[Evaluation of the accuracy of clinical diagnosis of conjunctival neoplasms : Comparison with histological findings after excision]. / Untersuchung der Genauigkeit klinischer Diagnosen von Neoplasien der Konjunktiva : Vergleich mit den histologischen Befunden nach Exzision.

BACKGROUND: Neoplasms of the conjunctiva include many different entities with a broad variety of clinical presentations. This can make a precise clinical diagnosis difficult. R0 resection is the gold standard treatment for most malignant conjunctival neoplasms, but not every benign lesions must treated by excision. In clinical practice it is important to make an accurate clinical diagnosis to enable the best possible management of conjunctival neoplasms. OBJECTIVE: The aim of this study was to determine the accuracy of clinical diagnosis of neoplasms of the conjunctiva. MATERIALS AND METHODS: Within a retrospective design, the data from all patients with excision of a conjunctival lesion between 2011 and 2020 in the Department of Ophthalmology of the UKSH Campus Kiel were extracted and analyzed. The specificity, sensitivity, and positive and negative predictive value for the preoperative clinical rating of dignity and diagnosis were evaluated based on the histological diagnostic findings. RESULTS: Of 220 included cases, 75% were benign and 25% malignant. The most frequent neoplasm of the conjunctiva was benign conjunctival nevus. The sensitivity for clinical prediction of a benign lesion was 0.86 (95% confidence interval [CI] 0.59-0.92), the specificity 0.95 (CI 0.85-0.99), and the positive predictive value 0.98 (CI 0.94-1.0). The sensitivity for clinical prediction of malign dignity was 0.95 (CI 0.85-0.99), the specificity 0.88 (CI 0.83-0.93), and the positive predictive value 0.73 (CI 0.61-0.83). CONCLUSION: The derived values for clinical diagnosis of conjunctival neoplasms can be rated as good. However, in clinical practice, untypical lesions can be hard to diagnose correctly, and the clinical diagnosis should be carefully reviewed; if in doubt, excision should be preferred.

Effectiveness and safety of VISULAS® green selective laser trabeculoplasty: a prospective, interventional multicenter clinical investigation.

PURPOSE: To evaluate the effectiveness and safety of Selective Laser Trabeculoplasty (SLT) with the SLT mode of the VISULAS® green laser in patients with primary open-angle glaucoma (POAG). METHODS: This prospective, interventional multicenter clinical investigation included patients with POAG who either needed a treatment escalation because the individual intraocular pressure (IOP) target was not met or treatment initiation and had an IOP ≥ 17 mmHg at baseline in the study eye. The study was conducted in five research centers across Germany. Approximately 100 laser applications were delivered to 360° of the trabecular meshwork. Glaucoma medications were not modified during the 3-month follow-up to allow evaluation of the sole effect of VISULAS® green with SLT. Efficacy outcomes were postoperatively absolute and relative IOP changes at 1 and 3 months. Safety outcomes analyzed the rate of intra- and postoperative adverse events. RESULTS: Thirty-four eyes of 34 POAG patients were included. The overall mean number of preoperative glaucoma medications was 2.2 ± 1.4 in 29 treated eyes, 5 eyes were treatment naïve. Mean baseline IOP (mmHg) was 21.0 ± 2.69 and was reduced by - 3.53 ± 3.34 [95% CI - 4.61; - 2.45] and - 3.59 ± 3.41 [95% CI - 4.64; - 2.53] at the 1- and 3-month follow-up, respectively (p < 0.0001), with 48.5% of cases achieving a ≥ 20% IOP reduction at 3 months [95% CI = 30.8%; 66.5%]. The mean relative IOP reduction was - 16.4% and - 16.3% at 1 and 3 months, respectively (p < 0.0001). Potentially device- or procedure-related adverse events were mild to moderate and included 3 postoperative IOP-spikes and 6 reports regarding eye pain and discomfort. All were resolved without sequelae. CONCLUSIONS: SLT performed with the VISULAS® green laser achieved clinically significant additional IOP reductions in medically treated as well as in treatment naïve eyes with POAG and there were no relevant safety issues. The results are comparable to other reported SLT studies.

Patients' perspective on emergency treatment of ophthalmologic diseases during the first phase of SARS-CoV2 pandemic in a tertiary referral center in Germany - the COVID-DETOUR questionnaire study.

BACKGROUND: During the first wave of the COVID-19 pandemic, the need of treatment of urgent ophthalmological diseases and the possible risk of a SARS-CoV-2 infection had to be weighed against each other. In this questionnaire study, we aimed to analyze potential barriers and patients' health beliefs during and after the lockdown early 2020 in a tertiary referral center in Kiel, Germany. METHODS: Patients admitted for the treatment of urgent ophthalmic diseases between March 1st, 2020, and June 3rd, 2020, were asked to participate in a questionnaire study. After informed consent was obtained, patients were interviewed using a standardized questionnaire which addressed aspects of their medical history, their health beliefs concerning the COVID-19 pandemic and barriers on their way to the treatment center. The study group was subdivided into two subgroups, depending on the occurrence of their symptoms, before and after the lockdown was ended on April 20th, 2020. RESULTS: Ninety-three patients were included, 43 in subgroup A (before April 20th) and 50 in subgroup B (April 20th or later). Retinal disorders were the most common causes for admission (approximately 60%).. Only 8 patients (8.6%) experienced a delay between their decision to visit a doctor until the actual examination. Every fourth patient was afraid of a COVID-19 infection, and expected a higher likelihood for an infection at the hospital. Patients with comorbidities tended to be more likely to be afraid of an infection (correlation coefficient 0.183, p = 0.0785) and were significantly more likely to be concerned about problems with organizing follow-up care (corr. Coefficient 0.222, p = 0.0328). Higher age was negatively correlated with fear of infection (corr. Coefficient - 0.218, p-value 0.034). CONCLUSION: In this questionnaire study, only a minority of patients indicated a delay in treatment, regardless of whether symptoms occurred before or after the lockdown before April 20th, 2020. While patients with comorbidities were more concerned about infection and problems during follow-up care, patients of higher age - who have a higher mortality - were less afraid. Protection of high-risk groups should be prioritized during the SARS-CoV-2 pandemic. TRIAL REGISTRATION: The study was registered as DRKS00021630 at the DRKS (Deutsches Register Klinischer Studien) before the conduction of the study on May 5th, 2020.

Questionnaire for the assessment of adherence barriers of intravitreal therapy: the ABQ-IVT.

OBJECTIVE: To develop and validate a questionnaire for the investigation of non-adherence (NA) barriers in patients receiving intravitreal injection (IVT). DESIGN: Questionnaire development and cross-sectional patient survey combined with a retrospective medical chart review. PARTICIPANTS: German patients with neovascular age-related macular degeneration (nAMD) or diabetic macular edema (DME) receiving anti-vascular endothelial growth factor (anti-VEGF) treatment via IVT. METHODS: The previously validated (indications: atrial fibrillation, human immunodeficiency virus, chronic inflammatory lung disease) Adherence Barriers Questionnaire (ABQ) was revised according to specifications of IVT, within the framework of an expert panel. The ABQ-IVT, which initially consisted of 24 items formulated as statements (4-point-Likert-scale ranging from "strongly agree" to "strongly disagree"), was applied in a cross-sectional survey. Evaluation of the questionnaire included an assessment of internal consistency and factor analysis. The occurrence of potential barriers in the patient sample was evaluated using descriptive statistics. To identify patient subpopulations, hierarchical cluster analysis was performed using ABQ-IVT answers as predictors. Due to difficulties in capturing NA as an external criterion, the evaluation of the questionnaire was limited to its internal validity and reliability. MAIN OUTCOME MEASURES: Patients' answers to the ABQ-IVT questionnaire and interviews. RESULTS: Of 253 patients, 234 (92%) were able to complete the ABQ-IVT questionnaire. Within the reliability analysis, the ABQ-IVT was reduced to 17 items. The condensed questionnaire demonstrated good internal consistency (Cronbach's alpha = 0.78), and factor analysis showed no evidence for subscales of the questionnaire. Nearly half of the patients (49%) reported being affected by at least three different barriers. On average, a patient was affected by 3.1 barriers. The most frequently reported barriers were "Challenge due to time commitment of physician visits" (45% of the patients), "Depression" (29%) and "Travel and opportunity costs" (27%). Cluster analysis identified six patient subpopulations, each affected by different sets of barriers and differed regarding their patient characteristics. CONCLUSIONS: The ABQ-IVT is a practical and reliable instrument for identifying patient-specific barriers to IVT treatment adherence. In practice, the questionnaire may be useful in assessing whether individual patients are at higher risk of NA due to specific adherence barriers. Aside from better awareness, this allows earlier interventions, though these still need to be validated. Patient subpopulations face different barriers and may, therefore, need distinct preventative care.

Self-examination low-cost full-field OCT (SELFF-OCT) for patients with various macular diseases.

PURPOSE: The treatment guidelines for many macular diseases rely on frequent monitoring with optical coherence tomography (OCT). However, the burden of frequent disease control leads to low therapy adherence in real life. OCT home monitoring would address this issue but requires an inexpensive and self-operable device. With self-examination low-cost full-field OCT (SELFF-OCT), our group has introduced a novel technology that may fulfill both requirements. In this pilot study, we report the initial experiences with a clinical prototype. METHODS: Fifty-one patients with different macular diseases were recruited in a cross-sectional study. The most common diseases were age-related macular degeneration (AMD; 39/51), diabetic macular edema (DME; 6/51), and retinal vein occlusion (RVO; 3/51). Patients received a short training in device usage and then performed multiple self-scans with the SELFF-OCT device. For comparison, scans with a standard clinical spectral domain (SD-)OCT were taken. RESULTS: After a brief training, 77% of the patients were able to successfully acquire images that were clinically gradable. No significant influence on success could be found for age (p = 0.08) or BCVA (p = 0.97). Relevant disease biomarkers in the most common retinal diseases could be detected. CONCLUSIONS: SELFF-OCT was used successfully for retinal self-examination and in the future could be used for retinal home monitoring. Future improvements in technology are expected to improve success rates and image quality. TRIAL REGISTRATION: The Trial was registered in the German Trial Register under the number DRKS00013755 on 14.03.2018.

[Adherence to anti-VEGF treatment-Considerations and practical recommendations]. / Adhärenz bei der Anti-VEGF-Therapie ­ Überlegungen und praktische Empfehlungen.

BACKGROUND: Numerous studies have identified a lack of treatment adherence as an important factor that often conflicts with the necessary number of anti-VEGF injections and therefore a better functional result. OBJECTIVE: This article discusses approaches and possible measures to reduce the risk of late and infrequent intravitreal injections leading to the major issue of undertreatment. MATERIAL AND METHOD: In the course of an expert dialogue, relevant parameters of treatment adherence and variables were identified. Meaningful processes were structured and assigned to organizational areas. RESULTS: The compilation of meaningful measures enables practitioners to optimize their own implementation in different areas. Regular monitoring measures can identify the extent of treatment interruption and discontinuation. For specific indicators (treatments per time interval, longest pause interval, minimum coverage per unit time, delay) an effect on the development of visual function was demonstrated. Organizational measures, training of teams and referring physicians, redundant and iterative information transfer to patients have been proven in the experience of experts. The firm integration of these processes into the structures is facilitated by working with checklists. CONCLUSION: An optimization of the processes is possible to improve the adherence and the functional results; however, interventional studies showing how adherence and persistence can be increased in the German treatment setting are still lacking.

Systematic review: non-adherence and non-persistence in intravitreal treatment.

PURPOSE: Intravitreal injection of VEGF inhibitors has become the standard of care for different macular diseases within the last years resulting in improved visual outcomes. Under real-life conditions, however, the necessity for frequent retreatments and reexaminations poses a burden for patients and treatment centers. Non-adherence and non-persistence to intravitreal treatment may lead to inferior clinical outcomes, and knowledge of contributing factors is crucial to improve adherence. This systematic review analyzes current literature for potential factors involved in non-adherence and non-persistence. METHODS: A systematic search was conducted in PubMed and Embase including three different aspects of intravitreal injection therapy: (1) diseases with intravitreal injections as treatment, (2) intravitreal injection, and (3) aspects of therapy adherence or therapy persistence. Data from identified quantitative studies were further extracted and grouped according to WHO criteria (condition, socio-economy, therapy, patient, and health system). The methodological quality of identified studies was graded. Identified qualitative studies (i.e., interviews) were descriptively analyzed and their findings narratively reported. RESULTS: Twenty-four publications were included. In 16 of those publications, a quantitative data analysis was conducted, analyzing factors associated with non-adherence. Worse visual acuity at baseline and unfavorable development of visual acuity, higher age, and greater distance to the treatment center were associated with non-adherence, while there was inconsistent evidence for an association of comorbidity. In qualitative studies, high follow-up/treatment burden, fear and anxiety, disappointed patient expectations, and lack of motivation to continue treatment were reported as reasons for non-persistence. CONCLUSIONS: Knowledge of potential barriers in IVT treatment may improve adherence and potentially clinical results. Improvements can be achieved particularly in the healthcare complex (organizational improvements) and the "patient" complex by establishing realistic expectations. Recurrent education of the patient may be necessary.

OCT Angiography of the Choriocapillaris in Central Serous Chorioretinopathy: A Quantitative Subgroup Analysis.

INTRODUCTION: To quantify optical coherence tomography angiography (OCTA) signal changes at the level of the choriocapillaris (CC) in patients with different stages of central serous chorioretinopathy (CSC) and to explore any correlation between subretinal fluid (SRF) and retinal pigment epithelium (RPE) alterations and the OCTA CC signal. METHODS: One hundred one CSC eyes and 42 healthy control eyes were included in this retrospective study. CSC patients were allocated into four groups: acute, non-resolving, chronic atrophic and inactive CSC. CC OCTA images (AngioPlex®, Zeiss) were automatically quantified using an image-processing algorithm. Spatial correlation analysis of OCTA signals was performed by overlapping macular edema heatmaps and fundus autofluorescence images with corresponding OCTA images. RESULTS: Active CSC subgroups demonstrated significantly more increased and decreased flow pixels in the CC compared with controls (p < 0.0001). No significant OCTA changes were seen within the active CSC groups or between the inactive and healthy subgroup. Spatial correlation analysis revealed a decreased OCTA signal in the SRF area and an increased signal outside the SRF area in acute CSC. Areas of RPE atrophy co-localized with areas of increased choriocapillaris OCTA signal, while areas with RPE alterations exhibited a normal signal compared with unaffected RPE. CONCLUSION: The decreased OCTA signal in the area of SRF in acute CSC could be evidence of localized CC hypoperfusion or due to shadowing artifacts. The missing CC OCTA changes in altered RPE adjacent to atrophy argues against CC injury. Studies with higher resolution and optimized image acquisition are warranted to further validate our findings.

Expression of Angiogenic and Inflammatory Factors in Choroidal Neovascularisation-Derived Retinal Pigment Epithelium.

PURPOSE: Anti-angiogenic treatment is well established in the management of exudative age-related macular degeneration (AMD), but not sufficient in all patients. The characterisation of factors driving this chronic disease could serve to identify additional treatment options. The purpose of this study was to assess gene expression patterns and distinct changes in cells derived from surgically extracted choroidal neovascularisation (CNV) membranes. MATERIALS AND METHODS: The expression of >11,000 genes was analysed by means of a microarray in cells cultured from 2 late-stage CNV membranes compared to primary human retinal pigment epithelium (RPE) and ARPE-19 cells. A pathway analysis was performed to identify gene expression patterns associated with exudative AMD. RESULTS: The analysis revealed significant alterations in gene sets associated with inflammatory processes in CNV-derived cells, involving the upregulation of pro-inflammatory factors IL6, C3, and C5, and downregulation of anti-inflammatory complement factor B and complement factor I. Factors associated with angiogenesis, such as VEGFA or ANGPT2, were not significantly regulated in the 2 RPE-derived cell lines. CONCLUSION: In late-stage CNV membrane-derived RPE, gene expression was shifted towards a pro-inflammatory state. Angiogenesis-associated factors were regulated differently in the 2 CNV-derived RPE membranes. While inflammation seems to be continuously stimulated by RPE associated with late exudative AMD, this appears not to be the case with regard to angioregulatory mechanisms.

Retinal volume change is a reliable OCT biomarker for disease activity in neovascular AMD.

PURPOSE: Current algorithms for automated computer interpretation of optical coherence tomography (OCT) imaging of patients suffering from neovascular age-related macular degeneration (AMD) mostly rely on fluid detection. However, fluid detection itself and correct interpretation of the fluid currently limits diagnostic accuracy. We therefore performed a detailed analysis of the requirements that would have to be met for fluid detection approaches. We further investigated if monitoring retinal volume would be a viable alternative to detect disease activity. METHODS: Retrospective analysis and manual grading of 764 OCT volume scans of 44 patients with exudative AMD treated with intravitreal anti-VEGF injections at a pro-re-nata (PRN) treatment regimen for at least 24 months. RESULTS: Detection of subretinal fluid (SRF) or intraretinal fluid (IRF) alone is not sufficient for disease detection. A combination of SRF and IRF can detect disease activity with a sensitivity of 98.6% and a specificity of 82%. With further characterization of IRF into exudative and degenerative cysts, specificity can be increased to 100%. However, correct characterization is currently not achieved by published fluid detection approaches. Change of macular retinal volume (MRV) can depict disease activity with sensitivity of 88.4% and specificity of 89.6%. Combination with the detection of SRF can further improve diagnostic accuracy to a specificity of 93.3% and sensitivity of 93.9% without relying on IRF or IRF characterization. CONCLUSION: Fluid detection without further characterization is not sufficient for AMD monitoring. Either further distinction between exudative and degenerative cysts is necessary, or other activity markers have to be taken into account. MRV offers good potential to fill this diagnostic gap and might become an important monitoring marker.

Subjective evaluation of visual acuity is not reliable to detect disease activity in different exudative maculopathies.

BACKGROUND: Patients with exudative maculopathies (neovascular age-related macular degeneration (nAMD), diabetic macular edema (DME), and retinal vein occlusion (RVO)) are faced with a high burden of examinations and treatments. This study was conceived to analyze the accuracy of a subjective evaluation of visual acuity (VA) and metamorphopsia to detect disease reactivation, compared to morphological signs of reactivation assessed by means of SD-OCT. METHODS: Retrospective study of 888 patients treated for nAMD (n = 638), DME (84), BRVO (110), and CRVO (56) was conducted. Subjective evaluation of the patient at an examination (i.e., change of VA and/or metamorphopsia) was compared to clinical evaluation of disease activity as assessed by SD-OCT. Sensitivity and specificity, negative and positive predictive values (PPV/NPV) for detection of active disease were calculated. Factors associated with false-negative subjective evaluation were analyzed by regression analysis. RESULTS: The sensitivity of the subjective evaluation to detect disease reactivation was < 0.50 in all exudative maculopathies. Sensitivity was increased to ≥ 0.60 by combining subjective worsening with loss of 1 line in the VA test in RVO, but not in DME and nAMD. The specificity was > 0.85 in all patients. PPV was > 0.85 in patients with RVO. Regression analysis did not reveal any factors that could reliably identify patient subgroups in which OCT could be omitted, though CRVO patients with a visual acuity of < 0.3 logMAR had an odds ratio of 0.20 for false-negative subjective evaluation (p = 0.009). CONCLUSION: The accuracy of subjective evaluation to discriminate disease activity in patients with different exudative maculopathies was low and cannot substitute for frequent SD-OCT exams. Routinely assessed clinical parameters such as age, visual acuity, or treatment experience were of no use to predict the validity of subjective evaluation of disease activity. TRIAL REGISTRATION: This trial was registered at the DRKS (Deutsches Register Klinischer Studien, drks.de; No 00006851) prior to the inclusion of the first patient.

Association of treatment adherence with real-life VA outcomes in AMD, DME, and BRVO patients.

PURPOSE: Real-life clinical outcomes of patients treated with anti-VEGF drugs for neovascular age-related macular degeneration (nAMD), diabetic macular edema (DME), or macular edema secondary to branch retinal vein occlusion (BRVO) are often inferior to results from randomized clinical trials. This observational cohort study investigates treatment adherence and real-life clinical outcomes within the first year of treatment. PATIENTS AND METHODS: A total of 708 treatment-naïve patients (466 nAMD, 134 DME, and 108 BRVO) were included. Patients were followed with a PRN treatment protocol with three intravitreal injections (IVIs) and a series of 3 monthly injections in case of persistent or recurrent disease activity, as determined by monthly follow-up exams including optical coherence tomographies. Occurrence of gaps of >56 days between treatments or follow-up (nonadherence [NA]) and the reasons for NA (patient- or center-associated) as well as disease activity within the first 12 months of treatment were analyzed. Visual acuity (VA) as well as numbers and dates of optical coherence tomography and IVI were extracted from medical records. RESULTS: NA occurred significantly more often in patients with DME (44%) than nAMD (32%) or BRVO (25%, p<0.01 between groups). NA was mainly patient-associated (nAMD: 80.0%, DME: 83.1%, BRVO: 70.4%, p=0.38 between groups). Patients with nAMD and DME and appropriate treatment/follow-up adherence had a better chance of significantly gaining or maintaining VA, respectively (19.9% vs 12.0% with 3-line-gain in nAMD and 1.3% vs 15.3% 3-line loss in DME; each p<0.05). NA did not correlate with VA outcomes in BRVO (3-line gain 30.9% vs 48.1% and 3-line loss 8.6% vs 7.4%; p>0.05). CONCLUSION: NA to treatment and follow-up regimens is a common problem in the management of patients with AMD and DME and limits clinical treatment outcomes under real-life conditions. Patients with DME have the highest risk of patient-associated NA, associated with a higher risk for significant VA loss.

TREATMENT OF NEOVASCULAR AGE-RELATED MACULAR DEGENERATION PATIENTS WITH VASCULAR ENDOTHELIAL GROWTH FACTOR INHIBITORS IN EVERYDAY PRACTICE: Identification of Health Care Constraints in Germany-The PONS Study.

PURPOSE: The PONS study was conceived to analyze the extent of nonpersistence (NP) and nonadherence (NA) in the treatment of patients with neovascular age-related macular degeneration in everyday clinical practice in Germany. Further objectives were to identify factors that can affect NP and NA and to analyze clinical outcomes under everyday conditions. METHODS: Nonpersistence (no contact with doctor for at least 3 months) and NA (no treatment or follow-up for at least 6 weeks) as well as clinical data were analyzed up to 24 months retrospectively and 12 months prospectively in 480 patients with neovascular age-related macular degeneration in 23 treatment centers. Patients were interviewed for factors possibly affecting NP and NA. RESULTS: One third of patients fulfilled criteria of NA in the first 3 months and two thirds after 6 months. The NP was 18.8% after 12 months. Treatment exclusively at one center, a higher number of patients with neovascular age-related macular degeneration at the treating center, and fixed appointments were associated with a lower risk for NP. An initial gain in visual acuity after upload was not preserved after 12 months (mean change -0.5 Early Treatment Diabetic Retinopathy Study letters). Whereas visual acuity declined by 7.5 Early Treatment Diabetic Retinopathy Study letters in patients with good baseline visual acuity >20/40, visual acuity improved by 8.5 letters in patients with baseline visual acuity of ≤20/200. Only 7.5% of patients underwent an optical coherence tomography scan after 3 upload injections, and only 2.0 optical coherence tomographies were performed in the first 12 months. CONCLUSION: The NP and NA were high in our study population and are likely to have contributed to a suboptimal clinical outcome compared with randomized clinical trials. Shortcomings in the management of patients with neovascular age-related macular degeneration, including restrictions in the timely and adequate follow-up (including optical coherence tomography) and retreatment, appear to be constraining factors in Germany.

Potential selection bias in candidates for stereotactic radiotherapy for neovascular AMD.

PURPOSE: Stereotactic radiotherapy (SRT, IRay) was able to reduce the need for intravitreal injections of anti-VEGF (IVI) in patients with neovascular AMD (nAMD) in a phase II randomized clinical trial. Certain morphologic characteristics, such as lesion size < 4 mm2 or lack of fibrosis, were associated with a better response. The purpose of this cross-sectional study was to investigate eligibility for SRT in a clinical routine setting and to compare clinical features of eligible and non-eligible patients. METHODS: Cross-sectional study of 468 patients treated for nAMD in one study center within a period of 4 months. Clinical features, such as visual acuity or number of IVI since diagnosis and within 6/12 months, as well as the presence for exclusion criteria for SRT were analyzed. Exclusion criteria were sub-divided into lesion-associated (relevant fibrosis, lesion size > 4 mm2, PE tear), ocular comorbidity (e.g., macular comorbidity, vascular disease) and systemic comorbidity (e.g., dementia or tremor). RESULTS: Exclusion criteria were met by 255 patients (54.5%). Exclusion was most dominantly associated with lesion-associated criteria (80.0%) and less often with ocular (20.8%) or systemic (9.4%) comorbidity. A total of 213 patients (45.5%) fulfilled eligibility criteria. Eligible patients had a better VA at time of analysis (0.36 vs. 0.56 logMAR, p < 0.0001) and at baseline (0.38 vs. 0.56 logMAR, p < 0.0001) compared to non-eligible patients. The numbers of previous intravitreal injections since diagnosis in strictly PRN-treated patients served as a surrogate marker for lesion activity and was comparable within the last 6/12 months. Non-eligible patients had a higher number of different anti-VEGF drugs (1.8 vs. 1.6, p = 0.038). CONCLUSIONS: SRT in addition to anti-VEGF can be an option in every second patient with nAMD. Due to morphological exclusion criteria, patients eligible for SRT had a better VA and a better clinical response compared to non-eligible patients.

Five-year visual acuity outcomes and injection patterns in patients with pro-re-nata treatments for AMD, DME, RVO and myopic CNV.

BACKGROUND: Anti vascular endothelial growth factor (VEGF) therapy is an established treatment for various retinal diseases. Long-term data on injection frequencies and visual acuity (VA), however, are still rare. METHODS: Five-year analysis of real-life VA developments and injection patterns from 2072 patients (2577 eyes; 33 187 injections) with chronically active disease undergoing pro-re-nata treatment for age-related macular degeneration (AMD), diabetic macular oedema (DME), retinal vein occlusion (RVO) and myopic choroidal neovascularisation (CNV). RESULTS: Maximum mean VA gain in year 1 was+5.2 letters in AMD, +6.2 in DME, +10 in RVO and+7.2 in myopic CNV. Over 5 years, however, VA in patients with AMD declined. By year 5, 34% of patients with AMD had experienced VA loss of >15 letters, 56% had remained stable and 10% had gained >15 letters. Long-term VA developments in DME and RVO were more favourable with 81% of DME and 79% of patients with RVO gaining or maintaining vision at 5 years. In AMD, median injection frequency was six in year 1 and between four and five in consecutive years. In DME and RVO, median injection frequency was six in year 1 but lower compared with AMD in consecutive years. Injection frequency in DME was weakly associated with patient age (rs=0.1; p=0.03). CONCLUSIONS: In AMD, the initial VA gain was not maintained long term despite higher injection numbers compared with DME, RVO and myopic CNV. The presented real-world data provide a peer-group-based estimate of VA developments and injection frequencies for counselling patients undergoing long-term anti-VEGF therapy.

Clinical experience with eplerenone to treat chronic central serous chorioretinopathy.

PURPOSE: Chronic central serous chorioretinopathy (CSC) is a vision-threatening eye disease for which there is still no approved treatment. Recent studies suggest that the corticosteroid pathway in the choroid is implicated in CSC pathogenesis, and that therapy with the aldosterone antagonist eplerenone improves clinical outcomes. However, there is still little clinical data to support this hypothesis. We performed a retrospective chart review to further investigate the clinical value of eplerenone treatment in patients with chronic CSC and to identify possible response predictors. METHODS: Twenty-four patients with chronic CSC resistant to conventional therapy over at least 4 months were included in this retrospective study. Patients were initially treated with 25 mg/day of eplerenone administered orally for 1 week, followed by a sustained daily dose of 50 mg. The primary outcome measure was percentage of eyes achieving complete resolution of subretinal fluid (SRF), recorded by spectral domain optical coherence tomography (SD-OCT). Secondary outcomes included changes in central macular thickness (CMT) and best-corrected visual acuity (BCVA). Baseline SD-OCT images were also evaluated as possible predictors of treatment response. RESULTS: Twenty-nine percent of patients experienced complete resolution of SRF after a median of 106 days of treatment, while 33 % of patients showed a transient initial decrease in SRF, and 25 % failed to respond to treatment. Treatment had to be stopped in 13 % of patients because of adverse effects of the eplerenone treatment. In the study population, CMT decreased from 342 to 275 µm after treatment, which was associated with a modest improvement in mean BCVA from 0.35 to 0.3 logMar. The integrity of the ellipsoid zone and the retinal pigment epithelium (RPE) at baseline were associated with a tendency towards a favourable visual outcome. CONCLUSION: This study confirms the proposed clinical value of eplerenone for treating patients with therapy-resistant CSC. However, patients presenting widespread RPE changes are less likely to benefit from eplerenone treatment, which may argue for an earlier intervention. Larger studies are needed to characterise patient subgroups that may benefit the most from eplerenone treatment.

Patient Preferences in the Treatment of Neovascular Age-Related Macular Degeneration: A Discrete Choice Experiment.

PURPOSE: The objective of our study was to investigate preferences of patients with neovascular age-related macular degeneration (nAMD) for different anti-vascular endothelial growth factor (VEGF) treatment schemes. DESIGN: We used a discrete choice experiment (DCE) design as part of a telephone interview. PARTICIPANTS: Patients with nAMD aged at least 50 years were included in the study. METHODS: Telephone interviews were done between November 2012 and October 2013. MAIN OUTCOME MEASURES: In our DCE survey, we measured patient preferences toward specific levels of attributes that describe different options in the everyday intravitreal injection treatment setting: (1) treatment scheme; (2) change of visual acuity (VA); and (3) time the patient needs for each visit to the eye specialist. RESULTS: A total of 284 patients with nAMD with a mean age of 77.4±7.1 years (women: 59.9%) completed the DCE interviews. Of them, 22.9% had poor VA at study inclusion, 54.9% had moderate VA, and 14.1% had good VA; VA was not available for 8.1% of the patients. Generally, patients preferred the attribute levels "improvement in VA" and "short time per specialist visit." The results for the attribute "treatment scheme" were inconclusive because none of the attribute levels (injections every 4 weeks, every 8 weeks, and pro re nata) were associated with statistically significant utility differences. This also mirrors the relative importance of the different attributes in patient decisions: "Change of VA" influenced decision making for a treatment option in 73.6% of cases; "waiting, treatment, and travel time" influenced decision making in 21.0% of cases; and "treatment scheme" influenced decision making for a treatment option in 5.4% of cases. To obtain improved VA instead of a worsening VA, patients in our study stated to be willing to accept a very long time needed per physician visit of 21.2 hours (8.5 hours for improved rather than stable VA and 12.7 hours for stable VA rather than worsening VA). CONCLUSIONS: To prevent deterioration of VA, patients with nAMD seem to be willing to accept a high treatment burden with regular intravitreal injections at short intervals and long periods of waiting, treatment, and traveling for their consultations.

Treatment as Required versus Regular Monthly Treatment in the Management of Neovascular Age-Related Macular Degeneration: A Systematic Review and Meta-Analysis.

BACKGROUND: To investigate whether treatment as required 'pro re nata' (PRN) versus regular monthly treatment regimens lead to differences in outcomes in neovascular age-related macular degeneration (nAMD). Regular monthly administration of vascular endothelial growth factor (VEGF) inhibitors is an established gold standard treatment, but this approach is costly. Replacement of monthly by PRN treatment can only be justified if there is no difference in patient relevant outcomes. METHODS: Systematic review and meta-analysis. The intervention was PRN treatment and the comparator was monthly treatment with VEGF-inhibitors. Four bibliographic databases were searched for randomised controlled trials comparing both treatment regimens directly (head-to-head studies). The last literature search was conducted in December 2014. Risk of bias assessment was performed after the Cochrane Handbook for Systematic Reviews of Interventions. FINDINGS: We included 3 head-to-head studies (6 reports) involving more than 2000 patients. After 2 years, the weighted mean difference in best corrected visual acuity (BCVA) was 1.9 (95% CI 0.5 to 3.3) ETDRS letters in favour of monthly treatment. Systemic adverse events were higher in PRN treated patients, but these differences were not statistically significant. After 2 years, the total number of intravitreal injections required by the patients in the PRN arms were 8.4 (95% CI 7.9 to 8.9) fewer than those having monthly treatment. The studies were considered to have a moderate risk of bias. CONCLUSIONS: PRN treatment resulted in minor but statistically significant decrease in mean BCVA which may not be clinically meaningful. There is a small increase in risk of systemic adverse events for PRN treated patients. Overall, the results indicate that an individualized treatment approach with anti-VEGF using visual acuity and OCT-guided re-treatment criteria may be appropriate for most patients with nAMD.

Increased expression of angiogenic and inflammatory proteins in the vitreous of patients with ischemic central retinal vein occlusion.

BACKGROUND: Central retinal vein occlusion (CRVO) is a common disease characterized by a disrupted retinal blood supply and a high risk of subsequent vision loss due to retinal edema and neovascular disease. This study was designed to assess the concentrations of selected signaling proteins in the vitreous and blood of patients with ischemic CRVO. METHODS: Vitreous and blood samples were collected from patients undergoing surgery for ischemic CRVO (radial optic neurotomy (RON), n = 13), epiretinal gliosis or macular hole (control group, n = 13). Concentrations of 40 different proteins were determined by an ELISA-type antibody microarray. RESULTS: Expression of proteins enriched in the vitreous (CCL2, IGFBP2, MMP10, HGF, TNFRSF11B (OPG)) was localized by immunohistochemistry in eyes of patients with severe ischemic CRVO followed by secondary glaucoma. Vitreal expression levels were higher in CRVO patients than in the control group (CRVO / control; p < 0.05) for ADIPOQ (13.6), ANGPT2 (20.5), CCL2 (MCP1) (3.2), HGF (4.7), IFNG (13.9), IGFBP1 (14.7), IGFBP2 (1.8), IGFBP3 (4.1), IGFBP4 (1.7), IL6 (10.8), LEP (3.4), MMP3 (4.3), MMP9 (3.6), MMP10 (5.4), PPBP (CXCL7 or NAP2) (11.8), TIMP4 (3.8), and VEGFA (85.3). In CRVO patients, vitreal levels of CCL2 (4.2), HGF (23.3), IGFBP2 (1.23), MMP10 (2.47), TNFRSF11B (2.96), and VEGFA (29.2) were higher than the blood levels (vitreous / blood, p < 0.05). Expression of CCL2, IGFBP2, MMP10, HGF, and TNFRSF11B was preferentially localized to the retina and the retinal pigment epithelium (RPE). CONCLUSION: Proteins related to hypoxia, angiogenesis, and inflammation were significantly elevated in the vitreous of CRVO patients. Moreover, some markers known to indicate atherosclerosis may be related to a basic vascular disease underlying RVO. This would imply that local therapeutic targeting might not be sufficient for a long term therapy in a systemic disease but hypothetically reduce local changes as an initial therapeutic approach.

Intra- and postoperative risks and complications of small-gauge (23-G) versus conventional (20-G) vitrectomy for macular surgery.

PURPOSE: To compare the complication spectrum and rate of 23-G and 20-G vitrectomy for macular surgery. METHODS: This was a retrospective comparative analysis of 20-G and 23-G vitrectomy (introduced in 2007) for macular surgery due to macular pucker or macular hole performed between 2006 and 2010 in 61 and 59 eyes, respectively, by 2 experienced surgeons and 2 trainees. We assessed the adjusted hazard ratio for vitrectomy 23-G vs 20-G with a Cox proportional hazard model. We counted retinal detachment, vitreous hemorrhage, endophthalmitis (as early postoperative complications), or cataract progression (as late postoperative complication) as endpoint. We adjusted for indication, surgeon, retinopexy method, and the endotamponade. RESULTS: Follow-up averaged 712 days. Median time to first event was 385 days in the 23-G group and 342 days in the 20-G group. Cox proportional hazard analysis showed no significant difference between vitrectomy 23-G vs 20-G with regard to postoperative complications (hazard ratio 0.79, 95% confidence interval 0.41-1.52). The other covariates did not exert a statistically significant effect on the risk of adverse events. Looking at individual complications, retinal detachment was exclusively found after 20-G. CONCLUSIONS: In this homogenous large cohort, we did not find a statistically significant difference in rates of complications between 23-G and 20-G vitrectomy techniques for macular surgery. Trainees performed equally well as experienced surgeons.