Normal tension glaucoma

Normal tension glaucoma

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: (RE): -6.00/-0.75x30 add +1.50ds 6/6,N6 (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.

9. 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

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

11. 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.

12. Pathogenesis Factors involved in the etiology of glaucomatous optic neuropathy

13. 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

14. Collaborative Normal-Tension Glaucoma Study Group PURPOSE: To determine if intraocular pressure plays a part in the pathogenic process of normal-tension glaucoma. METHODS: 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. 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.

15. 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) 28 (35%) of the control eyes 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.

16. 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

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

18. Systemic Hypotension Various study show the role of systemic hypotension in the pathogenesis of the optic neuropathy in NTG : Greater nocturnal decrease and a lower level of diastolic BP In both NTG and HTG groups, lower BP at night resulted in pts having progressive disease Overall glaucoma pts, those on antihypertensives who had a larger nocturnal decrease in systolic pressure tended to have deteriorating visual fields

19. 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

20. 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 .

21. 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%

22. 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.

23. 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.

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

25. History

26. 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

27. 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

28. 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.

29. 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 C 1 ,  Ugurlu S ,  Caprioli J .

30. 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

31. 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 G 1 ,  Kass MA ,  Kolker AE ,  Wax MB . Disk hemorrhage is a significantly negative prognostic factor in normal-tension glaucoma. Ishida K 1 ,  Yamamoto T ,  Sugiyama K ,  Kitazawa Y

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

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

34. 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

35. 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

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

37. 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

38. 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

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

40. 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

41. 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

42. 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 )

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

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

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

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

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

48. 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 T 1 ,  Liebmann JM ,  Greenfield DS ,  Ritch R ,  Gardiner S ;  Low-Pressure Glaucoma Study Group .

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

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

51. Thank You