The correlation of retinal ischemia with posterior segment neovascularization (PSNV) and anterior segment neovascularization (ASNV) in retinal vein occlusion led to the hypothesis of a diffusible factor arising from ischemic retina as the cause of the complication.3,26 Vascular endothelial growth factor (VEGF) was subsequently discovered to be that mediator (see Chap. 2).28 In this chapter, we focus on the clinical manifestations of PSNV in retinal vein occlusion (RVO). Chapter 11 takes the same approach for ASNV. Chapter 13 covers treatment of these complications. By definition, all RVOs covered in this chapter and Chap. 11 are ischemic, because intraocular neovascularization developed secondarily (see Chap. 9). Table 10.1 lists the abbreviations found in this chapter. Each abbreviation will be spelled out at its first occurrence.

10.1 Branch Retinal Vein Occlusion

In the Beaver Dam Eye Study (BDES) and Blue Mountains Eye Study (BMES), retinal new vessels were found in 9.7% and 7.3% of cases of BRVO, respectively13,22 In the BDES, 61 eyes suffered incident BRVO during 15 years of follow-up. Of these, three (5%) developed retinal neovascularization.14 In the Branch Vein Occlusion Study (BVOS), retinal neovascularization occurred in 36% of eyes with an area of capillary nonperfusion exceeding five disc diameters (DD).3 In case series, much

Table 10.1 Abbreviations used in posterior segment neovascularization and retinal vein occlusion

Abbreviation Term

higher frequencies of PSNV have been reported, probably reflecting the bias that only symptomatic BRVOs present for care.22 In case series, PSNV has been reported in 24–40% of cases.2,8-10,17,21,26 In a clinic-based study, PSNV occurred in no cases of macular BRVO.9 For clinicians, a simple rule to remember is that approximately one-quarter of BRVOs develop PSNV. Neovascularization elsewhere (NVE) (Fig. 10.1) is more common than neovascularization of the disc (NVD) (Fig. 10.2). Of eyes developing new vessels after BRVO, 71% develop NVE alone, 19% NVE and NVD together, and 10% NVD alone.26

The proportion of eyes that develop posterior segment neovascularization depends on the status

of the vitreous.1 In a case series of 18 ischemic BRVOs, 6 had total posterior vitreous detachment (PVD) and 12 did not. The proportion of total PVD cases that developed posterior segment neovascularization was 17% compared to 58% for the non-total PVD cases (P < 0.05).1 The status of the vitreous may explain why many eyes with ischemic BRVO do not develop NV.12,20

Vitreous hemorrhage (VH) develops in approximately 7% of cases of BRVO, in most cases from PSNV (Figs. 10.1 and 10.3).27 Sixty to ninety percent of eyes with BRVO and untreated NVE or NVD will experience recurrent vitreous hemorrhage.3,8 Sector PRP after development of NVE or NVD reduces that proportion to 30% (see Chap. 13).3 If NVE or NVD is present, duration of the BRVO influences the risk of VH. A shorter duration increases the risk.3 In the Standard Care Versus Corticosteroid for Retinal Vein Occlusion (SCORE) BRVO trial, the 36-month incidences of NVD with VH or NVE with VH were 5.8% and 3.8%, respectively.5 The incidence of NVD or NVE was not affected by treatment with intravitreal triamcinolone.5 New vessels tend to grow at the border zone between ischemic retina and

normal retina (Figs. 10.1 and 10.2). On fluorescein angiogram (FA), new vessels leak fluorescein, in contrast to retinal and disc collateral vessels (see Chap. 7) (Figs. 10.1 and 10.2).

10.2 Central Retinal Vein Occlusion

In the population-based BDES, 18 eyes suffered incident CRVO during 15 years of follow-up. Of these, three (17%) developed retinal neovascularization.14 PSNV develops less frequently after CRVO than BRVO. In case series, the proportion of eyes with CRVO that developed PSNV ranges from 10% to 26%, depending on the length of

follow-up.4,6,7,9,11,15,16,19,23,24,29 A simple rule to

remember is that approximately one-fifth of CRVOs develop PSNV. NVD is more common than NVE after CRVO. In two case series with a total of 168 cases of CRVO, the weighted averages for NVD and NVE were 22 and 4%, respectively.18 The proportions were similar whether an eye went on to develop NVG or not.18 The relative infrequency of PSNV compared to ASNV

Fig. 10.1 A 57-year-old man with hypertension, type 2 diabetes mellitus, hypercholesterolemia, and a previous history of smoking complained of floaters in the right eye. Examination showed a superotemporal BRVO with preretinal hemorrhage. (a) A montage color fundus photograph shows an old superotemporal BRVO with a featureless interior sector (inside the yellow polygon), ghost vessels, tufts of neovascularization at the border of

ischemic and normal retina (the green arrows), and a preretinal hemorrhage (the yellow arrow). (b) Frame from the mid-phase fluorescein angiogram shows capillary nonperfusion within the yellow polygon and new vessels leaking fluorescein (the green arrows). (c) Frame from the late-phase fluorescein angiogram shows spreading hyperfluorescence from the leaking new vessels. The preretinal hemorrhage blocks fluorescence

c

Fig. 10.1 (continued)

a

c

in cases of ischemic CRVO has been attributed to the relative absence of viable retinal capillary endothelial cells after ischemic CRVO.4

Posterior segment neovascularization in CRVO is affected by the vitreous status (Fig. 10.4). Retinal and disc neovascularization occur only in ischemic CRVOs in which the posterior vitreous is attached.11 In a case series of 52 ischemic CRVOs, 38 had total PVD and 14 did not. No patient with total PVD developed posterior segment neovascularization compared to 57% for the non-total PVD cases (P < 0.01).11 Therefore, the vitreous scaffold is necessary for the neovascularization to develop. Preexisting primary

b

Fig. 10.2 Fundus images of a 62-year-old female seen for a horseshoe retinal tear of the left eye and incidentally discovered to have a superotemporal branch retinal vein occlusion with neovascularization of the optic disc and the retina. (a) A montage fundus photograph shows the sheathed veins and ghost vein (the blue arrow) superotemporally. Tufts of retinal new vessels are present at the border of ischemic and perfused retina (the turquoise arrows). Elevated disc neovascularization is denoted by

the black arrow. (b) A frame from the mid-phase fluorescein angiogram shows the nonperfused vein (the blue arrow) and the hyperfluorescent tufts of new vessels which emanate from border zone arterioles and the optic disc (the yellow arrows). (c) A frame from the late-phase fluorescein angiogram shows leakage of fluorescein from the new vessels (the yellow arrows). The patient was treated with sector laser panretinal photocoagulation

Fig. 10.3 Fundus images of a 68-year-old patient with hypertension, hypercholesterolemia, and a history of smoking who presented with sudden visual loss secondary to vitreous hemorrhage. (a) Fundus photograph of the right eye shows a fibrovascular frond (arrow) and dispersed vitreous hemorrhage. The visual acuity was LP. No improvement was seen over 1 month of observation,

therefore vitrectomy was performed. At surgery, a superotemporal branch retinal vein occlusion was evident with neovascularization of the retina. (b) Postoperative appearance of the right eye showing the stumps of gliosis from which the neovascular fronds originated (the black arrows). The green arrow denotes venous sheathing

open-angle glaucoma is another risk factor for PSNV after CRVO.7 Treatment of macular edema after CRVO with intravitreal triamcinolone injection does not affect the incidence of PSNV.5

When PSNV occurs after CRVO, it typically occurs later than ASNV. In one series, the average time until onset of NVI was 4.3 months, but

the average time until onset of PSNV was 12 months.23 PRP for NVI may successfully cause regression of the NVI, yet NVD or NVE may appear subsequently despite the PRP, thus continued monitoring is important.23

In practice, it is common to detect preretinal or vitreous hemorrhage first and then to search