Identifying normal tension glaucoma presents a challenge for clinicians. This form of the disease does not present with significant intraocular pressure (IOP) increases — the most prominent clinical risk factor for glaucoma. Without an elevated IOP to increase suspicion, optometrists must be familiar with the unique characteristics associated with normal tension glaucoma to sharpen their diagnostic acumen during otherwise routine ophthalmic examinations. 

Normal tension glaucoma, researchers believe, exists upon the same disease continuum as primary open angle glaucoma (POAG) and accounts for up to 40% of patients with open angle glaucoma in the US.1 While normal tension glaucoma demonstrates the same progressive glaucomatous optic nerve damage and visual field loss as POAG, IOP is consistently measured below 21 mm Hg.  

Know Your Patient’s History

Obtaining a careful history is key to solving many diagnostic dilemmas, and normal tension glaucoma is no exception. Patients with normal tension glaucoma are often older than those with POAG and the condition is more prevalent among women and individuals of Japanese ancestry.2 As with POAG, a family history of glaucoma is a risk factor for normal tension glaucoma. 

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Glaucoma is a heterogeneous disease and familial forms of normal tension glaucoma involve genetic mutations inherited in an autosomal dominant pattern. Patients with these genetic mutations may develop normal tension glaucoma at a younger age and will likely have an extensive family history of glaucoma.3,4 

Poor blood flow and vascular dysfunction are significant contributing factors to normal tension glaucoma pathogenesis and have been identified as risk factors for progression. Low blood pressure, which may result from aggressively treating systemic hypertension, reduces ocular perfusion to the optic nerve head and contributes to low ocular perfusion pressure — a well-known risk factor for normal tension glaucoma. Clinicians can quickly estimate ocular perfusion pressure by subtracting IOP from systolic, diastolic, or mean arterial blood pressure.

Signs of faulty vascular autoregulation include migraine and abnormally reduced blood flow to the hands and feet in response to cold or stress. This can present as persistently cold extremities, sometimes with a whitening or bluing of the skin, as in Raynaud phenomenon. Both migraine and Raynaud phenomenon increase the risk of having or developing normal tension glaucoma.2,3 Research also shows that migraine is an independent risk factor for normal tension glaucoma progression.5 Obstructive sleep apnea, which may cause optic disc hypoperfusion and transient ischemia, is more prevalent among individuals with normal tension glaucoma.6 

Secondary forms of glaucoma can masquerade as normal tension glaucoma. A history of steroid therapy or significant ocular trauma or inflammatory conditions suggest an alternative diagnosis. 

Identifying these variables can help rule out other forms of glaucoma that are associated with more isolated episodes of increased IOP. By adding a few focused  history-related questions to an otherwise routine ophthalmic exam, optometrists can more astutely identify normal tension glaucoma risk and prime their attention toward additional key aspects of the examination. 

Identify the Clinical Characteristics

While IOP will not demonstrate a significant elevation in patients with normal tension glaucoma, it is generally skewed toward the higher range of normal. IOP is diurnal and often hits its highest peak outside of office hours, so isolated measurements obtained in-office do not provide a complete diurnal profile. When possible, clinicians should obtain multiple IOP measurements at various time points to better understand these diurnal variations. Patients with normal tension glaucoma show greater diurnal IOP fluctuations compared with those without glaucoma. If clinicians fail to account for this diurnal curve, POAG can be misdiagnosed as normal tension glaucoma and affect target IOP values. Higher IOP within the normal range and greater IOP fluctuations in patients with additional risk factors should be considered suspicious and often warrants additional testing.

Central corneal thickness (CCT) is an important clinical measurement that can give an IOP measurement context. Thinner CCTs may lead to underestimated IOP values, but adjusting IOP measurement based on pachymetry values is not recommended. CCT is thinner among patients with normal tension glaucoma compared with individuals with POAG and patients without glaucoma. A thinner CCT can support normal tension glaucoma suspicion in patients with additional risk factors.  

Clinical and historical findings may warrant gonioscopic evaluation. During this evaluation, clinicians view the angle directly, which is necessary to identify abnormalities that might alter the differential diagnosis. Patients with normal tension glaucoma have a normal anterior chamber angle, which cannot be properly evaluated without direct viewing. Abnormal gonioscopic findings, such as dense pigment, can alter the differential to include other etiologies, such as pigment dispersion or pseudoexfoliation.

Examine the Optic Nerve

Regardless of whether historical or clinical findings indicate normal tension glaucoma suspicion, scrutiny of the optic disc is the primary means of identifying patients with glaucoma or glaucoma suspects. As with POAG, a larger cup to disc (C/D) ratio or asymmetry of 0.2 or greater in the C/D ratio indicates glaucoma suspicion. Focal defects of the retinal nerve fiber layer (RNFL) can often be identified with good fundus imaging. Red-free imaging can enhance the appearance of RNFL defects, and some imaging systems allow wavelength manipulation after capture for better superficial retinal layer viewing. 

Figure 1. RNFL focal defects may be obtained through good fundus imaging.
Figure 2. Red-free imaging may enhance the appearance of RNFL defects.

Optic disc size provides context for the expected C/D ratio. This measurement can be obtained quickly during slit lamp evaluation using the vertical slit beam and a fundus lens. At first glance, a moderate C/D ratio may not create a concern, but when framed within the context of a small optic disc, a moderate C/D ratio is more suspicious.

An optic nerve damaged by normal tension glaucoma is often indistinguishable from a nerve damaged by POAG, but some patterns of damage are more commonly observed in normal tension glaucoma. The neuroretinal rim may be thinner in patients with normal tension glaucoma compared with individuals with POAG, especially within the inferior and inferotemporal sectors. Disc hemorrhages are more frequent in normal tension glaucoma and are a sign of poor control.3 While disc hemorrhages are not pathognomonic for glaucoma, patients who present with them should be considered glaucoma suspects unless another pathology is clearly responsible for this finding. Since glaucoma is defined as damage to the optic nerve, any suspicious disc findings should prompt further review of the patient’s medical history and more frequent follow-up visits. 

Optical coherence tomography (OCT) of the RNFL and ganglion cell layer (GCL) is a mainstay in glaucoma evaluation and management. Like the overlap in optic disc appearance, there is a significant overlap in patterns of RNFL and GCL loss in patients with POAG and NTG. However, some studies have shown that RNFL defects are more focal and closer to the macula in normal tension glaucoma and more diffuse in POAG.3 Summary measures, such as average RNFL or quadrant map values, can miss focal areas of RNFL and GCL thinning, so attention to the thickness maps and patterns of RNFL thinning can help identify focal thinning. A combination of anatomically correlating RNFL and GCL thinning creates a stronger suspicion of glaucoma than either variable alone. 

Figure 3. RNFL defects are more focal and closer to the macula in normal tension glaucoma.
Figure 4: Assessing GCL thickness in combination with RNFL thickness may be better for identifying glaucoma suspicion than either variable alone.

Understand Visual Field Patterns

Differences in patterns of visual field loss have been reported between patients with NTG and POAG. A 2023 comparison study revealed that arcuate defects were more common among patients with normal tension glaucoma compared with patients with POAG or primary angle closure glaucoma. Patients with normal tension glaucoma also had higher pattern standard deviation measures, suggesting more localized visual field loss.7 These findings are consistent with other reports detailing localized visual field loss and visual field loss closer to fixation in patients with normal tension glaucoma.8,9 

Patients with central visual field involvement at baseline are at increased risk of progression.9 Central visual field defects can be missed with the standard 24-2 grid pattern, so the finer grid pattern of the 10-2 visual field may be a better alternative for identifying central defects. Utilizing both 24-2 and 10-2 visual field testing is recommended in cases with central visual field loss or significant macular GCL loss.  

Figure 5: Standard 24-2 testing may potentially miss central visual field defects.
Figure 6: The finer grid pattern of the 12-2 visual field may make it a better alternative for identifying central visual field defects compared with 24-2 testing.

Identifying normal tension glaucoma is no easy task, but clinicians who familiarize themselves with the disorder’s unique risk factors and presentations can stand out from others who fail to recognize the clinical significance of their findings. With a combination of clinical testing, chart reviews, and clinical sleuthing, optometrists can identify and monitor normal tension glaucoma and provide superior care for their patients.

References

  1. Razeghinejad MR, Lee D. Managing normal tension glaucoma by lowering the intraocular pressure. Surv Ophthalmol. 2019;64(1):111-116. doi:10.1016/j.survophthal.2018.07.003
  2. Mallick J, Devi L, Malik PK, Mallick J. Update on normal tension glaucoma. J Ophthalmic Vis Res. 2016;11(2):204-8. doi:10.4103/2008-322X.183914
  3. Allingham RR, Moroi SE, Shields MB, Damji KF. Shield’s Textbook of Glaucoma. Seventh edition. Wolters Kluwer, 2021.
  4. Trivli A, Koliarakis I, Terzidou C, et al. Normal-tension glaucoma: pathogenesis and genetics. Exp Ther Med. 2019;17(1):563-574. doi:10.3892/etm.2018.7011
  5. Drance S, Anderson DR, Schulzer M. Risk factors for progression of visual field abnormalities in normal-tension glaucoma. Am J Ophthalmol. 2001;131(6):699-708. doi:10.1016/s0002-9394(01)00964-3
  6. Bilgin G. Normal-tension glaucoma and obstructive sleep apnea syndrome: a prospective study. BMC Ophthalmol. 2014;14:27. doi:10.1186/1471-2415-14-27
  7. Jiang J, Ye C, Zhang C, et al. The patterns of visual field defects in primary angle-closure glaucoma compared to high-tension glaucoma and normal-tension glaucoma. Ophthalmic Res. Published online April 14, 2023. doi:10.1159/000530175
  8. Thonginnetra O, Greenstein VC, Chu D, Liebmann JM, Ritch R, Hood DC. Normal versus high tension glaucoma: a comparison of functional and structural defects. J Glaucoma. 2010;19(3):151-157. doi:10.1097/IJG.0b013e318193c45c
  9. Raman P, Suliman NB, Zahari M, Mohamad NF, Kook MS, Ramli N. Baseline central visual field defect as a risk factor for NTG progression: a 5-year prospective study. J Glaucoma. 2019;28(11):952-957. doi:10.1097/IJG.0000000000001359

This article originally appeared on Optometry Advisor

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Glaucoma Other glaucoma