Continued anti-VEGF treatment does not prevent recurrences in eyes with stable neovascular age-related macular degeneration using a treat-and-extend regimen: a retrospective case series.

BACKGROUND: The continuation of anti-vascular endothelial growth factor (anti-VEGF) treatment after achieving stability in patients with neovascular age-related macular degeneration has generally been advocated. In our own patients, we thought to assess whether continued anti-VEGF treatment is capable of preventing recurrences. METHODS: In this retrospective observational case series, patients with stable disease either opted to continue treatment every 12-14 weeks (Group 1) or stopped treatment with subsequent follow-up visits every 8-12 weeks (Group 2). RESULTS: Of the 103 eyes of 103 patients achieving stability, 49 eyes continued treatment (Group 1), whereas treatment was stopped in 54 eyes undergoing regular follow-up (Group 2). Recurrent disease was observed in 21 (42.9%) and 33 (61.1%) cases in Group 1 and Group 2, respectively (p = 0.08). Time between achieving stable disease and recurrence was comparable between Group 1 and Group 2 (11.1 ± 8.2 months vs. 9.2 ± 6.7 months; p = 0.43). The number of visits between achieving stability and disease recurrence was similar, but not the number of injections (3.5 ± 2.0 vs. 0.2 ± 0.4; p < 0.001). CONCLUSIONS: Continuing anti-VEGF therapy after achieving functional and morphological stability every 12-14 weeks does not prevent recurrences. Patients deserve to be informed of a potential lifetime risk of recurrences, even under continued therapy.

Ocular TGF-ß, Matrix Metalloproteinases, and TIMP-1 Increase with the Development and Progression of Diabetic Retinopathy in Type 2 Diabetes Mellitus.

Diabetic retinopathy (DR) is a sight-threatening late complication of diabetes mellitus (DM). Even though its pathophysiology has not been fully elucidated, several studies suggested a role for transforming growth factor- (TGF-) ß, matrix metalloproteinases (MMPs), and tissue inhibitors of matrix metalloproteinase (TIMP) in the onset and progression of the disease. Consequently, the aim of this study was to analyze the concentrations of TGF-ß1, TGF-ß2, TGF-ß3, MMP-3, MMP-9, and TIMP-1 in patients with different stages of DR in order to identify stage-specific changes in their concentrations during the progression of the disease. Serum and aqueous humor (AH) samples were collected during intraocular surgery, and eyes were classified into the following groups: healthy controls (n = 17), diabetic patients with non-apparent DR (n = 23), mild/moderate nonproliferative DR (NPDR) (n = 13), and advanced NPDR/proliferative DR (PDR) without vitreal hemorrhage (n = 14). None of the patients had been under anti-VEGF or laser treatment within six months prior to surgery. In the AH, TGF-ß1 levels increased in advanced NPDR/PDR by a factor of 5.5 compared to the control group. Similarly, an increase in MMP-3 and TIMP-1 levels in the AH was evident in the later stages of DR, corresponding to a 7.7- and 2.4-fold increase compared to the control group, respectively, whereas serum levels of the studied proteins remained similar. In conclusion, increased concentrations of TGF-ß1, MMP-3, and TIMP-1 in the AH, but not in the serum, in advanced NPDR/PDR indicate that the intraocular regulation for these cytokines is independent of the systemic one and suggest their involvement in the progression of DR.

Visual Outcome after Intravitreal Anti-VEGF Therapy for Macular Neovascularisation Secondary to Sorsby's Fundus Dystrophy: A Systematic Review.

The aim of this paper is to summarise our own and to review published experience regarding the long-term outcome of intravitreal treatment for macular neovascularisation (MNV) secondary to Sorsby's fundus dystrophy (SFD). A systematic literature search using the MeSH terms [Sorsby] and [anti-vascular endothelial growth factor (VEGF)] was conducted in NCBI/PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), ScienceDirect, Google Scholar and ClinicalTrials.gov to identify publications reporting anti-VEGF treatment outcomes in SFD. Treatment outcomes were extracted for this meta-analysis from 14 publications and an own patient reporting a total of 31 cases with a mean follow-up (FU) of 54 months. Both eyes were affected in ten (32.3%) instances. Heterogenous reporting limited the comparability of the outcomes. All papers in common, however, reported satisfied to excellent responses to anti-VEGF therapy if patients were diagnosed and treated immediately after onset of symptoms. Of 20 eyes, for which visual acuity was reported before and after treatment, five worsened and seven improved by more than 1 line, whereas eight eyes maintained their function by end of the follow up, and 11 eyes (55%) maintained a driving vision (Snellen VA ≥ 0.5). Of six eyes with a VA < 0.5, VA improved in one to VA ≥ 0.5, whereas of 14 eyes with an initial VA ≥ 0.5, this dropped to <0.5 despite therapy. In MNV secondary to SFD, the delay between first symptoms and access to anti-VEGF treatment determines subretinal scar formation and thereby, functional prognosis. If treated early, this is generally favourable under regular controls and a consequent anti-VEGF treatment of MNV activity.

How are social stressors at work related to well-being and health? A systematic review and meta-analysis.

BACKGROUND: Social relationships are crucial for well-being and health, and considerable research has established social stressors as a risk for well-being and health. However, researchers have used many different constructs, and it is unclear if these are actually different or reflect a single overarching construct. Distinct patterns of associations with health/well-being would indicate separate constructs, similar patterns would indicate a common core construct, and remaining differences could be attributed to situational characteristics such as frequency or intensity. The current meta-analysis therefore investigated to what extent different social stressors show distinct (versus similar) patterns of associations with well-being and health. METHODS: We meta-analysed 557 studies and investigated correlations between social stressors and outcomes in terms of health and well-being (e.g. burnout), attitudes (e.g. job satisfaction), and behaviour (e.g. counterproductive work behaviour). Moderator analyses were performed to determine if there were differences in associations depending on the nature of the stressor, the outcome, or both. To be included, studies had to be published in peer-reviewed journals in English or German; participants had to be employed at least 50% of a full-time equivalent (FTE). RESULTS: The overall relation between social stressors and health/well-being was of medium size (r = -.30, p < .001). Type of social stressor and outcome category acted as moderators, with moderating effects being larger for outcomes than for stressors. The strongest effects emerged for job satisfaction, burnout, commitment, and counterproductive work behaviour. Type of stressor yielded a significant moderation, but differences in effect sizes for different stressors were rather small overall. Rather small effects were obtained for physical violence and sexual mistreatment, which is likely due to a restricted range because of rare occurrence and/or underreporting of such intense stressors. CONCLUSIONS: We propose integrating diverse social stressor constructs under the term "relational devaluation" and considering situational factors such as intensity or frequency to account for the remaining variance. Practical implications underscore the importance for supervisors to recognize relational devaluation in its many different forms and to avoid or minimize it as far as possible in order to prevent negative health-related outcomes for employees.

Long-term outcomes of intravitreal therapy for symptomatic diabetic macular oedema in a real-world setting in Switzerland.

OBJECTIVE: To assess the long-term visual outcomes in eyes with symptomatic diabetic macular oedema (DME) under intravitreal treatment (IVT) in a clinical routine setting. METHODS: Patients with newly diagnosed DME were included in this retrospective study if they had received at least three IVTs and a follow-up period ≥ 2 years. Due to altered treatment patterns since the approval of ranibizumab for DME in 2012, patients were subdivided according to their first IVT before 2013 (group 1) or thereafter (group 2). The primary outcome measure was the evolution of best-corrected visual acuity (BCVA) over time. RESULTS: Of 217 eyes (191 patients) with DME, 151 eyes (117 patients) fulfilled the inclusion criteria (63 eyes in the first period, 88 in the second period). Mean follow-up time was 7.9 ± 3.1 (group 1) and 4.1 ± 1.4 years (group 2; p < 0.001). Visual gains were similar in the first year (group 1: + 5.3 ± 15.5, group 2: + 7.3 ± 12.2 Early Treatment Diabetic Retinopathy Study (ETDRS) letters; p = 0.44), but not thereafter (after 2 years in group 1: + 4.4 ± 15.0, group 2: + 8.3 ± 13.0 ETDRS letters; p = 0.038). During the first year, group 1 patients received less clinical examinations (group 1: 6.6 ± 3.3, group 2: 7.5 ± 2.1; p = 0.007) and less injections (group 1: 3.6 ± 2.7, group 2: 6.1 ± 2.7; p < 0.001). CONCLUSION: A greater visual gain, in response to more intensive treatment during the first year, was maintained for at least 5 years in group 2 subjects. Our data confirm that in a real-world setting, early intensive treatment results in satisfying long-term visual outcomes.

Disease stability and extended dosing under anti-VEGF treatment of exudative age-related macular degeneration (AMD) - a meta-analysis.

PURPOSE: To assess disease stability (absence of intra- and/or subretinal fluid) and the portion of eyes being capable to extend their treatment interval to ≥ 12 weeks in exudative age-related macular degeneration (AMD). METHODS: A systematic literature search was performed in NCBI, PubMed, CENTRAL, and ClinicalTrials.gov to identify clinical studies reporting treatment outcomes for ranibizumab, aflibercept, and brolucizumab in exudative AMD under a treat-and-extend protocol and a follow-up of ≥ 12 months. Weighted mean differences and subgroup comparisons were used to integrate the different studies. RESULTS: This meta-analysis refers to 29 published series, including 27 independent samples and 5629 patients. In the pooled group, disease stability was reported in 62.9% and 56.0%, respectively, after 12 and 24 months of treatment, whereas treatment intervals were extended to ≥ 12 weeks in 37.7% and 42.6%, respectively. Ranibizumab, aflibercept, and brolucizumab differed regarding their potential to achieve disease stability (56.3%, 64.5%, and 71.5% after 12, and 50.0%, 52.7% and 75.7% after 24 months; p = < 0.001) and to allow an interval extension to ≥ 12 weeks (28.6%, 34.2%, and 53.3% after 12, and 34.2%, 47.7%, and 41.7% after 24 months; p = < 0.001). CONCLUSION: The portion of eyes achieving disease stability regressed in the second year, whereas the portion of eyes under a ≥ 12-week interval increased. This discrepancy may reflect the challenges in balancing between under-treatment and a reduced treatment burden.

Risks and Challenges in Interpreting Simultaneous Analyses of Multiple Cytokines.

Purpose: To determine the inherent risks of handling results below the lowest detectable value in the analysis of multiple cytokines in the aqueous humor of patients with retinal diseases by comparing possible statistical strategies to lower the risk of mis interpretation or over interpretation of results. Furthermore, in analyzing multiple cytokines simultaneously, the challenge of multiple comparison arises. Methods: The analyses were based on parallel testing of 43 cytokines in 58 aqueous humor samples from patients with macular hole or epiretinal membrane. Substitution of values below the detection limit with 0.1 ×, 0.5 ×, or 1.0× of the lowest level of quantitation was compared with handling as missing value. The impact of correction for multiple comparisons was assessed using the Holm correction. Results: When comparing macular hole with epiretinal membrane, not substituting the missing data revealed a difference (P < 0.05) for five compared with wight cytokines after their substitution, indicating an increased risk for under-estimating group differences (type II error). Correcting for multiple comparisons revealed a relevant risk of over estimating group differences (type I error). Conclusions: Physiologic cytokine concentrations in ocular fluids typically range at or below the lowest level of quantitation. Handling of results below this cutoff as missing leads to increased type II errors. Not correcting for multiple comparisons increases the risk of a type I error. Taken together, both harbor a systematic inherent risk of misinterpretation of the results. Translational Relevance: Ignoring the inherent risks of data misinterpretation in analyses of ocular fluid samples may result in mis leading conclusions regarding their biological relevance.

Outcome of treatment for neovascular age-related macular degeneration by practice-based ophthalmologists compared with a macula clinic.

PURPOSE: The aim of this study was to compare neovascular age-related macular degeneration (nAMD) treatment outcomes between ophthalmological practices and a specialized macula clinic. METHODS: In this case series, we included 347 treatment-naïve eyes with nAMD (332 patients). All patients received intravitreal anti-VEGF treatment using ranibizumab or aflibercept at the discretion of the treating physician using a treat-and-extend protocol either by one of 28 practice-based ophthalmologists (group 1; n = 215 eyes) or at a macula clinic (group 2; n = 132 eyes) over 24 months. RESULTS: Baseline characteristics of the patients in the two groups, including age, initial BCVA (group 1 58.2 ± 18.5, group 2 60.8 ± 16.1 ETDRS letters; p = 0.32), and baseline CRT, were comparable. By end of the observation period, both groups presented similar BCVA (group 1 67.4 ± 19.3, group 2 66.8 ± 17.2 letters; p = 0.51), visual gains (group 1 7.8 ± 16.9, group 2 5.8 ± 14.4 letters; p = 0.11), CRT values (group 1 259.6 ± 80.5, group 2 277.4 ± 87.1 µm; p = 0.10), and number of injections (group 1 13.0 ± 4.5, group 2 11.6 ± 4.1 injections; p = 0.09), as well as portion of eyes with stable disease (absence of any intraretinal fluid and absence or stability of subretinal fluid and pigment epithelial detachment: group 1 78% (n = 128), group 2 75% (n = 95); p = 0.63). However, there was a significant difference regarding the number of examinations (group 1 12.8 ± 5.0, group 2 9.7 ± 3.1 visits; p = 0.0005). CONCLUSIONS: nAMD treatment delivered by practice-based ophthalmologists is reasonable regarding functional outcomes and reduces the indirect treatment burden, which is partially outweighed by significantly more clinical examinations in ophthalmological practices.

Work and sleep quality in railway employees: an actigraphy study.

This actigraphy study tests whether daily work stressors (time pressure, social stressors), work resources (control, social support) and mental detachment from work predict sleep quality, when controlling for demands and control after work. Fifty-two railway employees participated during five consecutive workdays by completing diary questionnaires and wearing an actigraphy device. The results confirmed that social stressors from supervisors predicted more frequent sleep fragmentation and lower sleep efficiency the following night. Higher levels of daily time control at work predicted shorter sleep-onset latency and better self-reported sleep quality. Leisure time control as a covariate turned out to be a private resource, followed by fewer awakenings the following night. Detachment after work related negatively to social stressors and time pressure at work but was unrelated to indicators of sleep quality; detachment after work neither mediated nor moderated the relationship between social stressors from supervisors and sleep quality. Work redesign to increase time control and reduce social stressors is recommended to preserve daily recovery in railway employees. Practitioner summary: Sleep is important to renew health- and safety-related resources in railway employees. This diary and actigraphy study shows that higher daily work stressors were antecedents of lower sleep quality the following night, while more time control was followed by better sleep quality. Work redesign could promote health and safety by improving sleep quality.

Adding a Corticosteroid or Switching to Another Anti-VEGF in Insufficiently Responsive Wet Age-Related Macular Degeneration.

PURPOSE: To compare the effect of adding a corticosteroid or switching to another anti-VEGF treatment in patients with exudative age-related macular degeneration (eAMD) with persisting intraretinal fluid on anti-VEGF monotherapy. METHODS: This retrospective, interventional case series involved 43 pseudophakic eyes with eAMD and persistent intraretinal fluid on anti-VEGF treatment that switched treatment to a combination of Ozurdex® or Triamcinolone and anti-VEGF therapy (group 1) or to another anti-VEGF agent (group 2). The number of injections, time to re-injection, change in central retinal thickness (CRT), and best-corrected visual acuity (BCVA) from 12 months prior to 12 months after switch to third-line therapy were defined as primary outcomes. RESULTS: Whereas the treatment demand was reduced (from 8.8±2.2 to 4.6±2.9 injections; p=0.001) and the re-injection interval extended in group 1 (from 1.5±0.4 months to 4.4±3.8 months; p=0.001), these parameters did not change in group 2 (7.4±1.6 to 7.3±2.2; p=0.90 and 1.7±0.3 months to 1.9±0.8 months; p=0.75). Mean CRT decreased from 455.7±30.1 and 427.6±36.0µm (groups 1 and 2, respectively) to 359.1±38.2 and 303.1±44.4µm (intergroup p=0.03). The mean baseline BCVA of 62.6±3.8 letters (group 1) and 63.0±1.9 letters (group 2) remained stable under therapy in both groups (intergroup p=0.67). CONCLUSION: In eyes with eAMD with persistent intraretinal fluid on anti-VEGF monotherapy despite frequent re-injections, corticosteroids achieved a similar functional and morphological outcome over 12 months as switching to another anti-VEGF therapy, but with a reduced injection burden. In selected cases, corticosteroid treatment may thus be an option for third-line therapy in refractory exudative AMD.

IMPACT OF INNER LIMITING MEMBRANE PEELING ON VISUAL RECOVERY AFTER VITRECTOMY FOR PRIMARY RHEGMATOGENOUS RETINAL DETACHMENT INVOLVING THE FOVEA.

PURPOSE: To assess the impact of inner limiting membrane peeling during vitrectomy for macula-involving retinal detachment on best-corrected visual acuity (VA). METHODS: Retrospective analysis of 89 eyes with primary macula-involving retinal detachment, which was undergoing vitrectomy, endolaser, retinotomy, endodrainage, and SF6 tamponade. Membrane-blue-assisted membrane peeling had been performed in 61 of the eyes (Group 1) but not in the other 28 (Group 2), which served as controls. RESULTS: Age, lens status, and incidence of proliferative vitreoretinopathy 26.2% versus 39.3%; P = 0.23 in the 2 groups were comparable. The preoperative visual acuity (Early Treatment Diabetic Retinopathy Study letters) was 25.7 ± 27.9 in Group 1 and 28.8 ± 29.9 in Group 2 (P = 0.47). After surgery, these rose from 62.3 ± 30.5 (Group 1) and 34.2 ± 35.8 (Group 2) after 1 week (P = 0.090), through 83.1 ± 8.0 and 57.2 ± 32.4 at 1 month (P = 0.0005), to 92.1 ± 4.5 and 74.4 ± 23.1 Early Treatment Diabetic Retinopathy Study letters after 6 months (P = 0.0005). More than 6-month incidences of proliferative vitreoretinopathy (13.1% vs. 28.6%; P = 0.13) were similar, whereas the redetachment rate (9.8% vs. 32.1%; P = 0.014), the incidence of secondary epiretinal membranes (1.6% vs. 35.7%; P = 0.0005), and the revitrectomy rate were lower in group 1 (9.8% vs. 53.6%; P = 0.0005). CONCLUSION: Inner limiting membrane peeling during vitrectomy for macula-involving retinal detachment may substantially contribute to the visual recovery, reducing the incidence of secondary epiretinal membrane formation.

Cytokine profiles in the aqueous humor and serum of patients with dry and treated wet age-related macular degeneration.

PURPOSE: To identify disease-specific cytokine profile differences in the aqueous humor (AH) (other than the vascular endothelial growth factor) between patients with dry and treated wet age-related macular degeneration (AMD) and healthy controls. METHODS: This retrospective study drew on a case-series of patients diagnosed with dry AMD (n = 25) and treated wet AMD (n = 19), as well as on healthy controls (no systemic therapy; n = 20) undergoing phacoemulsification or vitrectomy. Samples of AH and serum were collected in parallel at the beginning of surgery. The levels of 43 cytokines were simultaneously determined using the Bio-Plex® multiplex beads system. Differences between the three groups were statistically compared using the Kruskal-Wallis H-Test after applying the Bonferroni correction for multiple comparisons (p<0.0012). RESULTS: The concentrations of three cytokines were elevated in the AH of patients with dry AMD (CXCL6; p = 0.00067) and treated wet AMD (CXCL5, CXCL6, MIG/XCXL; all p<0.001) relative to those in the healthy controls. No other differences between the three groups were identified. The AH levels of seven cytokines (16%), including CXCL6, ranged below the lower limit of quantitation of the assay. Without the correction for multiple comparisons (p<0.05), the levels of 31 of the 43 cytokines in the AH of patients with AMD would have differed significantly from those in the control. The systemic cytokine profiles (serum) were similar in all three groups. CONCLUSIONS: No systematic differences in the AH cytokine environment were identified between patients with dry AMD and those with treated wet AMD. This finding might indicate that AMD is either the result of a persistent imbalance in the physiological tissue milieu, or that the localized process induces no significant change in the cytokine environment of the anterior ocular segment.

The fate of eyes with wet AMD beyond four years of anti-VEGF therapy.

PURPOSE: Real-life studies on long-term functional outcome of anti-VEGF treatment for wet age-related macular degeneration (wAMD) are limited. We therefore assessed the 10-year outcomes in our patients. METHODS: In this retrospective study, all patients with newly diagnosed wAMD that had received minimally three intravitreal injections between 2007 and 2012 and a follow-up of ≥48 months were included. Primary outcome measure was the evolution of best-corrected visual acuity (BCVA) over time. For qualitative, quantitative and longitudinal data, Pearson's chi2 test, the Mann-Whitney U-test and Wilcoxon's signed-rank test were applied at a significance level of p < 0.05. RESULTS: Of 267 eyes (219 patients) with newly diagnosed wAMD treated during this period, 104 eyes (104 patients) had been followed for at least 48 months and were included. Fifty-nine eyes (57.8%) after 7 years were still under active treatment, 29 eyes (25.0%) had interrupted treatment [mean follow-up 7.5 years (4.0-10.1; SD 1.6)], whereas 16 patients had died. BCVA stabilized at -7.3 to -11.9 letters after 3-10 years of follow-up with a mean of 2.8 injections (median; 3.0, SD 1.0; 1-5) and 5.1 visits per year. In two thirds of eyes, treatment was switched to aflibercept or corticosteroid combinations without bearing on functional outcomes. Thirty-seven percent (37%) of eyes maintained driving vision for up to 10 years. CONCLUSIONS: Beyond 3 years of treatment, functional stability was maintained for up to 10 years. Further improvement of long-term outcomes might have required a more intensive treatment in the early phase.

Teacher's sleep quality: linked to social job characteristics?

Besides dealing with high workload, being a teacher is challenging with respect to the social context. There is increasing evidence that adverse social job characteristics challenge sleep quality. The current study tests whether restraint sleep quality (defined as worse sleep quality before than during vacation) is related to time-related job stressors, job resources, and social job characteristics. Forty-eight elementary school teachers (42% women) participated both during the last week before and the first week after vacation. Before vacation, teachers were asked for demographics and working conditions with reference to the last 30 d, and sleep quality with reference to the last 7 d. After vacation sleep quality during vacation was assessed and used as reference for working time sleep quality. Results showed mean levels of sleep quality increased during vacation. In teachers with restrained working time sleep quality (38%), experiences of failure at work, social exclusion, and emotional dissonance were more frequent than in teachers with unrestrained working time sleep quality (Ps<0.05). Groups did not differ in time-related stressors, time control and social support from supervisors. Emotion work, social exclusion and individual experience of failure seem to challenge sleep quality in teachers.

Long-Term Intravitreal Dexamethasone Treatment in Eyes with Pretreated Chronic Diabetic Macular Edema.

PURPOSE: The aim of this study is to assess the effect of repeated injections of dexamethasone implants in patients with persistent diabetic macular edema (DME) despite prior therapies. METHODS: This retrospective interventional study involved 47 DME-afflicted eyes, which were administered ≥2 intravitreal injections of dexamethasone. Group 1 (34 eyes) received a dexamethasone monotherapy, whereas group 2 (13 eyes) received a combination therapy with intravitreal antivascular endothelial growth factor as needed. The duration of dexamethasone effect until retreatment and the change in best-corrected visual acuity (BCVA) and central retinal thickness (CRT) were defined as outcome measures. RESULTS: A total of 197 injections of dexamethasone were administered in group 1 and 52 in group 2 during a mean follow-up of 23 ± 10 and 24 ± 13 months, respectively. Mean time to reinjection was 4.6 ± 0.5 (group 1) and 5.3 ± 1.0 months (group 2; P = 0.17). Reinjection intervals did not shorten over time for up to 10 dexamethasone injections per eye in group 1 and BCVA improved from before 1 month after the first implantation, 7.0 letters (P = 0.04). In group 2, there was no significant improvement in BCVA at any time point. CRT decreased from 534 ± 208 and 529 ± 215 µm to 287 ± 115 and 371 ± 78 µm at 3 months and increased to 460 ± 186 µm and 547 ± 175 µm before reinjection (groups1 and 2, respectively). The maximal CRT before each implantation remained stable over time. CONCLUSIONS: In eyes with chronic DME that respond incompletely to prior therapy or require frequent reinjections, dexamethasone shows promising long-term anatomic and functional improvement. The absence of a treatment effect reduction over time argues against a relevant rebound phenomenon.

Comparison of cytokine profiles in the aqueous humor of eyes with pseudoexfoliation syndrome and glaucoma.

PURPOSE: To compare the cyto- and chemokine profiles in the aqueous humor of PEXS eyes in the absence or presence of secondary glaucoma with or without luxation of the intraocular lens (IOL). METHODS: Samples of aqueous humor were collected intraoperatively from 20 healthy controls and from 73 eyes with PEX-syndrome, which was manifested in the absence of any other local or systemic desease. The latter group was sub-devided into eyes with an early form of PEX-syndrome in the absence of complications (PEX, n = 33), those with a late form of PEX-syndrome and glaucoma (PEXG, n = 30), and those with a late form of PEX-syndrome with luxation of the IOL that required surgery (PEXL, n = 10). The samples were analyzed in parallel after storage at -80°C. The levels of 40 cytokines were simultaneously quantified using the Bio-Plex® multiplex beads system. The inter-group data were statistically compared using the Kruskal-Wallis test (p ≤ 0.01). RESULTS: PEX and PEXG were comparable in their cytokine profiles for all 40 cytokines, whereas the cytokine profile in PEXL-eyes revealed higher levels of all but 5 cytokines (CXCL13, CCL27, IL-2, CCL3, CCL20; p ≤ 0.01). This latter finding is indicative of a non-specific inflammatory reaction in the context of IOL-luxation. The concentrations of 6 cytokines lay below the detection limit in all groups. CONCLUSIONS: The local up-regulation of 85% of the detectable cytokines in the aqueous humor of PEXL-eyes may be linked either with a progression of the disease or a breakdown of the antero-posterior barrier in the context of IOL-luxation.

Isoforms of TGF-ß in the aqueous humor of patients with pseudoexfoliation syndrome and a possible association with the long-term stability of the capsular bag after cataract surgery.

BACKGROUND: Pseudoexfoliation syndrome (PEXS) may go along with capsular bag shrinkage and luxation. In the present study, we focus on an association of isoforms of TGF-ß with capsular bag luxation. METHODS: Aqueous humor was collected intraoperatively from 20 healthy controls and from 73 otherwise healthy patients with PEXS [PEXS without complications (PEX, n = 33), late PEXS with glaucoma (PEXG, n = 30) and with IOL and capsular bag luxation (PEXL, n = 10)]. The concentrations of TGF-ß1, TGF-ß2 and TGF-ß3 were compared using the Bio-Plex® multiplex beads system based on the non-parametric Kruskal-Wallis H test (p < 0.01). RESULTS: Concentrations of TGF-ß 1, TGF-ß 2 and TGF-ß 3 were higher in the sub-groups PEX and PEXG than in controls (TGF-ß 1; p = 0.009 and 0.0005; TGF-ß 2; p = 0.002 and 0.005 and TGF-ß 3; 0.0005 and 0.0005; respectively), whereas for TGF ß2, no significant difference between controls and PEXL was revealed (p = 1.0). TGF-ß2 concentrations were elevated in a similar degree in early PEX and PEXG, but not in PEXL compared to controls (p = 0.002). The concentrations of of TGF-ß 1 and TGF-ß 3 increased in parallel with the progression of disease. The levels of TGF-ß 3, however, did not attain pathophysiological levels (>100 pg/ml) in any group. CONCLUSIONS: A stage-dependent increase in the concentrations of TGF-ß1 and TGF-ß3, but not of TGF-ß2, accords to the shrinkage of the capsular bag. This could increase the tension on the zonular fibers and contribute to luxation of the capsular bag.

Real-Life Experience with Aflibercept and Ranibizumab in the Treatment of Newly Diagnosed Neovascular Age-Related Macular Degeneration over 24 Months.

PURPOSE: Comparative data appertaining to the long-term effects of Aflibercept or Ranibizumab in newly diagnosed cases of neovascular age-related macular degeneration (nAMD) over follow-up periods exceeding 12 months in clinical routine are scarce. METHODS: In this retrospective comparative analysis, a case series of patients with treatment-naïve nAMD and requiring anti-vascular endothelial growth factor (VEGF) therapy in a routine clinical setting were treated with either Aflibercept [Afl (n = 106)] or Ranibizumab [Ran (n = 47)]. During the drug-loading phase, 3 monthly injections were administered. Thereafter, a treat-and-extend protocol was pursued for a maximum of 24 months. Ran was administered predominantly in eyes with classical lesions; Afl was administered in all others. The primary outcome parameters included anatomical and functional stability after 24 months. RESULTS: Patients were comparable regarding age, gender distribution, and lens status. Fewer patients presented with intraretinal fluid in the Afl- than in the Ran group at diagnosis (46.2% vs. 67.4%; P = 0.02), but not after the drug-loading phase. After the drug-loading phase, visual acuity [-4.2 letters (Afl) vs. -4.5 letters (Ran); P = 0.78] and the central foveal thickness remained stable. Linked to the lesion type, the number of scheduled clinical visits during the course of 24 months was higher for the Ran- than for the Afl group [11.9 ± 4.7 visits (Ran) vs. 8.4 ± 3.1 visits (Afl); P = 0.0005]. However, the total number of injections was similar [10.5 ± 2.8 (Ran) vs. 11.7 ± 3.6 (Afl); P = 0.06]. CONCLUSIONS: Based on tailoring according to the lesion type in cases of nAMD, the anatomical and the functional outcomes of treatment with either Afl or Ran were comparable for a maximum of 2 years.