Detection of a relative afferent pupillary defect (RAPD) and quantitation using neutral density filters provides useful information regarding ischemia in CRVO and is inexpensive.22 In addition, testing for an RAPD is useful from the first visit, at a time when FA may be useless because of heavy intraretinal hemorrhage.18 The sensitivity and specificity of presence of a 0.9 log unit RAPD in predicting ischemic status of CRVO are 80% and 97%, respectively.22 For the test to work, the fellow eye must not have optic nerve or extensive retinal disease.22 Quantitation of an RAPD is also possible using two optical polarizers that are crossed at variable angles to attenuate the light.

The signs of ischemia develop over time and can be difficult to assess. Capillary nonperfusion may take 3–4 weeks to develop and may be predominant in the retinal periphery and difficult to capture with conventional FA.25 Newer methods of retinal imaging that can more easily access the periphery are helpful, but not widely available.

9.3.2Conversion from Nonischemic to Ischemic Central Retinal Vein Occlusion

Rates of conversion from nonischemic to ischemic CRVO depend on length of follow-up, progressively increasing with longer follow-up until a plateau is reached at approximately 3 years. Conversion rates of 16% by 4 months and 34% by 3 years were reported in the Central Vein Occlusion Study (CVOS).32,49 Another prospective study defining ischemia in a different manner from the CVOS reported 54% rate of conversion over a mean follow-up of 2 years.14 In a clinicbased series of 620 CRVOs, the cumulative probability of conversion from a nonischemic to ischemic CRVO at 6 and 18 months was 13.2% and 18.6%, respectively, among patients of 65 years of age and older. For patients 45–64 years of age, the rates of conversion were 6.7% and 8.1%, respectively.24

Hayreh has suggested that all CRVOs begin as nonischemic CRVO and that many progress to

ischemic CRVO before the patient sees the doctor. In his view, conversion actually means conversion while under observation. This may further explain the variability in published rates of conversion from 5 to 54%.2,14,21,27,40,46,48,55 That is, in some samples, early presentation of the patient may be more common with an associated rate of conversion under observation.26 The mean or median time to conversion has ranged from 2.9 to 8 months2,17,26,40,44,55 For HCRVO, conversion from nonischemic to ischemic type has been reported to occur in 1% at 6 months and 2.2% at

18months.24

Many clinical findings, ancillary tests, and

laboratory variables have been examined to determine if converters differ from nonconverters.13,14,26,49 In the CVOS, three baseline factors were predictive of conversion from nonischemic to ischemic CRVO – duration of CRVO less than 1 month, baseline VA less than 20/200, and presence of five to nine DAs of capillary nonperfusion at baseline.49 In the observation arm of the SCORE CRVO study, the rate of conversion from nonischemic to ischemic CRVO was 10% and 21% at 12 and 24 months, respectively, based on a definition of ischemic as greater than 10 DAs of capillary nonperfusion.8 In one study, converters were older, and the proportion of patients under age 45 was smaller in the converters compared to the nonconverters.26 In another clinic-based, prospective study using a different definition of ischemia, the independent prognostic factors were male sex, increasing number of clinical risk factors (such as hypertension, hyperlipidemia, diabetes, and primary open-angle glaucoma), increasing erythrocyte aggregation index, and baseline extent of retinal capillary nonperfusion (greater extent associated with higher risk of further ischemia).14 In other studies, factors that have been associated with conversion include more severe macular edema and more severe intraretinal hemorrhage2,13,40 Factors found not to be predictive include gender, hypertension, ischemic heart disease, diabetes, and cerebrovascular disease.26 These results have not been reproducible across studies, and some studies have found no predictive factors.44