Diabetic Retinopathy - a Common Disease. / Volkskrankheit diabetische Retinopathie.

Diabetic retinopathy (DR) is one of the most common complications of diabetes mellitus and one of the leading causes of visual impairment in working age individuals in the western world. The treatment of DR depends on its severity, so it is of great importance to detect patients as early as possible, in order to initiate early treatment and preserve vision. Despite currently insufficient screening participation, patients with diabetes already visit ophthalmological practices and clinics above average. Their medical care, including DR diagnostics and treatment has been making up an increasing proportion of ophthalmic activity for years. Since the prevalence of diabetes is increasing dramatically worldwide and a further increase is also predicted for Germany, the challenge for ophthalmologists is likely to grow considerably. As the same time, the diagnostic possibilities for differentiating DR and the therapeutic measures, especially with IVOM therapy, are becoming more and more complex, which increases the time burden in everyday clinical practice. The hope to avoid healthcare deficits and to further improve screening rates and visual acuity prognosis in patients with DR is based, among other things, on camera-assisted screening supported by artificial intelligence. Better diabetes management to reduce the prevalence of DR, as well as longer-acting drugs to treat DR, could also improve the care and help reduce the burden on ophthalmology practices.

[Photo-based examination for diabetic eye pathologies in a German ophthalmological practice without personal doctor-patient contact]. / Fotobasierte Untersuchung auf diabetische Augenveränderungen in einer deutschen Augenarztpraxis ohne direkten Arzt-Patienten-Kontakt.

BACKGROUND: An increasing number of patients suffering from diabetes require regular ophthalmological check-ups to diagnose and/or treat potential diabetic retinal disease. Some countries have already implemented systematic fundus assessments including artificial intelligence-based programs in order to detect sight-threatening retinopathy. The aim of this study was to improve the detection of diabetic fundus changes in Germany without examination by a doctor and to create an easy access to ophthalmological examinations. MATERIAL AND METHODS: In this prospective monocentric study 93 patients in need for a routine check-up for diabetic retinopathy were included. The study participants took up an offer of an examination (visual examination, non-mydriatic camera-based fundus examination) without doctor-patient contact. Patient satisfaction with the organization and examinations was assessed using a questionnaire. RESULTS: The mean age was 53.5 years (SD 13.6 years, 49.5% female) and 17 eyes (18.3%) showed a diabetic retinopathy which was detected using a camera-based examination. Within the small sample, no patient had to repeat the examination due to poor image quality. All categories of the questionnaire showed a good to very good satisfaction, indicating a high acceptance of the other examination form that took place at the ophthalmologist's premises. CONCLUSION: In our study in an ophthalmological practice a high level of acceptance among the patients interested in the screening for diabetic retinopathy without any direct patient-doctor contact was achieved. Our study shows a very good acceptance and feasibility. Future use of artificial intelligence in clinical practice may help to be able to screen many more patients as in this study imaging quality was very good.

The Architecture of Macular Neovascularizations Predicts Treatment Responses to Anti-VEGF Therapy in Neovascular AMD.

Introduction: Anti-VEGF therapy is an effective option for improving and stabilizing the vision in neovascular age-related macular degeneration (nAMD). However, the response to treatment is markedly heterogeneous. The aim of this study was therefore to analyze the vascular characteristics of type 1,2, and 3 macular neovascularizations (MNV) in order to identify biomarkers that predict treatment response, especially with regard to changes in intraretinal and subretinal fluid. Materials and Methods: Overall, 90 treatment-naive eyes with nAMD confirmed by optic coherence tomography (OCT), fluorescein angiography, and OCT angiography (OCTA) were included in this retrospective study. The MNV detected by OCTA were subjected to quantitative vascular analysis by binarization and skeletonization of the vessel using ImageJ. We determined their area, total vascular length (sumL), fractal dimension (FD), flow density, number of vascular nodes (numN), and average vascular diameter (avgW). The results were correlated with the treatment response to the initial three injections of anti-VEGF and the changes in intraretinal (IRF) and subretinal fluid (SRF) and the occurrence of pigment epithelial detachements (PED). Results: All patients found to have no subretinal or intraretinal fluid following the initial three injections of anti-VEGF showed a significantly smaller MNV area (p < 0.001), a lower sumL (p < 0.0005), and lesser FD (p < 0.005) before treatment than those who still exhibited signs of activity. These parameters also showed a significant influence in the separate analysis of persistent SRF (p < 0.005) and a persistent PED (p < 0.05), whereas we could not detect any influence on changes in IRF. The vascular parameters avgW, numN, and flow density showed no significant influence on SRF/IRF or PED changes. Conclusions: The size, the total vessel length, and the fractal dimension of MNV at baseline are predictors for the treatment response to anti-VEGF therapy. Therefore, particularly regarding the development of new classes of drugs, these parameters could yield new insights into treatment response.

Correlation of retinal alterations with vascular structure of macular neovascularisation in swept-source optical coherence tomography angiography in age-related macular degeneration.

PURPOSE: The aim of this study was to find out whether the vascular architecture of untreated macular neovascularisations (MNV) in neovascular age-related macular degeneration (nAMD) as visualised with optic coherence tomography angiography (OCTA) is associated with functional and known morphological alterations of the retina in optic coherence tomography (SD-OCT). METHODS: The study design was retrospective with consecutive patient inclusion. In 107 patients with newly diagnosed nAMD, MNV were detected by means of OCTA and automated quantitative vascular analysis was performed. The MNV characteristics measured were area, flow density, total vascular length (sumL), density of vascular nodes (numN), fractal dimension (FD) and average vascular width (avgW). These parameters were assessed for associations with vision (BCVA), central retinal thickness (CRT), fluid distribution, the elevation of any pigment epithelial detachment (PED), the occurrence of subretinal haemorrhage and atrophy. RESULTS: BCVA was significantly worse with greater MNV area and sumL. Fluid distribution differed significantly in relation to area (p < 0.005), sumL (p < 0.005) and FD (p = 0.001). Greater PED height was significantly associated with higher numN (p < 0.05) and lower avgW (p < 0.05). Atrophy was present significantly more often in MNV with larger area (p < 0.05), higher sumL (p < 0.05) and higher flow density (p = 0.002). None of the MNV parameters had a significant association with CRT or the occurrence of haemorrhage. CONCLUSION: OCTA is not restricted to evaluation of secondary changes but offers the opportunity to analyse the vascular structure of MNV in detail. Differences in vascular morphology are associated with certain secondary changes in retinal morphology. There are thus grounds for optimism that further research may identify and classify OCTA-based markers to permit more individualised treatment of nAMD.

Clinically applicable deep learning-based decision aids for treatment of neovascular AMD.

PURPOSE: Anti-vascular endothelial growth factor (Anti-VEGF) therapy is currently seen as the standard for treatment of neovascular AMD (nAMD). However, while treatments are highly effective, decisions for initial treatment and retreatment are often challenging for non-retina specialists. The purpose of this study is to develop convolutional neural networks (CNN) that can differentiate treatment indicated presentations of nAMD for referral to treatment centre based solely on SD-OCT. This provides the basis for developing an applicable medical decision support system subsequently. METHODS: SD-OCT volumes of a consecutive real-life cohort of 1503 nAMD patients were analysed and two experiments were carried out. To differentiate between no treatment class vs. initial treatment nAMD class and stabilised nAMD vs. active nAMD, two novel CNNs, based on SD-OCT volume scans, were developed and tested for robustness and performance. In a step towards explainable artificial intelligence (AI), saliency maps of the SD-OCT volume scans of 24 initial indication decisions with a predicted probability of > 97.5% were analysed (score 0-2 in respect to staining intensity). An AI benchmark against retina specialists was performed. RESULTS: At the first experiment, the area under curve (AUC) of the receiver-operating characteristic (ROC) for the differentiation of patients for the initial analysis was 0.927 (standard deviation (SD): 0.018), for the second experiment (retreatment analysis) 0.865 (SD: 0.027). The results were robust to downsampling (» of the original resolution) and cross-validation (tenfold). In addition, there was a high correlation between the AI analysis and expert opinion in a sample of 102 cases for differentiation of patients needing treatment (κ = 0.824). On saliency maps, the relevant structures for individual initial indication decisions were the retina/vitreous interface, subretinal space, intraretinal cysts, subretinal pigment epithelium space, and the choroid. CONCLUSION: The developed AI algorithms can define and differentiate presentations of AMD, which should be referred for treatment or retreatment with anti-VEGF therapy. This may support non-retina specialists to interpret SD-OCT on expert opinion level. The individual decision of the algorithm can be supervised by saliency maps.

Observational outcomes in proliferative diabetic retinopathy patients following treatment with ranibizumab, panretinal laser photocoagulation or combination therapy - The non-interventional second year follow-up to the PRIDE study.

PURPOSE: Ranibizumab monotherapy showed stronger effects on area of retinal neovascularization (NV) reduction while offering better visual acuity (VA) results than panretinal laser photocoagulation (PRP) monotherapy during the first 12 months of the PRIDE study. The second year of PRIDE was an observational, non-interventional follow-up, performed to evaluate long-term anatomical and functional outcomes in proliferative diabetic retinopathy (PDR) patients under real-life conditions, prior to the approval of ranibizumab for PDR. METHODS: Seventy-three PDR patients (28 from the ranibizumab group; 20 from the PRP group; 25 from the combination group) were included in the observational follow-up phase and treated at the investigators discretion. Visual acuity (VA) measurements and retinal imaging were performed at Months 12, 18 and 24. RESULTS: Mean (± SD) NV area in the ranibizumab monotherapy and combination follow-up groups increased from 3.16 ± 4.30 mm2 and 1.13 ± 2.78 mm2 at Month 12 to 6.09 ± 10.79 mm2 and 2.14 ± 4.41 mm2 at Month 18 and 10.00 ± 17.63 mm2 and 3.26 ± 7.05 mm2 at Month 24, respectively. In the PRP follow-up group, NV area declined from 5.44 ± 14.55 mm2 at Month 12 to 1.22 ± 1.67 mm2 at Month 18, but increased again to 4.05 ± 11.66 mm2 at Month 24. During the observational phase, only 2 (6;8) patients in the ranibizumab (PRP;combination) follow-up group were treated with anti-VEGF medications, while 17 (6;10) patients received PRP laser therapy. CONCLUSION: Discontinuation of ranibizumab treatment in PDR patients may result in an increase of NV area and VA loss. Tight monitoring of disease activity and continued treatment beyond the first year is needed to maintain disease control.

High-Throughput Sequencing to Identify Mutations Associated with Retinal Dystrophies.

Retinal dystrophies (RD) are clinically and genetically heterogenous disorders showing mutations in over 270 disease-associated genes. Several millions of people worldwide are affected with different types of RD. Studying the relevance of disease-associated sequence alterations will assist in understanding disorders and may lead to the development of therapeutic approaches. Here, we established a whole exome sequencing (WES) pipeline to rapidly identify disease-associated mutations in patients. Sanger sequencing was applied to identify deep-intronic variants and to verify the co-segregation of WES results within families. We analyzed 26 unrelated patients with different syndromic and non-syndromic clinical manifestations of RD. All patients underwent ophthalmic examinations. We identified nine novel disease-associated sequence variants among 37 variants identified in total. The sequence variants located to 17 different genes. Interestingly, two cases presenting with Stargardt disease carried deep-intronic variants in ABCA4. We have classified 21 variants as pathogenic variants, 4 as benign/likely benign variants, and 12 as variants of uncertain significance. This study highlights the importance of WES-based mutation analyses in RD patients supporting clinical decisions, broadly based genetic diagnosis and support genetic counselling. It is essential for any genetic therapy to expand the mutation spectrum, understand the genes' function, and correlate phenotypes with genotypes.

NPHP1 gene-associated nephronophthisis is associated with an occult retinopathy.

Biallelic deletions in the NPHP1 gene are the most frequent molecular defect of nephronophthisis, a kidney ciliopathy and leading cause of hereditary end-stage kidney disease. Nephrocystin 1, the gene product of NPHP1, is also expressed in photoreceptors where it plays an important role in intra-flagellar transport between the inner and outer segments. However, the human retinal phenotype has never been investigated in detail. Here, we characterized retinal features of 16 patients with homozygous deletions of the entire NPHP1 gene. Retinal assessment included multimodal imaging (optical coherence tomography, fundus autofluorescence) and visual function testing (visual acuity, full-field electroretinography, color vision, visual field). Fifteen patients had a mild retinal phenotype that predominantly affected cones, but with relative sparing of the fovea. Despite a predominant cone dysfunction, night vision problems were an early symptom in some cases. The consistent retinal phenotype on optical coherence tomography images included reduced reflectivity and often a granular appearance of the ellipsoid zone, fading or loss of the interdigitation zone, and mild outer retinal thinning. However, there were usually no obvious structural changes visible upon clinical examination and fundus autofluorescence imaging (occult retinopathy). More advanced retinal degeneration might occur with ageing. An identified additional CEP290 variant in one patient with a more severe retinal degeneration may indicate a potential role for genetic modifiers, although this requires further investigation. Thus, diagnostic awareness about this distinct retinal phenotype has implications for the differential diagnosis of nephronophthisis and for individual prognosis of visual function.

[Analysis of the "Portal" Care Model - Examination of the Outcome Quality of IVOM Therapy with Regard to Latency Periods in Exudative AMD]. / Analyse des Versorgungsmodells "Portal" ­ Untersuchung der Ergebnisqualität der IVOM-Therapie im Hinblick auf Latenzzeiten bei exsudativer AMD.

BACKGROUND: For many maculopathies, the management of intravitreal injection (IVOM) presents a logistical challenge. To ensure contemporary and timely treatment, patients have to organise their rides to the surgery, and the clinic has to provide enough short term resources. The objective of this study is an evaluation of the IVOM therapy for patients with exudative AMD according to four quality indicators a) latency time within the treatment and monitoring cycle, b) the treatment and monitoring frequency, c) the adherence and d) the medical outcome. MATERIALS AND METHODS: For more than seven years, patients with exudative AMD have been treated by many ophthalmologists using a networked portal system. Therefore, conservative doctors and surgical eye centres exchange treatment-relevant data. In total there are documented 2283 eyes of 1850 patients. We evaluate these electronic medical records retrospectively according to the mentioned quality indicators. RESULTS: This evaluation results in a latency time from OCT monitoring and the start of a new IVOM series of 8.1 working days. Within the first two treatment years, we achieve 10.5 injections and 8.2 monitoring visits in average. After two years, 72.9% of the cases were still in treatment or monitoring. We observed stabilisation of mean visual accuracy of about 0.05 logMAR. CONCLUSIONS: To improve the visual acuity, it is essential to achieve consistent therapy over a long period of time, especially in the case of treatment-relevant exudative AMD. The evaluation of our treatment system demonstrated that the PRN-scheme can be implemented by a cooperatively organised IVOM therapy. It is possible to achieve rapid retreatment and good adherence over many treatment years. For treatment-relevant exudative AMD it is essential for the improvement of the visual accuracy to implement consistent therapy over a long period of time. The evaluation of our treatment system demonstrates that the PRN scheme can be implemented in a cooperatively organised IVOM therapy. It is possible to achieve rapid retreatment and good patients' adherence over many treatment years.

[Fibrovascular transformation of CNV in nAMD after long-term anti-VEGF therapy : Methodological evaluation of quantifying morphological changes]. / Die fibrovaskuläre Umwandlung der CNV bei nAMD unter lang andauernder Anti-VEGF-Therapie : Methodenevaluation zur Quantifizierung morphologischer Veränderungen.

BACKGROUND: Under long-term anti-VEGF therapy neovascular age-related macular degeneration (nAMD) may result in fibrovascular transformation of choroidal neovascularization (CNV). So far there is a lack of definitions on how a differentiated quantification of the associated morphological changes can best be carried out. This pilot study aimed to define the most appropriate imaging modalities. PATIENTS AND METHODS: In 56 eyes with fibrotic CNV after at least 2 years of anti-VEGF therapy and at least 12 intravitreal anti-VEGF injections, the following imaging modalities were investigated with respect to the delimitation of vascular and fibrous portions of CNV as well as associated atrophy of retinal pigment epithelium (RPE) and disruption of the ellipsoid zone (EZ): multicolor imaging (MC), fundus autofluorescence (FAF), fluorescein angiography (FA) and indocyanine green angiography (ICGA), spectral domain optical coherence tomography (SD-OCT) and OCT angiography (OCTA). RESULTS: The vascular portion of fibrotic CNV was best visualized by OCTA, the fibrous portion by SD-OCT. The RPE atrophy was best delimitated by FAF, but differentiation was also possible by MC and ICGA. Disruption of the EZ could be delineated by SD-OCT b­scan. CONCLUSION: The use of MC is suitable for visualization of RPE atrophy and the fibrous portion of fibrotic CNV and FAF is suitable for differentiation of RPE atrophy. The SD-OCT can be used to quantify the fibrous portion of CNV; the EZ interruption is delimitable in the b­scan but not in the transverse structure-scan. The vascular part can best be detected by OCTA.

Clinical Heterogeneity in Autosomal Recessive Bestrophinopathy with Biallelic Mutations in the BEST1 Gene.

Autosomal recessive bestrophinopathy (ARB) has been reported as clinically heterogeneous. Eighteen patients (mean age: 22.5 years; 15 unrelated families) underwent ophthalmological examination, fundus photography, fundus autofluorescence, and optical coherence tomography (OCT). Molecular genetic testing of the BEST1 gene was conducted by the chain-terminating dideoxynucleotide Sanger methodology. Onset of symptoms (3 to 50 years of age) and best-corrected visual acuity (0.02-1.0) were highly variable. Ophthalmoscopic and retinal imaging defined five phenotypes. Phenotype I presented with single or confluent yellow lesions at the posterior pole and midperiphery, serous retinal detachment, and intraretinal cystoid spaces. In phenotype II fleck-like lesions were smaller and extended to the far periphery. Phenotype III showed a widespread continuous lesion with sharp peripheral demarcation. Single (phenotype IV) or multifocal (phenotype V) vitelliform macular dystrophy-like lesions were observed as well. Phenotypes varied within families and in two eyes of one patient. In addition, OCT detected hyperreflective foci (13/36 eyes) and choroidal excavation (11/36). Biallelic mutations were identified in each patient, six of which have not been reported so far [c.454C>T/p.(Pro152Ser), c.620T>A/p.(Leu207His), c.287_298del/p.(Gln96_Asn99del), c.199_200del/p.(Leu67Valfs*164), c.524del/p.(Ser175Thrfs*19), c.590_615del/p.(Leu197Profs*26)]. BEST1-associated ARB presents with a variable age of onset and clinical findings, that can be categorized in 5 clinical phenotypes. Hyperreflective foci and choroidal excavation frequently develop as secondary manifestations.

Quantitative Comparison of the Vascular Structure of Macular Neovascularizations Between Swept-Source and Spectral-Domain Optical Coherence Tomography Angiography.

PURPOSE: The aim of this study was to ascertain and quantify the differences between swept-source (SS) and spectral-domain (SD) optical coherence tomography angiography (OCTA) imaging of macular neovascularizations (MNV) in neovascular age-related macular degeneration (nAMD). PATIENTS AND METHODS: SD-OCTA (RTVue Avanti) and SS-OCTA (PLEX® Elite 9000) were performed in 37 patients with MNV in nAMD. The MNV was delineated and the data were processed via ImageJ. The parameters MNV area, nodes per area, fractal dimension (FD), and flow density were analyzed using MatLab. RESULTS: There was close agreement between the two devices regarding MNV area (ICCc 0.977, ICCa 0.977, R2 0.977), but only slight agreement regarding nodes per area (ICCa 0.008, ICCc 0.548, R2 0.51), FD (ICCa 0.425, ICCc 0.846, R2 0.96), and flow density (ICCa 0.451, ICCc 0.656, R2 0.65). The difference between the two devices was insignificant for MNV area (type 1: p=0.328; type 2: p=0.426; type 3: p=0.615), but significant for nodes per area (type 1: p=0.002; type 2: p=0.00001; type 3: p=0.003), FD (type 1: p<0.00001; type 2: p<0.00001; type 3: p=0.015) and flow density (type 1: p=0.0004; type 2: p=0.004; type 3: p=0.052). CONCLUSION: MNV area is closely comparable between devices using SS-OCTA and SD-OCTA imaging. However, the two methods differ significantly in their precise assessment of the vascular morphology (FD, flow density, nodes per area). Therefore, results obtained using different devices are not comparable and should not be amalgamated in clinical trials.

Analysis of the Vascular Morphology of the Fibrotic Choroidal Neovascularization in Neovascular Age-Related Macular Degeneration Using Optical Coherence Tomography Angiography. / Analyse der Gefäßmorphologie der fibrosierten choroidalen Neovaskularisation bei neovaskulärer altersabhängiger Makuladegeneration mittels optischer Kohärenztomografie-Angiografie.

PURPOSE: Choroidal neovascularization (CNV) in neovascular age-related macular degeneration (nAMD) undergoing anti-VEGF therapy transforms into a fibrotic lesion. This fibrovascular transformation is associated with a great variety of functional and morphological effects. The aim of this study was to investigate the vascular morphology of fibrotic CNV, to compare it with its surrounding tissue and to identify phenotypes using optical coherence tomography angiography (OCTA). METHODS: In 18 eyes with fibrotic CNV in nAMD spectral domain OCT (SD-OCT) and OCTA were performed. The automated segmentation lines were manually adjusted. A slab from 60 µm beneath Bruch's membrane to the inner edge of the subretinal hyperreflective material was applied. Quantitative analysis of the vascular morphology was performed using skeletonized OCTA images. RESULTS: Compared to the perilesional rim, the number of segments per area was significantly lower (234.75 ± 25.68 vs. 255.30 ± 20.34 1/mm2, p = 0.0003) within the fibrovascular lesion. Two phenotypes could be identified within the lesion. The phenotypic traits of cluster 1 were few, long and thick vascular segments; Cluster 2 was characterized by many, short and thin vascular segments (number of segments per area: 219.4 ± 18.8 vs. 258.8 ± 13.2 1/mm2, p = 0.00009, segment length: 49.6 ± 2.7 vs. 45.0 ± 1.3 µm, p = 0.0002, vascular caliber: 26.6 ± 1.2 vs. 23.5 ± 1.8 µm, p = 0.003). The clusters did not differ significantly regarding visual acuity (0.52 ± 0.44 vs. 0.54 ± 0.18 logMAR, p = 0.25), differentiability of subretinal (OR = 3.43, CI = [0.30, 39.64], p = 0.6) and intraretinal fluid (OR = 5.34, CI = [0.48, 89.85], p = 0.14). Less normalized ellipsoid zone (EZ) loss could be observed in cluster 1 (131.0 ± 161.3 vs. 892.4 ± 955.6 1/m, p = 0.006). CONCLUSION: In this study the vascular morphology of fibrotic CNV was analyzed using OCTA. Differences between the lesion and a perilesional rim could be detected. Two phenotypes within the fibrovascular lesion were identified. These morphological clusters could indicate different patterns of fibrovascular transformation of the CNV under long-term anti-VEGF therapy and be useful identifying possible predictive biomarkers in future studies.

Morphologic analysis of macular neovascularizations by OCT angiography-Technical limitations in the comparison of 3×3mm and 6×6mm images.

BACKGROUND: The aim of this study was to ascertain whether there are relevant differences between the vascular morphology of macular neovascularizations (MNV) in 3×3mm and 6×6mm images, produced by optical coherence tomography angiography (OCTA). METHODS: MNV of 49 patients were automated quantitative analysed, measuring area, flow, the fractal dimension, average vessel length, vascular density, and average vessel caliber. These parameters were compared between the 3×3mm and the 6×6mm images. RESULTS: A strong linear association was found between the 3×3mm and the 6×6mm images. While area, flow, and FD of the MNV were very similar, the 3×3mm images showed significantly lower average total vessel length, greater vascular density, and lower average vessel caliber. CONCLUSION: In quantitative analysis of the morphologic parameters of MNV in 3×3mm and 6×6mm images, the structures are not directly equivalent in the two sizes of scan. The images must be evaluated on an individual basis.

Use of Imaging Modalities in Real Life: Impact on Visual Acuity Outcomes of Ranibizumab Treatment for Neovascular Age-Related Macular Degeneration in Germany.

BACKGROUND: To date, there are limited prospective real-world data on the impact of optical coherence tomography (OCT) diagnostics on treatment outcomes in neovascular age-related macular degeneration (nAMD). Therefore, the prospective, noninterventional OCEAN study (NCT02194803) evaluated the use of OCT imaging and its impact on functional outcomes in Germany. METHODS: The use of OCT imaging for treatment decisions was documented in nAMD patients receiving intravitreal ranibizumab injections at 347 study centres. Best-corrected visual acuity (BCVA) testing and treatment were performed according to routine clinical practice and documented over 24 months. RESULTS: The majority of the 3,631 nAMD patients (59.6%) received a combination of OCT and fluorescein angiography imaging within the first 6 months. Over the remaining study course, this combination was used infrequently (range: 7.6% to 13.4%) and continually decreased over time; most patients received only OCT examinations (range: 48.9% to 52.5%; median: 3 within 12 months and 4 within 24 months). Subgroups according to the number of OCT examinations (≤4, rarely OCT examined; 5-8, moderately OCT examined; ≥8, well monitored) were associated with different treatment frequencies and outcomes: Rarely OCT-examined patients had received a median of 4 injections (range: 1-19) at 24 months; well-monitored patients had received a median of 8 injections (range: 1-21) at 24 months. Rarely OCT-examined patients had a mean change of BCVA of -0.3 letters (±26.1) at 24 months (n = 165); well-monitored patients showed a change of +2.0 letters (±20.8) at 24 months (n = 249). Time-to-response was greater for rarely examined than well-monitored patients, while duration-of-response was similar. CONCLUSION: Low number of visits as well as high number of treatment decisions without the use of OCT may contribute to undertreatment and poorer functional outcomes in patients undergoing ranibizumab treatment for nAMD in Germany. One potential reason for this could be that OCT was not covered by insurance for all patients during the study.

Real-world outcomes with ranibizumab in branch retinal vein occlusion: The prospective, global, LUMINOUS study.

OBJECTIVE: To evaluate the effectiveness, safety, and treatment patterns of ranibizumab 0.5 mg in treatment-naïve patients with branch retinal vein occlusion (BRVO) enrolled in the LUMINOUS™ study. STUDY DESIGN: A 5-year, global, prospective, multicenter, observational, open-label study conducted in a clinical practice (real-world) setting at outpatient ophthalmology clinics that recruited 30,138 consenting adult patients from all approved indications for ranibizumab across 42 countries. Patients with BRVO were treated according to the local ranibizumab label of the participating countries. Mean change in visual acuity (VA) in Early Treatment Diabetic Retinopathy Study letters from baseline to Year 1, treatment exposure during Year 1, and adverse events (AEs) over 5 years were assessed. RESULTS: Of the 1366 recruited BRVO patients, 405 were treatment-naïve at baseline with a mean (standard deviation [SD]) age of 67.9 (12.5) years, 57.5% were female, and 71.8% were White. At Year 1 (n = 189), the mean (SD) VA gain was 11.9 (17.66) letters from a baseline of 49.2 (±20.32) letters with a mean (SD) of 5.0 (2.34) injections. VA gains were higher in patients (n = 83) who received 6-9 injections (13.6 [20.16] letters) than in those who received 2-5 injections (n = 92, 11.7 [15.43] letters), or 1 injection (n = 14, 3.6 [13.72] letters). Patients with baseline VA <23 letters had numerically highest VA gains (n = 20, 31.1 [24.48] letters). Over 5 years, the rate of ocular/non-ocular AEs was 7.4%/9.1% and serious AEs was 0.3%/4.4% in treatment-naïve BRVO patients (n = 405). CONCLUSIONS: One year results from the LUMINOUS real-world study showed a clinically meaningful VA improvement with ranibizumab in treatment-naïve patients with BRVO; numerically higher VA gains were achieved in patients who received more injections and those with poor baseline VA. No new safety signals were observed.

ORCA study: real-world versus reading centre assessment of disease activity of neovascular age-related macular degeneration (nAMD).

BACKGROUND/AIMS: The prospective, non-interventional ORCA module of the OCEAN study (Observation of Treatment Patterns with Lucentis in Approved Indications) evaluated the qualiy of spectral domain-optical coherence tomography (SD-OCT) image interpretation and treatment decisions by clinicians in Germany and the impact on visual outcomes over 24 months in patients with neovascular age-related macular degeneration (nAMD). METHODS: 2286 SD-OCT scans of 205 eyes were independently evaluated by clinicians and reading centres (RCs) regarding signs of choroidal neovascularisation (CNV) activity, including presence of intraretinal fluid, subretinal fluid, and/or increase in pigment epithelial detachments. Agreement between clinicians and RCs was calculated. Treatment decisions by clinicians and the impact on treatment outcomes were evaluated. RESULTS: CNV activity was detected by RCs on 1578 scans (69.0%) and by clinicians on 1392 scans (60.9%), with agreement in 74.9% of cases. Of the 1578 scans with RC detected CNV activity, anti-vascular endothelial growth factor injections were performed by clinicians in only 35.5% (560/1578). In 19.7% of cases (311/1578), lack of treatment was justified by patients request, termination criteria or chronic cystoid spaces without other signs for CNV activity. In 44.8% of cases (707/1578) with RC detected CNV activity, clinicians claimed no treatment was necessary despite having correctly detected CNV activity in about 2/3 of these cases. In 34% of cases with presumed undertreatment, visual acuity declined in the following visit. CONCLUSION: Although broad agreement on CNV activity parameters was observed between clinicians and RCs, correct identification of CNV activity did not always lead to the initiation of (re-)treatment. To preserve vision over time, correct interpretation of SD-OCT scans and careful retreatment decisions are required. TRIAL REGISTRATION NUMBER: NCT02194803.

[Second opinion in retinal imaging]. / Zweitbeurteilung der retinalen Bildgebung.

With the use of digital imaging systems and the possibilities of data exchange, the second opinion is becoming increasingly more important in retinal imaging. For a meaningful application, technical imaging requirements and medical assessment quality requirements have to be fulfilled. Responsibilities should be clearly defined. The aim must be to achieve a significant contribution to ensure high-quality patient care.