7.2.2 Chronic Phase

Central retinal vein occlusion often has a progressive course. For nonischemic CRVO, but not for ischemic CRVO, all signs can resolve and visual acuity can return to 20/20 (Fig. 7.15). The milder the CRVO at the time of diagnosis, the more likely it is that spontaneous resolution of signs and symptoms will occur. On the other hand, the severity of CRVO frequently worsens over time. With respect to ischemia, this is called conversion from a nonischemic to an ischemic form. Less well known, however, is the progression of CRVO within one category Ð for example, from nonischemic with fewer intraretinal hemorrhages without macular edema to nonischemic with more intraretinal hemorrhage plus macular edema (Fig. 7.16). A meta-analysis of 53 articles on CRVO found only three studies comprising six patients followed in such a way that development of macular edema when none was present at baseline could be assessed. Of those six patients, two progressed to develop macular edema.86 In the population-based BDES, 18 eyes suffered incident CRVO during 15 years of follow-up. Of these, seven (39%) developed macular edema.72

Conversion of CRVO from nonischemic to ischemic depends on the deÞnitions used for these terms. With the most rigorous deÞnition, 7% convert during follow-up.54 With a deÞnition that depends only on ßuorescein angiography, 3.3% convert by 4 months and 34% convert over 3 years.140 Conversion rates using different ßuorescein angiography-based deÞnitions as high as 25% have been reported over 1 year of follow-up and 54% over a mean of 2 years follow-up.2 The wide variability reßects unsatisfactory understanding of what ischemic means.86 As determined in multiple regression analysis, prognostic factors for conversion of nonischemic to ischemic CRVO are male gender, number of clinical risk factors, presence of hypertension, and presence of a history of cardiovascular disease.39 Studies for prognostic factors associated with spontaneous resolution of CRVO are lacking.

Untreated macular edema in CRVO typically persists for a long time.56 In one study, the median time to macular edema resolution was 23 months for nonischemic CRVO and 29 months for ischemic CRVO.56 The percentage of cases with spontaneous resolution in a sample of studies that have looked at the issue ranges from 0% to 73% over 7Ð18 months, a uselessly wide range that may

Fig. 7.15 Fundus photographs of an eye from a 56-year- old man with a nonischemic central retinal vein occlusion that spontaneously improved. (a) In 1990, this patient was seen with acute onset of blurred vision of the right eye. Visual acuity was 20/25. Dilated, tortuous veins, a few

intraretinal hemorrhages, and mild macular edema were present. The visual acuity was 20/25. (b) Over the next year, the fundus picture returned to normal. Note the resolution of venous dilation, tortuosity (compare the black arrows in (a) and (b)), and intraretinal hemorrhages

reßect the uncertainty of clinical detection of macular edema in the era before optical coherence tomography (OCT) (Table 7.3). In the OCT era, one study of Þve nonischemic CRVOs with macular edema reported a mean decrease in macular thickness of 173 m over 6 months.1 When macular edema persists, the risk of deterioration of visual acuity by greater than or equal to three Snellen lines is 3.22 times the risk in eyes in which macular edema resolves (95% CI 1.86Ð5.57).56 As determined in multiple logistic regression analysis, prognostic factors for persistence of macular edema in nonischemic CRVO are history of cardiovascular disease, hyperlipidemia, and initial severity of macular edema.39 Chronic macular edema and macular cysts in CRVO can result in a lamellar or full thickness macular hole (Fig. 7.17).37,131

Late changes that can follow CRVO are foveal hyperpigmentation (Figs. 7.18 and 7.19), macular retinal pigment epithelial atrophy (Fig. 7.20), and epiretinal membranes. All of these are associated with visual acuity deterioration in nonischemic CRVO cases with good initial visual acuity.56 Absence of foveal pigmentation, but not absence of epiretinal membrane, is associated with visual acuity improvement in nonischemic CRVO cases with poor initial visual acuity.56 Presence of foveal hyperpigmentation or epiretinal membrane had no effect on visual acuity outcome in ischemic CRVO.56

Retinochoroidal collateral veins that occur at the optic disc after CRVO have many synonyms in the literature, including retinociliary veins, optociliary veins, optociliary shunts, optociliary

Fig. 7.16 Progression in severity of a nonischemic central retinal vein occlusion. (a) Fundus photograph at presentation of an eye with a mild nonischemic CRVO. The retinal veins are dilated, only a few intraretinal hemorrhages are present, and there is no disc or macular edema. Visual acuity was 20/20. (b) Four weeks later, the visual acuity has dropped to 20/25, there are many more intraretinal hemorrhages, and the disc is edematous (compare black arrow in (a) to black arrow in (b)). (c) Horizontal SD-OCT line scan through the fovea at presentation shows a normal macular morphology and thickness (CSMT = 276 m). (d) Four weeks later, CSMT has increased to 287 m, the foveal depression is preserved, but some Þne morphological changes can be noted such as less deÞnition between the ganglion cell layer and the inner plexiform layer (compare the green arrow in (c) to the purple arrow in (d)) and a more pronounced pattern of interdigitating extensions of the outer plexiform layer and the outer nuclear layer (compare the orange arrow in (c) to the orange arrow in (d)). (e) Red-free fundus photo-

graph taken 9 months after presentation shows that the optic disc edema has resolved (compare the yellow arrow of (e) to the black arrow of (b)) and there are fewer intraretinal hemorrhages. (f) Frame from the early venous phase of the ßuorescein angiogram done 9 months after presentation shows good capillary perfusion, as was present peripherally as well (not shown), thus this CRVO has not converted from nonischemic to ischemic but has simply progressed along the severity path within the nonischemic category. (g) Frame from the late-phase ßuorescein angiogram shows insigniÞcant disc hyperßuorescence (the orange arrow), corresponding to the absence of disc edema, and the presence of cystoid macular edema (the yellow arrow). (h) Line scan from the SD-OCT taken 9 months after presentation shows macular edema (CSMT = 519 m) with morphologic cysts (the yellow arrow) that correspond to the petalloid cysts on the ßuorescein angiogram and subretinal ßuid (the orange arrow) that could not be appreciated clinically

Fig. 7.17 A 60-year-old female with hypertension was seen in 2004 with acute nonischemic CRVO of the right eye and visual acuity of 20/400 secondary to macular edema. Treatment options of intravitreal triamcinolone and bevacizumab were offered to her, but she elected observation due to lack of insurance and inability to afford the cost of care. In 2010, now on Medicare, she returned for reconsideration of treatment. Her visual acuity was counting Þngers at 5 ft, and she had developed a lamellar

macular hole (the green arrow and OCT inset). Disc collaterals (the black arrows), scant hard lipid exudate (the purple arrow), and intraretinal microvascular abnormalities (the yellow arrow and magnified inset) were present. The arterioles show chronic hypertensive changes, and arteriovenous nicking is present. The OCT shows that macular cysts are present in both the outer nuclear and inner nuclear layers

Fig. 7.18 Fundus images illustrating the effects of longstanding macular edema in central retinal vein occlusion. (A) Red-free photograph of the left fundus of a patient who experienced a central retinal vein occlusion 2 years earlier. Yellow arrow denotes an optic disc collateral vessels. Orange arrow denotes lipid exudate. (B) Frame from the early-phase ßuorescein angiogram showing the dilated microvasculature in the posterior pole. (C) Frame from the late-phase ßuorescein angiogram showing petalloid hyperßuorescence in the macula corresponding to cystoid macular edema. (D) OCT images of the same eye. The false-color map shows widespread macular thickening

with a central subÞeld macular thickness of 591 m. The line scan image shows cystoid spaces in the inner and outer nuclear layers. (E) Two years later, gray venous sheathing is apparent (turquoise arrow). The optic disc collateral vessel is unchanged (black arrow). The macular edema has spontaneously resolved leaving mottling of the retinal pigment epithelium (tan arrow). (F) OCT falsecolor map showing that the central subÞeld macular thickness has decreased to 215 m. (G) OCT line scan shows resolution of the cystoid edema and disruption of the inner segment/outer segment junction. The visual acuity at this time is 20/200

Fig. 7.19 Color fundus photographs of an eye that presented with a nonischemic central retinal vein occlusion, which became more ischemic, and eventually developed optic disc collateral vessels and foveal hyperpigmentation from chronic macular edema. (a) Appearance of the fundus at baseline. A nonischemic central retinal vein occlusion is shown. The visual acuity is 20/30. (b) Four months

later, the central retinal vein occlusion has worsened with more intraretinal hemorrhage and macular edema. The visual acuity is 20/125. (c) Appearance of the fundus 11 months after the baseline presentation. An optic disc collateral is present (the black arrow). Chronic macular edema has led to foveal pigment epithelial metaplasia (the blue arrow). The visual acuity is 20/160

Fig. 7.20 Color fundus photograph of a patient who developed a central retinal vein occlusion with macular edema of the right eye 4 years before this photograph. Without any treatment, the macular edema eventually resolved spontaneously, leaving geographic atrophy of the retinal pigment epithelium (the blue arrows). Optic disc collaterals developed as well (the black arrows). The visual acuity is 20/400

collaterals, papillary vascular loops, and optociliary anastomoses.35,38,136 In different studies, these collateral vessels develop at a median time of 4Ð15 months (range 1Ð18 months) after CRVO in 30Ð77% of patients.35,38,45,47,56,136,142 These are preexisting but hemodynamically unimportant

channels draining the retinal venous return into the choroid where it exits the eye via the vortex veins, primarily nasally.35,38,136 Disc collaterals are found more commonly in eyes with poor initial visual acuity.58 Eyes with CRVO that develop optic disc collateral vessels are associated with relative protection from anterior segment neovascularization, but not macular edema (Figs. 7.17 and 7.19).35 Eyes with ASNV are 25 times less likely to develop optic disc collateral vessels than eyes without ASNV, suggesting a strong protective effect of disc collaterals against ASNV.35 Although there is some inconsistency in the literature, the consensus is that the presence of collateral vessels does not correlate with improved Þnal visual acuity, Þnal resolution of macular edema, or ischemic status of the CRVO but is related to how long it takes for macular edema to resolve.8,38,45,47,56,110,112 Resolution of macular edema takes longer in eyes that develop disc collaterals.56 In fact, one series has reported worse visual acuity outcomes in nonischemic CRVOs with poorer initial visual acuity among the group that developed collaterals.56 In the ischemic CRVOs, development of collaterals was not associated with worse visual acuity outcomes.56 Younger patients develop optic disc collaterals at a rate similar to older patients.34 Retinochoroidal collateral vessels may be the only sign of an old CRVO, but other conditions, including glaucoma,