Glaucoma Update

From the Annual Clinical Conference, presented by the Kansas City Society of Ophthalmology and Otolaryngology

Leon W. Herndon, MD, Associate Professor of Ophthalmology, Duke University Medical Center, Durham, NC

Educational Objectives

The goal of this program is to improve the diagnosis and management of glaucoma. After hearing and assimilating this program, the participant will be better able to:

1.   Recognize the features of neovascular glaucoma (NVG) and describe approaches to managing retinal ischemia and intraocular pressure (IOP) in patients with NVG.

2.   Summarize-results of recent studies evaluating the use of anti-vascular endothelial growth factor therapy for NVG.

3.   Discuss the benefits of procedures for treating glaucoma, including aqueous shunt surgery and the
Ex-PRESS shunt.

4.   Compare and contrast safety and efficacy of tube shunts vs traditional trabeculectomy.

5.   Evaluate the contribution of corneal thickness and hysteresis to IOP and the risk of developing
glaucoma.

Faculty Disclosure

In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty and members of the planning committee to disclose relevant financial relationships within the past 12 months that might create any per­sonal conflicts of interest. Any identified conflicts were resolved to ensure that this educational activity promotes quality in health care and not a proprietary business or commercial interest. For this program, Dr. Herndon reported participating on the Speakers’ Bureaus for Alcon Laboratories, Allergan, Ista Pharmaceuticals, Optonol, and iScience. The planning committee reported nothing to disclose.

Acknowledgements

Dr. Herndon spoke at the Annual Clinical Conference, presented by the Kansas City Society of Ophthalmology and Otolaryngology, and held January 9-10, 2009, in Kansas City, MO. The Audio-Digest Foundation thanks Dr. Hern­don and the Kansas City Society of Ophthalmology and Otolaryngology for their cooperation in the production of this program.

The Use of VEGF Inhibitors in Neovascular Glaucoma

Background: in neovascular glaucoma (NVG), tissue proliferates onto angle, obstructs meshwork, and produces pe­ripheral anterior synechiae (PAS) and progressive angle closure; 97% of cases caused by retinal ischemia (usually diabetes mellitus, central retinal vein occlusion, or ocular ischemia); 3% of cases caused by inflammation

Study results: vascular endothelial growth factor (VEGF) found in aqueous of eyes with NVG at levels 40-fold and 113-fold higher than in eyes with primary open angle glaucoma (POAG) and cataracts, respectively; levels of VEGF higher in eyes with NVG than in those with proliferative diabetic retinopathy (PDR)

Features of NVG: early stage  —  tufts of new vessels at pupillary margin and fine vessels crossing scleral spur; late stage  —  high levels of intraocular pressure (IOP), corneal edema, florid iris neovascularization with ectropion uveae, and variable synechial angle closure; minimal neovascularization of iris possible with total angle closure; pigmented Schwalbe’s lines mimic chronic OAG on gonioscopy; neovascularization typically observed initially around pupil

Treatment goals: treat underlying disease and lower IOP; additional management  — in  early stage, includes panreti­nal photocoagulation (PRP), medical therapy, cyclophotocoagulation (CPC), and possibly panretinal cryotherapy; in late stages, includes PRP, medical therapy, filtration surgery with adjunctive antimetabolite therapy, aqueous shunts, and cyclodestruction by laser or cryotherapy

Managing retinal ischemia: PRP  —  study has shown PRP produces regression of rubeosis in 68% of patients and normalization of IOP in 42%; 1200 to 1600 spots required to achieve regression in 70% of patients; 400 to 650 spots produced only 37% regression; panretinal cryotherapy  —similar to PRP for regression of rubeosis; achieved 82% control of IOP after 1 yr in one study

Managing IOP: cyclodestruction with diode laser  —  produces less phthisis than with neodymium: yttrium aluminum garnet (Nd:YAG) laser; study showed mean reduction in IOP of 53% after transscleral diode cycloablation; how­ever, 71% 3-yr rate of failure in control of IOP observed with diode CPC vs 43% rate of failure with tube shunts; traditional filtration surgery  —  associated with poor outcome (eg, 28% rate of success after 5 yr in study); mitomy­cin (MMC) better than 5-fluorouracil (5FU); tube shunts  —study of 60 eyes using Molteno tubes showed 62% re­duction in IOP at <1 yr and 10.3% at 5 yr; Baerveldt tubes associated with 79% rate of success at 12 mo and 56% at 18 mo

Case Example

Presentation: 82-yr-old woman with 20-yr history of diabetes and POAG with IOP measurements of 14 and 28 mm Hg in right and left eyes, respectively; patient found to have NVG but no neovascularization of retina; previous medications included timolol (eg, Timoptic-XE) and latanoprost (Xalatan); prednisolone (eg, Pred Forte) and hom­atropine added to regimen for left eye; patient had visual acuity (VA) of 20/60 in right eye and 20/100 in left eye; slit-lamp examination showed neovascularization of iris (NVI) for 4 clock hours and 360° NVI on left; gonioscopy showed open angle on right and only 2 clock hours open angle on left; dilated funduscopic examination showed 3 clock hours neovascularization of disc on left and scattered dot blot hemorrhages

Treatment: traditional PRP performed (1327 spots on right, 602 on left); IOP remained uncontrolled despite treat­ment with acetazolamide (eg, Diamox), timolol, and brimonidine (Alphagan); patient underwent combined Ahmed valve implant and phacoemulsification and achieved IOP of 14 mm Hg; at day 6, VA dropped to hand motion and IOP increased to 40 mm Hg because fibrin and heme blocked tube; 1 mo later, patient received anterior chamber washout, vitrectomy, endolaser PRP, and flushing of tube; achieved IOP of 17 mm Hg (2 mo later, IOP 7 mm Hg)

Anti-VEGF Therapy

First study: retrospective study of 41 eyes with NVI or NVG that received 1 mg intravitreal bevacizumab (Avastin) as initial treatment; patients divided into 3 groups (those with NVI but without elevated IOP, NVG with elevated IOP and open angle, and NVG with angle closure); results in first group (9 eyes)  —  baseline IOP of 14.7 mm Hg and NVI regressed or resolved after one injection but recurred in 4 eyes by 6 mo; NVI stabilized after repeated in­jections, without elevation of IOP; second group (17 eyes)  —  baseline IOP 31 mm Hg; regression of NVI with suc­cessful lowering of IOP in 12 eyes at 1 wk; remaining 5 eyes required surgery by 6 mo, despite repeated injections; third group (15 eyes)  —baseline IOP 45 mm Hg; regression of NVI seen, but no effect on IOP; 14 eyes required surgery by 2 mo

Second study: retrospective study of 56 eyes with NVG and average IOP of 40 mm Hg; at 6 mo after injection, IOP decreased to 18 mm Hg; 71% of eyes underwent PRP, and 61% required glaucoma drainage device; significant number of patients had fibrin and anterior chamber heme after ³1 injection of bevacizumab

Proposed new treatment paradigm: consider injection of bevacizumab at time of diagnosis of NVG; administer PRP shortly thereafter if view of posterior pole adequate; provide medications to lower IOP; place drainage device if necessary; benefit of bevacizumab in eyes with closed angle glaucoma still undetermined

New Glaucoma Procedures

Background: use of trabeculectomy has declined and use of aqueous shunts and CPC (including endocyclo proce­dures) has increased

Aqueous shunt surgery: indications  —  previously reserved for patients with difficult glaucoma or patients consid­ered poor candidates for trabeculectomy; drainage devices  —include Molteno, Baerveldt, Krupin, and Ahmed im­plants; reduction of IOP related to surface area of plate; speaker uses Ahmed or Baerveldt devices; failure of cornea  —  may occur because of contact of tube with cornea; as well, eddy currents may contribute to inflamma­tion; to reduce risk, place tubes in sulcus behind iris or pars plana in eyes that have had vitrectomy

Descemet’s stripping endothelial keratoplasty (DSEK): new transplantation technique uses posterior layer of cor­nea (alternative to PK); difficult to maintain apposition of donor tissue to recipient stroma after glaucoma surgery; to reduce risk, keep patients supine for 1 to 1.5 hr after surgery to maintain air tamponade

Case example: 81-yr-old woman had undergone double glaucoma tube placement (to achieve early control of IOP with Ahmed device and long-term control with Baerveldt implant) and experienced corneal failure; patient under­went DSEK and achieved VA of 20/20 at 5 mo

Tube placement: when applying scleral patch graft, small space can remain between front of graft and cornea, creat­ing area vulnerable to erosion; placement at limbus creates more anterior positioning and may cause contact with cornea; speaker uses scleral tunnel technique to reinforce closure and protection of tube; placement of tube more posteriorly avoids erosion near limbus

Tube vs Trabeculectomy (TVT) study: compared safety and efficacy of tube shunt surgery to trabeculectomy with MMC in patients with previous ocular surgery; 2 treatment groups  —  tube group received 350 mm² Baerveldt tub­ing in superotemporal quadrant; trabeculectomy group received superior trabeculectomy and MMC for 4 min; in­clusion criteria  —  patients 18 to 85 yr of age; IOP ³18 mm Hg and £40 mm Hg if on therapy; previous cataract extraction, trabeculectomy, or both; 1-yr results  —  IOPs equivalent (»12 mm Hg); patients with tubes had fewer complications but required more medications; 3-yr results  —  no difference between groups in IOP or number of medications; failures —  inadequate control of IOP primary reason for failure of trabeculectomy or tubes; trabecu­lectomy group had more persistent hypotony, and one eye lost light perception; surgical complications  —  rate of serious complications equivalent

Ex-PRESS mini glaucoma shunt: previously, patients had shunt placed under conjunctival flap; technique recently improved, with shunt placed under scleral flap; eyes more quiet after treatment because iridectomy not needed; po­sition shunt flush to scleral bed; comparison of 76 eyes with Ex-PRESS shunt vs 77 eyes with standard trabeculec­tomy showed group with Ex-PRESS shunt had lower IOP 1 day after surgery (11 vs 16 mm Hg); at 9 mo, both groups had average IOPs of 11 mm Hg; rate of failure (ie, IOP £5 or >21 mm Hg) 14% with Ex-PRESS shunt vs 25% with standard trabeculectomy; only 3 eyes in Ex-PRESS shunt group had IOP £5 vs 11 eyes with trabeculec­tomy; standardization of lumen size may explain better success rate

Canalplasty procedure: unroofs Schlemm’s canal, which can collapse in POAG; provides sustained control of IOP in middle pressure range (15-17 mm Hg), with low rate of complications, minimal postoperative management, and reduced dependence on medication

Questions and Answers

Prevention of cystic and anterior blebs after trabeculectomy: newer techniques (eg, spreading MMC subconjunc­tivally and starting incision at limbus) produce more diffuse blebs

Changes observed using Ex-PRESS shunt: speaker still uses suture lysis aggressively, but sees less need for corti­costeroids; time of exposure to MMC unchanged

Closure of conjunctiva with Ex-PRESS shunt: speaker makes incision 9 mm back from limbus to avoid leaks; uses 9-0 vicryl at limbus, 2 wing closures, and central horizontal mattress suturing

Concentration of MMC: speaker uses 0.4 mg/mL for £5 min, depending on risk factors

Corneal Influences on Glaucoma Management

Ocular Hypertension Treatment Study (OHTS): central corneal thickness (CCT) measured in 912 white and 318 black patients; patients with ocular hypertension had very thick corneas (mean, 573 mm); 24% of patients had CCT >600 mm; black patients had thinner corneas (mean, 555 mm) than white patients (mean, 579 mm); thinner corneas increased risk of developing glaucoma

Correctional algorithms: multiple algorithms for correcting IOP for corneal thickness; differences in cornea biome­chanics across individuals has greater impact on errors in IOP measurement than CCT or curvature; speaker fol­lows patients with CCT <500 mm more closely; he puts patients whose CCT between 501 and 600 mm on routine schedule, and sees patients with CCT >600 mm less frequently

Relationship of CCT to severity of POAG: retrospective study of 350 eyes in 190 patients; patients had mild to moderate POAG with mean defect score of 8 in both eyes; thinner cornea predicted poorer Advanced Glaucoma In­tervention Study (AGIS) score, mean defect, and vertical or horizontal cup-disc ratio

Changes in corneal thickness over time: nonlongitudinal studies found CCT did not change over time in children (5-20 yr of age) or in older patients (16-75 yr of age), at 1 wk after trabeculectomy, or 3 mo after phacoemulsifi­cation; diurnal variation produces thickest CCT in morning, with mean value between 11:00 AM and 2:00 PM

Longitudinal study: followed 39 patients over 8 yr; CCT decreased 2.1 to 2.8 mm/yr (greater decrease in patients with POAG); initial CCTs of 567 mm in right and 574 mm in left eyes decreased by 17 and 23 mm, respectively

Study of 73% of patients from OHTS found CCT decreased 0.74 mm/yr over 3.8 yr: patients taking prostaglandins had significantly more thinning than those taking b-blockers; study of patients taking travoprost found mean de­crease of 7 mm after 6 wk of treatment; changes in CCT not associated with use of topical carbonic anhydrase in­hibitor

Tonometry: Pascal dynamic contour tonometer (DCT) measures pulsatile IOP; study of 16 enucleated cadaver eyes found DCT values 0.58 mm Hg higher than true manometric values; Goldmann applanation tonometer values 4 mm Hg lower; pneumotonometry values 5 mm Hg lower

Ocular response analyzer (ORA): uses bidirectional applanation process to determine corneal hysteresis (measure of viscoelastic properties of cornea); with Goldmann tonometers, measurements static; ocular response analyzer uses air puff and makes dynamic measurements; study of 230 patients found lower corneal hysteresis, not CCT, as­sociated with visual field progression; thinner corneas associated with state of glaucoma damage

Application: speaker uses DCT and ORA measurements to follow patients of concern (eg, those with thin corneas or worsening condition), especially after laser in situ keratomileusis

Suggested Reading

Al Obeidan SA et al: Full preoperative panretinal photocoagulation improves the outcome of trabeculectomy with mitomycin C for neovascular glaucoma. Eur J Ophthalmol 18:758, 2008; Andreoli CM, Miller JW: Antivascular endothelial growth factor ther­apy for ocular neovascular disease. Curr Opin Ophthalmol 18:502, 2007; Chihara E: Assessment of true intraocular pressure: the gap between theory and practical data. Surv Ophthalmol 53:203, 2008; Duch S et al: Intracameral bevacizumab (Avastin) for neo­vascular glaucoma: a pilot study in 6 patients. J Glaucoma 18:140, 2009; ElMallah MK, Asrani SG: New ways to measure intra­ocular pressure. Curr Opin Ophthalmol 19:122, 2008; Filippopoulos T, Rhee DJ: Novel surgical procedures in glaucoma: advances in penetrating glaucoma surgery. Curr Opin Ophthalmol 19:149, 2008; Godfrey DG et al: Canal surgery in adult glauco­mas. Curr Opin Ophthalmol 20:116, 2009; Hayreh SS: Neovascular glaucoma. Prog Retin Eye Res 26:470, 2007; Hendrick AM, Kahook MY: Ex-PRESS mini glaucoma shunt: surgical techniques and review of clinical experience. Expert Rev Med Devices 5:671, 2008; Kotecha A: What biomechanical properties of the cornea are relevant for the clinician? Surv Ophthalmol 52 (Supp l2):109, 2007; Lin SC: Endoscopic and transscleral cyclophotocoagulation for the treatment of refractory glaucoma. J Glaucoma 17:238, 2008; Lynch SS, Cheng CM: Bevacizumab for neovascular ocular diseases. Ann Pharmacother 41:614, 2007; Manni G et al: Intraocular pressure and central corneal thickness. Prog Brain Res 173:25, 2008;Sun L et al: Recovery of corneal hysteresis after reduction of intraocular pressure in chronic primary angle-closure glaucoma. Am J Ophthalmol Mar 25, 2009 [Epub ahead of print]; Takihara Y et al: Trabeculectomy with mitomycin C for neovascular glaucoma: prognostic factors for surgical failure. Am J Ophthalmol Feb 3, 2009 [Epub ahead of print]; Yildirim N et al: A comparative study between diode laser cyclophotocoagulation and the Ahmed glaucoma valve implant in neovascular glaucoma: a long-term follow-up. J Glaucoma 18:192, 2009.