Prospective PED-study of intravitreal aflibercept for refractory vascularized pigment epithelium detachment due to age-related macular degeneration: morphologic characteristics of non-responders in optical coherence tomography.

PURPOSE: The aim of this study was to investigate the outcomes of a fixed intravitreal aflibercept regimen in patients with vascular pigment epithelium detachment (vPED) secondary to age-related macular degeneration with refractory subretinal fluid. METHODS: A prospective, interventional case series involved 20 eyes of 20 patients with refractory subretinal fluid and vPED treated with at least three injections of intravitreal anti-VEGF prior to study inclusion. After study inclusion, patients were treated with three injections of intravitreal aflibercept 2 mg/0.05 mL monthly followed by injections every 8 weeks. Best-corrected visual acuity (BCVA) and spectral-domain optical coherence tomography (SD-OCT) were evaluated at all visits. Fluorescein angiography and indocyanine green angiography were performed at baseline and quarterly. Primary outcomes were effectivity of a fixed treatment as measured in change in BCVA, PED greatest linear diameter (GLD), and PED height from baseline to month 12. In an additional post hoc analysis, vPED patients were differentiated into two groups: (1) vPED lesions that showed persistence of subretinal fluid throughout 1 year of treatment and (2) vPED lesions that showed complete resolution of subretinal fluid at least at one of the monthly performed OCT volume scans. Reflectivity values were determined in the subretinal pigment epithelium (RPE) compartment in OCT scans at baseline, month 6 and 12. RESULTS: A total of 18 patients completed the study protocol. The mean age was 74.8 ± 10.6 years, and six patients were female. The median BCVA of all patients was 72.0 ± 8.0 EDTRS letters at baseline and 72.5 ± 9.5 EDTRS letters at 12-month follow-up (p = 0.7420). The median PED height in all patients as measured in the OCT images significantly decreased from 372.0 ± 140.0 µm to 149.0 ± 142.0 µm after 12 months of treatment (p = 0.0020). Persistent subretinal fluid was present at every OCT control in six patients (group 1). Twelve patients showed resolution of subretinal fluid at least at one OCT control (group 2). Reflectivity values in the sub-RPE compartment in OCT scans were 41.48 ± 4.48 (group 1) and 42.62 ± 12.34 (group 2) at baseline (p = 0.854) and 65.88 ± 6.74 and 50.87 ± 14.11 at month 12 (p = 0.038). CONCLUSIONS: Intravitreal aflibercept in refractory vPED leads to a significant reduction in PED height and disease activity as well as preservation of BCVA over 1 year. Persistent subretinal fluid was present in PED lesions with high values of reflectivity under the RPE, suggesting both a diffusion barrier and an increasing fibrovascular maturization of the choroidal neovascularization. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03370380.

Automated OCT angiography image quality assessment using a deep learning algorithm.

PURPOSE: To expedite and to standardize the process of image quality assessment in optical coherence tomography angiography (OCTA) using a specialized deep learning algorithm (DLA). METHODS: Two hundred randomly chosen en-face macular OCTA images of the central 3 × 3 mm2 superficial vascular plexus were evaluated retrospectively by an OCTA experienced reader. Images were defined either as sufficient (group 1, n = 100) or insufficient image quality (group 2, n = 100) based on Motion Artifact Score (MAS) and Segmentation Accuracy Score (SAS). Subsequently, a pre-trained multi-layer deep convolutional neural network (DCNN) was trained and validated with 160 of these en-face OCTA scans (group 1: 80; group 2: 80). Training accuracy, validation accuracy, and cross-entropy were computed. The DLA was tested in detecting 40 untrained OCTA images (group 1: 20; group 2: 20). An insufficient image quality probability score (IPS) and a sufficient image quality probability score (SPS) were calculated. RESULTS: Training accuracy was 97%, validation accuracy 100%, and cross entropy 0.12. A total of 90% (18/20) of the OCTA images with insufficient image quality and 90% (18/20) with sufficient image quality were correctly classified by the DLA. Mean IPS was 0.88 ± 0.21, and mean SPS was 0.84 ± 0.19. Discrimination between both groups was highly significant (p < 0.001). Sensitivity of the DLA was 90.0%, specificity 90.0%, and accuracy 90.0%. Coefficients of variation were 0.96 ± 1.9% (insufficient quality) and 1.14 ± 1.6% (sufficient quality). CONCLUSIONS: Deep learning (DL) appears to be a potential approach to automatically distinguish between sufficient and insufficient OCTA image quality. DL may contribute to establish image quality standards in this recent imaging modality.

Prevalences of segmentation errors and motion artifacts in OCT-angiography differ among retinal diseases.

PURPOSE: To assess the prevalences of segmentation errors and motion artifacts in optical coherence tomography angiography (OCT-A) in different retinal diseases METHODS: In a retrospective analysis, multimodal retinal imaging including OCT-A was performed in one eye of 57 healthy controls (50.96 ± 22.4 years) and 149 patients (66.42 ± 14.1 years) affected by different chorioretinal diseases: early/intermediate age-related macular degeneration (AMD; n = 26), neovascular AMD (nAMD; n = 22), geographic atrophy due to AMD (GA; n = 6), glaucoma (n = 28), central serous chorioretinopathy (CSC; n = 14), epiretinal membrane (EM; n = 26), retinal vein occlusion (RVO; n = 11), and retinitis pigmentosa (RP; n = 16). Central 3 × 3 mm2 OCT-A imaging was performed with active eye-tracking (AngioVue, Optovue). Best-corrected visual acuity (BCVA) and signal strength index (SSI) were recorded. Images were independently evaluated by two graders using the OCT-A motion artifact score (MAS; scores I-IV) as well as a newly introduced segmentation accuracy score (SAS; score I-IIB). RESULTS: Mean SSI was 63.67 ± 9.2 showing a negative correlation with increasing age (rSp = - 0.42, p < 0.001, n = 206). In the healthy cohort, mean MAS was 1.45 ± 0.8 and segmentation was accurate (SAS I) in all eyes. In eyes with retinal pathologies, mean MAS was 2.1 ± 0.9 (p < 0.001). Lowest MAS was observed in GA (2.67 ± 0.5) and RVO (2.45 ± 1.1). Compared to an accurate segmentation in 100% in healthy subjects, 34.2% (n = 51) of all patients showed highest segmentation quality (p < 0.001). 63.8% showed segmentation errors in more than 5% of all single b-scans in one (SAS IIA, n = 58) or at least two (SAS IIB, n = 40) segmentation boundaries. Highest percentages of inaccurate segmentation (SAS IIA or IIB) were observed in the nAMD group (90.1%). The inner plexiform layer was the segmentation boundary most prone to inaccurate segmentation in all pathologies compared to the inner limiting membrane (ILM) and retinal pigment epithelium (RPE) segmentation layer. Incorrect ILM segmentation was only seen in patients with EM. CONCLUSIONS: Prior to both qualitative and quantitative analysis, OCT-A images must be carefully reviewed as motion artifacts and segmentation errors in current OCT-A technology are frequent particularly in pathologically altered maculae.

Quantification of changes in foveal capillary architecture caused by idiopathic epiretinal membrane using OCT angiography.

PURPOSE: To quantify the extent and depth of distortion of the foveal capillary architecture due to traction of an idiopathic epiretinal membrane (ERM) using optical coherence tomography angiography (OCT-A). METHODS: Multimodal imaging including OCT-A (Angiovue, Optovue) was performed in 42 eyes with idiopathic ERM (72.4 years ±6.8). Best corrected visual acuity (BCVA), OCT-A vessel density of the foveal (VDfo) and parafoveal (VDp) region were assessed. Based on 6 × 6-mm2 OCT-A images, a macular vessel density ratio (MVR = VDfo/VDp) was calculated for the superficial (s), deep (d) and full-thickness (f) slabs to assess a depth-resolved, non-invasive evaluation of foveal distortion. The acquired data were subdivided in a patient group with mild and significant BCVA reduction due to ERM. Data was compared to age-matched healthy controls. RESULTS: In all three slabs, MVR was significantly smaller in the control group in comparison with the ERM group: MVRs: 0.63 ± 0.1 vs 0.83 ± 0.1 (p > 0.001); MVRd: 0.60 ± 0.1 vs 0.73 ± 0.1 (p < 0.001); MVRf: 0.68 ± 0.1 vs 0.82 ± 0.1 (p < 0.001). Group 1 (BCVA <0.4 LogMar) showed a significantly higher MVR in comparison with the control group in the superficial plexus only: MVRs: 0.64 ± 0.1 vs 0.78 ± 0.1 (p < 0.001); MVRd: 0.60 ± 0.1 vs 0.65 ± 0.2 (p = 0.3); MVRf: 0.68 ± 0.1 vs 0.77 ± 0.1 (p = 0.01). However, group 2 (BCVA > = 0.4 LogMar) showed a significantly higher MVR in all three slabs: MVRs: 0.64 ± 0.1 vs 0.86 ± 0.1 (p < 0.001); MVRd: 0.60 ± 0.1 vs 0.77 ± 0.2 (p < 0.001); MVRf: 0.68 ± 0.1 vs 0.85 ± 0.1 (p < 0.001). CONCLUSION: Assessing MVR using OCT-A may serve as a tool to quantify the extent and depth of distortion of the foveal capillary architecture due to traction of ERM. BCVA reduction appears to be associated with extent and depth of distortion.

Signal reduction in choriocapillaris and segmentation errors in spectral domain OCT angiography caused by soft drusen.

PURPOSE: To analyze signal reduction in choriocapillaris (CC) and segmentation errors in spectral domain optical coherence tomography angiography (OCT-A) caused by soft drusen due to age-related macular degeneration (AMD). METHODS: Twenty-four eyes of 24 patients underwent multimodal retinal imaging including central 3 × 3mm2 OCT-A (AngioVue, Optovue). Three drusen per study eye were randomly chosen and evaluated regarding drusen height, diameter, and accuracy of OCT-A layer segmentation in lesion proximity. Structural en-face OCT CC images were graded qualitatively and quantitatively regarding signal loss underneath the individual drusen area. Those drusen that showed no distinct signal loss in structural en-face OCT CC images were further evaluated in OCT-A. CC decorrelation signal index was measured within a 30-µm OCT-A CC slab in the exact area of drusen affection. Data were compared to healthy age-matched control subjects. Accuracy of layer segmentation, OCT CC data, and OCT-A CC data were correlated to morphological drusen parameters. RESULTS: Mean drusen height and diameter were 91.57 ± 19.5µm and 315.17 ± 116.7µm. OCT-A layer segmentation of the inner plexiform layer (IPL) was disturbed by more than 50 µm in proximity to 26 drusen (36.1%). In these patients, drusen height was significantly higher compared to those with accurate IPL segmentation (p = 0.0126). Sixty-six out of 72 drusen (91.7%) caused a distinct signal loss in the structural en-face OCT CC image. Drusen height and drusen diameter were significantly higher in this group compared to the six drusen with a sufficient signal (p = 0.0276, p = 0.0025). CC decorrelation signal index measured in the area of these six drusen without OCT signal loss (8.3%) was reduced compared to age-matched healthy controls (73.6 vs. 100.1; p = 0.001). CONCLUSIONS: Signal attenuation in CC slabs and segmentation errors of the IPL depend on drusen morphology. Both are frequent artifacts in OCT-A imaging in patients with soft drusen and must be considered during image analysis.

Impact of eye-tracking technology on OCT-angiography imaging quality in age-related macular degeneration.

OBJECTIVE: To evaluate the impact of eye-tracking (ET) technology on optical coherence tomography angiography (OCT-A) image quality and manifestation of motion artifacts in patients with age-related macular degeneration (AMD). METHODS: In a prospective trial, multimodal retinal imaging including OCT-A was performed in 30 patients (78.97 ± 9.7 years) affected by different stages of AMD. Central 3 × 3 mm2 OCT-A imaging was performed four times consecutively in each patient, twice with active, and twice with inactive ET. Parameters for image evaluation were signal strength index (SSI), variability of foveal vessel density (VD), acquisition time, presence of motion artifacts caused by eye movement (blink lines, displacement) and by software correction of eye movement (quilting, stretch artifacts, vessel doubling). Images were evaluated by two independent readers with subsequent senior reader arbitration for presence of artifacts, and an OCT-A motion artifact score (MAS) was calculated. RESULTS: Eight patients had early and eight patients had intermediate stages of AMD. Four patients had an atrophic late stage and ten patients an exudative stage of the disease. SSI was 53.55 with inactive and 57.18 with active ET (p = 0.0005). Coefficients of variability of VD between the first and second measurement were 8.9% with inactive and 5.7% with active ET. Mean image acquisition time was 15.97 s (active ET: 22.88 s, p < 0.001). Presence of motion artifacts was significantly higher with inactive ET (mean MAS 3.27 vs. 1.93; p < 0.0001). MAS correlated with AMD disease stage [p = 0.0031 (inactive ET) and p < 0.0001 (active ET)] and with SSI (p = 0.0072 and p = 0.0006). CONCLUSIONS: In patients with AMD, active ET technology offers an improved image quality in OCT-A imaging regarding presence of motion artifacts at the expense of higher acquisition time.

Characterisation of reticular pseudodrusen and their central target aspect in multi-spectral, confocal scanning laser ophthalmoscopy.

BACKGROUND: To analyse reticular pseudodrusen (RPD) in patients with age-related macular degeneration (AMD) using multi-spectral (MS), confocal scanning laser ophthalmoscopy (cSLO). METHODS: cSLO images (blue fundus autofluorescence [FAF; exc., λ = 488; em., λ = 500-700 nm], near-infrared reflectance [IR; λ = 820 nm], MS [blue reflectance (BR) λ = 488 nm, green reflectance (GR) λ = 515 nm, IR λ = 820 nm], as well as colour fundus photographs (CFP) were taken of 200 eyes from 100 AMD patients suspected to show RPD on the basis of funduscopy or previous fundus imaging. FAF and IR images were graded by two independent readers. If both readers concordantly confirmed the presence of RPD in both modalities, eyes were subsequently also graded for RPD in MS, BR, GR, green-blue enhanced mode (GBE), and CFP. Besides, FAF, IR, and MS images were evaluated for the presence of a target aspect, which represents a common feature of RPD lesions. RESULTS: The presence of RPD was confirmed using FAF and IR images by both readers in 130 eyes of 76 patients. In those eyes, both readers concordantly diagnosed RPD in MS images in 124 (95.4%) eyes (BR: 52 [40.0%], GR: 63 [48.5%], GBE: 101 [77.7%], CF: 27 [20.8%]). Cohen kappa statistics revealed excellent inter-observer agreement for MS (0.95) and GBE (0.85), substantial agreement for BR (0.75), GR (0.78), and moderate agreement for CFP (0.59). A target aspect within RPD lesions was detected in 45 of 130 (35.0%) included eyes using FAF and IR. The presence of a target aspect improved the recognition of RPD lesions in all modalities. If a target aspect was present, RPD were diagnosed in 45 eyes (100%) using MS (GBE: 42 eyes [93.3%], BR: 30 eyes [66.7%], GR: 37 eyes [82.2%], CFP: 17 eyes [37.8%]). Using MS cSLO, a target aspect could be identified in 75 of 130 (57.7%) included eyes. CONCLUSIONS: MS cSLO imaging is equivalent to FAF and IR in identifying RPD in AMD patients. Higher identification rates in BR and GR of those RPD lesions featuring a target aspect confirm the current hypothesis of RPD localisation and its progression further into the photoreceptor layers. MS seems to be more sensitive in identifying a central target aspect in RPD lesions compared to blue FAF and IR.

[Predictive near-infrared SLO signs for tears of the retinal pigment epithelium due to age-related macular degeneration]. / Prädiktive nahinfrarot-SLO-merkmale für risse des retinalen pigmentepithels bei altersabhängiger makuladegeneration.

PURPOSE: The aim of this study was to identify potential predictive markers in confocal scanning laser ophthalmoscopy (cSLO)-based imaging for tears of the retinal pigment epithelium (RPE) in the presence of pigment epithelial detachments (PED) due to age-related macular degeneration (AMD). METHODS: Fifteen eyes of 15 patients (mean age 77 years, SD ± 6) with RPE tears and pre-existing PEDs were retrospectively analysed for the presence of increased signals on near-infrared imaging (NIR) using confocal scanning laser ophthalmoscopy (cSLO). RESULTS: In 87 % of the cases increased reflectance signals on NIR in the area of the PED were noted prior to the development of an RPE tear. On average, these signals were recorded 58 days (SD ± 40) before the rip was diagnosed. In 62 % of the patients these signals were localised opposite to the rip location at the rim of the PED. CONCLUSION: Increased reflectance signals on NIR imaging may serve as a predictive marker for RPE tears in patients with PED in AMD. These signals recordable with a non-invasive imaging method should be prospectively validated in a larger cohort of patients with PEDs. It may be useful in the management of patients exhibiting this manifestation of exudative AMD.

[Analysis of the importance of e-learning in ophthalmology and evaluation of an e-learning app]. / Analyse des Stellenwertes von "eLearning" in der Augenheilkunde und Evaluierung einer "eLearning-App".

BACKGROUND: The aim of the study was to analyze the importance of e­learning in the learning and training behavior of ophthalmologists in Germany and to evaluate the acceptance of a new e­learning user software (app). MATERIAL AND METHODS: Ophthalmological residents and specialists were asked about continuing education activities by means of a questionnaire during continuing education events. Furthermore, a structured evaluation was carried out after the presentation and application of an e­learning app. RESULTS: A total of 149 ophthalmologists took part in the survey. While the majority of colleagues (74.3%) used specialist journals weekly or monthly for further education, 45.9% of ophthalmologists used digital print media (books, journals, articles) and 46.5% used specialist books in printed form. Only 35% of the interviewees used online training platforms, e.g. digital courses (CME courses) or portals for retrieving recorded lectures. The use of the offered e­learning app was generally accompanied by a positive acceptance. Of the interviewed colleagues 91.7% would recommend this form of interactive learning. DISCUSSION: Despite a progressive digitalization in all areas of life, e­learning continues to play a minor role as a learning medium in ophthalmological advanced training. Interestingly, the evaluation of app users showed a high level of acceptance, regardless of age or field of work.

[Retinal pigment epithelial detachment in hyperviscosity syndrome]. / Seröse Amotio retinae bei Hyperviskositätssyndrom.

We present a case of a 57-year-old woman who reported bilateral visual impairment since 2 weeks. She had a medical history of congenital, cyanotic heart failure. Funduscopic examination revealed serous retinal detachment on the left side, central subneurosensory detachment on the right side, retinal vessel tortuosity and multiple retinal haemorrhages in the periphery. As blood analysis showed a distinct increase in haemoglobin and haematocrit, hyperviscosity syndrome was suspected to have caused bilateral serous retinal detachment. Isovolemic haemodilution was performed in close cooperation with the cardiology department with repeated phlebotomy, which resulted in a significant reduction of subretinal fluid and, concurrently, an increase in visual acuity.

[Volumetric analysis of vascularized pigment epithelium detachment in AMD: post hoc analysis of the RECOVER study]. / Volumetrische Analyse der vaskularisierten Pigmentepithelabhebung bei AMD: Post-hoc-Analyse der RECOVER-Studie.

BACKGROUND: The ratio of choroidal neovascularization (CNV) and pigment epithelium detachment (PED) represents an important parameter regarding the risk of developing a tear of the retinal pigment epithelium (RPE) in patients with vascularized PED due to age-related macular degeneration (AMD). METHODS: Within the framework of the RECOVER study a total of 29 treatment-naive patients with vascularized PED underwent fluorescein angiography (FA), indocyanine green angiography (ICGA) and optical coherence tomography (OCT) volume scans. The CNV-PED ratio was evaluated retrospectively by two independent graders in three ways: 1) manually based on the en face image of the FA late phase and 2) manually based on the en face image of the ICGA late phase. 3) In every OCT scan encompassing the PED, the area between the RPE and Bruch's membrane and the CNV area was measured and multiplied by the distance between OCT scans in order to determine volumetric data of CNV, PED and the serous cavity. RESULTS: The FA and ICGA showed a mean serous area of 6.14 ± 4.21 mm2 (ICGA 5.94 ± 4.13 mm2), a mean CNV area of 3.25 ± 1.79 mm2 (ICGA 2.84 ± 1.68 mm2) and a mean PED area of 9.39 ± 4.27 mm2 (ICGA 8.79 ± 4.23 mm2) resulting in a mean two-dimensional morphological ratio of 0.35 ± 0.21 (ICGA 0.32 ± 0.22). The volumetric measurement revealed a mean CNV volume of 0.63 ± 0.67 mm3, a mean serous volume of 3.61 ± 3.83 mm3 and a mean total PED volume of 4.25 ± 3.68 mm3. The mean three-dimensional morphological ratio was 0.15 ± 0.29. The difference between the two-dimensional ratios of FA (p < 0.0001) and ICGA (p = 0.0004) was significant compared to the three-dimensional OCT ratio. CONCLUSION: Assessment of the CNV-PED ratio using volumetric OCT measurements is an additional tool to the en face modalities FA and ICGA. This seems to be clinically relevant regarding the risk stratification of RPE tear development in PED patients and for the planning of the treatment regimen.

[BOON (Bonn ophthalmology online network). Concept of an integrative databank for monitoring patients under intravitreal therapy]. / BOON (Bonn Ophthalmology Online Network). Konzept einer integrativen Datenbank zum Monitoring von Patienten unter intravitrealer Therapie.

BACKGROUND: Previous studies have proven that long-lasting success in the therapy of neovascular age-related macular degeneration (AMD) and other neovascular retinal diseases depends on monthly follow-up examinations to assess visual acuity and retinal morphology. MATERIALS AND METHODS: The interactive database Bonn ophthalmology online network (BOON) offers a platform for patient monitoring, increasing control reliability and providing a tool for permanent communication between treating centers and referring ophthalmologists. The BOON data-based project started in 2009 at the department of ophthalmology at Bonn University and ten referring ophthalmology practices. It was programmed to communicate diagnostic findings, images and patient appointments online. In order to react promptly the system gave immediate notice if patients had missed a follow-up appointment or the condition had worsened. Patients were recruited in 2009 and 2010 and were followed for 1 year. Each patient had an electronic master file with several registers in which, besides personal data, precise diagnostic findings, imaging and reports were quickly and easily entered by means of detailed check box and drop-down menus. Each follow-up was registered and an alert email was sent to the referring physician in cases of missed appointments or disease progression. RESULTS AND CONCLUSIONS: The BOON database supports the requirements for a fast and detailed communication between treating and referring physicians in the treatment of patients with AMD as well as other retinal diseases. It was programmed to support data exchange and monthly control visits and thus a better patient management. Results will show whether this helps to enhance long-term treatment success in neovascular diseases.

[Reliability and safety of intravitreal Ozurdex injections. The ZERO study]. / Zuverlässigkeit und Sicherheit von intravitrealen Ozurdex-Injektionen. Die ZERO-Studie.

BACKGROUND: Since July 2010 Ozurdex® is approved in Germany for treatment of macular edema from retinal vein occlusion (RVO). The objective of this observational study was a systemic summary and analysis of clinical experience regarding complications and side effects of intravitreal administration of dexamethasone. PATIENTS AND METHODS: In a retrospective, multicenter study conducted at 10 centers, 342 eyes with RVO were treated with intravitreal dexamethasone (Ozurdex®, Allergan). After treatment the patients were followed-up over a period of 8 months and intraoperative, perioperative and postoperative complications, such as elevated intraocular pressure and dislocation of implants were systematically recorded. RESULTS: No infections, endophthalmitis, perioperative hypotension, intraoperative lens injuries or retinal detachment occurred. Elevated intraocular pressure was the most common complication accounting for nearly 20 %. In 9 % of patients the intraocular pressure increased by more than 10 mmHg compared to baseline and in 6 patients to > 35 mmHg. In cases of known glaucoma intraocular pressure elevation was not significantly more frequent compared to non-glaucoma patients. In four cases a progression of lens opacity led to phacoemulsification and two implant dislocations in the anterior chamber required surgical repositioning in the vitreous cavity. In two cases a postinterventional macular hole was observed. CONCLUSIONS: In the clinical routine Ozurdex treatment has proven to be a therapy method with minimal side effects. In Ozurdex administration intraocular pressure elevation was observed as the most common side effect; however, this generally did not require surgical intervention. Caution is advised in patients with an anterior chamber lens and iridectomy. Macular holes as a rare complication might result from vitreous traction during the administration process. In summary, even in the clinical routine application of Ozurdex the complication rate was not higher than in registration studies.