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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.

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.

to evaluate new onset uveitis or reactivated uveitis by biologic agents and characterize their features.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.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.Biologic treatment-induced uveitis often presents as granulomatous disease.

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 evaluate...

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.

Simple Summary Vitreoretinal lymphoma is a variant of primary CNS lymphoma involving the retina and/or the vitreous. At the time of presentation, CNS involvement occurs in up to one-third of patients. However, 50–90% of patients develop a CNS and/or spinal cord disease within one year. Therefore, it is important to frequently examine and recognize the early symptoms of CNS involvement. This review summarizes the clinical signs, ocular diagnosis and treatment of vitreoretinal lymphoma. Abstract 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. Growing evidence suggests different systemic exposure of anti-vascular endothelial growth factor (anti-VEGF) agents with repeated intravitreal application. Since the penetration of anti-VEGF agents through vascular barrier was reported, the interaction of anti-VEGF with nonresident platelets has become a topic of interest. The purpose of this study was to evaluate, with the help of visualization techniques, whether platelets take up the anti-VEGF agents ranibizumab, aflibercept, and bevacizumab. Methods. The uptake of anti-VEGF agents with or without VEGF treatment was investigated using immunofluorescence and immunogold staining in human platelets. The role of actin filaments and clathrin-coated vesicles in the transport of ranibizumab, aflibercept, and bevacizumab was evaluated by two pharmacologic inhibitors: staurosporine (protein kinase C inhibitor) and cytochalasin D. Results. All three anti-VEGF agents were taken up by platelets and colocalized with VEGF. Ranibizumab and aflibercept were mainly detected in alpha-granules; however, bevacizumab was equally localized in alpha-granules and in platelet vesicles. Both staurosporine and cytochalasin D completely inhibited the uptake of aflibercept into platelets. Both pharmacological inhibitors also decreased the transport of ranibizumab and bevacizumab into platelets. Bevacizumab was significantly more frequently colocalized within clathrin-coated vesicles than ranibizumab and aflibercept. Conclusion. All three anti-VEGF agents are taken up by platelets and internalized in alpha-granules, which may result in a higher local exposure of anti-VEGF after the activation of platelets, potentially contributing to arterial thromboembolic events. Clathrin-coated vesicles seem to be more prominent in the transport of bevacizumab than ranibizumab and aflibercept. Nevertheless, whether the different localization and transport of bevacizumab are truly related to specific differences of receptor-mediated endocytosis has to be revealed by further research.

Aflibercept appears to accumulate in systemic circulation following intravitreal injections in therapy of neovascular age-related macular degeneration. This gives raise to the question of whether aflibercept affects platelets and their function such as activation and aggregation, which are substantial in the pathogenesis of an arterial thromboembolic event (ATE). In order to determine the effect of aflibercept in platelet activation, platelets from healthy volunteers were treated with aflibercept and its solvents at equal concentrations (0.04 μg/mL - 4 μg/mL - 40 μg/mL - 400 μg/mL - 4 mg/mL) for 10 and 30 min before addition of agonists. IgG1 antibody was used as a control. The surface expression of GPIIb/IIIa, P-selectin, and platelet-bound stromal-cell-derived factor-1, which are potential blood biomarkers for ATEs, was determined on resting and activated platelets by the multispectral imaging flow cytometry, combining the features of flow cytometry with fluorescence microscopy. Platelet aggregation was assessed with light transmission aggregometry. To determine whether aflibercept directly interacts with platelets, aflibercept was labeled with the fluorescence FITC. Co-treatment of platelets with thrombin or PAR-4-AP and aflibercept resulted in increased activation of the fibrinogen receptor GPIIb/IIIa in comparison to controls (P 0.05). Interestingly, the expression of platelet-derived P-selectin and SDF-1 was not affected by aflibercept, except thrombin-activated CD62P with 0.04 μg/mL aflibercept (aflibercept vs. its solvent: MSI = 1.54, IC = 1.201-1.879 vs. MSI = 1.37, IC = 1.136-1.604 [P = 0.031]) and SDF-1 with 4 mg/mL aflibercept (aflibercept vs. its solvent: MSI = 1.971, IC = 1.206-2.737 vs. MSI = 1.200, IC = 0.738-1.662 [P = 0.041]). Although the levels of platelet-bound aflibercept-FITC were significantly increased in all activated platelets, no effect was observed in platelet aggregation. Albeit no impact of aflibercept was found on platelet aggregation under the studied experimental conditions, the increased activation of the fibrinogen receptor GPIIb/IIIa and the presence of a direct interaction between aflibercept and platelets may partially explain the risk of ATE in patients under aflibercept treatment due to FcγRIIa mediated αIIbβ3 outside-in integrin signaling and transport of aflibercept into platelets. Therefore, the Fc domain seems to be involved in interactions between aflibercept and platelets. Further research is needed to explain the role of Fc containing aflibercept in the pathogenesis of drug-associated vascular events involving platelets, coagulation cascade, extracellular matrix proteins and other cells.

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.

Entzundliche Skleraerkrankungen lassen sich meist klar klinisch diagnostizieren und differenzieren, wobei am ehesten die posteriore Skleritis eine Herausforderung darstellt. Ein echografischer Befund oder ggf. eine bildgebende Untersuchung kann die Verdachtsdiagnose der posterioren Skleritis bestatigen. Bei allen Formen entzundlicher Skleraerkrankungen sollte eine Zusatzdiagnostik zur Erkennung moglicher systemischer Erkrankungen erfolgen. Bei einer Episkleritis ist meist eine lokale Behandlung mit nichtsteroidalen Antiphlogistika (NSAID) oder steroidhaltigen Augentropfen ausreichend. Bei der Skleritis dagegen fuhrt die topische Therapie alleine nicht zum Abklingen der Symptome, sodass orale NSAID, ggf. auch Kortikosteroide die Therapie der ersten Wahl sind. Bei schweren Verlaufsformen (nekrotisierende Skleritis) oder Skleraerkrankungen, die mit Systemerkrankungen assoziiert sind, kommen haufig Immunsuppressiva zum Einsatz.

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

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 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.

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 contr...

Objective.Cryopyrin-associated periodic syndrome (CAPS) is a group of inherited autoinflammatory disorders caused by mutations in theNLRP3gene 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 theNLRP3mutation. 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 theNLRP3gene 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.TheNLRP3mutation 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.

Biologicals are substances produced from living organisms such as recombinant proteins or antibodies, which target cytokines or cell surface receptors resulting in suppression of specific immune effectors potentially leading to ocular inflammatory diseases [45]. There are different classes of biologic agents, including anti-TNF agents, interferon, anti-IL agents, anti B-cell agents, and agents against specific cell surface antigens. All of these biologicals are used off-label in the treatment of ocular diseases. However, indications for considering treatment with biologic agents are primary inflammatory eye diseases refractory to corticosteroids and conventional immunosuppressive drugs. This chapter will bring an update for knowledge about the use of the biologic agents in the treatment of uveitis.

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.Potential risks of intraocular VEGF inhibition based on prospective studies, in vitro investigations, pharmacokinetics, and hints from anti-cancer treatment.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.

After the publication of this article [1], we were made aware that the osmolarity of aflibercept (Eylea) was incorrect and should have been 286 mOsm and not 1000 mOsm. The correct version of Table 1 is shown in this correction.

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.

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.

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.

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.

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.

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.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.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).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.

To assess the short-term and long-term efficacy of oral therapy with valganciclovir in patients with Posner-Schlossman Syndrome (PSS). This is a retrospective observational study on 11 patients with PSS treated with valganciclovir. The PSS was diagnosed clinically on the basis of recurrent episodes of anterior uveitis associated with attacks of elevated intraocular pressure (IOP). All patients who did not respond to aciclovir, or whose cytomegalovirus (CMV) DNA polymerase chain reaction (PCR) analysis of the aqueous humour was positive, were treated with valganciclovir (Valcyte®). Initially, the drug was given 900 mg twice daily for 3 weeks, followed by 450 mg twice daily for a mean period of 20 months (range 10–46 months). Eleven patients with mean age of 44 years were included in this study. Four of 11 patients were working in a sanitary profession. Before initiation of valgancicloivir therapy, the highest IOP was 68 mmHg (mean 45 mmHg ±9 mmHg). In the first week of treatment, the IOP decreased significantly (mean 16 mmHg ±10 mmHg) and maintained stability during the entire treatment period. In seven of 11 (63.6 %) patients, valganciclovir led to resolution of inflammatory activity and stable IOP. In six patients, the therapy could be discontinued after a mean of 14 months. However, two patients had a recurrence after discontinuation of valganciclovir treatment. No side effects of therapy were observed. Long-term oral therapy with valganciclovir seems to lower the recurrence rate in patients with clinically diagnosed PSS.

Purpose: To evaluate the antiproliferative and cytotoxic properties of moxifloxacin on cultured rat retinal ganglion cells (RGC5).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.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 (p0.001)) the number of viable cells and the proliferation rate of RGC5 were significantly reduced.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.

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.