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Faricimab is a bispecific antibody that acts through dual inhibition of both angiopoietin-2 and vascular endothelial growth factor A. We report primary results of two phase 3 trials evaluating intravitreal faricimab with extension up to every 16 weeks for neovascular age-related macular degeneration (nAMD).TENAYA and LUCERNE were randomised, double-masked, non-inferiority trials across 271 sites worldwide. Treatment-naive patients with nAMD aged 50 years or older were randomly assigned (1:1) to intravitreal faricimab 6·0 mg up to every 16 weeks, based on protocol-defined disease activity assessments at weeks 20 and 24, or aflibercept 2·0 mg every 8 weeks. Randomisation was performed through an interactive voice or web-based response system using a stratified permuted block randomisation method. Patients, investigators, those assessing outcomes, and the funder were masked to group assignments. The primary endpoint was mean change in best-corrected visual acuity (BCVA) from baseline averaged over weeks 40, 44, and 48 (prespecified non-inferiority margin of four letters), in the intention-to-treat population. Safety analyses included patients who received at least one dose of study treatment. These trials are registered with ClinicalTrials.gov (TENAYA NCT03823287 and LUCERNE NCT03823300).Across the two trials, 1329 patients were randomly assigned between Feb 19 and Nov 19, 2019 (TENAYA n=334 faricimab and n=337 aflibercept), and between March 11 and Nov 1, 2019 (LUCERNE n=331 faricimab and n=327 aflibercept). BCVA change from baseline with faricimab was non-inferior to aflibercept in both TENAYA (adjusted mean change 5·8 letters [95% CI 4·6 to 7·1] and 5·1 letters [3·9 to 6·4]; treatment difference 0·7 letters [-1·1 to 2·5]) and LUCERNE (6·6 letters [5·3 to 7·8] and 6·6 letters [5·3 to 7·8]; treatment difference 0·0 letters [-1·7 to 1·8]). Rates of ocular adverse events were comparable between faricimab and aflibercept (TENAYA n=121 [36·3%] vs n=128 [38·1%], and LUCERNE n=133 [40·2%] vs n=118 [36·2%]).Visual benefits with faricimab given at up to 16-week intervals demonstrates its potential to meaningfully extend the time between treatments with sustained efficacy, thereby reducing treatment burden in patients with nAMD.F Hoffmann-La Roche.

A 65-year-old woman was referred for sudden bilateral loss of vision. She was vaccinated a few days earlier. The ophthalmological examination showed a massive optic disc swelling on both eyes. Magnetic resonance imaging (MRI) revealed suspected bilateral optic neuritis without cerebral involvement or transverse myelitis. After serological detection of anti-MOG (myelin oligodendrocyte glycoprotein) antibodies, the patient was treated with high-dose corticosteroid pulse therapy until vision recovered. Discussion: an atypical optic neuritis may indicate a neuromyelitis optica spectrum disorder (NMOSD), which should be further characterized by determination of Aquaporin 4(AQP4)-IgG and MOG-IgG.Eine 65-jährige Frau wurde wegen plötzlicher beidseitiger Sehminderung überwiesen, nachdem sie kurz zuvor geimpft wurde. Augenärztlich zeigte sich beidseits eine ausgeprägte Papillenschwellung. In der Magnetresonanztomografie (MRT) fand sich keine zerebrale Beteiligung oder transverse Myelitis. Serologisch konnten wir Myelin-Oligodendrozyten-Glykoprotein(MOG)-IgG nachweisen, sodass wir mit Hochdosiskortikosteroidpulstherapie behandelten. Diskussion: Bei atypischer Optikusneuritis muss an eine Neuromyelitis-optica-Spektrum-Erkrankung (NMOSD) gedacht werden, die durch die Bestimmung von Aquaporin 4(AQP4)- und MOG-IgG weiter charakterisiert werden sollte.

Proliferative vitreoretinopathy (PVR) is the major cause for surgical failure after primary rhegmatogenous retinal detachment (RRD). So far, no therapy has been proven to prevent PVR. Promising results for 5-fluorouracil (5-FU) and low-molecular weight heparin (LMWH) in high-risk eyes have been reported previously. The objective of this trial was to examine the effect of adjuvant intravitreal therapy with 5-FU and LMWH compared with placebo on incidence of PVR in high-risk patients with primary RRD.Randomized, double-blind, controlled, multicenter, interventional trial with 1 interim analysis.Patients with RRD who were considered to be at high risk for PVR were included. Risk of PVR was assessed by noninvasive aqueous flare measurement using laser flare photometry.Patients were randomized 1:1 to verum (200 mg/ml 5-FU and 5 IU/ml dalteparin) and placebo (balanced salt solution) intravitreally applied during routine pars plana vitrectomy.Primary end point was the development of PVR grade CP (full-thickness retinal folds or subretinal strands in clock hours located posterior to equator) 1 or higher within 12 weeks after surgery. For grading, an end point committee assessed fundus photographs. Secondary end points included best-corrected visual acuity and redetachment rate. A group sequential design with 1 interim analysis was applied using the O'Brien and Fleming boundaries. Proliferative vitreoretinopathy grade CP incidence was compared using a Mantel-Haenszel test stratified by surgeon.A total of 325 patients in 13 German trial sites had been randomized (verum, n = 163; placebo, n = 162). In study eyes, mean laser flare was 31 ± 26 pc/ms. No significant difference was found in PVR rate. Primary analysis in the modified intention-to-treat population results were: verum 28% vs. placebo 23% (including not assessable cases as failures); odds ratio [OR], 1.25; 95% confidence interval [CI], 0.76-2.08; P = 0.77. Those in the per-protocol population were: 12% vs. 12%; OR, 1.05; 95% CI, 0.47-2.34; P = 0.47. None of the secondary end points showed any significant difference between treatment groups. During the study period, no relevant safety risks were identified.Rate of PVR did not differ between adjuvant therapy with 5-FU and LMWH and placebo treatment in eyes with RRD.

Summary Background The human cytokine erythropoietin conveys neuroprotection in animal models but has shown ambiguous results in phase 2 clinical trials in patients with optic neuritis. We assessed the safety and efficacy of erythropoietin in patients with optic neuritis as a clinically isolated syndrome in a multicentre, prospective, randomised clinical trial. Methods This randomised, placebo-controlled, double-blind phase 3 trial, conducted at 12 tertiary referral centres in Germany, included participants aged 18–50 years, within 10 days of onset of unilateral optic neuritis, with visual acuity of 0·5 or less, and without a previous diagnosis of multiple sclerosis. Participants were randomly assigned (1:1) to receive either 33 000 IU erythropoietin or placebo intravenously for 3 days as an adjunct to high-dose intravenous methylprednisolone (1000 mg per day). Block randomisation was performed by the trial statistician using an SAS code that generated randomly varying block sizes, stratified by study site and distributed using sealed envelopes. All trial participants and all study staff were masked to treatment assignment, except the trial pharmacist. The first primary outcome was atrophy of the peripapillary retinal nerve fibre layer (pRNFL), measured by optic coherence tomography (OCT) as the difference in pRNFL thickness between the affected eye at week 26 and the unaffected eye at baseline. The second primary outcome was low contrast letter acuity at week 26, measured as the 2·5% Sloan chart score of the affected eye. Analysis was performed in the full analysis set of all randomised participants for whom treatment was started and at least one follow-up OCT measurement was available. Safety was analysed in all patients who received at least one dose of the trial medication. This trial is registered at ClinicalTrials.gov, NCT01962571. Findings 108 participants were enrolled between Nov 25, 2014, and Oct 9, 2017, of whom 55 were assigned to erythropoietin and 53 to placebo. Five patients were excluded from the primary analysis due to not receiving the allocated medication, withdrawn consent, revised diagnosis, or loss to follow-up, yielding a full analysis set of 52 patients in the erythropoietin group and 51 in the placebo group. Mean pRNFL atrophy was 15·93 μm (SD 14·91) in the erythropoietin group and 14·65 μm (15·60) in the placebo group (adjusted mean treatment difference 1·02 μm; 95% CI −5·51 to 7·55; p=0·76). Mean low contrast letter acuity scores were 49·60 (21·31) in the erythropoietin group and 49·06 (21·93) in the placebo group (adjusted mean treatment difference −4·03; −13·06 to 5·01). Adverse events occurred in 43 (81%) participants in the erythropoietin group and in 42 (81%) in the placebo group. The most common adverse event was headache, occuring in 15 (28%) patients in the erythropoietin group and 13 (25%) patients in the placebo group. Serious adverse events occurred in eight (15%) participants in the erythropoietin and in four (8%) in the placebo group. One patient (2%) in the erythropoietin group developed a venous sinus thrombosis, which was treated with anticoagulants and resolved without sequelae. Interpretation Erythropoietin as an adjunct to corticosteroids conveyed neither functional nor structural neuroprotection in the visual pathways after optic neuritis. Future research could focus on modified erythropoietin administration, assess its efficacy independent of corticosteroids, and investigate whether it affects the conversion of optic neuritis to multiple sclerosis. Funding German Federal Ministry of Education and Research (BMBF).

Purpose The primary endpoint results from the comparing alternative ranibizumab dosages for safety and efficacy in retinopathy of prematurity (CARE-ROP) core study identified ranibizumab as an effective treatment to control acute retinopathy of prematurity (ROP). This study reports the 1- and 2-year follow-up data focusing on long-term functional outcomes and safety. Methods The CARE-ROP trial compared 0.12 mg versus 0.20 mg ranibizumab in 20 infants with ROP in a multicentric, prospective, randomized, double-blind, controlled study design. Sixteen patients entered the follow-up period. An ophthalmologic assessment at one year postbaseline was acquired from all 16 patients and a neurodevelopmental assessment at two years postbaseline was acquired from 15 patients. Results Fifteen of 16 infants were able to fixate and follow moving objects at one year postbaseline treatment. One child progressed to stage 5 ROP bilaterally between the end of the core study and the 1-year follow-up (first seen at PMA 75 weeks). Mean spherical equivalents were -1.9 diopters (D) and -0.75 D in the 0.12 mg and the 0.20 mg treatment arms. Strabismus was present in seven and nystagmus in five out of 16 infants. Mental development scores were within normal limits in six out of ten patients with available data. No statistically significant difference was observed between the two treatment arms. Conclusion Neurodevelopmental and functional ocular outcomes 1 and 2 years after treatment with ranibizumab are reassuring regarding long-term safety. Late reactivation of ROP, however, represents a challenge during the follow-up phase and it is of utmost importance that regular follow-ups are maintained.

Aging is a multidimensional process that may lead to physical, psychological and social changes. This is predominantly due to a decline of sensory functions and their central processing.Selective literature search in Medline and the Cochrane Library.In addition to specific disorders of the sensory organs, unspecific age-related degenerative processes are responsible for the high prevalence of sensory limitations in older people. This can lead to a significant reduction in the quality of life. Balance impairment, decreasing function of hearing, vision, smell and the somatosensory system are associated with an increased risk of falling and an increased mortality in older people. Furthermore, there is evidence for a link between hearing loss and cognitive decline. In addition to the functional ability of every sense on its own, the integration of multiple sensory perceptions plays an increasing role in age-related sensory limitations.Sensory impairments have to be considered when working with older people. Early detection and an interdisciplinary therapeutic approach can reduce the negative consequences. Multimodal stimulation appears to stimulate brain plasticity which helps to compensate age-related changes.HINTERGRUND: Altern ist ein multidimensionaler Prozess, der zu körperlichen, psychologischen und sozialen Veränderungen führt. Einschränkungen der peripheren Sensorik und ihrer zentralen Verarbeitung haben hieran einen erheblichen Anteil.Selektive Literaturrecherche.Neben spezifischen Erkrankungen der Sinnesorgane sind im fortgeschrittenen Lebensalter zusätzlich unspezifische altersbedingte degenerative Prozesse für die hohe Prävalenz von Sinneseinschränkungen in dieser Altersgruppe verantwortlich; diese können zu einer erheblichen Reduktion der Lebensqualität bei den Betroffenen führen. Einschränkungen der Gleichgewichtsfunktion, des Hörvermögens, Sehens, Riechens und der Somatosensorik sind mit einer Erhöhung der Sturzhäufigkeit und einer erhöhten Mortalität älterer Menschen assoziiert. Darüber hinaus gibt es Hinweise für einen Zusammenhang zwischen dem Vorliegen einer Hörstörung und der Wahrscheinlichkeit der Entwicklung einer Demenz. Neben der Funktionsfähigkeit jedes einzelnen Sinnesorgans für sich allein spielt die Fähigkeit der Integration teilweise widersprüchlicher Sinneswahrnehmungen eine zunehmende Rolle unter dem Einfluss altersbedingter Sinneseinschränkungen.Im Umgang mit älteren und alten Menschen ist gezielt auf die Entwicklung von Einschränkungen sensorischer Funktionen zu achten, um durch eine möglichst frühzeitige und ggf. interdisziplinäre Therapie die daraus resultierenden Folgeerkrankungen zu minimieren. Daneben könnten multimodale Therapieansätze dazu beitragen, die Plastizität des Gehirns im Alter anzuregen.

Background It is unknown whether microangiopathic ischemic strokes outside the visual pathway go along with subclinical changes of the retinal structure or the visual system. The objectives of this prospective non-interventional case series were to investigate if spectral-domain optical coherence tomography (SD-OCT) or multifocal visual evoked potentials (mfVEPs) can detect structural retinal changes or functional impairment of the visual system in patients with microangiopathic ischemic stroke. Methods We used SD-OCT to cross-sectionally analyze the retinal morphology of 15 patients with microangiopathic ischemic stroke according to the Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification not affecting the visual pathway. We employed semi-automated segmentation of macular volume scans to analyze the thickness of the macular retinal layers and peripapillary ring scans to investigate the retinal morphology in comparison to a control group without stroke. Visual function was assessed by the mfVEP technique in 13 microangiopathic ischemic stroke patients. Results First peak latency of mfVEPs was significantly delayed in the microangiopathic ischemic stroke group compared to the control patients. Neither the retinal layers nor the mfVEPs’ amplitude differed between the microangiopathic ischemic stroke patients and the control group. Conclusions In conclusion, microangiopathic ischemic stroke patients presented a delayed first peak latency in mfVEPs as a sign of subclinical functional impairment of the visual pathway. However, our case series suggests no influence on retinal structure resulting from microangiopathic ischemic stroke outside the visual system. Larger and longitudinal studies are needed to confirm these mfVEP findings.

The objectives of the study were to investigate the value of optical coherence tomography in detecting papilledema in patients with idiopathic intracranial hypertension (IIH), a disease which is difficult to monitor and which can lead to permanent visual deficits; to analyze retinal changes over time. In this non-interventional case-control study, spectral-domain optical coherence tomography (SD-OCT) was used to analyze the retinal and optic nerve head (ONH) morphology of 21 patients with IIH and 27 age- and sex-matched healthy controls over time. We analyzed the ONH volume using a custom-made algorithm and employed semi-automated segmentation of macular volume scans to assess the macular retinal nerve fiber layer (RNFL) and ganglion cell layer and inner plexiform layer complex as well as the total macular volume. In IIH patients, the ONH volume was increased and correlated with cerebrospinal fluid (CSF) pressure. The ONH volume decreased after the initiation of treatment with acetazolamide. The macular RNFL volume decreased by 5% in 3.5 months, and a stepwise multivariate regression analysis identified CSF pressure as the main influence on macular RNFL volume at diagnosis. The only factor predicting macular RNFL volume loss over time was ONH volume. SD-OCT can non-invasively monitor changes in retinal and ONH morphology in patients with IIH. Increased ONH volume leads to retinal atrophy in the form of macular RNFL volume loss, presumably due to mechanic jamming of the optic nerve at the disc and subsequent axonal loss.

BACKGROUND: Susac syndrome is characterised by the triad of encephalopathy with or without focal neurological signs, branch retinal artery occlusions and hearing loss. Establishment of the diagnosis is often delayed because the triad is complete only in a minority of patients at disease onset. This leads to a critical delay in the initiation of appropriate treatment. Our objective was to establish criteria for diagnosis of either definite or probable Susac syndrome. METHOD: The establishment of diagnostic criteria was based on the following three steps: (1) Definition of a reference group of 32 patients with an unambiguous diagnosis of Susac syndrome as assessed by all interdisciplinary experts of the European Susac Consortium (EuSaC) team (EuSaC cohort); (2) selection of diagnostic criteria, based on common clinical and paraclinical findings in the EuSaC cohort and on a review of the literature; and (3) validation of the proposed criteria in the previously published cohort of all Susac cases reported until 2012. RESULTS: Integrating the clinical presentation and paraclinical findings, we propose formal criteria and recommend a diagnostic workup to facilitate the diagnosis of Susac syndrome. More than 90% of the cases in the literature fulfilled the proposed criteria for probable or definite Susac syndrome. We surmise that more patients could have been diagnosed with the recommended diagnostic workup. CONCLUSIONS: We propose diagnostic criteria for Susac syndrome that may help both experts and physicians not familiar with Susac syndrome to make a correct diagnosis and to prevent delayed treatment initiation.

Introduction: Macular edema after cataract surgery (Irvine-Gass syndrome) or pars plana vitrectomy is a postoperative complication which can lead to permanent visual loss. Increased inflammatory substances, such as prostaglandins and cytokines, are discussed to be causative. Currently, there are no evidence-based guidelines for the treatment of postoperative macular edema. Intravitreal dexamethasone (DEX) could be effective by its anti-inflammatory effect. We examined the functional and morphological results of treatment with 0.7 mg intravitreal DEX implant (Ozurdex®). Methods: In an observational study, we analyzed visual acuity (logMAR), intraocular pressure (IOP), clinical findings, and the central macular thickness (CMT, optical coherence tomography [OCT] Spectralis®, Heidelberg Engineering, 30° macular scan, 19 scans) of 12 eyes before and 1 month after the last DEX implantation (off-label use, Ozurdex®, Allergan, Inc., Irvine, CA, USA) for macular edema after cataract surgery or vitrectomy. Re-implantation was performed when OCT showed new intraretinal fluid along with a decrease in the patient's visual acuity. The mean follow-up was 14.4 ± 10.6 months. Results: Twelve eyes of 12 patients (4 female, 8 male) with a mean age of 62.6 ± 11.9 years were treated with a mean of 2.5 ± 1.6 intravitreal DEX implant injections. Prior to injection, the visual acuity was 0.74 ± 0.34 logMAR and the CMT was 608 ± 129 µm. One month after the last injection (after a mean of 437 ± 322 days), the CMT normalized (300 ± 90 µm, p < 0.01) in all cases with a visual acuity of 0.49 ± 0.43 logMAR (p < 0.01). After 8.1 ± 5.3 months, recurring macular edema could be completely reduced by re-injection in 66% (8 patients). Four patients had no recurrence. Postinjection, the mean IOP was 17.4 ± 6.8 mm Hg. Postinjection, 7 patients required topical antiglaucomatous therapy. Conclusions: Treatment with an intravitreal DEX implant is an effective therapy for postoperative macular edema. Each injection leads to a complete resorption of the edema with a significant increase in visual acuity.

Purpose Recent studies highlighted that early diabetic neurodegeneration is present before microvascular changes are visible. Retinal neurodegeneration can decrease retinal layer thickness. We aimed to determine whether decreased retinal layer thickness is present already in the early time course of disease. Methods A cross-sectional analysis of patients and healthy adults from the German Diabetes Study (GDS, ClinicalTrials.gov Identifier number: CT01055093, https://clinicaltrials.gov/ct2/show/NCT01055093). Inclusion criteria were a diagnosis of diabetes mellitus (DM) within the last 12 months. Retinal layers thickness in the nasal pericentral segment was measured by spectral domain ocular coherence tomography (SD-OCT). For statistical analysis proc mixed (sas-version 9.4) was used. Results One hundred and seventy-eight eyes of 89 patients with type 1 DM (58 males, age 36 ± 11 years, BMI 25.5 ± 4.2 kg/m²) and 242 eyes of 121 patients with type 2 DM (84 males, age 53 ± 10 years, BMI 31.9 ± 6.3 kg/m²) with a disease duration of less than 1 year were compared to 76 eyes of 38 controls (27 males, age 41 ± 16 years, BMI 27.3 ± 6.4 kg/m²). Analysis of retinal layer thickness and visual function did not reveal a significant difference between patients and controls. Conclusion In the early course of DM potential, neurodegeneration does not relate to measureable changes of retinal layer thickness.

Optical coherence tomography (OCT) of the retina and corneal confocal laser scanning microscopy (CLSM) of the subbasal nerve plexus (SBP) are noninvasive techniques for quantification of the ocular neurodegenerative changes in individuals with type 1 diabetes mellitus (T1DM). In adult T1DM patients these changes are hardly related to T1DM only. Instead, ageing and/or lifestyle associated comorbidities have to be considered as putative confounding variables. Therefore, we investigated pediatric T1DM patients (n = 28; 14.2 ± 2.51 y; duration of disease: 5.39 ± 4.16 y) without clinical signs of diabetic retina disease, neuropathy, vasculopathy or nephropathy and compared our findings with those obtained in healthy controls (n = 46; 14.8 ± 1.89 y). The SBP was characterized by the averaged length, thickness, and tortuosity of nerve fibers as well as the number of branching and connecting points. OCT was used to determine the total thickness of the retina (ALL) and the thickness of each retinal layer. Both methods revealed signs of early neurodegenerative changes, e.g. thinning of distinct retinal layers at the pericentral ring and shortening of corneal nerve fibers that are already present in pediatric T1DM patients. Standardization of instruments and algorithms are urgently required to enable uniform comparison between different groups and define normative values to introduce in the clinical setting.

The aim of this non-interventional study was to characterize retinal layer pathology in Susac syndrome (SuS), a disease with presumably autoimmune-mediated microvessel occlusions in the retina, brain, and inner ear, in comparison to the most important differential diagnosis multiple sclerosis (MS).Seventeen patients with SuS and 17 age- and sex-matched patients with relapsing-remitting MS (RRMS) and healthy controls (HC) were prospectively investigated by spectral-domain optical coherence tomography (OCT) including intraretinal layer segmentation in a multicenter study. Patients with SuS additionally received retinal fluorescein angiography (FA) and automated perimetry.Patchy thinning of the retinal nerve fiber layer, ganglion cell layer, inner plexiform layer, inner nuclear layer, and outer plexiform layer compared to corresponding sectors in RRMS and HC eyes (p0.003 for SuS vs RRMS and HC) was observed in 23/34 (68%) SuS eyes, particularly in temporal quadrants. The outer nuclear layer (ONL) and photoreceptor layers (PRL) were not affected. FA performed in 15/17 patients with SuS was negative for disease-specific branch retinal artery occlusions in all but 1 eye at the time of OCT examination and revealed no additional vascular abnormalities, even in severely damaged OCT areas. In a subset of patients with SuS, associations of visual field data with distinct retinal layers were observed.Distinct OCT patterns of scattered, scar-like intraretinal pathology in SuS eyes, sparing the ONL and PRL, suggest a retinal, but not choroidal, vascular pathomechanism and clearly differentiate SuS from RRMS. Depending on the disease stage, OCT and FA provide specific complementary diagnostic information in SuS.

To study the long-term course in patients with idiopathic macular telangiectasia and report the effect of anti VEGF and laser treatment. A retrospective case series of 19 patients/38 eyes with symptomatic type 2 idiopathic macular telangiectasia was performed. Six eyes received intravitreal injections of bevacizumab (1–3 injections), four eyes received focal laser treatment. Follow up examinations comprised visual acuity, biomicroscopy, fluorescein angiography and assessment of macular morphology and thickness by time and spectral-domain optical coherence tomography (OCT). Mean follow-up time was 81 months (range 15–188 months) – the median added up to 80 months. Visual outcome at final visit varied substantially (20/200–20/20). On average visual acuity decreased 1,2 lines (range −0,5 to 6) by 3 years, 2 lines (range −0,5 to 7) by 5 years and 4,1 lines (range 0 to 12) by 10 years. Development of choroidal neovascularisation was observed in only one eye. There was no significant difference in visual acuity between eyes receiving no treatment, intravitreal bevacizumab or laser treatment after 3 and 5 years. Morphological studies by OCT revealed typical changes with retinal atrophy and intraretinal cysts. Visual acuity correlated with the eccentricity of the main manifestation–visual preservation was associated with mainly extrafoveal disease manifestation. Type 2 idiopathic macular telangiectasia is a chronic, often slowly progressing macular disease leading to retinal atrophy and visual impairment over decades. Thorough knowledge about the long term course of this disease is necessary to evaluate possible therapeutic options in the long run.

An association between coronary heart disease (CHD) and age-related macular degeneration (AMD) has long been postulated but results from epidemiological case-control studies, and genetic analyses have been ambiguous. In this study we illuminate the association between AMD and CHD with respect to genetic and environmental risk factors, age of disease onset and AMD subgroups. AMD patients (n = 1036) and age-matched control subjects (n = 412) between 68 and 95 years of age were included in the case-control study. A medical history of CHD, cerebral stroke and arterial hypertension was determined for each individual. The assessment of interacting factors included the current use of systemic medications and smoking habits. Analysis of AMD associated genetic variants included frequent polymorphisms at the complement factor H (CFH, MIM 134370) gene (rs1061170 [p.Y402H], rs800292 [p.I62V]), the complement factor H-related 3 (CFHR3, MIM 605336)/complement factor H-related 1 (CFHR1, MIM 134371) locus (rs6677604; proxy for ΔCFHR3/CFHR1; r(2) = 0.97) as well as the age-related maculopathy susceptibility 2 (ARMS2, MIM 611313) gene (rs10490924 [p.A69S]). Logistic regression identified a significant positive association of AMD with AMD-risk variants in CFH, ARMS2, and smoking ≥ 20 packs/year. A history of CHD and the current use of antihyperuricemic agents were inversely associated with the disease. Significantly fewer patients with rs6677604 nonrisk genotype A/A regularly used statins. ARMS2:p.A69S risk variant was significantly associated with exsudative AMD. AMD patients with risk variants at rs1061170 (CFH:p.Y402H) and ARMS2 and smokers (≥20 packs/year) were significantly earlier affected by AMD than those carrying the non-risk variants at each locus. Our data support three major conclusions. First, the age of AMD onset is significantly influenced by genetic and environmental risk factors. Second, in support of previous reports we also show that the ARMS2 rs10490924:T allele is significantly linked to exsudative AMD. And finally, a self-reported history of CHD was inversely associated with AMD in this study. Novel therapeutic strategies aiming at preventing the development of AMD may considerably differ from those that have been developed to treat cardiovascular disorders as both common disorders likely underlie different pathomechanisms.

A characteristic disease pattern may be reflected by retinal layer thickness changes in non-arteritic anterior ischaemic optic neuropathy measured using spectraldomain optical coherence tomography. Retinal layer segmentation is enabled by advanced software. In this study, retinal layer thicknesses in acute and chronic non-arteritic anterior ischaemic optic neuropathy were compared.A single-centre cross-sectional analysis was used.A total of 27 patients (20 age-matched healthy eyes) were included: 14 with acute (7 days) and 13 patients with chronic non-arteritic anterior ischaemic optic neuropathy.Macular volume and 12° peripapillary ring optical coherence tomography scans were used.The peripapillary thicknesses of the following layers were determined by manual segmentation: retinal nerve fibres, ganglion cells + inner plexiform layer, inner nuclear layer + outer plexiform layer, outer nuclear layer + inner segments of the photoreceptors and outer segments of the photoreceptors to Bruch's membrane. Macular retinal layer thicknesses were automatically determined in volume cubes centred on the fovea.Peripapillary retinal swelling in acute nonarteritic anterior ischaemic optic neuropathy was attributable to retinal nerve fibre layer, ganglion cell layer/inner plexiform layer and outer nuclear layer/segments of the photoreceptors thickening. In chronic cases, peripapillary retinal nerve fibre layer, macular ganglion cell layer and inner plexiform layer thinning were observed.In acute non-arteritic anterior ischaemic optic neuropathy, the inner and outer peripapillary retinal layers are affected by thickness changes. In chronic cases, atrophy of the ganglion cells and their axons and dendrites is evident by inner retinal layer thinning.

RESUME Objective: To assess the 3-year visual outcome of intravitreal bevacizumab in inflammatory ocular neovascularization. Design: Experimental study. Methods: Retrospective multicenter consecutive case series in 81 patients with inflammatory ocular neovascularization refractory to standard therapy and treated with intravitreal bevacizumab. The outcome measures included improvement of best corrected visual acuity expressed as logarithm of minimum angle of resolution (logMAR) and paired comparison decrease in central foveal thickness by optical coherence tomography. Results: Mean best corrected visual acuity improved from baseline 0.699 (6/30 or 20/101) (SD 0.434) to 0.426 (6/16 or 20/53) (SD 0.428) (n 81; p 0.001), a gain of 2.7 lines (median 3 injections; 81 eyes; 81 patients). Paired comparisons revealed significant central foveal flattening at 3 years of 97.9 m( n 51; p 0.001). In a subgroup analysis, visual improvement was significant for ocular histoplasmosis (p 0.026); multifocal choroiditis (p 0.05); serpiginous choroiditis (p 0.028); ocular toxoplasmosis (p 0.042); and punctate inner choroidopathy (p 0.015). In a subgroup analysis, foveal flattening was significant for ocular histoplasmosis (p 0.004); multifocal choroiditis (p 0.007); serpiginous choroiditis (p 0.011); and punctate inner choroidopathy (p 0.001). Of the group, 5 eyes developed submacular fibrosis, 1 eye retinal pigment epithelial tear, and 1 eye macular ischemia in the context of vasculitis. Conclusion: At 3 years, intravitreal bevacizumab sustained significant visual improvement of 2.7 lines and significant foveal flattening of 98 m in a wide variety of inflammatory ocular diseases without major complications after a median of 3 injections. Objet : Evaluation du resultat visuel de 3 annees de traitement intravitreen au bevacizumab pour une neovascularisation oculaire

Background: The Wuerzburg bleb classification score (WBCS) aims at an objective and standardized assessment of the developing filtering bleb after trabeculectomy, in order to detect and treat bleb scarring at the earliest possible stage of development. The purpose of this retrospective study was to evaluate the prognostic value of the early postoperative WBCS for the long-term outcome of trabeculectomy. Methods: The WBCS is a grading system for clinical bleb morphology. It evaluates the following parameters: vascularization, corkscrew vessels, encapsulation and microcysts. The WBCS of 113 eyes of 113 consecutive patients after trabeculectomy was determined 1 day, 1 and 2 weeks, 3, 6 and 12 months after surgery. Complete success was defined as an intra-ocular pressure (IOP) 20% pressure reduction without glaucoma medication after 1 year. Results: A complete success rate of 73.9% and a qualified success rate of 82.4% were achieved 1 year after surgery. The average total bleb score during follow-up in the success group was always higher than in the failure group, but there was no statistically significant difference at any time. The bleb average score for eyes with an IOP of ≤12 mm Hg after 2 weeks was significantly higher (p = 0.005) than for eyes with an IOP ≧13 mm Hg at the end of follow-up. Conclusion: Patients with a higher early WBCS postoperatively had a significantly lower IOP 1 year after surgery. However, the study could not reveal a certain prognostic value of the early total bleb score using the WBCS for the long-term complete success of trabeculectomy.

Purpose: Transient ocular hypotony commonly occurs after 23-gauge (23G) vitrectomy. To assess possible causes, we visualized the sclerotomy site and pars plana by anterior segment optical coherence tomography (AS-OCT). Procedures: We prospectively analyzed the intraocular pressure (IOP) and findings related to clinical hypotony, assessed by AS-OCT, in 13 consecutive eyes of 13 patients receiving 23G vitrectomy. Five patients receiving a 20G vitrectomy served as controls. Results: The mean IOP after 23G vitrectomy was 11 mm Hg (range: 5–32 mm Hg; 13 eyes) at postoperative day 1. In contrast to controls, AS-OCT showed a scleral gap at the incision site in 22/39 sclerotomies (10/13 eyes), and subclinical choroidal detachment in 9/13 eyes. Conclusions: A scleral gap and choroidal detachment at the incision site are frequent findings following 23G vitrectomy. These subclinical features may account for postoperative hypotony as they are absent in 20G vitrectomy and scleral sutures. Hypotony following 23G vitrectomy is a self-limiting phenomenon and usually does not require therapeutic intervention.

Purpose: Our aim was to evaluate differences in the outcome of bevacizumab or triamcinolone acetate (TA) treatment in patients with macular edema (ME) after central retinal vein occlusion (CRVO). Procedures: In a retrospective assessment 9 bevacizumab-treated patients and 9 TA-treated ones with ME after CRVO were pair-matched according to initial best-corrected visual acuity (BCVA) and central macular thickness (CMT) as measured by Stratus optical coherence tomography. BCVA and CMT were the main endpoints. Results: The initial BCVA of 0.15 ± 0.1 increased not significantly by 1.0 ± 3.1 lines in the bevacizumab-treated patients after a mean of 10 months. The initial BCVA of 0.17 ± 0.1 decreased by –1.0 ± 5.2 lines after a mean of 13 months following initial TA injection. The only significant decrease in mean CMT by 239 ± 209 µm occurred 8 weeks after initial bevacizumab injection. Conclusions: Both substances are able to stabilize CMT and BCVA in ME after CRVO, but only bevacizumab was devoid of unfavorable intraocular pressure elevation.

Fingolimod is a potent drug in relapsing forms of multiple sclerosis. Visual impairment due to fingolimod-associated macular edema (FAME) usually leads to discontinuation of fingolimod therapy. Methods : We report on a 24-year old woman with bilateral FAME. Results : We continued fingolimod and added oral acetazolamide, which led to recovery of visual acuity and regression of macular edema. However, fingolimod had to be discontinued when fluorescein angiography revealed an enlarged foveal avascular zone. Discussion and conclusion : Oral acetazolamide might be a treatment option for FAME, while ischemic conversion may be limiting. Ophthalmologic assessments are mandatory for follow-up when fingolimod therapy is continued after onset of FAME.

Congenital cystic eye is a rare ocular and orbital malformation describing an intraorbital cavity lined by neuroglial tissue. Clinical and histopathologic findings of a 3-year-old boy with a congenital cystic eye are presented. A 4-year-old otherwise healthy boy with anophthalmia of the right eye was referred because of progressive volume enlargement of his congenital cystic lesion of the right orbit. Imaging techniques revealed a hyperintense cystic tumor with calcifications of the wall. There was no evidence of a globe, no communication to the intracranial space and a normal bony orbit. The mass was excised and a 20-mm silicone orbital implant inserted. Microscopic examination of the cyst revealed irregularly shaped layers of fibrovascular tissue lined by neuroglial tissue with calcified bodies and positive immunohistochemical staining for glial fibrillary acid protein (GFAP), neuron-specific enolase (NSE) and neurofilament protein (NF). No structures like cornea, lens, retinal pigmented epithelium or rosettes were identified. Congenital cystic eye is a primary developmental abnormality of the globe caused by an invaginational arrest of the primary optic vesicle between the 2-mm and 7-mm stages of fetal development. The luminal neuroglial tissue contains dystrophic calcified bodies and degenerated primitive nerve fibers. The enlargement of the cyst may be due to fluid produced by glial tissue. The differential diagnoses for cystic anomalies without epithelial lining include microphthalmia with cyst, microphthalmia with cystic teratoma, ectopic brain tissue and meningoencephalocele.

To investigate whether patients with moyamoya angiopathy without obvious retinal pathologies such as retinal infarctions or the congenital morning glory anomaly may have subtle subclinical retinal changes.In this cross-sectional study, spectral domain optical coherence tomography was used to analyze the retinal morphology of 25 patients with idiopathic moyamoya angiopathy and 25 age- and sex-matched healthy controls. We analyzed the retinal vasculature with blue laser autofluorescence, lipofuscin deposits with MultiColor confocal scanning laser ophthalmoscopy, and the optic nerve head (ONH) volume with a custom postprocessing algorithm. In addition to the total retinal thickness, semiautomated segmentation was used for segmentation of retinal layers in macular cross scans, macular volume scans, and peripapillary ring scans.The main finding was a pronounced reduction of the ONH volume in moyamoya angiopathy compared with controls (0.76 ± 0.45 mm(3) and 1.47 ± 0.50 mm(3), respectively; p0.0001), which was associated with a less pronounced reduction of the retinal nerve fiber layer in macular volume scans (0.97 ± 0.11 mm(3) and 1.10 ± 0.10 mm(3), respectively; p0.001). Autofluorescence and MultiColor confocal scanning laser ophthalmoscopy images revealed no pathologies except for one branch retinal artery occlusion.Our results indicate that even patients with moyamoya angiopathy who do not have obvious retinal abnormalities have retinal abnormalities. These can be detected by spectral domain optical coherence tomography, and the association of ONH abnormalities with the vascular changes may suggest that idiopathic moyamoya angiography is a systemic disease involving abnormalities of the early mesodermal development.

Background West Indian punctate keratopathy (WIPK) is characterized by stable, asymptomatic, white superficial corneal opacities. We examined this patient's lesions with in vivo confocal microscopy. Methods A 47-year-old North American male patient presented with bilateral, dense, punctate, white opacities of the corneal epithelium. Confocal microscopy was performed using the Heidelberg Retina Tomograph II/Rostock Cornea Module. Results The patient was of Afro-Caribbean descent. In vivo confocal microscopy showed hyporeflective areas with multiple small hyperreflective dots inside at the level of the basal corneal epithelium with an unaffected Bowman layer. There was no round cell infiltration. Conclusions West Indian punctate keratopathy should be considered in the differential diagnosis of scattered spot-like opacities with a history of residence in the endemic West Indies. Inflammatory entities can be excluded by in vivo confocal microscopy.

To investigate the benefit of adding bevacizumab to intravitreal recombinant tissue plasminogen activator (rTPA) and gas as initial therapy in subretinal hemorrhage and choroidal neovascularization because of age-related macular degeneration.Thirty-eight consecutive patients with recent (1-31 days) subretinal hemorrhage who were treated with intravitreal rTPA and gas (26 patients) or with intravitreal bevacizumab, rTPA, and gas (12 patients) were included in this retrospective analysis. In all patients, a standardized antivascular endothelial growth factor therapy was followed. Testing of best-corrected visual acuity, biomicroscopy, and fundus examination were performed at 4 weeks and 7 months.The mean pretreatment best-corrected visual acuity in the rTPA/gas group was 0.08 ± 0.09 and 0.12 ± 0.13 in the bevacizumab/rTPA/gas group. After 4 weeks, it was significantly higher in the bevacizumab/rTPA/gas group (0.25 ± 0.26) than in the rTPA/gas (0.08 ± 0.1) group (P0.05). Also, after 7 months, best-corrected visual acuity was significantly higher in the bevacizumab/rTPA/gas group (0.07 ± 0.07 vs. 0.24 ± 0.35; P0.05). Reading vision could be restored in 0% (rTPA/gas) versus 50% (bevacizumab/rTPA/gas). Stabilization (0 ± 2 lines) or improvement of best-corrected visual acuity was obtained in 62% (rTPA/gas) versus 84% (bevacizumab/rTPA/gas).From our retrospective pilot study, there is a strong indication that the addition of intravitreal bevacizumab is safe and superior to the displacement of submacular hemorrhages alone with rTPA and gas.

Aims: The use of the chemotherapeutic cytosine arabinoside (Ara-C) causes an ocular toxic reaction, characterized by aspecific keratopathy. We examined the pathway of the damaged cells by in vivo confocal microscopy. Methods: Prospective study of 11 patients with acute myeloic leukemia treated with high-dose Ara-C. Ten eyes developed fluorescein-negative punctate keratopathy, and were examined by slit lamp and in vivo confocal biomicroscopy at days 1, 3–4 and 9–14 after the beginning of ocular symptoms. Results: In vivo confocal microscopy revealed disseminated highly reflective granular irregular intraepithelial elements in the central cornea, which affected about 3% of epithelial cells. At day 1 of symptoms, these elements were present only in the basal epithelial layer (median 275.5/mm2), at days 3–4 they were mainly found in the basal (187.5/mm2) but also in the apical layers (96/mm2), at days 9–14 they mainly presented in more superficial layers (115/mm2 apically vs. 15.5/mm2 in the basal layers). Discussion: The intraepithelial distribution of cells with a granular cytosolic signal evolved over time, reflecting the migration of the necrotic basal cells to the wing cell layer and finally to apical epithelial layers. The desquamation of the necrotic cells is related to the resolution of symptoms, according to the period of the epithelial cell turnover. By confocal microscopy, we could follow the intraepithelial route of cells damaged by Ara-C in vivo.

Purpose: To evaluate the role of anterior segment optical coherence tomography (OCT) in describing the morphology and outcome of encapsulated filtering blebs after bleb needling. Procedures: Prospective assessment of 9 patients – before, 2 days and 6 months after filtering bleb needling with 5-FU – using slit-lamp examination, Goldmann tonometry and OCT. Results: Before the needling, the average internal height of the cyst was 1.3 ± 0.8 mm. Two days after the needling procedure, the cyst collapsed in 5 patients. After 6 months, the average internal cyst height was 0.7 ± 0.4 mm. All patients with a collapsed cyst at day 2 after needling had controlled regulated IOP without glaucoma medication. Conclusions: The preoperative internal height of the cyst does not correlate with the outcome of the needling. A collapsed cyst at day 2 after needling is an indicator of controlled intraocular pressure, whereas a prominent cyst after 6 months indicates poor function.

Purpose To assess the long-term role of bevacizumab (Avastin; Genentech Inc, South San Francisco, California, USA) in inflammatory ocular neovascularization. Design Retrospective multicenter consecutive case series of inflammatory ocular neovascularization. Methods settings: Multicenter institutional and private practices. study population: Patients with inflammatory ocular neovascularization in one or both eyes of varying etiologies who failed standard therapy. intervention: Intravitreal injection of bevacizumab. main outcome measures: Improvement of best-corrected visual acuity (BCVA) expressed as logarithm of minimal angle of resolution (logMAR), and decrease in central foveal thickness as measured by optical coherence tomography at 6, 12, 18, and 24 months of follow-up. Results Mean logMAR BCVA (central foveal thickness) following intravitreal bevacizumab was as follows: baseline, 0.65 (6/27 or 20/90) (338 μm; 99 eyes of 96 patients); 6 months, 0.42 (6/16 or 20/53) (239 μm; 2.0 injections; 81 eyes); 12 months, 0.39 (6/15 or 20/49) (241 μm; 2.3 injections; 95 eyes); 18 months, 0.40 (6/15 or 20/50) (261 μm; 3.0 injections; 46 eyes); and 24 months, 0.34 (6/13 or 20/44) (265 μm; 3.6 injections; 27 eyes). Paired comparisons revealed significant visual improvement at 6 months of 2.4 lines ( P = .000), at 12 months of 2.5 lines ( P = .000), at 18 months of 2.5 lines ( P = .001), and at 24 months of 2.2 lines ( P = .013). Paired comparisons revealed significant central foveal flattening at 6 months of 78 μm ( P = .000), at 12 months of 85 μm ( P = .000), at 18 months of 90 μm ( P = .003), and at 24 months of 77 μm ( P = .022). Three eyes developed submacular fibrosis and 1 eye submacular hemorrhage. Conclusion Intravitreal bevacizumab led in the long-term to significant mean visual improvement of ≥2.2 lines and significant foveal flattening in a wide variety of inflammatory ocular diseases without major complications.

To correlate clinical filtering bleb function with characteristics as detected by in vivo confocal microscopy.In a case-matched cross-sectional study, 52 eyes of 48 patients were examined 1 day to 12.8 years after primary trabeculectomy (mean 375 d). The patients were examined clinically and by in vivo confocal microscopy (Rostock Cornea Module/Heidelberg Retina Tomograph II, Heidelberg Engineering, Inc, Heidelberg, Germany). Nine early and 17 late functioning blebs were pair-matched with malfunctioning blebs. Stromal fiber patterns, the number of intraepithelial and stromal cystic spaces, and the amount of cellular infiltrates were evaluated.Four stromal patterns (trabecular, reticular, corrugated, compacted) invisible to slit-lamp biomicroscopy could be distinguished by in vivo confocal microscopy. The trabecular pattern occurred only in functioning blebs, particularly early postoperatively. Intraepithelial cystic spaces were associated with functioning late blebs, whereas they were equally distributed in early blebs. In contrast, stromal cystic spaces indicate function in early blebs, whereas in late blebs the number of these cavities was similar in both groups. The density of intraepithelial and stromal round cells was higher in functioning late blebs compared with malfunctioning late blebs.In vivo confocal microscopy allows to assess filtering bleb structures that are invisible biomicroscopically. Some morphologic features detected by this technique seem to indicate filtering bleb function and time after surgery. The predictive value of these features deserves further clarification in a prospective longitudinal study.

Purpose: This study aimed to analyse visual outcome, surgical complications and recurrence rates 3 years after removal of subretinal choroidal neovascularization (CNV) in patients with age-related macular degeneration (AMD). Methods: The study involved a retrospective analysis of 50 eyes of 50 patients who underwent surgical removal of CNV in AMD between February 1996 and June 1998. The minimum follow-up period was 36 months. Improvement or worsening of visual acuity (VA) was defined as a change of more than two lines. Results: The mean reduction in VA was 2.2 ± 6.9 lines. Visual acuity improved in 12 eyes, remained stable in 16 eyes and worsened in 22 eyes. Recurrence of CNV occurred in three eyes. Conclusion: After surgical excision of age-related subfoveal CNV, VA improved or stabilized in a large group of patients. Considering the development of VA and the low recurrence rate, surgical treatment seems to be beneficial compared to the natural course of CNV over a longterm follow-up of more than 3 years.

Background: Multifocal choroiditis with panuveitis is a rare disease. The educational merit of this case presentation results from the good documentation and the impressive ocular fundus pictures. Case presentation: We illustrate the 3-year course of disease in a 22-year-old myopic white woman with multifocal choroiditis with panuveitis and secondary choroidal neovascularization. The activity of the disease was evaluated clinically by optical coherence tomography and fluorescein angiography. Choroidal neovascularization was treated by intravitreal bevacizumab (2.5 mg/0.1 ml). Our patient lacked systemic therapy for the first 11 months because of noncompliance. Conclusions: The case is remarkable as the delayed onset of peripheral lesions and the additional existence of high myopia made diagnosis difficult. In addition, it demonstrates that full outbreak of disease with multiple central and peripheral fundus lesions and secondary choroidal neovascularization can develop without systemic treatment.