9.4 Interaction of Ischemia with Effects of Treatments

Central retinal venous blood flow velocity as determined by color Doppler imaging is lower in ischemic CRVO than in nonischemic CRVO (see Chap. 8).54 In contrast, central retinal artery blood flow velocity is reduced in patients with CRVO, but not to a greater degree in those judged ischemic compared to those judged nonischemic.54

In a case-control study, patients with nonischemic CRVO had higher prothrombin fragment 1.2 and factor VII:C levels than patients with ischemic CRVO; they also had lower heparin cofactor II levels.3 In a case series, the proportion of patients with anemia was higher in those patients with ischemic CRVO(12 of 143, 8.4%) than in those with nonischemic CRVO (11 of 469, 2.3%).25 In a case-control study, the proportion of patients with elevated erythrocyte aggregation was higher in converters than nonconverters.13

The lack of reproducibility of predictive factors for conversion and the wide variation in definitions of ischemia suggest the absence of a clear risk profile for conversion. Therefore, clinical prudence suggests that all patients with CRVO be followed as though they were at risk for conversion to ischemia. Even eyes categorized definitively at baseline as nonischemic should be carefully monitored, because of the large fraction that will convert to ischemic status during follow-up.49

CRVO and HCRVO were pooled in a study by Hayreh et al. because the two groups did not differ when associations with systemic diseases were compared (see Chap. 6).25 There were no significant differences in the prevalence of systemic associations between patients who converted from nonischemia to ischemia and vice versa.25

Although less common, it is possible for an ischemic CRVO to convert to a nonischemic CRVO.4 In these cases, initially elevated aqueous VEGF levels have been documented to fall spontaneously.4

Although the proportion of eyes that develop ASNV is higher in ischemic than nonischemic CRVO, there are many ischemic eyes that do not progress to ASNV. For this reason, prophylactic laser panretinal photocoagulation (PRP) is not

recommended. Rather, PRP is held in reserve until ASNV develops (see Chap. 13).49

9.3.3 Outcomes by Ischemic Status

The VA outcomes in ischemic CRVO are largely independent of presence or absence of ME. The important factor is the death of macular ganglion cells.26 On the other hand, in nonischemic CRVO, the VA outcome depends on whether or not ME is present (see Chap. 12).26

The probability of a VA improvement of three or more Snellen lines over 2–5 years of follow-up is approximately three times greater for nonischemic than for ischemic CRVO.26 The change in visual field and change in VA generally track together in cases of nonischemic CRVO.26

Considering ischemia as a continuous variable, the extent of capillary nonperfusion correlates with the proportion of eyes developing NVI.48 In accord with that correlation, the incidence of neovascular glaucoma in nonischemic CRVO is 1%, but in ischemic, CRVO is 60%.35

9.4Interaction of Ischemia with Effects of Treatments

9.4.1 Branch Retinal Vein Occlusion

Grid laser for BRVO with ME in the presence of macular ischemia was ineffective in improving VA, although ME was reduced.47 Greater macular ischemia was associated with ineffectiveness of intravitreal triamcinolone injection (IVTI) for BRVO with ME.42 The efficacy of intravitreal bevacizumab injections (IVBI) for the treatment of BRVO with ME did not depend on macular perfusion status in one study.30 In another study, the visual prognosis was worse in cases with macular ischemia.9 In a study of vitrectomy and internal limiting membrane peeling for BRVO with ME, ischemic status had no effect on outcome.36

9.4.2 Central Retinal Vein Occlusion

Inconclusive evidence suggests that isovolemic hemodilution is more effective for ischemic CRVO than for nonischemic CRVO.15 The effect of posterior subtenons triamcinolone injection for CRVO with ME did not depend on ischemic status in one study, but VA changes did, with

improved outcomes only found in the nonischemic group.33 Ischemic status had no effect on macular thickness or visual acuity outcomes in a prospective randomized trial of IVTI, but the study was too small to exclude a small effect.45 The benefit of IVBI on CRVO with ME was unaffected by ischemia, but counterexamples exist (Fig. 9.6).43 The effect of intravitreal tissue plas-

Fig. 9.6 Fundus images of a 53-year-old man with diabetes and hypertension who developed an ischemic central retinal vein occlusion (CRVO) of the right eye. (a) Color fundus photograph of the right eye showing a chronic, ischemic CRVO. Yellow exudates are present in the inferior hemimacula (the black arrow). A partial annulus of retinal pigment epithelial atrophy surrounds the fovea (the green arrow) indicating the long-standing nature of the macular edema. (b) Frame from the midphase fluorescein angiogram (FA). The inferior hemimacula shows worse ischemia (the yellow oval) than the superior hemimacula (the green oval). The parafoveal

pigment epithelial atrophy produces window-type hyperfluorescence around the fovea (the turquoise arrow). (c) Frame from the late-phase FA showing more fluorescein leakage in the superior hemimacula (the green oval) than the inferior, more ischemic hemimacula (the yellow oval). (d) Spectral domain OCT image showing massive macular edema (ME). The central subfield mean thickness is 1,119 m. The visual acuity (VA) was counting fingers. (e) After one intravitreal injection of bevacizumab, the ME has resolved, but the VA remains counting fingers, exemplifying the interaction of ischemia with treatment efficacy

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Fig. 9.6 (continued)

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