Superoxide dismutase in the anterior chamber and the vitreous of diabetic patients.

Total superoxide dismutase (SOD) activity was examined in the anterior humor of 32 diabetic patients and 34 nondiabetic controls during cataract extraction. Median age (95% confidence interval) was 77.5 yr (73.3-81.0) and 79.3 yr (76.0-83.2), respectively. The SOD activity also was examined in posterior vitreous sampled peroperatively in 10 diabetics with proliferative retinopathy and post-mortem in seven diabetic patients and 35 nondiabetic controls. Ages were 57.2 yr (35.0-73.9), 74.4 yr (40.7-83.6), and 73.8 yr (65.0-80.2), respectively. In nondiabetic patients, the total SOD activity was much lower in the anterior chamber, 9.9 U/ml (8.1-12.6), than in the posterior vitreous, 106.3 U/ml (range 65.6-119.0), P < 0.001. We found no difference between the SOD levels in the anterior chamber of nondiabetic controls and diabetic patients, who had 9.6 U/ml (7.6-13.7). The SOD activity in posterior vitreous in diabetic patients sampled peroperatively, 23.9 U/ml (8.9-39.2), P < 0.0001, and post-mortem, 39.5 U/ml (6.5-214.2), P < 0.04, was significantly lower than in the controls sampled post-mortem, 106.3 U/ml (65.6-119.0). Low levels of SOD in the anterior chamber may be involved in cataract development, in diabetic patients and nondiabetic controls. That diabetics had decreased SOD activity in the posterior vitreous points to a possible role of SOD in the complex process of diabetic retinopathy development.

Evaluation of patients with obvious or suspected degenerative and dystrophic disorders of the retina, pigment epithelium and choroid. Experience from a Swedish referral center.

Between August 1, 1982, and December 31, 1988, 487 patients with clinically established or suspected diagnosis of a hereditary degenerative or dystrophic disorder of the ocular fundus or of a disorder of the optic pathways were evaluated with an extensive set of clinical and electrophysiological tests, 67% of the patients were referred from other eye departments. In order of magnitude the most frequently encountered diagnoses were: 1) 'functional' disturbances (18%), 2) disorders of the optic nerve (9%), 3) retinitis pigmentosa (8%), 4), 5) and 6) progressive cone dystrophy, disorders of the central optic pathways, and fundus flavimaculatus/Stargardt's disease (5% each), and 7) choriocapillaris atrophy (4%). Choriocapillaris atrophy affected older patients than retinitis pigmentosa (P less than 0.001). A male preponderance was observed for juvenile retinoschisis (P less than 0.005) and congenital stationary night blindness (P less than 0.05), and a female dominance in the groups of patients with 'functional' symptoms (P less than 0.01). A specific diagnosis was established in 469 patients. After exclusion of 16 patients referred because of a known hereditary disposition, 196 (43%) of the remaining 453 patients were referred under the same diagnosis as our final diagnosis, 153 (34%) under a different diagnosis and 104 (23%) without any clear diagnosis. Obviously, there is a need for regional centers specialized in these disorders.

Pneumatic retinopexy in 50 patients.

Pneumatic retinopexy was introduced in our clinic in 1986. This paper reports the results from the first 50 cases. Detachments with multiple breaks within 3 clock hours and proliferative vitreoretinopathy up to grade C1 were included. This technique compares favorably to buckling procedures in selected cases. The primary success rate was 83%, and the overall success rate was 90% (pneumatic retinopexy +/- scleral buckling +/- vitrectomy).

The DC-ERG as a highly sensitive measure of effects of prostaglandins.

A few microliters of a prostaglandin preparation (PGE2 or PGF2 alpha) were injected via the ora serrata into the posterior vitreous of one of the eyes in albino rabbits. The fellow eye received an equal volume of saline intravitreally and served as control. The DC electroretinogram (ERG) and the standing potential of the eye (SP) were recorded directly with corneal contact lenses, very stable calomel electrodes, and under very constant anesthesia. The b- and c-wave amplitudes increased in response to 0.1 and 1.0 microgram of PGE2 and PGF2 alpha, respectively. At medium doses there was an increase in the b- and c-wave amplitudes followed by a long-lasting reduction. At very high, nonphysiological doses of PGE2, b- and c-wave amplitudes decreased as compared with the control eye. Prostaglandins modify inflammatory reactions, influence ion transport across membranes, modulate synaptic transmission, and regulate blood flow to various organs. Effects of extremely low doses on the retina and pigment epithelium might indicate a transmitter-like nature of prostaglandins. The present experimental model might be of use in studies of inflammatory eye disease, prostaglandin inhibitors, and characteristics of the pigment epithelial membranes.

The c-wave of the electroretinogram and the standing potential of the eye as highly sensitive measures of effects of low doses of trichloroethylene, methylchloroform, and halothane.

Low and moderate intravenous doses of trichloroethylene, methylchloroform, and halothane dissolved in a lipid emulsion (Intralipid) were given to cynomolgus monkeys. The DC electroretinogram (ERG) and the standing potential of the eye (SP) were recorded directly with corneal contact lenses, very stable calomel electrodes, and under very constant general anesthesia. Even low doses of the substances (close to the hygienic threshold limit values in Sweden) clearly provoked slow variations with time in the amplitude of the c-wave of the ERG and in the SP level. Both potentials are generated mainly in the pigment epithelium. It is suggested that the effects reflect a direct influence of the chemicals upon the metabolism of the pigment epithelium or on the cell membrane. Thus the method used is a highly sensitive measure of effects of certain halogenated hydrocarbons on structures belonging to the central nervous system.

Photic damage to the eye: selective extinction of the c-wave of the electroretinogram.

Albino rabbits were exposed to strong visible light that had passed several infrared-absorbing filters. Photic damage to the retina and pigment epithelium was studied by means of the direct current electroretinogram (dc-ERG) which allows stable registrations of the slow c-wave from the pigment epithelium as well as the relatively fast a- and b-waves from the neuroretina. The exposure to light for 4 h gave rise to striking changes in the ERG: there was only a 25% decrease in the b-wave but a total disappearance of the normally very large c-wave. At the site of the c-wave in the ERG there appeared a negative trough. The electroretinographic evidence of this study seems to indicate a profound injury to the pigment epithelium (pigment epithelial cells and/or tight junctions) after exposure to strong visible light.

Fast and slow artificial diurnal rhythms (light-darkness-light) and the rate of progression of retinal degeneration in dystrophic RCS rats. An electroretinographic study.

The RCS rat strain is characterized by a hereditary progressive degeneration of retina and pigment epithelium. The possible influence of varying artificial diurnal rhythms on the rate of progression of the degeneration was investigated with electroretinography (ERG). Light intensity of the 'day'-periods and the total light exposure were constant in two groups of RCS rats subjected to 2 h light/2 h darkness and to 24 h light/24 h darkness periods respectively. No difference in the rate of degeneration as mirrored by the ERG was seen between the two groups. The ERGs were unrecordable after 7-8 weeks, and the experiments started at birth. No changes in the ERG of controls, genetically identical with the RCS strain except for the retinal dystrophy gene, were seen when they were subjected to the two diurnal rhythms. The results lessen the probability that careful long-term patching of an eye in patients with retinitis pigmentosa or other related hereditary degenerative diseases (in order to diminish the influence of diurnal illumination changes leading to shedding of receptor outer segments) will halt or modify the progression of the disease in man.

The c-wave of the electroretinogram in vitelliruptive macular degeneration (älvdalssjukan).

The d.c. ERG and the EOG were recorded from 6 patients with vitelliruptive macular degeneration (VMD, Alvdalssjukan). All EOGs were highly pathological. The a- and b-waves of the ERG were normal. These are pathognomonic findings in VMD, which starts as a generalized disturbance of the pigment epithelium. No signs of a c-wave were seen in 4 patients. Small c-waves occurred in 2 patients, but only under certain stimulus conditions. The major positive component of the c-wave is produced by the pigment epithelium -- receptor complex. Absent or pathological c-waves in VMD, a pigment epithelial disease, are in good agreement with what is known about the origin of the c-wave.

Changes in the c-wave of the electroretinogram and in the standing potential of the eye after small doses of toluene and styrene.

Low and moderate i.v. doses of toluene or styrene dissolved in a lipid emulsion (Intralipid) were given to cynomolgus monkeys. The d.c. ERG and the standing potential (SP) of the eye were recorded directly with corneal contact lenses, very stable calomel electrodes and under very constant general anaesthesia. Even small doses of the solvents, corresponding approximately to the Swedish hygienic threshold limit values for these solvents in air, clearly provoked slow variations with time in the amplitude of the c-wave of the ERG and in the SP level. Both potentials are generated mainly in the pigment epithelium. It is suggested that the effects reflect a direct influence of the solvents upon i.a. the cell membrane or the metabolism of the pigment epithelium.

The ERG c-wave in vitelliruptive macular degeneration (VMD).

D.c. ERG registrations and EOG recordings were obtained from six patients with vitelliruptive macular degeneration (VMD). In all cases the EOG was highly pathological, but the alpha- and beta-waves of the ERG were normal. This is typical of VMD, which starts as a generalized defect of the pigment epithelium. Four patients showed no evidence of a c-wave. The other patients demonstrated small c-waves, but only under certain stimulus conditions. Thus, varying stimulus durations, intensities and frequencies are sometimes needed to decide whether or not ERG c-waves can be elicited in different diseases or suspected disorders. The findings are in agreement with the presence of a generalized pigment epithelial defect in VMD, since the major positive component of the c-wave is generated by the pigment epithelium-receptor complex.

Studies on acute and late stages of experimental central retinal artery occlusion in the Cynomolgus monkey. I. Intensity-amplitude relations of the D.C. recorded ERG with special reference to the c-wave.

The main positive component of the c-wave of the ERG is generated by the pigment epithelium-receptor complex, which is supplied from the choroidal circulation. Occlusion of the central retinal artery (OCRA) causes serious morphological damage only to the inner retina. An effect on the c-wave is therefore not primarily to be expected. In this study on five Cynomolgus monkeys with unilateral, laser-induced OCRA the c-wave was decreased, slightly in the early stage and markedly in the late stage. A hypothetical explanation of the reduced c-wave amplitude, involving changes in potassium ion concentration, is discussed. The conflicting results in other reports may be explained by uncontrolled influence of slow c-wave amplitude oscillations, by differences between acute and late stages, and by possible surgical damage to the choroidal circulation in some cases.

Studies on acute and late stages of experimental central retinal artery occlusion in the Cynomolgus monkey. II. Influence on the cyclic changes in the amplitude of the c-wave of the ERG and in the standing potential of the eye.

The slow (2-3/h) oscillations of the c-wave amplitude and of the standing potential of the eye (SP) were studied in the Cynomolgus monkey during the acute and late stages after experimentally induced (laser photocoagulation) occlusion of the central retinal artery (OCRA). Whereas the healthy control eyes showed large cyclic variations in both the c-wave amplitude and the SP, no oscillations in the c-wave amplitude were observed in the OCRA eyes at any stage, and the SP oscillations were barely detectable in these eyes. OCRA causes morphological damage to the inner retina but not to the pigment epithelium-photoreceptor complex, which generates the positive component of the c-wave, and where the SP is also believed to originate. The findings of the present study strongly indicate that the SP and c-wave oscillations are related, and that they are either dependent on an intact inner retina or that the pigment epithelium-photoreceptor complex is functionally affected by OCRA. If not taken into consideration, the marked difference in oscillations between the OCRA eye and the healthy eye may be a major source of error when comparing c-waves from the two eyes, and it seems that some of the conflicting results reported by others can be explained in this way.

Effects of ethyl alcohol on the directly recorded standing potential of the human eye.

The effects of ethanol on the human standing potential (SP) were studied with a recently developed method, which allows direct SP recordings by means of a suction contact lens, temperature stabilized calomel electrodes and d.c. amplification. It is well known that the human SP oscillates with a frequency of about 2/hour in response to a sudden change in illumination. In the present paper marked cyclic variations of the SP, resembling damped oscillations, were provoked by a small oral dose of ethyl alcohol. A first maximum was reached after about 10 min. The difference in amplitude between the peak and the trough of the first oscillation was of the order of 4 mV. The oscillatory frequency was about 2/hour. The length of a cycle varied between 25 and 34 min in different volunteers, being fairly constant in the same subject on different occasions. The SP response to ethanol was similar both under scotopic and photopic conditions. The results correlate well with earlier findings of 2/hour oscillations in c-wave amplitude in response to ethanol, as may be expected considering the partly common origin of the c-wave and the SP.

Covariation of the simultaneously recorded c-wave and standing potential of the human eye.

The c-wave and the directly recorded standing potential (SP) of the human eye were studied with the aid of a recently developed method including matched temperature stabilized calomel electrodes, d.c. amplifiers and a suction contact lens. This technique, which does not require general anaesthesia, permits simultaneous direct d.c. recordings of the SP and the c-wave in human volunteers during long-term experiments. Upon repetitive light flashes (stimulus duration 1 sec, interval 20 sec and flash intensity 4.5 rel. log units above b-wave threshold) both variables responded with slow amplitude oscillations with a frequency of about 2/hour. The oscillations were similar as to phases and frequencies. Both the potentials are held to be generated mainly in the pigment epithelium. Considering this partly common origin the observed covariation was an interesting finding.