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A clinical perspective of neovascular glaucoma


Neovascular glaucoma is a potentially devastating ocular consequence of pathologic neovascularization of intraocular tissue. The symptoms include vision loss caused by both the underlying etiology (such as retinal vascular disease) as well as increased intraocular pressure (IOP), often accompanied by corneal edema, hyphema, or vitreous hemorrhage.

Neovascular glaucoma is a potentially devastating ocular consequence of pathologic neovascularization of intraocular tissue. The symptoms include vision loss caused by both the underlying etiology (such as retinal vascular disease) as well as increased intraocular pressure (IOP), often accompanied by corneal edema, hyphema, or vitreous hemorrhage. Patients may be experiencing a range of ocular pain caused by increased IOP, disruption of corneal surface, and/or mechanical iritis associated with iris neovascularization.

Signs of the disease include rubeosis or neovascularization of the iris (NVI) that may be noted at the pupillary margin, throughout the mid-iris stroma, or as neovascularization of the angle (NVA) (see Figure 1). Other typical findings are increased IOP, except in cases of carotid artery stenosis (ocular ischemic syndrome) in which IOP may remain in normal range. Corneal haze due to microcystic corneal edema and sub-epithelial bullae may be present due to elevated IOP. Concomitant finding may include anterior peri-lenticular vascularization, ciliary flush, and hyphema (see Figure 2). 

Pathogenesis of neovascular glaucoma

Pathologic neovascularization, or formation of new capillaries from preexisting blood vessels, is a common consequence of hypoxia and inflammation. Hypoxia-inducible factor alpha is upregulated in response to decreased tissue oxygen levels. This leads to increased production of vascular endothelial growth factor (VEGF), commonly resulting in neovascularization of ocular tissue following an ischemic event, such as retinal vascular occlusions (see Figure 3). Neovascular tissue may be considered an aberrant healing process, in which excessive proliferation of micro-capillaries results in bleeding, exudation, and fibrovascular scarring. Thus hyphema, vitreous hemorrhage, and edema may be common clinical features. The clinical consequence of fibrovascular scarring may be contraction or mechanical blockage, such as traction retinal detachment or synechial angle closure from neovascularization of the iris (NVI).

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Neovascular glaucoma occurs secondary to an underlying ischemic, or less commonly inflammatory, etiology. Neovascular glaucoma has long been considered a severe feature of retinal vein occlusion1 and diabetic retinopathy.2 NVG may develop in 33 to 64 percent of eyes with untreated, proliferative diabetic retinopathy (PDR).3 NVG occurs in central retinal vein occlusion (CRVO) in approximately 15 percent of cases. NVI and NVG may be encountered in previously treated eyes with PDR (see Figure 4). Other vascular causes of NVG include, retinal vein occlusion, sickle cell retinopathy, Coats disease, and carotid insufficiency4 (ocular ischemic syndrome) (see Figure 5).

The importance of pachymetry and CCT

Although vaso-occlusive disorders are common causes of NVI and NVG, there are a number of non-vascular causations. These include, chronic rhegmatogenous and exudative retinal detachment, posterior segment tumors (see Figure 6), and retinal infectious and inflammatory diseases. Inflammatory neovascularization may also lead to NVG and occurs following severe posterior segment inflammation, usually with retinal vasculitis, or may be the consequence of advanced intraocular infections. Intraocular malignancies may also lead to NVG, due either to inflammation or up-regulation of vasogenic tumor factors. NVG in chronic retinal detachment occurs secondary to outer retinal ischemia5 and is an indication for retinal reattachment procedure. Eyes with altered media density, such as post-vitrectomy eyes,6 eyes with aphakia, and indwelling silicone oil may have increased VEGF load in the anterior segment, and may have increased risk of NVG.

Clinical management

Slit lamp assessment of the iris-particularly in patients at risk to develop NVI-is crucial during the course of examination. Gonioscopy is necessary to evaluate the angle structure for presence of NVA or other signs or neovascularization, such as peripheral anterior synechiae. Undiagnosed iris and retinal neovascularization can lead to complications following intraocular surgery and are therefore critical in preoperative assessment. Fluorescein angiography is essential in cases in which NVI is suspected but not detected by slit lamp. It must be noted that topical agents used for pupillary dilation, particularly adrenergic receptor agonist such as phenylephrine, can mask the presence of NVI, although most NVI may still be detected following topical agents. 

Managing healthy aging and vision

Treatment of NVG involves attempts to decrease the level of hypoxia and intraocular pressure control. This is accomplished by use of intravitreal anti-VEGF7,8 such as Avastin (bevacizumab, Genentech) which can significantly reduce further need for glaucoma surgery (see Figure 7). Anti-VEGF therapy also treats any concomitant macular edema that is common to many retinal vascular diseases. Although anti-VEGF treatment is sufficient to rapidly reduce neovascularization, underlying retinal ischemia is treated with pan-retinal photocoagulation9-11 of retinal non-perfusion. Retrobulbar causes of eye ischemia may be successfully treated with improving ocular blood flow, particularly in cases of carotid occlusive disease.

Neovascular glaucoma is a common, potentially severe condition, and may present as an eye emergency. Characteristic findings are helpful in developing a differential diagnosis, and systemic co-morbidities must be ruled out. However, with prompt diagnosis and timely management patients can have improved and stable prognosis. 




1. Chan CC, Little HL. Infrequency of retinal neovascularization following central retinal vein occlusion. Ophthalmology. 1979 Feb;86(2):256-63.

2. Gartner S, Henkind P. Neovascularization of the iris (rubeosis iridis). Surv Ophthalmol. 1978 Mar-Apr;22(5):291-312.

3. Madsen PH. Rubeosis of the iris and haemorrhagic glaucoma in patients with proliferative diabetic retinopathy. Br J Ophthalmol. 1971 Jun;55(6):368-71.

4. Abedin S and Simmons RJ. Neovascular glaucoma in systemic occlusive vascular disease. Ann Ophthalmol. 1982 Mar;14(3):284-7.

5. Young NJ, Hitchings RA, Sehmi K, et al. Stickler's syndrome and neovascular glaucoma. Br J Ophthalmol. 1979;63:826-831.

6. Zakov ZN, Lewis ML. Iris fluorescein angiography in diabetic vitrectomy patients. Albrecht Von Graefes Arch Klin Exp Ophthalmol. 1978 Apr 7;206(1):17-24.

7. Luke J, Nassar K, Luke M, et al. Ranibizumab as adjuvant in the treatment of rubeosis iridis and neovascular glaucoma--results from a prospective interventional case series. Graefes Arch Clin Exp Ophthalmol. 2013 Oct;251(10):2403-13.

8. Yoshida N, Hisatomi T, Ikeda Y, et al. Intravitreal bevacizumab treatment for neovascular glaucoma: histopathological analysis of trabeculectomy specimens. Graefes Arch Clin Exp Ophthalmol. 2011 Oct;249(10):1547-52.

9. Laatikainen L. Preliminary report on effect of retinal panphotocoagulation on rubeosis iridis and neovascular glaucoma. Br J Ophthalmol. 1977 Apr;61(4):278-84.

10. Wand M, Dueker DK, Aiello LM, et al. Effects of panretinal photocoagulation on rubeosis iridis, angle neovascularization, and neovascular glaucoma. Am J Ophthalmol. 1978 Sep;86(3):332-9.

11. Mahdy RA, Nada WM, Fawzy KM, et al. Efficacy of intravitreal bevacizumab with panretinal photocoagulation followed by Ahmed valve implantation in neovascular glaucoma. J Glaucoma. 2013 Dec;22(9):768-72.


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