Expansion of visual receptive fields in experimental glaucoma

Glaucoma is a major cause of blindness and is characterized by death of retinal ganglion cells. In a rat model of glaucoma in which intraocular pressure is raised by cautery of episcleral veins, the somata and dendritic arbors of surviving retinal ganglion cells expand. To assess physiological consequences of this change, we have measured visual receptive-field size in a primary retinal target, the superior colliculus. Using multiunit recording, receptive-field sizes were measured for glaucomatous eyes and compared to both those measured for contralateral control eyes and to homolateral eyes of unoperated animals. Episcleral vein occlusion increased intraocular pressure. This was accompanied by a significant increase in receptive-field size across the superior colliculus. The expansion of receptive fields was proportional to both degree and duration of the increase of intraocular pressure. We suggest that this increase in the size of receptive fields of glaucomatous eyes may be related to the increase in the size of dendritic arbors of the surviving ganglion cells in retina.     

The pattern electroretinogram in glaucoma patients with confirmed visual field deficits

PURPOSE: To better understand the relationship between the amplitude of the pattern electroretinogram (PERG) and visual loss, measured with static automated perimetry. METHODS: Transient PERGs were recorded in 15 patients (31-77 years) and 16 normal individuals (26-65 years). An eye was considered to have glaucomatous damage only if there was an abnormal disc, an abnormal 24-2 Humphrey visual field result (pattern stand deviation, glaucoma hemifield test, and cluster) and an abnormal multifocal visual evoked potential. All the worse (more affected) eyes of the patients and six of the better eyes met these criteria. The N95 amplitude of the PERG was measured from the positive peak (P50) at approximately 50 ms to the trough at approximately 95 ms. The ratio of N95 to P50-the N95 amplitude divided by the P50 amplitude-was also measured. RESULTS: First, the PERG was within normal limits for 4 (26.7%) of the worse eyes. Overall, 6 (28.6%) of the 21 eyes that met the criteria for glaucomatous damage had normal PERGs on both PERG measures. Because the normal individuals were younger than the patients, an even larger number of normal PERGs might be expected with an age-appropriate control group. Second, the N95 amplitude was nonlinearly related to visual field sensitivity when sensitivity was plotted on a linear plot. Small field losses were associated with disproportionately large losses in PERG amplitude. Third, the PERG from both eyes of a patient were very similar, even when the visual fields suggested very different levels of damage. CONCLUSIONS: These results are consistent with the view that very early damage can affect the PERG, even before the visual field shows a loss. At the same time, it is clear that patients with clear glaucomatous damage can have normal-appearing PERGs. An explanation is proposed to account for these findings.     

Association of Vistech contrast sensitivity and visual field findings in glaucoma.

Single eye visual fields and contrast sensitivity were assessed in 60 subjects, who were being followed up in a glaucoma clinic for manifest glaucoma or a suspicion of glaucoma because of raised intraocular pressure. The Fieldmaster 5000 (static/kinetic perimeter) was used for the visual fields, and a Vistech wall chart sine wave grating test was used for contrast sensitivity measurements. The subjects were divided into three groups--defect (D), suspect (S) and normal (N)--on the basis of their perimetric findings by subjective grading of 16 perimetric scoring categories for each visual field. The mean Vistech sensitivity levels were not found to be significantly different between the D, S, and N field subgroups at any of the five spatial frequencies provided on the test charts (1.5, 3, 6, 12, and 18 cycles per degree). Complex algorithms combining results from two or more spatial frequencies also failed to yield any significant differences between the groups. Diagnostic sensitivity and specificities relating Vistech contrast sensitivity findings to groups N and D never concomitantly exceeded 60%.     

Depth perception deficits in glaucoma suspects

AIM: To investigate depth perception in glaucoma suspects compared to glaucoma patients and controls. METHODS: Glaucoma suspects (n = 16), patients (n = 18), and normal age matched controls (n = 19) aged 40-65 years were prospectively evaluated for depth perception deficits using the Frisby test. Stereoacuity was measured by stereothreshold in seconds of arc for each group. RESULTS: Glaucoma suspects showed significantly increased mean stereothreshold compared to age matched normals (144.1 (SE 35.2) v 26.6 (3.7) seconds of arc; p = 0.0004). The mean stereothreshold in glaucoma patients was also increased compared to age matched normals 148.1 (33.8) v 26.6 (3.7) seconds of arc; p = 0.0004). CONCLUSIONS: Glaucoma suspects show depth perception deficits. The impaired stereovision in glaucoma suspects suggests that binocular interactions can be disrupted in the presence of normal visual fields by standard achromatic automated perimetry.     

复方卡波姆诱发的兔高眼压模型与其它兔高眼压模型的比较研究

目的 建立适用于研究抗青光眼药物降眼压作用及保护视神经作用的兔青光眼模型。方法 将21只兔随机分为I、Ⅱ、Ⅲ及Ⅳ组,分别对其前房内注射复方卡波姆、甲基纤维素及复方甲基纤维素,结膜下注射地塞米松诱发青光眼,并对4种药物诱发的青光眼模型进行观察。结果 I组高眼压持续20－50d,平均眼压为29－35mmHg(1mmHg=0.133kPa),眼压峰值为37－45mmHg,青光眼模型成功率为91．7％。Ⅱ及Ⅲ级模型有10－20％的兔眼眼压升主持续3－4d,如按眼压为22mmHg持续1周的标准判断,Ⅱ及Ⅲ组模型均不理想。Ⅳ组眼压平均升高3mmHg,持续7d,亦为失败模型。结论 复方卡波姆诱发的兔青光眼模型具有引起眼压中度、稳定升高的时间长,方法简单,易于操作和控制等优点。可用于对青光眼性视神经视网膜损害的研究及对抗青光眼药物的研究,是一种较理想的兔青光眼模型。     

Morphological changes in the visual pathway induced by experimental glaucoma in Japanese monkeys

Glaucoma, an optic neuropathy, is the leading cause of world blindness. In this condition, the damage extends from the retina to the visual center in the brain, although the primary region of damage is thought to be the optic nerve head (ONH), with the lateral geniculate nucleus (LGN) being secondarily affected. We investigated time-dependent alterations in the ONH, the optic nerve (ON), and the LGN after intraocular pressure (IOP) elevation in Japanese monkeys (a species more similar to humans than other macaque species). Nine Japanese monkeys, each with an experimental glaucomatous left eye, and two naive monkeys were studied. Ocular-testing sessions (including IOP measurement and fundus photography) were held weekly. Eyes and brains were enucleated at 2-48 weeks after IOP elevation, and alterations in ONs and LGN were evaluated. The IOP of the treated eyes was monitored periodically and found to be elevated continuously throughout the observation period in each monkey. The ONH of the glaucomatous eyes exhibited time-dependent deep cupping and thinning of the rim area from 2 weeks after the IOP elevation. Loss of axons and a decrease in the area of ON were first observed at 4 and 28 weeks, respectively. Neuronal loss was first observed at 2 weeks in layers 1 and 2 of LGN [magnocellular (M)-layer] and at 12 weeks in layers 3-6 of LGN [parvocellular (P)-layer]. Neuronal shrinkage was first observed at 2 weeks in all layers in LGN. These findings indicate that in Japanese monkeys, damage to neurons in LGN can be detected in the early phase (first few weeks) after an IOP elevation, as can damage to ONH.     

Ganglion cell losses underlying visual field defects from experimental glaucoma.

PURPOSE: To investigate the relationship between ganglion cell losses and visual field defects caused by glaucoma. METHODS: Behavioral perimetry and histology data were obtained from 10 rhesus monkeys with unilateral experimental glaucoma that was induced by argon laser treatments to their trabecular meshwork. After significant visual field defects had developed, the retinas were collected for histologic analysis. The ganglion cells were counted by light microscopy in cresyl violet-stained retina sections, and the percentage of ganglion cell loss (treated to control eye counts) was compared with the depth of visual field defect (treated to control eye thresholds) at corresponding retinal and perimetry test locations. Sensitivity losses as a function of ganglion cell losses were analyzed for Goldmann III, white and Goldmann V, and short- and long-wavelength perimetry test stimuli. RESULTS: The relationship between the proportional losses of ganglion cells and visual sensitivity, measured with either white or colored stimuli, was nonlinear. With white stimuli, the visual sensitivity losses were relatively constant (approximately 6 dB) for ganglion cell losses of less than 30% to 50%, and then with greater amounts of cell loss the visual defects were more systematically related to ganglion cell loss (approximately 0.42 dB/percent cell loss). The forms of the neural-sensitivity relationships for visual defects measured with short- or long-wavelength perimetry stimuli were similar when the visual thresholds were normalized to compensate for differences in expected normal thresholds for white and colored perimetry stimuli. CONCLUSIONS: Current perimetry regimens with either white or monochromatic stimuli do not provide a useful estimate of ganglion cell loss until a substantial proportion have died. The variance in ganglion cell loss is large for mild defects that would be diagnostic of early glaucoma and for visual field locations near the fovea where sensitivity losses occur relatively late in the disease process. The neural-sensitivity relationships were essentially identical for both white and monochromatic test stimuli, and it therefore seems unlikely that the higher sensitivity for detecting glaucoma with monochromatic stimuli is based on the size-dependent susceptibility of ganglion cells to injury from glaucoma.     

Comparison of visual field defects in normal-tension glaucoma and high-tension glaucoma

In a prospective comparison of visual defects in 23 patients with normal-tension glaucoma and 23 with high-tension glaucoma, the groups were matched for equal involvement of the optic disk. F profiles on the Octopus 201 Perimeter were used to quantify thresholds at 1-degree intervals from fixation to define eccentricity, depth, and slope of the scotoma. The mean eccentricity of scotomas in the normal-tension group was 4.86 degrees from fixation; in the high-tension group it was 2.96 degrees. These differences were statistically significant (P less than .01). No statistically significant differences were found between the slopes of the scotomas or depths of the scotomas in the two groups.     

Long-term prognosis of visual field in glaucoma simplex and glaucoma capsular

The fate of visual fields in 42 eyes with capsular glaucoma followed for 5 to 14 years (mean 9.1 years) and 46 eyes with simple glaucoma followed for 5 to 14 years (mean 10.2 years) was studied retrospectively. In the treatment the IOP levels were around 19.5 mmHg. In both groups the visual field deteriorated in 70-80% of eyes, and 11% of patients became blind. In most cases the progression appeared during the first 4-6 years of follow-up, but in individual cases it did not occur until 8-10 years after the diagnosis. In 26 eyes disc cupping preceded the visual field loss. Five out of 42 eyes with capsular glaucoma developed retinal vein occlusion whereas this occurred in 2 out of 46 eyes with simple glaucoma. Two patients with IOP level of 9 mmHg maintained unchanged visual fields for 6 and 11 years, respectively.     

Early visual disturbances in glaucoma

Early visual loss in glaucoma may not be detected with conventional perimetry because this technique uses simple spots of light that are perceived by any type of ganglion cells. Visual tests for central or peripheral vision have been designed to more specifically address subsets of cells that are impaired in the early phases of the disease. The rationale for use of these tests and their current clinical evaluation are reviewed in this paper. Many tests assessing different visual pathways give abnormal results in patients with suspected glaucoma and ocular hypertensive patients, favoring the hypothesis that multiple pathomechanisms are involved in the onset of glaucoma.     

Binocular visual impairment in glaucoma

Monocular and binocular vision was assessed in patients with glaucoma (n = 21), in patients with ocular hypertension (n = 20), and in age-matched visual control subjects (n = 20) using three tests: color vision with the Lanthony Desaturated D-15 test, low spatial frequency contrast sensitivity with the Pelli-Robson chart, and stereoacuity with the RANDOT test. No significant differences were found among the groups in the severity or type of color vision loss. Monocular contrast sensitivity testing showed considerable overlap among groups but a significant loss of contrast sensitivity in the glaucoma patients relative to ocular hypertensives and control subjects. Binocular testing also showed a significant loss of contrast sensitivity in the glaucoma patients compared with both the ocular hypertensives and the control subjects. Stereoacuity also was significantly impaired in the glaucoma patients. These results indicate that two tests of binocular function, stereoacuity and binocular contrast sensitivity testing, may have utility in identifying early glaucomatous damage.     

高眼压的视觉电生理改变

高眼压是眼科临床常见的问题,相当部分的高眼压的后期往往造成不可逆的视野损害,而成为临床青光眼。虽然视野检测是评价青光眼损伤的金标准,但其属主观检测,因而检测结果往往会受到主观因素的影响,寻找较为敏感和客观的早期诊断指标已成为其防治的关键。近年来视觉电生理技术的飞速发展为青光眼的早期诊断提供了新的参考思路。我们就视觉电生理技术对青光眼的检测及应用进行综述。     

Dissociation of visual deficits in ocular hypertension

Both acquired color vision deficiencies and abnormal pattern electroretinograms (PERGs) are observed in patients with ocular hypertension (OHT) as well as in patients with glaucoma. In the present study we determined the prevalence of both of these functional deficits in a large group of OHT patients (N = 130). Color vision was tested with the desaturated D-15 and a color confusion score was used to quantitatively assess the magnitude of the color vision deficiency. Steady-state PERGs were evoked with rapidly alternating high contrast checkerboard patterns. Color vision deficits were detected in 23% of OHTs while 11.5% of the patients exhibited significant PERG amplitude reductions. Only 2.3% exhibited both abnormalities. The results suggest that although color vision deficiencies and PERG abnormalities are both evident in OHT, they are often dissociated findings.     

The pattern of visual deficits in amblyopia

Amblyopia is usually defined as a deficit in optotype (Snellen) acuity with no detectable organic cause. We asked whether this visual abnormality is completely characterized by the deficit in optotype acuity, or whether it has distinct forms that are determined by the conditions associated with the acuity loss, such as strabismus or anisometropia. To decide this issue, we measured optotype acuity, Vernier acuity, grating acuity, contrast sensitivity, and binocular function in 427 adults with amblyopia or with risk factors for amblyopia and in a comparison group of 68 normal observers. Optotype acuity accounts for much of the variance in Vernier and grating acuity, and somewhat less of the variance in contrast sensitivity. Nevertheless, there are differences in the patterns of visual loss among the clinically defined categories, particularly between strabismic and anisometropic categories. We used factor analysis to create a succinct representation of our measurement space. This analysis revealed two main dimensions of variation in the visual performance of our abnormal sample, one related to the visual acuity measures (optotype, Vernier, and grating acuity) and the other related to the contrast sensitivity measures (Pelli-Robson and edge contrast sensitivity). Representing our data in this space reveals distinctive distributions of visual loss for different patient categories, and suggests that two consequences of the associated conditions--reduced resolution and loss of binocularity--determine the pattern of visual deficit. Non-binocular observers with mild-to-moderate acuity deficits have, on average, better monocular contrast sensitivity than do binocular observers with the same acuity loss. Despite their superior contrast sensitivity, non-binocular observers typically have poorer optotype acuity and Vernier acuity, at a given level of grating acuity, than those with residual binocular function.     

Selecting visual field tests and assessing visual field deterioration in glaucoma

Testing the peripheral field of vision is the mainstay for detection of glaucoma deterioration. Various methods and algorithms are currently available for detection of early glaucoma or establishing disease progression. Alternative testing strategies such as frequency doubling technology perimetry or short-wavelength automated perimetry have been extensively explored over the last 2 decades. The former has been found most promising for detection of earliest evidence of functional glaucoma damage when the standard achromatic perimetry results are still within the normal range. However, standard achromatic perimetry remains the standard technique for establishing deterioration of the disease. Both trend and event analyses are used for establishing change within series of visual fields. Trend analyses provide the clinician with rates of progression, putting the speed of glaucoma progression in the context of patient longevity, whereas event analyses demonstrate a “step” change regardless of the length of time it took for this amount of change to occur. The two techniques are complementary and should be used concurrently.