The effect of body temperature on the murine electroretinogram

Purpose: To study the effect of body temperature on the murine electroretinogram (ERG). Methods: The corneal ERG elicited by a strobe flash from dark-adapted mice was recorded using a saline wick electrode while measuring rectal temperature continuously. The mouse was placed within a cylindrical coil of tubing through which water circulated from a temperature controlled bath. The body temperature of the mouse was changed stepwise between 30 and 37°C. Results: ERGs of approximately normal configuration were recorded at body temperature ranging between 30 and 37°C. The maximum amplitude of the a- and b-waves varied linearly with temperature. The rate of change of b-wave amplitude was about 100 V/degree. At 30°C, maximum b-wave amplitude was about 400 V; at 37°C it was about 1000 V. A change in body temperature produced a rapid change in ERG amplitude. Conclusion: The murine ERG is very sensitive to changes in temperature. In order to monitor the ERG accurately over time, continuous recording of body temperature is essential.     

Electrophysiologic characteristics of human and rat retinas in vitro

To promote studies on the human retina, we investigated the survival of function in postmortem specimens. Visual pigment has been regenerated in normal human retinas, 5 to 58 hours postmorten, by exposure to retinal isomers in the dark. Levels from 0.1 to 0.41 nmol/ mg protein were reached. Photoresponses were obtained in 9 of 13 retinas: P III maximum amplitudes ranged from 20–398 V and thresholds, taking the criterion amplitude as 3 V, ranged from 8.8–1340 quanta/m ². In three cases, the b-wave was also seen. The P III amplitude vs. log intensity curves gave values of n between 0.6 and 1.0, and (the stimulus intensity for a half maximal response) between 132–3700 quanta/m². Recovery of sensitivity did not always correspond to that of maximum response.     

Disturbed visual system function in methionine synthase deficiency

Background Isolated functional methionine synthase deficiency occurs in the cblE and cblG defects of methylcobalamin metabolism and is one of a number of causes of severely elevated plasma homocysteine. Clinical features are predominantly of a neurological nature but also include functional restriction of the visual system manifesting as loss of visual acuity and nystagmus. As yet, the origin and pathogenesis of impaired vision have not been explained.Materials and methods We investigated a patient who was proven by complementation analysis in cultured fibroblasts to belong to the cblG complementation group. Ganzfeld electroretinograms (ERG) and flash visual evoked potentials (VEP) were recorded over a period of 4 years.Results Amplitudes of all International Society for Clinical Electrophysiology of Vision (ISCEV) standard responses were below normal. The greatest reductions were of rod response to 24 V, of standard combined response (SC) b-wave to 120 V, of oscillatory potentials (OP) to 5 V, of cone response b-wave to 35 V, and of 30 Hz flicker response to 8 V. Except for SC and cone a-waves at age 2.5 and 3.5 years, as well as cone b-wave at 3.5 years, amplitudes remained at a subnormal level at follow-up examinations. Implicit times were slightly prolonged (SC b-wave 6 ms, OPs 2 ms, cone b-wave 2 ms, 30 Hz flicker 4 ms) or fell within the normal range. Responses of the flash VEP were severely deformed but reproducible.Conclusions This is the first report of detailed investigations of the visual system in a patient with isolated methionine synthase deficiency. Reduced oscillatory potentials suggest microvascular damage to the retina through homocysteine. Decreased photoreceptor function as well as ganglion cell loss as indicated by pathological flash VEPs may reflect a cytotoxic impact of homocysteine on neurons of the visual pathway.The authors have no competing interestsThe authors have full control of all primary data and they agree to allow Graefes Archives of Clinical and Experimental Ophthalmology to review their data if requested     

Effects of intravitreal perfusion with dopamine in different concentrations on the DC electroretinogram and the standing potential of the albino rabbit eye

The direct current electroretinogram and the standing potential were recorded from both eyes of 23 albino rabbits during intraocular perfusion of one of the eyes, which was vitrectomized, with a physiologic reference solution (PHS). PHS was then replaced by a test solution containing dopamine dissolved in PHS. The fluids were subsequently alternated (PHS-dopamine-PHS). During irrigation with 0.25–0.5 mM dopamine (11 rabbits) the c-wave amplitude was 140% higher (p < 0.001) and during irrigation with 25 mM dopamine (6 rabbits) 85% lower (p < 0.01) than it was during the corresponding initial perfusion with PHS. The simultaneously recorded b-wave amplitude was reduced (0.25–0.5 mM: -22%, p < 0.001; 25 mM: - 69%, p < 0.001) and the SP level increased (0.25–0.5 mM: +2375 V, p < 0.01; 25 mM: +2530 V, p < 0.05) compared with the values obtained during the corresponding preceding irrigation with PHS. Thus the changes in the b- and c-wave amplitudes during perfusion with dopamine were dependent on the concentration of the drug. In the contralateral control eye (23 rabbits) the c-wave amplitude was 21% higher (p < 0.001), the b-wave amplitude 14% higher (p < 0.001) and the standing potential 1007 V higher (p < 0.001) during intravitreal perfusion with dopamine in the other eye than during the preceding irrigation with PHS in that eye, possibly as a result of increasing dark adaptation.     

Toxicity of 1-(β-d-arabinofuranosyl)cytosine after intravitreal injection in the rabbit eye

The retinal toxicity of intravitreally injected 1-(-d-arabinofuranosyl)cytosine (cytarabine) was examined in 7 chinchilla rabbits to determine if cytarabine can be used as local therapy for vitreoretinal non-Hodgkin's lymphoma. Fractionated dose of 600 g, 1500 g, and 2700 g cytarabine in stabilized saline were given intravitreally in one eye (2 × 300 g, 5 × 300 g, and 3 × 900 g, respectively, with an interval time of 24 h) and stabilized saline in the other eye as control. Toxic effects were evaluated with biomicroscopy, direct ophthalmoscopy, fluorophotometry, electroretinography, light, and electron microscopy. Toxic effects were found with the 1500 g and 2700 g doses only. They consisted of a temporary impairment of the blood retina barrier function for fluorescein as measured by fluorophotometry and an irreversible change of the b-wave in the electroretinograms. No histopathologic changes were seen under the light microscope. Electron microscopic examination showed aberrations in the synaptic pedicles of the photoreceptor cells at a dose of 1500 g cytarabine. The results suggest that the cytarabine dose that is expected to be therapeutic for vitreoretinal non-Hodgkin's lymphoma (about 90 g given in three doses of 30 g) is non-toxic for ocular structures.Correspondence to: J.A. van Best     

Effects of β-agonists on b- and c-waves implicit for adrenergic mechanisms in cat retina

Nylidrin (buphenine) is a -adrenergic agonist known to dilate peripheral vessels and used therapeutically in retinal degeneration and glaucoma. We studied retinal function under -agonists in arterially perfused cat eyes and observed a dose-dependent, reversible increase in b-wave amplitude and a decrease in c-wave amplitude in concentrations from 4.5 to 120M. A half maximal response was obtained at 40 to 50M. The optic nerve response to light showed dose-dependent reversible changes under nylidrin. Standing potential, light peak, intraocular pressure, vascular resistance, and diameter of or retinal vessels showed no consistent changes under nylidrin.The effects were inhibited by each of the -blocking agents propranolol, ICI 118, and oxprenolol (in sequence of decreasing potency).Another potent ₂-agonist, clenbuterol, was used to determine the extent to which the responses to nylidrin were due to -receptor-mediated action. Clenbuterol had similar effects on the b-wave and optic nerve response at slightly higher concentrations (30–200 M) but more variable effects on the c-wave.The data are interpreted as functional evidence that -adrenergic mechanisms are involved in retinal signal processing. This concept is corroborated by identification of -adrenergic binding sites in cat retina (Bruinink et al., 1986).     

Die fixation des menschlichen auges

Zusammenfassung Während der Fixation wird ein Fixationsfeld beansprucht im Ausmaße von 100 , d.i. das Bereich der dünnsten und höchsten Zapfen, von 1 Durchmesser. In diesem Fixationsfeld ist der Fixationspunkt der Willkür entzogen. Während der strengen Fixation macht das Auge bekanntlich dreierlei Bewegungen, von denen die schnellen ebenfalls in einem Feld von 100 Durchmesser liegen. Das maculopapilläre Bündel führt die Erregungen aus dem auch in Bezug auf das Ableitungssystem ausgezeichneten Fixationsfeld ab. Die Sehschärfe unterschreitet weit die Grenze von 1 , was auf die Synapsenfunktionen der Retina, des Corpus geniculatum laterale und auf die cortikalen Bezirke zurückgeführt wird.

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Summary During fixation a fixation-field of 100 diameter is required, corresponding to the area of the thinnest and longest cones of 1 diameter. Within this fixation-field the position of the fixation point is involuntary and at random. The fast component of the three eye movements during fixation also covers a field of 100 diameter. Impulses from this field are conducted via the maculo-papillary bundle. The visual acuity is far below the limit of 1 ; this is attributed to the synaptic function of the retina, the lateral geniculate body and the cortical areas.

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Résumé Pendant la fixation un champ de 100 se trouve occupé, c'est-à-dire la région des cônes les plus hauts et les plus minces, qui ont pour diamètre 1 . Dans le champ de fixation le point de fixation n'est plus soumis à la volonté. Pendant la fixation précise l'oeil fait trois sortes de mouvements; les plus rapides d'entre eux intéressent aussi un champ d'un diamètre de 100 . Le faisceau papillo-maculaire conduit les influx nerveux hors du champ de fixation. L'acuité visuelle descend bien en-dessous de 1 . Ce fait est attribué aux fonctions synaptiques de la rétine, du corps genouillé externe et des régions corticales.

     

The negative response of the flash electroretinogram in glaucoma

The existence of a negative ERG component following the b-wave has been known for a long time. Recently, in unilateral macaque experimental glaucoma, a negative response in flash electroretinograms under scotopic as well as photopic conditions has been shown to be greatly reduced or absent compared to the healthy fellow eye. The aim of this pilot study was to test whether a late negative electroretinogram component is reduced also in human glaucoma patients under different stimulus conditions. Dark-adapted ganzfeld flash electroretinograms were recorded after 30 min of dark using two test conditions, obtained as optimal in pilot studies on controls. Under the scotopic condition I white Xenon-flashes of intensity 0.53 Log photopic Td s were presented on a low white background of 1.38 Log scotopic Td. Under the more photopic condition II orange flashes of intensity –0.37 Log photopic Td s were presented on a blue-adapting background of 2.5 Log scotopic Td. Nine controls and 18 patients with advanced glaucoma were analyzed. The amplitude of the negative response was not significantly reduced in glaucoma patients (condition I: –28.5±23.7 V; condition II: –25.2±19.7 V) compared to controls (condition I: –41.4±36.6 V; condition II: –31.3±26.2 V). The peak latency of the responses under condition I and II did not differ significantly between patients and controls. Thus, the late negative electroretinogram component in ganzfeld flash electroretinograms obtained under scotopic and more photopic conditions does not seem to distinguish as easy between human controls and glaucoma patients as animal experiments suggest.     

The effect of the water-drinking test on aqueous humor dynamics in healthy volunteers

In 19 healthy volunteers (9 men, 10 women) we studied the effect of drinking 1000 ml of water within 10 min on aqueous humor dynamics. Fluorescein was applied topically five times, 6 h before measurements. All readings were taken during the afternoon. The Wilcoxon signed-rank test was used to evaluate the statistical relevance of the data. Aqueous humor flow was measured 60 min before (F1) and 10 min (F2), 30 min (F3), 60 min (F4) and 90 min (F5) after drinking 11 of water. Flow (mean ± SD) changed as follows: F1, 2.25 ± 1.2 ll/min ; F2, –3.29 ± 3.4 /min (P < 0.0000); F3, 1.69 ± 1.0 gml/min (P=0.007); F4, 2.39±0.9 l/min (P=0.25); F5, 2.64±0.9 l/min (P=0.02). Three to four days later the identical procedure was performed in each individual: F1, 2.06 ± 1.0 l/min F2, –3.12 ± 2.4 l/min (P < 0.0000); F3, 1.09 ± 0.6 l/min (P < 0.0001); F4, 1.76 ± 0.6 l/min (P=0.15); F5, 2.54±0.8 l/min (P=0.01). The correlation coefficient for the left and night eyes (F1–F5, both days) was r=0.85. The mean flow in the 19 healthy volunteers during the afternoon hours was 2.25 ± 1.0 l/min. Water load consistently led to a reflux of unbound fluorescein into the eye about 10 min later. This is documented as a negative flow. Ninety minutes after drinking 1000 ml of water there is a significant increase in flow, which is in contrast to the normal diurnal curve of aqueous humor dynamics. Water load causes hydremia and an increase in episcleral venous pressure. Fluorophotometry together with water load may be useful to study the aqueous humor dynamics in healthy and glaucomatous eyes and eyes with ocular hypertension.     

Increased release of tenascin in tear fluid after photorefractive keratectomy

Background: Extracellular matrix protein tenascin (TN) is expressed in the anterior stroma during corneal wound healing. In this study we analysed TN release in tear fluid after photorefractive keratectomy (PRK). Methods: Tear fluid TN concentrations of ten PRK patients were measured with an immunoassay. Tear fluids were collected preoperatively and 1, 2 and 7 days after PRK. The tear fluid collection time and the volume of tears collected were registered. Because tear fluid flow was greatly increased postoperatively, tear fluid flow-corrected release (TN flux) was calculated. Results: The tear fluid flow was 4.50±0.94 l/min (mean±SEM) preoperatively, 55.48±16.70 l/min (P<0.01) on the 1st, 33.91±7.91 l/min (P<0.01) on the 2nd, and 13.79±5.49 l/min (P>0.05) on the 7th postoperative day. The preoperative TN concentration was 0.85±0.20 g/ml. On the 1st postoperative day it decreased to 0.37±0.17 g/ml (P>0.05), most likely due to the dilution effect caused by hypersecretion after PRK. The TN concentration was 0.67±0.12 g/ml (P>0.05) on the 2nd and 0.78±0.15 g/ml (P>0.05) on the 7th postoperative day. The preoperative TN flux was 5.23±1.88 ng/min. On the 1st and 2nd postoperative days the TN flux was 14.40±4.99 ng/min (P<0.05) and 22.66±6.I2 ng/min (P<0.05), respectively. On the 7th postoperative day a tendency towards decreased flux (14.00±6.02 ng/min, P>0.05) was observed. Conclusion: Although there is a minor decrease in TN concentration after PRK due to increased tear fluid flow, a significant increase in TN flux was observed. Complete reepithelialization of the ablated area was observed in all eyes at the follow-up visit on postoperative day 7.     

Nontoxic concentration of kanamycin and gentamicin for intravitreal use — evaluated by in vitro ERG

The effects of kanamycin (KM) and gentamicin (GM) on the in-vitro electroretinogram of the albino rabbit were studied. The b-wave and oscillatory potentials (OPs) were unchanged by 0.1 mM KM. The photopic b-wave and OPs were slightly suppressed by 0.4 mM. The b-wave and OPs were not deteriorated by 23 µg/ml (approximately 0.05 mM) GM. The photopic b-wave and OPs were slightly suppressed by 46 µg/ml (approximately 0.1 mM) GM. The minimum concentration affecting the ERG was tentatively defined as the mean of the minimum concentration needed to change the ERG and the maximum concentration which induced no discernible changes in the ERG. The minimum concentration of KM and GM affecting the ERG were 0.25mM (approximately 150 g/ml) and 35 g/ml (approximately 0.075 mM) respectively. The minimum concentration of KM affecting the ERG was higher than its minimum inhibitory concentration against Staphylococcus aureus and Streptococcus pneumoniae. The minimum concentration of GM affecting the ERG was higher than its mimimum inhibitory concentration against Staphylococcus aureus, Streptococcus pneumoniae and Pseudomonas aeruginosa.     

Nontoxic concentration of antibiotics for intravitreal use — evaluated by human in-vitro ERG

The effects of penicillin G (PC-G) sodium, procaine PC-G, cloxacillin sodium (MCIPC), disodium sulbenicillin (SBPC), cefazolin sodium (CEZ), gentamicin sulfate (GM) and fosfomycin sodium (FOM) on the electroretinogram (ERG) of the human in-vitro eye-cup were studied. The oscillatory potentials (OPs) were selectively and greatly suppressed by 1.0mM PC-G sodium. The OPs and c-wave were suppressed by 0.85mM procaine PC-G. The b-wave and OPs were slightly suppressed by 1.0mM MCIPC. The a-wave, b-wave, OPs and c-wave were not deteriorated by 1.0mM SBPC. The OPs appeared to be selectively suppressed by 1.0mM CEZ. The b-wave was suppressed and the peak latencies of the OPs were delayed by 184g/ml (approximately 0.4mM) GM. The amplitudes of the a-wave and c-wave were slightly enhanced and their peak latencies were slightly delayed by 184g/ml GM. The a-wave, b-wave, OPs and c-wave were not deteriorated by 1.0mM FOM. The results of the present study on the human retina were comparable to those on the albino rabbit retina in our previous studies.     

Untersuchungen über die Ultraviolettabsorption des normalen und des entzündlich veränderten Kammerwassers

Zusammenfassung In zahlreichen Untersuchungen wurde die Ultraviolettabsorption des menschlichen Kammerwassers vor und nach Bebrütung bei 37° C sowie vor und nach Zusatz von Hefenukleinsäure (Hoechst) im Bereiche zwischen 220 und 320 m untersucht. Das normale menschliche Kammerwasser zeigte eine UV-Absorptionskurve, wie sie bei allen eiweißhaltigen Flüssigkeiten beobachtet werden konnte. Nach der Bebrütung des Kammerwassers bei 37° C wurde ein Anstieg der Extinktion im gesamten Absorptionsbereich beobachtet. Kammerwasser, das bei der Hypopyon-Iritis gewonnen wurde, zeigte ein ausgeprägtes Absorptionsmaximum bei 280 m, das nach der Bebrütung bei 37° C anstieg. Zusatz von Hefenukleinsäure (Hoechst) zum Kammerwasser bei der Hypopyon-Iritis führte zum Auftreten eines Absorptionsmaximums bei 260 m. Durch Bebrütung bei 37° C wurde ein Ansteigen dieses Maximums erreicht. Aus den Untersuchungen wurde der Schluß gezogen, daß im Kammerwasser Enzyme eine Rolle spielen, die für die Beseitigung zelliger Elemente von Bedeutung sein könnten.

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Summary In numerous investigations the ultraviolet absorption of human aqueous humour was examined within the range of 220–320 m before and after being incubated at 37° C, as well as before and after addition of yeastnucleinic acid (Hoechst). The normal human aqueous humour showed an ultraviolet absorption curve similar to that which can be observed in all fluids containing proteins. After the incubation of aqueous humour at 37° C an increased extinction was noticed within the whole range of absorption. Aqueous humour derived from hypopyon iritis showed a marked maximum of absorption at 280 m which increased after incubation at 37° C. Addition of yeast-nucleinic acid (Hoechst) to the aqueous humour derived from hypopyon iritis resulted in the appearance of maximal absorption at 260 m. An increase of this maximum was reached by incubation at 37° C. It was deducted from these examinations that enzymes which could be of importance in removing cellulary elements, play an important part in the aqueous humour.

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Résumé Dans de nombreux cas on a examiné l'absorption des rayons ultraviolets par l'humeur aqueuse de l'homme dans une zone de 220 á 320 m. Ces examens furent faits avant et après maintien du liquide dans une couveuse à 37°, et avant et après addition de l'acide nucléique de levure. L'humeur aqueuse normale montrait une courbe d'absorption telle qu'on l'observe pour tous les liquides contenant des protéines. Après maintien de l'humeur aqueuse dans une température de 37° on a constaté une extinction plus grande dans tout le champ d'absorption. L'humeur aqueuse des yeux atteint d'une irite à hypopyon montre un maximum d'absorption très marqué à 280 m qui augmente encore après exposition à 37°. Après addition de l'acide nucléique de levure à l'humeur aqueuse le maximum fut constaté à 260 m, et après exposition à 37° ce maximum se trouvait encore accru. De ces observations on a conclu qu'il y a dans l'humeur aqueuse des enzymes qui pourraient avoir une importance dans l'elimination des élements cellulaires.

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Riassunto In numerose ricerche venne studiato l'assorbimento dei raggi ultravioletti dell'acqueo umano prima e dopo riscaldamento a 37° e prima e dopo aggiunta di acido nucleinico dei fermenti (Hoechst) in un campo oscillante fra 220 e 320 m. L'acqueo umano normale mostrava una curva di assorbimento quale si osserva in tutti i liquidi contenenti proteine. Nell'acqueo riscaldato a 37° si è notato un aumento dell'estinzione in tutto il campo di assorbimento. L'acqueo ottenuto da occhi affetti da ipopionirite mostrava un marcato massimo di assorbimento a 280 m che aumentava dopo riscaldamento a 37°. Con l'aggiunta di acido nucleinico dei fermenti (Hoechst) all'acqueo in caso di ipopion-irite, si osservò un massimo di assorbimento a 260 m, che aumenta dopo riscaldamento a 37° C. Si conclude da tali ricerche che gli enzimi nell'acqueo giuocano un ruolo che potrebbe avere importanza nell'eliminazione di elementi cellulari.

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Universitäts-Augenklinik, Würzburg.     

Distribution of calcium and sulphur in the blue-light-exposed rat retina

Background: Blue-light exposure inhibits cytochrome oxidase and may therefore inhibit retinal metabolism. The reduced metabolism decreases the extrusion of calcium from the photoreceptor cell. Overload of calcium is proposed as one of the factors that lead to photoreceptor degeneration after light exposure. The light-induced photoreceptor degeneration can be ameliorated by calcium overload blocker. In the present study the calcium concentration was measured in the inner and outer segment layer of the rat retina. Methods: Six eyes were exposed to blue (404 nm) light at a retinal dose of 380 kJ/m². Five eyes served as the control group. The calcium and sulphur distributions were measured with a nuclear microprobe in the freeze-dried rat retina. The proton beam size was 12 × 12 m and the energy of the protons was 2.55 MeV The calcium concentration was calculated using sulphur as a reference. Results: The level of calcium per milligram sulphur was 21 g (range 17–23 g) in the inner segment of the control retina. It increased to 62 g/mg sulphur (range 52–67 g) and 61 g/mg sulphur (range 58–66 g) 1 h and 12 h after blue-light exposure, respectively. Conclusion: The findings of the present study support the idea that accumulation of calcium in the inner segment layer is one of the factors that cause photoreceptor degeneration.     

Effects of retinal dopamine depletion on the rabbit electroretinogram

This study evaluated the effects of intravitreal injections of 300 g of 6-hydroxydopamine (6-OHDA) on electroretinogram (ERG) amplitudes and implicit response times of adult pigmented rabbits. One eye was injected intravitreally with 300 g 6-OHDA and 600 g ascorbic acid in a 0.3 ml 0.9% NaCl solution; the fellow eye received a similar solution containing only 600 g ascorbic acid. Following this treatment ERG recordings were performed at 1, 4, and 7 days. After the last recordings, animals were sacrificed and retinas were isolated for biochemical analyses. Significant and progressive reductions in retinal concentrations of dopamine (DA) and its main metabolites homovanilic acid (HVA), and dihydroxyphenylacetic acid (DOPAC) were found in treated retinas. Concentrations of norepinephrine (NE), serotonin (5HT), and 5 hydroxyindoleacetic acid (5-HIAA) were not affected, thus demonstrating the specific neurotoxic action of 6-OHDA on retinal dopaminergic neurons. Concurrently, significant increases in ERG a- and b-wave amplitudes as well as in implicit response times were observed. These electrophysiological changes were progressive reaching a maximum 7 days after intravitreal injections. Changes in b-wave amplitudes and response times were more pronounced at low intensities of stimulation. These results clearly show that, in rabbits, selective decreases in retinal DA concentrations result in pronounced ERG changes, which offer additional evidence supporting a role for this transmitter in lateral inhibition in the retina.This work was supported by MRC research Grants No. MT2593 and DG284.     

Ultrasound biomicroscopic analysis of the effect of pilocarpine on the anterior chamber angle

Background: This study was carried out to determine the effects of pilocarpine on the anterior chamber angle in healthy volunteers. Methods: We measured changes in anterior chamber depth (ACD), trabecular-iris angle (TIA), angle opening distance at 250 and 500 m from the scleral spur (AOD250 and AOD500), and iris thickness using ultrasound biomicroscopy in 48 eyes of 48 normal volunteers (ages 18–57 years, mean 34.8 years) before and 1 h after instillation of 2% pilocarpine. Results: Pilocarpine altered the TIA by –18.6° to + 10.5° (mean –4.16°), and change in the TIA increased significantly and linearly in relation with decrease in the pretreatment TIA (r = 0.929). Pilocarpine altered AOD250 change by –136 to +94 m (mean –38 m) and AOD500 by –151 to +157 m (mean –42 m); changes in the AOD250 and AOD500 were significantly correlated to the pretreatment AOD250 and AOD500 values, respectively (r = 0.923 andr = 0.896, respectively). The pilocarpine-induced change in the ACD showed a linear relationship to the pretreatment ACD (r = 0.887). The changes in the TIA, AOD250 and AOD500 showed greater increases in association with lower pretreatment ACD (r = 0.848,r = 0.891,r = 0.842) and smaller change in the ACD (r = 0.834,r = 0.839,r = 0.812). Conclusions: The response of the anterior chamber angle to pilocarpine, narrowing or widening, depended on its pretreatment state. The ability to predict the pilocarpine-induced change in the angle before the instillation of pilocarpine would be helpful in treating patients with glaucoma.     

The influence of ambient room lighting on the pattern electroretinogram (PERG)

It has been suggested that low ambient lighting conditions increase the amplitude of the PERG, but no data has been available on this issue. We recorded the transient PERG (0.8° check size) and steady-state PERG (15 rev/s, 0.8° and 16° check size) under three lighting conditions: dark room, only illuminated by the stimulus (resulting in 30 lux), our standard room lighting (windows occluded, one lighted lamp, 200 lux) and fully lit room (full ceiling illumination with eight fluorescent tubes) resulting in rather bright 2300 lux. The stimulus luminance was 50 cd/m². The sequence of lighting conditions varied for each subject and followed a balanced permutation of an ABCCBA scheme. Results showed a significant effect (P<0.01) across lighting conditions, with no relevant difference between the 30 and 200 lux conditions, but a reduction down to 70% at the 2300 lux condition. This obtained across all check sizes and temporal conditions. As an example, the transient PERG P50-amplitudes were as follows: dark, 5.6±0.8 V; medium, 5.3±0.6 V and bright, 3.8± V (mean ± SEM). Peak times decreased significantly with illumination (dark, medium or bright): 45.9±0.9, 43.1±0.6 or 40.8±0.8 ms. Contrast measurements quantitatively explained the noticeable reduction of PERG amplitude at the brightest illumination level simply by straylight, which reduced the display contrast. This suggests that bright sunlight should be excluded, and that lighting conditions should be moderately standardized at low or medium luminance levels for reproducible amplitudes and peak times.     

Functional imaging of the retinal microvasculature by Scanning Laser Doppler Flowmetry

Purpose: to image functionally perfused retinal vessels and to assess quantitatively the intercapillary space of the retinal microvasculature.Method: The base offunctional imaging and the quantitative assessment of the retinal vasculature is the two-dimensional map of the retina encoded by the laser Doppler frequency shift. By Scanning Laser Doppler Flowmetry (HRF. Heidelberg Engineering) the laser Doppler frequency shift of 16.384 retinal sites (256 pixels × 64 lines, spatial resolution10 m) of a retinal area of 2.7 × 0.7 mm was gained. The image processing was performed by a recently described algorithm (AFFPIA). Using the data of the laser Doppler frequency shift of every retinal site, a color-coded retinal image was establishedshowing perfused vessels and capillaries. By automatic pattern analysis of this image vessels and capillaries were identified and segmented. Based on this image the distances in [m] of every retinal site to the next vessel or capillary were calculated ("distanceto next capillary'). The functional imaging of the retinal perfusion was demonstrated in (1) normal retina, (2) retinal arterial occlusion, and (3) proliferative retinopathy. Intraobserverreliability of the quantitative assessment of the parameter ``distance to next capillary' was estimated by measuring 10 eyes of 10 subjects at 5 different days by one observer. Interobserver reliability of the quantitative assessment was evaluated by analysing10 perfusion maps by 5 different operators. In 93 eyes of 71 normal subjects (mean age 40.4 15 years) the juxtapapillary retina was quantitatively evaluated.Results: Qualitative evaluation: The functional images of the retinal perfusion of eyes with normal retina, with retinal arterial occlusion, and with proliferative retinopathy correspondedwell with the fluorescein angiography. Perfused vessels and capillaries became visible in a high local resolution. Quantititative assessment: The coefficient of reliability of the introobserver and interobserver reproducibility of the parameter ``mean distance to next capillary' was 0.74, and 0.95, respectively. The quantitative assessment of the perfusion showed that the major part of the retinal sites (>700%) had distancesto the next capillary lower than 30 m 46% of the retinal area had distances to the next capillary from 0–20 lm 26% of the retina had distances from 20–30 m, 12% of the retina had distances from 30–40 m 7% of the retina had distances from 40–50 m, 4% of the retina had distances from 50–60 m, and 4% of the retinal sites showed distances to the next capillary greater than 60 m. The mean distance tothe next capillary or vessel was calculated with 21 ± 6.5 m.Conclusion: By non-invasive Scanning Laser Doppler Flowmetry in combination with adequate softwareit is possible to perform a functional imaging of the retinal vasculature and to measure all index for the functional density of retinal capillaries and vessels.     

Topical and intravenous gentamicin in traumatically lacerated eyes

Intravenous or topical gentamicin may be the initial mode of treatment for lacerated or ruptured eyes by emergency room physicians while awaiting ophthalmic consultation and surgical repair. The purpose of this study was to determine the possibility of having retinotoxic intravitreal gentamicin concentrations in experimentally lacerated rabbit eyes treated with either intravenous or topical gentamicin separately or in combination with each other. Nontoxic concentrations of gentamicin were found in the vitreous bodies by all routes of drug administration. After 3 h intravitreal concentrations of gentamicin were: 0.20–0.30 g/ml when treated intravenously, 0–2.9 g/ml when treated topically, and 0.20–0.51 g/ml when treated both intravenously and topically. While the upper range of topically applied gentamicin concentrations (2.9 g/ml) is therapeutic for some pathogens, the wide range of intravitreal concentrations (0–2.9 g/ml) achieved does not indicate that topically applied gentamicin with or without intravenously administered gentamicin can reliably achieve therapeutic concentrations. Offprint requests to: M.O. Yoshizumi

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Retinal toxicity and ocular kinetics of 1-β-D-arabinofuranosyl-E-5-(2-bromovinyl)uracil in rabbits

The intraocular penetration of 1--d-arabinofuranosyl-E-5-(2-bromovinyl)uracil (BV-araU), a new antiviral drug, after oral administration, the effects of non-toxic intravitreal doses of BV-araU, and the intraocular kinetics of BV-araU after intraocular injection were studied in rabbits. The intravitreal penetration of BV-araU after oral administration was very poor: 0.11 ± 0.13 g/ml and 0.20 ±0.02 g/ml respectively in albino and pigmented rabbits 2 h after 30 mg/kg. An intravitreal injection of 200 g BV-araU caused transient electroretinographic (ERG) changes, whereas a 100-g injection and intravitreal irrigation with 20 g/ml BV-araU caused no ERG and histologic changes over the 4-week follow-up period. The half-life of the intravitreal concentration of BV-araU after an intravitreal injection was short (2.4 h). The results suggest that an intravitreal injection of 100 g BV-araU or an intravitreal irrigating solution containing 20 g/ml BV-araU is nontoxic to the retina and may be used for treatment of retinitis caused by varicella-zoster virus or herpes simplex virus type 1.