normal-tension glaucoma

DEFINITION / DIAGNOSIS: A subtype of primary open-angle glaucoma (POAG) with (1) glaucomatous optic disc cupping and neuroretinal rim thinning, (2) corresponding visual field loss, (3) open angles on gonioscopy, and (4) untreated IOP statistically in the normal range (≤21 mmHg) on repeated measurements, including diurnal variation. It is a diagnosis of exclusion: rule out secondary causes (prior steroid use, prior elevated IOP that has since normalized, e.g., from uveitis, pigmentary glaucoma, or trauma), intermittent angle closure, and non-glaucomatous optic neuropathies.

PATHOPHYSIOLOGY: Not fully understood. IOP-independent mechanisms are thought to contribute: (a) vascular dysregulation and reduced optic nerve head perfusion (vasospasm, migraine, Raynaud phenomenon, nocturnal systemic hypotension, over-treated hypertension, sleep apnea), (b) low CSF pressure, which increases the translaminar pressure gradient across the lamina cribrosa, (c) structural lamina cribrosa susceptibility, and (d) thin central corneal thickness, which may underestimate true IOP. Genetic associations include OPTN (optineurin) and TBK1 duplications. Retinal ganglion cell axons are damaged at the lamina cribrosa.

EPIDEMIOLOGY / RISK FACTORS: More common in women and older adults, with higher prevalence in Japanese and other East Asian populations (often the majority of POAG there). Associated with migraine, Raynaud, autoimmune disease, disc hemorrhages (a classic feature), and nocturnal hypotension.

CLINICAL FEATURES: Usually asymptomatic until late. Painless, gradual peripheral vision loss. Exam findings include disc hemorrhages (splinter/flame hemorrhages at the rim, more common than in high-tension POAG), acquired optic disc pits, peripapillary atrophy, and a larger cup-to-disc ratio. Visual field defects tend to be more focal, deeper, and closer to fixation (paracentral scotomas, nasal step, arcuate defects) than in high-tension POAG.

WORKUP: Tonometry (including diurnal curve), gonioscopy, pachymetry, dilated fundus exam, OCT of the RNFL, and automated perimetry. Because it is a diagnosis of exclusion, features atypical for glaucoma (pallor out of proportion to cupping, central or visual acuity loss, rapid progression, age <50, or neurologic findings) should prompt neuroimaging (MRI) and workup for compressive lesions (e.g., pituitary or suprasellar tumors), ischemic, inflammatory, or other optic neuropathies, and syphilis.

MANAGEMENT: IOP is still the only modifiable risk factor. The Collaborative Normal-Tension Glaucoma Study showed that lowering IOP by 30% slowed field progression, although some untreated eyes did not progress. Options: prostaglandin analogs (first line), beta-blockers, alpha-2 agonists (brimonidine may have neuroprotective effects, but beware that beta-blockers can worsen nocturnal hypotension), carbonic anhydrase inhibitors, and laser trabeculoplasty or surgery (trabeculectomy) if progressing. Also avoid excessive nocturnal blood pressure lowering, and consider treating vascular risk factors and sleep apnea. Calcium channel blockers have been investigated for vasospasm but are not standard.

BOARD PEARLS: (1) Open angle + optic nerve damage + visual field loss + IOP ≤21 = NTG. (2) Disc hemorrhages are classic. (3) Think about thin cornea, nocturnal hypotension, and vasospastic disease (migraine, Raynaud). (4) Atypical presentation → image the brain. (5) Treat by lowering IOP ≥30%. (6) Contrast with ocular hypertension (high IOP without damage), angle-closure glaucoma (painful, red eye, mid-dilated pupil, halos, shallow chamber), and high-tension POAG.