Normal Tension Glaucoma

Presenter: Dr. Niket GandhiModerator: Dr.Vijay Shetty

IntroductionNormal-tension glaucoma (NTG) is a form of

open-angle glaucoma characterized by glaucomatous optic neuropathy and corresponding visual field defects in patients with IOP measurements consistently lower than 21 mmHg

Case Presentation47 Year old, femaleTeacherMumbaiVisited our institute with primarily for a

squint opinion

HistoryH/o of using glassesShe reported as being a hypotensive patientFamily h/o: Mother – High myopia, ?

Glaucoma

ExaminationBCVA:

1. (RE): -6.00/-0.75x30 add +1.50ds 6/6,N62. (LE): -5.00/-1.00x130 add +1.50ds 6/6,N6

(LE) Exotropia On PBCT: 70 pd base in deviation for

distance and near with good fusion

RE LE

Lid N N

Conjunctiva Quiet Quiet

Cornea Clear Clear

AC Deep and quiet

Deep and quiet

Iris CPN CPN

Pupil 7mm 7mm

Lens Clear Clear

Fundus CDR=0.85 :1 Inferior NotchDull FR

CDR=0.85 :1 Inferior NotchDull FR

Investigation Perimetry GonioscopyOCTDVTPachymetry - (RE) 509 u (LE) 505 u

GonioscopyBE- PTM seen in all quadrants Hence, wide open angles were observed.

DVTBP- 94/60 mmhg to 110/70 mmhgIOP – (RE) 12-18 mmhg (LE) 10-16 mmhg For both eyes - Min : 2 am & Max : 2 pm

ManagementDiagnosed as NTGStarted on e/d Travaprost hsShe underwent B/L Lateral Rectus recession

and MR resection on 24/06/2014

EpidemiologyNTG is a disease of the elderly. Beaver Dam Eye Study:

The prevalence of likely NTG increased from 0.2% in the 43–54 years age group to 1.6% in those over 75 years of age

Below 50 years - 11% to 30% of all glaucoma casesMore prevalent in the female populationPositive family history - 5% to 40% * Higher prevalence in Japanese population

*1.Miglior M. Low critical tension glaucoma: present problems. Glaucoma 1987;9:77.*2.Geijssen HC. Studies on normal pressure glaucoma. Amsterdam: Kugler, 1991;1:1.

Pathogenesis

Pressure dependent Pressure independent groups

Factors involved in the etiology of glaucomatous optic neuropathy

Pressure dependent factorsIOP in NTG : A “risk factor” for the development

and progression of the diseaseImpaired optic nerve blood flow or a structurally

abnormal lamina cribrosa, which cannot withstand a normal range of IOP.

The effectiveness of intraocular pressure reduction in the treatment of normal-tension glaucoma was studied by:

Collaborative Normal-Tension Glaucoma Study Group

Collaborative Normal-Tension Glaucoma Study Group

PURPOSE: To determine if intraocular pressure plays a part in the pathogenic process of normal-tension glaucoma.

METHODS: 1. One eye of each eligible subject was randomized either

to be untreated as a control or to have intraocular pressure lowered by 30% from baseline.

2. Eyes were randomized if they met criteria for diagnosis of normal-tension glaucoma and showed documented progression or high-risk field defects that threatened fixation or the appearance of a new disk hemorrhage.

RESULTS:

Sample size: 140 eyes of 140 patients Groups : Treatment group : 61 Untreated control: 79 Patients reaching end points (specifically defined

criteria of glaucomatous optic disk progression or visual field loss)1. 28 (35%) of the control eyes2. 7 (12%) of the treated eyes

Of 34 cataracts developed during the study, 11 (14%) occurred in the control group and 23 (38%) in the treated group (P = .0075), with the highest incidence in those whose treatment included filtration surgery.

CONCLUSIONS

Intraocular pressure is part of the pathogenic process in normal-tension glaucoma.

Therapy that is effective in lowering intraocular pressure and free of adverse effects would be expected to be beneficial in patients who are at a risk of progression

Pressure independent factorsAbnormal blood flowSystemic hypotensionAbnormal blood coagulability,Misc.

Systemic Hypotension

Various study show the role of systemic hypotension in the pathogenesis of the optic

neuropathy in NTG :1. Greater nocturnal decrease and a lower level of

diastolic BP2. In both NTG and HTG groups, lower BP at night

resulted in pts having progressive disease 3. Overall glaucoma pts, those on

antihypertensives who had a larger nocturnal decrease in systolic pressure tended to have deteriorating visual fields

Abnormal Blood flowOptic nerve blood vessel diameter may be

affected by vasospasm and the association between vasospastic disorders

Drance et al found decreased finger capillary flow in NTG patients suggesting vasospasm as an underlying aetiological factor

Close associations: Migrainous headache and Raynaud’s phenomenon

Mean Ocular Perfusion Pressure

Ocular perfusion pressure (OPP), the relationship between systemic blood pressure and IOP

Mean ocular perfusion pressure(MOPP)MOPP = 2/3 [DBP + 1/3(SBP – DBP)] – IOP

Risk factor for open-angle glaucoma. Because low blood pressure lets OPP drop, and

low OPP is similar to elevated IOP,hence it has consistently and strongly been associated with OAG.

Misc factors

Other factors include:Abnormal blood coaguability Endothelin (ET1), a potent and continuous

vasoacting peptide is associated with NTG.Obstructive sleep apnea/hypopnea syndrome

(OSAHS)- Prevalence overall : 5.7% & In severe: 7.1%

Systemic AssociationsPatients with normal-tension glaucoma have been noted to

haveA higher prevalence of hemodynamic crisesHypercoagulability;Hypertension/Hypotension Increased blood viscosityElevated blood cholesterol and lipidsCarotid artery disease Slowed parapapillary, choroidal, and retinal circulationsPeripheral vasospasmMigraine.

Main CriteriaA mean IOP off treatment <=21 mm Hg on

diurnal testing, with no single measurement greater than 24 mm Hg

Open drainage angles on gonioscopyAbsence of any secondary cause for a

glaucomatous optic neuropathyTypical optic disc damage with glaucomatous

cupping and loss of neuroretinal rimVisual field defect compatible with the

glaucomatous cupping (disc/field correlation)Progression of glaucomatous damage.

Work Up for NTGHistoryPhysical ExaminationDiagnostic ProceduresDDxManangement

History

Neurologic symptoms :Headache, weakness, dizziness,

diplopia, or loss of consciousness

Ocular trauma or inflammation:

Possible prior intraocular pressure elevation or other causes of optic

neuropathy.

Medications:Systemic, topical, inhaled, or nasal

steroids, that can elevate intraocular pressure

Compromised ocular perfusion:

Sleep apnea, syncope, Raynaud’s phenomenon, anemia,

hypotension, blood transfusions.

Systemic hypertension or

hypotension and any current

treatments for these.

ExaminationVisual acuity Color vision testing (to help differentiate from non-

glaucomatous optic neuropathies) IOP measurement also Diurnal and if possible supine Pachymetry Afferent pupillary response testing Gonioscopy Complete slit lamp examination of the anterior segment  Dilated fundus examination with optic nerve head and

retinal nerve fiber layer (RNFL) assessment

SignsThe following features may be more frequently

seen in NTG compared to POAG:- Flame shaped hemorrhages of the optic nerve rim (Drance hemorrhage)

- Deep, focal notching of the rim - Peripapillary atrophy

Optic nerve in NTGOptic nerves with a larger surface area and with

thinner inferior/inferotemporal rimsPPA in a crescent or halo configuration PPA: adjacent to areas of greatest disc thinning

and corresponding visual field loss While thinning of the optic nerve rim is observed

in all POAG, focal thinning or ‘notching’ is more commonly observed in NTG.

Acquired pits of optic nerveAcquired pits of optic nerve [APON] which

are thought to be due to focal loss of neuroretinal rim tissue and shown as localised excavations of the lamina cribrosa, are more frequent in NTG.

More prevalent in lower pressure glaucoma than in higher pressure glaucoma.

Inferior part of disc> Superior

Acquired pits of the optic nerve in glaucoma: prevalence and associated visual field loss.Nduaguba C1, Ugurlu S, Caprioli J.

Disc Hemorrhages

Flame or splinter shaped, often with feathered ends, and is radially oriented and perpendicular to the disc margin

Extends from within the optic nerve head to the adjacent retina, crossing any peripapillary zone of absent or disrupted retinal pigment epithelium

13.8 to 28.0% in NTG

Soares AS, Artes PH, Andreou P, Leblanc RP, Chauhan BC, Nicolela MT. Factors associated with optic disc hemorrhages in glaucoma. Ophthalmology. 2004;111:1653-7.. Diehl DL, Quigley HA, Miller NR, Sommer A, Burney EN. Prevalence and significance of optic disc hemorrhage in a longitudinal study of glaucoma. Arch Ophthalmol. 1990;108:545-50

Disc HemorrhagesNerve fiber layer hemorrhage and arteriolar

narrowing were found more frequentlyOptic disk hemorrhages showed significantly

higher percentages of progressed points within the 10-degree area compared with the group without optic disk hemorrhage

Comparative optic disc analysis in normal pressure glaucoma, primary open-angle glaucoma, and ocular hypertension.Tezel G1, Kass MA, Kolker AE, Wax MB.Disk hemorrhage is a significantly negative prognostic factor in normal-tension glaucoma.Ishida K1, Yamamoto T, Sugiyama K, Kitazawa Y

SymptomsAsymptomatic until very advanced. Subjective scotoma near fixation as these

defects can occur early on in the disease process of NTG

Diagnostic TestsVisual Field testingPachymetryOptic Disc imagingOCT 24 Hr IOP evaluation

Visual field testingVisual field defects may include those

common to POAG including nasal step and arcuate scotoma.

However, defects noted in NTG tend to be more focal and occur closer to fixation early in the disease

Dense paracentral scotomas may characteristically be noted at initial diagnosis

Role of Corneal Thickness in NTGPatients with NTG have a thinner CCT than do

patients with POAG or controls. Underestimation of the IOP in patients with

POAG who have thin corneas may lead to a misdiagnosis of NTG, while overestimation of the IOP in normal subjects who have thick corneas may lead to a misdiagnosis of OHT.

Corneal Thickness in Ocular Hypertension, Primary Open-angle Glaucoma, and Normal Tension Glaucoma 

René-Pierre Copt, MD; Ravi Thomas, MD; André Mermoud, MD

Optic Disc ImagingOptic nerve head photography is important to

document the status of the optic nerve at baseline and for future comparisons

OCT RNFLNormally a double-hump pattern with a dual prominence

at the superior and inferior borders. Pattern lost with superior and inferior RNFL flattening in

glaucomatous eyes Inferior quadrant> Superior quadrantThe mean RNFL thickness/disc area ratio showed a

significantly lesser value for NTG despite the fact that absolute values for mean RNFL thickness and disc area was larger for NTG

24 Hr IOP evaluation24 Hour IOP evaluation helps to determine

the pressure spikes Normal eyes : between 3 and 6 mmHg and

the variation may increase in glaucomatous eyes

Progression

Signs:Increased disc cuppingOptic nerve disc hemorrahgesIncreased peripapillary atrophy Visual field lossMonitoring:Optic nerve head photosVisual field testingOCT

Neurological Work upMarked asymmetry or unilateral optic nerve

involvement Unexplained visual acuity loss Color vision deficits in the absence of visual field

deficits Visual field defects not corresponding or out of

proportion to optic nerve damage Vertically aligned visual field defects Atypical neurologic symptoms for glaucoma  Optic nerve pallor in excess of cupping Age less than 50 years

Differential DiagnosisGlaucomatous etiology

Primary open angle glaucoma with diurnal fluctuation between normal and elevated IOP

Diurnal Variation Test helps in detecting pressure spikes throughout the day

Intermittent acute angle closure glaucoma – r/o via Gonioscopy

Tonometric underestimation of actual IOP (e.g. thin central corneas) - Pachymetry

Resolved corticosteroid-induced, uveitic, or traumatic glaucoma

Uveitic glaucoma/glaucomatocyclitic crisis (Posner-Schlossman)

Burned out pigmentary glaucomaSigns: Iris transillumination defects, Pigmented

angle structures, krukrnberg spindles

Myopia with peripapillary atrophy Optic nerve coloboma or pits Congenital disc anomalies/cupping

Compressive, metabolic, toxic, inflammatory or infectious optic

neuropathy - Pituitary Adenoma

- Meningioma- Empty sella syndrome- Leber’s optic atrophy- Methanol optic neuropathy- Optic neuritis- Syphilis

Vascular injuries - Giant cell arteritis

- Non-arteritic anterior ischemic optic neuropathy- Posterior ischemic optic neuropathy- Central retinal artery occlusion- Carotid/ophthalmic artery occlusion

ManagmentThe main focus for treating NTG is on

lowering the INTRAOCULAR PRESSUREIt can be achieved by:

1. Medical Therapy2. Surgery

Medical RxStudies suggest a 25%-30% reduction in IOP Topical Prostaglandin analogues are the

preferred drug Adjuntive use of Carbonic anhydrase

inhibitors and B-blockersThough use of B-blockers should be avoided

at nightStudies show brimonidine showed less visual

field progression than twice daily use of timolol Low-Pressure Glaucoma Treatment Study.A randomized trial of brimonidine versus timolol in preserving visual function: results from the Low-Pressure Glaucoma Treatment Study.Krupin T1, Liebmann JM, Greenfield DS, Ritch R, Gardiner S; Low-Pressure Glaucoma Study Group.

SurgeryFilteration surgeries with peri/intra operative

use of anti- metabloites like MMC and 5-FU show enhanced success of surgery

Non IOP related RxThe role of different neuroprotective agents

still remains controversialAgents under study include

1. Memantine (NMDA blocker)2. Unoprostone( Prostanoid and synthetic

docasanoid)3. -Statins (HMG-CoA reductase inhibitor)4. Ginkgo Biloba5. Resveratrol

Calcium channel blockers use remains doubtful in cases where vasospasm is a factor

Thank You