1. Akram Rismanchian, MD
Feiz Hospital

2. Glaucoma in diabetic patients

3. 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

4. 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

5. 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.

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

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

8. 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.!

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

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

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

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

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

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

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

16. 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.

17. 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

19. 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)

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

22. 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

25. 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)

26. 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.

27. Differential diagnosis
Inflammatory glaucoma
ACG
FHI
ICE syndrome
Trauma

28. 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

29. 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:

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

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

32. 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

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

34. 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.

35. 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.

36. 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

37. 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

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

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

40. 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

41. IVBI
Pre-injection
Post-injection

42. IVBI
Pre-injection
Post-injection

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

45. 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: Epub 2011 Jun 22.

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

48. 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

50. 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

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

52. Thanks for your attention