Akram Rismanchian, MD Feiz Hospital

Glaucoma in diabetic patients

Studies have reported a higher prevalence of both elevated mean IOP and POAG among persons with diabetes. A)diabetes decrease microvascular perfusion of the small vessels around the optic nerve head,which leads to increased susceptibility to elevated IOP

B)increased permeability of the blood-occular barrier – presence of aqueous flare C)diabetic patients are at increased risk for developing neovascular glaucoma due to the development of diabetic retinopathy

Neovascular glaucoma Background First described in the late nineteenth century as a condition in which eye developed progresive neovascularization of the iris (NVI) and angle(NVA) Other terms: Congestive glaucoma Thrombotic glaucoma Rubeotic glaucoma Hemorrhagic glaucoma The term “Neovacular Glaucoma” was proposed be Weiss et al. Weiss DI, Shaffer RN, Nehrenberg TR. Neovascular glaucoma complicating carotid-cavernous fistula. Arch Ophthalmol l963; 69:304.

Predisposing factors Retinal ischemia: DR ROP CRVO BRVO CRAO BRAO RD Coat’s disease Eales disease ROP Sickle cell retinopathy PHPV Retinal vasculitis

Predisposing factors Inflammatory diseases: Behcet’s disease Chronic iridocyclitis VKH syndrome Sympathetic ophthalmia Sarcoidosis Crohn’s disease

Predisposing factors Tumors: Iris melanoma Ciliary body melanoma Choroidal melanoma Retinoblastoma Metastasis Medulloepithelioma Consider doing UBM for ciliary body tumor evaluation in any case with NVG without a known cause.!

Predisposing factors Extraocular diseases: CC fistula Dural shunt embolization Carotid artery obstructive disease (OIS) Temporal arteritis Takayasu’s syndrome Wyburn-Mason syndrome Systemic cryoglobulinemia

Predisposing factors Irradiation/Surgical: External beam irradiation Proton beam irradiation Plaques radiation Carotid extraction PP vitrectomy/lensectomy SB

Prevalence CRVO (36%) DR (32%) with PDR OIS (13%) carotid artery obstraction

Prevalence Among glaucoma patients: 3.9% More common in older patients

Pathogenesis NVG + Combination of: NVI & NVA Retinal ischemia → hypoxia→ VEGF release Few viable retinal capillary endothelial cells VEGF posterior iris NVI & NVA NVG

Diabetes-associated NVG Prevalence: Overall: 2% In PDR: 21% Frequency of NVI is much higher (up to 65%) Fellow eye is at higher risk

Watch out! Each sudden IOP rise in a diabetic patient should be considered as NVG until prove otherwise.

Watch out! Cataract extraction (especially complicated) in a metabolically uncontrolled diabetic patient can bring about NVG within several days. So, all diabetic patients should be evaluated for NVI within 2-3 weeks following cataract surgery.

Clinical Course of NVG Pre-rubeosis stage Preglaucoma stage (rubeosis iridis): NVI/NVA - normal IOP - open angles Open-angle glaucoma: NVI/NVA - high IOP - open angles Angle-closure glaucoma: NVI/NVA - high IOP - closed angles/PAS

Signs & Symptoms Stage I: Fine NVI/NVA iris fluorescein angiography has been shown to be more reliabe in detecting very early iris neovascularization Asymptomatic (except for sign and symptoms of underlying disease)

Signs & Symptoms Stage II: Prominent NVI/NVA(open angle) Fibrovascular membrane Elevated IOP Hyphema Moderate red eye

Signs & Symptoms Stage III: Severe NVI/NVA Marked IOP rise Contraction of fibrovascular membrane angle closure Marked IOP rise Severe conj. Injection/chemosis Corneal epithelial edema Ectropion uvea PAS – hyphema moderate inflamation Photophobia, reduced visual acuity, acute severe pain, headache, nausea, and/or vomiting

Diagnosis Be curious about NVG in susceptible patients. Perform Undilated slit lamp examination (pay especial attention to the pupillary margin) Do gonioscopy AS-FA (more reliable than clinical examination for detecting very early NVI)

Note! NVI starts from the posterior iris surface. Distinguish dilated iris vessels from new vessels. PAS ends at Schwalbe’s line. In suspected cases, always do Gonioscopy. New vessels may occasionally be found in the angle without evidence of iris neovascularization.

Differential diagnosis Inflammatory glaucoma ACG FHI ICE syndrome Trauma

CRVO-associated NVG Developing time: within 3- 5 month Incidence depends on: Extent of retinal ischemia (nonperfusion) Location of retinal ischemia Duration of retinal ischemia

CRVO-associated NVG Incidence of NVI: Overall: 16-20% Nonischemic: rare Ischemic: up to 60% Progression of nonischemic CRVO toward ischemic one: Within 4 months: 15% Within 32 months: 34% Central Vein Occlusion Study Group. Baseline and early natural history report. The Central Vein Occlusion Study. Arch Ophthalmol1993; 11:1087-1095.

CRVO-associated NVG Note: The most important predictive risk factor for NVG following CRVO: poor VA

Treatment Varies with the stage of the disease and clarity of the media.

Treatment Stage I Once rubeosis iridis has begun, the primmy goal of treatment is to reduce the ischemic drive of neovascularization This is best accomplished with (PRP) to destroy ischemic retina, minimize oxygen demand of the eye, and reduce the amount of VEGF being released IVBI 70-95% regression of new vessels IOP drop in some cases

Treatment The clarity of the media usually dictates what form of treatment can be initiated.

Clear media PRP is recommended In one study that reported using 1200 to 1600 laser spots, there was a regression of rubeosis in nearly 71% of diabetic patients, whereas using 400 to 650 spots produced a regression of only 36% The CVOS essentially recommended performing PRP only when two clock hours of NVI and/or NVA was observed.

Cloudy media Because of vitreous hemorrhage, a pars plana vitrectomy and endolaser treatment, which can be combined with direct laser coagulation of the ciliary processes, are likely to be most effective.

Cloudy media In conjunction with vitrectomy, the use of silicone oil infusion in severe PDR was found to be beneficial in treating rubeosis iridis, presumably by acting as a barrier for the flow of pro-angiogenic factors between the anterior and posterior segments

Cloudy media If the media is cloudy because of a visually significant cataract, cataract extraction and immediate PRP should be considered to prevent further worsening of the neovascularization, which can progress rapidly after cataract extraction. IVBI

Cloudy media Other treatment modalities when the media is not clear include peripheral transscleral retinal diode laser photocoagulation and panretinal cryotherapy.

Treatment Note: Bevacizumab is a full-length humanized monoclonal antibody that binds all isoforms of vascular endothelial growth factor (VEGF).

Optimal dose and route of administration of bevacizumab A 1.25mg dose may be as effective as a 2.5mg (double) dose Both doses are safe and well below toxicity levels Intravitreal injection seems to be the standard of care IVB is more biologically plausible Intracameral bevacizumab has also been reported However this may entail corneal endothelial cell toxicity

IVBI Pre-injection Post-injection

IVBI Pre-injection Post-injection

Treatment Stage II/III Medical therapy Abovementioned interventions Topical steroids, cycloplegics, antiglaucoma medications Avoid giving pilocarpine PGs analogs ? Abovementioned interventions

Treatment Glaucoma surgery Filtering surgery Reported success rate between 30 to 78% in patients with regressed NVI Pretreatment with PRP/IVBI dramatically increases the success rate Recurrence of iris neovessels: 20% at 4 months and70% at 8 months With time success rate decreases Almost always fails in patients with NVI Marey HM, Ellakwa AF. Intravitreal bevacizumab with or without mitomycin C trabeculectomy in the treatment of neovascular glaucoma. Clin Ophthalmol. 2011;5:841-5. Epub 2011 Jun 22.

Treatment Shunting procedure 1 Baerveldt implantation > Ahmed valve > molteno implants

Treatment PP deep vitrectomy / IVBI/ endolaser combined with shunting procedure (more reported success rate than shunting procedure alone) Cyclodestructive procedures (external, endoscopic) Severe fibrinous reaction in patients with NVI Around 50% of cases develop NLP vision

Treatment Future promising option Photodynamic therapy with verteporfin Intravitreal injection of crystaline triamcinolone Pigment-epithelium-derived factor (PEDF)an endogenous angiogenesis inhibitor Secreted by the RPE and a select number of other cell types in the eye, as well as by other tissues Aims at balancing the levels of pro-angiogenic and angiostatic molecules

Note: Poor visual prognosis in NVG is mainly related to underlying disease not to inadequate IOP control.

Thanks for your attention