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Looking Beyond the Optic Nerve Head in Normal-Tension Glaucoma

by | Jun 1, 2022 | Manuscripts | 0 comments

Khaarthiyaa Lokanathan, B.Optom

Undergraduate Research Student, Elite School of Optometry & SASTRA, Tamil Nadu

 

Glaucomatous optic neuropathy (GON) with normal Intraocular Pressure (IOP) and an evident visual field defect is considered as Normal-Tension Glaucoma (NTG).

Glaucomatous damage:

The aetiology for glaucoma has been linked to the biomechanical deformation of Lamina Cribrosa (LC) due to the elevated IOP, (1) progressing to axonal damage and retinal ganglion cell (RGC) death (Figure 1), but the pathogenesis behind NTG with normal IOP has ambiguous discoveries. Recent studies have shown that the pressure difference between the intraocular space and the retro-bulbar space (Figure 2) plays a major role in the development of NTG. (2,3)

 

Figure 1: (a) The retinal ganglion cell axons converge at the site of the optic nerve head, the NRR forms the optic disc and a shallow depression in the centre forms the optic cup. The axonal fibres make up the optic nerve and pass through the LC, to reach the LGN (b) In the glaucomatous eye, there is a significant axonal loss leading to an enlarged depression/ cupping, with simultaneous posterior displacement and thinning of LC [Image Courtesy – The organisation of the Retina and Visual System, 2019 (4) ]

 

Figure 2: The optic nerve head (ONH, posteriorly consisting of the lamina cribrosa) is the interface between the intraocular & retrobulbar compartments. The pressure exerted by the former compartment is the IOP and by the latter is the Cerebrospinal Fluid Pressure (CSFP) or the Intracranial pressure (ICP) (5)

The ONH, LC divide the two pressure-built regions, any variation from the normative range of IOP and ICP (Table 1) results in pressure imbalance and development of GON.

Table 1: Normative values of IOP and ICP (standard lumbar puncture measurement) (6)

Parameters Normative range (mmHg)
Intraocular pressure 11 to 21
Intracranial pressure (in supine position) 5 to 15
Non-Invasive calculation of ICP (mmHg)= 0.44 × BMI + 0.16 × diastolic pressure − 0.18 × age − 1.91
the formula derived ICP did not significantly differ from the measured ICP (7)
BMI: Body Mass Index
IOP and ICP are dependent upon anatomic positioning, for clinical measurements lateral decubitus and sitting posture respectively are to be followed (8)

Trans-Lamina Cribrosa Pressure Difference and Gradient (TLCPD & TLCPG)(9-11)

The optic nerve is ensheathed by three meningeal layers and is surrounded by the Subarachnoid Space (SAS). The ONH has pressure exertion from the IOP (anteriorly) and ICP (posteriorly). The TLCPD is the pressure difference between the IOP and ICP (Table 2). In healthy eyes, the TLCPD is posteriorly directed and accounts for around 4mmHg. Increased TLCPD has been associated with Neuro-retinal rim (NRR) loss and visual field defects.

The LC thickness is a crucial factor influencing optic nerve head damage. NTG patients are proven to have thinner LC compared to healthy eyes (450 microns). The TLCPD is altered by the LC thickness, this gradient across the LC is the TLCPG (Table 2).

Table 2: Calculation of TLCPD and TLCPG

Parameters Calculation
TLCPD (mmHg) IOP (mmHg)- ICP (mmHg)
TLCPG (mmHg) [IOP- ICP] (mmHg)/ LC thickness (microns)

It is hypothesised that an elevated IOP leads to a posteriorly oriented pressure exertion, leading to increased bowing of the LC, as in glaucoma and an elevated ICP leads to anteriorly oriented pressure exertion, leading to increased intracranial hypertension as in the case of papilledema.

Decreased ICP with normal IOP has been postulated to be an important risk factor for the development of NTG. Age, BMI, reduced ocular blood flow, lower systolic ocular perfusion pressure, low systolic blood pressure, cardiovascular diseases are other associated risk factors for the open- angle glaucoma, especially NTG.(12,13)

In the normal state of the eye, the IOP is usually slightly higher than that of the ICP, leading to an inconsiderable TLCPD. Either an elevation in the IOP or reduction in the ICP can further proceed to raise the TLCPD, leading to deep excavation of the ONH. (7)

NTG occurs due to both ocular & systemic pressure differences, its detection is more challenging than other types of glaucoma as there is an absence of elevated IOP, leading to misdiagnosis of NTG.(14) An increased TLCPD with a lower ICP could be a potential diagnostic marker for the detection of NTG. The ICP could be calculated with the generated formula from previous literature, as the invasive clinical measurement is time consuming and strenuous. Literature shows statistically significant differences in TLCPG in NTG and high-tension glaucoma patients. (13) Further research on TLCPD and TLPCG among cohorts of different ethnicities could bring more light upon the clinical utilisation of these parameters for effective early NTG diagnosis.

 

References

  1. Fazio, M. A., Clark, M. E., Bruno, L., & Girkin, C. A. (2018). In vivo optic nerve head mechanical response to intraocular and cerebrospinal fluid pressure: imaging protocol and quantification method. Scientific reports, 8(1), 12639.
  2. Jonas JB. Role of cerebrospinal fluid pressure in the pathogenesis of glaucoma. Acta ophthalmologica. 2011 Sep;89(6):505-14.
  3. Jonas JB, Wang N. Cerebrospinal fluid pressure and glaucoma. Journal of ophthalmic & vision research. 2013 Jul;8(3):257.
  4. Križaj D. What is glaucoma?. Webvision: The Organisation of the Retina and Visual System [Internet]. 2019 May 30.
  5. Jonas JB, Ritch R, Panda-Jonas S. Cerebrospinal fluid pressure in the pathogenesis of glaucoma. Progress in brain research. 2015 Jan 1;221:33-47.
  6. Berdahl JP, Fautsch MP, Stinnett SS, Allingham RR. Intracranial pressure in primary open angle glaucoma, normal tension glaucoma, and ocular hypertension: a case–control study. Investigative ophthalmology & visual science. 2008 Dec 1;49(12):5412-8.
  7. Landi L, Casciaro F, Telani S, Traverso CE, Harris A, Verticchio Vercellin AC, Saint L, Iester M. Evaluation of cerebrospinal fluid pressure by a formula and its role in the pathogenesis of Glaucoma. Journal of Ophthalmology. 2019 Nov 14;2019.
  8. Berdahl JP, Allingham RR. Intracranial pressure and glaucoma. Current opinion in ophthalmology. 2010 Mar 1; 21 (2): 106-11.
  9. Wostyn P, Killer HE, De Deyn PP. Glymphatic stasis at the site of the lamina cribrosa as a potential mechanism underlying open‐angle glaucoma. Clinical & experimental ophthalmology. 2017 Jul;45(5):539-47.
  10. Kwun Y, Han JC, Kee C. Comparison of lamina cribrosa thickness in normal tension glaucoma patients with unilateral visual field defect. American journal of ophthalmology. 2015 Mar 1;159(3):512-8.
  11. Fleischman D, Allingham RR. The role of cerebrospinal fluid pressure in glaucoma and other ophthalmic diseases: A review. Saudi Journal of Ophthalmology. 2013 Apr 1;27(2):97-106.
  12. Marek B, Harris A, Kanakamedala P, Lee E, Amireskandari A, Carichino L, Guidoboni G, Tobe LA, Siesky B. Cerebrospinal fluid pressure and glaucoma: regulation of trans-lamina cribrosa pressure. British Journal of Ophthalmology. 2014 Jun 1;98(6):721-5.
  13. Siaudvytyte L, Januleviciene I, Ragauskas A, Bartusis L, Meiliuniene I, Siesky B, Harris A. The difference in translaminar pressure gradient and neuroretinal rim area in glaucoma and healthy subjects. Journal of Ophthalmology. 2014 Apr 30;2014.
  14. Chen MJ. Normal tension glaucoma in Asia: Epidemiology, pathogenesis, diagnosis, and management. Taiwan Journal of Ophthalmology. 2020 Oct;10(4):250.

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