Pattern electroretinogram for monitoring the efficacy of intravitreal triamcinolone injection in diabetic macular edema

Purpose: To investigate the efficacy of intravitreal triamcinolone (IVT) by evaluation of pattern electroretinogram (PERG) in diabetic patients with clinically significant macular edema (CSME). Methods: Forty eyes of 40 diabetic patients were treated with 8 mg of IVT injection as primary therapy for CSME. The main outcome measures included best-corrected visual acuity, fundus fluorescein angiography, P₅₀ amplitudes of pattern electroretinogram (PERG) and intraocular pressures before and after injection. Results: The mean follow-up time was 6.1 months. Mean visual acuity improved significantly from a mean LogMAR value of 1.14 ± 0.16 at baseline to a maximum of 0.73 ± 0.30. The mean baseline P₅₀ amplitude of PERG before intravitreal injection was 1.5 ± 0.9 V. After the treatment, it was 2.l ± 1.1 V at 1-month, 2.4 ± 1.0 V at 3-month and 2.1 ± 0.9 V at last visit and the differences were significant when compared with baseline values (for each, p < 0.001). Temporary increases in intraocular pressures were controlled with topical antiglaucomatous medications, if required. Conclusion: IVT injection provides rapid improvement in visual acuity of diabetic patients with CSME that has been supported by P₅₀ amplitudes of PERG. P₅₀ amplitudes of PERG may be used as novel predictive value in the evaluation of the effectiveness of IVT injection.     

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 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.     

Ciliary body toxicity of cyclosporin A and octreotide acetate in rabbit eyes: a comparison with mitomycin C and 5-fluorouracil

Purpose To compare the toxicities of cyclosporin A, octreotide acetate, mitomycin C and 5-fluorouracil to the ciliary body.Method We applied sponges soaked in these compounds to the open scleras of rabbit eyes. Histopathological specimens were obtained from the operation site and at 180° from it on the 14th day after surgery.Results Mean ciliary epithelial thickness in the study groups was as follows: 12.29±2.69 m in group 1 (mitomycin C), 13.85±4.56 m in group 2 (5-fluorouracil), 17.71±3.09 m in group 3 (cyclosporin A), 11.64±2.92 m in group 4 (octreotide acetate), 11.92±2.89 m in group 5 (topically applied octreotide acetate) and 21.85±4.29 m in group 6 (control). The ciliary epithelial thickness in groups 1, 2, 4 and 5 was statistically different from that in the control group. Intracellular vacuolisation and degenerative changes of the non-pigmented epithelium, and pigment loss of the pigmented epithelium, were found mostly in group 1 and moderately in group 2 and 3.Conclusion Octreotide acetate and cyclosporin A are less toxic alternatives to mitomycin C and 5-fluorouracil in glaucoma filtration surgery.     

Macular pigment density in age-related maculopathy

Purpose Macular pigment (MP) is believed to have a protective role in the development and progression of age-related maculopathy (ARM). We present results of measurements of macular pigment density (MPD) in patients with ARM at different stages with a modified confocal scanning laser ophthalmoscope (HRA, Heidelberg Engineering, Heidelberg, Germany).Method ARM patients were categorized into four groups. Staging depended upon the size of drusen, geographic atrophy, and loss of visual acuity due to ARMD in the fellow eye; 1: drusen size <125 m, 2: drusen size >125 m, 3: drusen size <125 m+ARMD in fellow eye, and 4: drusen size >125 m+ARMD in fellow eye. We took autofluorescence images at 488 nm and 514 nm with a modified HRA. MP density was evaluated within 2° around the center of the fovea. In this study, we included 146 patients with ARM: 26 in group 1, 19 in group 2, 80 in group 3, and 21 in group 4.Results The mean MPD of the different stages of ARM was: in group 1, 0.233±0.091 DU; group 2, 0.218±0.102 density units (DU); group 3, 0.252±0.085 DU; and group 4, 0.208±0.100 DU. Statistical analysis (Kruskal–Wallis test) showed no differences between groups.Conclusions Recent studies in ARM did not result in significant differences of MPD between the various stages of ARM. Further longitudinal studies are requested to compare the incidence of ARMD in eyes with high and low MPD in order to provide definite evidence of the influence of MPD on the progression of ARMD.Presented in part at the annual meeting of the Deutsche Ophthalmologische Gesellschaft (DOG), Berlin, 2003.     

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.     

Clinical application of the pattern electroretinogram with lid skin electrode

Pattern evoked potentials were recorded simultaneously with an electrode placed on the skin of the lower eyelid, gold foil electrodes hooked on the right and left eyelids, and a skin electrode at Oz in normal subjects and in patients with optic nerve and macular diseases. Peak latencies and amplitudes of the pattern electroretinogram (PERG) were compared between the two electrodes.In both records, the peak latency showed no difference at 56.7 ± 2.9ms (mean ± S.D.), while the amplitude of the PERG with the lid skin electrode was at 1.2 ± 0.3 V, approximately one-third of that obtained with the gold foil electrode.Although the skin electrode did not always record responses as well as the gold foil, its advantages recommend its use in clinical cases.     

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.     

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.

     

Experimental evaluation of online optical coherence pachymetry for corneal refractive surgery

Purpose Online optical coherence pachymetry (OCP) allows to monitor central changes of the corneal cross section intraoperatively. In this experimental evaluation the validity of the optical measurements for corneal refractive surgery was assessed.Methods Online OCP based on low-coherence interferometry with a wavelength of 1310 nm and a measurement frequency of 74 Hz was directly integrated in a clinical excimer laser. In 16 patients the central corneal thickness was measured with online OCP and ultrasound pachymetry (US). Furthermore, the ablation characteristics were assessed in corneoscleral discs unsuitable for transplantation (n=12) and PMMA samples (n=18).Results Online OCP was possible in all patients and materials studied. The mean central corneal thickness was 537±31 m (OCP) and 546±33 m (US). The corneal reproducibility was ±4.3 m (coefficient of variation [CV] 0.8%) with online OCP and ±3.7 m (CV 0.68%) with US. The reproducibility in PMMA samples was ±1.0 m (CV 0.16%). There was a significant correlation between online OCP and US measurements (r=0.93, P<0.001). The mean difference was 9.1 m or 1.69% (P=0.01), and the limits of agreement (95% CI) ranged from –15 m to 33 m. There was a significant linear relationship (r=0,95; P<0.001) between the calculated and the optically determined ablation depth with online OCP. Also ablation depth measurements in PMMA correlated positively with spectrophotometric values (r=0.98; P<0.001).Conclusion In this experimental evaluation, online OCP revealed to be a precise and reproducible method to assess the central corneal thickness and its changes intraoperatively. This could be important to monitor incisional and excimer laser-based corneal refractive procedures, such as PRK or LASIK.The authors have no commercial, proprietary or financial interest in any research or devices described in the presented study     

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.     

Does aqueous humor secretion decrease with age?

Aqueous humor flow was calculated during day-time in 148 healthy volunteers and 75 older patients using the Fluorotron Master II anterior chamber protocol (Coherent, Palo Alto, USA). Healthy volunteers as well as patients had no history of ocular pathology, surgery or laser treatment. Slitlamp examination revealed no ocular pathology. Hypertension, diabetes, local and systemic drug therapy, neoplasia, kidney or liver disease, contact lens and ocular trauma were excluded. Mean age of volunteers was 26.5±3.8 years; age of patients: 65.5±10.5 years. Aqueous humor flow during day-time in healthy volunteers in the OD: (mean± s.d.) 2.26±1.0l/min, in the OS: 2.17±1.0l/min. Correlation coefficient: r=0.8. The mean aqueous humor flow in the older patients during day-time: OD: 1.91±1.1 l/min, OS: 1.86±1.1 l/min. Correlation coefficient: r=0.54. The Mann-Whitney-U-test revealed a significant difference when comparing the right eyes of healthy volunteers with the right eyes of patients (p<0.01). When comparing all left eyes the difference is also significant (p=0.01). The results of the study underline, that the mean aqueous humor secretion does significantly decrease with age. However, the data show that there is only a slight decrease of flow of approximately 2.5% per decade. From the clinical point of view it should be concluded, that although the aqueous humor secretion does decrease with age, this is not of clinical importance, even in cases of glaucoma surgery. Afterall we still don't know, whether this decrease of aqueous humor flow is caused by a decrease of the pigmented and non-pigmented epithelium cells, or via a decrease of outflow facility, or via a decrease of CNS-stimulation.     

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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Pattern electroretinogram in glaucoma and ocular hypertension

We recorded the pattern electroretinogram (PERG) to small (0.8°) and very large (15°) check sizes in normal subjects, in patients with early-stage glaucoma, and in patients with ocular hypertension. In glaucoma, the PERG amplitude was reduced. This reduction was more prominent for a check size of 0.8° as compared with 15° stimuli and for high (16/s) as compared with low (7.8/s) reversal rates. Using a discriminant analysis of the amplitudes for two different check sizes, we could distinguish the normal and the glaucoma groups with a specificity of 96% and a sensitivity of 91%. Of the ocular hypertension patients, 43% were classified as pathologic by the discriminant analysis. Thus multivariate analysis of the PERG may increase its diagnostic value.     

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     

Dependence of the b-wave on the potassium concentration in the isolated superfused rabbit retina

The amplitude of the b-wave of the isolated superfused rabbit retina is drastically reduced with increasing potassium concentration (10 and 20 mM respectively) in the perfusate like in frog retina. These results are in agreement with the idea of the glial origin of the b-wave, but an influence of potassium on synaptic transmission remains a possibility. For these results the conditions for tissue survival are imperative. When the retina was superfused with a plasma saline mixture kept at 35°C, b-wave amplitudes for different preparations varied between 300 V and 900 V and loss of sensitivity was tolerated till 15% in one preparation. The temperature quotient for the amplitude of b-wave was 4–6 between 35° and 25°C, for the peak time about two.     

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.     

Count and density of human retinal photoreceptors

This investigation was directed at determining the count and regional distribution of photoreceptors in the eyes of 21 human cornea donors aged between 2 and 90 years. Mean count of rods was 60 123 000 ±12907000, and mean cone count was 3173000 ± 555000. Determined 40 m away from the foveola, cone density measured 125 500 cones/mm². Extrapolating the distribution curve, cone concentration in the foveal center can be assumed to be about 150 000 cells/mm² to 180 000 cones/mm². Towards the retinal periphery, cone density decreased from 6000 cones/mm² at a distance of 1.5 mm from the fovea to 2500 cells/mm² close to the ora serrata. Comparing different fundus regions, cone concentration was significantly highest in the nasal region. Cone diameter increased from the center towards the periphery. At a distance of 40 m away from the foveola, it measured about 3.3 m, and in the outer retinal regions about 10 m Rod density was highest in a ring-like area at a distance of about 3–5 mm from the foveola with a mean of 72 246 ± 17 295 cells/mm². Rod density peaked at 150 000 rods/mm². It decreased towards the retinal periphery to 30 000–40 000 rods/mm². Rod diameter increased from 3 m at the area with the highest rod density to 5.5 m in the periphery. The hexagonal rod and cone inner segments were regularly arranged in a honey-comb fashion.Supported by the Deutsche Forschungsgemeinschaft (Klinische Forschergruppe Glaukome Na 55/6-1/Jo) Correspondence to: J.B. Jonas     

Transition from Upbeat to Downbeat Nystagmus Observed in a Patient with Wernicke’s Encephalopathy

Background We report an unusual case of Wernickes encephalopathy presenting with transient upbeat nystagmus that changed to a persistent downbeat nystagmus.Case A 27-year-old man presented with upbeat nystagmus. Three months earlier, he had been diagnosed with Wernickes encephalopathy after fasting for a month.Observations This diagnosis was supported by his symptoms (ataxia, a confused state). Clinical recovery followed thiamine therapy. His upbeat nystagmus had linear slow phases with average amplitude and frequency (±SD) during fixation straight ahead of 2.8 ± 0.7° and 4.6 ± 2.2Hz, respectively. Two months later, the primary position upbeat nystagmus had diminished and downbeat nystagmus (0.9 ± 0.5° and 3.2 ± 0.7Hz on average) for a 20° downward gaze had developed. Then, 8 months later, he showed only downbeat nystagmus, which obeyed Alexanders law. His primary position downbeat nystagmus was completely suppressed by clonazepam, a -aminobutyric acid (GABA) agonist.Conclusions Owing to an underlying central vestibular imbalance, even after the recovery of acute neurological symptoms, Wernickes encephalopathy can be complicated by persistent downbeat nystagmus, which can be treated by a GABA agonist. Jpn J Ophthalmol 2005;49:220–222 © Japanese Ophthalmological Society 2005