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Normal-tension Glaucoma: Evaluation and Treatment

Mark L. Moster MD

Professor of Neurology

Thomas Jefferson Univ. School of Medicine Neuro-ophthalmology Service

Einstein Medical Center and Wills Eye Institute

Marlene R. Moster MD Professor of Ophthalmology

Thomas Jefferson Univ. School of Medicine Atttending Surgeon - Glaucoma Service

Wills Eye Institute Philadelphia

OBJECTIVES DEFINE NORMAL TENSION GLAUCOMA PATHOPHYSIOLOGY IN COMPARISON TO POAG DEFINE CLINICAL PROBLEMS OF MIMICKERS OF LTG DIFFERENTIAL DIAGNOSIS AND EVALUATION TREATMENT OF LTG Historical background 1857 Von Graefe noted-

“Nerve head excavation without a palpable increase in IOP” NORMAL TENSION GLAUCOMA- how do you define it? Progressive optic neuropathy Significant disc cupping Significant visual field loss Open angle, IOP less than 21 mm Hg No other systemic or ocular disorders TO MAKE THE DIAGNOSIS Optic nerve assessment Retinal nerve fiber layer assessment Computerized visual field Gonioscopy Diurnal pressure curve You should ask: Is there a history of shock, steroids, trauma? Migraine history is helpful Blindness in family? Family history often positive in 20% of cases WHO GETS IT? 6th or 7th decade of life No racial predilection

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Women greater than men Inheritance polygenic or multifactorial Prevalence of Open-Angle Glaucoma in the United States 0.4% <40 Y.O. 1.3% 60-69 Y.O. 4.7% 70-79 Y.O. 11.4% > 80 Y.O. Mean IOP in the white population 15.6% mm Hg with 97% <24 mm Hg Typical presentation Unlike POAG, IOP is not the tip off Damage to the visual field or disc usually occurs before detection by the M.D. Most pts with NTG are diagnosed late in the disease HOW COMMON IS NTG IN THE POPULATION Baltimore Eye Study 1991 - 10,444 eyes 194 cases open angle glaucoma 114 (58.8%) had IOP<21 mm Hg. Sommers 1996 concluded (conservative estimate) 20-30% have IOP<21 mm

Hg. Other investigators- 50% have LTG Is the optic nerve in NTG different? OPTIC NERVE HEAD Can you tell LTG from POAG just by looking at the disc? CAPRIOLI & SPAETH noted Inferotemporal and temporal rims thinner in LTG ARE ACQUIRED PITS OR NOTCHES MORE COMMON IN NORMAL TENSION GLAUCOMA? Javitt et al Odds of an acquired pit in the optic nerve is 16X greater with NTG Acquired pits are more common with NTG

– 74% NTG vs. 15% POAG ACQUIRED PIT OF THE OPTIC NERVE Urgurlu and Caprioli et al, 1997 Pits more common inferiorly than superiorly (76% vs.24% ) 64% of patients with pits progress (follow up 7.9 years) Visual field progression was common in 56% of study group Disc hemorrhage in 40% of study group ARE DISC HEMORRHAGES MORE COMMON WITH NORMAL TENSION GLAUCOMA? Bjerrum described disc hemorrhage first in 1899 Drance 1972 - 20% disc hemorrhages with LTG Kitazowa et al 2001- 30.5% incidence of disc hemorrhages in Japan USA-Disc hemorrhage normal population 0.33%

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DISC HEMORRHAGES Located in the pre-laminar area of the optic disc within the superficial retinal

layer. More common upper & lower poles. More common in the inferotemporal quadrant. OPTIC DISC HEMORRHAGES Healey et al, Ophthalmol 1998;105:216-223 Blue Mountain Eye Study; Australia

– Optic disc hemorrhages are present in • 13.8% of open angle glaucoma patients • 25% of low tension glaucoma patients • 8% of high tension glaucoma patients • 1% of people with a normal optic nerve

– Risk factors for hemorrhage: increased IOP, PSXF, diabetes, increased vertical cup

Drance in 1973 Found that 3 months after a hemorrhage of the optic nerve, a notch occurred

in the same place What else is associated with disc hemorrhage? Localized damage to both the rim and RNFL Where? In the inferotemporal sector more commonly Liou et al, Morphologic characteristics of optic disc with disc hemorrhage in NTG,

AJO 2001, 132:618-625 Peripapillary defects—what are they? They represent the absence of RPE adjacent to the disc Question: is peripapillary atrophy more common in NTG patients? Answer: controversial What about peripapillary atrophy in NTG---is it important? Jonas et al, Arch Ophthalmol, 1992 Peripapillary atrophy enlarges with optic nerve damage Clinical point: that’s why optic nerve photos are so important Peripapillary retinal blood flow in normal-tension glaucoma

Chung, Harris, Kagemann et al, Br J Ophthalmol 1999;83:466-469

NTG is characterized by reduced blood flow in the peripapillary retina, suggesting that blood flow deficits may accompany and contribute to disease development.

Summary of peripapillary defects Peripapillary Defects are Not More Common in Normal-Tension Glaucoma.

However, Enlargement of Atrophic Zones is Suggestive of Continuing Disease What About the Neuroretinal rim Loss in NTG? Jonas et al, AJO1998:125;137-144

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Patients with NTG had thinner neuroretinal rims and more pronounced optic nerve damage than eyes with higher IOP glaucoma (98 eyes with color stereo discs)

Summary of optic disc appearance Cannot differentiate high tension from low tension glaucoma on optic disc

appearance alone BUT Optic nerve pits or notches more common in normal-tension glaucoma Optic disc hemorrhage more common in normal-tension glaucoma and more

common at the inferior and superior poles Are there findings that help identify a normal tension glaucoma disc? Pts with NTG tend to have more focal loss of the rim, more peripapillary

atrophy and more disc hemorrhages. Caprioli, Spaeth, Arch Ophthalmol 1985,103;1145-1149. Buus, Anderson, Ophthalmology 1986, 93;853-857. Kitazawa et al, Ophthalmology 1986, 93853-857. What about the pattern of visual field loss in normal vs. high tension glaucoma? Pattern of Visual Field Defects in Normal-tension glaucoma Cannot differentiate high versus low tension glaucoma based on visual field,

however normal-tension glaucoma visual field defects are – More localized, closer to fixation, denser in superior nasal quadrant – May be more prominent in lower hemifield

Does IOP play a role in visual field loss in NTG? Controversial : Cartwright & Anderson

– There is greater visual field loss in the eye with the highest pressure Orgul and Flammer

– There is no relationship between the eye with a higher IOP and visual field loss in glaucoma

It has been my clinical experience that the eye with the higher IOP tends to have more severe disease.

NTG patients with unilateral field loss are at risk of developing field loss in the eye with an initial normal visual field What are the risk factors to predict visual field loss? Severity of the visual field damage in the contralateral eye at presentation Fontana et al, Br J Ophthalmol 1999;83:1001-1005 Frequency doubling perimetry Frequency doubling technology (FDT) detected abnormalities in POAG cases

more sensitively than in NTG cases Other studies have found FDT equal to or superior to Humphrey visual field in

detecting early defects in NTG

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Is Progression of Visual Fields in Normal-Tension Glaucoma common? Answer: Yes Levene 1980 - 41% of eyes progressed Anderson 1985 - 40% progressed in a 10.5 year period NTG patients with unilateral field loss are at higher risk of developing field loss

in the eyes with an initial normal visual field Does NTG Progress More than HTG? Yes! Glicklich and Spaeth, 1988 5 year follow up, 62% NTG had visual field progression compared to 42% of POAG IOP was lowered 20% either with meds or surg. Is progression of NTG common? 160 patients randomized to no treatment 50% showed confirmed visual fields deterioration by 7 years — but the

change was slow What is the Relationship between Corneal Thickness and Curvature in NTG? Morad et al, AJO 1998:125;164-168 Corneal thickness is significantly reduced in NTG compared with POAG

(p=.002) and normals This may lead to underestimation of IOP and misdiagnosis in some pts. The Ocular Hypertensive Treatment Study Patients who developed POAG

– Mean corneal thickness 553 +/- 38 microns

Patients who did not develop POAG – Mean corneal thickness 574 +/- 37 microns

What are other associated findings in Normal-tension glaucoma? Phelps and Corbett (1985) found: 48% of NTG patients had migraine Other investigators: (2001) found: 24% of patients with NTG had migraine What are other risk factors for progression? Myopes have a higher chance of progressing within 10 years with early

cecocentral defects and a distinct chance of visual acuity loss The association between myopia and NTG was strong Vasospasm as a risk factor-what is the relationship?

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NTG patients appear to have a higher prevalence of vasospastic disorders, a

higher prevalence of acute vascular collapse, and greater blood pressure drops during a 24-hour period.

Gasser and Drance found that vasospasm made NTG worse Abnormal capillary response to cold in the digital circulation (hands) One hand of a patient placed in cold water, the visual field was repeated---the

visual field got worse Higher incidence of Raynaud’s disease in this population OTHER RISK FACTORS Migraine Raynaud’s disease Prinzmetal’s angina Sleep apnea High resistance wind instruments WEIGHTS PATHOGENESIS: ISCHEMIC THEORY Elevated IOP causes the ischemia Ischemia causes retinal ganglion cell death by neurotrophic deprivation Poor optic nerve perfusion initiates the cascade that ends in cell death Pathogenesis: Mechanical theory Increased IOP distorts the lamina cribrosa Get compression of the axons This interferes and disrupts axoplasmic flow This may lead to cell death What predisposes to this? Abnormal lamina cribrosa, structural

factors, abnormal connective tissue bundles?

Hypoperfusion theory Either: Postural hypotension Nocturnal hypotension with optic nerve hypoperfusion Sleep apnea contributing to optic nerve hypoperfusion Increased resistance to blood flow in the ophthalmic and retinal arteries Hypoperfusion theory The optic nerve has inadequate perfusion pressure and the optic nerve blood

flow is compromised You get ischemia to the optic nerve even at normal IOP Poor auto-regulation?

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Role of systemic hypotension 24 hour ambulatory monitoring There is a greater nocturnal decrease and lower level of diastolic blood

pressure in the NTG patients Those pts on anti-hypertensives who had greater systolic dips in BP, tended

to have more deterioration of visual fields Greater nocturnal fluctuation with BP dips may disturb the microcirculation.

This may damage the optic nerve resulting in increasing visual field loss in NTG.

Theory of APOPTOSIS Ischemia causing a chain of events leading to programmed cell death. Can there be an immune basis for NTG?

Wax et al, AJO 1998, 125:145-157 9 of 10 patients with NTG studied No other signs of connective tissues. Positive elevated serum immunoreactivity bacterial heat shock protein 60 Confirmed by Kitazawa, 2001 IS THERE A GENETIC BASIS FOR NTG? OPA 1 GENE GENOTYPE IVS+4 C/T;32T/C May be strongly associated with NTG Neuro-ophthalmogic ddx: objective

To prevent erroneous diagnosis of glaucoma in patients with neuro-ophthalmologic disorders requiring other treatments

Why consider neuro-ophthalmic disease? Iop is normal Visual field defects may be identical Cupping occurs in optic neuropathies Nonglaucomatous optic atrophy 20% of optic atrophy eyes have cupping 6% have typical glaucomatous cupping

– Trobe, arch ophth, 1980 Non-glaucomatous cupping Congenital Hereditary optic neuropathy Inflammatory optic neuropathy Compressive optic neuropathy Ischemic optic neuropathy

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Toxic optic neuropathy Radiation optic neuropathy Degenerative disease Cupping: glaucoma vs. Nonglaucoma

Slides reviewed by 2 glaucoma specialists and 1 neuro-ophthalmologist 44% of nonglaucoma misdiagnosed by at least 1 examiner

– Trobe, arch ophth, 1980 Glaucoma vs. Nonglaucoma Rim pallor 94% specific for nonglaucoma Focal or diffuse rim obliteration 87% specific for glaucoma Rim thinning only 47% specific for glaucoma Is it glaucoma? Red flags Atypical history Atypical exam Atypical optic disc Atypical visual field 29 yo man Followed as unilateral glaucoma History of pain o.d. With progressive visual loss over days Stable for 8 months Mri normal Neuro-ophthalmic exam Va: 20/200 o.d., 20/20 o.s. Color: 1/13 o.d., 13/13 o.s. Pupils: 3+ apd o.d. Iop: 8 mm hg o.d., 10 mm hg o.s. Evaluation Cxr: hilar adenopathy Ace level: 100 Bronchoscopy: non- caseating granulomas Treatment Pulsed solumedrol Oral prednisone taper No improvement 38 y o woman Followed as glaucoma suspect because of cupping

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Multiple sclerosis diagnosed for 3 years Recurrent optic neuritis o.u. Iop always in teens Neuro-ophthalmic exam Va 20/30 o.d., 20/200 o.s. Color: 3/13 o.d., 0/13 o.s Pupils: 2 + rl o.d., 1+ o.s., 2+ apd o.s. Vf: central scotoma o.s., superotemporal defect o.d. (junctional pattern) fundi Inflammatory optic neuropathy Optic neuritis Sarcoidosis Syphilis Optic neuritis: typical presentation Sudden painful visual loss Young adult Va, color, field loss, apd normal or swollen disc Eventual optic pallor Rarely cupping 75 yo woman with possible glaucoma

Abrupt visual loss o.u. 2 years ago Va 20/200 o.u. Color: 0/13 ishihara Pupils 1+ reactive o.u. Vf: central and inf. Altitudinal defects o.u. Iop never above 20 mm hg Cupping + pallor Past medical history Polymyalgia rheumatica Headache Biopsy (+) for giant cell arteritis Stable on prednisone 5 mg/d Cupping in nonarteritic aion Hayreh, 1974: 2/14 Quigley, 1977: 6/61

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Radius, 1979: 1/25 (large contralateral cup) Danesh-meyer et al, 2001: 2% cupping in arteritic aion Hayreh, 1974: 11/11 Quigley, 1977: 5 ( 2 with elevated iop, 3 large cup in fellow eye) Sebag, 1986: 5 with (-) glaucoma evaluation Danesh-meyer et al, 2001: 92% Anterior ischemic optic neuropathy: typical presentation Painless, sudden visual loss Older adult Decreased acuity, color, vf, apd Swollen optic disc Eventual pallor, cupping in gca Ischemic Aion - giant cell arteritis Aion - non-arteritic Shock induced ntg Central retinal artery occlusion 70 yo woman with ltg Neuro-ophth referral for headache Iop always <19 mm hg Past medical history Diabetes Coronary artery disease S/p cabg and carotid endarterectomies Medications

– Insulin, mevacor, zantac, betagan, pilocarpine , neptazane Neuro-ophthalmic exam Va: 20/20 o.u. Color: 7/7 ishihara o.u. Pupils: miotic from pilocarpine Vf: temporal > nasal loss fundus Treatment Stereotactic radiosurgery Stable for 1 year

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Died from cardiac disease Compressive lesions 16/250 patients with structural lesions

– 8 pituitary adenoma – 5 meningioma – 2 chiasmal glioma – 1 aneurysm

– Kupersmith, ann ophthalmol, 1984 Compressive lesions 5/16 misdiagnosed as glaucoma All 16 with normal iop 1/7 with borderline outflow on tonography C/d for color > c/d for contour

– Kupersmith, ann ophthalmol, 1984 Cupping in compression Retrospective masked review C/d 0.37 compared with o.10 in controls Intereye difference 0.13 vs. O.04 in controls – showing it was acquired

• Bianchi-marzoli s et al, ophthalmol 1995 Ntg and neuroimaging Studied pts. With ntg who had neuroimaging over a 10 yr period Control group of those with intracranial masses, with c/d at least o.4 31 pts. 2 excluded, 1 with homonymous hemianopsia, 1 with 6th nerve paresis

– Greenfield ds et al: ophthalmology, 1998 Ntg and neuroimaging No ntg pts. Had a related tumor 2 ntg pts. Had clinically silent tumors unrelated to vf defect (6.9%)

– Greenfield ds et al: ophthalmology, 1998 Ntg eyes Better va Vertical cup elongation Splinter hemorrhages Peripapillary atrophy Vf defects that were nerve fiber bundle or bordering horizontal meridian

• Greenfield ds et al: ophthalmology, 1998 Specific for glaucoma Splinter disc hemorhage 100%

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Family hx of glaucoma 96% Nerve fiber bundle vf defect 84% Vertical loss of neuroretinal rim 77% Specific for nonglaucomatous Neuroretinal rim pallor 90% Vf defect bordering vertical meridian 81% Visual acuity < 20/40 77% Age < 5o years 93%

– Greenfield ds et al: ophthalmology, 1998 Compressive lesions: typical presentation Progressive visual loss Nerve, chiasmal, or homonymous vf loss Headache, diplopia or other symptoms Disc normal, swollen or pale, occasional cupping Hereditary optic neuropathy Leber’s optic neuropathy Familial optic neuropathy (mendelian) Dominant optic atrophy

• focal temporal triangular cupping • Kline lb, glaser js, arch ophthalmol, 1979

Leber’s hereditary optic neuropathy 0.7 - 0.9 c/d in 7 patients after visual loss

– Ortiz, ajo, 1992 Lhon mutation in ntg Screened 54 ntg patients for lhon mtdna mutations at nucleotides 3460, 11778

and 14484 None had lhon mutations

• Opial d et al, graefes arch…., 2001 Congenital cupping Colloboma Optic pit Myopia Physiologic cupping Physiologic cupping Large discs

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Normal rim area Horizontal cup > vertical cup

– Jonas, ajo, 1989 Toxic optic neuropathy

Methanol – Stelmach, aust-n-z-ophth, 1992

Is glaucoma more common in alzheimer’s disease? 112 pts. With probable ad Found vf defects or cupping in 29 (26%) Ocular hypertension was not seen Propose that on less resistant than normal in ad

• Bayer au et al, eur neurology, 2002 Degenerative Perhaps cupping and vf are an optic neuropathy from ad and not glaucoma

– Tsai, arch ophth, 1991 Thyroid disease 6/25 ntg patients had thyroid disease Thyroid group more hyperopic Postulate risk factor for glaucoma or optic neuropathy mimicking ntg

• Jamsen, acta ophth scand, 1996 6.5% prevalence of ntg in japanese pts. With graves (2.0% expected)

• Ohtsuka, ajo, 2000 0/100 hypothyroid pts. Had findings of glaucoma

• Karadimas et al, ajo, 2001 Is it glaucoma? Red flags Atypical history Atypical exam Atypical optic disc Atypical visual field History favoring neurologic Abrupt visual loss Rapid progression Headache, ocular pain Ocular motility defects Neurologic symptoms/signs Visual acuity: glaucoma vs. Neurologic Poor va compared to c/d in neurologic

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Good va compared to c/d in glaucoma Visual field favoring neurologic Central or cecocentral loss Hemianopic field loss Inferior altitudinal defect Disc features: glaucoma vs. Neurologic • Pallor of preserved rim is neurologic Obliteration of rim is usually glaucoma Cupping is a late finding in neurologic Retinal arteriolar narrowing in vascular or trauma Whom to work up? Young age Decreased acuity Asymmetry of color or apd Neuro symptoms Neuro field defects Rim pallor Atypical course of progression Evaluation of ntg directed by individual situation Cat scan or mri scan Serologic evaluation Chest x-ray Csf examination Evaluation of ntg: neuroimaging Mri preferred, especially for chiasm Cat scan is a good second choice Crucial to obtain appropriately focused study Evaluation of ntg: serologic tests Cbc, b12 Ana, esr Ace level Rpr, fta, lyme Mitochondrial dna studies ? Thyroid function tests

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Cxr Rule out sarcoidosis Lumbar Puncture Rule out meningeal process

– Inflammatory – Neoplastic – Infectious

How do we treat NTG? What are the guidelines? Collaborative Normal-Tension Glaucoma Study Group AJO 1998;126-487-492 Answer the following questions

– To what extent is IOP involved in the mechanism of nerve damage? – Should we be aggressively lowering the IOP in NTG?

The Collaborative Glaucoma Study Followed patients until progression Randomized to treatment or no treatment If treatment, the end point was a 30% drop in IOP The Collaborative Glaucoma Study Results

– 140 eyes of 140 patients – 61 treated (meds, ALT, surgery) – 79 controls (no treatment)

RESULTS 8-Year Follow UP 35% of untreated eyes progressed by VF criteria and disc progression 12% of treated eyes progressed This demonstrates that IOP is part of the pathogenesis of NTG Collaborative Low Tension Glaucoma Study 14% developed cataracts in the untreated group 38% developed cataracts in the treated groups. (Higher in those after filtering

surgery) Low IOP Slows or Halts Vision Loss in Normal-Tension Glaucoma How Do We Treat NTG?

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The study showed unequivocally that once an IOP reduction of 30% was achieved, there was a slower rate of progression of visual field defects than in untreated eyes AND

30% IOP reduction was achieved with meds, laser or both in 50% of the patients

Stephen Drance, Can J Ophthalmol; Vol 34 No 1, 1999. TREATMENT OPTIONS New commitment: lower the IOP 30% but how??? Current Medical Treatment to Lower Intraocular Pressure Listed in order of US prescription volume†: • Prostaglandin derivatives • β-Adrenergic antagonists (β -blockers) • Adrenergic agonists (sympathomimetics) • Carbonic anhydrase inhibitors • Cholinergic agonists (miotics) Pathways to Lower Intraocular Pressure Current strategies: Start with a prostaglandin or beta blocker Switch before adding, keeping number of drops to a minimum to improve

compliance Alpha agonist or topical CAI consider next Keep adding and subtracting until the drops are efficacious and tolerated What happened to neuroprotection? Betoptic S- calcium channel blocker Alphagan – up regulates growth factors and secondary neuroprotection to cells

at risk Prostaglandins- may be neuroprotective by just lowering the IOP 30% What Drugs Effect Optic Nerve Blood Flow? Beta blockers- (nonspecific) have no effect Betaxolol -decreases resistance to flow Latanoprost - improves ocular perfusion Brimonidine - no effect on flow Dorzolamide - accelerates inferotemporal retinal dye transit with increased

pulsatile blood flow Carteolol-with sympathomimetic activity may decrease vascular resistance in

NTG What is available systemically? Memantine

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NMDA antagonist that blocks glutamate and should block the apoptotic event Multicenter 5 year study Patients get the drug or placebo, same glaucoma meds Outcome measures: visual field and optic nerve change. This drug does not

lower IOP What else can you use systemically? Calcium channel blockers Do we have the correct one?

– Nimodipine? – Brovincamine? – Nilvadipine? – Verapamil? Commonly used in Japan, not in the USA

Oral calcium channel blocker stabilize the visual fields in NTG Pts on 2mg nilvadipine with laser-Doppler flowmetry, showed decreased vascular resistance in 12 pts. avg

57 yo Gifu Univ. Japan How do calcium channel blockers work? Calcium channel blockers relax the blood vessel walls thereby decreasing

vascular resistance Blood Flow = Blood Pressure – IOP

Vascular Resistance Why Not Use Calcium Channel Blockers in Everyone? Routine use of Nifedipine or any other Calcium channel blocker has not been

shown to provide uniform improvement in visual function or retrobulbar hemodynamic response in this country

Routine use of Nifedipine or Cardiazem for NTG is not advantageous LASER OPTIONS FOR NTG Laser trabeculoplasty for treatment of NTG

Argon Nd:YAG (SLT) 50 micron 400 micron 0.1 second 3 nanosecond 514 nm wavelength 532 nm 1 argon “application” carries 6,000 times the energy of one SLT “shot”

Why consider a laser?

Good results for the majority of patients

80% of patients will experience a 20% drop in IOP

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50% of patients will experience a sustained IOP drop for the next 5 years

The rate of decay of failure is 10% per year OTHER OPTIONS THAT HAVE BEEN TRIED Optic nerve sheath decompression but with poor results Carbon dioxide rebreathing - causes vasodilation CO2 inhalation may predict who will do well with certain Ca# channel blockers.

– Niwa et al J Glaucoma, Vol 9, No3, 2000 DOES EARLY SURGERY HELP NTG PROGRESSION? Hitchings et al, 1995 and 1998 suggests early surgery for progressive disease Early surgery appears to slow or halt visual field loss in patients with

progressive NTG compared with controls Glaucoma surgery with or without adjunctive antiproliferatives in NTG Membrey et al, BJO 2001, June;85(6):696-701

– Reduction of IOP 20-30% slows progression – Patients followed by progressor VF analysis – Conclusion: MMC is associated with greater risk of VF progression despite

a greater fall in IOP – Explanation: late postoperative complications with MMC compared with 5-

FU

TREATMENT OF NTG SHOULD INCLUDE: Insure IOP is normal over 24 hours, if not- treat Rule out other causes of treatable optic neuropathy Frequent visual fields to show progression and if so, be more aggressive HRT or GDX to follow the nerve fiber layer Rule out hypotension at night, hyperviscosity Lower the pressure 30% Consider antimetabolites TREATMENT OPTIONS Aggressive topical therapy Argon or Selective laser trabeculoplasty Calcium channel blockers for selective use only C-Pap for sleep apnea Kremer et al, Klin Monatobl Aug 2001 Watch for dips in B.P. at night by alerting the internist about over zealous anti-

hypertensive Rx Aggressive filtration surgery

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References

1. Clinical efficacy of topical nipradilol and timolol on visual field performance in normal-tension glaucoma: a multicenter, randomized, double-masked comparative study.Araie M, Shirato S, Yamazaki Y, Kitazawa Y, Ohashi Y; the Nipradilol-Timolol Study Group. Jpn J Ophthalmol. 2008 Jul;52(4):255-264

2. Ocular pulse amplitude in normal tension and primary open angle glaucoma. Stalmans I, Harris A, Vanbellinghen V, Zeyen T, Siesky B. J Glaucoma. 2008 Aug;17(5):403-7.

3. Twenty-four-hour intraocular pressure and blood pressure levels with bimatoprost versus latanoprost in patients with normal-tension glaucoma. Quaranta L, Pizzolante T, Riva I, Haidich AB, Konstas AG, Stewart WC. Br J Ophthalmol. 2008 Sep;92(9):1227-31

4. Corneal biomechanical properties in primary open angle glaucoma and normal tension glaucoma.Ang GS, Bochmann F, Townend J, Azuara-Blanco A. J Glaucoma. 2008 Jun-Jul;17(4):259-62.

5. The effect of travoprost on daytime intraocular pressure in normal tension glaucoma: a randomised controlled trial.Ang GS, Kersey JP, Shepstone L, Broadway DC. Br J Ophthalmol. 2008 Aug;92(8):1129-33

6. Comparison of ocular hypotensive effect and safety of brinzolamide and timolol added to latanoprost. Miura K, Ito K, Okawa C, Sugimoto K, Matsunaga K, Uji Y. J Glaucoma. 2008 Apr-May;17(3):233-7.

7. Prolonged retinal arteriovenous passage time is correlated to ocular perfusion pressure in normal tension glaucoma. Plange N, Kaup M, Remky A, Arend KO. : Graefes Arch Clin Exp Ophthalmol. 2008 Aug;246(8):1147-52

8. Reduced choroidal blood flow can induce visual field defect in open angle glaucoma patients without intraocular pressure elevation following encircling scleral buckling. Sato EA, Shinoda K, Inoue M, Ohtake Y, Kimura I. Retina. 2008 Mar;28 (3):493-7.

9. Normal-tension glaucoma: is it different from primary open-angle glaucoma? Shields MB, Curr Opin Ophthalmol. 2008 Mar;19(2):85-8 10. Glaucoma is associated with peripheral vascular endothelial dysfunction.

Su WW, Cheng ST, Ho WJ, Tsay PK, Wu SC, Chang SH. Ophthalmology. 2008 Jul;115(7):1173-1178.

11.Prevalence of normal tension glaucoma in obstructive sleep apnea syndrome patients.Sergi M, Salerno DE, Rizzi M, Blini M, Andreoli A, Messenio D, Pecis M, Bertoni G. J Glaucoma. 2007 Jan;16(1):42-6.

References for the Neuro-Ophthalmologic DDX of Glaucoma 1. Trobe, J.D., J.S. Glaser, and J.C. Cassady, Optic atrophy. Differential diagnosis by fundus observation alone. Arch Ophthalmol, 1980. 98(6): p. 1040-5 2. Trobe, J.D., et al., Nonglaucomatous excavation of the optic disc. Arch Ophthalmol, 1980. 98(6): p. 1046-50.

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