11.2Clinical Picture of Anterior Segment Neovascularization

Anterior segment neovascularization (ASNV) is comprised of neovascularization of the iris (NVI), also called rubeosis iridis, and neovascularization of the angle (NVA).22 Whereas normal iris vessels follow a regular radial path, iris new vessels are tortuous and irregular.22 ASNV starts separately at the pupillary margin and the iris base. In CRVO, it is detectable first at the pupillary margin (in approximately 88% of cases) and later at the iris base or in the angle.55 However, in approximately 12% of cases, NVA precedes NVI after ischemic CRVO.11 With further growth, a network develops that connects the two initiating regions of NVI.22 Eventually, a vascular membrane develops that causes peripheral anterior synechiae and ectropion uvea.22 Iris new vessels have thin walls in comparison to the thicker walls of normal iris veins. In severe cases, a vascular membrane covers the pupil producing seclusion pupillae.22

The frequency of detection of ASNV depends on the method used. Slit lamp biomicroscopy is the least sensitive, iris and angle fluorescein angiography are more sensitive, and histopathological examination of surgical specimens or postmortem tissue is the most sensitive.22 Dilation of the pupil makes detection of NVI more difficult (Figs. 11.4 and 11.5).9,69 Nonspecific fluorescein leakage on iris fluorescein angiography can be seen in the elderly, but can be distinguished from the more prominent leakage associated with NVI.46

Clinical detection of NVI is clouded by the difficulty of distinguishing dilated normal iris vessels from NVI. Eyes with inflammation can have dilated iris vessels that may masquerade as NVI. Iris neovascularization must also be distinguished from iris vascular tufts which are located along the pupillary margin and do not occur on the surface of the iris stroma or in the angle.13,14 Iris vascular tufts have been associated with aging, diabetes, myotonic dystrophy, and rarely RVO (Fig. 11.6).49

Iris color influences the ease of detection of NVI.54 Clinical detection at the slit lamp is easier

Fig. 11.4 In the undilated state, NVI is shown (arrowhead)

Fig. 11.5 In the dilated state, the NVI cannot be detected

in a light-colored iris.22 Subtle NVI may be difficult to discern in a dark-colored iris.45 Redfree light may make detection of the red NVI easier.16 In difficult cases, iris fluorescein angiography and gonioangiography can make detection of NVI and NVA easier.24,53 Iris fluorescein angiography is more sensitive than slit lamp biomicroscopy in the detection of NVI and NVA, but is also less specific.6,53,59 Dilated iris vessels in eyes with iritis, normal iris vessels in older patients, and eyes of diabetics with retinopathy, but no NVI, can leak fluorescein on angiography just as does NVI. Therefore, iris fluorescein angiography is not always a reliable method for distinguishing NVI and NVA.34,37,77,78

Figures 11.7, 11.8 and 11.9 show standards useful in interpreting iris fluorescein angiograms.

Fig. 11.6 Images from an eye mistakenly thought to have iris neovascularization but having an iris vascular hamartoma instead. This 71-year-old man woke up with blurred vision in the left eye and was found to have visual acuity of 20/50 of the left eye, an intraocular pressure of 38, and a hyphema. The patient’s ophthalmologist thought that neovascularization was present at 8 o’clock on the pupillary margin and made a provisional diagnosis of ischemic ocular syndrome. A carotid Doppler study was scheduled, and the patient was referred to the author for panretinal photocoagulation. There was no evidence of ischemic ocular syndrome. Rather, the lesion at the 8 o’clock pupillary margin was an iris vascular hamartoma which had bled spontaneously. (a) Slit lamp photograph showing a mulberry-type red lesion at the pupillary margin (the black arrow). (b) Magnified slit

lamp photograph of the iris vascular hamartoma (blue oval). Neovascularization of the iris associated with ischemic retinopathies is flat and forms an irregular, lacy network on the surface of the iris, not a discrete, elevated lesion. (c) The fundus photograph of this eye showed no ischemic signs. An insignificant and unrelated epiretinal membrane is present (the black arrow). (d) A frame from the early-phase fluorescein angiogram (25 s) shows normal arterial filling. (e) A frame from the mid-phase fluorescein angiogram (34 s) shows normal venous filling. The carotid Doppler study was normal. The hyphema cleared in a few days during which the intraocular pressure was controlled with topical hypotensive drops. The patient was educated that occasional anterior chamber hemorrhages were a possibility and was advised to return if a similar episode reoccurred

11.3Classification of Anterior Segment Neovascularization

Several classification schemes for NVI have been proposed, and none is accepted by the majority of clinicians (Table 11.2).7,24,66,67 There are also different classification schemes for the clinical and histopathologic stages of NVA (Table 11.3 and

Fig. 11.10).38,51,53 The purpose of these schemes is to attempt to provide a prognosis for visual outcome. They differ not only in conception but also in the method used for detecting NVI and NVA. Although standardized classifications have attraction to researchers, the relative uncommonness of NVI makes the ability to recall details of any system difficult for the clinician, and the author favors a method of straightforward

Fig. 11.7 Example of a normal iris fluorescein angiogram. No dye leakage is present, although in patients over the age of 50 years, a small amount of pupillary margin leakage of fluorescein can be considered normal (Reprinted with permission from Bandello et al.7)

Fig. 11.9 Example of iris neovascularization present around the entire pupillary margin and at several places on the iris stroma (Reprinted with permission from Bandello et al.7)

description of pupillary margin and angle involvement by neovascularization as being most practical (Figs. 11.11 and 11.12).

Fig. 11.8 Example of nonproliferative diabetic iridopathy. Dye leakage is prominent in the late phase, but neovascularization is absent (Reprinted with permission from Bandello et al.7)

11.4Anterior Segment Neovascularization in Branch Retinal Vein Occlusion

Anterior segment neovascularization is less common after ischemic BRVO than ischemic CRVO because the area of capillary nonperfusion is smaller. Nevertheless, ASNV can occur after BRVO.12 In the Standard Care Versus Corticosteroid for Retinal Vein Occlusion (SCORE) BRVO study, the 36-month incidence of NVI and NVG were 0.3% and 2.2%, respectively.12 In one large case series, NVI developed in 1.6% of cases of major BRVO.25 NVA developed in 0.5% of cases of major BRVO.25 Treatment with intravitreal triamcinolone did not reduce the incidence of ASNV after BRVO in the SCORE BRVO study.12

Grading systems for neovascularization of the iris

Not all the grading systems use the same numbering. Some start at zero and some start at one. For comparison purposes, they have all been converted to a scale starting at zero. Ciliary zone – the outer zone of the iris separated from the pupillary zone by the collarette

Grading systems for neovascularization of the angle

Not all the grading systems use the same numbering. Some start at zero and some start at one. For comparison purposes, they have all been converted to a scale starting at zero

Occlusion Vein Retinal Branch in Neovascularization Segment Anterior 4.11

255

Fig. 11.10 Classification of neovascularization of the angle using fluorescein gonioangiography for detection. In grade 1, dot proliferations are seen at the iris root. In grade 2, a linear vessel arising from these dot proliferations rises at a perpendicular to the iris root to connect to the trabecular meshwork. In grade 3, an arborization of the vessel over the surface of the trabecular meshwork is seen. In grade 4, contracture of the neofibromyovascularization occurs with synechia (Redrawn from Ohnishi53)

Fig. 11.12 A 71-year-old man with diabetes mellitus and hypertension developed a CRVO of the left eye and NVI which did not regress despite laser PRP. At the time of this slit lamp photograph, the visual acuity was NLP, the intraocular pressure was 54, and he was comfortable. Note that NVI is in various stages of development in different regions of the iris. NVI typically begins at the pupillary margin (the yellow arrows) and iris base (the black arrows). The zone of iris stroma is usually uninvolved at an earlier stage (the green oval) but becomes involved later (the blue oval). Eventually, the fibrovascular membrane on the surface of the iris contracts, inducing ectropion uvea (purple arrows, compare absence at yellow arrows)