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6 Systemic and Ocular Associations of Retinal Vein Occlusions |
occlusions, untangling relative degrees of importance is difÞcult, and the appropriate therapeutic response to Þnding the presence of a risk factor can be controversial.103
Risk factors may not only be independently important but also may have synergistic interactions. For example, in a population-based study
from Japan, hypertension and hematocrit were independent risk factors for prevalence of pooled RVO with odds ratios (ORs) of 4.25 and 2.09/ (10% increase in hematocrit), respectively. However, subjects with both hypertension and an elevated hematocrit had synergistically increased risk with an OR of 36.0.206
Systemic Associations with Retinal Vein Occlusion Depend on the Classification System Used
Beaumont and colleagues examined systemic and ocular associations using a novel classiÞcation system for RVO based on site of the occlusion and the presence or absence of optic disc edema (see Chap. 4).14 When systolic blood pressure (SBP), diastolic blood pressure (DBP), and intraocular pressure (IOP) were examined across this classiÞcation, there were insigniÞcant differences across groups. On the other hand, intraocular pressure was signiÞcantly higher in the optic cup-sited RVOs (19.3 ± SD5.5 mmHg) compared to all other groups (varying from 16.6 ± SD3.7 to 17.6 ± SD5.4 mmHg) (P < 0.01 to 0.0001).14 In accord with this result, the prevalence of primary open-angle glaucoma (POAG) was higher in optic cup-sited RVOs (41.4%) than all other groups (9.5Ð19.2%) (P < 0.0001).14 POAG was also more prevalent in optic nervesited RVOs without disc swelling than in those with disc swelling and than in arteriovenous crossing RVOs (P < 0.0083). Prevalence of hypertension was statistically greater in those with arteriovenous RVOs than in those with optic nerve-sited RVOs (i.e., pooled CRVOs and HCRVOs regardless of optic disc swelling) (P < 0.05).14 While this classiÞcation system is attractive for its pathophysiologic rationale, it has not been widely adopted in the 10 years since it was introduced. It is difÞcult to compare the associations reported using BeaumontÕs classiÞcation system with those reported using more widely adopted systems, such as that used in the BDES and BMES.95,132
6.2.1 Hypertension
Hypertension is a strong risk factor for all forms of RVO and for plausible biologic reasons. The pathogenesis of all forms of RVO centers upon an arteriosclerotic artery indenting a vein at a point where the two are held in close contact by an indistensible Þbrous sheath. Hypertension increases arteriolar sclerosis, thus an association with RVO is logical.190 Endothelial cellular damage in hypertension may also lead to abnormalities of intercellular adhesion molecules (ICAM-1) with leukostasis predisposing the subject to
RVO.141 RVO of any type is commonly the pre-
senting sign of previously undetected hyperten- 6.2.1.1 Pooled Retinal Vein Occlusions sion, so it is important in patients with RVO to
look for underlying hypertension.41 Some studies
6.2 Systemic Associations |
129 |
pooled RVO in the BDES and BMES were 89.2% and 89.7%, respectively.31 These percentages were signiÞcantly higher than those for subjects in the study without RVO (50.2% and 71.1%, respectively; P < 0.001 and P = 0.002, respectively).31 In a retrospective study using a national insurance database, the prevalence of hypertension among patients with RVO was 85.5% compared to 6.3% among ageand gender-matched controls (P < 0.001).81
In a meta-analysis of 21 pooled studies, the overall OR for systemic hypertension as a risk factor for RVO was 3.5 (95% CI 2.5Ð5.1). Other studies since then are in agreement.36,142,147,151 The population attributable risk percentage (PAR%) for systemic hypertension as a factor contributing to RVO has been estimated to be 47.9% (95% CI 31.2Ð63.1%).142 In many studies, baseline SBP and DBP are also risk factors, in consonance with a history of hypertension.159 In the BMES, both DBP and SBP at baseline were risk factors for pooled RVO.181 The DBP conferred higher risk per 10 mmHg increase than did SBP.181 In a pop- ulation-based study from Japan, after adjusting for age and gender and after multivariable analysis, hypertension was the most important independent risk factor for RVO (OR 4.25; 95% CI 1.82Ð9.94).206
Evidence suggests that presence of an RVO does not increase the probability of Þnding undetected hypertension. In the BMES, although 14% of patients with RVO had undetected hypertension, 13% of subjects in the same age group without RVO had undetected hypertension.132
The importance of hypertension as a risk factor for RVO is emphasized by a study of pooled recurrent RVOs in which the prevalence of hypertension was 88% compared to a prevalence of 48% in a series of single occurrence RVOs from the same center (P < 0.01).40
6.2.1.2 Branch Retinal Vein Occlusion
In a case series that compared prevalences of systemic associations to a gender-, race-, and agematched national cohort, hypertension was more prevalent in BRVO than in the comparison group.75 The prevalence of hypertension in
patients with BRVO has been reported in 37Ð79%
in various series.6,17,58,69,75,84,89,90,132,146,148,163,179,194,195,207
In the Eye Disease Case Control Study (EDCCS), hypertension was a risk factor for BRVO and a greater risk factor for BRVO than for CRVO.174,180 In the EDCCS analysis, BRVO in half of the patients with BRVO could be attributed to the single factor of hypertension.180 Other case-con- trol studies have also found that hypertension was signiÞcantly associated with BRVO.84,147 In a meta-analysis of 11 pooled, mostly case-control studies, the overall OR for systemic hypertension as a risk factor for BRVO was 3.0 (95% CI 2.0Ð4.4).142
In the Beaver Dam Eye Study (BDES), hypertension was associated with prevalence of BRVO. Untreated and uncontrolled hypertension, treated and controlled hypertension, and treated and uncontrolled hypertension were all associated with prevalence of BRVO with ORs of 6.85 (95% CI 2.07Ð22.69), 3.79 (95% CI 1.38Ð10.42), and 10.24(95% CI 3.47Ð30.22), respectively.95 The ORs linking DBP and SBP to prevalence of BRVO were 1.68 (95% CI 1.23Ð2.30) and 1.30 (95% CI 1.13Ð1.50), respectively. Similar results were found in a population-based study from China.115 In contrast, in the BDES, hypertension, DBP, and SBP were not associated with incidence of BRVO.95,96
A similar relationship was found between macular BRVO and hypertension.75 In two case series, hypertension was more prevalent in patients with major BRVO than in patients with macular BRVO.78,83 There is some evidence that hypertension may be more strongly associated with BRVO than CRVO.8 The prevalence of hypertension was found to be higher in BRVO than CRVO or HCRVO in 1,090 consecutive cases of pooled RVO.75
A retrospective study of cases of bilateral BRVO found that hypertension was the only predictive risk factor.119
6.2.1.3 Central Retinal Vein Occlusion
The prevalence of hypertension among patients with CRVO in various case series is
34Ð75%.6,39,58-60,69,74,84,89,90,117,118,179,207 In a case series