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.     

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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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.     

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.     

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.

     

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.     

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.     

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.     

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     

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.     

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.     

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.

     

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.     

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.

     

Evaluation of toxicity and efficacy of a combination of antineoplastic agents in the prevention of PVR

The retinal toxicity of a combination of antineoplastic drugs in free and liposome-encapsulated form was determined in the rabbit eye. Bleomycin sulfate and 5-fluorouridine were evaluated by clinical observation, electroretinogram, and histological study. Forty-five eyes were injected with combinations of various doses of bleomycin and 5-FUR in free and encapsulated form; 10 eyes served as controls. The nontoxic free dose was found to be 3.5g bleomycin and 150g 5-FUR. Liposome encapsulation increased the nontoxic dose to 4.7g bleomycin and 200g 5-FUR. Four groups of rabbits in which proliferative vitreoretinopathy had been induced were used for the efficacy study; the control group received an injection of PBS; the second group was injected with a combination of 3.5g bleomycin and 150g 5-FUR in free form; the third group was injected with the identical doses in liposome-encapsulated form; and the fourth group received encapsulated bleomycin (4.7g) and 5-FUR (200g). The dose used in Group 4 was significantly more effective (P<0.01) in preventing tractional retinal detachment and marginally more effective (P=0.054) in preventing neovascularization.Supported in part by U.S. Public Health Service grants EY07541 and EY02377 from the National Eye Institute, the National Institutes of Health Services, Bethesda, MD     

„Aberrante“ Ganglienzellen in der Wurzel des Nervus oculomotorius des Menschen

Zusammenfassung 56 Nn. oculomotorii von 37 Erwachsenen (mittleres Alter 66 Jahre) wurden untersucht. In 25 der 56 Nerven (44,6%) bzw. bei 19 der 37 Erwachsenen (51%) wurden insgesamt 243 Ganglienzellen in der Nervenwurzel gefunden. Der mittlere Durchmesser von 100 Zellen betrug 43.7 (range: 26,8–69,8 ; größte Frequenz bei 35–45 ). Histologisch ähneln sie den sensiblen Zellen eines Spinalganglions. Es wird die Frage aufgeworfen, ob es sich um aberrante Ganglienzellen oder ein Zellsystem handelt.Der Befund eines sensiblen Ganglion mit 46 Ganglienzellen im Verlauf des N. trochlearis wird erwähnt.

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Aberrant ganglion cells in the human ocullomotor nerve

Summary 56 oculomotor nerves of 37 adult men (mean age 66 years) were examined. A total amount of 243 nerve cells were counted in 25 nerves (44.6%) that is to say in 19 men (51%). The mean diameter of 100 cells was 43.7 (range: 26.8–69.8 ,). The diameter of most of the cells fell between 35 to 45 . Histologically they look like sensory cells of a spinal ganglion. The question arises, whether these neurones represent aberrant cells or an independent neuronal grouping.The finding of a sensory ganglion in the course of the trochlear nerve with 46 nerve cells in it is mentioned.

     

Intraocularer Druck und Kammerwasserzirkulations-Untersuchungen an Kaninchenaugen nach intravenöser Verabreichung von Propranolol (Inderal®)

Zusammenfassung Der intraoculare Druck der mit Urethan anaesthesierten Kaninchen betrug 20,8 mm Hg. I.v. verabreichtes Propranolol (Inderal, 0,3 mg/kg Körpergewicht) verringerte diesen Druck auf 18,8±1,3 mm Hg. Die totale Leichtigkeit des Kammerwasserabflusses an den Kontrollaugen betrug 0,309±0,090 l/mm Hg/min, während sich nach Verabreichung von Propranolol dieser Wert auf 0,237 ±0,083 l/mm Hg/min veränderte. Die Kammerwasserproduktion in den Kontrollaugen betrug 2,16±0,78 l/min. Nach Verabreichung von Propranolol ging sie auf 1,15±0,64 l/min zurück. Die Differenzen erwiesen sich als statistisch signifikant. Die Abnahme der Abflußleichtigkeit erscheint den Daten nach geringer als die Abnahme der Kammerwasserproduktion. Dadurch erklärt sich die Verringerung des intraocularen Druckes. Aufgrund des Vergleiches der verschiedenen und von einander abweichenden Literaturangaben vermuten die Verfasser, daß das Propranolol außer der tonusverringernden Wirkung auf die -adrenergen Receptoren auch noch einen anderen Wirkungsmechanismus entfalten kann.

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Intraocular pressure and circulation of aqueous humour in rabbit eyes following intravenous administration of propranolol (Inderal^®)

Summary The intraocular pressure of rabbits under urethan anaesthesia was found to be 20.8±2.4 mm Hg. 0.3 mg/kg body weight propranolol given intravenously lowered intraocular pressure to 18.8±1.3 mm Hg. The total facility of outflow from control eyes examined at constant pressures of perfusion was 0.309 ±0.09 l/mm Hg/min, which was reduced to 0.237±0.08 l/mm Hg/min by propranolol given systemically. The formation of aqueous humor in the control eyes was 2.16±0.78 l/min, which was diminished to 1.15±0.64 l/min by propranolol. The differences are statistically significant. The decrease in facility of outflow is smaller than the decrease in formation of aqueous humour, which accounts for the lower intraocular pressure. On the basis of the various and gently differing data in the literature it is assumed that propranolol may have some other mode of action in addition to its -adrenolytic effect on receptors.

     

Diclofenac sodium and cyclosporin A inhibit human lens epithelial cell proliferation in culture

Purpose: To investigate the effect of diclofenac sodium salt and cyclosporin A (CsA) on human lens epithelial cell (HLEC) growth in culture. Methods: Cultures of HLEC were obtained from anterior capsules from extracapsular cataract surgery. Third-passage cells were seeded in 96-well plates in 0.1 ml culture medium. Cytotoxicity was estimated by the tetrazolium test in confluent monolayers after 24 h exposure to a wide range of concentrations of diclofenac and CsA. The effect of subcytotoxic concentrations of diclofenac and CsA on HLEC proliferation in subconfluent cultures was evaluated after 24 and 72 h of exposure. To investigate the relationship between PGEZ synthesis and the inhibitory effect of these drugs, after 24 h of exposure to diclofenac and CsA the production of PGE₂ was measured by radioimmunoassay. We also tested the effect of exogenous PGE₂ addition to diclofenac 72-h-treated cultures. Results: Diclofenac and CsA (at concentrations 65 M and 2.5 M, respectively) inhibited the proliferation of subconfluent cultures of HLEC in a dose-dependent fashion. Diclofenac inhibits PGE₂ synthesis, while CsA at high doses stimulates PGE₂ synthesis of cultured HLEC. Exogenous PGE₂ addition reversed in part the inhibitory effect of diclofenac. Conclusions: Diclofenac and CsA at appropriate doses are effective in inhibiting cultured HLEC proliferation. This could be of interest to prevent posterior capsule opacification. Further in vivo experimental studies seem worthwhile.None of the authors have financial or proprietary interests in any of the products mentioned in this article     

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.     

Vitreous Fluid Levels of β-Amyloid(1–42) and Tau in Patients with Retinal Diseases

Purpose A decrease in -amyloid_1–42 (A42) and an increase in tau in the cerebrospinal fluid are reported to be characteristic phenomena in Alzheimers disease patients. To test the idea that A42 and tau contribute to the development of retinal diseases, we measured A42 and tau concentrations in the vitreous fluid from patients with macular hole (n = 13), diabetic retinopathy (n = 15), or glaucoma concurrent with other ocular diseases (n = 8).Methods Vitreous samples were collected from patients who underwent vitrectomy, and sensitive and specific enzyme-linked immunosorbent assays were used to determine the concentrations of A42 and tau.Results By comparison with the levels in the control macular-hole patients (33.9 ± 7.1pg/ml for A42; 3.3 ± 3.2pg/ml for tau), there was a significant decrease in the A42 level and a significant increase in the tau level in patients with diabetic retinopathy (1.8 ± 1.9pg/ml for A42, P = 0.002; 153.7 ± 71.6pg/ml for tau, P = 0.041) or glaucoma concurrent with other ocular diseases (2.8 ± 1.8pg/ml for A42, P = 0.006; 113.6 ± 43.1pg/ml for tau, P = 0.023).Conclusions Our findings indicate the possibility of a role for A42 and tau in the pathogenesis of some retinal diseases. Jpn J Ophthalmol 2005;49:106–108 © Japanese Ophthalmological Society 2005