Central corneal thickness in low-tension glaucoma

BACKGROUND: It is possible that the intraocular pressure (IOP) is underestimated in eyes whose central cornea is thinner than normal. The objective of this study was to determine and establish the significance of central corneal thickness in patients with low-tension (normal-tension) glaucoma compared with those with chronic open-angle glaucoma (COAG) or ocular hypertension and healthy eyes. METHODS: The study was carried out from February 1998 to May 1999. Central corneal thickness was measured by ultrasonic pachymetry and IOP was measured by Goldmann applanation tonometry in 25 patients with low-tension glaucoma (untreated IOP less than 21 mm Hg with evidence of optic nerve head damage and corresponding visual field loss on automated perimetry), 80 patients with COAG (untreated IOP 21 mm Hg or greater with evidence of optic nerve head damage and corresponding visual field loss on automated perimetry), 16 patients with ocular hypertension (untreated IOP 21 mm Hg or greater, with normal optic nerve head and no history of glaucoma or elevated IOP, and normal visual field on automated perimetry) and 50 control subjects (untreated IOP less than 21 mm Hg with normal optic nerve head and no history of glaucoma or elevated IOP). Analysis with Pearson's product-moment correlation was performed to determine the correlation of IOP and central corneal thickness, and one-way analysis of variance was used to compare corneal thickness between groups. RESULTS: The central cornea was significantly thinner in the low-tension glaucoma group (mean 513.2 mu [standard deviation (SD) 26.1 mu]) than in the COAG group (mean 548.2 mu [SD 35.0 mu]) and the control group (mean 556.7 mu [SD 35.9 mu]) (p < 0.001). No significant difference in corneal thickness was found between the COAG and control groups. The ocular hypertension group had significantly thicker corneas (mean 597.5 mu [SD 23.6 mu]) than the three other groups (p < 0.001). INTERPRETATION: Patients with low-tension glaucoma may have thinner corneas than patients with COAG and healthy subjects. This results in underestimation of their IOP. Corneal thickness should be taken into account when managing these patients to avoid undertreatment.     

Difference of optic disc topography between a low-tension group and a high-tension group in normal-tension glaucoma patients

PURPOSE: Glaucomatous visual field loss and optic disc damage differ by intraocular pressure (IOP) levels. In this study, we compared the optic disc topography in the high-tension group and the low-tension group in normal-tension glaucoma (NTG). METHOD: We selected NTG patients with mean deviation (MD) > or = -10.00 dB and the highest recorded IOP of < 14 mmHg or > or = 17 mmHg without glaucoma treatment. We classified NTG eyes into the following two groups: 1) a low-tension group with the highest recorded IOP of < 14 mmHg, 2) a high-tension group with the highest recorded IOP of > or = 17 mmHg. The optic disc parameters in the low-tension group eyes were compared with those in the high-tension group eyes using a Heidelberg Retina Tomograph. RESULTS: Nineteen eyes of nineteen patients were selected for each group. The cup/disc area ratio in the global sector, and the rim volume in the nasal sector of the low-tension group had deteriorated more than in the high-tension group. CONCLUSIONS: The disc topography is different between the low-tension group and the high-tension group in the nasal sector, suggesting that different pathogenetic mechanisms exist in the optic disc damage in NTG.     

Glaucoma without ocular hypertension. A clinical study

One hundred eighty-four glaucomatous eyes (125 patients) with visual field defects of Stage I and II in the central visual field were examined with the Octopus perimeter 201, Program 31 or 33, and were divided into 3 groups according to maximum intraocular pressures: (1) low-tension glaucoma (21 mm Hg), (2) glaucoma simplex (22-29 mm Hg), (3) glaucoma simplex (30-39 mm Hg). In these three groups of glaucomatous eyes the cupping of the optic disk, vision and blood pressure were examined and a further check for cardiovascular risk factors was carried out by the internist. All three groups proved to have an equally high incidence of cardiac insufficiency, abnormal EKG changes and diabetes. However, a low systolic blood pressure was found to be the risk factor more often in patients with low-tension glaucoma than with glaucoma simplex. Furthermore, intraocular pressures in the low-tension glaucoma group were higher than those in the normal population. The occurrence of cupping of the optic disk, which is not present with purely vascular optic nerve diseases, and the location of visual field defects in low-tension glaucoma, which is similar to that in glaucoma simplex but different from vascular diseases, as well as the increased diurnal tension variations of diurnal tension curves compared to the normal population are all factors which indicate that low-tension glaucoma is not a purely vascular optic nerve disease, and that pressure-lowering therapy is necessary.(ABSTRACT TRUNCATED AT 250 WORDS)     

超声乳化白内障手术对剥脱综合征性青光眼的降眼压作用

目的 观察和分析剥脱综合征性青光眼患者行超声乳化白内障摘除人工晶体植入术后的眼压变化。方法 对7例伴有高眼压、明显影响视力的白内障但尚无严重的视神经、视野损害的剥脱综合征患者施行超声乳化白内障摘除人工晶体植入术，比较手术前后的眼压变化。结果 术前平均眼压31．57mmHg，术后1周时平均眼压18．19mmHg，降幅为13．38mmHg，术前术后眼压差异极显著。结论 伴有明显影响视力白内障的剥脱综合征性青光眼病人在行超声乳化白内障摘除人工晶体植入术后眼压会显著下降，对那些尚未发生明显视神经视野损害的剥脱综合征性青光眼患者，行超声乳化白内障摘除人工晶体植入术可有效降低眼压。     

颅内压与青光眼及其无创测量技术的研究进展

青光眼是世界上第二位致盲性眼病,第一位不可复性致盲性眼病。尽管眼压增高被认为是青光眼性视神经损害的主要危险因素,但是50%的原发性开角型青光眼患者的日常眼压正常,还有一些患者尽管眼压控制良好,但青光眼性视神经损害仍继续发展。这些现象无法用高眼压理论来解释,青光眼患者视神经损害的发病机制仍待探讨。目前国内外的一些研究表明：（1）视神经周围的生物力学的解剖结构包括眼内压,筛板和球后的脑脊液压力在原发性开角型青光眼的发病机制中发挥重要的作用;（2）正常眼压性青光眼患者的脑脊液压力比正常人低,而跨筛板压力差比正常人高;（3）高眼压症患者的脑脊液压力比正常人群高,而跨筛板压力差和正常人之间没有统计学意义。基于以上研究,本文就颅内压与青光眼性视神经损害之间关系的相关研究进展及临床上可行的无创颅内压测量方法作一综述。     

Is open‐angle glaucoma caused by impaired cerebrospinal fluid circulation: around the optic nerve?

Chronic open-angle glaucoma is the most frequent type of glaucoma and a leading cause for blindness. The role of intraocular pressure (IOP) in the pathogenesis of open-angle glaucoma has been challenged by patients with typical glaucomatous optic disc changes and visual field loss in whom the IOP never exceeded normal values (normal-tension glaucoma), as well as by patients with persistently elevated IOP who do not develop glaucomatous disc or field changes. Recent research has demonstrated that the cerebrospinal fluid (CSF) is not evenly distributed in all CSF spaces and that the subarachnoid space of the optic nerve can turn into a CSF compartment on its own. The biochemical components in this optic nerve compartment can differ markedly from normal CSF and some of its components (such as L-PGDS) may produce a toxic effect on the optic nerve and may therefore play an important role in the pathophysiology of open-angle glaucoma.     

Postural change of IOP in normal persons and in patients with primary wide open-angle glaucoma and low-tension glaucoma.

The values of intraocular pressure (IOP) measurements by an Alcon pneumatic tonometer and a Goldmann applanation tonometer were found to be close, with a correlation coefficient of 0.92. Measured by the pneumatonograph the IOP after 30 minutes in the supine position was highest in normal persons, in patients with primary wide open-angle glaucoma and low-tension glaucoma. The greatest difference in IOP between subjects sitting and supine was observed in patients with low-tension glaucoma.     

The case for autoimmunity in glaucoma

Although the majority of patients with glaucoma have elevated intraocular pressure as the presumed etiology for their resultant neuropathy, it is well known that approximately 25% of patients with glaucoma have intraocular pressure within the normal range for their race. These patients may have conditions that facilitate non-pressure related stress to the retina and optic nerve that might directly contribute to their glaucomatous neuropathy and include chronic or intermittent ischemia (i.e atherosclerosis, heart disease, vasospasm, migraine, sleep apnea), altered scleral/optic nerve head morphology that predisposes to glaucomatous stress (i.e myopia); genetic mutations that predispose to glaucoma damage at normal IOP (OPA-1,optineurin, myocilin) and evidence of aberrant immunity that suggests that their glaucoma might be a form of an autoimmune neuropathy (i.e. presumed autoimmune glaucoma). This review provides a critical assessment of the potential role for autoimmunity as an initiating or exacerbating etiology in some patients with glaucoma.     

Reversal of optic disc cupping after glaucoma surgery analyzed with a scanning laser tomograph.

OBJECTIVE: To detect and quantitate changes in optic nerve morphology after glaucoma surgery using the Heidelberg Retina Tomograph (HRT, Heidelberg Instruments, Heidelberg, Germany). DESIGN: Nonconsecutive observational case series. PARTICIPANTS AND INTERVENTION: The authors prospectively enrolled 21 adult patients undergoing incisional glaucoma surgery for progressive glaucoma damage. Quantitative analysis of the optic nerve head by scanning laser tomography and automated perimetry were performed before and after glaucoma surgery. MAIN OUTCOME MEASURES: Changes in optic nerve parameters were subjected to linear regression analysis with respect to percent of postoperative reduction of intraocular pressure (IOP), as well as with respect to age, refraction, preoperative cup:disc ratio, and change in visual field parameters. RESULTS: Seventeen patients had pre- and postoperative images suitable for analysis. Mean IOP at the time of image acquisition before surgery was 30.5+/-12 mm Hg, and after surgery 11.8+/-5.2 mm Hg (mean follow-up, 26+/-7 weeks). Eleven of 13 (85%) patients having IOP reduction of greater than 40% showed improvement in optic disc parameters. All four patients with less than 25% reduction in IOP showed worsening of most parameters. Changes in optic disc parameters were highly correlated with percent IOP reduction and with age. The parameters in which change most strongly correlated with percent change of IOP were cup area, rim area, cup:disc ratio, and mean cup depth (each, P<0.005). The age of the patient correlated highly with change in maximum cup depth (P<0.005). Refraction and clinically determined cup:disc ratio correlated poorly with changes in measured optic disc parameters. Clinical improvement in visual fields was correlated with the degree of improvement of cup:disc ratio (P = 0.025). CONCLUSION: Most patients showing a 40% lowering of IOP after glaucoma surgery show improved optic nerve morphology as measured by the HRT. The amount of improvement correlated highly with the percent reduction of IOP.     

Central corneal thickness and glaucoma in aphakic and pseudophakic children.

BACKGROUND: The risk of glaucoma among aphakic children is as high as 32%, based primarily on intraocular pressure (IOP) measurements. Although IOP may be falsely elevated by increased central corneal thickness, central corneal thickness (CCT) values have not been reported in this population. METHODS: Patients from the practices of 2 pediatric ophthalmologists and 2 glaucoma specialists had measurements of CCT, IOP, and optic nerve cupping, with visual field analysis when possible. Normal fellow eyes of unilateral aphakes and pseudophakes were included as controls. RESULTS: In 36 aphakic and 6 pseudophakic eyes CCT averaged 660 microns compared with 576 microns for phakic fellow eyes (P < 0.0001). Glaucoma, defined by IOP at least 35 mm Hg or by IOP at least 22 mm Hg associated with optic nerve changes, occurred in 21% of 28 aphakic patients but in no pseudophakic patient. CONCLUSIONS: CCT in aphakic/pseudophakic children is substantially increased compared with control patients. These values may be important in interpreting IOP measurements in these children.     

A comparative study of optic disc appearances in progressive and non-progressive low-tension glaucoma

The relation between the optic disc appearances and the progression of visual field defects was studied by retrospective case review of 148 eyes of 74 patients with a diagnosis of low-tension glaucoma (LTG). Visual fields were tested by a Goldmann perimeter and the subjects were divided into two groups, i.e. 43 eyes (29.1%) with progression and 105 eyes (70.9%) without progression, according to Esterman's scale. In the group which showed progression, mean IOP (p less than 0.05), level of change in IOP and maximum of IOP (p less than 0.01) were significantly higher. No differences were observed in any of the following parameters: prevalence of peripapillary hemorrhage or crescent, rim pallor, disc/arteriole ratio, number of rim-crossing vessels. Mildly hypoplastic disc, however, was statistically more frequent in the progressive group (p less than 0.05). The authors suspect that not only IOP but some inherent factors concerning the optic nerve head may play an important role in the progression of LTG.     

Diagnostics and therapy for normal tension glaucoma

Pooled data from "The Baltimore Eye Survey", "The Blue Mountains Eye Study", "The Beaver Dam Eye Study", "The Rotterdam Study" and "The Melbourne VIP" showed a strong age-dependent prevalence of open angle glaucoma. Patients younger than 60 years have a prevalence of open angle glaucoma of less than 1 %. Beginning with the age of 60 the prevalence increases exponentially. The prevalence of open angle glaucoma in persons in the 8(th) age decade reaches up to 5 %. Among these patients, 30-50 % have normal intraocular pressure. The diagnostics and therapy for open angle glaucoma with normal intraocular pressure (IOP), also called normal tension glaucoma, is a complex and often interdisciplinary challenge. Established causative factors for developing a glaucomatous optic nerve atrophy in normal tension glaucoma are: relatively increased IOP, older age, non-dippers (0-10 %) or extreme dippers (> 20 %) concerning nocturnal arterial blood pressure drop, small vessel disease with cardiovascular disease and cerebral microgliosis (white matter lesions), decreased blood flow in the optic nerve head, extreme dip of the optic nerve head blood flow in the morning, cerebral blood flow dysregulation and the epsilon4-allele polymorphism of the apolipoprotein E-gene. Clinical pathways are presented for the diagnostics and therapy for normal tension glaucoma.     

Comparison of visual field defects in the low-tension glaucomas with those in the high-tension glaucomas

We compared the visual fields of 79 eyes (48 patients) with low-tension glaucoma (intraocular pressure less than 21 mm Hg) to the visual fields of 106 eyes (74 patients) with high-tension glaucoma (intraocular pressure greater than 30 mm Hg). Both groups had similar amounts of total field loss as determined by computerized threshold perimetry. Scotomas in the low-tension group had a steeper slope (P less than .001), were significantly closer to fixation (P less than .001), and had greater depth (P less than .001) than those in the high-tension group. These findings suggested that more than one causative factor is important in the production of optic nerve damage in glaucoma.     

Measurement of peripapillary retinal nerve fiber layer volume in glaucoma

PURPOSE: To measure peripapillary retinal nerve fiber layer volume in normal subjects and patients with ocular hypertension, primary open-angle glaucoma, and low-tension glaucoma. METHODS: Sixty-five subjects were classified into four groups of normal subjects and subjects with ocular hypertension, primary open-angle glaucoma, and low-tension glaucoma on the basis of intraocular pressure measurements, visual field loss, and optic disk appearance. Groups were matched for sex, age, and optic disk area. Peripapillary retinal nerve fiber layer volume measurements were made with a modification of software version 1.11 of the Heidelberg Retina Tomograph confocal scanning laser ophthalmoscope. Retinal nerve fiber layer volume measurements were taken at 0.1-mm increments from the disk margin for a global 360-degree assessment and at four predefined segments using two different reference planes. Statistical analysis was carried out using analysis of variance with Bonferroni correction. RESULTS: Retinal nerve fiber layer volume measurements showed a gradation from normal to ocular hypertension and from ocular hypertension to glaucoma groups. Mean group measurements showed statistically significant differences (P <.05) in peripapillary retinal nerve fiber layer volume for most segmental measures between the groups. Measurements with the default reference plane in the 0.0-mm to 0.1-mm and 0.1-mm to 0.2-mm increments for the superotemporal segment showed the greatest differences between groups (P <.00005). CONCLUSION: Peripapillary retinal nerve fiber layer volume measurements differ between groups of normal subjects and patients with ocular hypertension, primary open-angle glaucoma, and low-tension glaucoma. This measure offers a further method of assessment of retinal nerve fiber layer in patients with glaucoma and glaucoma suspects.     

低颅压与正常眼压性青光眼的关系

青光眼作为导致人类不可逆性盲的头号杀手,是一组慢性进行性视神经病变疾病。虽然病理性眼压增高是青光眼发展的主要危险因素,但是其视神经病变机制始终不明。而且有部分患者眼压处于正常值范围内,却依然发生了青光眼性视神经损害,被称为“正常眼压性青光眼”。因此,我们不得不考虑,除眼压外还有其他因素参与青光眼视神经的损害。近年来有研究表明:颅内压与眼压的失衡有可能是正常眼压性青光眼的原因之一,本文就颅内压与正常眼压性青光眼的关系做一综述。     

Investigations into a vascular etiology for low-tension glaucoma

Increased intraocular pressure is accepted as a primary etiologic factor for the atrophy of the optic nerve head and visual field defects of high-tension glaucoma. Other factors must be present to explain these findings in low-tension glaucoma. One of the current theories is that low-tension glaucoma is the result of decreased optic nerve perfusion on the basis of vascular disease or other factors such as altered blood viscosity. This study compared the non-invasive vascular profiles, coagulation tests, and rheological profiles of 46 consecutive cases of low-tension glaucoma with 69 similarly unselected cases of high-tension glaucoma and 47 age-matched controls. Despite the multifactorial approach and the use of previously validated objective tests, no significant group differences were detected with any of the above investigations. If vascular disease is important in the etiology of low-tension glaucoma, then it must be localized or vasospastic since this study does not support the concept of a generalized vascular etiology, either of an atheromatous or hyperviscous nature, for the genesis of low-tension glaucoma.     

Unequal intraocular pressure and its relation to asymmetric visual field defects in low-tension glaucoma

Fifty-nine low-tension glaucoma patients were reviewed with respect to asymmetry of intraocular pressure (IOP) and visual field defects. In the presence of unequal IOP the visual field damage is almost always greater on the side with higher mean IOP. However, only 13 of 47 patients with asymmetric visual field defects had a mean IOP difference between the two eyes of greater than or equal to 1 mmHg. Although in the case of IOP asymmetry visual field damage is greater in the eye with higher mean IOP, other factors must also play an important role in the development of visual field defects in low-tension glaucoma.     

Fluorescein angiography in chronic simple and low-tension glaucoma.

Fluorescein angiograms were performed on a group of low-tension glaucoma and chronic simple glaucoma patients with similar extent of visual field loss, under standardised conditions, to see whether differences attributable to chronic intraocular pressure elevation could be detected. There was no evidence for difference in circulation times between these two groups. There was no evidence that hypoperfusion of the peripapillary choroid contributed to optic nerve hypoperfusion. Low-tension glaucoma patients demonstrated focal sector hypoperfusion of the optic nerve in every case, while the chronic simple glaucoma patients demonstrated a wide range of optic nerve fluorescence, suggesting both focal and diffuse optic nerve head hypoperfusion. It was concluded that, while focal hypoperfusion of the optic nerve may reflect susceptible vasculature at the nerve head with or without intraocular pressure elevation, diffuse hypoperfusion suggested that prolonged intraocular pressure elevation may simultaneously affect the whole of the optic nerve head. This could be a direct effect on blood vessels or a mechanical effect with secondary vascular changes.     

Retrograde axonal transport of BDNF in retinal ganglion cells is blocked by acute IOP elevation in rats

PURPOSE: To determine whether acute experimental glaucoma in rats obstructs retrograde transport of brain-derived neurotrophic factor (BDNF) to retinal ganglion cells (RGCs). METHODS: Forty rats had unilateral injection of either (125)I-BDNF (20 animals) or a mixture of (125)I-BDNF and 100-fold excess nonradiolabeled BDNF (20 animals). In each group of 20 animals, eyes contralateral to injection had either normal intraocular pressure (IOP; 10 animals) or IOP elevated to 25 mm Hg below the systolic blood pressure of the eye (10 animals). In each group of 20 rats, ipsilateral eyes had IOP set at systolic blood pressure (4 eyes), had optic nerve transection (10 eyes), or had normal IOP (6 eyes). Six hours after injection, animals were killed and tissues were fixed, embedded, and sectioned for autoradiography. Grain counts were performed over retina and optic nerve using automated image analysis. RESULTS: IOP elevation to 25 mm Hg below systolic blood pressure (perfusion pressure [PP] 25) decreased median retinal nerve fiber layer (NFL) grains by 38% compared with controls (P: < 0.001). Competition by cold BDNF reduced NFL grains by 28% (P: = 0.013). Considering only the radioactivity representing specific retrograde transport of BDNF, IOP elevation to PP25 reduced transport by 74%, whereas elevation to PP0 (equaling systolic blood pressure) reduced specific transport by 83%. CONCLUSIONS: BDNF is transported retrogradely from the superior colliculus in adult rats, and this transport is substantially inhibited by acute IOP elevation. Deprivation of BDNF among RGCs may contribute to neuron loss in glaucoma.     

The use of cyclodialysis to limit exposure to elevated intraocular pressure in rat glaucoma models

Elevated intraocular pressure (IOP) is the most common risk factor for glaucoma and pressure control is the goal of current clinical glaucoma therapy. Yet, recent clinical studies have documented that, even after therapeutic lowering of IOP, glaucomatous visual field loss can progress in many patients. Experimental elevation of IOP in the rat is commonly used to model human glaucomatous injury. However, there currently is no rodent model for the clinical situation of glaucomatous progression in eyes with apparently controlled IOP. The purpose of this study was to evaluate the ability of surgical cyclodialysis to produce both prolonged, non-injurious reduction of IOP in rat eyes and to stably normalize IOP in eyes with experimental pressure elevation. To perform cyclodialysis, a blunted spatula was fashioned from a hypodermic needle and used to separate a portion of the ciliary body from the sclera, opening a channel into the suprachoroidal space to allow aqueous outflow. Experimental IOP elevation was produced in rats by unilateral injection of hypertonic saline. Cyclodialysis in normal eyes resulted in an average 40 +/- 4% reduction in IOP, without marked hypotony. IOP lowering could be sustained for at least 6 months. The risk of retinal or optic nerve injury following a single cyclodialysis procedure was minimal as evidenced by unaltered levels of four injury-responsive retinal mRNAs and by normal optic nerve morphology. Cyclodialysis in eyes with experimental IOP elevation resulted in IOP normalization that was sustained for durations of 7 and 21 days in 88% and 53% of eyes, respectively. In addition, in eyes with the same cumulative dose of elevated IOP prior to the procedure, successful IOP normalization by cyclodialysis resulted in significantly less optic nerve injury than that seen in eyes in which IOP control was ineffective (p = 0.03). These studies show that cyclodialysis provides a simple, non-injurious method to reduce experimentally elevated IOP in rats that can be used to model the clinical situation of eyes previously damaged by pressure. This tool offers new opportunities for identifying and studying the molecular processes associated with glaucomatous progression and for testing potential neuroprotective therapies in a clinically relevant situation.