1. Glaucoma conference
Neovascular Glaucoma
Pf. 문정일/ St.강규동/ R3신혜영

2. Introduction
In 1906, neovascularization was first reported in CRVO pts.
In 1963, the term neovascular glaucoma was used
to replace the older terms, such as
Hemorrhagic glaucoma, thrombotic glaucoma,
congestive glaucoma, rubeotic glaucoma,
diabetic hemorrhagic glaucoma, and 100 day glaucoma
NVG is a severe form of glaucoma with devastating visual outcome attributed to new blood vessels obstructing aqueous humor outflow, usually secondary to widespread posterior segment ischemia.
NVG occurs when new fibrovascular tissue proliferates onto the chamber angle, obstructs the trabecular meshwork, and produces peripheral anterior synechia and progressive angle closure.
Neovascular glaucoma (NVG) is a severe form of glaucoma with devastating visual outcome attributed
to new blood vessels obstructing aqueous humor outflow, usually secondary to widespread
posterior segment ischemia. Invasion of the anterior chamber by a fibrovascular membrane initially
obstructs aqueous outflow in an open-angle fashion and later contracts to produce secondary
synechial angle-closure glaucoma. The full blown picture of NVG is characteristized by iris neovascularization,
a closed anterior chamber angle, and extremely high intraocular pressure (IOP) with
severe ocular pain and usually poor vision. Shazly TA, Latina MA. Neovascular glaucoma: etiology, diagnosis and prognosis.
Semin Ophthalmol ;24:
Sivak-Callcott JA, et al. Ophthalmology. 2001;108:

3. Etiology
Factors predisposing to iris neovascularization and neovascular glaucoma

4. Etiology Diabetic retinopathy
NVI classically develops in patients with longstanding DM
usually in relation to PDR, especially with NVD
1/3 of pts c rubeosis iridis (m/c)
After ppV for DMR,
Ix. of rubeosis iridis : 25-42%, Ix. of NVG : 10-23%
During the first 6 months after surgery
Much higher in aphakic eyes
Unrepaired RD after vitrectomy for DMR
Peripheral retinal traction RD
Neovascular glaucoma (NVG) is a severe form of glaucoma with devastating visual outcome attributed
to new blood vessels obstructing aqueous humor outflow, usually secondary to widespread
posterior segment ischemia. Invasion of the anterior chamber by a fibrovascular membrane initially
obstructs aqueous outflow in an open-angle fashion and later contracts to produce secondary
synechial angle-closure glaucoma. The full blown picture of NVG is characteristized by iris neovascularization,
a closed anterior chamber angle, and extremely high intraocular pressure (IOP) with
severe ocular pain and usually poor vision.

5. Etiology Diabetic retinopathy CRVO 28% of cases of rubeosis iridis
A Completely attached retina and aggressive anterior or peripheral photocoagulation therapy - controlling or preventing NVG after vitrectomy for PDR
Intraocular silicone oil - reduces the incidence of NVI
A Completely attached retina and aggressive anterior or peripheral photocoagulation therapy - controlling or preventing NVG after vitrectomy for PDR
Intraocular silicone oil - reduces the incidence of NVI
Etiology
Diabetic retinopathy
CRVO
28% of cases of rubeosis iridis
Ix. of NVG, following ischemic CRVO was 45%
Carotid artery obstructive disease
3rd m/c, being responsible for 13% of all cases
Initially present with normal or even low IOP
due to ischemia of the ciliary body c reduced aqueous production.

6. Pathogenesis Retinal hypoxia PDR or CRVO with capillary nonperfusion
Diminished perfusion of retina
 Formation of new vessels on the iris, AC angle
Angiogenesis factors
Retinal ischemia  diffusible factor  neovascularization
VEGF (vascular endothelial growth factor)
several cell types in the retina (Muller cell : primary source)
IL-6 (Interleukin-6) : in CRVO pt.
Chronic dilatation of ocular vessels
Local hypoxia of the iris  vessels dilatation  neovascularization
Vasoinhibitory Factors
Vitreous, lens, RPE cells : possible source
3. PATHOGENESIS AND PATHOLOGY OF NVG
Chen et al. (Chen et al. 1999) reported that increase in the inflammatory cytokine interleukin (IL) - 6 in
aqueous humor correlated spatially and temporally with the grade of iris NV in patients of
NVG secondary to CRVO. They postulated that the increased level of IL-6 might have a
putative role, along with other angiogenic factors in angiogenesis of NVG.
Since 1996, several studies have implicated vascular endothelial growth factor (VEGF) as an
important and likely the predominant factor in the pathogenesis of intraocular NV and NVG
(Pe’'er et al. 1996, 1998; Sone et al. 1996; Tolentino et al. 1996; Kozawa et al. 1998; Tripathi
et al. 1998; Atmaca et al. 2002; Hu et al. 2002).
Boyd et al. (2002) found a close temporal correlation between aqueous VEGF levels and the course of iris NV and permeability in ischemic CRVO, indicating that increased aqueous VEGF level may predict the need for treatment.
Itakura et al. (2004) reported that in proliferative diabetic retinopathy a high VEGF
level was maintained in the vitreous cavity after vitrectomy. They stated that their results
suggest that there is persistent secretion of VEGF into the vitreous cavity even after vitrectomy
in these eyes. This observation is supported by the experimental findings of ocular NV in rhesus
monkeys, where Virdi and Hayreh (1982) found a correlation between retinal vascular leakage
and the development of ocular NV.
The main reason for visual loss with high IOP in NVG is ischemia of the optic nerve head and/
or retina. Blood flow in the various intraocular vascular beds can be calculated by using the
following formula:
According to this formula and assuming no change in vascular resistance, a rise of IOP reduces
the perfusion pressure and thus decreases the blood flow in the retina, choroid and optic nerve
head. Therefore, the higher the IOP and the lower the blood pressure, the greater is the reduction
of blood flow, and the worse the ischemic damage to the optic nerve head and retina,
particularly the former. Thus, in the management of NVG, although lowering the IOP is crucial,
one also has to make sure that the treatment does not lower the systemic arterial blood pressure.
Iris and angle NV almost invariably develops before the pressure rises. This is associated with
the development of a fibrovascular membrane on the anterior surface of the iris and iridocorneal
angle of anterior chamber. Membrane development is followed by development of progressive
anterior synechiae, and angle closure, and precipitous rise of IOP, which may be of fairly acute
onset. In some of the eyes, anterior segment NV may be associated with development of
hyphema, which may contribute or precipitate an acute rise of IOP. It is worth remembering
that the iridocorneal membrane may be difficult to visualize and that the angle may appear to
be open and the IOP elevated before synechiae develop.
Shazly TA, Latina MA. Semin Ophthalmol. 2009;24:

7. Clinicopathologic course
Preglaucomatic stage
1. Prerubeosis stage
2. Preglaucoma Stage
: Rubeosis iridis
3. Open-Angle Glaucoma stage
4. Angle-Closure Glaucoma stage
OAG stage
abnormal blood vessels on the surface of the iris
ACG stage
Rubeosis iridis : new abnormal blood vessels on the surface of the iris
( rubeosis (roo″be-o´sis) : redness)

8. Clinicopathologic course
1.Prerubeosis stage
Diabetic retinopathy
Risk is correlation with
arteriolar or capillary nonperfusion
after vitrectomy or lensectomy
FAG of iris : peripupillary leakage
Slit lamp exam (less reliable) : the pupillary margin of the iris
Gonioscopy : NVA may precede NVI
CRVO
Risk is correlation with retinal capillary nonperfusion
FAG, Slit lamp exam, FAG of iris, RAPD 
Both amplitude and implicit time should be measured for selected ERG signals.
b-wave amplitudes of the “rod response”, maximal combined response and
single flash “cone response” and
the b-wave time-to-peak of the single flash “cone response” or 30 Hz flicker response.
According to current convention, the a-wave amplitude is measured from baseline to a-wave trough, the b-wave amplitude is measured from a-wave trough to b-wave peak, and the b-wave time-to-peak is measured from the time of the flash to the peak of the wave (see Fig. 1).
Wittström E, et al. Acta Ophthalmol. 2010;88:86-90.
Electrophysiological evaluation and visual outcome in patients with central retinal vein occlusion, primary open-angle glaucoma and neovascular glaucoma.
Ponjavic V, Lövestam-Adrian M, Larsson J, Andréasson S.
, FAG of iris, RAPD, Infrared pupillometry

9. Clinicopathologic course
2. Preglaucoma Stage : Rubeosis iridis
Clinical features : Normal IOP
dilated tufts of preexisting capillaries, NVI, NVA...
Histopathologic features :
NVI : from normal iris a., drain into iris & ciliary body v.
( intrastromally  surface of iris )
NVA : from iris & ciliary body a., connect with pph. NVI
Thin fenestrated walls & arranged in irregular patterns
Ghosh S, et al. Clin Experiment Ophthalmol. 2010;38:333-4.
Ant. Ciliary a.
Long ciliary a
Shazly TA, Latina MA. Semin Ophthalmol. 2009;24:
Ghosh S, et al. Clin Experiment Ophthalmol. 2010;38:333-4.

10. Clinicopathologic course
3. Open-Angle glaucoma stage
Clinical features : 13-41% of DM with rubeosis iridis
CRVO : 3 months
Florid NVI, AC inflammation reaction
Gonioscopy : Open angle, intense NVA
Elevated IOP
Hyphema
Histopathologic features : fibrovascular membrane(FVM)
: AC angle & ant. surface of iris, may extend to post. iris
Obstruction of the trabecular meshwork by the FVM,
with inflammation & hemorrhage  elevated IOP
florid : 불그레 혈색좋은
elevated IOP : TM막아서, inflammation, Hm,
Shazly TA, Latina MA. Semin Ophthalmol ;24:

11. Clinicopathologic course
4. Angle-Closure Glaucoma Stage
Clinical features :
Flattened iris stroma c a smooth appearance
Entropion uvea
Dilated & pulled anteriorly iris
PAS -> total synechial closure of the angle
Histopathologic features :
Due to FVM contraction
Overlying the new vessels
inapparent, superficial layer of myofibroblast
 tissue contraction
Shazly TA, Latina MA. Semin Ophthalmol ;24:

12. Treatment Treatment of the underlying disease process
Panretinal photocoagulation
Panretinal cryotherapy, panretinal diathermy etc.
Goniophotocoagulation
Treatment of the increased IOP
Medical Tx : Pharmacologic agents
Glaucoma Surgical Procedures

13. Treatment Panretinal photocoagulation Mechanism : uncertain
may be related decreasing the retinal oxygen demand
reduce the stimulus for release of an angiogenesis factor
or may reduce the hypoxia in the anterior ocular segment.
Treatment of glaucoma : reverse IOP elevation
Prophylactic therapy : against the development of NVG
Ix. in DM
vitrectomy/lensectomy c peripupillary fluorescein leakage
endophotoagulation in conjunction with PPV
** PRP in ischemic CRVO ; does not prevent iris & angle NV
marked loss of peripheral visual fields
Hayreh, et al. Progress in Retinal and Eye Research 2007;26:470–85.

14. Treatment Panretinal photocoagulation Panretinal Cryotherapy
When cloudy media,
Transscleral panretinal cryotherapy with cyclocryotherapy
Goniophotocoagulation
Direct application of argon laser to new vessels in the AC angle
to prevent synechial closure
PRP가 성공적이지 못하거나 망막 치료가 불가능할때

15. Treatment Medical management
IOP lowering agent : suppressing aqueous production
& increasing uveoscleral outflow
carbonic anhydrase inhibitors : topical & oral
beta blockers
alpha2 agonist
Topical corticosteroid : relief of inflammation & pain
Atropine : cycloplegic effect, relief of pain
Hyperosmotic agents
Prostaglandin analogs : should be used impirically (with caution)
d/t uveoscleral route may be impaired
Sivak-Callcott JA, et al. Ophthalmology. 2001;108:

16. Treatment Medical management Anti-VEGF agents
Bevacizumab : humanized monoclonal antibody
antiangiogenic & antifibroblastic
- Direct effect on vascular & fibroblast proliferation
- Indirect effect of decreasing the influx of proinflammatory
cytokines into the bleb by way of surrounding vessels
Short term, a rapid regression of NV & IOP lowering
Preoperative IVB : adjuvant to the trabeculectomy/Ahmed valve imp.
: decreased postoperative hyphema
increased surgical success rate
( fibroblast function & growth of new vessels  bleb healing )
NVG 수술 성공률이 낮은 이유 : 전방 출혈에 의한 유출로의 직접적인 폐쇄
방수유출장치 내의 섬유 혈관의 증식을 보고 하였다.
diode laser cyclophotocoagulation : under peribulbar anaesthesia (2% lignocaine)
Transillumination was used to identify the ciliary body and 20–30 laser ‘shots’ were applied,
10 in each quadrant of the ciliary body sparing the 3- and 9-o’clock positions.
transscleral Nd:YAG cyclophotocoagulation : 8 J
the aiming beam was positioned 1.5 mm from the limbus at the 12-o'clock position, and 30 evenly
spaced laser lesions were applied for 360 degrees. The distance from the
limbus was tapered to 1 mm at the 3- and 9-o'clock positions.
In some patients, retrobulbar anesthesia was insufficient, which was

17. Treatment
One intracameral injection of bevacizumab caused a dramatic reduction of leakage from rubeotic vessels.
Peripheral anterior synechiae (PAS).
Grisanti S, et al. Am J Ophthalmol. 2006;142:

18. Treatment Glaucoma Surgical Procedures Cyclodestructive procedures
Cyclocryotherapy
Cyclophotocoagulation
Transscleral Nd:YAG cyclophotocoagulation
Transscleral diode laser cyclophotocoagulation
Transpupillary argon laser cyclophotocoagulation
Ultrasound destruction
Surgical removal of part of the ciliary body
Filtering surgery
Aqueous drainage devices
Other surgical procedures 
Partial destruction of the ciliary body lowers aqueous humor production and therefore lowers IOP. Photocoagulation, cryotherapy,
ultrasound destruction, and surgical removal of part of the
ciliary body have all been used for this purpose. Recently transscleral
photocoagulation has become the cyclodestructive procedure
of choice.
In 1972 Beckman

19. Treatment Transscleral Nd:YAG cyclophotocoagulation
Nd:YAG laser
Handheld sapphire-tipped probe
Semiconductor diode laser
‘‘G probe’’ handpiece
Lin SC. J Glaucoma. 2008;17:
Transscleral Nd:YAG cyclophotocoagulation
Transscleral diode laser
cyclophotocoagulation
NVG 수술 성공률이 낮은 이유 : 전방 출혈에 의한 유출로의 직접적인 폐쇄
방수유출장치 내의 섬유 혈관의 증식을 보고 하였다.
diode laser cyclophotocoagulation : under peribulbar anaesthesia (2% lignocaine)
Transillumination was used to identify the ciliary body and 20–30 laser ‘shots’ were applied,
10 in each quadrant of the ciliary body sparing the 3- and 9-o’clock positions.
transscleral Nd:YAG cyclophotocoagulation : 8 J
the aiming beam was positioned 1.5 mm from the limbus at the 12-o'clock position, and 30 evenly
spaced laser lesions were applied for 360 degrees. The distance from the
limbus was tapered to 1 mm at the 3- and 9-o'clock positions.
In some patients, retrobulbar anesthesia was insufficient, which was

20. Treatment Glaucoma Surgical Procedures (Continued)
Cyclodestructive procedures
Filtering surgery
High risk of intraoperative bleeding &
postoperative progression of the fibrovascular membrane
Trabeculectomy or full thickness filtering procedures
Intraoperative MMC or 5-FU
Modified trabeculectomy
with intraocular bipolar cautery of pph. Iris & ciliary processes
& creation of a limbal fistula with a carbon dioxide laser
Preoperative IVB
Anti-VEGF agents
NVG 수술 성공률이 낮은 이유 : 전방 출혈에 의한 유출로의 직접적인 폐쇄
방수유출장치 내의 섬유 혈관의 증식을 보고 하였다.
diode laser cyclophotocoagulation : under peribulbar anaesthesia (2% lignocaine)
Transillumination was used to identify the ciliary body and 20–30 laser ‘shots’ were applied,
10 in each quadrant of the ciliary body sparing the 3- and 9-o’clock positions.
transscleral Nd:YAG cyclophotocoagulation : 8 J
the aiming beam was positioned 1.5 mm from the limbus at the 12-o'clock position, and 30 evenly
spaced laser lesions were applied for 360 degrees. The distance from the
limbus was tapered to 1 mm at the 3- and 9-o'clock positions.
In some patients, retrobulbar anesthesia was insufficient, which was

21. Treatment Glaucoma Surgical Procedures (Continued)
Aqueous drainage devices
Implantation of drainage tubes/valve into the AC
or through the pars plana
pars plana drainage tube implant with ppV
Intraoperative MMC or 5-FU
Preoperative IVB
Other surgical procedures
SO inj. during revision of vitrectomy
Intravit. Inj. of crystalline triamcinolone acetonide
Photosensitization of vessels
IV hematoporphyrin inj.  exposure to red light
IV rose bengal inj.  exposure to filtered light c a wavelength of 550nm  
Alvarado JA, Hollander DA, Juster RP, Lee LC. Ahmed valve
implantation with adjunctive mitomycin C and 5-fluorouracil :
long-term outcomes. Am J Ophthalmol 2008;146:
diode laser cyclophotocoagulation : under peribulbar anaesthesia (2% lignocaine)
Transillumination was used to identify the ciliary body and 20–30 laser ‘shots’ were applied,
10 in each quadrant of the ciliary body sparing the 3- and 9-o’clock positions.
transscleral Nd:YAG cyclophotocoagulation : 8 J
the aiming beam was positioned 1.5 mm from the limbus at the 12-o'clock position, and 30 evenly
spaced laser lesions were applied for 360 degrees. The distance from the
limbus was tapered to 1 mm at the 3- and 9-o'clock positions.
In some patients, retrobulbar anesthesia was insufficient, which was

22. Treatment Glaucoma Surgical Procedures (Continued)
Endoscopic cyclophotocoagulation (ECP)
Treated processes
: white & shrunken
Endoscopic view
of ciliary processes
Untreated processes
In the limbal approach, after dilatation of the pupil with
a paracentesis is created and the anterior chamber is filled with viscoelastic agent
which is further used to expand the nasal posterior sulcus.
This viscoelastic expansion of the posterior chamber allows for easier approach to the pars plicata with the ECP
probe. A 2.2 mm keratome is then used to enter into the anterior chamber at the temporal limbus. After orientation of the
probe image outside of the eye, the 20 gauge probe is inserted through the incision and into the posterior sulcus.
At this time, the ciliary processes are viewed on the monitor and treatment can begin. The laser is set at continuous wave and
energy settings are 60–90mW.
ECP probe (20G)
Lin SC. J Glaucoma. 2008;17:

23. Sivak-Callcott JA, et al. Ophthalmology. 2001;108:1767-76.
Anti-VEGF agents
clinicopathologic stages of NVG
A Preglaucomatic stage : NVI and NVA
B OAG stage : fibrovascular memb증가
C ACG stage : contracture of the fibrovascular memb.(e:corectopia, ectropion uvea)
f: iris flattening
G: PAS
Sivak-Callcott JA, et al. Ophthalmology. 2001;108:
Anti-VEGF agents
Sivak-Callcott JA, et al. Ophthalmology. 2001;108:

24. NVG is difficult to treat, sometimes requiring many
therapeutic procedures and having poor results.
The diagnosis of NVG should be made as early as possible
if the pt is to be provided the best chance to maintain vision.
clinicopathologic stages of NVG
A Preglaucomatic stage : NVI and NVA
B OAG stage : fibrovascular memb증가
C ACG stage : contracture of the fibrovascular memb.(e:corectopia, ectropion uvea)
f: iris flattening
G: PAS
Sivak-Callcott JA, et al. Ophthalmology. 2001;108:
This requires that the doctor have a high index of suspicion.

25. Thank you for your attention !

26. Thank you for your attention !

27. Differential diagnosis
AACG
Glaucoma associated with anterior uveitis
Fuchs' heterochromic iridocyclitis
Iridocorneal endothelial syndrome
Old trauma

28. Clinicopathologic course
1.Prerubeosis stage
Diabetic retinopathy
CRVO
b-wave implicit time delay
Reduced b-wave/a-wave amplitude ratio
Wittström E, et al. Acta Ophthalmol. 2010;88:86-90.
full-field ERG
Both amplitude and implicit time should be measured for selected ERG signals.
b-wave amplitudes of the “rod response”, maximal combined response and
single flash “cone response” and
the b-wave time-to-peak of the single flash “cone response” or 30 Hz flicker response.
According to current convention, the a-wave amplitude is measured from baseline to a-wave trough, the b-wave amplitude is measured from a-wave trough to b-wave peak, and the b-wave time-to-peak is measured from the time of the flash to the peak of the wave (see Fig. 1).
Wittström E, et al. Acta Ophthalmol. 2010;88:86-90.
Electrophysiological evaluation and visual outcome in patients with central retinal vein occlusion, primary open-angle glaucoma and neovascular glaucoma.
Ponjavic V, Lövestam-Adrian M, Larsson J, Andréasson S.
, FAG of iris, RAPD, Infrared pupillometry