[Juvenile glaucoma in propionic acidemia]. / Juveniles Glaukom bei Propionazidämie.

Propionic acidemia (PA) is a rare autosomal recessive disorder resulting from deficiency of the biotin-dependent enzyme propionyl-CoA carboxylase, which is necessary for the catabolism of branched chain amino acids and odd-chain fatty acids. Although optic atrophy was documented in four cases, no glaucomatous optic atrophy has yet been described. This article describes the first case of a 12-year-old boy with PA showing bilateral glaucomatous optic disc atrophy due to dysgenetic changes of the angle of the anterior chamber.

[Subconjunctival or general anaesthesia in trabeculectomy--a retrospective analysis of the bleeding risk from a glaucoma surgeon's point of view]. / Subkonjunktivalanästhesie oder Vollnarkose bei der Trabekulektomie--retrospektive Analyse des perioperativen Blutungsrisikos aus Sicht des Glaukomchirurgen.

INTRODUCTION: The aim of this study was to compare the intraoperative and early postoperative outcome of trabeculectomy with mitomycin C in glaucoma patients undergoing general anaesthesia compared to those undergoing subconjunctival anaesthesia. METHODS: The perioperative results of consecutive glaucoma patients receiving a trabeculectomy with mitomycin C either under general anaesthesia (group 1, n = 60) or in subconjunctival anaesthesia (group 2, n = 60) were analysed in a retrospective study. All surgical procedures were performed by one surgeon and only one eye of each patient with no history of previous conjunctival surgery was included in the study. RESULTS: No significant peri- and postoperative differences concerning period of hospitalisation, intraocular pressure, filtration-bleb bleedings, hyphaema, frequency of laser suture lysis, hypotony, chorioidal detachment or revision surgery could be shown between the two groups. Considering all patients together, there was a significant correlation between the occurrence of postoperative filtering bleb bleedings and the absolute number of topical antiglaucomatous substances used prior to surgery. CONCLUSIONS: The perioperative risk profile of penetrating glaucoma surgery with subconjunctival anaesthesia seems to be similar to that of procedures under general anaesthesia. For prevention of postoperative filtering bleb bleedings, the administration of topical antiglaucomatous drugs should be stopped before surgery.

[Combined phacoemulsification with trabecular aspiration with differing outcomes in pseudoexfoliative glaucoma - a retrospective study]. / Kombinierte Phakoemulsifikation mit Trabekelaspiration bei Pseudoexfoliations-Glaukom mit unterschiedlichem Ausgangsdruck - eine retrospektive Studie.

INTRODUCTION: The aim of this study was to differentiate the pressure-reducing results following trabecular aspiration combined with small incision cataract surgery in eyes with pseudoexfoliation depending on preoperative pressure and medication score. PATIENTS AND METHODS: A retrospective analysis was made of 104 exfoliative eyes of 104 patients who underwent combined phaco/trabecular aspiration. Success was defined as a relative reduction of IOP of at least 20 %, absolute IOP of ≤ 20 mmHg, stable or reduced medication score and a lack of any further pressure-reducing surgery. RESULTS: The success rate was 0.68 and 0.64 after 1 and 2 years. In eyes with medically uncontrolled preoperative IOP (> 20 mmHg) the IOP dropped significantly from 25.4 ± 4.3 mmHg to 17.0 ± 3.4 mmHg after two years. In eyes with preoperative controlled IOP the pressure lowering effect was low (17.1 ± 2.3 to 15.9 ± 2.3 mmHg) with a significant reduction of medication. CONCLUSIONS: Combined cataract surgery and trabecular aspiration is a reasonable option in exfoliative eyes with IOP values in the low twenties in order to achieve a reduction of topical medications and to reach a stable IOP level.

Accuracy and reproducibility of axial length measurement in eyes with silicone oil endotamponade.

AIM: To assess the accuracy and signal quality of axial length measurements by partial coherence laser interferometry (PCI) for optical biometry in eyes with conventional silicone oil (SO) or heavy silicone oil (HSO) as endotamponade. METHODS: We included 26 eyes with SO endotamponade (SO, n = 15; HSO, n = 11) using a Zeiss IOLMaster for measurement of axial length the day before and at least 6 weeks after SO removal. We analysed the intra-individual deviation between both measurements and signal-to-noise ratio (SNR) as a marker for signal quality. We included 16 contralateral eyes without history of vitreoretinal surgery to act as the control group. RESULTS: The mean axial length was 24.76 (SD 2.07) mm (SO 24.63 (SD 2.12) mm, HSO 24.93 (SD 2.10) mm, control 24.95 (SD 2.61) mm) before and 24.75 (SD 1.96) mm after oil removal with a mean intra-individual deviation of 0.13 (SD 0.11) mm (SO 0.13 (SD 0.12) mm, HSO 0.13 (SD 0.09) mm, control 0.02 (SD 0.01) mm) while SNR at baseline was 5.7 (SD 3.5) (SO 6.6 (SD 4.0), HSO 4.4 (SD 2.2), control 8.6 (SD 3.9)). CONCLUSION: In our analysis, optical biometry using PCI generated results with acceptable accuracy and signal quality for measurement of axial length in SO-filled eyes.

[Bilateral anterior panuveitis as early manifestation of syphilis in a patient with HIV infection]. / Beidseitige Panuveitis als okuläre Frühmanifestation einer Lues bei einem Patienten mit HIV-1-Infektion.

INTRODUCTION: Syphilis is a dangerous sexually transmitted infection which can be effectively treated with penicillin to avoid late-onset diseases. Even if syphilis is diagnosed an HIV infection should be excluded. PATIENT: A 32-year-old homosexual man complained about a decreased bilateral visual acuity after a feverish infection with lymphadenitis colli. With slit-lamp biomicroscopy a bilateral panuveitis with papillary edema, endothelial cells and episcleritis was found. After antimycotic and antiviral therapy, his visual acuity decreased and symptoms progressed. In the lab routine we found lues and HIV infections and started an intravenous penicillin therapy immediately. A few days later the symptoms improved and visual acuity increased. CONCLUSION: Lues serology should be incorporated into routine lab diagnostics to aid the detection and to start the right therapy as soon as possible.

[Early postoperative spikes of the intraocular pressure (IOP) following phacoemulsification in late-stage glaucoma]. / Frühe postoperative Augeninnendruckspitzen nach Phakoemulsifikation bei terminalen Glaukomen.

BACKGROUND: Modern cataract surgery with use of viscoelastics can induce remarkable early spikes of the intraocular pressure (IOP) in patients with glaucoma. PATIENTS AND METHODS: The purpose of this prospective study was to investigate risk factors for an early increase of the IOP following cataract surgery in eyes with end-stage glaucoma. Clear cornea phacoemulsification with implantation of a foldable acrylic lens was performed in 25 eyes with end-stage glaucoma (primary open-angle glaucoma including normal tension glaucoma or exfoliative glaucoma) either under topical anesthesia or under general anesthesia. In eyes with exfoliative glaucoma, trabecular aspiration was performed additionally. IOP measurements were conducted at the day before surgery, 4 hours following surgery and on the first morning following surgery. RESULTS: Cataract surgery was performed without complications. The mean IOP was 18.5 +/- 4.2 mm Hg with 2.1 +/- 1.0 topical medications. 4 hours postoperatively, mean IOP was 31.3 +/- 11.9 mm Hg. In eyes with exfoliative glaucoma (n = 12) the early postoperative IOP was 28.5 +/- 12.0 mm Hg, but without significant difference compared to eyes with POAG (n = 13). The early postoperative IOP showed significant correlation with the maximum IOP in patient's history (p = 0.014). CONCLUSIONS: Patients with late-stage glaucoma can experience considerable early IOP spikes following uneventful cataract surgery, although preoperatively IOP is controlled by topical medications. Postoperative IOP monitoring is recommended at the day of surgery, especially if high IOP values are reported in patient's history.

[New aspects of corneal pachymetry in congenital glaucoma and pediatric aphakic glaucoma]. / Neue Aspekte der Hornhautpachymetrie beim kongenitalen Glaukom und kindlichen Aphakieglaukom.

BACKGROUND: Knowledge of individual corneal thickness in individual eyes is proving to be more and more crucial for correcting Goldmann applanation tonometry, as well as to assess its predictive value regarding the possible progression of glaucomatous damage. It has become an important factor in determining appropriate glaucoma therapy. Only few pachymetric data exist about eyes with congenital or secondary pediatric aphakic glaucoma. METHODS: 12 eyes with congenital glaucoma (6 patients, mean age 3.3 years, mean 3.9 previous operations) and 7 eyes with secondary pediatric aphakic glaucoma (4 patients, mean age 14.8 years, mean 3 previous operations) without clinical signs of corneal decompensation were investigated by ultrasound pachymetry. RESULTS: Eyes with glaucoma due to aphakia had a mean corneal thickness of 708 +/- 77.3 microm. Mean corneal thickness of the eyes with congenital glaucoma was 688.1 +/- 115.9 microm, which is far above the values known from the literature. Two eyes, which had a central corneal thickness of 646 microm and 640 microm, presented with a localised paracentral corneal thickness of only 402 microm and 405 microm, respectively, correlating with microscopic descemet scars. CONCLUSIONS: Congenital glaucoma and the pediatric aphakic glaucoma present with very heterogeneous clinical pictures. Especially for congenital glaucoma, this is confirmed by the high interindividual, but also intraindividual, variability of corneal pachymetry.

[Three conventional eye drops versus a single lyophilisate. A comparative bioavailability study]. / Comparaison de deux formes d'application de médicaments: collyre versus lyophilisat.

PURPOSE: The ocular bioavailability of a single application of a triple dose of sodium fluorescein to the human anterior segment of the eye was studied as a novel drug delivery device. METHODS: The lyophilisate contained a fluorescein dose of 204 microg corresponding to three conventional, preservative-free eye drops of 40 microl Fluorescein SE Thilo 0.17% (68microg each) (Alcon). A single lyophilisate was applied to one eye of 22 healthy volunteers (+1 min) and three conventional eye drops (+1, 16, 31 min) were applied to their fellow eye. In this randomized, open label study, fluorophotometry was performed (Fluorotron Master IItrade mark, Ocumetrics, Mountain View, California, USA) before and +15, 30, 45, 60, 120, 180, 240, 300, 360, 420 min after application. The fluorescein concentrations of the corneal stroma (C), mid-anterior chamber (AC) were analyzed by paired t-test. RESULTS: Cornea and AC mean values (ng/ml) were significantly higher (p < 0.018, paired t-test) in the lyophilisate group up to 7 h after application, with the exception of +45 min. The mean fluorescein bioavailability from the lyophilisate was up to 11 times higher in the C and up to 8.7 times higher in the AC compared with the three preservative-free eye drops. DISCUSSION: For the first time a triple dose was delivered to the human eye with a single lyophilisate application. Significantly better bioavailability was achieved in the C and AC for up to 7 h using this new device. The treatment of glaucoma, bacterial, viral, and fungal infections, as well as dry eye syndrome, for example, will be improved using lyophilisate.

[The effect of brimonidine on the pupillary reflex. A pupillographic study in healthy volunteers]. / Beeinflussung der Pupillenreaktion durch Brimonidin. Eine pupillographische Studie an Normalpersonen.

PURPOSE: The effect of brimonidine in comparison with acetazolamide on pupillary reflex was investigated in 18 volunteers. METHODS: Infrared pupillography was performed with white diode light of 200 ms duration to measure pupil diameter, constriction latency, reaction time, constriction amplitude, and relative constriction amplitude. The measurements were performed according to a fixed schedule including a phase without medication to determine the baseline level. Data were analyzed by Student's paired t-test. RESULTS: Application of brimonidine and acetazolamide led to a significantly reduced intraocular pressure as well as static and dynamic differences in the pupillary reflex. The pupil diameter measurements were significantly smaller after both medications in comparison to baseline. The reduction of pupil diameter after brimonidine led to significantly reduced contraction amplitude and prolonged latency. CONCLUSION: Application of brimonidine leads to significant miosis, which might due to the affinity to alpha(2)-receptors with reduction of noradrenaline release in the synapse. This effect may play a role in a higher decrease of intraocular pressure by increasing aqueous humor outflow in comparison to clonidine and apraclonidine, but further investigations are required.

[Patient characteristics in a tertiary glaucoma center. Circumstances of treatment and attitudes of patients]. / Profil einer universitären Glaukomsprechstunde. Objektive Behandlungsumstände und subjektive Einstellungen der Patienten.

BACKGROUND: In order to look for conceptual improvements in the practical management of patients sent to our glaucoma department, we analyzed the structures, behaviour, and knowledge about the disease in this patient group. METHODS: Glaucoma patients who were sent for the first time to our department were included prospectively. Before being examined 129 patients were asked to answer a questionnaire concerning their individual characteristics, their behaviour, and patterns of treatment. RESULTS: Of the patients 74% had open-angle glaucoma (including normal tension, exfoliative, and pigment glaucoma), 22% had secondary glaucoma (including neovascular, congenital, and chronic closed-angle glaucoma), and 4% had suspected glaucoma. Written documentation of previously performed intraocular pressure measurements was not available for 84% of the patients. Younger patients had significantly more knowledge about glaucoma and used more possibilities to get information about the disease than elder patients. CONCLUSION: Education about glaucoma disease should be optimized especially for elder glaucoma patients. Documentation of intraocular pressure measurements is insufficient in our patient group.

A comparative bioavailability study of three conventional eye drops versus a single lyophilisate.

AIM: To study the ocular bioavailability of a triple dose, single application of sodium fluorescein to the human anterior segment from a novel drug delivery device. METHODS: In a randomised, open label study 22 healthy volunteers applied a single lyophilisate to one eye (+1 minute) and three conventional eye drops (+1, 16, 31 minutes) of fluorescein ophthalmic solution to the fellow eye. The fluorescein dose of the lyophilisate was 204 mg corresponding to three conventional, preservative-free eye drops of 40 ml fluorescein SE Thilo 0.17% (68 micro g each) (Alcon). Fluorophotometry was performed (Fluorotron Master II Ocumetrics, USA) before and +15, 30, 45, 60, 120, 180, 240, 300, 360, 420 minutes after application. The fluorescein concentrations of the corneal stroma and mid-anterior chamber were analysed by paired t test. RESULTS: Cornea and anterior chamber mean values (ng/ml) were significantly higher (p<0.018, paired t test) in the lyophilisate group up to 7 hours after application with the exception of +45 minutes. The mean fluorescein bioavailability from the lyophilisate was up to 11 times higher in the cornea and up to 8.7 times higher in the anterior chamber compared with the three preservative-free eye drops. CONCLUSION: A triple dose was delivered to the human eye with a single lyophilisate application for the first time. A significantly better bioavailability was achieved in the cornea and anterior chamber for up to 7 hours by means of drug application with lyophilisates. The application of medications by means of the lyophilisate will improve the treatment of, for example, glaucoma, bacterial, viral and fungal infections, as well as dry eye syndrome.

Lyophilisates for drug delivery in ophthalmology: pharmacokinetics of fluorescein in the human anterior segment.

AIMS: To assess the ocular bioavailability of fluorescein from a novel water free, freeze dried ophthalmic drug delivery system compared to conventional preservative-free fluorescein eye drops. METHODS: Sodium fluorescein 0.17% was dissolved in an aqueous solution of hydroxypropylmethyl cellulose 1.0% (HPMC), deposited on sterilised flexible hydrophobic poly(tetrafluoroethylene) (PTFE) carrier strips and freeze dried under aseptic conditions. The fluorescein dose of the lyophilisate was 68 micro g, corresponding to a single conventional drop of 40 micro l fluorescein 0.17% solution. In a randomised, open label study 12 healthy volunteers applied the lyophilised fluorescein to one eye and one drop of conventional fluorescein ophthalmic solution to the fellow eye. Fluorophotometry measurements of fluorescein concentrations in the anterior segment were performed with the Fluorotron Master II (Ocumetrics, USA) before and +15, 30, 45, 60, 120, and 180 minutes after application. RESULTS: At all times anterior chamber fluorescein concentration was greater in the lyophysilate treated eye than the solution treated eye. The magnitude of this difference ranged from 2-5.3 times and was statistically significant. CONCLUSION: The greater intraocular bioavailability of fluorescein from the lyophilisate relative to the solution suggests that it may be a useful method for delivering substances to the eye.

Development of a completely encapsulated intraocular pressure sensor.

A completely encapsulated intraocular pressure (IOP) sensor equipped with telemetric signal and energy transfer is introduced integrated into a silicone disc for implantation into the eye. After implantation into enucleated pig eyes and into rabbit eyes in vivo, the IOP was recorded and compared to established techniques of IOP measurement. Pressure chamber tests showed that the sensor functioned correctly after biocompatible encapsulation in polydimethylsiloxane. In vivo and in vitro tests in rabbit and pig eyes demonstrated that the implanted system worked with the same precision as established techniques for IOP determination. The correlation between the measurements with the implanted device and pneumotonometry in several experiments was between 0.9 and 0.99. This device serves as a functioning model for the realization of a telemetric IOP sensor for integration into an artificial intraocular lens. Such a device will open new perspectives, not only in the management of glaucoma, but also in basic research for mechanisms of glaucoma.

[The effect of latanoprost 0.005% on pupillary reaction of the human eye]. / Der Einfluss von Latanoprost 0,005% auf die Pupillenreaktion des menschlichen Auges.

PURPOSE: Infrared pupillography was performed to investigate the effect of one week topical treatment with the prostaglandin analogue Latanoprost 0.005% on pupillary reflex to light stimuli in glaucomatous human eyes. METHODS: Infrared pupillography using the compact integrated pupillograph was performed in 20 glaucomatous eyes of 11 patients. After 10 minutes dark adaptation one pupil was stimulated with a blue, yellow and white diode light of 100 ms duration. Measurements of pupil diameter, constriction latency, constriction amplitude and relative constriction amplitude were taken twice for each light source in a time interval of 15 seconds. After a 2 week wash-out period the measurements were performed from 8:00 to 10:00 a.m. before and one week after topical treatment with Latanoprost 0.005% applied as single dose once in the evening. RESULTS: The measurements after 1 week treatment with Latanoprost showed a significantly smaller pupil diameter for blue (p = 0.044) and white stimulus (p = 0.039) and the latency was significantly reduced (p = 0.029) as well. CONCLUSIONS: Although the statistical analysis shows some small significant differences in pupil diameter and constriction latency there were no clinical signs of changes in pupillary response due to Latanoprost. The system turned out as easy to use and showed reliable measurements during the study. How far latanoprost may lead to miosis and a decrease of constriction latency has to be investigated in further studies with larger study populations. Other topics concerning drug influence, diurnal rhythm and glaucomatous damage in pupillary light reaction will be investigated in the near future.

Intraocular pressure in rabbits by telemetry II: effects of animal handling and drugs.

PURPOSE: To measure under carefully controlled conditions the effects in the rabbit eye of commonly used therapeutic agents for glaucoma. METHODS: Rabbits were outfitted in one eye with an implantable telemetric pressure transducer and monitored for several months under controlled conditions of light/ dark and handling. Effects of tonometry, handling, water drinking, and instillation of topical ophthalmic medications on intraocular pressure were recorded during each 24-hour day/night cycle. RESULTS: Pneumatonometry, animal handling, and water drinking all had an effect on intraocular pressure that in many instances was of the same magnitude as the effects of pharmacologic agents. Dorzolamide and timolol caused a sustained reduction of intraocular pressure during the nocturnal period. Epinephrine had a biphasic effect, causing an immediate pressure elevation followed by a prolonged depression. Apraclonidine, latanoprost, and pilocarpine had no measurable effect. CONCLUSIONS: Continuous telemetric measurement of intraocular pressure in rabbits permits the measurement of uncontrollable artifacts that occur with tonometric measurements and animal handling. If environmental conditions are rigidly controlled, this method is very sensitive for detecting therapeutic effects of candidates for ocular hypotensive drugs. When healthy animals are used, the method appears to be more sensitive for drugs that affect aqueous humor formation than for drugs that affect aqueous humor outflow resistance.

Measuring oxygen tension in the anterior chamber of rabbits.

PURPOSE: Measuring the concentration of oxygen in the aqueous humor without penetrating the eye would provide a new dimension in understanding aqueous humor and corneal dynamics. In this study a preinvasive method was developed for determining the cameral oxygen concentration in anesthetized rabbits by measuring the excited-state lifetime of a phosphorescent dye. METHODS: A scanning ocular fluorometer was designed to excite phosphorescence with a brief flash of light and to measure the decay of luminescence for as long as 1000 microsec after excitation. The measurement window was scanned through the depth of the anterior chamber or fixed at the mid-anterior chamber. A depot of the phosphorescent dye Pd-uroporphyrin was injected into the vitreous of eight pigmented rabbits, and within a few days the dye was measurable in the anterior chamber. The excited-state lifetime of this dye is inversely correlated to oxygen concentration and was calibrated by measuring the lifetime of dye in cuvettes equilibrated with oxygen-nitrogen mixtures. Oxygen tensions were determined from lifetimes measured in the open eye, under a polymethylmethacrylate (PMMA) contact lens, under two oxygen-permeable contact lenses, and immediately after lid closure. RESULTS: Oxygen tension in the mid-anterior chamber before placing a PMMA contact lens was 23 +/- 3 mm Hg (mean +/- SD; n = 6). After 20 minutes of PMMA lens wear, oxygen tension decreased to 4 +/- 2 mm Hg. When the focal diamond was scanned through the anterior chamber, oxygen tension was 24 +/- 5 mm Hg near the corneal endothelium and decreased to 17 +/- 8 mm Hg near the crystalline lens. Under the PMMA contact lens this gradient reversed: Oxygen tensions near the endothelium and lens were 3 +/- 2 mm Hg and 6 +/- 2 mm Hg, respectively. Lid closure for 10 minutes or longer decreased the mid-anterior chamber oxygen tension from 21 +/- 2 mm Hg (n = 19 measurements from seven animals) to 10 +/- 3 mm Hg (n = 15 measurements from five animals). CONCLUSIONS: Measuring excited-state lifetime of phosphorescent dyes in the anterior chamber provides a useful method for determining oxygen concentration in vivo, without penetrating the eye. Cameral oxygen tension under PMMA contact lenses are significantly lower than in the uncovered eye. The profile of oxygen tension through the anterior chamber suggests that oxygen is supplied transcorneally to the aqueous humor.

Effect of 3.0 mm tunnel and 6.0 mm corneoscleral incisions on the blood-aqueous barrier.

PURPOSE: To study of the effect of silicone intraocular lens (IOL) implantation using a 3.0 mm tunnel incision with that of implantation though a 6.0 mm corneoscleral incision after phacoemulsification in human eyes. SETTING: Department of Ophthalmology, University of Köln, Germany. METHODS: In a prospective, randomized clinical study, 50 patients with senile cataract had phacoemulsification and IOL implantation through a 3.0 mm tunnel or a 6.0 mm corneoscleral incision. To assess blood-aqueous barrier (BAB) disruption, preoperative and postoperative sodium fluorescein concentrations in the anterior chamber were measured with the Fluorotron Master II. Diclofenac sodium 0.1% was applied to the operative eyes five times a day for 5 days. The contralateral eyes served as controls. RESULTS: There was no significant between-group difference in sodium fluorescein concentrations in the 5 days after surgery. CONCLUSION: The findings underline our clinical impression that BAB disruption 5 days after surgery does not differ significantly with the type and length of scleral incision used for IOL implantation.

A new transdermal delivery system for pilocarpine in glaucoma treatment.

We studied the intraocular pressure (IOP)-lowering effect and the side effects of a new transdermal delivery system (TDS) containing pilocarpine. After giving their written informed consent, patients were randomly assigned to receive a pilocarpine TDS or a placebo TDS. Two patches, each containing 30 mg of pilocarpine or placebo, were applied to the supraclavicular skin of 24 patients. The IOP was recorded before and at +12, 16, and 20 h after application. Plasma samples were analyzed for pilocarpine before treatment and 12 and 20 h later via high-performance liquid chromatography. The amount of drug remaining on the dermal patches was analyzed at 20 h. The mean IOP recorded before application was 22.7 +/- 5.8 mmHg. As compared with the placebo TDS, the pilocarpine TDS did not significantly reduce IOP at 12, 16, or 20 h after application (P = 0.42). The mean plasma concentrations were 2.9 ng/ml at 12 h and 1.3 ng/ml at 20 h. The verum TDS showed a residual mean drug concentration of 35.3 mg pilocarpine on the TDS. A substantial amount of pilocarpine was released from the TDS to the dermis, causing detectable plasma levels of pilocarpine at 12 and 20 h after administration. The pilocarpine TDS is a new nonocular pharmaceutical device that should avoid the side effects well known in glaucoma treatment when conventional eye drops are used.