Two-Year Performance and Safety Results of the MINIject Supraciliary Implant in Patients With Primary Open-Angle Glaucoma: Meta-Analysis of the STAR-I, II, III Trials.

PURPOSE: To evaluate the performance and safety of minimally invasive glaucoma surgery with a supraciliary drainage device (MINIject; iSTAR Medical, Wavre, Belgium) in primary open-angle glaucoma (POAG) as a stand-alone procedure. DESIGN: Meta-analysis. METHODS: At 11 sites in Colombia, France, Germany, India, Panama, and Spain, 82 patients were treated in 3 prospective, multicenter, interventional, nonrandomized trials (STAR-I, II, III). Data were pooled in a meta-analysis of up to 2 years of follow-up postimplantation. The main outcome measures were mean relative and absolute reduction in diurnal intraocular pressure (IOP) compared to baseline. Secondary outcomes included patients with IOP ≤18 mmHg, patients with IOP reduction ≥20%, number of IOP-lowering medications, adverse events, and endothelial cell density loss. RESULTS: At the 2-year follow-up (n = 66), mean IOP was reduced from 23.8 ± 3.3 mmHg at baseline to 14.4 ± 4.5 mmHg (-39.3%; P < 0.0001). An IOP reduction of ≥20% was achieved in 89.4% of patients, with 84.8% having an IOP ≤18 mmHg. IOP-lowering medications were reduced from a mean of 2.4 ± 1.1 to 1.4 ± 1.4 (P < 0.0001), with 37.9% of patients being medication-free at 2 years. Mean endothelial cell density loss at 2 years was 6.2 ± 9.1% compared to baseline and no patient had a loss >30%. CONCLUSIONS: This meta-analysis demonstrates the favorable safety and efficacy profile of a supraciliary device implanted in a stand-alone, ab-interno procedure in patients with mild-to-moderate POAG. The data demonstrate that MINIject is a safe and effective, bleb-free treatment option for patients requiring low target IOP up to 2 years.

Two-year outcomes of the MINIject drainage system for uncontrolled glaucoma from the STAR-I first-in-human trial.

BACKGROUND/AIMS: The current study evaluates the efficacy and safety of the stand-alone implantation of the MINIject (iSTAR Medical, Wavre, Belgium) supraciliary, microinvasive glaucoma drainage device in patients with medically uncontrolled open-angle glaucoma. METHODS: This prospective, multicentre, first-in-human, single-arm interventional study evaluated stand-alone, ab interno implantation in 25 patients of a 5 mm long uveoscleral device made of STAR biocompatible material, which is a soft, microporous, flexible silicone. The primary outcome was the reduction of intraocular pressure (IOP) at 6 months compared with baseline, and follow-up continued until 2 years for 21 patients. Secondary outcomes included success defined as diurnal IOP of ≤21 mmHg and >5 mmHg with an IOP reduction of 20% without (complete) or with/without (qualified) glaucoma medication. RESULTS: Mean baseline IOP was 23.2±2.9 mmHg on 2.0±1.1 glaucoma medication ingredients and decreased to 13.8±3.5 mmHg (-40.7% reduction) on 1.0±1.3 medications 2 years after implantation. Complete success was achieved in 47.6% of patients (10/21) and qualified success in 100% of patients (21/21) at the 2-year follow-up. All patients achieved a 20% IOP reduction with 48% of patients medication-free. No serious ocular adverse events or additional glaucoma surgery were reported. Mean central endothelial cell density (ECD) mildly decreased from 2411 cells/mm2 (n=26) to 2341 cells/mm2 (n=21) at 24 months, which represents a 5% decrease for matched eyes. No patient had a ≥30% decrease in central ECD. CONCLUSION: This first-in-human study on the stand-alone implantation of the MINIject supraciliary drainage system shows promising IOP-lowering results and medication reduction over 24 months with few adverse events. TRIAL REGISTRATION NUMBER: NCT03193736.

Changes of Neuroretinal Rim and Retinal Nerve Fiber Layer Thickness Assessed by Optical Coherence Tomography After Filtration Surgery in Glaucomatous Eyes.

PURPOSE: Lowering the intraocular pressure (IOP) in patients with primary open-angle glaucoma (POAG) with filtration surgery can induce morphological changes to the bulbus and structures of the retina. In this study, we have evaluated changes of Bruch's membrane-based parameters and retinal nerve fiber layer (RNFL) derived by spectral-domain optical coherence tomography (SD-OCT) in eyes that have undergone glaucoma filtration surgery. PATIENTS AND METHODS: SD-OCT imaging of the optic nerve head (ONH) and of the RNFL was performed in 54 eyes of 54 patients with medically uncontrolled POAG before and after IOP-lowering surgery (trabeculectomy or deep sclerectomy). The ONH parameter minimum rim width (MRW) and the size of the Bruch's membrane opening (BMO-Area) were derived from 24 radial B-scans centered on the ONH. RESULTS: The average preoperative IOP was 23.1 ± 7.5 mmHg. One month postoperatively, the average IOP decreased to 12.1 ± 4.6 mmHg (p < 0.01), which caused a significant increase in the thickness of neuroretinal rim. There was no significant change in the automatically detected BMO-Area (p = 0.32). The pressure-related increase in MRW correlated well with the postoperative IOP and cup-to-disc ratio (CDR). In regression analysis, the alteration in thickness of the neuroretinal rim could be well predicted in a model including CDR, change of IOP and mean deviation (MD) (R2 = 0.414, p < 0.001). RNFL showed a significant increase as well. CONCLUSION: IOP-lowering surgery in patients with medically uncontrolled POAG causes an increased thickness of the SD-OCT derived ONH parameters. The changes of the RNFL after surgery showed no significant correlations with IOP changes. In contrast to this, highly significant correlations of MRW values with the IOP could be observed. The BMO-Area remained completely stable A preferred use of RNFL for follow-up should be discussed.

A European Study of the Performance and Safety of MINIject in Patients With Medically Uncontrolled Open-angle Glaucoma (STAR-II).

PRECIS: In this European study (STAR-II), MINIject, a novel, ab-interno, supraciliary minimally invasive glaucoma surgery device, effectively lowered intraocular pressure (IOP) and the need for IOP-lowering medications in patients with primary open-angle glaucoma. PURPOSE: This study evaluates the safety and performance of a minimally invasive supraciliary glaucoma drainage device (MINIject DO627) for surgical treatment of primary open-angle glaucoma in patients refractory to topical hypotensive medications. METHODS: In a prospective, interventional, single-arm, multicenter, European study (STAR-II), MINIject was successfully implanted in a stand-alone procedure in 29 of 31 patients in 8 sites in 3 countries. The primary endpoint was the success rate 6 months after surgery >60% (defined as diurnal IOP ≤21 and >5 mm Hg with ≥20% IOP reduction from baseline, with/without glaucoma hypotensive medication). ClinicalTrials.gov: NCT03624361. RESULTS: At the 6-month follow-up, the primary endpoint was fulfilled, with 75.9% of patients reaching prospectively defined success. The mean IOP was reduced by 40.2% (9.9 mm Hg) to 14.7±6.0 mm Hg at 6 months from 24.6±3.8 mm Hg at baseline. The use of IOP-lowering medication ingredients was reduced by 63.4% from 2.9±1.2 at baseline to 1.0±1.3. Furthermore, 79.3% of the patients had mean IOP ≤18 mm Hg, 82.8% achieved a ≥20% IOP reduction, and 55.2% were medication free at 6 months. Six device-related serious adverse events were reported in the study eye: IOP increase (3/31 patients, 9.7%), and single reports of eye pain, corneal erosion, and chorioretinal folds (1/31, 3.2%), all of which resolved. There was minimal change to corneal endothelial cell density. CONCLUSION: Ab-interno supraciliary surgical implantation using MINIject DO627 in a stand-alone procedure significantly lowers IOP by 40% at the 6-month follow-up, while reducing the need for IOP-lowering medication.

A First-in-Human Study of the Efficacy and Safety of MINIject in Patients with Medically Uncontrolled Open-Angle Glaucoma (STAR-I).

PURPOSE: To describe the safety and efficacy of a novel, supraciliary, microinvasive glaucoma surgery drainage system, MINIject (iSTAR Medical, Wavre, Belgium), in the study. DESIGN: Prospective, multicenter, interventional, single-arm trial. PARTICIPANTS: Twenty-six patients with primary open-angle glaucoma uncontrolled with 1 or more intraocular pressure (IOP)-lowering medications. METHODS: Using an ab interno approach, 25 eyes were implanted successfully in a stand-alone procedure with a 5-mm long device made of biocompatible STAR material, which is soft and flexible silicone in a microporous, network design. Intraocular pressure, medication use, and other ocular parameters were evaluated before surgery, 1 day, 1 and 2 weeks, and 1, 3, and 6 months after surgery. MAIN OUTCOME MEASURES: Intraocular pressure reduction at 6 months compared with baseline analyzed using a paired t test. Safety evaluation entailed tabulation of the nature and frequency of adverse events. RESULTS: Mean baseline diurnal IOP was 23.2 mmHg (standard error, 0.6 mmHg) using a mean ± standard deviation of 2.0±1.1 IOP-lowering medication classes. During the 6-month follow-up period, mean IOP ranged from 10.0-16.3 mmHg (mean reductions, 6.9-13.2 mmHg or 31.0%-56.8%). Six months after surgery, mean diurnal IOP was 14.2 mmHg (standard error, 0.9 mmHg), equivalent to a reduction of 9.0 mmHg or 39.1% (P < 0.0001). The mean ± standard deviation number of IOP-lowering medications was 0.3±0.7. Of 24 patients seen at 6-month follow-up, 21 (87.5%) were medication-free and 23 (95.8%) achieved a minimum 20% IOP reduction from baseline. There were no serious adverse events related to the device or procedure, and no additional glaucoma surgery was required. Frequently reported events included anterior chamber inflammation (n = 8), IOP elevation (n = 6), of which 1 event was an IOP spike per protocol, visual acuity reduction (n = 3), and hyphema (n = 3), all of which resolved. There was no change to mean central or peripheral corneal endothelial cell density. No device-related adverse events were reported. CONCLUSIONS: The MINIject glaucoma drainage system significantly lowered IOP and eliminated the need for medication in most patients 6 months after surgery when implanted in a standalone procedure. There were no serious ocular adverse events.

[Required Framework for the Collection of Real-life Data: An Example from University Eye Hospital Munich]. / Rahmenbedingungen zur Sammlung von "Real-Life"-Daten am Beispiel der Augenklinik der Universität München.

Background The importance of evaluating real-life data is constantly increasing. Currently available computer systems better allow for analyses of data, as more and more data is available in a digital form. Before a project for real-life data analyses is started, technical considerations and staff, legal, and data protection procedures need to be addressed. In this manuscript, experiences made at the University Eye Hospital in Munich will be shared. Materials and Methods Legal requirements, as found in laws and guidelines governing documentation and data privacy, are highlighted. Technical requirements for information technology infrastructure and software are defined. A survey conducted by the German Ophthalmological Society, among German eye hospitals investigating the current state of digitalization, was conducted. Also, staff requirements are outlined. Results A database comprising results of 330,801 patients was set up. It includes all diagnoses, procedures, clinical findings and results from diagnostic devices. This database was approved by the local data protection officer. In less than half of German eye hospitals (n = 21) that participated in the survey (n = 54), a complete electronic documentation is done. Fourteen institutions are completely paper-based, and the remainder of the hospitals used a mixed system. Conclusion In this work, we examined the framework that is required to develop a comprehensive database containing real-life data from clinics. In future, these databases will become increasingly important as more and more innovation are made in decision support systems. The base for this is comprehensive and well-curated databases.

Using Electronic Health Records to Build an Ophthalmologic Data Warehouse and Visualize Patients' Data.

PURPOSE: To develop a near-real-time data warehouse (DW) in an academic ophthalmologic center to gain scientific use of increasing digital data from electronic medical records (EMR) and diagnostic devices. DESIGN: Database development. METHODS: Specific macular clinic user interfaces within the institutional hospital information system were created. Orders for imaging modalities were sent by an EMR-linked picture-archiving and communications system to the respective devices. All data of 325 767 patients since 2002 were gathered in a DW running on an SQL database. A data discovery tool was developed. An exemplary search for patients with age-related macular degeneration, performed cataract surgery, and at least 10 intravitreal (excluding bevacizumab) injections was conducted. RESULTS: Data related to those patients (3 142 204 diagnoses [including diagnoses from other fields of medicine], 720 721 procedures [eg, surgery], and 45 416 intravitreal injections) were stored, including 81 274 optical coherence tomography measurements. A web-based browsing tool was successfully developed for data visualization and filtering data by several linked criteria, for example, minimum number of intravitreal injections of a specific drug and visual acuity interval. The exemplary search identified 450 patients with 516 eyes meeting all criteria. CONCLUSIONS: A DW was successfully implemented in an ophthalmologic academic environment to support and facilitate research by using increasing EMR and measurement data. The identification of eligible patients for studies was simplified. In future, software for decision support can be developed based on the DW and its structured data. The improved classification of diseases and semiautomatic validation of data via machine learning are warranted.

The influence of a specific ophthalmological electronic health record on ICD-10 coding.

BACKGROUND: A specific Electronic Health Record (EHR) for ophthalmology was introduced in an academic center in Germany. As diagnoses coding corresponding to the International Classification of Diseases Version 10 (ICD-10) is mandatory for billing reasons in Germany, we analyzed whether a change occurred in the diversity and number of diagnoses after the EHR introduction. The number of patients was also analyzed. Proper diagnoses coding is of the utmost importance for further data analysis or billing. METHODS: Graphical User Interfaces (GUIs) were created by using Advanced Business Application Programming language in EHR "i.s.h.med." Development of an EHR was conducted in close collaboration between physicians and software engineers. ICD-10 coding was implemented by using a "hit list" and a search engine for diagnoses. An observational analysis of a 6-month period prior to and after the introduction of an ophthalmological specific EHR was conducted by investigating the diversity and number of diagnoses in various ophthalmological disease categories and the number of patient consultations. RESULTS: During the introduction of a specific ophthalmological EHR, we observed a significant increase in the emergency department cases (323.9 vs. 359.9 cases per week), possibly related to documentation requirements. The number of scheduled outpatients didn't change significantly (355.12 vs. 360.24 cases per week). The variety of diagnoses also changed: on average, 156.2 different diagnoses were made per week throughout our hospital before the EHR launch, compared to 186.8 different diagnoses per week thereafter (p < 0.05). Additionally, a significantly higher number of diagnoses per case and per week were observed in both emergency and subspecialty outpatient clinics (1.15 vs. 1.22 and 1.10 vs. 1.47, respectively). CONCLUSIONS: An optimized EHR was created for ophthalmological needs and for simplified ICD-10 coding. The implementation of digital patient recording increased the diversity of the diagnoses used per case as well as the number of diagnoses coded per case. A general limitation to date is the suboptimal precision of ICD-10 coding in ophthalmology. Correct coding is of utmost importance for future data analysis.

Dermis fat grafts as primary and secondary orbital implants.

INTRODUCTION: This study was performed to evaluate the outcome after autologous dermis-fat graft [DFG] orbital implants in a large sample. MATERIALS AND METHODS: A retrospective chart review of all primary and secondary DFGs in a 16-year period was done. Aesthetic and functional results, patients' satisfaction and postoperative complications were evaluated. RESULTS: In total 468 DFGs were performed in the study period (315 primary [I°] and 153 secondary [II°] DGFs). In the analysis, 173 DFG I° and 66 DFG II° were included as sufficient follow-up was available. Median follow-up after DFG I° was 21.5 months and 14 months after DFG II°. After DFG I°, in 76% of patients motility of the graft was possible in all directions; 81% had good fitting of the prosthesis and 83% were highly satisfied with the results. Mean width of palpebral apertures was 0.2 mm smaller and Hertel exophthalmometry revealed a mean enophthalmus of 1.6 mm on the operated side compared to the fellow-eye. After DFG II°, motility was possible in all directions in 34% of patients. Fitting of the prosthesis was good/reasonable in 49%/41% and patients were highly satisfied in 57%. On average, on the operated side palpebral apertures were 0.6 mm smaller and Hertel measurements showed an enophthalmus of 2.6 mm. Major complications were uncommon. Complete necrosis of the implant was more often observed after II° (6.1%) than after I° DFG (3.5%). DISCUSSION: In this large sample, DFG proved to be an effective and safe method for the reconstruction of anophthalmic sockets.

Idebenone prevents human optic nerve head astrocytes from oxidative stress, apoptosis, and senescence by stabilizing BAX/Bcl-2 ratio.

PURPOSE: Oxidative stress plays an important role in the pathogenesis of several neurodegenerative diseases including glaucoma. Astrocytes are supposed to play a role in glaucoma pathogenesis. This study investigates the antiapoptotic and cytoprotective effects of idebenone on optic nerve head astrocytes (ONHA) under oxidative stress. METHODS: ONHA were treated with 1 to 150 µM idebenone. Cell viability (MTT assay and live-dead assay), induction of intracellular reactive oxygen species, senescence-associated ß-galactosidase activity were investigated. In addition, apoptosis (detection of histone-associated DNA fragmentation), and expression of BAX and Bcl-2, and their mRNA were determined after 48 hours and after hydrogen peroxide (H2O2) treatment. RESULTS: Idebenone concentrations from 1 to 50 µM showed no effects on ONHA viability. Pretreatment with 10 µM idebenone led to an increase in viability of ONHA after H2O2 treatment. In addition, idebenone pretreatment significantly attenuated the increase of histone-associated DNA fragmentation, induction of senescence-associated ß-galactosidase, and intracellular reactive oxygen species after treatment with H2O2. When ONHA cells were treated with idebenone and H2O2, real-time polymerase chain reaction and Western blot analysis yielded an increased expression of Bcl-2 and a decrease of BAX compared with those cells that were treated with H2O2 only. CONCLUSIONS: Idebenone reduced senescence, oxidative stress, and apoptotic cell death in cultured ONHA in vitro. Our results suggest that idebenone may help to protect ONHA in vivo, and therefore might be helpful in preventing the progression of glaucomatous degeneration.

Patients' preferences in treatment for neovascular age-related macular degeneration in clinical routine.

PURPOSE: To assess the effect of ranibizumab treatment for neovascular age-related macular degeneration (nvAMD) on patients' preferences and vision-related quality of life (VRQoL) in a routine clinical setting. METHODS: 55 treatment naïve patients were examined before and after the initial upload of three monthly injections of 0.5 mg ranibizumab. VRQoL was assessed using a Rasch-adjusted NEI-VFQ-25. Time trade-off (TTO), standard gamble, a visual analogue scale and the European Quality of Life Questionnaire (EQ-5D) were used to calculate utilities, and multiple logistic regression models were conducted to determine independent factors associated with utilities. RESULTS: Mean ± SD age was 75 ± 7 years, and 40 patients (73%) were female. Mean ± SD best-corrected visual acuity of the treated eye increased from 20/80 at baseline (logMAR 0.60 ± 0.35) to 20/63 (logMAR 0.52 ± 0.36; p=0.020) at follow-up after three injections. Utility score increases ranged from 2 utils (standard gamble anchored for death) up to 6.6 utils (EQ-5D German TTO, p=0.023) and visual functioning improved (Rasch adjusted composite NEI-VFQ score 50 ± 21 to 54 ± 21, p=0.042). Whether the worse or better eye was treated was not significantly associated with improvements in utility or VRQoL, whereas VA improvement in the treated eye was associated with an increase in utility (TTO, p=0.020). CONCLUSIONS: TTO performed best in this sample of elderly nvAMD patients undergoing anti-VEGF therapy. Better or worse eye treatment was not associated with a change in reported utilities or visual functioning in patients with newly diagnosed nvAMD. Directly elicited, vision-specific utilities gained with TTO seem to be sensitive to a change in vision status.

Inhibitory activity of ranibizumab, sorafenib, and pazopanib on light-induced overexpression of platelet-derived growth factor and vascular endothelial growth factor A and the vascular endothelial growth factor A receptors 1 and 2 and neuropilin 1 and 2.

BACKGROUND: Cumulative light exposure is significantly associated with progression of age-related macular degeneration. Growth factors and growth factor receptor signaling are known to have a substantial impact on the development of age-related macular degeneration. This study explored the effects of ranibizumab, sorafenib, and pazopanib on vascular endothelial growth factor A (VEGF) receptors 1 and 2 and neuropilin 1 and 2 expression in human retinal pigment epithelial cells. In addition, their effects on light-induced overexpression of VEGF and platelet-derived growth factor were investigated. METHODS: Primary human retinal pigment epithelial cells were exposed to white light and then treated with ranibizumab (0.125 mg/mL), sorafenib (1 µg/mL), or pazopanib (1 µg/mL). Viability of cells, expression of VEGF receptors 1 and 2 and neuropilin 1 and 2 and their mRNA, and secretion of VEGF and platelet-derived growth factor were investigated by reverse transcription-polymerase chain reactions, immunohistochemistry, and enzyme-linked immunosorbent assays. RESULTS: Treatment with sorafenib or pazopanib reduced the expression of VEGF receptors 1 and 2 and neuropilin 1, and sorafenib also reduced neuropilin 2. Light exposure decreased cell viability and increased expression and secretion of VEGF and platelet-derived growth factor. Sorafenib and pazopanib significantly reduced light-induced overexpression and secretion of VEGF and platelet-derived growth factor. Ranibizumab reduced secreted VEGF in cell culture supernatants only. CONCLUSION: Our in vitro results suggest that multikinase inhibitors have promising properties as a potential antiangiogenic treatment for age-related macular degeneration.

Indocyanine green increases light-induced oxidative stress, senescence, and matrix metalloproteinases 1 and 3 in human RPE cells.

PURPOSE: Indocyanine green (ICG) is a commonly used vital dye for macular surgery. Recent reports implicate that its use might be associated with less favourable results regarding postoperative visual outcome and damage of retinal cells, and atrophic degeneration of the retinal pigment epithelium (RPE) has been described. This study investigates the effects of ICG on light-induced senescence of RPE cells. METHODS: Primary human RPE cells were either pre-incubated with ICG in concentrations of 0.005% and 0.05% or not and then exposed to white light. After 10 min of irradiation viability, induction of intracellular reactive oxygen species (ROS) and senescence-associated ß-galactosidase activity (SA ß-Gal) were determined. Expression and secretion of matrix metalloproteinases (MMPs) 1 and 3 and their mRNA were determined by RT-PCR and ELISA. RESULTS: Light exposure decreased RPE cell viability by 46%. Treatment with 0.005% and 0.05% ICG alone decreased RPE cell viability by 7% and 21%. In addition, expression of ROS, SA ß-Gal, and MMP-1 and 3 was significantly increased. When 0.005% and 0.05% ICG treatments were combined with light exposure, viability decreased by 69% and 82% compared to the untreated control. Effects on the expression of ROS, SA ß-Gal, and MMP-1 and 3 were, depending on the ICG dose, significantly increased when cells were pre-incubated with ICG and then illuminated. CONCLUSION: In this study, pretreatment with ICG significantly increased light-induced oxidative stress and senescence. This might indicate a potential, supplementary mechanism that could explain RPE alterations and reduced functional results after ICG-assisted internal limiting membrane peeling.

Coenzyme Q10 prevents human lens epithelial cells from light-induced apoptotic cell death by reducing oxidative stress and stabilizing BAX / Bcl-2 ratio.

BACKGROUND: Cataract is one of the most prevalent eye disease and a major cause for legal blindness in the world. Beside others, cumulative light-exposure and apoptotic cell death are significantly associated with cataract development. In contrast, supplementation with antioxidants has been suggested to prevent premature cataractogenesis. This study investigates possible protective effects of Coenzyme Q10 (CoQ10) regarding light-induced stress and apoptotic cell death in human lens epithelial cells (LEC). METHODS: Human LEC were either pre-incubated with CoQ10 or not and then exposed to white light. After 10-40 min of irradiation viability, induction of intracellular reactive oxygen species (ROS), apoptosis and cell death was determined. Expression of apoptotic BAX and anti-apoptotic Bcl-2 protein and their mRNA were determined by RT-PCR and Western blot analysis. RESULTS: Light exposure decreased LEC viability and Bcl-2 expression and increased intracellular ROS, apoptotic cell death, and BAX expression in a time-of-irradiation-dependent manner. Phototoxic cell death and apoptosis, as well as decrease of Bcl-2 and increase in BAX expression was significantly reduced, when cells were pre-incubated with CoQ10. CONCLUSIONS: In this study, CoQ10 significantly reduced light-induced LEC-damage and attenuated phototoxic effects on BAX and Bcl-2 expression. Therefore, CoQ10 supplementation might also be useful in preventing LEC death and consecutive cataract formation in vivo.

Utility values in patients with acquired anophthalmus.

BACKGROUND: Loss of an eye can be supposed to lead to reduced health-related quality of life. This can be due to monophthalmia in acquired anophthalmus and/or because of cosmetic impairment. Meanwhile several methods exist to evaluate the quality of life and the impairment in utility values in patients with ophthalmological diseases. METHODS: Twenty-three patients who underwent enucleation of one eye with good visual acuity of the fellow eye (>20/30) were included. All patients were asked to complete a standardized time trade-off (TTO) utility assessment form as well as the self-administered National Eye Institute Visual Function Questionnaire 25 (VFQ 25). TTO was assessed for restoring vision (TTO-A) and for restoring cosmetic appearance (TTO-B). RESULTS: The mean TTO value for visual function (TTO-A) was 0.87, the mean TTO value for cosmetic restoration (TTO-B) was 0.90 with a significant correlation. These values are surprisingly high compared to current TTO data. Visual acuity of the last eye and utility values were not correlated. TTO was not influenced by the underlying diagnosis. Patients older than 50 years were willing to trade off relatively more years than younger patients. TTO values were independent from the duration of the acquired anophthalmus. The mean VFQ-25 composite score was 81.0 and significantly lower than in the normal population. There was no significant correlation between TTO and the VFQ-25 composite score or any of the 12 subscales of the VFQ-25. CONCLUSION: Utility of patients with acquired anophthalmus and good vision of the last eye is very similar to patients with two eyes of which one is worse and good binocular vision. The VFQ-25 is no predictor for time trade-off.

Endothelial cell density in donor corneas: a comparison of automatic software programs with manual counting.

PURPOSE: Several automated systems have become available to determine endothelial cell density (ECD) of donor corneas. The purpose of this study was the comparison of 2 systems, the Endothelial Analysis System EAT V1.4 (Rhinetec, Duesseldorf, Germany) and the NAVIS Cell Count Version 3.4.1 (Nidek Technologies, Erlangen, Germany), against manual ECD counts. METHODS: During organ culture, the endothelium of 50 human corneas was photographed on both conventional film and digitally. Manual fixed-frame counting was performed on 2 photographs by 3 experienced ophthalmologists. Three digital pictures of each cornea were analyzed semiautomatically on the Rhinetec EAT system V1.4. Images were imported and analyzed by the fully automatic mode of the NAVIS system V3.4.1 (which also offers a semiautomatic counting mode). In an additional experiment on 11 corneas, the NAVIS counts on the microscopy system previously used only for manual cell counts were directly compared with manual counts. RESULTS: Mean endothelial cell density obtained by manual counting of all observers was 2679 +/- 313 (SD) cells/mm. Values obtained by digital analysis with EAT were a mean of 1.3% higher (2713 +/- 286 cells/mm), which is not a significant difference. In contrast, analysis of the digital pictures with the fully automated NAVIS software mode showed a mean of 7.0% higher measurements (2867 +/- 111 cells/ mm), a significant difference (P = 0.0001). Altman-Bland analysis revealed that the fully automated NAVIS counts gave too low results for high ECDs and too high results for low ECDs. This result was confirmed by the direct comparison with manual counting. CONCLUSIONS: Fully automated analysis of ECD remains problematic. Validation of any computer-assisted system against manual counting is of importance.

Visual quality of life after macular hole surgery: outcome and predictive factors.

BACKGROUND: In the present study we evaluated the functional success after macular hole surgery in correlation to visual quality of life and looked for predictive factors determining surgical success. METHODS: Fifty-nine patients that underwent pars plana vitrectomy for idiopathic macular hole were included. Follow-up visits were performed in regular intervals after surgery and included a clinical examination, optical coherence tomography (OCT) and measurement of visual acuity. To assess the visual quality of life patients filled out the National Eye Institute 25-item Visual Function Questionnaire (VFQ-25) before and three months and one year after surgery. RESULTS: Macular hole closure was achieved in 57 of 59 patients (97%). Mean visual acuity increased from 20/100 preoperatively to 20/34 one year after surgery (p = 0.02). Despite good visual acuity (20/27) in the fellow eye, visual quality of life (VFQ composite score) rose from 75.9 +/- 14.4 (SD) to 81.5 +/- 14.2 one year after surgery (p<0.001). Although there was no correlation between the increase in visual quality of life and visual acuity, the increase in VFQ-25 could be well predicted: low visual acuity and significant impairment on VFQ-25 testing preoperatively made patients most likely to benefit from macular hole surgery. A relatively high retinal thickness measurement at the hole border measured on OCT further increases the predictive value. CONCLUSION: Macular hole surgery is associated with an increase in visual quality of life despite good visual acuity of the fellow eye. Preoperative visual acuity, VFQ-25 value and partly OCT may help to predict the increase in patients' vision related quality of life after surgery.

TGF-beta2-induced cell surface tissue transglutaminase increases adhesion and migration of RPE cells on fibronectin through the gelatin-binding domain.

PURPOSE: Migration and adhesion of dislocated retinal pigment epithelial (RPE) cells to a fibronectin-rich extracellular matrix is an initial step in proliferative vitreoretinopathy (PVR). In the present study, the functional role of cell surface tissue transglutaminase (tTG) in adhesion and migration of RPE cells on fibronectin (Fn) and collagen type I (Col I) after stimulation with TGF-beta2 was investigated. METHODS: Cultured human RPE cells were treated with 1.0 ng/mL TGF-beta2 for 24 hours. Cell surface tTG expression was determined by cell fraction analysis. Attachment on Col I, full-length Fn, and its 45-kDa gelatin-binding and 110-kDa cell-binding fragment was measured with an MTT assay. Migration of RPE cells was measured by a Boyden chamber assay, and cell spreading was determined. Experiments were performed in the presence or absence of anti-tTG antibodies and anti-integrin alpha5 and beta1 antibodies. RESULTS: TGF-beta2 markedly induced expression of cell-surface tTG on RPE cells and increased attachment and migration on Fn and Col I. Blocking cell surface tTG inhibited attachment, migration, and spreading on Fn and its 45-kDa gelatin-binding fragment, whereas no effect was seen on Col I and the 110-kDa cell-binding Fn fragment. In contrast, blocking of integrin alpha5 and beta1 suppressed adhesion and migration on full-length Fn and the 110-kDa Fn fragment. CONCLUSIONS: These data demonstrate that TGF-beta2 increases expression of cell surface tTG, which in turn strengthens adhesion, migration, and spreading of RPE cells on Fn through the 45-kDa gelatin-binding Fn fragment. At the onset of PVR, this mechanism may help RPE cells to attach and migrate on Fn-containing matrices.

Tele-screening for diabetic retinopathy with the retinal thickness analyzer.

OBJECTIVE: To compare the effectiveness of tele-screening using a novel enhanced retinal thickness analyzer (RTA) with onsite routine ophthalmologic examination for diabetic retinopathy. RESEARCH DESIGN AND METHODS: A consecutive series of 31 eyes from diabetic patients were included. All underwent ophthalmologic examination, including stereoscopic dilated funduscopy and scanning with the RTA. The RTA reports consisted of a wide-angle, red-free fundus photograph and a macular-region retinal thickness map. Reports were graded by three independent graders in a masked manner. The diagnoses of proliferative retinopathy, macular edema, and treatment decisions made by the RTA graders and the clinical examiner were compared. RESULTS: On clinical examination 5 of 31 eyes were diagnosed with proliferative diabetic retinopathy (PDR). All five were referred for treatment by two graders and four eyes by one grader. All eyes with PDR and 12 of the 26 eyes with nonproliferative diabetic retinopathy showed severe macular edema. Seven of the 12 eyes with macular edema were clinically eligible for focal laser treatment, and all of them were detected by all RTA graders. Macular thickening was detected in eight eyes by RTA where no treatment was necessary, as judged by clinical examination. Thus, sensitivity was 93% (mean) for detecting PDR and 100% for detecting macular edema, with a specificity of 58-96% depending on the grader. The RTA did not allow valid assessment due to poor image quality in only one case. CONCLUSIONS: Screening for diabetic retinopathy with a combination of wide-angle fundus photography and macular thickness mapping by an objective method, such as optical coherence tomography or the RTA, offers the prerequisites for establishing a successful tele-screening program.