This document summarizes a presentation on normal tension glaucoma (NTG). It begins with an introduction defining NTG as open-angle glaucoma with characteristic optic nerve damage and visual field defects in patients with consistently low intraocular pressure (IOP) below 21 mmHg. It then describes a case presentation of a 47-year-old female patient. The remainder of the document discusses the history, examination, investigations, differential diagnosis, management, pathogenesis involving both IOP-dependent and independent factors, and epidemiology of NTG. Key points are that lowering IOP through medication or surgery can help prevent progression even in NTG, and that NTG may have an underlying vascular component involving low ocular perfusion pressure

1. Normal Tension Glaucoma
Presenter: Dr. Niket Gandhi
Moderator: Dr.Vijay Shetty

2. Introduction
 Normal-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

3. Case Presentation
 47 Year old, female
 Teacher
 Mumbai
 Visited our institute with primarily for a squint
opinion

4. History
 H/o of using glasses
 She reported as being a hypotensive patient
 Family h/o: Mother – High myopia, ? Glaucoma

5. Examination
 BCVA:
1. (RE): -6.00/-0.75x30 add +1.50ds 6/6,N6
2. (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

6. 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 Notch
Dull FR
CDR=0.85 :1
Inferior Notch
Dull FR

7. Investigation
 Perimetry
 Gonioscopy
 OCT
 DVT
 Pachymetry - (RE) 509 u
(LE) 505 u

8. Gonioscopy
 BE- PTM seen in all quadrants
 Hence, wide open angles were observed.

12. DVT
 BP- 94/60 mmhg to 110/70 mmhg
 IOP – (RE) 12-18 mmhg
(LE) 10-16 mmhg
 For both eyes - Min : 2 am & Max : 2 pm

13. Management
 Diagnosed as NTG
 Started on e/d Travaprost hs
 She underwent B/L Lateral Rectus recession and MR
resection on 24/06/2014

14. Epidemiology
 NTG 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 cases
 More prevalent in the female population
 Positive 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.

15. Pathogenesis
Pressure dependent Pressure independent
groups
Factors involved in the etiology of
glaucomatous optic neuropathy

16. Pressure dependent factors
 IOP in NTG : A “risk factor” for the development and
progression of the disease
 Impaired 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

17. 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.

18. 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 eyes
2. 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.

19. 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

20. Pressure independent factors
 Abnormal blood flow
 Systemic hypotension
 Abnormal blood coagulability,
 Misc.

21. 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
BP
2. 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

22. Abnormal Blood flow
 Optic 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

23. 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.

24. 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%

25. Systemic Associations
Patients with normal-tension glaucoma have been noted to have
 A higher prevalence of hemodynamic crises
 Hypercoagulability;
 Hypertension/Hypotension
 Increased blood viscosity
 Elevated blood cholesterol and lipids
 Carotid artery disease
 Slowed parapapillary, choroidal, and retinal circulations
 Peripheral vasospasm
 Migraine.

26. Main Criteria
 A mean IOP off treatment <=21 mm Hg on diurnal testing,
with no single measurement greater than 24 mm Hg
 Open drainage angles on gonioscopy
 Absence of any secondary cause for a glaucomatous optic
neuropathy
 Typical optic disc damage with glaucomatous cupping and
loss of neuroretinal rim
 Visual field defect compatible with the glaucomatous
cupping (disc/field correlation)
 Progression of glaucomatous damage.

27. Work Up for NTG
 History
 Physical Examination
 Diagnostic Procedures
 DDx
 Manangement

28. 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.

29. Examination
 Visual 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

30. Signs
 The 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

31. Optic nerve in NTG
 Optic nerves with a larger surface area and with thinner
inferior/inferotemporal rims
 PPA 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.

32. Acquired pits of optic nerve
 Acquired 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.

33. 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

34. Disc Hemorrhages
 Nerve fiber layer hemorrhage and arteriolar narrowing
were found more frequently
 Optic 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

35. Symptoms
 Asymptomatic until very advanced.
 Subjective scotoma near fixation as these defects can
occur early on in the disease process of NTG

36. Diagnostic Tests
 Visual Field testing
 Pachymetry
 Optic Disc imaging
 OCT
 24 Hr IOP evaluation

37. Visual field testing
 Visual 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

38. Role of Corneal Thickness in NTG
 Patients 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

39. Optic Disc Imaging
 Optic nerve head photography is important to
document the status of the optic nerve at baseline and
for future comparisons

40. OCT RNFL
 Normally 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 quadrant
 The 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

41. 24 Hr IOP evaluation
 24 Hour IOP evaluation helps to determine the
pressure spikes
 Normal eyes : between 3 and 6 mmHg and the
variation may increase in glaucomatous eyes

42. Progression
Signs:
 Increased disc cupping
 Optic nerve disc hemorrahges
 Increased peripapillary atrophy
 Visual field loss
Monitoring:
 Optic nerve head photos
 Visual field testing
 OCT

43. Neurological Work up
 Marked 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

44. Differential Diagnosis
Glaucomatous etiology
 Primary open angle glaucoma with diurnal fluctuation
between normal and elevated IOP
 Diurnal Variation Test helps in detecting pressure spikes
throughout the day

45.  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)

46.  Burned out pigmentary glaucoma
 Signs: Iris transillumination defects, Pigmented angle
structures, krukrnberg spindles

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

48. Compressive, metabolic, toxic, inflammatory or
infectious optic neuropathy
- Pituitary Adenoma
- Meningioma
- Empty sella syndrome
- Leber’s optic atrophy
- Methanol optic neuropathy
- Optic neuritis
- Syphilis

49. Vascular injuries
- Giant cell arteritis
- Non-arteritic anterior ischemic optic neuropathy
- Posterior ischemic optic neuropathy
- Central retinal artery occlusion
- Carotid/ophthalmic artery occlusion

50. Managment
 The main focus for treating NTG is on lowering the
INTRAOCULAR PRESSURE
 It can be achieved by:
1. Medical Therapy
2. Surgery

51. Medical Rx
 Studies suggest a 25%-30% reduction in IOP
 Topical Prostaglandin analogues are the preferred
drug
 Adjuntive use of Carbonic anhydrase inhibitors and B-
blockers
 Though use of B-blockers should be avoided at night
 Studies 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.

52. Surgery
 Filteration surgeries with peri/intra operative use of
anti- metabloites like MMC and 5-FU show enhanced
success of surgery

53. Non IOP related Rx
 The role of different neuroprotective agents still
remains controversial
 Agents under study include
1. Memantine (NMDA blocker)
2. Unoprostone( Prostanoid and synthetic docasanoid)
3. -Statins (HMG-CoA reductase inhibitor)
4. Ginkgo Biloba
5. Resveratrol
 Calcium channel blockers use remains doubtful in
cases where vasospasm is a factor

55. Thank You