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Bianka Sobolewska,1 Muhammed Sabsabi,1 Focke Ziemssen2,3 1Center for Ophthalmology, Eberhard- Karls University, Tuebingen, Germany; 2University Eye Hospital, Center for Ophthalmology, University of Tübingen, Tuebingen, Germany; 3Department of Ophthalmology, University Hospital Leipzig, Leipzig, GermanyCorrespondence: Bianka SobolewskaCenter of Ophthalmology, Eberhard-Karls University, Elfriede-Aulhorn-Straße 7, Tuebingen, 72076, GermanyTel +49 7071 29-88088Fax +49 7071 29-3730Email bianka.sob@gmx.dePurpose: Since non-adherence (NA) to intravitreal therapy with VEGF drugs is one of the most important modifiable factors compromising treatment outcome of nAMD, the purpose of this study was to investigate the contributing factors and barriers during long-term nAMD treatment.Methods: Barriers and potential reasons for NA were prospectively measured using the Adherence Barriers Questionnaire Intravitreal Therapy (ABQ-IVT). A random sample of patients receiving intravitreal therapy was drawn based on data for different treatment periods. Three age-sex matched groups included the treatment periods of ≤ 30 months (group 1), between > 30 months and ≤ 60 months (group 2), and > 60 months (group 3). The occurrence of gaps between treatments and/or OCT visits was evaluated.Results: NA with gaps of > 56 days after the scheduled appointment was detected in 39%, 89%, and 100% of patients in group 1, 2, and 3, respectively (groups 1 and 2 vs group 3, p < 0.001). Two or more of such gaps were observed in 6%, 72%, and 94% of patients in group 1, 2, and 3, respectively. The overall ABQ-IVT score showed corresponding differences between the groups: 25.89 ± 7.68 (group 1, 95% CI 22.07– 29.71), 34.72 ± 10.32 (group 2, 95% CI: 29.59– 38.86), and 33.28 ± 9.04 (group 3, 95% CI 28.78– 37.77). Accordingly, the score was inversely correlated with the number of regular follow-up visits in groups 2 and 3 (Pearson correlation coefficient r = − 0.65 (p = 0.003) and r = − 0.5 (p = 0.034), respectively). Within the groups of longer treatment duration, univariate logistic regression analysis showed higher odds of time commitment and challenge accompanying person to be relevant barriers.Conclusion: NA is an arising problem with increasing duration of intravitreal therapy. Treatment barriers, detected by the ABQ-IVT, might change or increase during the course of the treatment.Keywords: non-adherence, anti-VEGF, treatment barriers, age-related macular degeneration, ABQ-IVT

Purpose: To investigate the efficacy of once-daily topical treatment of ocular and cutaneous rosacea with ivermectin 1% cream (Soolantra®, Galderma). Methods: Ten patients with rosacea were evaluated in a retrospective monocentric pilot study. Subjective symptoms (measured with the Ocular Surface Disease Index), skin findings, and ocular changes (blepharitis with telangiectasia and meibomian gland dysfunction, conjunctival redness, tear breakup time (TBUT), and fluorescein staining of the cornea) were evaluated. The follow-up was 8 months (range: 5–12 months). Results: The OSDI score decreased in the 8th week of treatment (38.5 ± 21.7, P =.004). After 16 weeks, blepharitis (P =.004), and conjunctival redness (P =.008) had strongly improved, and grade 1 was seen in all patients until the end of follow-up. Fluorescein staining of the cornea (P =.001) and TBUT (P =.016) showed significant improvement until the last follow-up visit. No side effects were observed. Conclusion: Topical ivermectin cream 1% given daily is an effective and safe therapy against rosacea. [ABSTRACT FROM AUTHOR]

Purpose/objectives: to evaluate new onset uveitis or reactivated uveitis by biologic agents and characterize their features., Materials and Methods: This is a multicenter, retrospective case series. Patients under biologic therapy were included if they developed uveitis for the first time or experienced intraocular inflammation which was different in location or laterality to previous inflammation., Results: Sixteen patients were identified. The underlying disorders included ankylosing spondylitis, juvenile idiopathic arthritis, rheumatoid arthritis, and Behçet's Disease. The biologic agents associated with a first episode of uveitis (n = 11) or with a new recurrence of uveitis (n = 5) were etanercept, adalimumab, abatacept, infliximab, and golimumab. Sarcoidosis based on bihilar lymphadenopathy, other computer tomography-findings, or biopsy was diagnosed in five patients under therapy with etanercep, adalimumab, and abatacept. Additionally, seven patients developed clinical changes in their uveitis pattern, suggesting sarcoid uveitis., Conclusions: Biologic treatment-induced uveitis often presents as granulomatous disease.

Ocular rosacea is a chronic potentially sight-threatening inflammatory condition, which can occur in approximately 20% of patients without skin involvement. However, an accurate diagnosis of ocular rosacea has not been defined yet due to its rather nonspecific symptoms and clinical findings. Therefore, this article updates the current recommendations for diagnosis and treatment of ocular rosacea and the previously published consensus recommendations from the ROSCO expert panel on the management of rosacea.

Vitreoretinal lymphoma (VRL) is a rare variant of primary central nervous system lymphoma (PCNSL), mostly of diffuse large B cell lymphoma, which affects the retina and/or the vitreous with or without optic nerve involvement. The disease course is aggressive. Up to 90% of the patients develop central nervous system lymphoma within one year. The diagnosis of VRL is challenging due to nonspecific chronic and relapsing uveitis and is made by anterior chamber tab or vitreous aspirate biopsy. There is no established treatment protocol for VRL patients with bilateral involvement without CNS involvement. There are suggestions to use only intravitreal chemotherapy with methotrexate and/or rituximab. Alternatively, systemic high-dose MTX treatment or external beam radiotherapy is used. Further studies are needed to prove and confirm the prophylactic systemic therapy in preventing CNS involvement in limited VRL.

Purpose: To provide recommendations for diagnosis of vitreoretinal lymphoma (VRL)., Methods: Literature was reviewed for reports supporting the diagnosis of VRL. A questionnaire (Delphi 1 round) was distributed to 28 participants. In the second round (Delphi 2), items of the questionnaire not reaching consensus (75% agreement) were discussed to finalize the recommendations., Results: Presenting symptoms include floaters and painless loss of vision, vitreous cells organized into sheets or clumps. Retinal lesions are usually multifocal creamy/white in the outer retina. Other findings include retinal lesions with "leopard-skin" appearance and retinal pigment epithelium atrophy. Severe vitreous infiltration without macular edema is the most likely presentation. Diagnostic vitrectomy should be performed. Systemic corticosteroid should be discontinued at least 2 weeks before surgery. An interleukin (IL)-10:IL-6 ratio > 1, positive mutation for the myeloid differentiation primary response 88 gene and monoclonality are indicators of VRL. Multi-modal imaging (optical coherence tomography, fundus autofluorescence) are recommended., Conclusions: A consensus meeting allowed the establishment of recommendations important for the diagnosis of VRL.

Viral anterior uveitis (VAU) needs to be suspected in anterior uveitis (AU) associated with elevated intraocular pressure, corneal involvement, and iris atrophic changes. Common etiologies of VAU include herpes simplex, varicella-zoster, cytomegalovirus, and rubella virus. Clinical presentations can vary from granulomatous AU with corneal involvement, Posner-Schlossman syndrome, Fuchs uveitis syndrome, and endothelitis. Due to overlapping clinical manifestations between the different viruses, diagnostic tests like polymerase chain reaction and Goldmann-Witmer coefficient analysis on the aqueous humor may help in identifying etiology to plan and monitor treatment., Competing Interests: None

Objectives: Therapeutic hypothermia TH became broadly used in the management of the asphyxiated newborns. Although two cooling methods are used, so far the superiority of none of them has been established. The purpose of the study is to compare two cooling methods: selective head cooling (SHC) and whole body cooling (WBC) MATERIAL AND METHODS: We conducted a prospective observational study in newborns with HIE. The patients received one of methods: SHC or WBC. The eligibility criteria were similar to previous studies. Stability of cardio-respiratory parameters and short term outcomes were analyzed., Results: 78 neonates with hypoxic-ischemic encephalopathy due to perinatal asphyxia were involved in this study. The SHC group consisted of 51 newborns, the WBC group consisted of 27 patients. Both study groups had similar baseline characteristics and condition at birth. There were no significant differences in hospital course, neurological status and adverse effects associated with cooling procedure between groups. Analyzing the rate of thrombocytopenia and the number of transfusions of blood components no statistically significant differences were found between the groups., Conclusions: Results of our study indicate that two compared methods of TH despite varied target core temperature ranges do not differ significantly according to clinical course and risk of adverse events. Further observations are conducted and we look forward to the results of the long neurodevelopmental care.

Purpose: The aim of the study was to evaluate the bacterial contamination level of contact surfaces on slit lamps and the grip areas of lenses., Methods: Within unannounced audits, two regions of the slit lamps (headrest and joystick), indirect ophthalmoscopy devices, and ultrasound probes were obtained with rayon-tipped swab. Non-contact lenses used for indirect fundoscopy were pressed on RODAC (Replicate Organism Detection and Counting) plates. One hundred and eighty-one surfaces were sampled. The total number of colony-forming units was assessed and bacterial species were identified. Spa-typing and antimicrobial susceptibility testing were performed from Staphylococcus aureus isolates., Results: Among the total bacterial isolates from ophthalmological equipment (lenses: 51 of 78, slit lamps: 43 of 88, ophthalmoscopy helmets: 3 of 8, ultrasound probes: 2 of 7), coagulase-negative staphylococci (CNS) was most frequently found, followed by Micrococcus spp. (lenses vs. slit lamps: P < 0.001 and P = 0.01, respectively). The bacterial contamination of lenses (76%) was significantly higher than that of slit lamps (54%) (P < 0.003). A significantly higher contamination with CNS was observed on lenses from residents vs. from consultants (78% vs. 35%, P = 0.01). A total of seven different spa-types of S. aureus were isolated. No correlation was found between S. aureus contamination of different ophthalmological equipments (Spearman's rank correlation coefficient, ρ = 0.04, P = 0.75). Methicillin-resistant S. aureus was not detected., Conclusion: Bacterial species of the normal skin flora were isolated from the ophthalmological equipment. The bacterial contamination of the portable devices was significantly higher than that of slit lamps. Therefore, proper hygiene of the mobile instruments should be monitored in order to prevent transmission of bacteria in residents and consultants.

Purpose: To evaluate the response to treatment in patients with tubulointerstitial nephritis and uveitis (TINU) syndrome over a long-term follow-up period., Methods: Nine patients with TINU syndrome were retrospectively reviewed. The mean follow-up was 54.8 months (range: 24-133 months)., Results: The mean number of recurrences per year declined from 1.7 in the 1st year to 0.66 in the 2nd year of treatment. The ocular inflammation responded to local corticosteroids in two patients, systemic corticosteroids in two patients, immunosuppressive therapy in four patients, and anti-TNF-α blocking agent in one patient. The therapy could be discontinued in six (67%) patients after a mean treatment period of 29.5 months. In five patients, remission with the recurrence-free period of 12.8 months was achieved., Conclusions: TINU syndrome was characterized by limited responsiveness to corticosteroid therapy and less by severe complications. A long-term course of immunosuppressants or biologics was necessary to control the uveitis and led to induction of remission.

[This corrects the article DOI: 10.1186/s40942-017-0075-x.].

Background: The aim of the study was to measure pH changes of the human vitreous caused by the intravitreal drugs bevacizumab, ranibizumab, aflibercept, and ziv-aflibercept., Methods: Fresh human vitreous samples were obtained during core vitrectomy (23-gauge) from patients with epiretinal gliosis. Aliquots of bevacizumab, ranibizumab, aflibercept or ziv-aflibercept (2 µl) were added consecutively to 200 µl of vitreous samples or 0.9% NaCl saline. The pH was measured using a pH-sensitive microelectrode. Rituximab, in off-label use against intraocular lymphoma, was tested as an IgG1 antibody., Results: The pH of the administered drugs was 5.91 for bevacizumab (95% CI 5.63-6.19), 5.32 for ranibizumab (95% CI 5.0-5.63), 6.05 for aflibercept (95% CI 5.78-6.31), ziv-aflibercept 6.1 (95% CI 6.05-6.15), and 6.29 for rituximab (95% CI 5.97-6.61). While the fresh and undiluted vitreous fluid showed pH values of 7.0-7.4, pH values increased if saline or rituximab were added. In contrast, the pH decreased slightly if aflibercept, bevacizumab, ranibizumab or ziv-aflibercept were supplemented. The observed pH decreases were not significant after ranibizumab was added. Significant changes were only notable with higher-than-normal amounts of bevacizumab (26-40 µl). The vitreous showed the most robust buffering capacity towards ranibizumab and rituximab., Conclusions: The pH changes in vitreous samples elicited by the usual intravitreal anti-VEGF drugs differed clearly, but only by much higher concentrations than used in the clinical routine. Although the ingredient solution of ranibizumab showed the lowest pH, it caused only moderate changes of vitreal pH compared to bevacizumab, aflibercept or ziv-aflibercept.

Purpose: To analyze the efficacy of tocilizumab in uveitic macular edema (ME) resistant to various immunomodulatory drugs., Methods: Patients received tocilizumab every 4 weeks intravenously. Central foveal thickness (CFT) was assessed by optical coherence tomography (OCT)., Results: Five patients (8 eyes) who were ineffectively pretreated with systemic prednisolone, at least one immunosuppressive drug, and at least one biologic drug for uveitic macular edema were included in the study. At 3 months, a response of ME (≥25% reduction in CFT) was observed in 6 eyes (75.0%) of 5 patients. During follow-up, complete resolution of ME was achieved in 5 eyes (62.5%) of 4 patients. Improvement of BCVA was observed in 3 eyes of 3 patients, and stabilization in 3 eyes of 3 patients. Tocilizumab was well tolerated, and no severe side effects occurred., Conclusions: Treatment with tocilizumab can be considered in chronic uveitic macular edema even if previous immunomodulatory therapy has failed.

Aim: To assess the efficacy and tolerability of mycophenolate sodium (MPS) in the therapy of children with chronic non-infectious uveitis., Methods: Retrospective analysis of 23 children with chronic uveitis, treated with MPS, with a follow-up of at least 6 months. The main outcome measures were time to uveitis reactivation and corticosteroid-sparing effect under MPS treatment. The secondary outcome measures were best-corrected visual acuity (BCVA) and treatment-related side effects., Results: From 23 patients included in the study, 2 patients had anterior uveitis, 19 had intermediate uveitis and 2 had panuveitis. The probability of reactivation-free survival after MPS initiation was estimated as 65% at both 1 and 2 years. The probability of discontinuing systemic corticosteroids after 1 year of treatment was 39% and after 2 years 51%. The probability to taper corticosteroids to a daily dosage of ≤0.1 mg/kg after 1 and 2 years was 62% and 85%, respectively. BCVA improved or remained stable in 96% of eyes after 1 year of therapy. Treatment-related side effects were found in nine children (rate: 0.17/patient-year). No therapy discontinuation because of side effects was needed., Conclusion: Our data suggest that MPS is useful and well tolerated in children with chronic uveitis. MPS seems to be an effective drug for the treatment of chronic non-infectious uveitis of childhood and may be preferred as a first-line steroid-sparing agent in this form of uveitis., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Objective: Cryopyrin-associated periodic syndrome (CAPS) is a group of inherited autoinflammatory disorders caused by mutations in the NLRP3 gene resulting in the overproduction of interleukin 1β. NLRP3 mutations cause a broad clinical phenotype of CAPS. The aims of the study were to evaluate clinical, laboratory, and genetic features of a 5-generation family with CAPS focusing in detail on ocular symptoms., Methods: In a retrospective observational cohort study, consecutive family members were screened for the presence of the NLRP3 mutation. Patients underwent standardized clinical, laboratory, and ophthalmological assessments. The genotype-specific risk of ophthalmological findings and other organ symptoms was determined., Results: Twenty-nine patients were clinically affected. The A439V mutation encoded by exon 3 of the NLRP3 gene was found in 15 of 37 family members (41%). The most common clinical features were musculoskeletal symptoms, headaches, and ophthalmological symptoms. The mutation-positive patients were characterized by more frequent skin rashes, ocular symptoms, arthralgia, arthritis, and severe Muckle-Wells syndrome (MWS) Disease Activity Score. Rosacea was diagnosed in 8 patients., Conclusion: The NLRP3 mutation A439V is associated with a heterogeneous clinical spectrum of familial cold autoinflammatory syndrome/MWS-overlap syndrome. Skin rash and eye diseases, such as conjunctivitis and uveitis, were positively correlated with this mutation.

Introduction: The vascular endothelial growth factor (VEGF) inhibitors most widely used to treat neovascular age-dependent macular degeneration (nAMD) are different proteins with structural features potentially relevant to adverse effects (AEs). Two of these are also established in cancer therapy (with higher dosages and AEs). The importance of ocular AE and extraocular activities is still a subject of controversy and ongoing research., Areas Covered: Potential risks of intraocular VEGF inhibition based on prospective studies, in vitro investigations, pharmacokinetics, and hints from anti-cancer treatment., Expert Opinion: nAMD is a frequently observed chronic clinical condition severely affecting the visual function of elderly persons. Intravitreal injection of VEGF-inactivating proteins is highly effective to prevent loss of vision. Anti-VEGF therapy is well tolerated, and low rates of ocular and systemic AEs in smaller trials suggest a very high benefit/risk ratio. The proteins established in nAMD therapy show similar efficacies. In the controversy over the off-label use of bevacizumab purely on grounds of much lower cost, the small, but potentially relevant differences between the available drugs are easily either dramatized (by pharmaceutical companies) or trivialized (by health insurances) and even political interference is involved. Facing the lack of a convincing body of evidence regarding safety, further long-term study results seem necessary.

Carl Friedrich Richard Foerster (1825-1902) was a German who was born in the Polish city Leszno. He studied medicine at the Medical Faculty of Breslau (now Wroclaw, Poland) University, and later in Heidelberg and Berlin. From 1855, he worked in Breslau, where he established in 1857 the first ophthalmology clinic. Later, he became a professor in ophthalmology, the first director of the Department of Ophthalmology at the University of Breslau, and even the rector of this University. Forster did many pioneering works on visual fields, invented a photometer and the first perimeter, known for many years as the Foerster perimeter. Moreover, he studied night blindness, visual field changes due to different pathologies, and many eye diseases, including glaucoma, cataract, retinal and choroidal diseases., (© 2015 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

A multitude of stem cell types has been extensively studied and used for myocardial regenerative therapy. Amongst these endothelial progenitor cells form a promising source. In our present study, we investigated a one-staged approach for isolation and application of autologous endothelial progenitor cells in a pig model of myocardial infarction. Endothelial progenitor cell isolation was performed by immediately preprocedural bone marrow aspiration and consecutive positive selection by aptamer-based magnetic cell sorting. Animals were divided in three groups receiving endothelial progenitor cells, saline, or no intramyocardial injection respectively. Postprocedural follow-up consisted of weekly echocardiographic evaluations. Postmortem histological analysis after four weeks focused on detection of transplanted PKH26-positive endothelial progenitor cells and neovascularization within the infarcted myocardium. A significant difference in left ventricular ejection fraction could not be shown between the three groups. PKH26-stained endothelial progenitor cells could be found in the endothelial progenitor cells transplanted group, although detection was scarce. Large-sized capillaries were found to be significantly more in endothelial progenitor cells treated myocardium. The one-stage approach of endothelial progenitor cells isolation and application presented herein offers a new therapeutic concept. Even though a beneficial impact on myocardial function could not be assessed, increased neovascularization may indicate positive effects on remodeling processes. Being able to harvest endothelial progenitor cells right before application provides a wider scope of action in urgent cases.

Importance: The best treatment option for primary vitreoretinal lymphoma (PVRL) without signs of central nervous system lymphoma (CNSL) involvement determined on magnetic resonance imaging or in cerebrospinal fluid is unknown., Objective: To evaluate the outcomes of treatment regimens used for PVRL in the prevention of subsequent CNSL., Design, Setting, and Participants: A retrospective cohort study was conducted at 17 referral ophthalmologic centers in Europe. We reviewed clinical, laboratory, and imaging data on 78 patients with PVRL who did not have CNSL on presentation between January 1, 1991, and December 31, 2012, with a focus on the incidence of CNS manifestations during the follow-up period., Interventions: The term extensive treatment was used for various combinations of systemic and intrathecal chemotherapy, whole-brain radiotherapy, and peripheral blood stem cell transplantation. Therapy to prevent CNSL included ocular radiotherapy and/or ocular chemotherapy (group A, 31 patients), extensive systemic treatment (group B, 21 patients), and a combination of ocular and extensive treatment (group C, 23 patients); 3 patients did not receive treatment. A total of 40 patients received systemic chemotherapy., Main Outcomes and Measures: Development of CNSL following the diagnosis of PVRL relative to the use or nonuse of systemic chemotherapy and other treatment regimens., Results: Overall, CNSL developed in 28 of 78 patients (36%) at a median follow-up of 49 months. Specifically, CNSL developed in 10 of 31 (32%) in group A, 9 of 21 (43%) in group B, and 9 of 23 (39%) in group C. The 5-year cumulative survival rate was lower in patients with CNSL (35% [95% CI, 50% to 86%]) than in patients without CNSL (68% [95% CI, 19% to 51%]; P = .003) and was similar among all treatment groups (P = .10). Adverse systemic effects occurred in 9 of 40 (23%) patients receiving systemic chemotherapy; the most common of these effects was acute renal failure., Conclusions and Relevance: In the present series of patients with isolated PVRL, the use of systemic chemotherapy was not proven to prevent CNSL and was associated with more severe adverse effects compared with local treatment.

Purpose: The aim of the study was to evaluate the potential influence of ranibizumab and bevacizumab on platelet activation and aggregation, which are critical processes in the pathogenesis of arterial thromboembolic events (ATEs)., Methods: For the assessment of platelet function, flow cytometry and aggregometry were employed. Platelets were isolated from healthy volunteers and exposed to ranibizumab (1 mg/ml and 150 ng/ml) and bevacizumab (2.5 mg/ml and 3 μg/ml) or their solvents for 10 and 30 min prior to the addition of TRAP (25 μM), PAR-4-AP (25 μM) or thrombin (0.02 U/ml). The surface expression of activated GP IIb/IIIa, P-selectin (CD62P) and platelet-bound stromal cell-derived factor-1 (SDF-1) was measured on resting (nonactivated) and activated platelets by flow cytometry. The platelet aggregation capacity was examined using light transmission aggregometry., Results: The expression of surface activation markers did not differ significantly between nonstimulated and TRAP-, PAR-4-AP- or thrombin-activated platelets after incubating with ranibizumab. However, GP IIb/IIIa, CD62P and SDF-1 were significantly downregulated in PAR-4-AP- and thrombin-activated platelets after exposure to bevacizumab 2.5 mg/ml. In addition, ranibizumab- and bevacizumab-FITC were significantly increased in all activated platelets. No significant differences were observed in the aggregation of activated platelets after incubation with ranibizumab or bevacizumab., Conclusion: All ranibizumab concentrations as well as the bevacizumab concentration of 3 μg/ml had no influence on platelet activation and aggregation. Therefore, this in vitro study did not show any relationship between the exposition of activated platelets to ranibizumab or bevacizumab and the development of ATEs. However, the highest level of bevacizumab interfered with platelet activation, leading to downregulation of platelet activation markers. This observation might explain why the systemic treatment with high-dose bevacizumab could be associated with an increased risk of bleeding. Regarding the use of lower intravitreal dosages, further research should focus on the complex interactions between platelets and other cells, such as endothelial cells, which might stronger relate to a potentially increased risk of ATEs and depend on systemic vascular endothelial growth factor levels. Facing the different activation profiles, the diverse effects of the drugs on the cellular level have to be critically scrutinized for their clinical relevance., (© 2015 S. Karger AG, Basel.)

Background: To assess the cytotoxic properties of voriconazole and sulfobutylether-β-cyclodextrin (SBECD) on cultured primary human corneal epithelial cells., Methods: Human corneal epithelial cells were cultured and exposed to various concentrations of SBECD (0.016-32 mg/ml) and voriconazole (0.001-2 mg/ml). Cellular cytotoxicity of SBECD and voriconazole on human corneal epithelial cells was evaluated using the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide test and the LIVE/DEAD Viability/Cytotoxicity Assay with fluorescence microscopy analysis. Cell damage was assessed with phase-contrast microscopy after 24 h of exposure to SBECD and voriconazole., Results: The cytotoxicity tests and the morphological characteristic demonstrated the dose-dependent toxic effect of SBECD and voriconazole on human corneal epithelial cells. No corneal epithelial cytotoxicity was observed below the concentration of 0.08 and 0.025 mg/ml after 24-hour exposure to SBECD and voriconazole, respectively., Conclusions: The results of the study reveal the dose-dependent cytotoxic effect of SBECD and voriconazole on cultured human corneal epithelial cells. Therefore, voriconazole eye drops should be used cautiously in the treatment of fungal corneal ulcers., (© 2015 S. Karger AG, Basel.)

Purpose: To investigate the long-term functional outcome and its predictive factors of treatment of acute submacular hemorrhage secondary to age-related macular degeneration with intravitreal application of recombinant tissue plasminogen activator (rt-PA) and gas., Methods: Twenty-six patients were enrolled in the retrospective case series. A complete history and ocular examination, including fluorescein angiography, were performed. The best-corrected visual acuity was measured with a Snellen chart. Patients were followed up for 12 to 131 months (mean: 49 months). All patients underwent intravitreal injection of rt-PA (50 μg) and expansile gas. Primary outcome measures were best postoperative and final visual acuity and degree of blood displacement., Results: The size of the subretinal hemorrhage ranged from 0.5 to 28 disc diameters, and the degree of blood displacement was defined as complete (≥1 disc area from the center of the fovea), partial, or no displacement. Twenty-one (81%) patients showed partial or complete displacement of hemorrhage. Due to lack of displacement of hemorrhage in 5 patients (19%), submacular surgery was performed. In 13 of 21 (62%; P=0.0001) patients with displacement of hemorrhage, the best postoperative visual acuity improved ≥2 lines. The final visual acuity improved ≥2 lines in 42.9% (9 of 21), was stable in 23.8% (5 of 21), and worse ≥2 lines in 33.3% (7 of 21) of patients. The short duration of hemorrhage (≤4 days) and complete displacement of blood, independent of the hemorrhage size, were significantly associated with better postoperative visual acuity (P=0.0001, P=0.0001, respectively)., Conclusion: Intravitreal injection of rt-PA and gas seem to be more effective when applied within the first 4 days of acute submacular hemorrhage. Preoperative visual acuity as well as displacement of hemorrhage might be useful to predict final visual acuity.

Purpose: The aim of this study was to determine the efficacy of once-daily systemic treatment of ocular rosacea with a slow-release form of 40 mg of doxycycline., Methods: Fifteen patients with ocular rosacea were enrolled between February 2010 and October 2012 in a retrospective observational case series. Patient complaints and clinical findings including blepharitis with telangiectasia and meibomian gland dysfunction, conjunctival redness, and fluorescein staining of the cornea were evaluated. The ocular manifestations were scored as follows: 0-absent, 1-mild, 2-moderate, and 3-severe. All measurements were repeated at the 6-week follow-up visit. The mean duration of treatment was 8 months (range, 5-12 months), and the mean duration of the follow-up was 9 months (range, 6-17 months)., Results: At the baseline visit, 73.3% of the patients had severe complaints, and 80% had severe blepharitis despite topical therapy with artificial tears and eyelid hygiene. After 12 weeks of systemic therapy, severe complaints and blepharitis strongly improved and were seen in only 13.3% and 20% of the patients (P = 0.01). Follow-up investigations 6 to 17 months after discontinuation of the treatment showed further significant improvement of complaints (absent or mild in 66.7% and 20% of the patients, respectively) and blepharitis (absent or mild in 26.7% and 60% of the patients, respectively). One patient had a mild stomach ache so that therapy was shortened to 5 months., Conclusions: An antiinflammatory dose of slow-release doxycycline 40 mg given daily may be an effective and safe therapy of ocular rosacea.

Ocular mucous membrane pemphigoid (MMP), as a potentially blinding disease, is an indication for systemic immunosuppressive treatment. Immunosuppressive agents are chosen with a "stepladder" approach, beginning with drugs having the fewest side effects. Dapsone, sulfapyridine/sulfasalazine and azathioprine are less successful in controlling inflammation than mycophenolate mofetil (MMF) and methotrexate (MTX). Moreover, compared to other immunosuppressive agents, MMF, followed by MTX, has the lowest rate of discontinuation due to side effects. Cyclophosphamide is the most potent immunosuppressive agent used for ocular MMP, but it should be used with caution because of life-threatening adverse effects. Intravenous immunoglobulin therapy (IVIg) should be considered for patients who are resistant to conventional immunosuppressive therapy, have significant adverse effects or contraindications to conventional therapy, or have uncontrolled rapidly progressive disease. If IVIg monotherapy is not successful after a period of ≥ 1 year, therapy with biological agents, such as rituximab or anti-TNF-α drugs, is suggested., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Unlabelled: Abstract Purpose: To evaluate the antiproliferative and cytotoxic properties of moxifloxacin on cultured rat retinal ganglion cells (RGC5)., Materials and Methods: Rat retinal ganglion cells were exposed to various concentration of moxifloxacin (5-1500 μg/mL). For antiproliferative properties, the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) test was performed. Cellular cytotoxicity was assessed by using the Live/Dead viability/cytotoxicity assay and analyzed by fluorescence microscopy after 24 and 72 h of incubation, respectively., Results: Neither cytotoxic nor antiproliferative effect of moxifloxacin was observed below 50 μg/mL on RGC5 cells after 24 and 72 h of incubation. At higher concentrations of moxifloxacin (150 μg/mL, 500 μg/mL, and 1500 μg/mL (p < 0.001)) the number of viable cells and the proliferation rate of RGC5 were significantly reduced., Conclusions: These results suggest a dose-dependent cytotoxic and antiproliferative effect of moxifloxacin on RGC5. Therefore, intracameral application of moxifloxacin should be used cautiously in patients with increased risk of retinal ganglion cells damage, particularly in glaucoma patients.

CATT (Comparison of Age-related macular degeneration [AMD] Treatment Trials) examined the efficacy of ranibizumab and bevacizumab for the treatment of neovascular AMD. This prospective, randomized, but unblinded trial revealed a significant improvement in vision with both treatments in terms of visual acuity; importantly, patients with juxtafoveal choroidal neovascularization (CNV) and retinal pigment epithelial detachments were not excluded from the study. Monthly treatment with the drugs resulted in similar increases in visual acuity, although angiograms indicated that ranibizumab was superior in terms of reducing retinal fluid and leakage. As the study also differentiated between a fixed regimen and an as-needed (pro re nata [PRN]) dosing regimen, a larger sample size and Bonferroni statistical correction were necessary. The equivalence of the PRN dosing of bevacizumab to the monthly treatment could not be confirmed. Almost all of the frequent deviations from the protocol (referring to retreatment criteria: 25.7-28.5%) resulted in under-treatment. Since this applied to both drugs equally, under-treatment alone could not explain the larger loss of visual acuity observed in the bevacizumab PRN arm. The PRN regimen was generally associated with a larger lesion size after 12 months compared with the fixed treatment regimens. The investigators accepted the drawbacks of an incomplete masking to allow co-payment by Medicare. As assessments of drug trials are often politically motivated, the higher demands of a non-inferiority trial compared with a superiority design must be emphasized. A comparison of the per-protocol and last-observation-carried-forward analysis has not yet been published; ongoing subgroup analysis might highlight the impact of different lesion characteristics. While CATT provided further evidence for the efficacy of bevacizumab treatment, differences in adverse events between the two treatments (e.g. a higher rate of serious adverse events with bevacizumab compared with ranibizumab) were reported; however, these still have to be analysed, with the larger sample sizes of previous ranibizumab studies needing to be taken into account. Preclinical studies imply some differences between the drugs in terms of their adverse event profiles. A possible increased risk of adverse events could not be ruled out by previous clinical case series and CATT because the sample sizes and the follow-up intervals were not adequate. The large discrepancy in the price of bevacizumab versus ranibizumab in the US means a cost-benefit analysis is warranted. A lack of quality-of-life data has prevented calculation of an appropriate bevacizumab price in the context of its performance in the ophthalmological setting. Thus, CATT suggests that a favourable visual acuity might be achieved by very frequent administration of bevacizumab in patients with neovascular AMD. Although there are certain safety caveats, increased focus on subgroup analyses and obtaining longer follow-up data are expected to yield additional information of clinical relevance.

Objectives: Magnesium sulfate has been recognized as a neuroprotective agent against hypoxia-ischemia, mainly by the protection from the excitotoxicity associated with increased glutamate concentration. However, the mechanism of MgSO4 action is not fully understood and is considerably controversial., Design and Methods: During the 2 first hours of life, the asphyxiated full-term newborns were treated intravenously with one dose of MgSO4 250 mg/kg body weight. At birth, after 6 and 48 h of life the activity of ATP-dependent enzymes in erythrocyte membranes: Mg2+-ATPase, Ca2+-ATPase, protein kinases A and C, were determined. Using monoclonal antibodies, the band 3 and its phosphotyrosine level were also assayed., Results: The time-dependent decrease of Ca2+-ATPase activity was detected in untreated newborns, whereas MgSO4 prevented this reduction. After 48 h, protein kinases activities differed in MgSO4-treated and untreated groups. Magnesium therapy increased the amount of band 3 and diminished proteolytic degradation of this protein., Conclusion: Our results demonstrated, for the first time, that magnesium sulfate treatment significantly altered the activities of some important enzymes in erythrocyte membrane from asphyxiated newborns. It also reduced the post-asphyxial damages of membrane compounds. These data may partly explain the molecular mechanisms of MgSO4 action in asphyxiated newborns.

Objectives: Perinatal asphyxia represents a major cause of acute brain impairment and mortality in neonates. To develop the effective therapies able to reduce post-asphyxial damages, the understanding of biochemical processes accompanying asphyxia appears to be of the great relevance., Design and Methods: The activities of protein kinases A and C, and tyrosine kinases in erythrocyte membranes of healthy and asphyxiated neonatals were compared. Using monoclonal antibodies the band 3 presence and its phosphotyrosine levels were assayed., Results: In asphyxiated erythrocyte membranes the activities of PKA and tyrosine kinases increased, whereas the activity of PKC was reduced in relation to healthy newborns. Under asphyxia the band 3 has been overphosphorylated; however, its amount decreased., Conclusion: These findings may provide some evidence for a potential role of asphyxia in disturbance of phosphorylation processes in erythrocytes, as reflected by altered protein kinases activities. The diminished band 3 presence may be partially responsible for the impairment of erythrocyte function.

The authors compared efficacy of two different NCPAP techniques in VLBW newborn with respiratory insufficiency. Among the patients with IFD support the higher weaning rate and the lower supplemental oxygen requirement as well as secondary infections incidents was observed.