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Normal Tension Glaucoma

Home / Glaucoma / Introduction to Glaucoma

Title: Normal Tension Glaucoma
Authors: William Clark, BA; Brian Stagg, MD
Date: 05/22/20
Keywords/Main Subjects: Glaucoma, Open-Angle Glaucoma, Normal Tension Glaucoma

-Glaucoma: array of clinical disorders characterized by progressive optic neuropathy and visual field loss1

-Normal intraocular pressure (IOP): Gaussian distribution with an established mean of 15 mmHg and upper limit of normal of 21 mmHg2,3,4

-Normal tension glaucoma (NTG):  open chamber angles and glaucomatous optic neuropathy without a measured elevation (>21mmHG) in IOP 1,5

 

-Optic disc: Progressive inferior and superior temporal rim thinning; focal rim atrophy or “notching”; disc hemorrhages; increased inferior and superior cup-to-disc ratios6,7

-Retinal nerve fiber layer (RNFL): focal band-like defects and diffuse atrophy in the peripapillary region8

-Visual field: Nasal step-like defects, paracentral and arcuate scotomas obeying the horizontal midline9,10

–Overlooking NTG: in the setting of normal IOP, diagnosis requires clinical suspicion and vigilant optic nerve examination; single center study found NTG was diagnosed via population screening 4 times more often than during routine clinical examination11

–Diagnosis of exclusion: imperative to investigate multiple etiologies for optic neuropathy and visual field loss; masquerading syndromes are often misdiagnosed as NTG and vice versa12,13,14

-Nonglaucomatous etiologies:

-Developmental: colobomas, megalopapilla, congenital pits, tilted optic nerve, physiologic cupping [visual field defects are non-progressive]12,1

-Acquired: compressive lesions of anterior visual pathway, anterior ischemic optic neuropathy (AION), optic neuritis, syphilis, toxic-metabolic optic neuropathy (methanol poisoning, heavy metal exposure, B12/folate deficiency) [predominately optic nerve pallor, but may cause cupping]12,14,15

-Glaucomatous etiologies:

-Primary open angle glaucoma: underestimated IOP [ruled out with pachymetry and diurnal curve of IOP measurement]12

-Secondary open angle glaucoma: pigment dispersion, exfoliation syndrome, neovascularization, inflammation [ruled out with anterior segment examination]12

-Angle-closure glaucoma [ruled out with gonioscopy]

-Previous insult: steroids, uveitis, trauma, systemic hypotension [visual deficits typically stable]12

-Collaborative Normal Tension Glaucoma Study (CNTGS):

-IOP reduction by 30% lowers risk of visual field progression 16

-Majority (65%) of non-treated eyes showed no progression after 5 years and 12% of subjects progressed despite IOP reduction16

-Benefits of IOP reduction on visual field progression blunted by cataract formation17

-Natural history and risk factors should be weighed before initiating aggressive IOP reduction therapy17

-Low-Pressure Glaucoma Treatment Study (LGTS):

-Brimonidine tartrate 0.2% and timolol maleate 0.5% have similar efficacy in lowering IOP18

-Brimonidine is more likely to prevent progressive visual loss than timolol18

-9% of brimonidine patients had visual field progression as opposed to 39% of timolol patients over the 4 year study period18

-Brimonidine patients had a 28% drop-out rate due to ocular side effects, compared to a 11% drop-out rate in timolol patients18

-Proposed explanations: timolol may cause greater systemic hypotension and reduced ocular perfusion, brimonidine has demonstrated neuroprotective effects in animal models18

 

Clinical Epidemiology

-Asian populations: NTG represents 47-92% of open angle glaucoma (OAG) cases19,20

-White populations: NTG represents 30-39% of OAG cases19,20

-African populations: NTG represents 21% of OAG cases in a Ghanaian population and 57% in a South African population21,20

-High-normal IOP and wide diurnal IOP fluctuation22

-Systemic hypotension, especially nocturnal hypotension23,24,25

-Vasospastic disease (especially migraine and Raynaud’s phenomenon)26,27

-Sleep apnea28

-Myopia19

-Large optic discs29

-Family history30

 

Pathophysiology

-Vascular dysregulation: leads to unstable ocular perfusion, ischemia and optic nerve damage31,12

-Elevated translaminar pressure: may be due to structural variation in the lamina cribosa or low intracranial pressure 32,33

-Increased sensitivity to normal IOP: may be due to anatomic or genetic variation34

 

Evaluation

-History of Present Illness: [assess for episodes of acute vision loss or color vision loss; visual impairment in everyday activities; episodes of eye irritation]35,12

-Pertinent Review of Systems:[assess for dizziness, headaches, weakness, syncope, fatigue, vasospasm]36

-Past Medical/Surgical History: [assess for anemia, cardiovascular disease, hypotensive crisis, hypercholesterolemia, diabetes, respiratory disease, renal disease, vasospasm, migraine headaches, sleep apnea, vitamin deficiency, heavy metal exposure]35,12

-Past Ocular History: [assess for myopia, glaucoma, inflammation, trauma, steroid use, elevated IOP, ocular surgery including laser in situ keratomileusis (LASIK)]12,35

-Family History: [assess for congenital ocular disease, blindness and glaucoma] 1

-Medication History: [assess with special attention to steroid and antihypertensive use]12

-Best-corrected visual acuity (VA): VA disproportionate to optic nerve exam or visual field testing warrants further workup12

-Pupillary response: abnormal pupillary light reflexes may occur37

-Intraocular pressure: measurement <22 mmHg required for diagnosis12

-Slit lamp examination: exclusion of masquerading syndromes required

-Gonioscopy: exclusion of angle closure and angle recession required; narrow-angle NTG shown to be more progressive than wide-angle NTG38

-Dilated fundus examination: increased frequency of splinter hemorrhages near the optic nerve head and more localized RNFL defects near fixation compared to OAG39,40

-Visual fields: (automatic static perimetry) scotomas are deeper, more focal and closer to fixation compared to OAG; dense paracentral scotomas are common41,42,12

-Pachymetry: central corneal thickness (CCT) affects IOP measurement, especially when measured via applanation tonometry (thinner CCT underestimates IOP)43,12,35

-Color vision testing: abnormalities raise suspicion for underlying neurological disorder12,13

-Neuroimaging: several patient factors have been linked with a higher probability of positive neuroradiological findings (age<50, lower visual acuity, and optic rim pallor>cupping)30

-Laboratory workup: toxic-metabolic [heavy metals and vitamin B12/folate], infectious [syphilis and lyme antibody testing], and inflammatory [erythrocyte sedimentation rate and C-reactive protein levels]12

-24-hour blood pressure monitoring: assesses ocular blood flow12

-Optical coherence tomography: provides quantitative imaging of optic nerve head and RNFL35

 

Management

-Target IOP: reduce IOP relative to the extent of glaucomatous damage and risk factors for progression, with 30% reduction as a general target1,16,35

-Forms of therapy: medication, laser trabeculoplasty and incisional surgery35

-Mitigate risk factors: coordinate with primary care physician regarding adequate cardiac/respiratory/renal functioning, sleep apnea, blood pressure control (avoid nocturnal anti-hypertensive dosing), and iron levels44,12,28

-IOP-lowering medications: prostaglandin analogs, selective alpha-2 adrenergic agonists and carbonic anhydrase inhibitors12

-Evidence: prostaglandins typically first-line due to efficacy and safety profile; brimonidine more efficacious than timolol in preventing visual field loss18,12,35

-Selective laser trabeculoplasty (SLT): effective as initial therapy; proven to lower mean IOP and variability of IOP between visits; shown to lower IOP by 15% and topical medication use by 27% at 1 year post-procedure12,45,46,47

-Trabeculectomy: reduces IOP to sub-normal and single-digit levels; reduces IOP fluctuation; mitomycin-C augmented trabeculectomy shown to have a >60% success rate (>30% IOP reduction from baseline) at 4-year follow up; shown to slow further progression of visual field loss48,49,50

-Evaluation: perform thorough interval history with special attention to medication adherence and side effects; measure IOP and VA; perform slit lamp exam; evaluate optic nerves; assess visual fields12,35

-Interval: Progressive optic nerve or visual field damage (1-2 months); unachieved target IOP( 3-6 months); achieved target IOP (6-12 months)12,35

 

References

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  21. Ntim-Amponsah CT, Amoaku WMK, Ofosu-Amaah S, et al. Prevalence of glaucoma in an African population. Eye. 2004;18(5):491-497. doi:10.1038/sj.eye.6700674
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  23. Hulsman CAA, Vingerling JR, Hofman A, Witteman JCM, de Jong PTVM. Blood pressure, arterial stiffness, and open-angle glaucoma: the Rotterdam study. Arch Ophthalmol Chic Ill 1960. 2007;125(6):805-812. doi:10.1001/archopht.125.6.805
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  26. Drance SM, Douglas GR, Wijsman K, Schulzer M, Britton RJ. Response of blood flow to warm and cold in normal and low-tension glaucoma patients. Am J Ophthalmol. 1988;105(1):35-39. doi:10.1016/0002-9394(88)90118-3
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  29. Burk RO, Rohrschneider K, Noack H, Völcker HE. Are large optic nerve heads susceptible to glaucomatous damage at normal intraocular pressure? A three-dimensional study by laser scanning tomography. Graefes Arch Clin Exp Ophthalmol Albrecht Von Graefes Arch Klin Exp Ophthalmol. 1992;230(6):552-560. doi:10.1007/bf00181778
  30. Greenfield DS, Siatkowski RM, Glaser JS, Schatz NJ, Parrish RK. The cupped disc. Who needs neuroimaging? Ophthalmology. 1998;105(10):1866-1874. doi:10.1016/S0161-6420(98)91031-4
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  40. Woo SJ, Park KH, Kim DM. Comparison of localised nerve fibre layer defects in normal tension glaucoma and primary open angle glaucoma. Br J Ophthalmol. 2003;87(6):695-698.
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  45. El Mallah MK, Walsh MM, Stinnett SS, Asrani SG. Selective laser trabeculoplasty reduces mean IOP and IOP variation in normal tension glaucoma patients. Clin Ophthalmol Auckl NZ. 2010;4:889-893. doi:10.2147/opth.s11787
  46. Lee JW, Ho WL, Chan JC, Lai JS. Efficacy of selective laser trabeculoplasty for normal tension glaucoma: 1 year results. BMC Ophthalmol. 2015;15. doi:10.1186/1471-2415-15-1
  47. Nitta K, Sugiyama K, Mawatari Y, Tanahashi T. [Results of selective laser trabeculoplasty (SLT) as initial treatment for normal tension glaucoma]. Nippon Ganka Gakkai Zasshi. 2013;117(4):335-343.
  48. Hitchings RA, Wu J, Poinoosawmy D, McNaught A. Surgery for normal tension glaucoma. Br J Ophthalmol. 1995;79(5):402-406.
  49. Schultz SK, Iverson SM, Shi W, Greenfield DS. Safety And Efficacy Of Achieving Single-Digit Intraocular Pressure Targets With Filtration Surgery In Eyes With Progressive Normal-Tension Glaucoma. J Glaucoma. 2016;25(2):217-222. doi:10.1097/IJG.0000000000000145
  50. Jayaram H, Strouthidis NG, Kamal DS. Trabeculectomy for normal tension glaucoma: outcomes using the Moorfields Safer Surgery technique. Br J Ophthalmol. 2016;100(3):332-338. doi:10.1136/bjophthalmol-2015-306872

 

Faculty Approval by: Brian Stagg, MD
Identifier: Moran_CORE_27919
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