Covid Alert

Print ISSN:-2395-1443

Online ISSN:-2395-1451


Current Issue

Year 2020

Volume: 6 , Issue: 2

  • Article highlights
  • Article tables
  • Article images

Article Access statistics

Viewed: 93

Emailed: 0

PDF Downloaded: 66

Khayoom and Mayuri: A prospective observational study to evaluate the etiology and staging of neovascular glaucoma


Neovascular glaucoma (NVG) is a severe form of secondary glaucoma characterized by development of new vessels on iris and formation of fibrovascular tissue in the anterior chamber angle with increase in IOP.1 NVG was previously known as hemorrhagic glaucoma, congestive glaucoma, thrombotic glaucoma, and rubeotic glaucoma.2  Weiss and colleagues named it asneovascular glaucoma in 1963.3


NVG is a severe form of glaucoma with formation of new blood vessels and obstructing aqueous humor outflow, most commonly due to posterior segment ischemia.4 It shows the development of a fibrovascular membrane on the anterior surface of the iris and iridocorneal angle.5 The fibrovascular membrane in the anterior chamber obstructs aqueous outflow in open-angle initially and later it contracts causingsynechial angle-closure which in turn causes high IOP.4 Usually iris and angle new vessels develop before the intraocular pressure rises.5

The formation of new vessels is influenced by imbalance between pro-angiogenic factors (such as, vascular endothelial growth factor-VEGF) and anti-angiogenic factors (such as pigment-epithelium-derived factor).6 VEGF plays an important role in formation of new vessels in patients with ischemic retinal diseases.7 VEGF and insulin growth-1 factors are produced by Mueller cells, retinal pigment epithelial cells, retinal capillary pericytes, endothelial cells and ganglion cells.8

Accumulation of Insulin growth-1 factor in aqueous humorcausesrubeosisiridis and later the formation of adhesions between cornea and iris block the aqueous humor drainage.9 VEGF concentration decreases after the regression of new vessels. 10 The non-pigmented ciliary epithelium is the major site of synthesis of VEGF in patients with NVG.11 Increased Interleukin-6 was noted in the aqueous of patients with NVG secondary to central retinal vein occlusion.12 Studies have shown increased levels of basic fibroblast growth factor (bFGF),13 transforming growth factor-beta1 and beta 2,14 nitric oxide,15 endothelin-116 and free-radicals such as the superoxide17 in the aqueous humor of patients with NVG.

Normal iris vessels have nonfenestrated endothelial cells with tight intercellular junctions whereas new vessels are thin walled without muscular layer or supporting tissue. New vessels show basement membrane changes, gaps and fenestrations in the endothelial cells on electron microscopy.19, 18 The new vessels are mostly accompanied by a fibrovascular membrane consisting of proliferating myofibroblasts.20


Thecommoncauses of NVG are diabetic retinopathy, retinal vein occlusions and carotid artery obstruction. Other causes are uveitis, pars planavitrectomy, irradiation, ocular tumors.4

Clinical course

NVG can be classified into four stages: pre-rubeosis, rubeosis, open angle glaucoma, and angle-closure glaucoma.

In the pre-rubeosis stage, iris new vessels or the angle new vessels are not detectable. Iris fluorescein angiography is useful in detecting occult neovascularization.

In the rubeosis stage, new vessels appear on the iris usually at the papillary margin. The angle is spared of new vessels and the intraocular pressure is normal.

In the third or open-angle glaucoma stage, new vessels start invading the iris stroma and the angle. Gonioscopy shows open angle and the intraocular pressure may be elevatedor normal.

In the final stage or angle-closure glaucoma stage, the new vessels become more prominent forming a fibrovascular membrane resulting in total synechial closure of the angle.

Justification of study

We, the authors wanted to know the most common cause and stage of presentation of NVG in our setup. So the present study was taken up.

Aims and objectives of the study

To identify the most common cause and the most frequent stage of presentation of the patient in neovascular glaucoma.

Materials and Methods

The present study is a prospective observational study, 136 eyes of 109 patients who underwent ophthalmological examination and diagnosed as having neovascular glaucoma in one eye or both the eyes at a tertiary eye care center in South India between November 2018 and August 2019 were included in the study. Patients were explained about the study and informed consent for the same was obtained. Relevant detailed medical and ocular history were obtained from all the patients.

All patients underwent thorough ocular examination i.e., visual acuity, slit lamp bio-microscopy, intraocular pressure (IOP) measurement by Goldmannapplanation tonometry, gonioscopy with Posner 4 mirror indirect gonioscope and dilated fundus examination with +90 D lens. Neovascularization of iris (NVI) was identified as tuft of new vessels on iris mostly at the pupillary margin in an undilated state, presence of ectropionuveae, hyphema was noted [Figure 3, Figure 2, Figure 1] A single tonometer used throughout the study and IOP was measured by a single person throughout the study. Indirect ophthalmoscopy or B-Scan was done in eyes with hazy media due to corneal edema and/or dense cataract.

Gonioscopy was done to identify new vessels and to grade the angle As open or closed. The number of quadrants with new vessels in the angle were noted.

Figure 1

NVI with ectropion uveae and hyphema

Figure 2

Neovascularization of iris with ectropion uveae

Figure 3

VI with ectropion uveae and hyphema

Statistical analysis

The data collected was entered in excel sheet and is analyzed using SPSS version 20.0. Descriptive variables were given with frequency (percentage) or mean (standard deviation). The association of various variables like Cause of NVG with stage of NVG and stage of NVG with IOP were analyzed using appropriate parametric and non-parametric tests like chi-square test (p-value) and ANOVA- test.


The present study was conducted in 136 eyes of 109 patients out of which 82 patients had either eye involvement and 27 patients had both eyes involvement. All Patients were aged between 14–84 years with a mean of 57.59 ± 12.6 years. Out of 109 patients, 88 (80.73%) were males and 21 (19.26%) were females.

IOP and gonioscopy

The range of intraocular pressure (IOP) was 2-76 mm of Hg with mean of 27.14 ± 11.3 mm of Hg. IOP of 2 mm of Hg was noted in 4 patients out of which 2 had chronic retinal detachment, 1 had chronic uveitis and 1 had vitreous haemorrhage with combined rhegmatogenous and tractional retinal detachment. IOP of 76 mm of Hg was noted in 1 case which had proliferative diabetic retinopathy. IOP < 10 mm of Hg IOP was noted in 27 out of 136 eyes of which 3 had chronic uveitis, 5 had retinal detachment, 17 had diabetic retinopathy in variable severity, 1 had central retinal vein occlusion and 1 underwent parsplanavitrectomy. >50 mm of Hg IOP was noted in 12 eyes out of which 4 had CRVO, 3 had PDR, 2 had PDR and VH, 2 had chronic uveitis and 1 had chronic pseudoexfoliative glaucoma.

On gonioscopic examination, most of the cases i.e., 74 (54.4%) had only rubeosisiridis without involvement of the angle, 27 (19.9%), 15 (11%), 8 (5.9%), 12 (8.8%) had neovascularization of angle (NVA) in one, two, three and four quadrants respectively. 4 cases had hyphema.

In the present study, most of the patients i.e., 74 (54.4%) presented in rubeosisiridis stage, 38 (27.9%) in angle closure stage and 24 (17.6%) in open angle stage [Table 1]. The number of eyes and the respective stage of NVG is plotted in the graph [Figure 4]

Table 1
Stage of NVG n %
Angle closure stage 38 27.9
Open angle stage 24 17.6
Rubeosisiridis 74 54.4
Total 136 100.0

Stage of NVG

Figure 4

Number of eyes in each stage of NVG

Table 2
Cause n %
Chronic RRD 2 1.5
DR 89 65.4
Glaucoma 14 10.3
Inflammation 16 11.8
S/P PPV 1 .7
Vein occlusion 14 10.3
Total 136 100.0

Causes of NVG

Chronic RD

Chronic Rhegmatogenous Retinal Detachment, DR – Diabetic retinopathy, Glaucoma – pseudoexfoliative glaucoma (PXG) and absolute glaucoma, Inflammation – Chronic uveitis, Vasculitis and Eales disease, S/P PPV – status post parsplanavitrectomy, Vein occlusion – central retinal vein occlusion and branch retinal vein occlusion.

Figure 5

Causes of NVG

Out of 136 eyes, 89 (65.4%) had diabetic retinopathy in variable severity, 16 (11.8%) had inflammatory etiology, 14 (10.3%) had retinal vein occlusion and 14 (10.3%) had glaucoma (PXG and absolute glaucoma) [Table 2]. The percentage of eyes and the respective cause of NVG is plotted in the graph [Figure 5]. 27 patients had bilateral involvement, of which 26 had bilateral diabetic retinopathy in variable severity and 1 patient had bilateral absolute glaucoma.

Table 3

Mean IOP in three stages of NVG

Stage of NVG Mean IOP (mm of Hg)
Angle closure stage 36.53±16.259
Rubeosis iridis 23.65±15.857
Open angle stage 23.08±18.472

Compares the mean IOP in different stages of NVG. Mean IOP in Angle closure stage is significantly higher than the mean IOP in other two stages (P = 0.000). Whereas there is no statistically significant difference between the mean IOP in rubeosisiridis stage and open angle stage (P = 0.988).

81 eyes (59.5%) had IOP < 30 mm of Hg of which 51 were in rubeosisiridis stage. 55 eyes (40.4%) had IOP > 30 mm of Hg of which 25 were in angle closure stage. IOP ˂ 30mm of Hg was found mostly in rubeosisiridis stage and ˃30 mm of Hg was found in angle closure stage.

On assessing the Cause of NVG in relation to stage of NVG (P= 0.107), 89 eyes (65.4%) had diabetic retinopathy in variable severity, of these 49, 22 and 18 were in rubeosisiridis, angle closure and open angle stage respectively. 9 had severe NPDR and all 9 were in rubeosisiridis stage. 22 had vitreous haemorrhage out of which 10, 10 and 6 were in rubeosisiridis, angle closure and open angle stage respectively. One had vitreous haemorrhage with combined rhegmatogenous and tractional retinal detachment, presented in rubeosisiridis stage.


Neovascular glaucoma (NVG) is a form of secondary glaucoma characterized by formation of new vessels and proliferation of fibrovascular tissue on iris and in the angle. Slit lamp examination can reveal new vessels on iris, ciliary injection, corneal edema due to increase in IOP, anterior chamber reaction and ectropion uvea due to contraction of the fibrovascular membrane on the iris. Rubeosis can be missed in early stages as it can’t be seen unless the iris is examined under high magnification in undilated stage. New vessels on iris usually appear before the appearance of new vessels in angle but in rare conditions like ischemic central retinal vein occlusion, new vessels in the angle are seen without involvement of the iris. Therefore, it is very important to perform gonioscopy even though new vesselsare not present on iris. Initially, the anterior chamber angle is open on gonioscopy but later, new vessels appear in the angle andin the final stages, due to formation of fibrovascularmembrane and tissue contraction synechiae can occur leading to synechial angle closure.21, 4

136 eyes of 109 patients were included in the present study out of which 82 patients had either eye involvement and 27 patients had both eyes involvement.

44.8% of patients were in the age group of 60 – 80 years which is comparable to the study done by Vasconcelloset al.22 in which 46.16 % of the patients were between 60 and 79 years of age.

In the present study, 106 (77.9%) had hypoxic and ischemic changes in retina like diabetic retinopathy, vein occlusion, chronic retinal detachment and S/P PPV and 16 (11.8%) had inflammatory diseases like uveitis, vasculitis and eales disease. It is comparable to the study done by Vancea PP et al.23 which states that 81% had NVG secondary to ischemic retinal changes and in another study done by Haefliger IO et al.24 they found that the majority (97%) of cases are associated with hypoxia and retinal ischemia. The remaining 3% cases are secondary to inflammatory diseases like chronic uveitis and intraocular neoplasms.

The commonest causes of NVG are Proliferative Diabetic Retinopathy (PDR) and central retinal vein occlusion.4 In our study 63 (46.4%) cases had PDR, 16 (11.8%) had uveitis and 14 (10.2%) had retinal vein occlusion and hence PDR is the most common cause of NVG in the present study. The formation of new vessels is influenced by imbalance between pro-angiogenic factors (such as, vascular endothelial growth factor-VEGF) and anti-angiogenic factors (such as pigment-epithelium-derived factor). Studies have shown that increased levels of VEGF and decreased levels of PEDF was found in the vitreous of patients with proliferative diabetic retinopathy.26, 25

In the present study one case who underwent pars planavitrectomy had developed NVG. Surgical intervention like pars planavitrectomy for PDR increases the incidence of rubeosis iridis.27 Retinal hypoxia is frequently seen in proliferative retinopathies. A portion of oxygen from the aqueous humor diffuses posteriorly towards the hypoxic retina causing the iris hypoxia. This explains the risk of rubeosis after surgery like vitrectomywhere oxygen reaches the ischemic retina faster leading severe iris hypoxia.28

In our study 9 cases (6.6%) had NVG due to pseudoexfoliative material on iris. Studies found that pseudoexfoliative material gets deposited adjacent to the endothelial wall and causes thinning of the basement membrane, endothelial wall fenestration and reduction of lumen of the vessel thus causing iris hypoxia and ischemia leading to neovascularization.30, 29

In the present study 2 (1.5%) had developed NVG due to chronic retinal detachment. Studies described NVG can develop rarely due to ischemia caused by chronic RD.32, 31

In our study, most of the cases presented in rubeosisiridis stage followed by angle closure stage and open angle stage. 74 eyes (54.4%) were in rubeosisiridis stage, 38 eyes (27.9%) were in angle closure stage and 24 eyes (17.6%) were in open angle stage.

In Rubeosisiridis stage most of the patients present with normal IOP and are usually asymptomatic. IOP begins to rise in Open angle glaucoma stage. In Angle closure glaucoma stage, IOP usually raises very high even up to 60 mmHg. Rubeosismay be severe with hyphema, anterior chamber reaction, conjunctival congestion and corneal edema.33 In the present study, the mean IOP in angle closure stage was found to be 36.53±16.259 mm of Hg which is significantly higher than the other two stages (P = 0.000). Four cases had hyphema and all 4 were in angle closure stage.


Neovascular glaucoma is a severe form of secondary glaucoma most commonly because of diseases causing retinal ischemia. So, early diagnosis and prompt treatment of the underlying retinal pathology can prevent neovascular glaucoma. In the present study, it was found that Proliferative diabetic retinopathy is the most common cause and rubeosisiridis is the most frequent stage of presentation in NVG.

Source of Funding


Conflict of Interest




M Wand R Ritch M B Shields T Krupin Neovascular Glaucoma. The Glaucoma - Clinical Science. 2nd, Ch 51St. LouisMosby 199610731129


G Coats Further cases of thrombosis of the central veinRoy Lond Ophthal Hosp Rep190616516


D I Weiss R N Shaffer Nehrenberg TR Neovascular glaucoma complicating carotid-cavernous fistulaArch Ophthalmol1963693304307


Tarek A. Shazly Mark A. Latina Neovascular Glaucoma: Etiology, Diagnosis and PrognosisSemin Ophthalmol2009242113121


Sohan Singh Hayreh Neovascular glaucomaProg Retin Eye Res2007265470485


J W Wang J W Wang M W Zhou X Zhang W B Huang X B Gao Short-term effect of intravitreal ranibizumab on intraocular concentrations of vascular endothelial growth factor-A and pigment epithelium-derived factor in neovascular glaucomaClin Exp Ophthalmol2015435415421


Lloyd Paul Aiello Robert L. Avery Paul G. Arrigg Bruce A. Keyt Henry D. Jampel Sabera T. Shah Vascular Endothelial Growth Factor in Ocular Fluid of Patients with Diabetic Retinopathy and Other Retinal DisordersN Engl J Med19943312214801487


Jeffrey W. Sall Dino D. Klisovic M.Sue O'Dorisio Steven E. Katz Somatostatin inhibits IGF-1 mediated induction of VEGF in human retinal pigment epithelial cellsExp Eye Res2004794465476


Jesús Ruberte Eduard Ayuso Marc Navarro Ana Carretero Víctor Nacher Virginia Haurigot Increased ocular levels of IGF-1 in transgenic mice lead to diabetes-like eye diseaseJ Clin Invest2004113811491157


T Chen S Q Zeng Y Y Lu L Y Huang H Dai The change of the level of the vascular endothelial growth factor in aqueous humor of patients with neovascular glaucoma before and after anterior retinal cryotherapyZhonghua Yan Ke Za Zhi2007437622625


Kakarla V. Chalam Vikram S. Brar Ravi K. Murthy Human Ciliary Epithelium as a Source of Synthesis and Secretion of Vascular Endothelial Growth Factor in Neovascular GlaucomaJAMA Ophthalmol20141321113501354


K-H Chen C-C Wu Roy S Lee S M Liu J H Increased interleukin-6 in aqueous humor of neovascular glaucomaInvest Ophthalmol Vis Sci19994011262726262758


Ramesh C. Tripathi Navaneet S.C. Borisuth Brenda J. Tripathi Detection, quantification, and significance of basic fibroblast growth factor in the aqueous humor of man, cat, dog and pigExp Eye Res1992543447454


X B Yu Increased levels of transforming growth factor-betal and -beta2 in the aqueous humor of patients with neovascular glaucomaOphthalmic Surg Lasers Imaging2007381614


Shih Hwa Chiou Charn Jung Chang Ching Kuang Chou Wen Ming Hsu Jorn Hon Liu Chiao Chiang Increased nitric oxide levels in aqueous humor of diabetic patients with neovascular glaucomaDiabetes Care1999225861862


Simone Iwabe Mónica Lamas Carlos G. Vásquez Pélaez Félix Gil Carrasco Aqueous Humor Endothelin-1 (Et-1), Vascular Endothelial Growth Factor (VEGF) and Cyclooxygenase-2 (COX-2) levels in Mexican Glaucomatous PatientsCurr Eye Res2010354287294


Eiki Oshida Kiyomi Arai Miki Sakai Makoto Chikuda Study of free radicals in aqueous humor in glaucoma and cataracts: differences in presence or absence of diabetes mellitus and neovascular glaucomaNihon Ganka Gakkai Zasshi20141189759767


T Tamura Electron microscopic study on the small blood vessels in rubeosis iridis diabeticaJ Japanese Ophthalmol Soc1968721123402352


A Vannas Fluorescein angiography of the vessels of the iris in pseudoe-exfoliation of the lens capsule, capsular glaucoma, and some other forms of glaucomaActa Ophthalmol Suppl1969105175


Thomas John Joseph W. Sassani Ralph C. Eagle The Myofibroblastic Component of Rubeosis IridisOphthalmol1983906721728


Sohan Singh Hayreh Neovascular glaucomaProg Retin Eye Res2007265470485


J P Vasconcellos V P Costa Kara-Jose N Neovascular glaucoma: epidemiology and prognostic factorsArq Bras Oftalmol1998615519524


P P Vancea A Abu-Taleb Current trends in neovascular glaucoma treatmentRev Med Chir Soc Med Nat Iasi20051092264268


I O Haefliger A Zschaner D R Anderson Relaxation of retinal pericyte contractile tone through the nitric oxide cyclic guanosine monophosphate pathwayInvest Opth Vis Sci1994353991997


K Evans P K Wishart J N McGalliard Neovascular complications after central retinal vein occlusionEye19937520524


Leonard A Levin Albert M Daniel Ocular Diseases, Mechanisms and Management2010514518Elsevier


Horst Helbig Ulrich Kellner Norbert Bornfeld Michael H. Foerster Rubeosis iridis after vitrectomy for diabetic retinopathyGraefes Arch Clin Exp Ophthalmol 199823610730733


I Ramona Barac Monica D Aniela Pop Andrei I Gheorghe Corina Onut Taban Neovascular secondary glaucoma, etiology and pathogenesisRom J Ophthalmol20155912428


A Ringvold M Davanger Iris neovascularisation in eyes with pseudoexfoliation syndrome.British Journal of Ophthalmology19816521381410007-116110.1136/bjo.65.2.138BMJ


Anne M.V. Brooks W.E. Gillies The Development of Microneovascular Changes in the Iris in Pseudoexfoliation of the Lens CapsuleOphthalmol198794910901097


Lisa C. Olmos Richard K. Lee Medical and Surgical Treatment of Neovascular GlaucomaInt Ophthalmol Clin2011513273610.1097/iio.0b013e31821e5960


B A Scruggs T S Quist N A Syed Wlm Alward Neovascular Glaucoma Eye Rounds Org2018


P Sharma N Agarwal R M Choudhry Neovascular Glaucoma - A ReviewDelhi J Ophthalmol2016263170175


© 2020 Published by Innovative Publication Creative Commons Attribution - NonCommercial 4.0 International (CC BY-NC 4.0) license (