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.     

Cytotoxic effects of antiproliferative agents on human retinal glial cells in vitro

Purpose: Proliferative vitreoretinopathy (PVR) is characterizedby the formation of cellular membranes on the detached retina and also in the vitreous. Glial cellscan be found in epiretinal and subretinal membranes from eyes with PVR, proliferative diabeticretinopathy (PDR), idiopathic macular pucker, uveitis and other diseases affecting theretina. Proliferation and contraction of glial cells appears to play a role in the pathogenesisof PVR. This study is designed to inspect the effectiveness of harringtonine, as well as colchicine,daunomycin and fluorouracil, against cellular proliferation of cultured human retinal glial cellsthat might be involved in the retinal and/or vitreous proliferation. Methods: Cultures of human retinal glial cells were preparedusing the enzyme digesting method. Cells that had been in culture for 2–5 passages were usedin this study. Harringtonine (0.063 g/ml 2.0 g/ml), colchicines(0.5 g/ml 16.0 g/ml), daunomycin (0.1 g/ml 3.2 g/ml) and 5-fluorouracil(0.5 g/ml 16.0 g/ml) were added to cultures of human retinal glial cellsand the proliferation rates of the cells were measured by the MTT method. Results: Harringtonine at the dosage of 0.063 g/mlinduced suppression of cellular growth, but the changes were not statistically significant (p > 0.05).At a dosage ranging from 0.125 g/ml to 2.0 g/ml, harringtonine significantly suppressedcellular growth according to the test (p < 0.01). Likewise, other antiproliferativeagents inhibited cellular growth significantly at a dosage from 1.0 g/ml to 16.0 g/ml(colchicine), 0.2 g/ml to 3.2 g/ml (daunomycin) and 1.0 g/ml to 16.0 g/ml(5-fluorouracil), but not at 0.5 g/ml (colchicine), 0.1 g/ml (daunomycin) and0.5 g/ml (5-fluorouracil). The ID₅₀ were 0.33 g/ml (harringtonine), 3.11 g/ml (colchicine), 0.79 g/ml (daunomycin) and 5.23 g/ml (5-fluorouracil), respectively.Conclusions: Harringtonine was extremely effective ininhibiting human retinal glial cell proliferation, like other antiproliferative drugs such as colchicine,daunomycin and 5-fluorouracil. Harringtonine, therefore, may be a candidate for further studies regardingthe treatment of experimental PVR.     

Use of vancomycin in vitrectomy infusion solution and evaluation of retinal toxicity

The retinal toxicity of vancomycin in infusion solution used in vitrectomy and lensectomy was investigated in rabbit eyes by means of electroretinography and histologie study (light microscopy). Concentrations of 8g/ ml, 16g/ml, and 32g/ml of vancomycin in balanced salt solution caused no abnormal ERG or histologic changes. However, ERG amplitude depression and abnormal histologie changes occurred when the concentration of 100g/ml of vancomycin was used.Supported in part by U.S. Public Health Service grants EY07541 and EY02377 from the National Eye Institute, National Institutes of Health, Bethesda, MD.     

Penetration of five beta-adrenergic antagonists into the rabbit eye after ocular instillation

Aqueous humor and serum levels of five beta-adrenergic blockers were measured using gas Chromatographic techniques following ocular instillation of 1% solutions to rabbits. Octanol/buffer partition ratios were also determined. No apparent relationship was found betweeen the peak levels of the agents in aqueous humor and their octanol/buffer partition ratios. However, peak aqueous humor levels of timolol (461 ng/100 mg) and practolol (919 ng/100 mg), whose partition ratios were less than unity, occurred somewhat later (1 h) than the peaks of propranolol (859 ng/100 mg at 30 min), oxprenolol (1,771 ng/100 mg at 30 min) or alprenolol (1,004 ng/ 100 mg at 10 min) whose partition ratios exceeded unity. Peak levels in serum of timolol (8.0 ng/100 l), propranolol (4.2 ng/100 l), oxprenolol (11.5 ng/100 l), and alprenolol (4.5 ng/100 l) were achieved within 10 min and reduced to less than 15% within 4 h. Peak serum levels of practolol (9.9 ng/100 l) occurred somewhat later (2 h) and remained high (41%) 6 h later.     

In-vivo-Messungen der Breite des Schlemmschen Kanals beim Hydrophthalmus

Zusammenfassung In-vivo-Messungen der Breite des Schlemmschen Kanals ergaben bei 9 Hydrophthalmusaugen einen Mittelwert von 678 m. Die Extremwerte lagen bei 600 m und 800 m. Damit unterscheiden sich diese Werte signifikant von denen, die bei Glaucoma-simplex-Augen in vivo ermittelt worden waren (Mittelwert ¯x: 542 m, Extremwerte 425 m und 625 m).Die Kanalbreite bei Hydrophthalmusaugen nimmt sowohl mit dem Hornhautdurchmesser als auch mit der Höhe des Augeninnendrucks zu.Die Erfolgsaussichten einer Trabekulotomie bei Hydrophthalmusaugen sind offenbar besser, wenn die Kanalbreite unter 650 m liegt. Die Trabekulotomie sollte deshalb so früh wie möglich ausgeführt werden.

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In vivo-measurements of the latitude of Schlemm's canal in buphthalmos

Summary In 9 cases of buphthalmos in vivo-measurements of the latitude of Schlemm's canal gave us a mean value of 678 m. The extreme values ranged between 600 m and 800 m. Therefore these values differ significantly from those measured in vivo in chronic simple glaucoma (¯x: 542 m, extreme values 425 m and 625 m). The latitude of Schlemm's canal correlates with the diameter of cornea and the rise of intra-oculare pressure.In cases of buphthalmos the success of trabeculotomy seems to be better, if the latitude of Schlemm's canal is less than 650 m. Trabeculotomy should therefore be performed as soon as possible.

     

The routes for bulk drainage of aqueous humour in rabbits with and without cyclodialysis

Summary The bulk drainage of aqueous humour into the general circulation and into the orbital tissues was studied with ¹³¹I-labelled albumin and red dextran (molecular weight 40,000) in rabbits with and without cyclodilaysis.In animals at a normal intraocular pressure of about 20 mm Hg and without an artificial cleft between the anterior chamber and the suprachoroid the rate of aqueous bulk flow into the general circulation was 3.99 ± 0.55 l/min. There seemed to be some outflow also through other routes ending up in the episcleral tissues in the limbus region but less than 0.11 ± 0.02 l/min was drained in that way.Even in dead eyes maintained at an intraocular pressure of 14 mm Hg only negligible quantities of labelled anterior chamber fluid passed into the tissues with bulk flow.In acute experiments in living animals, after a cleft had been opened between the anterior chamber and the suprachoroid without damaging the sclera, the rate of aqueous production was 5.64 ± 0.65 l/min. On an average 54% of the aqueous humour was drained into the suprachoroid from where great amounts penetrated the sclera in part by way of perivascular spaces in part directly through the scleral substance. Before the cleft was produced the facility of outflow was 0.237 ± 0.038 l/min per mm Hg, afterwards it was on an average 0.505 ± 0.092 l/min per mm Hg higher.

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Zusammenfassung Der bulk Abfluß von Kammerwasser in den Blutstrom und in die Gewebe der Orbita wurde in normalen und cyclodialysierten Kaninchen mit ¹³¹I-Albumin and rotem Dextran (Molekulargewicht 40,000) studiert. In Tieren mit normalem intraocularen Druck (20 mm Hg) war der Abfluß ins Blut 3.99 ± 0.55 l/Min. Es gab wahrscheinlich auch einen Abfluß in die Gewebe, aber dieser Abfluß war geringer als 0.11 ± 0.02 l/Min. Auch in toten, perfundierten, Augen gab es bei einem intraocularen Druck von 14 mm Hg nur einen sehr geringen Abfluß in die Gewebe.Nachdem in akuten Experimenten ein Spalt zwischen der Vorderkammer und dem Suprachoroidalraum geöffnet war, war die Kammerwasserproduktion 5.64 ± 0.65 l/Min. Durchschnittlich 54% davon wurden zum Suprachoroidalraum drainiert, von wo große Mengen die Sklera zum Teil durch perivaskulare Spatien, zum Teil direkt durch die Skleralsubstanz durchsetzten. Bevor der Spalt geöffnet wurde, war die Abflußfazilität 0.237 ± 0.038 l/Min per mm Hg, nachher war sie um 0.505 ± 0.092 l/Min per mm Hg gesteigert.

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Résumé Le bulk drainage d'humeur aqueuse dans la circulation générale et dans les tissues orbitaux était étudié avec d'albumine marquée par ¹³¹I et de dextrane rouge (poids moléculaire 40,000) chez des lapins avec et sans cyclodialyse. Chez des animaux avec une pression intraoculaire normale d'environ 20 mm Hg et sans une communication artificielle entre la chambre antérieure et la suprachoroïde la vitesse du bulk flux aqueux dans la circulation générale était 3.99 ± 0.55 l/min. Il semblait avoir quelque flux aussi par d'autres voies directement dans le tissue épiscléral dans la région limbale; mais moins que 0.11 ± 0.02 l/min. était drainé ainsi.Même dans des yeux morts maintenus sous une pression intraoculaire de 14 mm Hg seulement des quantités insignifiantes d'humeur aqueuse marquée filtraient de la chambre antérieure dans le tissu épiscléral comme bulk flux. Dans des expériences aiguëes avec des animaux vivants, après avoir fait une ouverture entre la chambre antérieure et la suprachoroïde sans blesser la sclérotique, le débit de l'humeur aqueuse était 5.64 ± 0.65 l/min. En moyenne 54% de l'humeur aqueuse étaient drainés dans la suprachoroïde, et de là partiellement par des espaces périvasculaires partiellement par la substance sclérotique. Avant que l'ouverture était créée la facilité du flux était 0.237 ± 0.038 l/min per mm Hg, après elle était en moyenne 0.505 ± 0.092 l/min per mm Hg plus haut.

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Department of Pharmacology, University of Uppsala.     

Die Stereo-Ultrastruktur der Cornealoberfläche bei der Ratte

Zusammenfassung Die dreidimensionale Beschaffenheit der Cornealoberfläche der Ratte wurde mittels des Scanning Electron Microscope und anhand konventioneller elektronenmikroskopischer Schnittpräparate untersucht. Dabei konnte das Vorhandensein von Mikrovilli (0,15 breit, bis 1,0 hoch) und von Mikroplicae (0,1–0,2 breit, 0,3–0,4 hoch, 1–3 lang) nachgewiesen werden. Bei diesen Strukturen dürfte es sich um während der Desquamation entstandene Ausstülpungen der Epithelzellmembran im Bereiche der Desmosomen handeln.

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The stereo ultrastructure of the corneal surface in rat

Summary Combined morphological examination of the corneal surface of rat both with the scanning and the transmission electron microscope reveals two kinds of protrusions covering the polygonal, regularly arranged epithelial cells: Mikrovilli and Mikroplicae; the former being approximatively 0.15 large and up to 1.0 high, the latter being 0.1–0.2 large, 0.3–0.4 high and 1–3 long. These formations are with high probability the remnants of desmosomes having been formed during desquamation.

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Diese Untersuchungen wurden mit Unterstützung des Fonds National suisse de la recherche scientifique (Nr. 5322.3) durchgeführt.     

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.     

Toxicity and clearance of intravitreal cefotetan

Direct, intravitreal injection of antibiotics plays an important role in the management of bacterial endophthalmitis. In the present study we investigated the toxicity and clearance of intravitreally injected cefotetan in a rabbit model. No toxic ocular side effects could be detected by electroretinography (ERG) or light and electron microscopy up to and including a single intravitreal dose of 1000 g. Intravitreal injection of 2000 g cefotetan resulted in mild degeneration of photoreceptor outer segments and, sporadically, in cataract formation. After intravitreal injection of 4000 g, moderate toxic degeneration of photoreceptors occurred, with displacement and mitochondrial swelling of inner segments. In addition, lysosomal lamellar inclusion bodies could be detected in pigment epithelial cells. After a single intravitreal injection of 1000 g cefotetan, concentrations greater than the minimum necessary for the inhibition of most commonly occurring intraocular pathogens (exceptPseudomonas aeruginosa andStaphylococcus epidermidis) were maintained in the vitreous humor for > 48 h. Cefotetan may be a potentially important drug for intravitreal injection, especially in cases of gram-negative and suspected anaerobic endophthalmitis.     

Lamellar excimer laser keratoplasty: Reproducible photoablation of corneal tissue

We examined the depth of ablation of the recipient bed with different counts of oscillations of excimer laser beam, to determine the correlation between planned and real depth. The ablation rate per oscillation was tested preoperatively by blackened photographic paper of defined thickness and thus was calculated to be 5 m. Forty pig eyes were used for the first study. Each eight eyes were ablated in the planned depth 100 m, 200 m, 300 m, 400 m and 500 m. The corneal thickness was measured with an ultrasonic pachymeter before and after the procedure. The depth measured after the photoablation was 99.4 ± 36.4 m for 100 m planned depth, 186.7 ± 55.3 m for 200 m, 298.4 ± 68.5 m for 300 m, 373.9 ± 65.7 m for 400 m and 480.1 ± 59.3 m for 500 m. Comparing the depth measured after the photoablation to planned depth, there was a significant correlation (correlation coefficient: R = 0.93; p < 0.0001). Five other corneas trephinated from pig cadaver eyes were ablated from the endothelial side to the desired thickness (100 to 500 m) of lamellar graft. In a second step a donor mask was placed onto the cornea and a laser light spot was led until perforating on all sides. The lamellar keratoplasty was completed by suturing the corneal graft into the bed. Macroscopic and microscopic examination of sutured eyes after fixation showed a good fit of wound margins and stromal interface. These results indicate that excimer laser is useful for reproducible corneal photoablation in lamellar keratoplasty.     

Methods of visual acuity determination with the spatial frequency sweep visual evoked potential

Purpose The spatial frequency sweep visual evoked potential (sVEP) is used to rapidly determine visual acuity in children or non-responsive patients. Two techniques have been used to separate signal from noise: (1) the 95% confidence interval for the signal amplitude (95% CI) or (2) the amplitude of a Fourier frequency adjacent to 2×the signal frequency (DFT). The purpose of this study is to determine if there is a significant difference in acuity estimates with these techniques.Methods Ten normal subjects (approximately 0.00logMAR acuity) and 11 patients with decreased visual acuity took part in this project. Stimulus production and data analysis were done with an Enfant 4010 (Neuroscientific Corp). Standard VEP recording techniques were employed. The stimulus was a horizontal-oriented, sine wave grating that swept up the spatial frequency spectrum (contrast 80%, temporal reversal rate 7.5Hz). Sweeps were repeated until the confidence intervals for the data were no longer decreasing. The Bailey LovielogMAR chart was used to determine visual acuity. A line was fit to the high spatial frequency data using either the 95% CI or the DFT as the noise estimate. By using these linear equations, acuity estimates were obtained at 0, 1, and 2V signal amplitudes.Results The average logMAR acuity for the subjects with normal acuity was –0.06±0.070 (SD). The sVEP acuity estimates were 0.08±0.098, 0.18±0.092, and 0.33±0.195 (0, 1, and 2V extrapolations) with the 95% CI used as noise and 0.07±0.100, 0.18±0.103, and 0.33±0.202 (0, 1, and 2V extrapolations) with the DFT used as noise. By using the average noise from the Fourier frequency as the extrapolation level, the acuity was 0.10±0.098logMAR. The averagelogMAR acuity for the subjects with decreased visual acuity was 0.67±0.306 (SD). The sVEP acuity estimates were 0.53±0.175, 0.66±0.171, and 0.88±0.295 (0, 1, and 2V extrapolations) with the 95% CI used as noise and 0.53±0.179, 0.65±0.176, and 0.86±0.268 (0, 1, and 2V extrapolations) with the DFT used as noise. By using the average noise from the Fourier frequency as the extrapolation level, the acuity was 0.57±0.186logMAR. No significant difference was found between the two acuity estimate techniques for all of the subjects (repeated measures ANOVA, p=0.16, F₂₀=2.131). The sVEP estimates of acuity to the 0V and noise levels were not significantly different from the logMAR acuity (paired t-test, all p values >0.05).Conclusions The results indicate that the sVEP acuity does not depend on the noise estimation technique. In agreement with prior studies, the sVEP acuity underestimates the logMAR acuity in normally sighted individuals by about an octave.     

Human conjunctival surface mucins: A quantitative study of normal and diseased (KCS) tissue

The architecture and distribution of surface mucins were studied qualitatively and quantitatively by transmission electron microscopy in ruthenium red stained biopsies of the human conjunctiva. Six control specimens were compared with three from early keratoconjunctivitis sicca (KCS) and with three specimens from severe KCS cases. The area of the ruthenium red/Os04/mucin reaction product on the conjunctival epithelial surface was measured by image analysis and the values were expressed in m² per m length of epithelium. The total area of surface mucins was differentiated from the narrow zone of mucins in close contact with the microplicae. The value for total mucins in two cases of early KCS was higher (0.4 m²/m) than the control range (0.1–0.3 m²/m) due to the presence of large clumps of mucins on the surface. The values for microplical mucins in early and severe KCS were within the control range, but were an overestimate owing to the presence of abnormal structures, e.g. vesicles, and abnormal clumps on the surface. This morphometric technique has limitations, but with appropriate material it might be a useful tool for the identification of conjunctival surface mucins.This paper was presented in part at the Eighth Annual Meeting of the European Club for Ophthalmic Fine Structure in West Berlin on 28th, 29th March, 1980     

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.     

Effects of norfloxacin on the retina in rabbits

Background: Fluoroquinolones have a strong affinity with melanin, and their ocular effects have been reevaluated. Norfloxacin, one of the fluoroquinolones, has broad-spectrum activity against aerobic gram-positive and gram-negative bacteria. We examined the retinal toxicity and intraocular pharmacokinetics of intravitreal norfloxacin in rabbits. Methods: Twenty-three albino and 23 pigmented rabbits were divided into three groups to evaluate retinal toxicity and two groups to investigate the intraocular pharmacokinetics. Each of these five groups was further divided into two subgroups (albino rabbits and pigmented rabbits). Results: With 500 Etg norfloxacin, the oscillatory potential of the electroretinogram was transiently and selectively deteriorated in albino and pigmented rabbits, whereas the electroretinogram remained unchanged with 50 g in pigmented rabbits. No changes were observed in the visual evoked potential or on histology of the retina 7 days after an intravitreal injection of 50 or 500 ltg norfloxacin. The electroretinogram and the retinal histology became abnormal 7 days after four intravitreal injections of 500 g norfloxacin at 7-day intervals. As regards the intraocular pharmacokinetics after an intravitreal injection, the norfloxacin concentration in the chorioretina was as high as that in the vitreous 3 h after injection and was much higher than that in the vitreous 7 days after injection. Similar results were obtained after multiple injections. Conclusion: These results indicate a high concentration of norfloxacin in the melanin-containing ocular tissues.     

Effect of Prostaglandin E2 on aqueous humor flow in the rabbit eye

Summary The examinations were carried out in albino rabbits under urethane anaestesia. After intracameral injection of 0.5 g Prostaglandin E₂, dissolved in 10 l 10% ethanol, intraocular pressure increased by 20.5±4.9 mm Hg. Aqueous humor protein concentration in the uninjected control eyes was 0.176±0.03 g%. Thirty minutes after intracameral injection of 10 l 10% ethanol solution the concentration rose to 0.38±0.19 g-%, and after of 0.5 g Prostaglandin E₂ to 1.85 ±0.41 g% These interventions were not followed by significant changes in aqueous humor osmolarity (normal value 313.7±17.9 mOsm, after ethanol 330 5±18. 0, and after prostaglandin E₂ 329.3±6.9).In a special series of experiments the rate of aqueous humor production was determined. In the uninjected control eyes a value of 1.57±0.61 l/min was found, but after intracameral injection of 0.5 g prostaglandin E₂, 5.45±1.99 l/min.The authors draw the conclusion that prostaglandin E₂ increases intraocular tension not by enhancing aqueous humor production but by disrupting the bloodaqueous humor barrier.

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Zusammenfassung Die Untersuchungen wurden an Albinokaninchen in Urethannarkose durchgeführt. Nach Injektion von 0,5 g Prostaglandin E₂ (in 10 l10%iger Äthanollösung) in die Vorderkammer stieg der Augenbinnendruck um 20,5±-4,9 mm Hg an. Der Gesamteiweißgehalt im Kammerwasser der intakten Kontrollaugen betrug 0,176±0,03 g-%. 30 min nach Einspritzung von 10 l 10%iger Äthanollösung in die Vorderkammer erhöhte sich der Gesamteiweißgehalt auf 0,38±0,19 g-%. Diese Einwirkungen hatten keine signifikante Änderung der Kammerwasser-Osmolarität zur Folge (Normalwert 313,7±17,9 mOsm, nach Äthanol 330,5±18,1 und nach Prostaglandin E₂ 329,3±6,9).In einer besonderen Versuchsreihe wurde die Kammerwasserproduktion bestimmt. In den intakten Kontrollaugen ergab sich hierbei ein Wert von 1,57±0,61 (l/m, nach Gabe von 0,5 g Prostaglandin E₂ aber 5,45±1,99 l/min.Die Autoren ziehen den Schluß, daß Prostaglandin E₂ den Augenbinnendruck nicht durch Steigerung der Kammerwasserproduktion, sondern durch Schädigung der Blut-Kammerwasserschranke erhöht.

     

Toxicity and efficacy of intravitreal injection of spartanamicin B* in the treatment of Candida endophthalmitis **

Aims/Background: We evaluated the retinal toxicity of spartanamicin B and its efficacy in a rabbit model of Candidal endophthalmitis. Methods: Toxicity. Fourteen albino rabbit eyes were injected intravitreally with spartanamicin B (1, 2, 5, 10, 25, 50, and 100 g) ; 2 eyes received the vehicle alone. Efficacy. Ten rabbit eyes were inoculated with 3000 Candida organisms which caused endophthalmitis in 24 hours. Eight eyes were treated with intravitreal spartanamicin B in doses of 1, 2, 5, or 10 g/0.1 ml; 2 untreated eyes served as controls. Results: Toxicity. The eyes injected with 10 g and the control group eyes exhibited no clinical, histological, or electroretinographic evidence of retinal toxicity. Doses > 10 g caused vitritis. Efficacy. Clinical examination of the treated eyes showed a gradual improvement over 3–6 days; mild opacities remained until day 14. Results of cultures performed 15 days after infection were negative in all treated eyes. Conclusions: Intravitreally injected spartanamicin B (10 g) is nontoxic to the retina, effective against C. albicans in the endophthalmitis model in the rabbit eye and caused no discernible histological changes in the retina.     

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.     

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.

     

Ocular hypotensive effect of sublingual administration of timolol

Purpose: A randomized clinical trial to assess ocular hypotensive effect of sublingual administration of timolol was performed. Patients and methods: Seventeen (9 male, 8 female; age range 45 to 68 years) with bilateral ocular hypertension were selected for the study. Each patient was evaluated with regard to IOP, arterial blood pressure and heart rate before and after each of the following experimental treatment: unilateral ocular administration of 20 l of 0.5% timolol solution; sublingual administration of 20 l of 0.5% timolol solution; unilateral ocular administration of 20 l of saline solution (placebo); sublingual administration of 20 l of saline solution (placebo). The sequence of the treatments and the eye topically treated were randomly chosen. At least four weeks wash-out elapsed between each experimental treatment. Results: Our results showed that sublingual administration of timolol was able to induce a bilateral significant reduction of the IOP. This reduction was not statistically different from that obtained in the eye treated with timolol. A significantly greater reduction of the IOP was obtained by sublingual timolol than in the contralateral eye after unilateral topical administration of timolol solution. No significant modification of arterial blood pressure and heart rate were evidenced after the treatment. Conclusions: Sublingual administration seems to be a new interesting way for reducing the IOP. Long term studies are required in order to test efficacy and safety of this new treatment.     

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.