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!