NORMAL TENSION GLAUCOMA – a diagnosis of exclusion

GEORGE T. BANYAS, OD, FAAO

POAG can be easy

High pressures Rim defects, typically Pre- perimetric defects Classic field defects Typically no ocular or systemic

history Family history Race

But what about NTG?

Low pressures Normal anatomy Often good discs since slowly

progressive Masquerade syndrome? No symptoms until late in disease

Is it really glaucoma?

Open angle glaucoma is more common in

Africans Elderly High myopes/ large disc Elevated IOP Positive family history Low systolic BP with reduced

perfusion Thinner central corneas Autonomic dysregulation

NTG by definition

Untreated IOP typically < 21mm Open , non-pigmented filtration

angles Acquired progressive

“glaucomatous” injury Progressive “glaucomatous” field

loss Females, autonomic dysregulation A different type of optic neuropathy?

NTG facts

1/3 of glaucoma patients possess NTG

1/3 of NTG patients have unilateral cupping

Progression is slow. No hasty decisions!

Chairside presentation will always include IOP 21 or less

Systemic disorders not required Systemic disease may be the cause

Rule out pale discs

Juvenile optic atrophy Simple congenital optic atrophy Recessive optic atrophy Leber’s disease (through age 80)

Rule our past NTG imposters

Burned out pigmentary glaucoma Past history of steroid use Severe blood loss/cardiac surgery Post –traumatic optic neuropathy Old BAO Systemic beta blocker use Past subdural hematoma

Past NTG imposters

Old ION Posterior ciliary infarct Intrasellar tumor Syphilitic optic neuritis RBON

Present NTG imposters

Subacute angle closure Nocturnal hypotension Systemic beta blocker use Toxic optic neuropathy Compression ( pituitary adenoma,

meningioma) Sleep apnea (low O2 partial

pressure) Diurnal or nocturnal IOP swings

Present NTG imposters

Pachymetry under 550 um Pigment dispersion or

pseudoexfoliation Compression by ICA or anterior

cerebral artery

Anatomy – middle cranial fossa

Optic nerve, sellar, parasellar lesions

ICA and anterior cerebral disorders - abnormal juxtaposition - sclerosis - aneurysms - pituitary tumors,

craniopharyngiomas, meningiomas , sarcoidosis, Wegener’s

MRI with contrast is the imaging mode of choice for sellar and chiasmal lesions

Meningioma

Optic nerve, sellar, parasellar lesions

Intracavernous sinus lesions - thrombosis/ blood dyscrasias -infection - ICA aneurysm - inflammation

Company kept includes III, IV, VI, V1, V2, and oculosympathetic fibers. IF note a Horner’s in unilateral “NTG” eye, must R/O cavernous s.

Optic nerve – canal

Sarcoid, pseudotumor

Acromegaly (pituitary hypersecretion of HGH)

Paget’s disease – 1% of adults over 50, may see angioid streaks

Optic nerve

Optic nerve perfusion

Pial vessels, posterior ciliary and short posterior ciliary vessels, CRA, ophthalmic a.

Thrombosis, inflammation, autonomic dysregulation, infection , metabolic syndrome resulting in ischemia

genuine ischemic optic

neuropathy

Perfusion issues

Sarcoid Autoimmune disease Anemia Hypotension Hypertension/diabetes Vasospasm Paraproteinemias Hyperhomocysteinemia

Venous resistance

RETINA - perfusion retinal arteries - retinal veins – CRV –

cavernous s.

UVEA/ciliary body – aqueous outflow 2 long posterior ciliary arteries - several

anterior ciliary arteries – short posterior ciliary arteries - choroidal plexus – vortex veins – superior and inferior orbital veins – cavernous s.

Venous resistance

Sclera/episclera/conjunctiva/canal of Schlemm

anterior ciliary arteries – surface arterioles - venous plexus of sclera/episclera/conjunctiva – anterior ciliary veins – inferior/superior orbital vein – cavernous sinus

Retinal antibodies/ autoantigens

Wax and Associates found high titers of antibodies against retinal proteins

- rhodopsin - heat shock proteins

What is normal?

C/D may be meaningless Large disc has large cup Small disc has small cup Average size disc is consistent with 5

degree spot size on direct Disc size does not determine

susceptibility to glaucoma

What is normal?

Normal disc shape is oval Vertical diameter is 10 degrees

greater than horizontal Optic disc shape does not increase

susceptibility High astigmia may alter appearance

What is normal? - rim

Thickness – inferior -> superior-> nasal-> temporal ( ISNT rule )

Inferior and superior temporal rim effected first

With advanced glaucoma, only nasal sector remains

So, vertical margins effected first

ISNT rule observed

Disc doesn’t obey ISNT

Disc progression

What is normal?

Various shades of pink and symmetric

Pseudophakes appear more pale If advanced, pallor more an artifact

due to excavation Pallor that exceeds cupping requires

neuro-ophthalmic work up Rarely, pallor may exceed cupping

What is normal?

Cup is defined by contour , not color Stereoscopic viewing Disc shape is vertical, however cup

shape is usually horizontal Place emphasis on the rim! Glaucoma experts assess disc better

than OCT!

What is suspect?

Disc hemorrhages are not typically normal

Detected in less than 8% of glaucoma patients

Greater association with NTG than other glaucomas

Indication of progression

Disc hemorrhage

What is suspect?

Peripapillary chorioretinal atrophy may be associated with glaucoma

Central beta (RPE atrophy and visible choroidal vessels)

Peripheral alpha (pigmentary changes and CR atrophy)

Greater with damage?

Peripapillary atrophy

What is suspect?

A.D. disc drusen may result in NFL loss and field defects identical to glaucoma

Disc drusen might mask cupping Single most common cause of

glaucoma without cupping B scan or auto fluorescence to

diagnose

Disc drusen

Disc drusen – B scan

Disc drusen – field loss in NTG

Its not easy

Crescents Tilts Physiologic differences Very slow progression Disc drusen

Discus software/ discusproject.blogspot.com

Suspicion

Most early cases will be missed! Add FDT screening fields and may

capture a few Perform routine pachymetry and

may capture some Add threshold perimetry and may

capture a few more Discs that do not respect ISNT

caught

Now that you think you caught him

Managing a condition with unknown pathogenesis

May be secondary to systemic disease

Systemic disease may result in morbidity/mortality if not managed

Disorder may progress regardless of your intervention

Really good history

Very good history - previous history of any IOP

elevation - ocular trauma/ inflammation/

steroid use -sleep apnea (may need to ask

spouse) -nocturnal BP dips - erectile dysfunction drugs -hemodynamic crisis (blood loss,

hypotension, anemia, syncope, blood transfusions, surgery (usually open chest)

Externals

Weakness in extremities, dizziness, headache, loss of consciousness, diplopia

Color vision testing, ruling out dyschromatopsia, particularly if asymmetric cupping

Pupil testing Systemic medications Gonioscopy

Serology

CBC to rule out anemia ESR – rarely elevated, but more to

R/O ION RPR, if positive then FTA-ABS ANA to rule out collagen vascular AP Abs, rhodopsin Abs, HSP Abs Serum immunofixation for

monoclonal gammopathy….10% of NTG patients

C reactive protein…. Often high in NTG

Imaging

Chest X-ray to rule out sarcoidosis, superior vena cava obstruction

Carotid Doppler to rule out carotid insufficiency

Scanning

Imaging studies – CT vs. MRI

Which one? - the anatomic site - the pathophysiology - the cost Who should order? - the person treating - suggestions are welcomed

Imaging studies – globe

Disc drusen – CT

Imaging studies – orbit

CT for Grave’s – axial and coronal views with contrast

CT for vascular abnormalities – varices, hemangiomas, and lymphomas

Pseudotumor – CT or MRI Optic nerve tumor – MRI with fat

suppression and contrast* Contrast presumed in all instance of CT

Imaging studies – sella/ para sellar

MRI is choice for sellar and chiasmal lesions

Craniopharyngiomas, pituitary adenomas, and meningiomas

Intracavernous lesions – look for constriction of the carotid arteries

ICA or anterior cerebral artery abnormalities

Imaging studies - vascular

MR angiography – evaluates flow CT angiography – evaluates blood

volume Either good for aneurysms Can not definitively R/O aneurysm Not good for lesions < 5mm Catheter angiography is still the gold

standard

Pachymetry

Done before gonioscopy Preferably before dilation At least two hours after awakening Stability following contact lens wear? Normal population 544+ 34um 2.5-3.5mm per 50um 3 readings with SD of 5um or less

Pachymetry

37 published studies have demonstrated CCT is a risk factor for progression to glaucoma

German study determined relationship between CCT and field loss

NTG patients tend to have thinner CCT

“thin” cornea may be masking POAG Optic nerve photos before LASIK?

Nerve fiber layer

Automated diagnostics

Structural changes before functional changes

OHTS demonstrated 93% chance of not developing glaucoma with normals

Greatly expanded database heightens sensitivity

May identify changes in visual fields up to 8 years earlier

Disc and nerve fiber layer

Tomography – in reality

Baseline images to compare patients to norms

Detection of progression may disagree with perimetry

Irregularities, even before field change may be predictors

Still possible to have field loss before structural changes!

Tomography - concerns

Functional changes may precede structural

Diagnostic ability demonstrated to be less accurate than disc assessments by a glaucoma specialist

Tells how much tissue is there, but is it healthy

5,000 axons lost on average per year Variable normal disc topography Specificity not 100% for glaucoma

Fields

Required! Possible to have field loss before structural changes

C30-2 SAP SWAP may provide earlier diagnosis

– stimulus V blue (440 nm) on yellow, that’s about all

FDT matrix may provide earlier diagnosis than SWAP and SAP. That’s about all

FDT matrix vs. SITA SWAPRight field is WNL. Left finds correlation between the two

Fields Not looking for:

Fields different with NTG

Focal defects are not uncommon Defects are closer to fixation often Defects are deeper Less slope from seeing to non-seeing

Should you treat?

Collaborative NTG Group Study showed slow or non-progression in NTG

Risk factors such as migraine or disc hemorrhage should be followed closely

With conclusive demonstration of progression consider treatment

50% of eyes without progression showed no progression by 7 years

Reduce IOP 30%

Treatment

Assess ocular environment Most common comorbidity in

glaucoma patients is dysfunctional tear syndrome

DTS present in 8-20% of population Topical glaucoma therapy daily, for

years, may further compromise the surface

48% of glaucoma patients report mild to severe symptoms

Assess the anterior segment

Would you give a pillto someone thatcan’t swallow?

Just check 3 things

Nafl tear BUT

Corneal/conjunctival staining

Meibomian gland inspissation

Treat anterior segment first!

Anterior blepharitis - Steri-lid HS - warm compresses/massage - antibiotic or antibiotic/steroid ung

HS - soft preserved tears daytime

Treat anterior segment first!

Posterior blepharitis - Steri-lid HS - warm compresses/massage - steroid/antibiotic ointment HS x 1-

2 weeks - cyclosporin BID if MGD appears

primary - doxycycline 100mg QD - omega 3’s ( fish oil/flax), good

hydration - soft preserved lubrication daily

Azithromycin

60 times better penetrationthan other topical antibiotics

MGD - azithromycin

Topical 1% solution (Azasite, Inspire Pharma)

Warm compresses/massage with 1% Azasite BID x2days, then QD x 12 days

Well documented anti-inflammatory activity

75% of patients Macrolides have demonstrated anti-

inflammatory properties by inhibiting MMPs

Treat anterior segment first!

Lacrimal gland disease - soft preserved tears daily such as

Systane - gels HS - consider cyclosporin - omega 3’s, good hydration - question systemic medications - plugs

Treat anterior segment first

Canthal tendon laxity - poor tear ejection - ectropion - floppy eyelid syndrome Conjunctivalchalasis Pinguecula EBMD – muro 128

drops/ung/debridement Allergies - Patanol

Preserved vs. non-preserved

BAK – a detergent that disrupts cell membranes

- reduced TBUT -conjunctival fibrosis - concentration-dependent cell

mortality - goblet cell reduction/loss of

microvilli - basement membrane damage - not all patients suffer

Non-BAK options

Benzododecium bromide – timolol gel

Purite – brimonidine Sofzia – travoprost Newer reduced concentration - Lumigan 0.1% Unit doses - Timoptic - Zioptan - Cosopt PF

General treatment options – prostaglandins

Shown to lower IOP 15-30% in NTG Interestingly, not utilized in the

CNTGS Little circadian variation in IOP Some work better than others in

some patients non-BAK option – Travoprost/Zioptan Could exacerbate inflammation with

OSD

Other prostaglandin facts

Travoprost has shown efficacy beyond 24 hours

DuBiner et.al. observed IOP significantly reduced out to 84 hours.

Sit et.al. showed efficacy 41-63 hours

Peace et.al. showed travoprost with and without BAK effectively lowered IOP at all times out to 60 hours

Prostaglandin-associated periorbitopathy

Partially reversible after a few months

General treatment options – beta blocker

Safe systemically, really, but use Betoptic

QD dosing usually enough Should be reconsidered for NTG.

Possible reduction in perfusion to disc, where Betoptic shown to possibly enhance optic nerve perfusion

OK for patients with asthma. Clear with their physician first.

General treatment options – alpha agonists

May be neuroprotective (increased ganglion cell survival in rat optic nerve crush injury)

Concern about reduced perfusion Good peak effect, reduced trough

effect with short duration of action Less effect between midnight and 6

a.m. Tachyphylaxis / allergy

General treatment options - CAI

Dorzolamide – increased retinal blood flow in humans

Brinzolamide (Azopt, Alcon) Better 24 hour efficacy vs. B blockers

or alpha agonists Diamox – may be necessary when

intervening in surface disease May be better adjunctive drug to use

with prostaglandins

Adjunctive therapy

Prostaglandins and……

CAI> alpha agonists> beta blockers Prostaglandins + CAB

General treatment options - combinations

Cosopt – dorzolamide /timolol maleate

Xalacom – latanoprost / timolol (not here)

Combigan – brimonidine / timolol (adjunct)

travoprost/timolol - (not here)

the presence of beta blockers might contraindicate use with NTG

Systemic BP

Antihypertensives in AM

Seek to maintain diastolic no less than 80mm

Tell MD to change their regimen or else

Surgical treatment options

Non-adherence to medications Inability to lower IOP 30% Impression of greater diurnal shift Surface disease Progression Cognitive impairment

Factors that contribute to dosing adherence

Patient characteristics Provider characteristics Characteristics of the medical

regimen Situational/logistical factors,

including cost

Adherence in glaucoma therapy

Difficulty detecting non-compliance Non-compliance increases with

increasing meds, dosages Tsai and colleagues identified 20

specific barriers that patients reported interfered with using glaucoma meds

Provider communication and concern about future consequences drive adherence

Glaucoma Adherence and Persistence Study (GAPS)

13,956 patients 89% claimed taking meds daily Medication possession ratio revealed

an average of drug taken 64% of time

Drug taking ranged from 36% of time to 100% of time

Only 10% fit the 100% category

Point system for estimating 5 year risk (OHTS – EGPS Glaucoma Risk Point System)

Risk

Google OHTS risk calculator I phone app for glaucoma risk

calculator

LET’S EAT!