB) Help with pdf files Figure S1 Download .pdf (.06 MB) Help with pdf files Figure S2 Download .pdf (.1 MB) Help with pdf files Table S1