| disease | Low-tension Glaucoma |
The concept that glaucomatous optic nerve atrophy, optic disc cupping, and glaucomatous visual field defects are often attributed to elevated intraocular pressure has been called into doubt, as some patients develop these changes without high intraocular pressure. This condition was first described by von Graefe (1857) and has since drawn the attention of ophthalmologists, leading to various names for it. Although some doctors have noted that conditions such as carotid artery calcification, alcoholism, pituitary tumors, and other pathologies may cause similar changes, long-term observations have found no such causes in many patients with these alterations. For cases where no definitive cause can be identified, intraocular pressure remains within the normal range, and glaucomatous optic nerve atrophy, cupping, and visual field damage are present, the condition is classified as low-tension glaucoma (LTG). In modern literature, it is often referred to as normal-tension glaucoma. The incidence of LTG in the population is approximately 0.15%, accounting for 18–20% of all open-angle glaucoma cases.
bubble_chart Pathogenesis
The disease cause of LTG is highly complex, and to date, its exact pathogenesis remains unclear, with numerous proposed causative factors. The most widely supported theory involves vascular factors, followed by local anatomical factors, which are elaborated below:
1. Vascular Factors Many researchers have observed that LTG patients exhibit a higher incidence of hemodynamic crises, as well as a greater prevalence of cardiovascular and cerebrovascular diseases and hypotension. They also frequently present with abnormalities in hemorheology, such as increased whole blood viscosity. Additionally, these patients show a higher incidence of disc hemorrhages, impaired autoregulation of small blood vessels in the optic disc, and fluorescein angiography revealing filling defects in the optic disc. These phenomena collectively suggest that the occurrence of LTG is closely related to ischemia of the optic nerve head. The causes of optic disc ischemia may include the following aspects: ① Systemic or local small vessel pathologies may lead to occlusion of certain small vessels supplying the optic disc, resulting in segmental necrosis of the disc rim and subsequent atrophy of nerve fibers, leading to visual field defects. Worsening or increased numbers of small vessel occlusions can further progress nerve fiber atrophy, causing continuous expansion of visual field defects. ② Hemodynamic crises, such as massive hemorrhage, severe myocardial infarction, arrhythmia, or shock, may lead to decreased blood pressure or chronic hypotension, reducing ocular perfusion pressure and causing poor blood supply to the optic disc, resulting in ischemia. ③ Abnormalities in hemorheology, such as increased blood viscosity, elevated platelet adhesion rates, and impaired fibrinolytic systems, increase vascular resistance and predispose to thrombosis, all of which are associated with ischemia.
Some scholars propose that although both LTG and ischemic optic neuropathy are ischemic diseases, the affected vessels may differ. Moreover, the former is the result of long-term chronic insufficient blood supply to the optic disc due to the interaction of multiple factors.2. Local Anatomical Factors Proponents of this view argue that the atrophy and cupping of the optic nerve head in LTG patients stem from certain anatomical defects in the lamina cribrosa. For instance, the lamina cribrosa may have fewer cross-linking fibers, thinner connective tissue, and larger pore sizes—especially in the superior and inferior regions—compared to normal individuals. These structural weaknesses make the lamina cribrosa abnormally fragile and less resistant to intraocular pressure. Even under normal intraocular pressure, the lamina cribrosa may collapse posteriorly, distorting the pores and injuring nerve fibers or compressing them, disrupting axoplasmic transport and leading to nerve fiber atrophy. Concurrently, capillaries in the area may also become twisted, indirectly impairing blood supply and further exacerbating nerve fiber atrophy. Additionally, it has been observed that LTG patients tend to have longer axial lengths and larger vitreous cavities, with relatively larger cup-to-disc ratios, which may also be related to the pathogenesis of LTG.
In summary, the pathogenesis of this disease has not yet been fully elucidated, and its causative factors are complex. Current evidence suggests that the development of LTG may be linked to structural differences in ocular tissues, particularly the lamina cribrosa of the optic disc, which render them abnormally sensitive to intraocular pressure or poor perfusion. These structural variations may be congenital or acquired.
The onset is very insidious, and the disease often occurs imperceptibly. Due to the lack of subjective symptoms, patients are usually only detected when they seek medical attention at the middle or advanced stage, or during routine examinations.
1. Medical history: In the early stage, the vast majority of patients have no subjective symptoms, while a few may experience discomfort such as eye distension or visual fatigue. Complaints of decreased vision are mostly related to refractive errors, internal visual obstruction, and macular lesions. Patients at the middle or advanced stage may have reduced central vision.
2. Intraocular pressure (IOP):
(1) Average IOP: The IOP of LTG patients is within the statistically normal range. However, many scholars have observed that the IOP of these patients fluctuates near the upper limit of normal, with a higher baseline IOP, and their average IOP seems higher than that of normal individuals.
(2) 24-hour IOP: In normal individuals, IOP can fluctuate within 24 hours due to physiological factors, but the fluctuation is generally ≤0.67 kPa. Some scholars have also noted that in some patients, the 24-hour IOP fluctuation exceeds 0.67 kPa or even 1.06 kPa.
(3) Effect of posture on IOP: In normal individuals, the IOP measured in the supine position is higher than that in the sitting position, but the difference is ≤0.79 kPa. Some LTG patients show a larger IOP difference between these two postures, with reported values ranging from 1.14 to 1.33 kPa.
(4) Long-term changes in IOP: Some scholars have observed during long-term monitoring of LTG patients that the IOP of a few patients tends to rise, shifting from the lower to the upper limit of the normal range, such as from 1.33 kPa to 2.66 kPa, or even exceeding the normal range and converting to open-angle glaucoma. However, not all LTG patients exhibit these characteristics; some have lower and more stable IOP.
4. Provocative tests: The results of provocative tests in LTG patients are inconsistent. Some scholars report that most patients exhibit moderate to high IOP elevation in response to corticosteroids, while others report no difference from normal individuals. The water-drinking test shows similar variability. In summary, the value of these tests remains uncertain.
5. Refraction and ocular biometry: The incidence of myopia in LTG patients is higher than in the general population. Their vitreous cavity and axial length are longer than normal, and the vertical corneal curvature radius is also larger, with a tendency toward larger C/D ratios.
6. Optic disc: The optic disc changes in LTG patients are similar to those in POAG. However, recent studies have observed that the neuroretinal rim in LTG is narrower than in POAG, with the narrowest area located inferiorly or inferotemporally. The characteristics of the optic cup also differ: in LTG, the cup slopes inferotemporally, whereas in POAG, the cup wall is steeper, and rim narrowing is more uniform. Slit-like lamina cribrosa defects and vascular overpass phenomena are more common in open-angle glaucoma. These features help differentiate the two conditions.
The incidence of optic disc hemorrhages in LTG is significantly higher than in POAG and normal eyes. These hemorrhages often appear flame-shaped or linear, typically occurring at the rim notch or appearing 2–3 months before the notch develops. They can recur and are usually located at the 7 or 11 o'clock position in the right eye and the 1 or 5 o'clock position in the left eye. Many scholars believe that optic disc hemorrhages result from vascular infarction in the optic nerve head, while others attribute them to vascular injury caused by deformation of the lamina cribrosa. The high incidence of disc hemorrhages in LTG patients may be related to the fragility of the lamina cribrosa structure. Regardless of the cause, the occurrence of optic disc hemorrhage is a sign of disease progression and worsening.
7. Retinal Nerve Fiber Layer Defect (RNFLD) The RNFLD in LTG is similar to that in DOAG, manifesting as localized or diffuse defects. In the early stages, it often affects the nerve fiber bundles in the inferotemporal and superotemporal regions, appearing as slit-like or wedge-shaped dark bands, or as diffuse thinning and sparseness, resembling a combed-hair appearance. In the advanced stage, it mostly presents as complete atrophy, with the retina showing a dark granular appearance. Some researchers have observed that RNFLD in LTG more frequently involves the inferotemporal nerve fiber bundles compared to POAG.
8. Optic Nerve Damage It is generally believed that the optic nerve damage in this disease is similar to that of POAG. However, some scholars have observed that the visual field defects occur earlier, are more frequently located near the fixation point, have steeper slopes, deeper defects, and are more common in the upper visual field than the lower, which is related to the fact that rim changes often occur in the inferotemporal region. The differences in visual field damage between LTG and POAG suggest that the mechanisms of damage may differ.
9. Fluorescein Fundus Angiography Fluorescein fundus angiography reveals that most LTG patients exhibit filling defects in the optic disc, often presenting as segmental hypofluorescence, suggesting optic nerve head ischemia. Some scholars have observed that when filling defects progress from comparative to absolute, visual field damage occurs. New visual field defects are always accompanied by new optic disc filling defects or the expansion of existing ones, and optic disc filling defects appear before visual field damage. This seems to indicate that the visual functional damage is directly related to optic disc ischemia. However, Quigley (1986) argued that optic disc filling defects do not provide evidence of primary vascular insufficiency but may instead result from tissue atrophy accompanied by vascular disappearance.
10. Ocular Pulse Pressure and Perfusion Pressure Drance (1973) reported that LTG patients have lower ocular pulse pressure than suspected POAG patients. Goldberg (1981) suggested that the diastolic ocular pulse pressure in LTG is lower than in suspected POAG, while Spaeth (1975) found no difference in ocular pulse pressure among LTG, POAG, and normal individuals.
Regarding perfusion pressure, Goldberg (1981) reported that the diastolic perfusion pressure in LTG patients is similar to or possibly lower than in suspected POAG, whereas Kramer (1987) found no difference between LTG patients and normal individuals. He also noted that perfusion pressure is easily influenced by blood pressure, making conclusions unreliable. Instead, the resistance of the ciliary choroidal vascular network, measured by ocular pulse amplitude and blood flow, better reflects blood supply conditions. He proposed that the resistance of the ciliary choroidal vascular network in LTG patients is 2–3 times higher than in normal individuals, leading to reduced blood flow due to increased resistance. Perkine (1981) also studied this aspect, mentioning in one report that the ocular pulse amplitude in LTG is lower than in normal eyes, while in another report, he found no difference, though the variability in amplitude was greater in LTG.
In summary, observations on ocular pulse pressure and perfusion pressure in LTG are inconsistent, but they may be lower than in normal eyes and suspected POAG.
11. Systemic Conditions LTG patients have a higher incidence of hypotension, and many authors consider low diastolic pressure a risk factor for the disease. The incidence of hemodynamic crises and cardiovascular or cerebrovascular diseases is also significantly higher than in normal individuals. Additionally, it has been noted that LTG patients experience migraines more frequently. In terms of hemorheology, LTG patients tend to have higher whole blood viscosity, and abnormalities in the coagulation and fibrinolytic systems are more common.
12. Progressive and Non-progressive LTG. Some scholars have observed that in some LTG patients, optic disc atrophy and visual field defects do not progress, while in others they do. Based on this manifestation, the disease is classified into progressive and non-progressive types. The underlying causes of these two types may differ. Drance (1985) suggested that among patients diagnosed with LTG who had previously experienced hemodynamic crises, most of their visual field and optic disc damage did not progress, whereas in patients without such crises, most visual field defects progressed. The former may be due to hemodynamic crises or vascular sexually transmitted diseases causing optic disc and segmental infarction; if no further infarction occurs, the damage will not progress. Regarding progressive LTG, Chandler (1979) proposed that such patients often have intraocular pressure at the upper limit of normal and aqueous outflow facility at the lower limit of normal, with abnormally fragile lamina cribrosa structures that are highly sensitive to pressure-induced damage. To halt the progression of optic disc and visual field damage in these patients, their intraocular pressure must be lowered even further.
13. LTG with and without anterior segment lesions. Some scholars have proposed additional conditions and restrictions for the diagnosis of this disease, such as requiring multiple provocative tests to be normal, the coefficient of aqueous outflow and the pressure-flow ratio to be normal, and intraocular pressure fluctuations ≤0.67 kPa, among others. On the other hand, some scholars believe that the diagnosis of LTG requires abnormalities in the aforementioned criteria. Levene (1982) argued that adding these conditions to diagnose or exclude the disease is inappropriate and subjective, and that classification is necessary to truly and objectively understand LTG. Therefore, he advocated dividing the disease into: ① LTG accompanied by glaucomatous aqueous humor dynamics abnormalities (referring to abnormal C value, po/c, daily intraocular pressure fluctuations, positive provocative tests, etc.); ② LTG not accompanied by glaucomatous (aqueous humor dynamics abnormalities). He believed that at least one-third of LTG patients have abnormalities in aqueous humor dynamics.
14. Klaver's classification: Klaver (1985) further divided LTG patients into the focal ischemic subgroup (FILTG), the senile sclerotic subgroup (SSLTG), and the miscellaneous subgroup (LTGmisc), which does not belong to either FILTG or SSLTG, based on medical history, age, and characteristics of optic disc changes. The characteristics of optic disc changes in FILTG include localized excavation of the disc rim tissue, vertical expansion of the optic cup upward or downward, accompanied by corresponding localized peripapillary atrophy. SSLTG, on the other hand, presents with a pale optic disc, a moth-eaten and obliquely excavated disc rim, accompanied by extensive choroidal sclerosis and peripapillary atrophy.
POAG-like optic disc changes, RNFLD, and visual field defects that are acquired postnatally, with untreated natural intraocular pressure ≤2.79 kPa (Goldmann applanation tonometry), open anterior chamber angles, and exclusion of other diseases causing optic disc atrophy and visual field defects, can establish the diagnosis. Therefore, the diagnosis of LTG relies on ruling out other conditions, making differential diagnosis particularly important.
bubble_chart Treatment Measures
Since the disease cause of this condition is unknown and the contributing factors are complex, there is currently no effective treatment available. Some scholars have adopted various measures such as medication, laser therapy, and filtration surgery to further lower intraocular pressure in an attempt to halt the progression of visual field damage, but the results are generally inconclusive. Abedin (1982) suggested that intraocular pressure must be reduced to at least below 1.59 kPa to be effective, while Bloomfield (1953) believed that surgery is not helpful in preventing further deterioration of visual function in this disease. The use of agents to improve blood circulation has also yielded unsatisfactory results. Topical application of 1% levonorepinephrine can elevate the ocular stirred pulse pressure and reduce intraocular pressure. Intravenous injection of strophanthin can eliminate the blood pressure difference between the orbital blood pressure and the upper arm blood pressure. Treatment should also address other abnormalities present in the patient, such as gastrointestinal disorders, anemia, congestive heart failure, orthostatic hypotension, transient ischemic attacks, arrhythmias, and cardiovascular diseases, to improve blood supply to the optic disc.
In summary, there is currently no effective treatment to halt the progression of optic disc and visual field damage in LTG patients. Early detection, timely treatment, effective reduction of intraocular pressure, and improvement of poor optic disc blood perfusion may help slow the progression of the disease. Most LTG patients experience a slow progression of the disease, with visual function maintained for a relatively long period, and the final outcome is similar to that of POAG. Recently, Shirai (1988) reported preliminary efficacy using calcium antagonists, and Yoshihiko Shiose (1988) reported initial therapeutic effects with methylcolamin in treating low-tension glaucoma, which warrants further research.
1. Primary open-angle glaucoma (POAG): Due to the lack of 24-hour intraocular pressure (IOP) monitoring, peak IOP may go undetected. In myopic eyes, the sclera may be softer, leading to underestimation of IOP when measured with a Schiotz tonometer. Additionally, patients taking β-blockers or cardiac glycosides may exhibit artificially lowered IOP, leading to misdiagnosis as low-tension glaucoma (LTG). Therefore, all IOP-lowering medications should be discontinued, and repeated IOP measurements, including 24-hour IOP monitoring, should be performed. For myopic eyes, applanation tonometry should be used to confirm that IOP remains within the normal range before diagnosing LTG.
2. Other types of glaucoma: Conditions such as corticosteroid-induced glaucoma, glaucomatocyclitic crisis (Posner-Schlossman syndrome), pigment dispersion syndrome, trauma-related glaucoma, and uveitis-associated glaucoma may present with transient IOP elevation followed by a quiescent phase, leading to misdiagnosis as LTG. A detailed medical history and thorough ocular examination can help exclude these conditions.
3. Congenital or acquired optic nerve head abnormalities
, such as physiological large optic cup, optic disc coloboma, congenital optic pit, or optic nerve hypoplasia, may mimic glaucomatous optic nerve cupping and atrophy. However, careful consideration of the patient’s age, detailed optic disc examination, and assessment of visual field defects (including their characteristics and progression) can help differentiate these conditions.
4. Ischemic optic neuropathy
: Typically, ischemic optic neuropathy does not cause optic disc cupping or enlargement of the optic cup. However, some reports suggest that anterior ischemic optic neuropathy (AION), particularly arteritic AION (e.g., giant cell arteritis), may lead to optic disc changes resembling glaucomatous cupping, potentially confusing it with LTG. Key distinguishing features include: ① Sudden or subacute onset with self-reported acute vision loss, possibly accompanied by headache or eye pain, whereas LTG patients often lack symptoms and progress insidiously. ② In ischemic optic neuropathy, optic disc pallor exceeds cupping, and the neuroretinal rim appears pale, whereas in glaucoma, cupping involves an enlarged and deepened cup with a remaining pinkish rim. ③ Visual field defects in ischemic optic neuropathy often involve fixation, presenting as altitudinal or quadrantanopic defects (not respecting the horizontal or vertical midline), with an arcuate defect extending from the blind spot. The severity of visual field loss exceeds the degree of cupping. ④ Fluorescein angiography: In ischemic optic neuropathy, early-phase disc fluorescence shows abnormal vessel dilation and leakage, creating a blurred hyperfluorescent disc. Late-phase may reveal delayed filling or hypofluorescence. ⑤ Systemic associations: Often linked to giant cell arteritis, collagen vascular diseases, diabetes, syphilitic arteritis, or hypertensive arteriosclerosis.
5. Myopia
: In myopic eyes, particularly high myopia, the optic disc may exhibit shallow cupping resembling glaucomatous changes. Additionally, chorioretinal atrophy may cause visual field defects, leading to misdiagnosis. High myopia with coexisting glaucoma is also easily misdiagnosed. Key differentiating factors include careful slit-lamp biomicroscopy (using a three-mirror lens) to assess optic disc morphology and detect any chorioretinal lesions causing visual field defects. Fluorescein angiography may also aid diagnosis, as myopic optic disc cupping does not show the absolute filling defects seen in LTG. 6. Retinal disorders: Schreiber (1906) proposed that retinal vascular occlusions causing ganglion cell death could lead to ascending optic atrophy, mimicking glaucomatous optic disc cupping. However, while some retinal disorders may produce glaucoma-like visual field defects, they typically do not exhibit glaucomatous optic disc changes.
7. Others: Hereditary optic atrophy, optic neuritis, arachnoiditis, nonspecific giant cell arteritis, pituitary tumors, carotid artery calcification and ecchymosis compressing the optic nerve, hysteria may occasionally be misdiagnosed as this disease, and alcohol intoxication may also cause optic disc atrophy and excavation. All these conditions should be carefully excluded one by one.
