High occurrence rate of glaucoma among patients with Alzheimer's disease.

The purpose of the current study was to reveal the occurrence rate of glaucoma among patients with Alzheimer's disease (AD). All 112 patients of four nursing homes in Upper Bavaria, Germany, who met the diagnostic criteria of probable AD, were incorporated into the study. Visual field defects and/or optic disc cupping compatible with the diagnosis of glaucoma were found in 29 out of 112 patients with AD (25.9%). When compared to a control group (5.2%) and to the prevalence of glaucoma in western countries revealed in a number of glaucoma surveys (2.6-4.7%), patients with AD may have a significantly increased occurrence rate of glaucoma. In addition, ocular hypertension with normal visual fields and normal optic nerve heads was not found in patients with AD. The prevalence of ocular hypertension in the control group was 7.8% and parallels previous surveys. Therefore, we assume that the optic nerve seems to be less resistant to elevated intraocular pressure levels in AD patients.

Evaluation of different recording parameters to establish a standard for flash electroretinography in rodents.

Different electrodes and stimulus protocols commonly used for electroretinography in rodent eyes were compared for convenience of use, degree of damage to corneal epithelium, and for magnitude of amplitude, reproducibility, left versus right eye accuracy, and reliability of recorded parameters of the flash electroretinogram (ERG). Adult C57BL/6 pigmented mice and albino Wistar rats were used to determine scotopic ERGs in response to Ganzfeld or strobe-light stimulation and light-adapted (photopic) ERGs recorded from both eyes at the same time. Test-retest data were used for statistical analyses to compare a monopolar gold-wire contact lens electrode (CLE), a cotton-wick silver-silver chloride electrode (CSCE), a DTL fiber electrode (DTLE), and a circular stainless steel wire electrode (SSE). Corneas were evaluated for abrasion after ERG recordings using fluorescein staining and also for the time taken, ease of insertion, and re-insertions required for the different electrodes. Compared to CSCE, DTLE, and SSE, the ERG potentials recorded by CLE had significantly larger scotopic amplitudes and oscillatory potentials under strobe or Ganzfeld stimulation and for light-adapted ERG b-wave amplitudes in both mice and rats. In analyzing test-retest data of scotopic ERG a-wave and b-wave amplitudes, the intraclass correlation coefficient showed the best agreement for the CLE (range 0.61-0.94) compared to the SSE (0.13-0.77), DTLE (0.02-0.69), and CSCE (0.12-0.51). In mice and rats, logistic regression analyses revealed significant correlations for amplitudes of most scotopic ERG parameters between contralateral eyes obtained with CLE and for some ERG components recorded by SSE. When comparing ERG amplitudes for stimulation by strobe or Ganzfeld, the difference was least with the CLE compared to DTLE, CSCE, or SSE. The time taken to insert the four different electrodes was greatest for the CLE in both mice and rats. The extent of corneal abrasion resulting from electrode use in mice was largest for the SSE followed by the CLE. However, in rats there was almost no corneal damage after ERG recordings with the CLE. Because of the stability of eye contact, the CLE allows ERGs to be determined over a longer recording session. Recording of scotopic and photopic (light-adapted) ERGs in rodents with monopolar gold-wire contact lens electrodes provides greater amplitudes and higher reproducibility when compared to other commonly used corneal electrodes. These electrodes are significantly better overall than others that were evaluated and should be considered for a standard protocol to monitor retinal function in rodent eyes.

Electroretinographic abnormalities in a rat glaucoma model with chronic elevated intraocular pressure.

The purpose of this study was to determine the ability of electroretinographic (ERG) measurements to document progression of the retinopathy in a rat glaucoma model. Thirty four rats with a chronic intraocular pressure (IOP) elevation induced in one eye by cautery of three episcleral/extra-orbital veins were studied in four separate groups. ERGs were recorded sequentially in Group A rats (n = 12) at baseline, and after approximately 20, 40 and 60 days of high IOP, and in three additional groups of rats (n = 6 or 10 per group) after approximately 58, 30 and 175 days of high IOP, respectively. Scotopic ERG parameters recorded simultaneously from both eyes in Group A rats were: a- and b-wave amplitudes, implicit times, oscillatory potential amplitudes (OPs) determined at three different light-flash intensities, and the light-adapted (photopic) ERG b-wave amplitude. In the other groups of rats, only scotopic ERG a-wave, b-wave and OP amplitudes were measured.In Group A rats that were followed sequentially, all the ERG parameters recorded with attenuated stimuli showed significant time-dependent changes in glaucomatous eyes relative to their contralateral normal eyes, with OPs showing the earliest significant difference after only 3 weeks of high IOP. When different groups of unilateral glaucomatous rats were compared beyond 8 weeks of elevated IOP only the OPs showed a continued decrease with time and good discrimination between glaucoma and normal eyes. Over a 25 week period of high IOP the scotopic OPs measured with attenuated light stimuli declined at the rate of approximately 1.5% per week and provided the best ERG measure to monitor progression of retinal pathophysiology in the vein-occlusion rat glaucoma model.

Retinal morphology and ERG response in the DBA/2NNia mouse model of angle-closure glaucoma.

PURPOSE: To document the time course of retinal dysfunction by scotopic electroretinography (ERG) and by quantitative morphology in eyes of the DBA/2NNia substrain of mouse (DBA) with inherited angle-closure glaucoma. METHODS: DBA and control C57BL/6J (C57) mice were studied by ERG recordings from 5 to 15 months of age, and by morphology from 1 to 14 months of age. Scotopic ERGs were simultaneously recorded from both eyes of dark-adapted anesthetized mice. Changes in the central neuronal retina were evaluated by quantitative morphometry performed on serial semithin sections of Epon-embedded eyes. RESULTS: When compared with normal C57 mice, DBA mice showed significant reductions of the a-wave and b-wave amplitudes by 7 to 8 months, and the decline continued as the animals aged. The b-wave implicit time in DBA mice showed a gradual prolongation beginning at 8 months of age, when compared with C57 mice. Logistic regression analyses revealed significant correlations in a- and b-wave amplitude reductions between ipsilateral and contralateral eyes of DBA mice at ages when ERG parameters were greatly altered. Morphologically, thinning of the whole retina was already evident in DBA mice at 4 months of age, but loss of ganglion cells and thinning of the outer plexiform layer were first seen in 7- to 8-month-old animals. These changes progressed to the end of the 13-month period studied. CONCLUSIONS: Progressive thinning of the outer retinal layers in DBA mice was found to correlate with decreases in ERG a- and b-wave amplitudes, both occurring from the age of 7 to 8 months onward. Similarities with the findings in human late-stage glaucomatous retinopathy indicate the relevance of this animal model in further glaucoma research.

[Pilot study of pattern-electroretinographic changes in the DBA/2NNia mouse. Animal model of congenital angle-closure glaucoma]. / Pilotstudie zu musterelektroretinographischen Veränderungen bei der DBA/2NNia-Maus. Tiermodell eines angeborenen Engwinkelglaukoms.

PURPOSE: The aim of this study was to document the time-course of retinal dysfunction by pattern-electroretinography (PERG) in eyes of the DBA/2NNia substrain of mouse that develop an inherited angle-closure glaucoma. METHODS: Twelve DBA/2NNia mice and 12 control C57BL/6 J mice were studied by PERG recordings from 2 to 10 months of age. PERGs were recorded using different spatial and temporal frequencies. RESULTS: PERGs recorded with a temporal frequency of 7.5 Hz and a spatial frequency of 0.4 cycles/degree performed best to discriminate between DBA/2NNia mice and C57BL/6 J mice. When compared with normal C57BL/6 J mice, significant amplitude reductions of the PERG (Student's t-test; p < 0.01) were found in DBA/2NNia mice by 5 months of age and continued to decline as the animals aged. At beginning of follow-up, the mean PERG amplitude in DBA/2NNia mice was 2.3 +/- 0.5 microV. At 5 months of age, the mean PERG amplitude was reduced by 0.9 +/- 0.45 microV (paired t-test; p < 0.0001). CONCLUSION: Previously, a significant loss of retinal ganglion cells was found in the DBA/2NNia mouse substrain at 6-7 months of age. In the present study, we found decreases in PERG amplitudes, occurring from the age of 5 months onward. Similarities with the findings in human glaucoma indicate the relevance of this animal model for further glaucoma research.

Psychological characteristics of patients with normal-tension glaucoma.

BACKGROUND: A study was carried out to evaluate the extent of psychosomatic complaints in patients with normal-tension glaucoma. METHODS: Twenty-four patients (M:F=3:21; mean age 58+/-15.3 years) with normal-tension glaucoma were rated according to the von Zerssen Symptom List (psychosomatic discomfort), the Maudsley Personality Inventory (MPI-N, emotional status and MPI-E, extroverted-introverted), the Beck Depression Inventory (BDI), and the Sixteen Personality Factor Questionnaire (16PF). An age- and sex-matched control group (n=24; M:F=3:21; mean age 56+/-13 years) without any ocular or other general chronic disease was selected. RESULTS: In comparison with the control group the patients with normal-tension glaucoma showed significantly more complaints (von Zerssen Symptom List) and were more emotionally unstable (MPI-N). No group differences were found regarding extroversion-introversion (MPI-E) and depression (BDI). In the 16PF, patients with normal-tension glaucoma were remarkable, only for a significant negative correlation between the duration of illness and psychic endurance. CONCLUSION: The results demonstrate that patients with normal-tension glaucoma show evident psychosomatic involvement. However, the sequence of the pathogenetic development remains unclear. Therefore, it is not known whether these psychological disturbances are factors contributing to the development of normal-tension glaucoma or whether they are a result of normal-tension glaucoma. Nevertheless, some patients with normal-tension glaucoma had these disturbances. Besides reduction of intraocular pressure and improvement of vascular condition, those who display psychological disturbances should receive psychological support, such as autogenic training.

Comparisons of the amplitude size and the reproducibility of three different electrodes to record the corneal flash electroretinogram in rodents.

To compare corneal electrodes commonly used in rodent eyes for repeat and left versus right eye accuracy and variability to record the flash electroretinogram (ERG). Animals studied were eight C57BL/6 mice and eight rats of the Wistar strain. Scotopic ERGs were recorded from eyes of dark-adapted anesthetized rodents to compare a custom-made gold-wire contact lens electrode (CLE), a cotton-wick silver-silver chloride electrode (SCLE), and a coiled stainless steel wire electrode (SSE). Compared to SCLE and SSE. the potentials recorded by CLE are characterized by significantly larger ERG amplitudes and oscillatory potentials in both rats and mice (p <0.0001). In analyzing test-retest data comparing the three different electrodes the coefficient of variation was smaller (range, 10.3-15.5%) and the interclass correlation coefficient (0.77-0.93) showed a better agreement for the CLE. Recording scotopic ERGs with custom-made gold-wire contact lens electrodes records large amplitudes and shows a good reproducibility and reliability to monitor retinal function in rodent eyes.

Light-induced retinal damage in mice carrying a mutated SOD I gene.

Transgenic mice expressing mutated mouse Cu/Zn superoxide dismutase (SOD I), corresponding to a mutation associated with familial amyotrophic lateral sclerosis, develop a fatal motorneuron degeneration that resembles the human disease. The biochemical properties of some mutant SOD I enzymes indicate that a gain of catalytic functions, (such as increased peroxidase activity) may be the pathologic factor(s). However, at the present time there is little in vivo evidence that a mutation-induced change in the catalytic activity of SOD I is directly involved in neuronal cell death or that vulnerability to cell death is related to the level of functional/metabolic activity of cells carrying mutated SOD I. In pigmented mice carrying the G86R mutation of mouse SOD I, exposure to constant bright light for 20 days caused a diminution of electroretinographic activity and specific degeneration of photoreceptor cells, while no pathological effects were seen in transgenic littermates not exposed to bright light or in light exposed non-transgenic littermates. These findings are the first to indicate that one mechanism for neuronal cell death by mutated SOD I is use-dependent and/or related to metabolic activity, and therefore may be due to a gain in function of catalytic activities involving superoxide/hydrogen peroxide. The light-exposure pathology in this transgenic mouse model indicates an essential role for SOD I in the protection of photoreceptors from light-damage.

Color vision tests for early detection of antiepileptic drug toxicity.

A previous suggestion that antiepileptic drugs may induce color vision deficiencies prompted us to examine whether color vision deficiencies may occur at lower drug serum concentrations than those associated with symptoms of neurotoxicity. Eighty patients presenting with epilepsy received monotherapies of valproic acid, phenytoin, or carbamazepine; 18 patients did not receive antiepileptic drug therapy. Color vision was tested by the Farnsworth-Munsell 100-hue test, spectral sensitivity, and the newly developed tritan screening plates. Patients treated with phenytoin or carbamazepine developed blue-yellow color vision deficiencies. In contrast, patients exposed to valproic acid or receiving no drug treatment showed normal color vision. There was a significant correlation (p < 0.0001) between signs of neurotoxicity induced by phenytoin or carbamazepine and blue-yellow color vision deficiencies. In contrast, we found no correlation between these signs of neurotoxicity and the drug serum concentrations (p = 0.0637). Color vision testing in epileptic patients treated with phenytoin or carbamazepine appears to be a sensitive method for early detection and monitoring of clinical neurotoxicity.

The Tübingen Glaucoma Study. Glaucoma filtering surgery--a retrospective long-term follow-up of 254 eyes with glaucoma.

A major focus of our study was the ability to predict the long-term success of filtering surgery. The results of glaucoma filtering surgery (trabeculectomy) as performed by the staff of the University Eye Hospital of Tübingen from 1988 through 1994 on 254 eyes of 214 patients are presented, with particular emphasis being placed not only on intraocular pressure (IOP) control but also the progression of glaucomatous damage (visual field loss or disc damage) and the etiology of visual acuity losses. There was an overall success rate of 64%. Rigid criteria for success included an IOP of less than 30 mmHg, no further visual field loss or disc damage, and no glaucomatous etiology for a decrease in visual acuity. A total of 35 eyes (13.8%) showed a loss of visual acuity after 6 months amounting to 2 or more Snellen lines, caused mainly by lens opacification, hypotony maculopathy, and "wipeout" (loss of the central visual field in the absence of another explanation). We found that there is a considerable risk for sudden loss of visual acuity after operation on older patients with small residual visual fields and severe hypotony on the 1st postoperative day. There was a 13% incidence of failure of blebs. A total of 34 eyes had an early IOP rise of more than 30 mmHg after surgery. A postoperative hypotony of less than 3 mmHg was more significantly seen in patients treated with 5-fluorouracil. Moreover, the results show that in some instances, a long-term use of topically applied glaucoma medication can adversely affect the results of fistulizing surgery.(ABSTRACT TRUNCATED AT 250 WORDS)

[Psychiatric manifestations in patients with primary open-angle glaucoma]. / Psychiatrische Auffäligkeiten bei Patienten mit primärem Offenwinkelglaukom.

In a comparative study, 21 in-patient and 27 out-patients with primary open-angle glaucoma and 18 cataract patients were investigated to determine whether psychiatric symptoms were more frequent in patients with primary open-angle glaucoma. In all three groups we used Beck's Depression Inventory, the Zerssen Symptom List and the Maudsley Personality Inventory. In addition, in the case of the glaucoma in patients we applied the unsteadiness Test, the Social Interview Schedule and a psychiatric interview. Two-thirds of the glaucoma inpatients showed psychiatric symptoms, had higher scores for depression and psychosomatic complaints and had reduced emotional stability. The glaucoma out-patients had statistically significantly high scores for psychosomatic complaints. The control group showed normal scores in all tests. The present tests seem to pick up psychiatric symptoms in patients with primary open-angle glaucoma. Therefore, we can recommend them as an aid to orientation in hospital and private practice.