eMedicine Specialties > Ophthalmology > Intraocular Pressure

Glaucoma, Neovascular: Treatment & Medication

Author: Yasser A Khan, MD, Consulting Staff, Credit Valley Eye Care
Coauthor(s): Iqbal Ike K Ahmed, MD, FRCSC, Clinical Assistant Professor, Department of Ophthalmology, University of Utah; Khalid Hasanee, MD, Glaucoma and Anterior Segment Fellow, Department of Ophthalmology, University of Toronto; Baseer U Khan, MD, Staff Physician, Department of Ophthalmology, University of Toronto, Canada
Contributor Information and Disclosures

Updated: Jun 26, 2006

Treatment

Medical Care

• General principles for treating patients with NVG include the following:
  • Identifying the underlying etiology is fundamental in the management of NVG.
  • CRVO, diabetic retinopathy, CAOD, and CRAO require systemic workup and appropriate intervention to prevent further complications.
  • The management of NVG is approached through the following 4 stages that reflect the progression of the disease: prophylactic treatment, early-stage treatment, advanced-stage treatment, and end-stage treatment.
• Prophylactic treatment
  • Most patients are either at high risk for developing NVI/NVG or have early NVI with normal IOP. Prevention of NVG is the single most important aspect in its management.
  • Reducing the amount of viable retina is known to inhibit and even to reverse new vessel proliferation in the anterior segment. The mainstay in prevention is retinal ablation achieved via panretinal photocoagulation (PRP) or cryophototherapy because of media opacities (ie, corneal edema, cataract, vitreous hemorrhage) or other patient factors. Other treatment options in this stage include goniophotocoagulation.
  • PRP can be delivered in the following 3 ways: slit lamp delivery system, indirect laser, or endolaser at time of vitrectomy.
  • The amount of PRP required varies. The Diabetic Retinopathy Study (DRS) guidelines recommend 1200-1500 burns, with a spot size of 500 µm to be applied to the peripheral retina. Many retina specialists recommend 1500-2000 burns, with a spot size of 500-800 µm, using a wide-angle fundus contact lens (eg, Rodenstock). The types of laser include argon, krypton (better with media opacities and retinal hemorrhages), and diode (same utility as krypton laser).
  • To begin, a 360° peritomy is performed with isolation of the 4 recti muscles. A 2.5-mm retinal cryoprobe is used to create cryoapplication burns just anterior to the equator. Three spots are placed between each rectus muscle. Two additional rows of application are performed posterior to the first so that the third row is just outside the major vascular arcades. In total, 32 cryoapplications are performed under direct visualization. The probe tip remains in contact with the sclera until 70° has been maintained for 5-10 seconds. This procedure causes considerable inflammation, and complications (eg, tractional and exudative retinal detachment, vitreous hemorrhage) can occur.
  • Goniophotocoagulation, another laser therapy, is performed directly to NVI before the development of NVG. Its role in management of NVG is unclear, and it has not proven to be beneficial in preventing synechial closure of angle or advanced NVG.
  • All patients should undergo fluorescein angiography to delineate nonischemic CRVO from ischemic CRVO. Virtually no patients with nonischemic CRVO develop NVG. Overall incidence of NVG is 40% for an ischemic CRVO. NVI and NVG can appear from 2 weeks to 2 years. More than 80% of patients with NVI/NVG present within the first 6 months. Fifteen percent of patients with nonischemic CRVO can convert to ischemic CRVO within 8 months. The strongest predictors of NVI/NVG following CRVO include extensive retinal capillary nonperfusion of intravenous fluorescein angiography (IVFA), extensive retinal hemorrhages, short duration of occlusion, and male sex. In the Central Retinal Vein Occlusion Study, PRP was indicated for IVFA confirmed ischemic CRVO if development of 2 clock hours of NVI occurred or any NVA was present. No benefit occurred when prophylactic PRP was performed prior to the development of NVI or NVA when frequent follow-up care was provided.
  • Prophylactic PRP still is recommended by many retinal specialists before the development of NVI or NVA, especially in case of the following: clear extensive capillary nonperfusion, extensive systemic vascular disease, patient who is monocular, and/or noncompliance or poor follow-up results. Preoperative care is fundamental for all types of cataract surgery, capsulotomy, and vitreous surgery.
  • For patients with diabetic retinopathy, ensure frequent follow-up care and tight glycemic control. If proliferative diabetic retinopathy exists, then complete PRP is recommended as treatment.
• Early-stage treatment: This stage is characterized by the development of a fibrovascular membrane across some or all of the angle, obstructing the trabecular meshwork, and an increase in IOP.
  • With secondary open-angle glaucoma, treatment is identical to prophylactic treatment and includes PRP (filler PRP if already performed initially), panretinal cryotherapy, and medical therapy.
  • The most important medical therapy for this stage includes topical atropine 1% to decrease ocular congestion and topical steroids (eg, Pred Forte, Inflamase Forte) to decrease inflammation. Standard antiglaucoma medications to treat secondary open-angle glaucoma are recommended. Other agents include topical beta-blockers (eg, Betagan, Timoptic), topical brimonidine (eg, Alphagan), topical carbonic anhydrase inhibitor (eg, Trusopt, Azopt), and oral carbonic anhydrase inhibitor (eg, Diamox). Topical pilocarpine is contraindicated because it may increase inflammation. The role of topical latanoprost (eg, Xalatan) is unclear in the treatment of early NVG.
  • The successful use of photodynamic therapy with verteporfin directed at the iris and the angle to obliterate neovascularization and to reduce IOP has been reported.
• Advanced-stage treatment: This stage is characterized by synechial closure of the angle and secondary angle-closure glaucoma.
  • PRP is still the initial and most important treatment, both to prevent further NVI/NVA and angle closure and to prepare the eye for surgical intervention (see Surgical Care). Surgical intervention is indicated in eyes with potential for useful vision.
  • Medical therapy is indicated, with topical atropine and steroids being the most important agents. Antiglaucoma medications, topical beta-blockers, and carbonic anhydrase inhibitors also are recommended. The role of topical brimonidine and latanoprost in advanced disease is unclear. Topical pilocarpine and echothiophate iodide are contraindicated (may cause increased inflammation and hyperemia). Oral glycerol and intravenous mannitol are recommended only if IOP is elevated symptomatically.
• End-stage treatment: This stage is characterized by complete angle closure by peripheral anterior synechiae with no remaining useful vision.
  • The primary goal of treatment in this stage is pain control. Medical therapy includes topical atropine 1% and steroids. If corneal decompensation occurs, use a bandage contact lens. Cyclodestructive procedures are performed if medical therapy fails to provide symptomatic relief. With cyclocryotherapy, the IOP-lowering effect is achieved by destroying secretory ciliary epithelium and/or reducing blood flow to the ciliary body. It is indicated as a last resort only if relief of pain is the main goal. In a large series, 34% of eyes achieved IOP of less than 25 mm Hg; however, 34% of eyes became phthisical and 57% of eyes lost all light perception. Other complications include sympathetic ophthalmia and anterior segment ischemia.
  • With Nd:YAG laser transscleral cyclophotocoagulation, 2 approaches, contact and noncontact, are used. In the contact approach, one study reported a 40% decrease in IOP to less than 19 mm Hg in eyes with NVG. In the noncontact approach, out of 27 eyes with NVG, only 15% achieved satisfactory IOP control.
  • The results of diode laser transscleral cyclophotocoagulation are similar to Nd:YAG cyclophotocoagulation.
  • Direct laser cyclophotocoagulation is performed under direct observation using the argon laser. Two approaches, transpupil or with endoscopy, are used. Its role in NVG management is secondary. Success in controlling IOP is limited (may have less inflammation and pain versus cyclocryotherapy).
  • Retrobulbar alcohol injection is indicated after all medical and surgical options have been explored and the patient does not want an enucleation. Complications include external ophthalmoplegia and blepharoptosis. Enucleation is indicated only if intractable pain is not relieved by any other treatment modality.

Surgical Care

• With surgical care, ensure that adequate PRP is completed to reduce vasoproliferative stimulus. Atropine and steroids are indicated to decrease inflammation, and antiglaucoma medication is indicated to decrease IOP. Wait approximately 3-4 weeks to allow the eye to quiet down.
• Surgical modalities include trabeculectomy with or without an antifibrotic agent and valve implant surgery.
  • Trabeculectomy with the antifibrotic agents mitomycin-C and 5-fluorouracil (5-FU) is one modality. Trabeculectomy in NVG has a significant failure rate. Using standard trabeculectomy (without antifibrosis), an IOP of less than 25 mm Hg on one medication or less has been reported to occur in 67-100% of patients in 3 studies. Using injections of 5-FU subconjunctivally in the postoperative period, the surgical success has been reported to be 68% over 3 years. Inject 0.1 mL of 5 mg/mL 5-FU subconjunctivally either superiorly above the bleb or inferiorly (just above the lower fornix). Mitomycin-C used intraoperatively has been shown to be more effective than 5-FU in routine trabeculectomies. No significant follow-up studies exist on the use of mitomycin-C with trabeculectomy in NVG.
  • Valve implant surgery is another modality and is indicated when trabeculectomy fails or extensive conjunctival scarring exists, thereby preventing a standard filtering procedure. Molteno, Krupin, and Ahmed valve implants commonly are used. One large series using the Krupin valve reported 79% of eyes with NVG had a 67% success rate in controlling IOP (<24 mm Hg) with mean follow-up of 23 months. Long-term results are mixed. Using the Molteno implant, 60 eyes with NVG achieved a satisfactory IOP (<21 mm Hg) and maintenance of visual acuity over 5 years of only 10.3%. If combined with the need for vitrectomy, consideration of pars plana tube-shunt insertion may reduce anterior segment complications.
  • Complications include postoperative hypotony with associated complications, blockage of internal fistula, blockage of external filtration site (fibrosis of the filtering bleb), and corneal endothelial loss.

Medication

The most important medications include a regimen of topical steroids and atropine. Antiglaucoma medications include both topical and oral agents.

Cycloplegic drugs

Paralyze ciliary muscle, preventing ciliary muscle spasm; provide pain relief; and decrease ocular congestion.

Atropine sulfate 1% (Isopto, Atropair, Atropisol)

Acts at parasympathetic sites in smooth muscle to block response of sphincter muscle of iris and muscle of ciliary body to acetylcholine, causing mydriasis and cycloplegia.

Steroidal anti-inflammatory

Decreases ocular inflammation.

Prednisolone acetate 1% (Pred Forte)

Treats acute inflammations following eye surgery or other types of insults to eye. Decreases inflammation and corneal neovascularization. Suppresses migration of polymorphonuclear leukocytes and reverses increased capillary permeability. In cases of bacterial infections, concomitant use of anti-infective agents is mandatory; if signs and symptoms do not improve after 2 days, reevaluate patient. Dosing may be reduced, but advise patients not to discontinue therapy prematurely.

Alpha2-adrenergic agonists

Decrease IOP by reducing aqueous humor production.

Brimonidine tartrate 0.5% (Alphagan)

Selective alpha2-receptor that reduces aqueous humor formation.

Carbonic anhydrase inhibitors

By slowing the formation of bicarbonate ions with subsequent reduction in sodium and fluid transport, it may inhibit carbonic anhydrase in the ciliary processes of the eye. This effect decreases aqueous humor secretion, reducing IOP.

Dorzolamide hydrochloride 2.0% (Trusopt)

Used concomitantly with other topical ophthalmic drug products to lower IOP. If more than one ophthalmic drug is being used, administer drugs at least 10 min apart. Reversibly inhibits carbonic anhydrase, reducing hydrogen ion secretion at renal tubule and increasing renal excretion of sodium, potassium bicarbonate, and water to decrease production of aqueous humor.

Acetazolamide (Diamox, Diamox Sequels)

Inhibits enzyme carbonic anhydrase, reducing rate of aqueous humor formation, which, in turn, reduces IOP. Used for adjunctive treatment of chronic simple (open-angle) glaucoma and secondary glaucoma and preoperatively in acute angle-closure glaucoma when delay of surgery desired to lower IOP.

Prostaglandins

Used to reduce IOP in patients who are intolerant or resistant to other IOP-lowering medications. They are contraindicated in glaucomas in which inflammation is a prominent ocular finding.

Bimatoprost (Lumigan)

Prostaglandin analog that selectively mimics effects of naturally occurring substances, prostamides. Exact mechanism of action unknown but believed to reduce IOP by increasing outflow of aqueous humor through trabecular meshwork and uveoscleral routes.

Travoprost ophthalmic solution (Travatan)

Prostaglandin F2-alpha analog and selective FP prostanoid receptor agonist. Exact mechanism of action unknown but believed to reduce IOP by increasing uveoscleral outflow.

Unoprostone ophthalmic solution (Rescula)

Prostaglandin F2-alpha analog and selective FP prostanoid receptor agonist. Exact mechanism of action unknown but believed to reduce IOP by increasing uveoscleral outflow and facilitating conventional outflow through the trabecular meshwork

Beta-adrenergic blockers

The exact mechanism of ocular antihypertensive action is not established, but it appears to be a reduction of aqueous humor production.

Levobunolol (AKBeta, Betagan)

Nonselective beta-adrenergic blocking agent that lowers IOP by reducing aqueous humor production.

Timolol maleate 0.5% (Timoptic, Timoptic XE, Blocadren)

May reduce elevated and normal IOP, with or without glaucoma, by reducing production of aqueous humor.

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