Glaucoma Pearls

Educational Objectives

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

1.   Describe the prevalence of diagnosed and undiagnosed glaucoma and recognize the role of intraocular pressure in the diagnosis of glaucoma.

2.   Recognize the causes and risks of overdiagnosis of glaucoma and estimate the risk for progression of glaucoma in individuals.

3.   Choose effective strategies to manage open angle glaucoma.

4. Summarize the disease process, mechanism, and treatment of angle closure in acute angle glaucoma.

5.   Evaluate and choose the appropriate strategy for patients with normal tension 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. Singh reported con­sulting agreements with Alcon, Allergan, Pfizer, Novartis Pharmaceuticals, Santen Pharmaceutical, and Bausch and Lomb. Drs. Quigley, Tanaka, and Flach, and the planning committee reported nothing to disclose.

Acknowledgements

Lectures by Drs. Quigley and Flach were recorded at Ophthalmology 2008, held December 12–13, 2008, in San Francisco, CA, and presented by the Department of Ophthalmology, University of California, San Francisco, Beckman Vision Center. Drs. Tanaka and Singh were recorded at Glaucoma Update 2009, held February 7, 2009, in San Francisco, and presented by Glaucoma Research and Education Group. The Audio-Digest Foundation thanks the speakers and the sponsors for their cooperation in the production of this program.

What I Used to Do Wrong in the Management of Glaucoma

Harry A. Quigley, MD, Professor of Ophthalmology, Johns Hopkins University School of Medicine, Wilmer Eye Institute, Baltimore, MD

Intraocular pressure (IOP): 50% of patients with open angle glaucoma (OAG) rarely have IOP >21 mm Hg; true risk factor not elevated IOP, but level of pressure in patient who shows glaucomatous optic neuropathy; obtain baseline IOP, then set target IOP for individual; low tension glaucoma —speaker posits that it does not exist; pa­tients cannot be separated according to single IOP value

Case example: 38-yr-old woman had pallor of rim of disc (especially left eye); right-eye visual field test (VFT) showed upper altitudinal defect; 20/40 vision declined centrally in left eye; symptoms did not fit diagnosis of glaucoma; patient had aneurysm

Prevalence: 50% of patients with OAG in San Francisco undiagnosed because suspicious discs go unrecognized and insufficient VFTs performed

Screening: no adequate screening tests for OAG; identify family members of existing glaucoma patients; one in 8 pa­tients with OAG has one living relative with undiagnosed OAG; speaker’s study showed 30% of family members of patients with OAG were not told they should have examination for OAG, 20% of patients did not know OAG runs in families, and 50% who had eye examination within past year had not had VFT

Overdiagnosis: patients with central corneal thickness may have higher than normal IOP that is not pathologic

Risks: eye drop treatment causes cataracts; b-blockers raise cholesterol; carbonic anhydrase inhibitors likely asso­ciated with kidney stones; a-agonists lead to depressed mental state; eye drops increase risk for falls

Causes: wide variance of diameters of optic discs; important to measure disc by Heidelberg retinal tomography (HRT) or slit lamp; people of African ancestry tend to have large discs and cup/disc ratios; false-positive imaging or VFT (results do not fit clinical picture)

Risk for field defect: for average ocular hypertensive patient, risk 2% per year; eg, white man, 65 yr of age, with cup of 0.6, normal field, IOP of 26 mm Hg, and no other risk factors, who lives additional 17 yr, has 33% chance of having field defect during lifetime

Age: older age represents risk factor, but important to treat younger patients because they have greater lifetime risk

Ethnicity: black patients at 3- to 4-times higher risk

Treatment: establish baseline IOP  —  important to test patients’ IOP 3 times before starting therapy; set target  —  IOP should decrease 20% and fall below 24 mm Hg; set lower target for patients with more damage

Adherence: <50% of patients continue to use eye drops at end of 1 yr of treatment; 60% of patients take prostaglan­dins after 3 yr; adherence worse with b blockers and other agents; recommended that patients apply drops while in horizontal position (more efficient); 95% of patients claim to take 100% of drops, but study showed only 70% of drops taken when monitored

Strategy: 10% to 15% of patients with OAG have severe bilateral functional impairment in lifetime, with or without treatment; study showed patients under treatment with most advanced OAG lost only 3 decibels (dB) in 8 yr; most patients with OAG do well, but some have greater than average visual field (VF) loss per year; frequent VFT best way to identify these patients (2-3 tests in first year), then every 6 mo or 1 yr; if patient’s VFT remains stable over 2 to 3 yr, patient likely to remain in group that loses only 0.1 dB/yr; if VFT or imaging deteriorates, or disc hemor­rhage occurs, patient possibly among 15% who worsen; see patient frequently and lower target pressure

Quality of life: OAG affects ability to read, drive, and enjoy life; patients with OAG 3 times more likely to discon­tinue driving

Progression: important to monitor progression by imaging and VFT; optical coherence tomography (OCT) not back­wards compatible; HRT overly sensitive measure of progression; increase frequency of monitoring before acting on apparent progression; deterioration in VFT apparent over 4 to 6 tests; glaucoma progression analysis (GPA) of VFT does not indicate improved points, only those that worsen; therefore, GPA also overly sensitive

Future advances: systems that merge structure and function (eg, match images with results from VFT)

Asian Angle Closure Glaucoma

H. George Tanaka, MD, Clinical Instructor, California Pacific Medical Center, San Francisco, CA

Epidemiology: OAG more common in Western populations; angle closure glaucoma (ACG) more common in Asian populations; ACG major cause of blindness worldwide; causes »50% of blindness from glaucoma (even though only »25% of 60 million people with glaucoma worldwide have ACG); 90% of people in China with blindness due to glaucoma have ACG; ACG causes 10 times more blindness than OAG

Diagnosis: defined as physical contact between iris and trabecular meshwork (TM; ie, iridotrabecular contact [ITC])

Categories: primary angle closure suspect (PACS)  —patients have 270° of ITC on gonioscopy and no peripheral anterior synechiae; discs, IOPs, and VF normal; PAC  —  patients have 270° of ITC and trabecular dysfunction, ei­ther structural (ie, peripheral anterior synechiae) or functional (ie, elevated IOP); discs and VF normal; PAC glaucoma (PACG)  —  patients have 270° of ITC plus typical glaucomatous cupping, change in VF, and optic neu­ropathy

Disease process: anatomically predisposed patients develop reversible ITC; further development of trabecular dys­function causes elevation of IOP; disease progresses to permanent synechial closure of angle and blocked TM, op­tic neuropathy, and VF loss

Mechanisms of angle closure: anatomic  —  aqueous, lens, iris, ciliary body, and choroid located behind angle; multi­ple mechanisms can occur in single patient

Aqueous: pupillary block  —  normal flow from posterior to anterior chamber; impediment occurs at lens-iris chan­nel, leading to build-up of pressure in posterior chamber and pressure differential across iris; this causes iris to bow forward and block angle; treatment  —  laser iridotomy to create opening in iris with yttrium aluminum garnet (YAG) or argon laser to equalize pressure

Lens: phacomorphic angle closure  —  rarely occurs in isolation; characterized by shallow anterior chamber because lens pushes angle closed from behind

Iris: bulky peripheral iris or prominent iris roll (seen in many Asian individuals) contributes to angle closure and makes iridotomy more difficult

Ciliary body: anteriorly displaced ciliary processes push iris forward (ie, plateau iris); in patients with plateau iris, angle opens during illumination but closes again in dark; pilocarpine one of treatments used

Choroid: many patients with angle closure attacks have choroidal effusions; choroidal expansion causes vitreous to move forward, moving entire lens-iris diaphragm forward and compromising depth of anterior chamber

Timing of intervention: no risk profiles available for individuals with narrow angles; however, studies do provide data on relative risk for populations; 22% of patients with PACS develop PAC after 5 yr, and 28% of these develop PACG; if only those patients with PAC treated with iridotomy, number needed to treat drops to »4

Acute angle closure: paracentesis  —  as initial treatment (ie, using needle to decompress anterior chamber), provides immediate decrease in IOP, rapid pain relief, and clearing of corneal edema; allows subsequent iridotomy; risks in­clude damage to lens

Alternative treatments: many treated Asian patients go on to develop PACG (nerve damage), require surgery, de­velop cataracts, and finally have posterior chamber intraocular lens and filtering bleb; studies in Asia compared la­ser iridotomy to early phacoemulsification and intraocular lens implant; preliminary results showed group with early phacoemulsification had wider angles, lower IOP, and used fewer medications

Normal Tension Glaucoma: A Different Disease?

Kuldev Singh, MD, MPH, Professor, Department of Ophthalmology, Stanford University School of Medicine, Palo Alto, CA

Limitations in measurement of IOP: study showed that »50% of patients with glaucoma had IOP <21 mm Hg; an­other study showed that Japanese population had mean IOP of 13 mm Hg (rather than 16 mm Hg) and 18 mm Hg upper limit of normal; measurement of IOP affected by central corneal thickness and elasticity; IOP cannot be mea­sured continuously

Collaborative Normal Tension Glaucoma Study: investigated whether IOP-lowering therapy appropriate for pa­tients with normal tension glaucoma (NTG) in 145 patients; enrollment criteria included loss of VF, disc hemor­rhage, VF defect that threatened fixation, and median IOP value of £20 mm Hg over 10 measurements with £1 IOP reading >24 mm Hg; patients randomized to either observation or medication, laser therapy, and surgery to produce 30% lowering of IOP; found 3-times higher rate of progression in untreated patients

Caveats: IOP lowered by 30% in >50% of patients without glaucoma filtration surgery; »50% of eyes with no pre­vious history of progression did not progress when left untreated for 7 yr; surgical therapy associated with in­creased risk for cataracts

Risk factors for progression: included disc hemorrhage, migraine headaches, female sex, and non-Asian ethnicity; OAG increasing in urban Chinese populations because of increasing myopia

Treatment: no consensus that NTG represents different disease from primary OAG; treatment decisions made on ba­sis of benefit vs risk at each step; as patient advances in treatment algorithm, marginal lowering of IOP per mm Hg decreases and risk increases; in treating NTG, safer first-line therapies do not achieve desired reductions in IOP be­cause of lower initial pressures; consequently, surgery needed more often (although study showed »50% of patients do not progress); speaker more often advocates following (rather than treating) patients with signs of early OAG but normal IOP, as compared to patients with higher IOP; also appropriate to look for nonglaucomatous causes of abnormality (eg, with neural imaging), depending on clinical picture; glaucoma filtration surgery needed more fre­quently in patients with IOP in normal range; NTG not fundamentally different from OAG, but management of OAG patient with low or normal IOP uniquely challenging

Eyelid Closure for the Treatment of Glaucoma

Allan J. Flach, MD, PharmD, Professor, Department of Ophthalmology, University of California, San Fran­cisco, Beckman Vision Center

Background: study showed 5 min of nasolacrimal occlusion (NLO) decreased systemic absorption of timolol by £65% and increased intraocular penetration of fluorescein by »70%; if more viscous solution used, contact time increases by 300% or 350% for ointment or gel; eyelid closure clinically important, but no trials include eyelid closure in protocol; touching eye involves risk for injury, but eyelid closure does not increase risk

Compliance argument: asking patients to take time to close eyelids for 5 min might reduce compliance; studies de­signed to mimic the way patients actually take medication

Factors influencing compliance: today’s patients better informed than those 20 yr ago; pilocarpine studies using eye drop monitor (which showed poor compliance) and study of compliance using timolol, did not educate or en­courage patients to adhere to regimen

Recent study: reports of 96% rate of adherence to once-daily dosing, even with 2-drug therapy

Benefits of using eyelid closure (results of clinical trials): potentially reduces adverse effects; improves consistency of drug instillation; increases clinical applicability of data; improves therapeutic index (defined as ratio of toxic dose to effective dose) by minimizing variability of systemic and intraocular absorption; studies become more re­producible

Suggested Reading

Alm A et al: Side effects associated with prostaglandin analog therapy. Surv Ophthalmol 53 (Suppl 1):S93, 2008; Ang LP: Current understanding of the treatment and outcome of acute primary angle-closure glaucoma: an Asian perspective. Ann Acad Med Singapore 37:210, 2008; Casson RJ: Anterior chamber depth and primary angle-closure glaucoma: an evolutionary perspective. Clin Experiment Ophthalmol 36:70, 2008; Cedrone C et al: Epidemiology of primary glaucoma: prevalence, incidence, and blinding effects. Prog Brain Res 173:3, 2008; Chang RT, Budenz DL: Diagnosing glaucoma progression. Int Ophthalmol Clin 48:13, 2008; Coleman AL, Miglior S: Risk factors for glau­coma onset and progression. Surv Ophthalmol 53 (Suppl 1):S3, 2008; Drance SM: What can we learn from the disc appearance about the risk factors in glaucoma? Can J Ophthalmol 43:322, 2008; Garway-Heath DF: Early diagno­sis in glaucoma. Prog Brain Res 173:47, 2008; Geringer CC, Imami NR: Medical management of glaucoma. Int Ophthalmol Clin 48:47, 2008; Ikeda H et al: Clinical significance of topical instillation technique in Japanese glau­coma patients. Pharmazie 63:81, 2008; Manni G et al: Intraocular pressure and corneal thickness. Prog Brain Res 173:25, 2008; Mowatt G et al: Screening tests for detecting open-angle glaucoma: systematic review and meta-anal­ysis. Invest Ophthalmol Vis Sci 49:5373, 2008; Schwartx GF, Quigley HA: Adherence and persistence with glau­coma therapy. Surv Ophthalmol 53 (Suppl 1):S57, 2008; Sharma P et al: Diagnostic tools for glaucoma detection and management. Surv Ophthalmol 53 (Suppl 1):S17, 2008; Shields MB: Normal-tension glaucoma: is it different from primary open-angle glaucoma? Curr Opin Ophthalmol 19:85, 2008; Singh K, Shrivastava A: Early aggressive intraocular pressure lowering, target intraocular pressure, and a novel concept for glaucoma care. Surv Ophthalmol 53 (Suppl 1):S33, 2008;  Townsend KA et al: Imaging of the retinal nerve fibre layer for glaucoma. Br J Ophthalmol 93:139, 2009; Vetrugno M et al: Primary open angle glaucoma: an overview on medical therapy. Prog Brain Res 173:181, 2008.