[Prospective noninterventional BLUE SKY study evaluating the efficacy of brolucizumab in treatment-naïve and previously treated patients with neovascular AMD]. / Prospektive nichtinterventionelle BLUE SKY-Studie zur Beurteilung der Wirksamkeit von Brolucizumab bei unbehandelten und vorbehandelten Patienten mit neovaskulärer AMD.

Intravitreal injection of anti-vascular endothelial growth factor (VEGF) is the standard treatment for patients with neovascular age-related macular degeneration (nAMD). In addition to the approved substances ranibizumab (Lucentis®, Novartis) and aflibercept (Eylea®, Bayer), bevacizumab (Avastin®, Roche) is also available. Furthermore, brolucizumab (Beovu®, Novartis) has been approved and has been available in Germany since April 2020. The multicenter, noninterventional prospective BLUE SKY study investigates brolucizumab treatment with different schemes in 600 treatment-naive and pretreated nAMD patients in routine clinical practice over a 24-month period. Besides general patient data, visual acuity and treatment data will be documented. Fluorescein angiography, fundus photography, spectral domain optical coherence tomography and swept-source optical coherence tomography angiography will be performed and analyzed by reading centers. The focus of the analysis will be on the intraretinal and subretinal fluid distribution as well as morphological MNV changes and injection frequency. Also, safety and adverse drug effects of brolucizumab, with a specific focus on inflammatory complications, particularly retinal (occlusive) vasculitis will be evaluated.

[Cancer-associated retinopathy (CAR) in neuroendocrine carcinoma of the uterus]. / Karzinomassoziierte Retinopathie (CAR) bei neuroendokrinem Uteruskarzinom.

A 75-year-old female patient presented with bilateral progressive loss of vision. Best corrected visual acuity (BCVA) was hand movements in the right eye and 1/50 in the left eye. The spectral domain optical coherence tomography (SD-OCT) showed thinning of the outer retina suspected to be due to autoimmune retinopathy. A neuroendocrine carcinoma of the uterus was diagnosed during tumor screening. Under systemic therapy with corticosteroids the visual acuity improved to 20/200 in the right eye and 20/80 in the left eye. Cancer-associated retinopathy (CAR) is a paraneoplastic autoimmune retinopathy.

[Pitfalls in retinal optical coherence tomography imaging]. / Fallstricke in der Netzhautbildgebung mittels optischer Kohärenztomographie.

Optical coherence tomography (OCT) imaging now plays an important role in the management of macular and retinal diseases. In addition to the many advantages of this noninvasive imaging modality, limitations and pitfalls should be taken into consideration. The aim of this review is to discuss several possible sources of error in the conduct and interpretation of OCT imaging. Ultimately, this article should add to a meaningful and focused use in clinical practice.

[Design of the ORCA module in the OCEAN study : Evaluation of SD-OCT results in daily routine practice]. / Design des ORCA-Moduls der OCEAN-Studie : Evaluierung der SD-OCT-Befunderhebung in der täglichen Praxisroutine.

BACKGROUND: The prevalence of blindness as defined by law could be reduced by the introduction of anti-vascular endothelial growth factor (VEGF) therapy. Because the treatment is governed by patient needs, mostly using morphological criteria, imaging diagnostics are of particular importance. The non-interventional OCEAN study investigates the treatment with ranibizumab in the clinical routine practice. In a subgroup of patients the interpretation of spectral domain optical coherence tomography (SD-OCT) scans by the treating physicians will be analyzed (ORCA module). METHODS: Over a period of 24 months data from patients with exudative age-related macular degeneration (AMD), macular edema due to retinal vein occlusion or diabetes mellitus, who are receiving intravitreal injections of ranibizumab, will be assessed. Information on examinations, visual acuity, treatment and recordings from imaging techniques will be documented using a questionnaire. The SD-OCT scans, fluorescence angiography and fundus photography will be independently analyzed by the ophthalmologist of the study center and by three reading centers (CIRCL Cologne, GRADE Bonn and M3 Münster). Automated measurements of retinal thickness by the manufacturers' software will be checked and if necessary manually corrected. A qualitative interpretation in terms of morphological criteria for (further) treatment will be performed. CONCLUSION: A thorough assessment of SD-OCT images during anti-VEGF therapy provides the basis for the best possible needs-oriented treatment regimen. The control of the quality of data from daily routine practice may indicate possible weaknesses allowing explicit training and therefore optimization of patient treatment.

Extramacular drusen are highly associated with age-related macular degeneration, but not with CFH and ARMS2 genotypes.

BACKGROUND: To evaluate the association of extramacular drusen (EMD) with age-related macular degeneration (AMD) and with complement factor H (CFH rs1061170) and age-related maculopathy susceptibility 2 (ARMS2 rs10490924) polymorphisms in individuals with and without AMD. METHODS: In this case-control study, AMD staging was performed in 622 individuals. EMD were defined as ≥10 drusen (including ≥1 intermediate drusen) outside the Early Treatment of Diabetic Retinopathy Study Grid within field 2. Genotype associations for CFH and ARMS2 variants were assessed using logistic regression analysis. RESULTS: EMD (n=213) showed a strong association with AMD (OR=3.85; p=1.66×10(-13)). AMD (n=316) was strongly associated with CFH (p=1.78×10(-7)) and ARMS2 genotypes (p=1.67×10(-8)). After adjustment for AMD, age and gender, EMD were neither associated with CFH (p=0.11) nor with ARMS2 (p=0.45) genotypes. In individuals without AMD, the groups with and without EMD showed no differences regarding both genetic variants. CONCLUSIONS: The strong association between drusen within and outside of the macula suggests a common pathogenesis. However, EMD were not AMD-independently associated with CFH or ARMS2 genotypes. Our results indicate that patients without AMD but with EMD can serve as controls in studies evaluating AMD risk factors. Further studies are required to elucidate the aetiology and clinical relevance of EMD.

[Delayed treatment initiation of more than 2 weeks. Relevance for possible gain of visual acuity after anti-VEGF therapy under real life conditions (interim analysis of the prospective OCEAN study)]. / Verzögerung des Behandlungsbeginns um mehr als 2 Wochen. Relevanz für möglichen Visusgewinn nach Anti-VEGF-Therapie unter Real-Life-Bedingungen (Interimanalyse der prospektiven OCEAN-Studie).

BACKGROUND: The largest German prospective non-interventional ophthalmological study OCEAN (NCT02194803) investigates the treatment of retinal diseases with ranibizumab in routine patient care. A feature of this study is the participation of ophthalmic surgeons in surgical centers as well as general ophthalmologists who do not perform intravitreal injections themselves. OBJECTIVES: The functional outcome following administration of three intravitreal injections was analyzed with respect to the time from initial examination to the first injection (defined as treatment delay) as well as potentially confounding factors. MATERIAL AND METHODS: This interim analysis included only data from therapy naïve patients participating in the OCEAN study, who received at least three ranibizumab injections. The potential impact of various factors on treatment delay was analyzed by the χ(2)-test. RESULTS: Data of 1333 patients were analyzed. The median delay before treatment was 15 days (range 0-90 days). Patients with a delay of more than 28 days showed a significantly lower gain in visual acuity than patients with a delay of less than 14 days. Age, gender and baseline visual acuity did not show an association with the treatment delay; however, referral from a primary care ophthalmologist, undertaking fluorescein angiography in an external practice and the underlying indications did affect the observed treatment delays. CONCLUSION: Every patient should be treated within 14 days, following recent recommendations of the ophthalmological societies. Liability issues have to be considered as the statistical evaluation of real life data showed unambiguous results.

[Choroidal tumor in a young woman]. / Aderhauttumor bei junger Frau.

A 33-year-old woman presented with unilateral visual impairment since 2 months. A yellowish, prominent lesion was visible in the macula on funduscopy. Spectral domain OCT revealed a choroidal tumor with overlying subretinal fluid and subretinal hyperreflective material. Following a thorough examination including MRI, CT, coloscopy, bone scintigraphy, positron emission tomography and lymph node biopsy, the diagnosis of a choroidal granuloma with systemic sarcoidosis was made. After treatment with systemic steroids over 2 months the choroidal tumor flattened and visual acuity increased from 20/50 to 20/20.

[Case report on OCT findings in a patient with hereditary optic neuropathy and a patient with autosomal dominant optic atrophy]. / Kasuistik über OCT-Befunde bei einem Patienten mit Leberscher hereditärer Optikusneuropathie und einem Patienten mit autosomal dominanter Optikusatrophie.

BACKGROUND: Hereditary optic neuropathies lead to a decrease in visual acuity corresponding to a reduction of the ganglion cell layer and the nerve fibre layer. The most common neuropathies, Leber hereditary optic neuropathy (LHON) and autosomal dominant optic atrophy (ADOA), are mitochondrial disorders. CASE REPORT: We describe two cases, one with LHON and one with ADOA, and demonstrate the decrease in thickness of the ganglion cell layer using spectral domain OCT (optical coherence tomography). RESULTS: In the case with LHON, the ganglion cell layer and the nerve fibre layer showed a considerable reduction from the initial occurrence of symptoms to the 1? years follow-up examination. In the patient with ADOA, the atrophy of the ganglion cell layer and the nerve fibre layer was clearly visible on OCT corresponding to the poor visual acuity of the patient. CONCLUSIONS: Spectral domain OCT instruments allow for high resolution imaging and quantitative analysis of the various retinal layers. Using this technology, it is possible to distinguish between retinal disorders of the outer retinal layers and disorders of the inner retinal layers, like in our cases with LHON and ADOA.

[A 34-year-old patient with retinal vascular abnormality as a coincidental finding]. / 34-jähriger Patient mit auffälligen retinalen Gefäßen als Zufallsbefund.

A young patient presented with recurring blurred vision. Abnormal vessels were found on the retina, which extended as far as the fovea. The diagnosis was congenital vascular malformation in terms of retinal macrovessels.

Accuracy of retinal thickness measurements obtained with Cirrus optical coherence tomography.

AIM: To report the frequency and severity of retinal thickness measurement errors in a Fourier domain optical coherence tomography (FDOCT) device, Cirrus OCT. METHODS: Data from 209 eyes undergoing Cirrus OCT imaging with the Macular Cube protocol were collected. For each eye, the position of the automated retinal boundary lines used by the Cirrus OCT software for thickness calculations was assessed using a 6-point categorical scale. The presence of errors was correlated with various parameters including: retinal morphological features and disease diagnosis. RESULTS: Errors of retinal boundary detection were observed in 57.5% of eyes but were severe in only 9.6% of eyes. The identification of subretinal fluid, subretinal tissue, pigment epithelium detachment or a diagnosis of choroidal neovascularisation was associated with more severe errors. Retinal cysts or a diagnosis of retinal vascular disease were less likely to be associated with significant error. CONCLUSIONS: Retinal thickness measurement errors appear to occur less frequently with Fourier domain OCT (Cirrus OCT), but segmentation errors remain a concern, particularly in assessment of eyes with structurally complex retinal disease. With the recent release of multiple FDOCT systems, assessment of segmentation error may be an important factor in determining the relative merits of these systems.

Comparison of the optical coherence tomographic features of choroidal neovascular membranes in pathological myopia versus age-related macular degeneration, using quantitative subanalysis.

AIM: To compare the retinal morphological characteristics of eyes with choroidal neovascularisation (CNV) secondary to pathological myopia versus eyes with CNV secondary to age-related macular degeneration (AMD), using quantitative optical coherence tomography (OCT) subanalysis. METHODS: Twenty-one eyes of 21 patients newly diagnosed as having CNV secondary to pathological myopia, and 43 consecutive cases of eyes with newly diagnosed subfoveal CNV secondary to AMD were retrospectively collected. In all patients, StratusOCT images and fluorescein angiograms (FA) were available for analysis. StratusOCT images were analysed using custom software (termed "OCTOR"), which allowed calculation of the thickness/volume of the neurosensory retina, subretinal fluid (SRF), subretinal tissue (SRT) and pigment epithelial detachments (PEDs). FA images were used to calculate CNV leakage area and CNV lesion size for each eye. RESULTS: The total volume of neurosensory retina in the pathological myopia group was significantly less than in the AMD group (7.10 (SD 0.50) mm3 vs 7.76 (0.93) mm3, p = 0.004). The total volume of SRF in the pathological myopia group was less than in the AMD group, but the difference was not statistically significant (0.33 (1.38) mm3 vs 0.55 (0.82) mm3, p = 0.434). The total volume of SRT in the pathological myopia group was less than in the AMD group, but the difference was not statistically significant (0.16 (0.15) mm3 vs 0.36 (0.60) mm3, p = 0.144). The total volume of PED in the pathological myopia group was markedly less than in the AMD group (0.01 (0.03) mm3 vs 1.09 (1.89) mm3, p<0.001). On FA, the total leakage of CNV in the AMD group was significantly greater than in the pathological myopia group (4.17 (3.29) DAs vs 0.53 (0.58) DAs, p<0.001). CONCLUSIONS: CNV lesions in pathological myopia were associated with considerably less retinal oedema, SRF and SRT compared with CNV associated with AMD. PEDs were almost negligible in myopic lesions compared with AMD. These findings are consistent with previous clinical and angiographic descriptions of myopic CNV as relatively small lesions with modest exudation.