4.3.1Conversion from Nonischemic to Ischemic Forms of Retinal Vein Occlusion

Retinal vein occlusions of all types except MCBRVO that present in a nonischemic form may evolveintoanischemicform,andthusclassification is dependent on time. The proportions that convert vary according to type. The rate of conversion depends on the definition used for ischemia and nonischemia, the method of detection of conversion, and the time after diagnosis, all of which vary among studies, thus the proportions published are rough estimates. Greater detail on this topic is found in the chapter on ischemia (Chap. 9).

4.4 Summary of Key Points

•Many classifications for RVO have been proposed based on etiology, arterial status, location of occlusion, status regarding macular edema or neovascularization, and ischemia.

•The reproducibility of classifications for RVO has not been tested.

•Classification of BRVO based on location of occlusion is the most important.

•Subclassification of BRVO by ischemia is common. A cutpoint of 5 DA is most commonly chosen to categorize BRVO as nonischemic or ischemic.

•Classification of CRVO and HCRVO by ischemia is most prevalent but is beset by variability in definitions and scant evidence of reproducibility in practice. A cutpoint of 10 DA is most commonly chosen to categorize CRVO and HCRVO as nonischemic or ischemic.

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5.1 Introduction and Definitions

Epidemiology is the study of factors that determine the occurrence and distribution of disease in a population. Reports on the epidemiology of retinal vein occlusions (RVOs) generally display information in multidimensional grids. The dimensions can be categorized as follows:

•Outcome variables – indices of visual loss or improvement

•Rates of prevalence and incidence

•Risk factors for outcomes

•Types of RVO

•Populations sampled

•Eras of sampling

This chapter presents a broad view of these dimensions of the epidemiology of RVO. The cited references provide greater detail.

The outcome variables reported typically are presence of RVO and measures of vision loss. There are many other outcome variables, and their meanings often differ slightly among studies, but the most common ones found in the literature are defined as follows:

•Presence of RVO – a diagnostic set of fundus findings indicating that the eye has RVO. Definitions vary among studies, but an example would be venous dilation and tortuosity with intraretinal hemorrhages in a wedge-shaped region with the apex pointing toward an arteriovenous crossing in a study of BRVO.55

•Presence of Macular Edema – presence of thickening of the macula determined by stereoscopic fundus photography or optical coherence tomography (OCT).

•Moderate Visual Loss – on the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity chart, a doubling of the visual angle, which means that the visual acuity has dropped by three lines or 15 letters; synonyms include visual impairment and visual angle doubling.34

•Visual impairment – best corrected visual acuity in the better seeing eye worse than 20/40.53

•Moderate Visual Impairment – best corrected visual acuity in the better seeing eye worse than 20/40 but better than 20/20060; studies use different cutpoints for the definition.27

•Severe Visual Impairment – best corrected visual acuity in the better seeing eye of 20/200 or worse.60

•Severe Visual Loss – on the ETDRS visual acuity chart, a visual acuity of less than or equal to 5/200 on two consecutive visits separated by 4 months or more.

•Blindness – visual acuity of 20/200 or worse.28 Some studies use a 20/400 threshold.46

Epidemiologic studies report rates of prevalence, incidence, or both. These are measures of frequency of disease at one time, or over time, respectively. These terms are often confused:

•Prevalence – the number of cases of the disease divided by the population at one time, expressed as a percentage.24 A prevalence study is sometimes called a cross-sectional study.54

•Incidence – the number of new cases that arise during a span of time divided by the population at risk but disease-free at the beginning of that time.24 The time span is specified, for example, 5-year incidence.

A table of abbreviations that will be used in this chapter follows (Table 5.1). The abbreviations will be spelled out at their first occurrence.

Prevalence studies are easier to perform than incidence studies because data are collected once rather than twice. However, they are not helpful in discovering the temporal sequence of associations and RVO.38 Incidence studies can determine temporal relationships, but have the problem of nonparticipation in the follow-up examination, which potentially biases the data.27 If an incidence study collects data at widely separated times, the problem of spontaneous onset and resolution of the condition can arise, leading to underestimation of the true incidence.

Many variables have been explored as possible risk and protective factors for RVOs including demographic, systemic, and ocular factors.54 For example, age is an informative demographic risk factor for all types of RVO. Among the systemic variables, vascular risk factors are important for all types of RVO, but the lists and relative risks of the factors vary among the types of RVO. Primary open-angle glaucoma is the chief ocular risk factor for RVO. It is more important for

Table 5.1 Abbreviations used in epidemiology of retinal vein occlusions

Abbreviation

BDES

BES

BMES

BMI

BRVO

CRVO

CVOS

EDCCS

ETDRS

HR

HCRVO

OR

PAR%

RR

RVO

central retinal vein occlusion (CRVO) and hemicentral retinal vein occlusion (HCRVO) than for BRVO. Risk factors may differ for prevalence rates and incidence rates.

This chapter emphasizes associations of RVO with demographic factors such as age, gender, ethnicity, and season. Chapter 6 uses the same methods and framework, but emphasizes associations with systemic and ocular factors. Genetic variables important for risk and protection are reviewed in Chap. 3.

The last two dimensions considered in epidemiologic reports are the populations and eras studied. These are important because populations across the world differ and risk factors for RVO change over time.

Comparison of epidemiologic studies is difficult. Methodologies differ among studies, including the criteria for RVO, the tests for ascertaining RVO, and the formats for reporting data.9 For example, in the Blue Mountains Eye Study (BMES), seven 30° fields were photographed, whereas in the Beaver Dam Eye Study (BDES), three 30° fields were photographed.29 That the prevalence and incidence figures reported in the BMES were higher than those reported in the BDES could have been due to investigating more of the retina of each patient in the study, instead of from differences due to the populations sampled.29

Populations may differ in levels of interacting variables, such as blood pressure, smoking, and level of serum lipids. In general terms, many studies must be reviewed to look for a consistent pattern of risk and protective factors.57 Moreover, epidemiologic studies cannot determine causation. Rather, they reveal associations that can be explored in studies meant to define causation and effective treatment.

Many associations in epidemiologic studies are univariate and vanish when multivariate analyses are carried out.31 That is, the predictive power of a variable in a univariate study may be accounted for by some other variable. An example of this is the reported higher prevalence of neovascular glaucoma in ischemic CRVO in patients who do not develop optic disk collaterals, a difference that vanishes when the presence of an afferent pupillary defect is taken into account in a multivariate analysis.5

It is important to differentiate the varieties of RVO in epidemiologic studies because the risk and protective factors are not identical for branch retinal vein occlusion (BRVO), central retinal vein occlusion (CRVO), and hemicentral retinal vein occlusion (HCRVO). Even when a risk factor is common to all types of RVO, such as hypertension, the weighting of the factor often differs over the types of RVO. It follows that the classification system used for RVOs matters (see Chap. 4). For example, Beaumont and colleagues examined epidemiologic associations in