Risk Evaluation for Myocardial Infarction and Cerebrovascular Accident in Retinal Vein Occlusion
Retina specialists frequently treat patients with branch retinal vein occlusion (BRVO) and central retinal vein occlusion (CRVO). It is common to see numerous systemic comorbidities in these patients’ full medical histories, despite the fact that they are, in general, younger than our patients with age-related macular degeneration (AMD). Risk factors identified for retinal vein occlusion (RVO) include hypertension, vascular disease, and diabetes mellitus. Several of these factors are in turn risk factors for myocardial infarction (MI) and cerebrovascular accident (CVA).
My colleagues and I asked the question whether patients with RVO have a higher incidence of MI or CVA than patients without RVO. Previous reports in the literature were inconclusive, limited by small patient populations or by selected ethnic populations. We undertook a project to estimate incidence rates of MI and CVA separately in RVO patients compared with age-matched non- RVO controls in the United States. The results of the study were presented in 2010,1 and published in the Archives of Ophthalmology this year.2 This article summarizes the results of our study.
A retrospective cohort analysis was performed using a large US population-based health care claims database that captured the medical services provided to 30 million people. This database, which had a demographic distribution similar to that found in the US population as a whole, was used to establish rates of MI and CVA in patients with and without RVO.
Between January 1, 2002, and December 31, 2005, the annual incidence rates of MI and CVA events prompting hospitalization in patients with and without RVO were separately calculated. Because this was a casecontrol study, cases were identified by two separate medical claims carrying the ICD-9 code for BRVO or CRVO. Controls were considered patients without evidence of ICD-9 coding for RVO during the study period. Three control patients were randomly selected for each case of RVO. Patients were matched by sex and age. Acute MI and ischemic or hemorrhagic CVA events were also identified by the ICD-9-CM codes consistent with hospitalization. It is important to note that the time period of this study predates the use of, intravitreal vascular endothelial growth factor (VEGF) inhibition therapy for treatment of RVO.
The study included 4500 patients with RVO and 13,500 controls. Of the patients with RVO, 62.9% had BRVO and 37.1% had CRVO. This is consistent with experience in our retina clinics where BRVO is almost twice as common as CRVO (Figure 1).
The Charlson comorbidity index (CCI) is a method for estimating the risk of death from comorbid disease.3 The CCI is weighted by the number and severity of comorbid diseases, including but not limited to MI, cerebrovascular disease, chronic pulmonary disease, dementia, diabetes, and various malignancies. In this study, a modified version of the CCI was used for assessing comorbidity among RVO patients compared with controls. Patients with RVO had a significantly higher percentage of claims for angina, cardiac arrhythmia, diabetes, heart disease, hyperlipidemia, hypertension, and cerebrovascular events than did controls. CCI scores were higher in RVO patients than in the control patients, reflecting their greater disease burden (Figure 2).
RISK OF MI AND CVA
The rate of MI events was not significantly different between the RVO and control cohorts (adjusted risk ratio [RR], 1.03; 95% confidence interval [CI], 0.75-1.42; P=.85). The rate of CVA events in the RVO cohort was almost double that of the control cohort (adjusted RR, 1.72; 95% CI, 1.27-2.34; P=.001; Figure 3).
The RRs for CVA events were similar but slightly higher for BRVO (adjusted RR, 1.79; 95% CI, 1.18-2.72; P=.01) than CRVO (adjusted RR 1.57; 0.99-2.49; P=.06; Figure 4).
Patients with RVO had an almost twofold higher incidence of CVA than that of age- and sex-matched controls. This significantly higher incidence of CVA in patients with RVO held true when adjusting for cardiovascular comorbidities. Ours is the first study to report an increased incidence of CVA in patients with RVO in a US population. In contrast, the incidence of MI was not statistically significantly different between patients with RVO and age- and sex-matched controls. Both physicians and patients alike should be aware of the possible increased risk of CVA in patients with RVO.
It is interesting to compare these results with the results of a study using similar methodology for patients with AMD by Alexander et al.4 In their retrospective, case-control analysis of a small portion of the Medicare database from 2001 to 2003, patients with AMD and previous arterial thromboembolic events were at higher risk for subsequent events: 7.4% increased risk for MI and 35.1% for CVA. Patients with RVO tend to be younger than those with AMD, but both retinal conditions have a strong association with systemic cardiovascular diseases.
RVO is characterized by numerous systemic risk factors. In our large retrospective cohort study representing a broad demographic of the US population, it was not surprising to find that patients with RVO carried a significant disease burden. Patients with RVO had a significantly higher percentage of claims for angina, cardiac arrhythmia, diabetes, heart disease, hyperlipidemia, hypertension, and cerebrovascular events other than stroke compared with age- and sex-matched controls.
The information derived from this study may become important when assessing the systemic safety profiles of new interventions for RVO. It may be useful for retinal specialists to know the baseline incidence of MI, CVA, and other comorbidities in this patient population when collecting safety information on new treatments for RVO that may have systemic biologic activity.
Nancy M. Holekamp, MD, is Director of the Retina Service at the Pepose Vision Institute and a Professor of Clinical Ophthalmology at Washington University School of Medicine in St. Louis. Dr. Holekamp states that she has no proprietary interests in the material presented in this article. She can be reached at +1 314 367 1181; fax: +1 314 962 2770
- Holekamp NM. Myocardial infarction and cerebrovascular accident in patients with retinal vein occlusion. Paper presented at: the Annual Meeting of the American Society of Retina Specialists; Vancouver, British Columbia; August 28-September 1, 2010.
- Werther W, Chu L, Holekamp N, Do DV, Rubio RG. Myocardial infarction and cerebrovascular accident in patients with retinal vein occlusion. Arch Ophthalmol. 2011;129(3):326-331.
- Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis. 1987;40(5):373-383.
- Alexander SL, Linde-Zwirble WT, Werther W, et al. Annual rates of arterial thromboembolic events in Medicare neovascular age-related macular degeneration patients. Ophthalmology. 2007;114(12):2174-2178.
TOP 5 ARTICLES FROM 2011
- Subthreshold Micropulse Laser Therapy for Retinal Disorders
By Christine Kiire, MD; Sobha Sivaprasad, MD; and Victor Chong, MD
- Evaluating and Integrating New Evidence In The Treatment Of Diabetic Macular Edema
- Surgery for Macular Hole Repair: A Conversation
Is face-down positioning necessary?
By NANCY HOLEKAMP, MD; AND PAUL TORNAMBE, MD
- RETINA PEARLS: Hybrid Technique for Silicone Oil Removal
Pearls for reducing complications.
By MANISH NAGPAL, MS, DO, FRCS(UK); RITURAJ VIDEKAR, MD; AND NAVNEET MEHROTRA, MD
- GLOBAL PERSPECTIVES: Choroidal Imaging With Spectral-domain Optical Coherence Tomography
Enhanced depth imaging may lead to a broader understanding of the pathogenesis of several eye diseases.
By Lihteh Wu, MD; Marisse Masis, MD; and Erick Hernandez-Bogantes, MD