The XEN45 Gel Stent as a minimally invasive procedure in glaucoma surgery: success rates, risk profile, and rates of re-surgery after 261 surgeries.

PURPOSE: The XEN45 Gel Stent is a flexible hydrophilic tube placed under the conjunctiva via the anterior chamber. This study investigates the IOP (intraocular pressure)-lowering potential, the risk profile, and the success rate of the XEN45 Gel Stent. METHODS: Two hundred and sixty-one eyes underwent surgery. The mean follow-up time was 8.5 months. The aim of the treatment was to achieve adequate IOP reduction without medication. Therefore, all patients who did not show sufficiently reduced IOP underwent a surgical revision with opening of the conjunctiva. To determinate the success rate, we carried out two kinds of analysis: 1) the primary success rate: eyes with appropiate IOP control without medication or surgical revision, and 2) overall success rate: one surgical revision was allowed. RESULTS: Intraocular pressure was lowered from 24.3 mmHg (SD 6.6) to 16.8 mmHg (SD 7.6), and the medication score was lowered from 2.6 (SD 1.1) to 0.2 (SD 0.7). Revisional surgery was performed in 80 eyes (34%). After a first revision, intraocular pressure was lowered to 14.0 mmHg (SD 5.1), and the medication score was lowered to 0.2 (SD 0.6). The primary success rate was 66% and the overall success rate 90%. The primary success rate was higher in pseudophakic eyes (73%) than in phakic eyes (53%) or combined surgery (55%). CONCLUSIONS: We conclude from our data that the XEN45 Gel Stent has an IOP-lowering potential and few side-effects. Pseudophakic eyes seem to have a better primary prognosis compared to combined surgery or surgery in phakic eyes.

Partial Coherence Laser Interferometry in Highly Myopic versus Emmetropic Eyes.

PURPOSE: To investigate the reliability of partial coherence laser interferometry for optical biometry in highly myopic eyes. METHODS: Axial length measurements by the IOLMaster (Carl Zeiss Meditec, Germany) with signal-to-noise ratio (SNR) ≥2 were performed in 52 consecutive myopic subjects with axial length ≥26.5 mm and 45 emmetropic patients before cataract surgery. Axial length measurements and SNR were analyzed and compared among the two study groups. RESULTS: Axial length measurements were feasible in 46 of 52 (88.5%) highly myopic eyes and in 41 of 45 (91.1%) eyes with normal axial length. To achieve two reliable axial length values with SNR ≥2, a mean number of 2.06±0.25 measurements was necessary in myopic eyes and 2.10±0.37 in emmetropic counterparts. Mean SNR after two measurements was 4.98±2.44 in myopic eyes versus 5.56±2.32 in control eyes. Even though successful measurement was independent of preoperative visual acuity, patients with visual acuity better than 20/63 showed significantly higher SNR values. CONCLUSIONS: Partial coherence laser interferometry shows satisfying feasibility and good signal quality for axial length determination in highly myopic eyes with stable retinal condition and clear media.

A new surgical triple procedure in pseudoexfoliation glaucoma using cataract surgery, Trabectome, and trabecular aspiration.

BACKGROUND: To evaluate the potential of lowering intraocular pressure in pseudoexfoliation glaucoma with combined phacoemulsification, Trabectome, and trabecular aspiration (triple procedure) compared to phacoemulsification and trabecular aspiration alone. METHODS: Using a case-matched retrospective study design, 30 patients were included into each group. The main outcome measures were the reduction of intraocular pressure and medication score at the end of follow-up. Clinical data were collected from the patients' medical records. RESULTS: Mean follow-up was 15 months in both groups. Intraocular pressure decreased from 25.3 ± 6.3 mmHg to 14.4 ± 3.7 mmHg (p < 0.0001) in the triple procedure group and from 25.3 ± 4.2 mmHg to 18.1 ± 4.2 mmHg (p < 0.0001) in the control group. The medication score was lowered from 3.4 ± 1.7 to 2.1 ± 1.2 (p = 0.0017) in the triple procedure group and from 3.8 ± 1.8 to 2.3 ± 1.5 (p < 0.008) in the control group. The reduction of intraocular pressure was higher (p < 0.004) in the triple procedure group (38.4 ± 17.3 %) compared to the control group (26.8 ± 19.6 %) The reduction of the medication score did not differ significantly. CONCLUSIONS: The triple procedure is more effective in lowering intraocular pressure compared to phacoemulsification and trabecular aspiration alone in pseudoexfoliation glaucoma.

Accuracy of intraocular lens power calculation using partial coherence interferometry in patients with high myopia.

PURPOSE: Ultrasound-A-scan-biometry intraocular lens power calculation for cataract surgery sometimes shows lack of accuracy in patients with high myopia. The purpose of this retrospective study was to assess the accuracy of lens power calculation with optical biometry using the Zeiss IOLMaster across a large range of myopia levels. METHODS: We included 37 consecutive, myopic eyes with an axial length >26.5mm (31 patients, 62±13years old, average preoperative refraction of -14.46±6.61D, range -3.5 to -32.0D which underwent phacoemulsification and implantation of an intraocular lens following biometry using the IOLMaster. For lens power calculation, the Haigis formula was used in all cases. For comparison, refraction was back-calculated using the SRK/T and Holladay I formulae. RESULTS: The preoperative mean axial length was 29.37±2.44 mm with a range of 26.50-35.52mm. Thirty eyes (81.1%) showed a postoperative spherical equivalent which differed 1.00D or less from the predicted value, in 20 cases (54.1%) the postoperative refractive error was within±0.50D. The mean absolute error (MAE) was 0.70±0.59D (Holladay I, 0.85±0.68; SRK/T, 1.01±0.61D). CONCLUSIONS: Optical biometry for intraocular lens power calculation seems to deliver reliable results for cataract surgery in patients with high myopia, although our data describe an increasing lack of accuracy beyond an axial length of 30mm. The Haigis formula provided the best predictability of postoperative refractive outcome for myopic eyes in general.

Biodegradable implant for tissue repair after glaucoma drainage device surgery.

AIM/BACKGROUND: To report a novel technique using biodegradable material to cover exposed glaucoma tube shunts. METHODS: A case report of a single patient who underwent drainage tube shunt surgery with the Baerveldt drainage device for intractable glaucoma. Four months post operation the tube became exposed through necrosis of the overlying scleral flap and conjunctiva. The defect was repaired by fixation of the tube to the sclera, with a slice of an ologen implant as a patch, covered by the adjacent conjunctiva. The patient was followed over a period of 1 year after the surgery. RESULTS: Successful, lasting closure of the conjunctival defect was achieved without any side effects or complications. CONCLUSIONS: Erosion of the drainage tube after shunt surgery is a potentially serious problem. It can be successfully managed using a biodegradable implant as a patch before closing the conjunctiva.

Effect of a capsular tension ring on refractive outcomes in eyes with high myopia.

PURPOSE: To evaluate the effect of capsular tension ring (CTR) implantation on refractive outcomes in patients with high myopia. SETTING: University of Cologne, Department of Ophthalmology, Cologne, Germany. DESIGN: Comparative case series. METHODS: The refractive outcomes in myopic eyes were compared between phacoemulsification and IOL implantation with a CTR (CTR group) and without a CTR (control group). Optical biometry (IOLMaster) was obtained. The power of the IOL was used to calculate the predicted postoperative spherical equivalent using the Haigis and SRK/T formulas. The main outcome measures were the mean error and mean absolute error of the refractive prediction error. RESULTS: The mean axial length was 29.1 mm (range 26.5 to 34.1 mm) in the CTR group and 28.2 mm (range 25.6 to 31.1 mm) in the control group. There was no statistically significant difference in the mean absolute refractive prediction error between the CTR group and the control group with the Haigis formula (P = .921) or SRK/T formula (P = .693). However, there was lower variance in the absolute refractive prediction error in the CTR group with both formulas (P = .014 and P = .027, respectively). Intragroup differences between formulas were not statistically significant (CTR, P = .069; control P = .551). CONCLUSIONS: Implantation of a CTR had no consistent effect on refractive outcomes compared with routine phacoemulsification in highly myopic eyes. There was a tendency toward higher precision in outcomes with a CTR. Results indicate IOL power calculation does not have to be changed when a CTR is used.

Intra-individual comparison after combined phaco-trabecular aspiration in pairs of pseudoexfoliative eyes.

BACKGROUND: Trabecular aspiration is used for combined glaucoma-cataract surgery in coexisting pseudoexfoliation syndrome (XFS) or glaucoma (XFG). Reports on this technique are limited to a few small-scale studies. In this study, we wanted to elucidate whether the result of combined phacoemulsification with trabecular aspiration in the first operated eye is predictive for outcome in the contralateral eye. METHODS: In a retrospective analysis we compared the results from 80 eyes of 40 patients with pseudoexfoliation syndrome or glaucoma, who had undergone bilateral but consecutive phacoemulsification with implantation of a posterior chamber lens combined with trabecular aspiration between 2003 and 2005. RESULTS: The IOP level and medication score after phaco-trabecular aspiration were shown to be significantly lower than the preoperative values after 2 years (p < 0.0001 and p = 0.047). A significant correlation between the first and second eye was detected for reduction of IOP and medication score after 1 year. Kaplan-Meier graphs of the first and second eyes showed an almost parallel trend from 1 day after surgery until 35 months after surgery. CONCLUSIONS: The postoperative outcome in an eye after combined phaco-trabecular aspiration is predictive for the second eye. If this procedure succeeded in the first eye, the prognosis for the same strategy in the fellow eye is also good.

Self-application of single-use eyedrop containers in an elderly population: comparisons with standard eyedrop bottle and with younger patients.

PURPOSE: To test whether patients aged >or=80 years can safely and successfully apply eyedrops from a single-use eyedrop container without support, and to compare the results with those of younger patients using single-use containers and older patients using standard eyedrop bottles. METHODS: Patients aged >or=80 years who had no physical or mental conditions hindering self-application of eyedrops and actually did so because of glaucoma or dry eyes were included consecutively in the study group (n = 44) in order to perform self-application of eyedrops from single-use eyedrop containers. Patients were observed meticulously by two investigators, who documented practical problems during the procedure in a checklist. In control group A (n = 22), glaucoma or sicca patients aged between 50 and 65 years applied drops from single-use eyedrop containers; in control group B (n = 28), glaucoma or sicca patients aged >or=80 years used a traditional eyedrop bottle. RESULTS: Successful application of the drops into the conjunctival sac was achieved by 57% in the study group (95% and 89% in control groups A and B, respectively). Scratching of the eyedrop container along the conjunctiva or cornea was observed in 68% of the study group (41% and 61% in control groups A and B, respectively). Frequency of problems during opening and self-application of single-use eyedrop containers in the study group showed an inverse correlation to visual acuity in the better eye and previous experience with this kind of eyedrop container. CONCLUSION: Older patients have massive problems in self-administering eyedrops from single-use containers. Factors influencing the success of self-application may include the patient's previous experience with this kind of eyedrop container and the patient's visual acuity.

Modelling ocular pharmacokinetics of fluorescein administered as lyophilisate or conventional eye drops.

OBJECTIVE: The objective of this evaluation was to model ocular pharmacokinetics of fluorescein administered as conventional eye drops and as lyophilisate to healthy volunteers in order to assess the relative bioavailability of the lyophilisate formulation. METHODS: A total of 44 healthy subjects received equivalent doses of fluorescein as lyophilisate to one eye and as eye drops to the fellow eye in three individual studies. Fluorescein concentrations in the cornea and anterior chamber were measured by fluorophotometry. Data were analyzed by noncompartmental methods (WinNonlin software) and by compartmental population pharmacokinetic methods (NONMEM software). RESULTS: Compared to eye drops, both maximum fluorescein concentrations (C(max)) and the areas under the concentration-time curve (AUC(0-t )) values of fluorescein in the cornea and anterior chamber for lyophilisate were increased in the noncompartmental analysis: mean lyophilisate C(max) in the studies was 6.3- to 14.6-fold higher and mean AUC(0-t ) was 4.7- to 8.9-fold higher for ocular concentrations in the three studies. A three-compartment open model with first-order elimination from the anterior chamber adequately described population data. Estimated fluorescein systemic bioavailability (F) via the ocular route from lyophilisate relative to eye drops was 3.7-fold higher (95% CI 2.6-4.8). CONCLUSION: The data clearly show a considerably superior intraocular bioavailability of fluorescein when given as lyophilisate compared to conventional eye drops. There is a clear pharmacokinetic advantage of the lyophilisate preparation.

Cyclodialysis ab interno as a surgical approach to intractable glaucoma.

PURPOSE: In glaucoma filtration surgery, the problem of subconjunctival scarring has still not been satisfactorily solved. Suprachoroidal drainage of aqueous humour offers a promising, alternative option for intractable glaucoma. We here present a clinical study on the surgical approach of gonioscopic cyclodialysis ab interno. PATIENTS AND METHODS: Twenty-eight eyes of 20 patients with intractable glaucoma were included in this prospective, consecutive, case-control study. The eyes had had a mean of 4.4 +/- 2.4 previous antiglaucomatous interventions. Baseline intraocular pressure (IOP) was 34.3 +/- 10.5 mmHg despite maximum therapy. Under gonioscopic control, cyclodialysis ab interno was performed over two clock times to gain access to the suprachoroidal space. No additional trabecular meshwork surgery was performed. Success was defined as a lowering of IOP to below 21 mmHg without the need for further medication or intervention. RESULTS: Mean postoperative IOP was 14.6 +/- 12.4 mmHg. Mean follow-up (FU) for all eyes was 121.8 days. After a mean of 60 days, 21 eyes (75%) needed further surgical intervention. Qualified success was seen in four eyes (14.3%), with a mean FU of 383.6 days. Three eyes (10.7%) showed absolute success after a mean FU period of 202.7 days. In our series, we obtained the best results for phakic eyes, followed by pseudophakic and aphakic eyes. CONCLUSION: The results of this study do not provide convincing evidence of the functional efficacy of cyclodialysis ab interno. Nevertheless, the technique is easy to perform and offers safe and atraumatic access to the resorptive capability of the choroid. Conjunctival manipulation is avoided. Contrary to reports in the current literature, in our series, the best results were obtained for phakic eyes, though the small number of eyes included does not allow reliable statistics. Further studies will need to focus on the use of different space-retaining substances or a widening of the cyclodialysis cleft to improve surgical outcome.

A novel approach to suprachoroidal drainage for the surgical treatment of intractable glaucoma.

PURPOSE: In glaucoma surgery, scarring of the artificial fistula is the limiting factor for long-term control of intraocular pressure (IOP). Several devices and surgical techniques have been developed for artificial aqueous humor drainage in intractable glaucoma. The authors describe a novel surgical technique that uses a silicone tube as a shunt for aqueous flow from the anterior chamber to the suprachoroidal space. PATIENTS AND METHODS: Thirty-one eyes of 31 patients with uncontrollable refractory glaucoma were included in this prospective consecutive case-control study. Each eye had undergone an average of 3.5+/-1.9 previous interventions for glaucoma. The baseline IOP was 44.25+/-8.7 mm Hg despite maximum therapy. As in trabeculectomy, a limbus-based scleral flap was prepared. The suprachoroidal space was accessed via a deep posterior scleral flap. The silicone tube was inserted as an intrascleral connection from the anterior chamber to the suprachoroidal space. Cyclodialysis was avoided by this surgical approach. Success was defined as a lowering of IOP to below 21 mm Hg without the need for further medication or intervention. RESULTS: The mean functional shunt survival was 55.9+/-45.6 weeks. IOP was reduced to 12.9+/-5.2 mm Hg in 70% of all eyes after 30 weeks postoperatively. After 52 weeks, 60% of the eyes could be classified as representing success, and 76 weeks after surgery, 40% of the eyes still showed controlled IOP. In none of the eyes were severe postoperative hypotony or suprachoroidal bleeding observed. No localized or general inflammation or infection was seen in connection with the silicon tube. Two patients needed anterior chamber lavage because of bleeding. In 2 patients the tube had to be removed because of corneal endothelial contact. Shunt failure of the tube was caused in some cases by connective tissue formation at the posterior lumen of the tube. CONCLUSION: This novel surgical approach and the placement of the silicone tube described here have several advantages. Its intrascleral course minimizes the risk of conjunctival erosion and associated infections. No cyclodialysis is performed. Connection to the suprachoroidal space exploits the resorptive capability of the choroid. It guarantees drainage but also provides a natural counterpressure, avoiding severe postoperative hypotony. The suprachoroidal shunt presented here achieves good follow-up results in terms of IOP control. No serious complications have been observed. This new method promises to be an effective surgical technique and presents a new therapeutic option in intractable glaucoma. Fibroblast reaction obstructing the posterior lumen, seemed to be the only factor limiting drainage. Further studies and experiments will be needed to elucidate the exact physiologic mechanisms underlying the draining, the capacity and duration of the draining effect, and the histologic background of suprachoroidal scarring.

Characteristics of iris and retinal pigment epithelial cells cultured on collagen type I membranes.

PURPOSE: Transplantation of pigment epithelial cells is a promising treatment modality to repair retinal damage in age-related macular degeneration. For this purpose, it is necessary to establish cell culture techniques that allow acquisition of proper functional and morphological characteristics by the cells to be transplanted. METHODS: Primary retinal pigment epithelial (RPE) and iris pigment epithelial (IPE) cells grown to confluence on collagen membranes were examined for morphology, adhesion, proliferation, apoptosis, as well as viability after ex vivo transplantation. RESULTS: Pigment epithelial cells adhere, proliferate, form monolayers, acquire differentiated properties, and remain viable during transplantation to the subretinal space. CONCLUSIONS: Pigment epithelial cells cultured on collagen membranes acquire differentiated characteristics and are amenable to be transplanted as cell monolayers.

Central and paracentral corneal pachymetry in patients with normal tension glaucoma and ocular hypertension.

PURPOSE: The difference in central corneal thickness among subgroups of glaucoma patients, as well as its influence on Goldmann applanation tonometry, has been well documented in several clinical trials. In the present study, possible similarities and differences between central corneal thickness and corneal thickness of paracentral quadrants in patients with normal tension glaucoma (NTG) and ocular hypertension (OHT) were investigated. METHODS: Central and paracentral corneal thickness was measured by optical slit scan pachymetry (Orbscan II). Fourteen patients (28 eyes) with NTG and 11 patients (22 eyes) with OHT were included in this study. t-Test was performed for statistical analysis. To evaluate overall corneal topography, the mean and SD values of the differences between the central corneal thickness and each peripheral quadrant were analysed. RESULTS: The following data was obtained (microm): (central, upper, temporal, nasal, inferior paracentral quadrant): OHT group 617-695-663-687-660. NTG group 568-629-593-612-616. Corneal thickness of all four paracentral quadrants differed significantly between the OHT and NTG groups. There was a more heterogeneous intraindividual pattern of overall corneal topography in the OHT group, and a more heterogeneous pattern of corneal topography among the individuals of the NTG group (interindividual heterogeneity). CONCLUSIONS: A comparison of central corneal thickness and paracentral corneal thickness revealed clinically relevant differences between the OHT and NTG groups. The presented data underlines the importance of correlating the site of applanation with the corresponding corneal thickness, especially in OHT patients. It further substantiates the necessity to obtain individual pachymetric data for each NTG patient.

What do glaucoma specialists know about their patients?

BACKGROUND: Although interaction between doctor and patient is undoubtedly influenced by their mutual expectations, little information is available about the knowledge and expectations of glaucoma doctors concerning their patients' attitudes and treatment patterns. The aim of our prospective study was to compare the actual responses of glaucoma patients concerning various issues related to their disease and the responses the glaucoma doctors expected their patients to give. METHODS: Glaucoma patients consecutively sent to our glaucoma centre were asked to complete a standardised questionnaire about their glaucoma history, treatment routines and opinions on issues related to glaucoma. Ophthalmologists at the glaucoma centre were asked to predict patients' answers. RESULTS: One hundred and twenty-eight consecutive glaucoma patients completed the patients' questionnaire and 12 glaucoma specialists completed the corresponding questionnaire for doctors. Frequency of intraocular pressure (IOP) measurements and visual field testing, as well as the number of topical medications, were relatively accurately predicted by the glaucoma doctors. Differences between the doctors' predictions and patients' responses were found concerning discomfort after surgery and the influence of stress or environmental factors on IOP. The largest range of doctors' predictions (0-100%) was observed concerning the portion of patients claiming a 100% adherence to glaucoma medication. CONCLUSION: Glaucoma specialists are familiar with the treatment patterns of their patients. The knowledge of glaucoma specialists of their patients' subjective attitudes to glaucoma-related issues deserves further investigation, as discrepancies between doctors' and patients' responses were observed in this area.

Signal quality of biometry in silicone oil-filled eyes using partial coherence laser interferometry.

PURPOSE: To assess the practical feasibility and signal quality of axial length measurements by partial coherence laser interferometry in silicone oil-filled eyes with previous complicated vitreoretinal surgery. SETTINGS: Department of Ophthalmology, University Cologne, Cologne, Germany. METHODS: Using a Zeiss IOLMaster, axial length measurements and signal-to-noise ratios of optical biometry in silicone oil-filled eyes (n=45) and contralateral eyes without tamponade (n=41) were analyzed. RESULTS: Axial length measurements with signal-to-noise ratio > or =2 were feasible in 41 of 45 silicone oil-filled eyes (91%) and 37 of 41 eyes without tamponade (90%). Cataract, central retinal detachment, vitreous hemorrhage, and emulsified oil droplets attached to the intraocular lens were reasons for failure of partial coherence laser interferometry. The signal-to-noise ratio of the first 2 measurements was significantly smaller (P=.04) in silicone-filled eyes (4.4 +/- 2.0) than in eyes without tamponade (5.5 +/- 3.0). Axial lengths of the oil-filled eye and the contralateral eye showed a significant intraindividual correlation (P<.0001, Spearman r=0.84). CONCLUSIONS: Partial coherence laser interferometry shows good clinical practicability in silicone oil-filled eyes with previous complicated vitreoretinal surgery. Further studies are needed to assess the reliability of these measurements with regard to postoperative refraction after combined oil removal and cataract surgery.

The influence of Latanoprost 0.005% on aqueous humor flow and outflow facility in glaucoma patients: a double-masked placebo-controlled clinical study.

BACKGROUND: Fluorophotometry and pneumotonography were performed to investigate the effect of Latanoprost 0.005% and Placebo on aqueous humor flow and total outflow facility in human glaucomatous eyes. METHODS: In a randomized double-blind clinical study patients with POAG and OHT receive either Latanoprost 0.005% or placebo once in the evening. Fluorophotometry (Fluorotron Master II, Ocumetrics) and, Pneumotonography, Mentor) was performed in 20 eyes of 10 patients (verum) and 22 eyes of 11 patients (placebo). During a 2 week wash-out period all patients received a systemic antiglaucomatous therapy (Acetazolamide) up to 3 days before baseline measurement. Patients with IOP higher than 28 mmHg at baseline were excluded. Fluorophotometry, tonography and IOP were measured at baseline after 1 and 2 weeks of treatment. Data was analysed by the Student's paired t test. RESULTS: All patients completed the protocol. The IOP significantly decreased (25%) after 1 and 2 weeks of treatment with Latanoprost(p<0.01). Fluorophotometry measurements showed no difference in flow over time in both groups. Although tonographic mean C values in both groups did not show any difference over time, the estimated total outflow facility C (Goldmann) increased significantly (p<0.05) in the verum-treated eyes after 2 weeks. A significant difference of outflow co-efficient correlated to normal pressure (P0/C) was found after 2 weeks of treatment with Latanoprost (p<0.05). CONCLUSIONS: In accordance with the literature we found a mean 25% decrease in IOP after 2 weeks of treatment with Latanoprost 0.005%. The analysis of the flow values in both groups showed no increase or decrease in aqueous humor dynamics as proved in many previous studies. The known effect of Latanoprost increase uveoscleral outflow by remodeling extracellular matrix and widening intermuscular spaces in the ciliary body may not detected by pneumotonography after 2 weeks of treatment. The significant increase in estimated total outflow facility (Goldmann formula) in latanoprost-treated eyes and the decrease of IOP took place at constant flow rates. The increase in conventional outflow facility may indicate trabecular meshwork changes, but it cannot explain the significant decrease in IOP. Furthermore, an additional effect, e.g. uveoscleral outflow, may play the major role as considered in many previous studies.

The ophthalmic lyophilisate carrier system (OLCS): development of a novel dosage form, freeze-drying technique, and in vitro quality control tests.

The ophthalmic lyophilisate carrier system (OLCS) is a novel dosage form for delivery of pharmacologically active ingredients or other substances improving the structure of the tear film to the eye. A drop of lyophilisate containing the drug and bulk forming water-soluble or swelling excipients is attached to a flexible hydrophobic carrier. Placebo OLCS and OLCS containing several drugs commonly used in ophthalmology were compared to conventional eye drops containing the same ingredients. A novel lyophilization procedure for the production of this dosage form is described, which allows stricter control of the freezing and drying conditions and shortens the production cycle by at least an order of magnitude. In clinical studies it was found that OLCS are easy to administer and well tolerated if the force of adhesion between lyophilisates and carrier strips and the structural firmness of the lyophilisates themselves are well controlled. These parameters are critical for convenient administration and complete delivery of the dose of active ingredients incorporated, therefore suitable in vitro tests were developed with which their values can be determined for the purpose of process validation. A study of fluorescein OLCS in humans indicated that concentration profiles in the cornea and anterior chamber are significantly higher than after administration of equal doses of the diagnostic in conventional eye drops.

Apoptosis-mediating receptor-ligand systems in human retinal pigment epithelial cells.

BACKGROUND: To establish new strategies for the treatment of proliferative vitreoretinopathy (PVR), we investigated new members of a recently discovered apoptosis-inducing receptor-ligand system in human retinal pigment epithelial (RPE) cells. TRAIL (Apo2-L) and Apo3-L are capable of inducing cell death via their receptors Trail-R1 to Trail-R4 and TRAMP. The goal of this study was to prove the existence of these new apoptosis-inducing receptors and ligands in RPE cells. METHODS: Human RPE cells, cultured or prepared directly from the eye, were examined by RT-PCR. Immunohistochemistry of epiretinal membranes of traumatic PVR was performed for the detection of TRAIL and Trail-R1. Protein expression of Trail-R1 was examined in cultured human RPE cells by western blot. Cell death after TRAIL treatment of human RPE cells was measured by crystal violet staining. RESULTS: For RPE cells derived directly from the eye, we detected mRNAs of Trail-R2, Trail-R3, TRAIL, and APO3-L, but not Trail-R1, Trail-R4, and TRAMP. All the examined transcripts were detected in human P0 RPE cells in vitro. Immunohistochemical studies on PVR membranes identified TRAIL and Trail-R1. Western blot confirmed the presence of Trail-R1 in cultured human RPE cells. TRAIL failed to kill RPE cells in vitro, but showed a strong synergistic killing effect when coincubated with protein (cycloheximide) or RNA (actinomycin D) synthesis inhibitor. CONCLUSIONS: We detected a novel apoptosis-inducing receptor-ligand system in RPE cells. An induction of apoptosis as a treatment of PVR seems to be possible. Further investigations are needed including an animal model of PVR.

Tolerability and safety of two new preservative-free tear film substitutes.

PURPOSE: The tolerability, safety, and visual comfort of two new tear film substitutes were studied in a phase I clinical study. METHODS: Two amphipathic lipids (phosphatidylcholine, cholesterol, sphingomyelin, and gangliosides) containing solutions (I and II) of well-defined stoichiometry, free of preservatives, were studied in 20 eyes of 20 healthy volunteers (age range, 26-32 years) in a randomized, double-blind, crossover study. Randomization was achieved by treating one eye of each volunteer four times daily for 7 days with composite solution I. The contralateral eye served as a control. After a washout interval of 7 days, the same eye was treated similarly four times daily with the solution II under randomizing conditions. Slit-lamp biomicroscopy, visual acuity, visual analog scales, and side effects were monitored at the beginning of the study weekly and for 3 weeks. RESULTS: The tear substitutes proved to have no influence on the visual acuity and were safe and well tolerated. No allergic reactions or any other side effects such as hyperemia, corneal disturbance, and foreign body deposits were observed in any volunteer. CONCLUSION: The biophysical properties of the amphipathic lipids comprising the two preservative-free tear film substitutes were studied in monolayer experiments. They form reversibly compressible and expandable monomolecular films at the air-water interface, a prerequisite for the mimicry of the tear film produced normally by meibomian glands. The efficacy and safety of both medications will be investigated in patients with keratoconjunctivitis sicca and dry eye syndrome in future experiments.