Neovascular GlaucomaNeovascular Glaucoma(NVG)(NVG)

Saleh A. Al-Obeidan, MDSaleh A. Al-Obeidan, MDDepartment of OphthalmologyDepartment of Ophthalmology

College of MedicineCollege of MedicineKing Saud UniversityKing Saud University

Neovascular GlaucomaNeovascular Glaucoma(NVG)(NVG)

Neovascular Glaucoma is one of the mostChallenging forms of secondary glaucomas. It

occurs when the fibrovascular tissue proliferates onto the chamber angle, obstructs the trabecular

meshwork, and produces peripheral anterior synechiae and progressive angle closure. The

elevated intraocular pressure is often difficult to control and frequently results in loss of vision.

NVG NVG

1871 Pagenstetcher Hemorrhagic

1963 Weiss, et al. NVG

NVG NVG PathogenesisPathogenesis

Leading causes:Leading causes:

Retinal Ischemia Responsible for 97%Retinal Ischemia Responsible for 97%

- Diabetic Retinopathy- Diabetic Retinopathy

- Central Retinal Vein Occlusion- Central Retinal Vein Occlusion

Brown GC et al. Ophthalmology 1984

NVGNVGPathogenesisPathogenesis

X-FactorX-Factor VEGF VEGF - - Vascular Endothelial Growth FactorVascular Endothelial Growth Factor

1 of 9 non polypeptide growth factors 1 of 9 non polypeptide growth factors

Specific for endothelial cells (EC) Specific for endothelial cells (EC)

Causes EC migration and mitosis Causes EC migration and mitosis

Increases EC permeabilityIncreases EC permeability

NVGNVGPathogenesisPathogenesis

VEGF VEGF (source in the eye)(source in the eye)

Expressed and produced by: Corneal Expressed and produced by: Corneal endothelium, Iris pigment epithelium, endothelium, Iris pigment epithelium, RPE, Ganglion cells, Astrocytes, RPE, Ganglion cells, Astrocytes, Muller cells, Uveal melanocyte, and Muller cells, Uveal melanocyte, and Choroidal fibroblasts.Choroidal fibroblasts.

J Glaucoma 2002

NVGNVGPathogenesisPathogenesis

VEGFVEGF

Markedly elevated in aqueous Markedly elevated in aqueous humor of patients with NVG.humor of patients with NVG.

Diabetes Care Nov. 1996Ophthalmology 1998J Glaucoma 2002

NVGNVGPathogenesisPathogenesis

VEGFVEGF (210 Vitrectomy samples)

- Vitreous (VEGF) PDR 36x NPDR- Vitreous (VEGF) PDR 36x NPDR - Vitreous (VEGF) > Aqueous (VEGF)- Vitreous (VEGF) > Aqueous (VEGF) - (VEGF) - (VEGF) 75% post PRP 75% post PRP VEGF plays a major part in mediating VEGF plays a major part in mediating

active intraocular neovascularization in active intraocular neovascularization in patients with ischemic retinal diseases.patients with ischemic retinal diseases.

N Engl J Med 1994;331:1480-7

NVGNVGPathogenesis Pathogenesis

Anti Angiogenic Therapy:Anti Angiogenic Therapy:

Intravitreal injection of crystalline Intravitreal injection of crystalline cortisone causes regression of iris cortisone causes regression of iris neovascularization neovascularization

Jonas et al. J Glaucoma 2001

NVGNVGPathogenesisPathogenesis

Anti-Angiogenic Therapy:Anti-Angiogenic Therapy:

Anti VEGFAnti VEGF (Ranibizumab, Lucentis) (Ranibizumab, Lucentis)

Intravitreal injection prevented Intravitreal injection prevented formation of CNV in monkeys and formation of CNV in monkeys and decreased leakage of already decreased leakage of already formed formed

CNV with no significant CNV with no significant toxic effects toxic effects Arch Ophthalmol 2002

Kim, et al. Invest Ophthalmol. Vis Sci 2006

NVGNVGPathogenesisPathogenesis

Anti Angiogenic Therapy:Anti Angiogenic Therapy:

Anti VEGF [Anti VEGF [SU 5416 (Semaxinib)] SU 5416 (Semaxinib)]

Durable and rapid recovery of Durable and rapid recovery of visual visual functions in a patient with functions in a patient with von von Hippel-Lindau syndromeHippel-Lindau syndrome

Ophthalmology, Feb 2002J Clin Oncol. May 2005

NVGNVGPathogenesisPathogenesis

Anti Angiogenic Therapy:Anti Angiogenic Therapy:

Anti VEGF [Aptamer (Macugen)] Anti VEGF [Aptamer (Macugen)] Remarkable reduction in the size of Remarkable reduction in the size of

CNV CNV Remarkable visual improvement Remarkable visual improvement

“26.7% gained 3 lines or more”“26.7% gained 3 lines or more” The Eye Tech Study Group, Retina 2002

Exp Eye Res. May 2006Ophthalmology. Apr 2006

NVGNVGPathogenesisPathogenesis

Anti Angiogenic Therapy:Anti Angiogenic Therapy:

Bevacizumab [Avastatin]Bevacizumab [Avastatin]

Davidorf, et al. Retina 2006Kehook, et al. Ophtha Surg 2006

NVGNVGPathogenesisPathogenesis

Panretinal Photocoagulation and Panretinal Photocoagulation and Ocular NeovascularizationOcular Neovascularization PRP upregulate expression of transforming growth factor- (TGF- ) TGF- is a powerful vascular endothelial cell proliferation inhibitor.

Invest Ophthalmol Vis Sci 1998

NVGNVGPathogenesisPathogenesis

Panretinal Photocoagulation and Panretinal Photocoagulation and Ocular NeovascularizationOcular Neovascularization Photo coagulated cultured human RPE

& rat retinas upregulate expression of high level of Pigment Epithelium Derived Factor (PEDF)

PEDF has been shown to be a potent inhibitor of ocular angiogenesis

Am J Ophthalmol, Sep 2001Am J Ophthalmol Aug 2002Invest Ophthalmol Vis Sci 2002

NVGNVGPathogenesis Pathogenesis

Panretinal Photocoagulation and Panretinal Photocoagulation and Ocular NeovascularizationOcular Neovascularization

Major benefit of PRP may be Major benefit of PRP may be destruction of VEGF source.destruction of VEGF source.

NVGNVGClinical PresentationClinical Presentation

Reduced vision Injected eye A/C reaction Elevated IOP < 40 mmHg Middilated, non reactive pupil Rubeosis irides (NVI) Neovascularization of the angle (NVA))

NVG NVG

Enucleation is only practical treatment

No means are known to prevent NVG

The treatment of NVG is disheartening

Duke Elder, 1969

Grant, 1974

Hoskins, 1974

NVG NVG

Outcomes have improved dramatically.

New medical and surgical approaches.

Better understanding and control of angiogenesis.

NVG NVG

“If the neovascular element can be removed and further neovascularisation

prevented, then we are left with an uncomplicated angle-closure problem which should be amenable to classical

drainage surgery.”

Flanagan D.W. & Blach R.K. Br J. Ophtamol 1983;67,526-8

NVGNVGManagementManagement

Recognition of patients at HIGH RISK

Recognition of NVI before angle closure is critical

Treatment

NVGNVGManagementManagement

Recognition high risk patients

Correction of the underlying pathology

Close observation (NVI & NVA)

Efficient & sufficient PRP

Prevention:Prevention:

TreatmentTreatment

NVGNVGTreatmentTreatment

Visual potential

Clarity of the media

DeterminantsDeterminants

NVGNVGTreatment Treatment (cont.)

Control inflammation & pain

Cycloplegia

Steroids

Medical TherapyMedical Therapy

NVGNVGTreatment Treatment (cont.)

Control IOP

Aqueous suppressants

Avoid miotics & prostaglandines

Medical TherapyMedical Therapy

NVGNVGTreatment Treatment (cont.)

Panretinal photocoagulation (PRP)

1st line of therapy (if possible)

Reduces & can eliminate ant. seg. neovascularization.

Panretinal cryoablation

Laser TherapyLaser Therapy

Cryo TherapyCryo Therapy

NVGNVGTreatment Treatment (cont.)

Filteration surgery

Tube surgery

Cyclodystructive procedures

Others

Conventional SurgeryConventional Surgery

NVGNVGTreatment

CyclophotocoagulationVisual loss up to 46.6%

Shields & Shields 1994

Cyclocryotherapy

Visual loss of up to 70% Caprioli et al. Ophthalmology 1985

Phthisis Bulbi 34% Krupin T et al. Am J Ophthalmol 1978;86:24-6

Cyclodestructive procedures:Cyclodestructive procedures:High rate of serious complications and visual loss

NVGNVGTreatment Treatment

Tube shunts:Tube shunts: Variable success rates Probably more suitable

for previously operated eyes (e.g. failed filter proced. Aphakia)

High rate of visual loss (19-48%) and phthisis bulbi (11-25%)

Mermoud et al. Ophthalmology 1993

NVGNVGTreatment Treatment (cont.)

Filteration surgery

Full PRP Improves the Outcome Full PRP Improves the Outcome of Trabeculectomy in NVGof Trabeculectomy in NVG

Procedure - Standard Trabeculectomy

- Mitomycin “C” 0.2mg/ml/2mins.

Precautions - Gradual decompression

of the eye

Surgical Technique

Full PRP Improves the Outcome Full PRP Improves the Outcome of Trabeculectomy in NVGof Trabeculectomy in NVG

Short Term Complications: - Transient hypotony - 14/23 (61%) - Hyphema - 8/23 (35%) - Choroidal Detachment - 2/23 (9%) - Leaking Bleb - 1/23 (4%)

Long Term Complications: - Cataract prog. – 2/23 (9%) - NLP - Hypotony Maculopathy Non - Phthisis Bulbi

Full PRP Improves the Outcome Full PRP Improves the Outcome of Trabeculectomy in NVGof Trabeculectomy in NVG

Complete Success 20/23 (87%)

Qualified Success 3/23 (13%)

Results

Treatment Treatment

NVG

Seeing eye NLP

- Medical Rx - Cyclodestructive procedure Clear

media PRPPoor media Cryoablation

Vitreous hge Vitrectomy+ endolaser

Trabeculectomy & Mitomycin

Tube shunts cyclophotocoagulation

NVGNVGPoints to RememberPoints to Remember

It is a preventable condition.It is a preventable condition.

NVGNVGPoints to RememberPoints to Remember

It is a treatable condition.It is a treatable condition.