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Purpose: To analyze changes in demographic parameters and retreatment patterns over a 10-year period in a clinical routine setting of infants with retinopathy of prematurity (ROP) requiring treatment documented in the German Retina.net ROP registry., Design: Multicenter, noninterventional, observational registry study recruiting patients treated for ROP., Subjects: A total of 692 eyes of 353 infants treated for ROP were documented in the Retina.net ROP registry over a 10-year period between 2011 and 2020. These cases cover about 15% of all infants treated for ROP in Germany., Methods: The Retina.net ROP registry was established in 2012 to jointly collect information on infants treated for ROP. The database collects information on demographic parameters (gestational age [GA], birth weight, neonatal comorbidities) as well as treatment parameters (type of treatment, weight and age at treatment, and stage of ROP). A total of 19 centers contributed to the analysis. This is the 10-year analysis of data from 2011 to 2020, in which we focus on changes over time regarding the respective parameters., Main Outcome Measures: Changes over time in demographic parameters and treatment patterns for ROP in Germany., Results: The overall incidence of treatment requiring ROP was 3.5% of all infants screened for ROP at participating centers. Gestational age, weight at birth, and weight at treatment remained stable over the 10-year period, whereas postmenstrual and postnatal age at treatment increased moderately but statistically significantly over the years. The most prevalent ROP severity stage at treatment was stage 3+ in zone II (76.6% of all treated eyes). Treatment patterns changed considerably from predominantly laser treatments in 2011 (75% of all treated eyes) to predominantly ranibizumab treatments in 2020 (60.9% of all treated eyes). The overall retreatment rate was 15.6%. Retreatment rates differed between initial treatment modalities (14.1% after laser coagulation, 12% after bevacizumab and 24.5% after ranibizumab). Treatment-associated systemic or ophthalmic complications were rare., Conclusions: This data analysis represents one of the largest documented cohorts of infants treated for ROP. The data on demographic parameters and treatment patterns provide useful information for further improvement of ROP management., Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (Copyright © 2023 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: The German Retina.net ROP registry and its Europe-wide successor, the EU-ROP registry, collect data from patients treated for ROP. This analysis compares input parameters of these two registries to establish a procedure for joint analyses of different registry data using exemplary datasets from the two registries., Methods: Exemplary datasets from the two databases over a 1-year period each (German Retina.net ROP Registry, 2011, 22 infants; EU-ROP Registry, 2021, 44 infants) were compared. The parameters documented in the two databases were aligned and analysed regarding demographic parameters, treatment modalities, complications within first 24 h and retreatments., Results: The current analysis showed that data can be aligned for joint analyses with some adjustments within the data structure. The registry with more detailed data collection (EU-ROP) needs to be reduced regarding granularity in order to align the different registries, as the registry with lower granularity determines the level of analyses that can be performed in a comparative approach. In the exemplary datasets, we observed that the overall most common ROP severity in both registries was zone II, 3+ (2011: 70.5%; 2021: 65%), with decreasing numbers of clock hours showing preretinal neovascularisations (2011: 10-12 clock hours in 29% of cases, 2021: 4-6 clock hours in 38%). The most prevalent treatment method was laser coagulation in 2011 (75%) and anti-VEGF therapy in 2021 (86.1%). Within the anti-VEGF group, all patients were treated with bevacizumab in 2011 and with ranibizumab in 2021. Retreatment rates were comparable in 2011 and 2021., Conclusion: Data from two different ROP registries can be aligned and jointly analysed. The analysis reveals a paradigm shift in treatment modalities, from predominantly laser to anti-VEGF, and within the anti-VEGF group from bevacizumab to ranibizumab in Germany. In addition, there was a trend towards earlier treatment in 2021., (© 2023 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

This study assessed barriers to testicular self-examination (TSE) performance in a population of US Modern Orthodox Jewish undergraduate students. Participants answered questionnaires that measured their TSE performance and their attitudes toward TSEs. Out of 541 participants, 301 (55.6%) had heard of TSEs, 177 (32.7%) had ever performed a TSE, and 21 (3.9%) performed TSEs once per month in the past year. Significant positive associations of TSE awareness and practice included self-efficacy and engagement with medical professionals vis-à-vis testicular health. Shame and adherence to certain religious beliefs negatively correlated with awareness and performance of TSEs. The results demonstrate medical professionals' integral role in educating young individuals about TSEs., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: To investigate whether vaccination against SARS-CoV-2 is associated with the onset of retinal vascular occlusive disease (RVOD)., Methods: In this multicentre study, data from patients with central and branch retinal vein occlusion (CRVO and BRVO), central and branch retinal artery occlusion (CRAO and BRAO), and anterior ischaemic optic neuropathy (AION) were retrospectively collected during a 2-month index period (1 June-31 July 2021) according to a defined protocol. The relation to any previous vaccination was documented for the consecutive case series. Numbers of RVOD and COVID-19 vaccination were investigated in a case-by-case analysis. A case-control study using age- and sex-matched controls from the general population (study participants from the Gutenberg Health Study) and an adjusted conditional logistic regression analysis was conducted., Results: Four hundred and twenty-one subjects presenting during the index period (61 days) were enrolled: one hundred and twenty-one patients with CRVO, seventy-five with BRVO, fifty-six with CRAO, sixty-five with BRAO, and one hundred and four with AION. Three hundred and thirty-two (78.9%) patients had been vaccinated before the onset of RVOD. The vaccines given were BNT162b2/BioNTech/Pfizer ( n = 221), followed by ChadOx1/AstraZeneca ( n = 57), mRNA-1273/Moderna ( n = 21), and Ad26.COV2.S/Johnson & Johnson ( n = 11; unknown n = 22). Our case-control analysis integrating population-based data from the GHS yielded no evidence of an increased risk after COVID-19 vaccination (OR = 0.93; 95% CI: 0.60-1.45, p = 0.75) in connection with a vaccination within a 4-week window., Conclusions: To date, there has been no evidence of any association between SARS-CoV-2 vaccination and a higher RVOD risk.

Retinal dystrophies (RD) are clinically and genetically heterogenous disorders showing mutations in over 270 disease-associated genes. Several millions of people worldwide are affected with different types of RD. Studying the relevance of disease-associated sequence alterations will assist in understanding disorders and may lead to the development of therapeutic approaches. Here, we established a whole exome sequencing (WES) pipeline to rapidly identify disease-associated mutations in patients. Sanger sequencing was applied to identify deep-intronic variants and to verify the co-segregation of WES results within families. We analyzed 26 unrelated patients with different syndromic and non-syndromic clinical manifestations of RD. All patients underwent ophthalmic examinations. We identified nine novel disease-associated sequence variants among 37 variants identified in total. The sequence variants located to 17 different genes. Interestingly, two cases presenting with Stargardt disease carried deep-intronic variants in ABCA4 . We have classified 21 variants as pathogenic variants, 4 as benign/likely benign variants, and 12 as variants of uncertain significance. This study highlights the importance of WES-based mutation analyses in RD patients supporting clinical decisions, broadly based genetic diagnosis and support genetic counselling. It is essential for any genetic therapy to expand the mutation spectrum, understand the genes' function, and correlate phenotypes with genotypes.

Background: At present minimum nursing staff numbers have been defined and are being implemented. In December 2019 the German Medical Association asked the German professional associations about their general experience with planning of medical personnel in hospital departments. As no structured data were available on this subject, the German Ophthalmological Society (DOG) founded a working group in March 2020 to answer this request., Method: In the course of several consensus meetings, the working group on personnel planning for physicians in hospitals of the DOG prepared a questionnaire on previous experiences in personnel planning of eye hospitals, which was sent to the heads of all university eye hospitals and departments of ophthalmology in Germany. The questionnaire consisted of individual items with fixed choices and free answers regarding the procedure and current situation of staffing as well as the range of tasks and organization of the medical service., Results: Out of 104 departments 53 (51%) responded, of which 25 were from university departments (64% response), 23 from departments of other public or non-profit ownership (46%) and 5 from departments with private hospital ownership (33%). Of these 49% stated that there was no transparent basis for calculation of the number of medical positions in their hospital. Of the surveyed departments, outpatient tasks, services and revenues were considered in the calculations in only 47%. There was a statistically significant higher ratio of full-time personnel to the numbers of beds in university departments compared to private and publicly owned non-profit institutions (p < 0.001, t‑test). All departments have to cope with multiple additional tasks in addition to clinical patient care, which are taken into account only to a limited extent in the staffing. Approximately 70% of the departments provide a 24 h/7 day (24/7) medical on-call service on site, 91% have a 24/7 surgery on-call service and 34% have a cooperation with emergency services run by the Association of Statutory Health Insurance Physicians., Conclusion: The results show how heterogeneously and nontransparent German departments of ophthalmology are staffed in terms of medical doctors. On average, university departments have higher personnel resources per hospital bed to cope with additional tasks in research and teaching. Outpatient tasks, which contribute significantly to the revenues of an eye department, and multiple other tasks are often not taken into account in the personnel calculation. A transparent and uniform basis for calculation of the medical staff of the departments is desirable in order to achieve a sufficient personnel staffing for a patient and employee-oriented working environment.

Background: Retinopathy of prematurity (ROP) is one of the main reasons for childhood blindness. The number of infants requiring treatment, however, is low for individual centers. The Retina.net ROP registry has been founded to allow a joint analysis of treatment patterns and courses post treatment., Objective: This paper reports treatment patterns over 5 years., Material and Methods: All infants born between January 2011 and December 2015 who were entered into the treatment registry by one of the 12 participating centers were analyzed., Results: The data of 150 infants (292 eyes) were analyzed and ROP 3+ in zone II was the most prevalent treatment indication. Gestational age and birth weight remained stable over the years. The treatment patterns, however, changed with anti-VEGF treatment (bevacizumab or ranibizumab) accounting for only 10% of treated eyes in 2011 but for 56% and 30% in 2014 and 2015, respectively. Almost all eyes with AP-ROP or zone I disease received anti-VEGF treatment. Zone II disease was predominantly treated with laser photocoagulation. Recurrences were more common and appeared later in the anti-VEGF group compared to the laser group (23%/interval 60 days vs. 17%/interval 23 days). Perioperative complications were evenly distributed across treatment groups., Conclusion: The data in this analysis represent about 10-15% of treated infants in Germany. The results provide evidence for an increasing use of anti-VEGF agents for ROP. The data reflect a selection bias for anti-VEGF treatment in eyes with a more aggressive disease. This needs to be considered when interpreting data such as disease recurrence rates. The risk for late recurrences after anti-VEGF treatment is of particular clinical significance.

Importance: Anti-vascular endothelial growth factor (VEGF) therapies are a novel treatment option in retinopathy of prematurity (ROP). Data on dosing, efficacy, and safety are insufficient., Objective: To investigate lower doses of anti-VEGF therapy with ranibizumab, a substance with a significantly shorter systemic half-life than the standard treatment, bevacizumab., Design, Setting, and Participants: This randomized, multicenter, double-blind, investigator-initiated trial at 9 academic medical centers in Germany compared ranibizumab doses of 0.12 mg vs 0.20 mg in infants with bilateral aggressive posterior ROP; ROP stage 1 with plus disease, 2 with plus disease, or 3 with or without plus disease in zone I; or ROP stage 3 with plus disease in posterior zone II. Patients were recruited between September 2014 and August 2016. Twenty infants were screened and 19 were randomized., Interventions: All infants received 1 baseline ranibizumab injection per eye. Reinjections were allowed in case of ROP recurrence after at least 28 days., Main Outcomes and Measures: The primary end point was the number of infants who did not require rescue therapy at 24 weeks. Key secondary end points included time-to-event analyses, progression of physiologic vascularization, and plasma VEGF levels. Stages of ROP were photodocumented and reviewed by an expert committee., Results: Nineteen infants with ROP were enrolled (9 [47.4%] female; median [range] postmenstrual age at first treatment, 36.4 [34.7-39.7] weeks), 3 of whom died during the study (1 in the 0.12-mg group and 2 in the 0.20-mg group). Of the surviving infants, 8 (88.9%) (17 eyes [94.4%]) in the 0.12-mg group and 6 (85.7%) (13 eyes [92.9%]) in the 0.20-mg group did not require rescue therapy. Both ranibizumab doses were equally successful in controlling acute ROP (Cochran-Mantel-Haenszel analysis; odds ratio, 1.88; 95% CI, 0.26-13.49; P = .53). Physiologic intraretinal vascularization was superior in the 0.12-mg group. The VEGF plasma levels were not systematically altered in either group., Conclusions and Relevance: This pilot study demonstrates that ranibizumab is effective in controlling acute ROP and that 24% of the standard adult dose (0.12 mg) appears equally effective as 40% (0.20 mg). Superior vascularization of the peripheral retina with 0.12 mg of ranibizumab indicates that the lower dose may be favorable. Unchanged plasma VEGF levels point toward a limited systemic drug exposure after ranibizumab., Trial Registration: clinicaltrials.gov Identifier: NCT02134457 and clinicaltrialsregister.eu Identifier: 2013-002539-13.

Purpose: The German retinopathy of prematurity (ROP) Registry collects data on treated ROP in a multicentre approach to analyse epidemiology and treatment patterns of severe ROP., Methods: Nine centres entered data from 90 treated ROP infants (born between January 2011 and December 2013) into a central database. Analysis included incidence rate of severe ROP, demographic data, stage of ROP, treatment patterns, recurrence rates, relevant comorbidities and ophthalmological or systemic complications associated with treatment., Results: Treatment rate for ROP was 3.2% of the screened population. The most frequent ROP stage at time of treatment was zone II, stage 3 +  (137 eyes). Treatment was bilateral in 97% of infants. Treatment patterns changed over time from 7% anti-vascular endothelial growth factor (VEGF) monotherapy in 2011 to 32% in 2014. Overall, laser treatment was the predominant treatment. However, all infants with zone I disease received anti-VEGF treatment. About 19% of infants required retreatment (16% of laser-treated and 21% of anti-VEGF treated infants). Mean time between first and second treatment was 3.8 weeks (± 11 days) for laser-treated and 10.4 weeks (± 60 days) for anti-VEGF-treated infants., Conclusion: This study is the first multicentre analysis of severe ROP in Germany. The identified treatment patterns find laser as the most prevalent form of therapy, with an increasing use of anti-VEGF therapy over recent years. Recurrence rates were relatively high overall with slightly higher recurrence rates and later recurrence times in the anti-VEGF group. Anti-VEGF was predominantly used for high-risk stages like AP-ROP and zone I disease., (© 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Purpose: To report anatomical and functional outcome of 20-gauge versus 25-gauge primary pars plana vitrectomy for management of complex rhegmatogenous retinal detachment in pseudophakic eyes., Methods: Prospective single-centre randomized comparative pilot trial. Fifty patients with retinal detachment (RD) not complicated by proliferative vitreoretinopathy grade B or C, who cannot be treated with a single meridional sponge, were randomized (1:1) from November 2006 to January 2010 to either 20-gauge or 25-gauge vitrectomy as first surgical intervention and followed up over a 12-month period, evaluating change in best-corrected visual acuity, anatomical success and intraocular pressure dysregulation., Results: Mean visual acuity improved by 0.88 (SD 0.67) from 1.22 logMAR (SD 0.63) to 0.34 logMAR (SD 0.31) in the 20-gauge group and by 0.53 (SD 0.91) from 0.86 logMAR (SD 0.73) to 0.34 logMAR (SD 0.46) in the 25-gauge group. Final anatomical success rate was 100% and primary success rate was 69% at 6 months of follow-up. In the 20-gauge group, the retina was attached after one single procedure in 18 eyes (72%) and in 21 eyes (84%) of the 25-gauge group. Two patients in the 25-gauge group had hypotony at the first postoperative day which normalized within 6 weeks., Conclusion: In our series, transconjunctival sutureless 25-gauge and 20-gauge vitrectomy showed comparable results in pseudophakic RD not suitable for single sponge surgery with respect to visual outcome and retinal reattachment. Postoperative hypotony does not seem to be a significant problem of transconjunctival sutureless vitrectomy., (© 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Purpose: Clinical evidence of retinal pigment epithelium (RPE) alterations after intra-arterial (IAC) and intravitreal chemotherapy (IViC) of retinoblastoma has been reported. We, therefore, investigated the cellular toxic effects of melphalan, topotecan and carboplatin on the RPE in a cell culture model., Methods: The effects of melphalan, carboplatin and topotecan on ARPE19 cell morphology were examined by phase contrast microscopy. Cell proliferation was quantified by BrdU incorporation, cell viability studied via MTS assays, and cell densities were estimated by Crystal Violet staining, and apoptosis induction studied via caspase 3/7-activity assays after a 24-hr incubation period. Staurosporine, media without fetal bovine serum, diluents of melphalan, carboplatin and topotecan were applied as positive and negative controls, respectively., Results: We observed a concentration-dependent increase in the number and size of gaps in the ARPE19 cell layer with each drug. There was a significant decrease in proliferative activity and cell viability of RPE cells as well as an increase in apoptosis after 24 hrs culture in media supplemented with melphalan and topotecan. Carboplatin had comparable effects on cell proliferation and cell viability; however, no significant apoptotic impacts were observed. The three cytostatic drugs had insignificant effects on cell density measurements., Conclusions: Morphological monitoring and toxicity assays indicate a direct toxic effect of melphalan and the other two cytostatic drugs on ARPE19 cells. Thus, a direct toxic effect of melphalan in vivo after IAC or IViC on the RPE seems probable and may explain the clinical and angiographic RPE alterations observed in some retinoblastoma patients., (© 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Background: Melphalan, as a treatment for retinoblastoma, has been applied intra-arterially by catheterisation of the ophthalmic artery or intravitreally, aiming to reduce systemic side effects of intravenous drug therapy. This study evaluates retinal toxicity of different melphalan concentrations measured by electroretinogram (ERG) in an isolated and perfused retinal whole mount culture., Methods: For functional testing, bovine retinas were prepared and perfused with an oxygen-saturated standard solution and the ERG was recorded until stable b-wave or a-wave amplitudes were reached. Thereafter, retinae were exposed to 80, 160 and 320 μg/ml of melphalan for 30 min. After exposure, a washout was performed thrice for 5 min each and the ERG amplitude recovery was monitored for 60 min. To investigate the effects on photoreceptor function, 1-mM asparate was added to suppress the b-wave and obtain isolated a-waves., Results: While no toxic effects for a concentration of 80 μg/ml were observed, both b- and a-waves were significantly reduced after application of 160 (b-wave 43.8 %, p = 0.03; a-wave 28.2 %, p = 0.04) and 320 μg/ml (b-wave 20.0 %, p = 0.04; a-wave 35.8 %, p = 0.02). For 320 μg/ml, this reduction remained significant at the end of the washout (b-wave 40.0 % p = 0.02; a-wave 26.4 %, p = 0.02)., Conclusions: Epiretinal or intraretinal concentrations of 80-μg/ml melphalan do not cause toxic effects in this in vitro model. Concentrations higher than 160 μg/ml should be avoided.

Background: To present a modified surgical technique in the treatment of retinal detachment secondary to advanced Coats' disease in children, and report on long-term anatomical and functional outcome., Methods: We analysed an interventional case series of 13 patients (13 eyes) with advanced Coats' disease characterised by retinal detachment in addition to massive subretinal exudates and vascular malformation. The presented patients underwent pars plana vitrectomy (PPV), including a modified technique of exocryotherapy applied after fluid-air exchange in order to achieve complete treatment of the vascular changes, to reduce associated side-effects, and to avoid retinectomy and silicone oil tamponade., Results: Within a median follow-up period of 37 months (range: 18-66 months), no enucleation was necessary. Four eyes (31 %) did not need any further therapy, and in nine eyes (69 %) additional treatments were performed. Six patients (46 %) required revisional surgery with silicone oil tamponade. In ten eyes (77 %), the pathologic vessels and exudates finally regressed and the retina reattached. Visual acuity (VA) could be stabilized in the majority of patients: in three eyes (27 %) VA improved, in four eyes (36 %) VA remained stable, in four eyes (36 %) visual acuity (VA) deteriorated, and in two eyes VA could not be evaluated., Conclusions: The presented modified technique allows for sufficient cryotherapy of vascular malformations, even in the presence of massive exudation, in a subset of patients with advanced Coats' disease, and thus may reduce surgery-related complications and improve the rehabilitation process of these young patients.

Purpose: Age-related macular degeneration (AMD) is the leading cause of visual impairment in Western nations. Since the discovery of the importance of vascular endothelial growth factor (VEGF) in the pathogenesis of neovascular AMD, anti-VEGF agents including pegaptanib, ranibizumab and bevacizumab provide a treatment option to improve vision in affected persons. VEGF Trap-Eye (Aflibercept) is a new agent available for the treatment of exudative AMD. The molecule is a receptor decoy with a longer half-life and a higher affinity to VEGF compared with ranibizumab or bevacizumab. The presented study has been designed to evaluate the short-term toxic effects of VEGF Trap-Eye on retinal function during and after direct exposure to the drug., Methods: Isolated bovine retinas were perfused with an oxygen-saturated nutrient solution, and the electroretinogram (ERG) was recorded using silver/silver chloride electrodes. A total of 0.5 mg or 2 mg VEGF Trap-Eye was added to the nutrient solution and retinas were exposed for 45 min, followed by a washout period of 100 min. The percentage of a- and b-wave reduction at the end of the washout was compared with the baseline values. Additionally, retinal whole mount cultures were exposed for 24 hr to VEGF Trap-Eye, and the amount of apoptotic cells were determined using the terminal deoxynucleotidyl transferase-mediated uridine 5'-triphosphate-biotin nick end labelling (TUNEL) assay., Results: During simulation of intraocular application, no significant reduction in the a-wave amplitude for 0.5 mg (2.70%, p = 0.37) and 2 mg (3.84%, p = 0.37) VEGF Trap-Eye and b-wave amplitude for 0.5 mg (19.68%, p = 0.17) and 2 mg (24.1%, p = 0.06) VEGF Trap-Eye was observed at the end of the washout. However, there were significant changes in a-wave and b-wave amplitudes directly after exposure to 0.5 mg VEGF Trap-Eye (18.4%, p = 0.004 and 43.1%, p = 0.006, respectively)., Conclusions: The presented data suggest that intraocular application of up to 2 mg VEGF Trap-Eye does not induce irreversible toxic retinal damage. However, short-term results showed a negative effect directly after the application for 0.5 mg and 2 mg VEGF Trap-Eye., (© 2013 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Purpose: To delineate and discuss a not yet described possible ocular complication of selective intra-arterial chemotherapy (SIAC) for treatment of retinoblastoma., Methods: A 23-month-old girl with a large unilateral retinoblastoma was treated with repeated SIAC using 5 mg melphalan between July 2010 and January 2012. Clinical course of tumor and further ocular changes after therapy and histopathologic findings are described., Results: In total, 5 SIAC were performed over a time period of 18 months. After the last SIAC, diffuse dense cataract prevented further funduscopy. In addition, anterior chamber seeding was obvious, leading to the decision to enucleate the eye. Histopathologically, nearly complete regression of the main tumor mass with prominent calcifications, but vital tumor seeding in the vitreous, on the lens surface, on the ciliary body, and in the anterior chamber, was observed. Peculiar vacuolation of the lens epithelial cells, liquefaction of the subepithelial lens fibers, and diffuse small vacuoles within the lens were striking., Conclusions: Repeated SIAC with melphalan may induce cataract formation, possibly as a toxic effect of the chemotherapeutic to the lens, maybe combined with radiation exposure during fluoroscopy. This ocular complication should be taken into consideration as a limitation of the number of feasible repeated treatments.

Background/aims: Vascular endothelial growth factor (VEGF) is a key factor in the pathogenesis of neovascular retinal diseases including age-related macular degeneration. VEGF inhibitors including ranibizumab, pegaptanib or bevacizumab improve retinal morphology and vision in many patients. The recently approved drug aflibercept (VEGF Trap-Eye/Eyelea, Regeneron, Tarrytown, New York, USA) offers a new therapy modality. We therefore tested for toxic and anti-proliferating effects of aflibercept., Methods: The effects of aflibercept (0.125, 0.5, 2 mg), ranibizumab (0.125 mg) and bevacizumab (0.3125 mg) after 1, 24, 48 and 72 h on cell morphology via phase contrast pictures, cell viability via MTS assay, total cell amount via crystal violet staining, apoptosis induction via caspase 3/7 assay and proliferation via BrdU assay were investigated. Three ocular cell lines were chosen for toxicology testing: ARPE19 cells, RGC-5 cells and 661W cells., Results: Aflibercept did not cause changes in cell morphology, induce apoptosis or cause permanent decrease in cell viability, cell density or proliferation in any cell line or concentration investigated. In general, aflibercept had fewer effects (upregulation or downregulation) compared with controls than bevacizumab or ranibizumab., Conclusions: In our experiments, aflibercept did not lead to any negative effects on retinal cell lines and might therefore be used safely in clinical applications.

Background: Congenital anterior staphyloma is a rare, complex malformation syndrome of the anterior segment. Only a few reports on associated systemic malformations have been published. We herein present a rare manifestation of congenital anterior staphyloma (CAS) combined with amniotic band disruption syndrome (ABS)., Patient and Methods: Shortly after birth, a massive enlargement of the left eye was observed in a female child. Furthermore, an extensive bilateral congenital cleft lip and cleft alveolar ridge with oblique facial cleft extending into the left medial canthal region, coloboma(s) of the left eyelids, extensive adhesions between lids and eye bulb, as well as circumferential grooves, clubfeet, and terminal transverse defects in both hands and feet were present. Due to severe progression of eye bulb protrusion with thinning of the sclera, enucleation of the left eye was performed at the age of 3 years in order to prevent complications including perforation of the globe and with the aim of improving cosmetic aspects., Results: Histopathological examination of the enucleated eye disclosed findings typical of congenital anterior staphyloma, including massive corneal staphylomatic deformation with superficial vascularization and elapsed corneoscleral margin, destruction of Bowman's layer, absence of Descemet's layer, corneal endothelium, and angle structures. The lens was only partially formed, and had mainly dissolved. The neural retina appeared normal. The optic nerve disc revealed a pronounced excavation. Facial clefts, lid colobomas, congenital constriction bands, and amputation of distal limbs match ABS. This malformation complex develops in early pregnancy, probably prior to 35 days post conception., Conclusion: This is the first report on an association of these two rare complex congenital malformations, congenital anterior staphyloma and amniotic band syndrome. The anterior staphyloma was unilateral, and related to facial clefts and lid coloboma in the area adjacent to the anterior staphyloma. Furthermore, the systemic deformities are clearly due to the amniotic bands, and the timing of the development of both complex malformations seems to be similar. All findings suggest that the presence of amniotic bands is a causative factor for all observed abnormalities including anterior staphyloma.

Retinopathy of prematurity is one of only few potentially blinding retinal diseases of infancy amenable to prevention of visual loss by appropriate and timely therapeutic measures. Retinal ablative therapies, such as laser coagulation eliminate the disease-causing secretion of vascular endothelial growth factor (VEGF) by the avascular peripheral retina. Blockage of VEGF activity by intravitreal administration of VEGF-inhibitory drugs has likewise proven effective in recent clinical studies. Advanced stages of the disease may require surgical intervention. Knowledge of indications and techniques of the different currently available treatment options is crucial to ensure an optimal visual outcome for the affected children.

Retinopathy of prematurity (ROP), like other angioproliferative retinal disorders, has witnessed the advent of anti-VEGF therapy in clinical practice. The first report from the BEAT-ROP study published in 2011 represents the first comparison of anti-VEGF therapy versus conventional laser treatment in a randomised controlled trial. This review article investigates these novel aspects of ROP therapy from a pathophysiological angle and delineates the stages of ROP in which anti-VEGF treatment appears as a reasonable option. Furthermore, the novel chances of anti-VEGF therapy are being weighed against some still unanswered questions and novel study concepts are being presented., (Georg Thieme Verlag KG Stuttgart · New York.)

Purpose: To identify the genetic defect in a four-generation Croatian family presenting with autosomal dominant cataract., Methods: Genome-wide linkage analysis with 250K single nucleotide polymorphism (SNP) arrays was performed using DNA from one unaffected and seven affected individuals. Mutation screening of candidate genes was performed by bidirectional Sanger sequencing., Results: Evidence for linkage was observed for eight genomic regions. Among these was a locus on chromosome 22 which encompasses the β-crystallin gene cluster. This cluster includes four genes, namely beta-crystallin B1 (CRYBB1), beta-crystallin B2 (CRYBB2), beta-crystallin B3 (CRYBB3), and beta-crystallin A4 (CRYBA4). A novel sequence variant was found in the CRYBB2 gene (p.Arg188His). This variant cosegregated with the disease phenotype in all affected individuals but was not present in the unaffected family members and 100 healthy control subjects., Conclusions: We report a novel missense mutation, p.Arg188His, in CRYBB2 associated with congenital cataract in a family of Croatian origin. This variant is the most COOH-terminal missense mutation in CRYBB2 that has been identified so far.

Purpose: We aimed to evaluate the longterm effects of intraocular bevacizumab (Avastin) injections as adjuvant treatment in patients with neovascular glaucoma., Methods: Twenty eyes of 18 consecutive patients with secondary neovascular glaucoma caused by proliferative diabetic retinopathy (n = 7), ischaemic central retinal vein occlusion (n = 7), ischaemic ophthalmopathy (n = 2) and retinal ischaemia resulting from persistent detachment (n = 2) were treated with intraocular bevacizumab injections (1.25 mg/0.05 ml) in addition to other treatments. The main outcome measure was the change in degree of iris rubeosis. Secondary outcomes included intraocular pressure (IOP), best corrected visual acuity (BCVA) and numbers of additional interventions or antiglaucoma medications administered after injection., Results: Mean (+/- standard deviation) follow-up was 67.7 +/- 13.8 weeks (range 50-93 weeks). At the last follow-up, complete regression of rubeosis was detectable in five (20%) eyes, incomplete regression in seven (35%), stabilization in six (30%), and an increase in two (10%) eyes. Mean IOP was 26.0 +/- 8.9 mmHg at baseline and significantly decreased to 14.75 +/- 5.3 mmHg at the last follow-up visit (p = 0.000005). Mean baseline BCVA (logMAR [logarithm of the minimum angle of resolution] 1.43 +/- 0.89) was stabilized during the follow-up period (logMAR 1.5 +/- 0.98). Patients received an average of 2.75 injections. Additional treatments were laser photocoagulation in 13 (65%) eyes, cyclodestructive procedure in 14 (70%), cryopexy in six (30%), drainage procedures in two (10%), and vitrectomy in five (25%) eyes., Conclusions: Bevacizumab may be beneficial as adjuvant treatment in neovascular glaucoma because of its anti-angiogenic properties and its ability to prevent establishment or progression of angular obstruction. The causative disease inducing the angiogenic process requires treatment in all cases. Antiglaucoma treatment is needed in cases of persistent elevated IOP.

The presented Z-suture is a simple, rapid and safe knotless technique that facilitates transscleral suture fixation of various intraocular implants in the ciliary sulcus, such as sutured intraocular lenses, artificial iris prostheses and iris diaphragms. As the knotless approach reliably avoids suture erosion, external fixation can be performed without any protecting scleral flaps or lamellar grooves. The needle is simply passed through the sulcus and the emerging polypropylene suture is secured in the sclera using a zigzag-shaped intrascleral suture (Z-suture). Each pass starts directly adjacent to the exiting site. Five passes are sufficient to reliably fix the suture so that it resists even maximum tractive forces. Once this procedure is done, the suture can be cut without any knot. By avoiding suture knots, and hence the need for intrascleral flaps, this knotless approach may help to reduce suture-related complications such as scleral atrophy, suture erosion and infections.

Background: To report a case of nonarteritic anterior ischemic optic neuropathy (NA-AION) following intravitreal injection of bevacizumab (Avastin)., Methods: Interventional case report with an 18-month follow-up., Results: A 51-year-old male with pseudoxanthoma elasticum presented with NA-AION 2 weeks after treatment with intravitreal of bevazicumab (Avastin) for choroidal neovascularisation secondary to angioid streaks. Except from a small optic disc without cupping he did not show further risk factors., Discussion: Risk of NA-AION should be taken into consideration when deciding for intravitreal application of drugs including anti-vascular endothelial growth factors (VEGF) agents like bevacizumab (Avastin) in the treatment of retinal vascular diseases.

This article examines the differential effects of changes in family formations on men's and women's economic vulnerability. The motivating question is whether investments in education provide sufficient resources to escape the risk of poverty in the low-income sector or if changes in household characteristics are more important determinants of one's living standard. Changes in household characteristics are defined in terms of partners' entry into and exit from households and partners' different labour market profiles. The analysis focuses on households in the low-income sector in Germany, a population that is at high risk of poverty in a social welfare state that is expected to mitigate the effects of changes in family formation independent of gender. Findings from panel regression analysis demonstrate that women, in contrast to men, benefit economically as much as or more from investing in traditional family formations than in their own labour market position. This is especially the case for women with lower levels of education.

Background: Indocyanine green-assisted internal limiting membrane (ILM) peeling was suspected to disrupt the innermost layer of the neural retina. We examined whether surgically excised specimens contain remnants of neuronal tissue., Methods: Ten patients with macular hole underwent pars plana vitrectomy and indocyanine green-assisted ILM peeling. A total of 0.1 mL of a 0.5% indocyanine green solution was applied for 15 seconds. The ILM specimens were prepared for immunohistochemistry, using a polyclonal antibody against protein gene product 9.5. Protein gene product 9.5 is a pan-neuronal marker labeling human neuronal cells. Appropriate controls to show selectivity of the antibody were performed on neuronal tissue of donor eyes. One ILM was prepared for electron microscopy., Results: A selective expression of protein gene product 9.5 was found in neuronal fibers of the retina and optic nerve of donor eyes. Only 1 of the 10 surgical ILM specimens showed a minimal focal positivity for protein gene product 9.5. No neuronal tissue was detected on the ILM by electron microscopy., Conclusion: Focal expression of protein gene product 9.5 in only 1 of 10 surgical ILM specimens argues against a general indocyanine green-related disruption of the innermost retinal layers. However, higher concentrations of the dye, longer incubation times or different solvents than used in this study may lead to different results.

Purpose: To evaluate the release kinetics, biocompatibility and antiproliferative potential of a concentrated hydrophilic steroid formulation from commercially available sodium hyaluronate gels as a potential adjunct in glaucoma surgery., Methods: Dexamethasone and sodium hyaluronate 1% (Healon) and sodium hyaluronate 2.3% (Healon 5) were mixed to yield sodium hyaluronate formulations containing dexamethasone in concentrations of 4-20 mg/ml (7.7-38 mm). Non-cumulative and cumulative release into balanced salt solution (BSS) or phosphate buffered saline (PBS) was measured spectrophotometrically over 2-6 days. For cytotoxicity assays, human tenon fibroblasts (HTFB) and human retinal pigment epithelium cells (ARPE19) were cultured in a serum-deficient medium to ensure a static milieu; 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazoliumbromide (MTT) assay and Live/Dead cell-mediated cytotoxicity assay were used to exclude cytotoxicity. Cellular proliferative activity was monitored by 5'-bromo-2'-deoxyuridine (BrdU)-incorporation into cellular DNA., Results: The release kinetics from sodium hyaluronate 1% and 2.3% were almost identical. Steady state was achieved after approximately 44 hrs in non-cumulative measurements. The release plotted as a function of the square root of time was consistent with a largely diffusion-controlled release system. No cytotoxicity could be observed. Dexamethasone-loaded sodium hyaluronate showed a significant antiproliferative effect on HTFB and ARPE19 cells., Conclusion: Dexamethasone-loaded sodium hyaluronate shows extended release of steroid over almost 2 days in concentrations high enough to inhibit the proliferation of HTFB and RPE cells without evoking cytotoxic effects. Thus, this formulation may be an easy-to-prepare adjunct in glaucoma surgery or other procedures in which cellular growth inhibition is desired.

Purpose: To investigate the vitreous levels of bevacizumab and vascular endothelial growth factor-A (VEGF-A) after intravitreal injection of the drug in patients with choroidal neovascularization (CNV)., Design: Interventional case series., Participants: Eleven eyes of 11 patients with submacular hemorrhage and CNV due to age-related macular degeneration (n = 10) or angioid streaks (n = 1)., Methods: All patients were treatment naïve except for a single dose of intravitreal injection of bevacizumab (1.25 mg/50 muL dose) and subsequent vitrectomy after various intervals (1-101 days) because of active and progressive lesion. Intravitreal free bevacizumab and VEGF-A levels were measured using enzyme-linked immunosorbent assay and microsphere-based immunoassay, respectively. Vitreous VEGF-A isoforms were analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis and Western blotting., Main Outcome Measures: Intravitreal bevacizumab and VEGF-A levels were measured and pharmacokinetic parameters were calculated., Results: Pharmacokinetics of intravitreal bevacizumab followed a 2-compartment model with initial and terminal half-lives of 0.5 and 6.7 days, respectively. Bevacizumab could be detected in all cases, ranging from 2.63 ng/ml to 165 microg/ml. The peak concentration was observed on the second day after intravitreal bevacizumab injection. Vitreous free VEGF-A levels ranged from 0.2 to 33.9 pg/ml and showed a negative correlation with the bevacizumab concentration (P<0.001; r = -0.955) and a positive correlation with time (P<0.001; r = 0.964). However, the percentage expression of VEGF-A(165) exhibited a positive correlation with the bevacizumab concentration (P = 0.032, r = 0.645) and a negative correlation with time (P = 0.007, r = -0.755). A time-dependent increase was found for the percentage expression of VEGF-A(189) (P = 0.023, r = 0.673). Neither bevacizumab- nor time-related alterations were found for VEGF-A(121)., Conclusions: Based on pharmacokinetics, the interval of 6-7 weeks would be appropriate for efficacy, although clinical trials should guide dosing recommendations. Vitreous levels of free VEGF-A showed a negative correlation with the bevacizumab concentration, which confirmed the in vivo binding affinity of bevacizumab to VEGF-A. The analysis of the VEGF-A isoforms suggests differences of interaction between bevacizumab and individual VEGF-A isoforms.

Purpose: To describe the efficacy of intravitreal bevacizumab (Avastin) in patients with cystoid macular edema (CME) after cataract surgery (Irvine-Gass syndrome)., Methods: This retrospective case series comprised 16 eyes of 16 patients with CME after cataract surgery refractory to current standard treatment who received an injection of 1.25 mg intravitreal Avastin. The main outcome measures were visual acuity, retinal thickness on optical coherence tomography (OCT), and complications related to treatment., Results: The median duration of CME before treatment with intravitreal Avastin was 14 weeks (range 3 to 84 weeks). Although the mean retinal thickness decreased slightly after intravitreal Avastin, the mean visual acuity remained unchanged. Visual acuity improved by 2 Early Treatment Diabetic Retinopathy Study lines in 1 patient, remained unchanged in 12 patients, and decreased by 2 lines in 2 patients. Repeated Avastin injections did not result in a better outcome. Other than mild ocular irritation, there were no adverse effects of the intravitreal injections., Conclusions: Intravitreal injection of Avastin, although safe, did not result in improved visual function in patients with postoperative CME. In contrast to findings in a previous case report, the beneficial effect of vascular endothelial growth factor inhibition in Irvine-Gass syndrome was not observed.

Objective: To assess long-term functional and morphological changes after macular translocation in patients with exudative age-related macular degeneration., Methods: Evaluation of a noncomparative cohort study of 90 patients with a follow-up of 14 to 79 months (mean, 38.2 months)., Results: Visual acuity increased by 3 or more lines in 15 patients, remained stable in 35 patients, and deteriorated in 40 patients at final examination. Pigment epithelium atrophy extending to the new fovea was detected in 44 patients; in 25 patients this new atrophy was associated with loss of visual function., Conclusions: Long-term follow-up of macular translocation with 360 degrees retinotomy showed stabilization or improvement in half of the patients. Progressive atrophy of the pigment epithelium represented one major limiting factor of the beneficial effect of the treatment. Macular translocation may be an option for cases of exudative age-related macular degeneration that are not eligible for or do not respond to alternative treatments.

Purpose: To study the corneal biocompatibility of bevacizumab on various cultured human corneal cells., Methods: Cell cultures of corneal keratinocytes (CKs), corneal fibroblasts (CFs), and corneal endothelial cells (CECs) were harvested from human donor eyes and exposed to various concentrations of bevacizumab (0.25-5.0 mg/mL). Cell viability was assessed by using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay at days 1 and 4 after exposure. For cytotoxicity testing, confluent cells were cultured in serum-depleted medium, and the MTT test was performed after 24 hours of incubation. Expression of vascular endothelial growth factor (VEGF), VEGF receptors (VEGFR1 and VEGFR2), keratan sulphate (KS), and cytokeratin-3 (AE5) was studied by immunohistochemistry. Live/dead viability/cytotoxicity assay was performed and analyzed by fluorescence microscopy after 24 hours of incubation. Cell morphology was assessed with a phase-contrast microscope after 7 days of exposure with different concentrations of bevacizumab (0.25-5.0 mg/mL), and signs of cellular damage were assessed., Results: No cytotoxic effect of bevacizumab on CKs, CFs, and CECs could be observed when used at a concentration of 5.0 mg/mL or lower. Bevacizumab-treated cells showed no signs of cellular damage compared with the control. CKs, CFs, and CECs stained positively for VEGF, VEGFR1, and VEGFR2. CKs and CECs stained positively for AE5, whereas CFs were immunopositive for KS., Conclusions: Bevacizumab is not toxic to corneal cells of human origin in vitro at doses usually used for treatment of corneal neovascularization, which is 20-fold higher than that used for intravitreal application.

Objective: To report the functional and morphological outcome of surgical treatment of peripapillary choroidal neovascularisation due to age-related macular degeneration., Methods: Consecutive interventional case series of eight patients with extensive peripapillary choroidal neovascularisation and accompanying haemorrhage who underwent subretinal surgery including extraction of the neovascular complex. Ophthalmic examination, including visual acuity testing, colour photography and fluorescein angiography, was performed at baseline and at 3, 6, 9 and 12 months, and then yearly., Results: Mean follow-up was 26 months (12-60 months). Preoperative best corrected visual acuity (BCVA) ranged from logMAR (logarithm of minimum angle of acuity) 1.0 (20/200) to logMAR 0.0 (20/20), with a mean of logMAR 0.5 (20/63). Mean postoperative BCVA was logMAR 0.3 (20/40). BCVA improved in six patients, was stable in one patient and deteriorated in one patient. Two years after surgery, one patient developed recurrence of the CNV that was removed surgically. One patient showed retinal detachment 5 years after subretinal surgery., Conclusions: In this small case series of PPCNV, functional improvement was achieved after surgery in the majority of patients. Surgical extraction of the CNV represents an alternative treatment option in eyes with vision-threatening extensive PPCNV. Randomised controlled studies seem to be justified to evaluate further the beneficial effect and long-term functional outcome of this therapy approach.

Background: The purpose of this study was to compare full macular translocation (FMT) with photodynamic therapy (PDT) in the treatment of neovascular age-related macular degeneration (AMD)., Methods: In a prospective, randomised, non-masked, mono-center, pilot-trial, 50 eyes of 50 patients were assigned to either FMT or PDT. Baseline and control examinations in 3-monthly intervals over a 12-month period included standardized protocol refraction, visual acuity testing and fluorescein angiography. Primary outcome measurements were made to establish the change in distant visual acuity from the baseline to the 12-month examination. The statistical analyses were carried out on the intent-to-treat principle., Results: The improvement of one or more ETDRS lines was 56% (14/25) of the eyes in the FMT and 16% (4/25) of the eyes in the PDT arm (P = 0.007). Twenty eyes (80%) in the FMT and 16 eyes (64%) in the PDT group had less than three ETDRS lines of vision loss (P = 0.35). Retinal detachment (six eyes) and diplopia (five patients) were recorded in the FMT group. None of the eyes treated in the FMT group had phtysis., Conclusion: This pilot study showed that no statistically significant difference existed between the FMT and PDT in terms of the vision loss of less than three ETDRS lines in eyes with neovascular AMD. The chance of vision improvement was significantly higher for the patients in the FMT group. However, in the era of promising therapy with anti-vascular endothelial growth factor for neovascular AMD, FMT should not be offered as a standard primary procedure for neovascular AMD.

Background: The purpose of the study is to report data on short-term safety of intravitreal bevacizumab treatment and its effect on visual function, central retinal thickness, and angiographical changes of occult choroidal neovascularization due to age-related macular degeneration., Methods: A consecutive interventional case series of 30 patients with active subfoveal occult choroidal neovascularization secondary to age-related macular degeneration was followed after one intravitreal injection of 1.25 mg bevacizumab at baseline and subsequent injections following standardized criteria. At baseline and follow-up visits patients had visual acuity assessment, intraocular pressure measurement, fluorescein angiography, and optical coherence tomography imaging., Results: No serious ocular or systemic adverse events were identified. A significant increase of intraocular pressure or signs of retinal toxicity or endophthalmitis were not detected in any patient. Optical coherence tomography revealed significant decrease (p < 0.001) in central retinal thickness after 1 week, 4 weeks, and 12 weeks, respectively. Fluorescein leakage decreased within 1 week and improvement was maintained at week 12 in the majority of patients. Visual acuity improved or remained stable in 29 of 30 patients; improvement of 3 or more lines was seen in 14 of 30 patients; one patients showed improvement of 6 lines. No patient had severe vision loss of 6 lines or more; moderate vision loss of 3 lines was seen in one patient. Re-injections of bevacizumab according to standard criteria were performed one to two times during the follow-up period of 12 weeks with a re-injection interval of 4 to 18 weeks (median 8 weeks)., Conclusions: Short-term results suggest that intravitreal injection of bevacizumab is well tolerated and for the majority of patients with occult choroidal neovascularization in AMD results in improvement of visual acuity, decrease in central retina thickness, and reduction of angiographic leakage of the lesion. Bevacizumab as intravitreal treatment may provide a novel therapeutic option for selected patients with exudative AMD. Randomized prospective multicenter trials seem justified to further evaluate long term effects and impact of intravitreal bevacizumab on different subtypes of AMD compared to established therapies.

Purpose: To report a corneal transplant complication associated with intracameral recombinant tissue plasminogen activator (rTPA) treatment of postoperative fibrin reaction., Methods: In a 71-year-old patient, a triple procedure was performed for perforated rheumatic ulcer and secondary cataract., Results: A dense band keratopathy developed rapidly within 36 hours after the use of intracameral injection of rTPA for the treatment of a dense fibrin clot., Conclusions: This is the first report of rapid development of massive band keratopathy in a corneal graft after triple procedure and treatment with intracameral rTPA. Intracameral rTPA should be used with caution in patients with attenuated endothelium.

Purpose: To evaluate the long-term outcome of pars plana vitrectomy and primary silicone oil tamponade in patients with severe intraocular foreign body (IOFB) injuries and high risk of proliferative vitreoretinopathy (PVR)., Methods: This retrospective consecutive study included 23 patients with severe IOFB injuries who had extensive lacerations including sclera, choroid, and retina, and were complicated by predictive factors for elevated proliferative activity and an unfavorable outcome. All patients underwent pars plana vitrectomy, removal of the IOFB, and primary silicone oil tamponade and were followed up for a mean 8.9 years. Main functional outcome was assessed as final best-corrected visual acuity. Anatomic success was defined as permanent retinal attachment., Results: PVR occurred in 70% of all eyes and required 16 revisions. Silicone oil was removed in 78% of the eyes after a mean tamponade duration of 9.1 months. Complete retinal attachment was achieved in 83% of the eyes. Three eyes developed a persisting hypotony that was stabilized under permanent silicone oil. Functional stabilization was observed in the third year resulting in a final visual acuity of 20/630. Useful vision of better than 20/400 could be preserved in 55% of the patients. Only one eye underwent a late enucleation after 6.8 years., Conclusions: Primary silicone oil stabilizes the retina during the critical period of active PVR and may limit the visual loss in selected high-risk eyes in the long term.

Background: The aim of the present study was to evaluate potential electrophysiological changes after 360 degrees retinotomy and macular translocation for subfoveal choroidal neovascularisation in patients with age-related macular degeneration., Methods: A consecutive series of 32 patients suffering from subfoveal choroidal neovascularisation secondary to age-related macular degeneration underwent 360 degrees retinotomy and macular translocation. The scotopic triple-flash ERG (TERG) served as the main parameter of the study and was recorded one day prior to the translocation surgery and no earlier than 4 weeks after the silicone oil removal., Results: The TERG amplitudes were significantly reduced after translocation surgery. Depending on the applied flash luminance the mean amplitude reduction of the first b-wave varied between 67 % (0.2 cds/m (2)) and 74 % (0.03 cds/m (2)). The latency of the second b-wave of the preoperative TERG proved to have predictive power with reference to the postoperative visual acuity. A statistically significant correlation between the latency of the second b-wave for a flash intensity of 0.03 and 0.1 cds/m (2) and the postoperative visual acuity was shown (p = 0,016 and p = 0,049)., Conclusions: In accordance with previous studies the present study indicates that a significant electrophysiological decrease is caused by surgical procedures associated with macular translocation. In future, due to predictive parameters of the TERG the preoperative selection of patients could be improved.

Background: Cutis marmorata telangiectatica congenita is a rare, cutaneous and vascular anomaly characterised by congenital cutis marmorata, telangiectasis, and phlebectasia. Systemic abnormalities are frequently associated with this condition, although they may be highly variable. Ocular abnormalities are quite rare and include retinal detachment and congenital glaucoma. If glaucoma is present it is unilateral in most cases., Case Report: A case of bilateral congenital glaucoma associated with cutis marmorata telangiectatica congenita in a 4-month-old girl is presented. Follow-up and treatment over a four-year period are reported., Conclusion: Congenital glaucoma is a rare ophthalmic condition encountered in patients with cutis marmorata telangiectatica congenita. If glaucoma is present it is most likely unilateral, although cases of bilateral glaucoma in these patients occur. Regular ophthalmological examinations are recommended for children with cutis marmorata telangiectatica congenita--especially if characteristic skin changes are present in the face.

Purpose: Retinal diseases are often accompanied by changes in the structure of the multilayered extracellular matrix underlying the retina, Bruch's membrane (BrM). These structural revisions potentially lead to alterations in retinal pigment epithelium (RPE) adhesion, likely via modification of interactions with extracellular matrix (ECM) proteins including laminins in BrM. The purpose of this study was to identify specific laminins in BrM and their receptors in RPE cells., Methods: The laminin composition of BrM was determined using biochemical, molecular biological, and immunohistochemical techniques of rat, bovine, and human tissue and cell lines. An adhesion assay was used to test RPE attachment to laminins and the receptors used for this attachment., Results: BrM contained laminin chains that could form laminin heterotrimers including laminins 1, 5, 10, and 11. RPE cells synthesized these laminin chains in vitro. Therefore, RPE cells may synthesize BrM laminins. The RPE cells preferentially adhered to potential BrM laminins. Although the cells adhered to the BrM component collagen IV, these cells preferentially adhered to laminins. Of the laminins tested, the RPE cells adhered preferentially to laminin 5. The cells interacted with these laminins via specific integrins and attained a different morphology on each laminin. In particular, the RPE cells rapidly attached and flattened on laminin 5., Conclusions: BrM contains specific laminins, and RPE cells express integrin receptors for those laminins. The interaction of these specific laminins and integrins most likely leads to differential behavior of RPE cells.

Purpose: Artificial retinal detachment is increasingly used in submacular surgery. However, overcoming physiological retinal adhesiveness by subretinal fluid injection is suspected to cause cellular damage and thus to limit visual rehabilitation. This experimental study was designed to examine the ultrastructural changes induced by retinal detachment under vitrectomy conditions and to evaluate factors that reduce adhesiveness and minimize cellular damage., Methods: Twenty-one pigmented rabbits underwent vitrectomy, and the vitreous cavity was perfused for 10 minutes with various solutions. These included variations in osmolarity (314 and 500 mOsM), Ca(2+) ion concentration (Ca(2+)-supplemented, low Ca(2+), active Ca(2+) deprivation via 1 mM EDTA), temperature (19 degrees C and 34 degrees C), and ischemia (5 minutes). Nonvitrectomized eyes served as the control. Consecutively, an artificial bleb detachment was created underneath the visual streak by injecting 1 mL of buffered saline solution subretinally. Eyes were enucleated within 3 minutes, fixed with 2% glutaraldehyde/0.1 M cacodylate buffer (pH 7.4) containing 100 mM sucrose and processed for transmission electron microscopy and scanning electron microscopy., Results: If a Ca(2+)-containing standard solution was used during vitrectomy, retinal adhesiveness was strong, and a forced bleb detachment caused substantial cellular damage characterized by swollen and fragmented photoreceptor outer segments and disruption of retinal pigment epithelial cells. Use of a Ca(2+)-free solution moderately reduced the adhesive strength with consequently less ultrastructural damage. Active Ca(2+)-deprivation further reduced the retinal adhesion, but may have induced damage as suggested by intracellular vacuolization. Hyperosmolarity and ischemic conditions had toxic effects on both the photoreceptors and RPE cells. In contrast, the use of a preheated Ca(2+)-free solution (34 degrees C) substantially reduced retinal adhesiveness under vitrectomy conditions and hence ultrastructural damage., Conclusions: Artificial retinal detachment causes substantial ultrastructural damage in eyes with physiological retinal adhesiveness if performed under vitrectomy conditions similar to surgery in humans. The use of a preheated Ca(2+)-free physiologic saline solution seems to be suitable to reduce retinal adhesion sufficiently, without causing significant cellular damage.

The aim of the study was to evaluate the antiproliferative and cytotoxic properties of triamcinolone acetonide (TA) on human retinal pigment epithelium cells (ARPE19) and the role of epicellular crystalline deposits. Monolayer cultures of ARPE19 cells were used. Purified or unpurified crystalline TA suspension (0.01-1.0 mg/ml) or the vehicle alone (benzyl alcohol, 0.025%-0.00025%), diluted in culture medium, were added to the cells that were either grown on cell culture dishes covered by a protecting membrane filter insert or without a filter. After 1, 3, 5 and 7 days mitochondrial activity was measured using the MTT assay and the morphology assessed microscopically. Cellular proliferative activity was monitored by BrdU-incorporation into cellular DNA. For cytotoxicity assays ARPE19 cells were grown to confluence and then cultured in a serum-deficient medium to ensure a static milieu. Annexin V-FITC and propidium iodide co-staining was performed and analyzed by flow cytometry. Exposure to TA without direct cellular contact showed a moderate antiproliferative activity resulting in a dose-dependent suppression of DNA synthesis (maximum 42.7%), but not a cytotoxic effect. In contrast, adherent deposits of crystalline TA particles on top of the cell layer caused a rapid-progressive and dose-dependent cell death preceded by an early phosphatidylserine externalization to the outer leaflet of the plasma membrane. Within a healthy, confluent cell layer the number of viable cells decreased by 14.2, 20.8 and 68.8%, respectively, after one day of direct exposure. Exposure to the vehicle alone caused only a slight growth inhibitory effect in a proliferating cell layer, but early signs of cell death were detected even at the lowest concentration tested. In conclusion, the effect of the vehicle is less pronounced than formerly assumed, but not negligible, thus indicating a beneficial effect of purification. While non-adherent TA, if purified, appears to be safe in clinically used concentrations, direct physical contact with crystalline particles might cause a local, rapid-progressive cytotoxicity that involves the induction of the apoptotic cascade. Therefore, epiretinal deposits after intravitreal TA administration might be critical in terms of long-term biocompatibility.

Purpose: Amniotic membrane transplantation has become an important treatment option for corneal surface reconstruction. However, suture fixation of the transplant has various disadvantages like corneal irritation, scarring, graft loss due to membrane shrinkage, and the need for subsequent suture removal. Replacement of sutures by bioadhesives might be an advantageous alternative. This controlled study was designed to evaluate a new sutureless technique for amniotic membrane fixation onto the corneal surface by using fibrin glue., Methods: Standardized disks of cryopreserved amniotic membranes were transplanted onto the deepithelialized cornea of 12 rabbits using either conventional suture fixation or a new fibrin glue technique. The rabbits were followed-up with slit-lamp examination and fluorescein staining until epithelialization was completed. Consecutively, the rabbits were killed and the eyes processed for histology and immunohistochemistry for cytokeratin-3., Results: All membranes of both groups stayed in place throughout the follow-up time and showed a progressive graft epithelialization that was completed after 12 days. Whereas suture-fixated membranes showed progressive tissue shrinkage, fibrin-glued sheets remained unaltered. In the bioadhesive group, histology revealed a smooth fibrin layer in the graft-host interface and a continuous, stratified layer of cytokeratin-3 expressing corneal epithelial cells on the membrane surface. In contrast, suture-fixated membranes showed contracted and prominent membrane edges with epithelial ingrowth into the submembrane interface., Conclusion: Our results demonstrate the general feasibility of reproducible and reliable sutureless amniotic membrane fixation onto the corneal surface in rabbits. Stable adherence is maintained until epithelialization is completed. The sutureless technique gives sufficient manipulation time for the sheet before the final cross-linking process is completed. Furthermore, several advantageous characteristics could be demonstrated as increased biocompatibility, better epithelialization pattern and the lack of membrane shrinkage.

Objective: To report the functional and anatomical outcome of 20 patients who underwent surgical removal of choroidal neovascularization combined with transplantation of autologous iris pigment epithelial cells to the subretinal space 3 years after treatment., Methods: Freshly isolated autologous iris pigment epithelial cells were translocated to the subretinal space in 20 patients after membrane extraction. Patients were followed up by funduscopy, angiography, microperimetry, and visual acuity testing., Results: After a follow-up of 3 years, 1 patient showed improved visual acuity, 13 patients retained stable visual acuity, and 3 patients had reduced visual acuity. No macular edema or recurrent choroidal neovascularization was apparent at any time during the follow-up., Conclusions: Transplanted autologous iris pigment epithelial cells were well tolerated for 3 years and stabilization of visual acuity was achieved in most patients. These results suggest that iris pigment epithelial cells may serve as a substitute for retinal pigment epithelial cells after choroidal neovascularization removal in patients with exudative macular degeneration; however, whether these cells will be of any value for the restoration of vision and possible protection against choroidal neovascularization recurrence awaits further clinical observation and additional research.

Purpose: The controlled orientation of subretinal or intraretinal delivery of delicate tissue sheets is a critical problem in retinal transplantation research., Methods: A surgical device (explant injector) was designed and built for the controlled delivery of tissue explants into the subretinal or intraretinal space via a vitrectomy approach. The technical feasibility was demonstrated in enucleated porcine eyes., Results: Using negative pressure, the injector allows for the fixation of an explant, such as a monolayer of cells cultured on a collagen membrane, on the carrier platform. The sheet can then be placed safely without loss of orientation in the subretinal space., Conclusions: With the aid of the explant injector, it is possible to deliver an explant with the proper orientation to a precise location in the subretinal space.