Effects of three intravitreal injections of aflibercept on the ocular circulation in eyes with age-related maculopathy

Aims: To investigate changes in ocular perfusion following three consecutive intravitreal injections with aflibercept for treatment of neovascular age-related macular degeneration (nAMD). Methods The study included 20 eyes from 20 Caucasian patients with unilateral nAMD and 20 fellow eyes. All nAMD eyes were treated with standard intravitreal injection of aflibercept (IVA;2 mg). Measurements of ocular perfusion at the optic nerve head (ONH) and the choroid were performed with laser speckle flowgraphy (LSFG). Measurements were conducted at baseline, 1 week after the first injection, at the time point of the second and third injection as well as 1 month after the third injection. Results In treated eyes, mean blur rate (the main output parameter of LSFG) in the ONH microvasculature and in the choroid was significantly reduced 1 week after the first IVA treatment. The effect persisted throughout the entire follow-up period (p<0.001). No change in ocular perfusion was observed in fellow eyes. Conclusions: IVA for treatment of nAMD leads to a reduction in perfusion of the ONH and the choroid in the treated eye with no apparent effect on the fellow eye

Differences in optic nerve head blood flow regulation in normal tension glaucoma patients and healthy controls as assessed with laser speckle flowgraphy during the water drinking test

Précis: Optic nerve head (ONH) perfusion was not significantly altered in subjects with normal tension glaucoma (NTG) nor in healthy individuals after performing the water drinking test (WDT), because of its limited effect on ocular perfusion pressure (OPP). Purpose: ONH blood flow can be maintained stable in healthy individuals because of a physiological phenomenon called autoregulation. Impairment of autoregulation has been shown especially under condition of NTG. The purpose of this study was to investigate the ONH blood flow autoregulation in patients with NTG by influencing the OPP with the WDT. Methods: The study included 9 eyes from 9 white patients with a diagnosis of NTG and 9 eyes from age-matched and sex-matched healthy individuals. In the glaucoma group, the antiglaucomatous therapy was paused 3 weeks before the investigations. Measurements of ONH blood flow were performed with laser speckle flowgraphy. After baseline measurements, individuals ingested 800 mL of water in <5 minutes. Measurements were repeated after 15, 30, and 45 minutes. Results: The water ingestion led to a significant rise in intraocular pressure (P<0.001) but also mean arterial pressure (P<0.001) in both groups. This resulted in stable OPP (P=0.051) with no significant difference between the groups (P=0.43). ONH blood flow remained stable over time in both groups (P=0.719). No significant interaction of time and group was shown for all parameters. Conclusions: Our findings show that the WDT does not significantly influence the OPP and therefore has to be considered inferior to other methods used to assess blood flow autoregulation

Laser speckle flowgraphy derived characteristics of optic nerve head perfusion in normal tension glaucoma and healthy individuals : a Pilot study

The purpose of this prospective, case control study was to investigate the differences in optic nerve head blood flow measured with Laser Speckle Flowgraphy (LSFG) between Caucasian patients with normal tension glaucoma and healthy subjects. It included 20 eyes from 20 Caucasian patients with diagnosis of normal tension glaucoma and 20 eyes from age- and sex-matched healthy individuals. In the glaucoma group the antiglaucomatous therapy was paused 3 weeks prior to the investigations. Measurement of optic nerve head blood flow was performed with LSFG. The mean blur rate was obtained for different vascular compartments of the optic nerve head. Parameters for the characterization of pulse-waveform of the mean blur rate were calculated. It was shown that the mean blur rate was significantly lower in the glaucoma group compared to the control group (P < 0.001). The significant differences in the pulse-waveform parameters blow out time (P=0.028) and flow acceleration time index (P < 0.001) indicate a flatter curve in NTG patients. In conclusion, LSFG can detect differences in optic nerve head blood flow between eyes with normal tension glaucoma and healthy eyes.Published versio

Shortterm effect on the ocular circulation induced by unilateral intravitreal injection of aflibercept in agerelated maculopathy

Purpose: Intravitreal injection of antivascular endothelial growth factor (antiVEGF) is the standard treatment for neovascular agerelated macular degeneration (AMD). As VEGF is a physiological key player for regulating retinal vascular tone, questions have been raised whether the application of antiVEGF could induce alterations in ocular perfusion. Methods: The study included 20 eyes from 20 Caucasian patients with unilateral neovascular AMD and 20 fellow eyes. All eyes were treated with standard intravitreal injection of aflibercept (IVA). Measurements of blood flow at the optic nerve head (ONH) and the choroid were performed with laser speckle flowgraphy (LSFG). The intraocular pressure (IOP), systolic and diastolic blood pressure, heart rate, mean arterial pressure (MAP) and ocular perfusion pressure (OPP) were analysed. Measurements were performed at baseline and repeated immediately after the injection and 30 and 45 min later. Results: Mean time between injection of aflibercept and first followup was 8:56 4:25 min. The injection led to significant rise in IOP. In the injected eyes, mean blur rate (MBR, i.e. a relative measure of perfusion and the main outcome parameter of LSFG) within the major vessels of the ONH as well as at the entire ONH region decreased significantly (p < 0.001). No change in MBR was observed in the fellow eye. Choroidal blood flow was maintained stable in both eyes. Conclusion: Intravitreal injection of aflibercept (IVA) led to a shortterm reduction in perfusion only in the treated eye. This was independent from IOP, indicating a direct pharmacological effect. No changes in choroidal perfusion were observed during the first 45 min after the injection.(VLID)360086

Evaluating the impact of vitreomacular adhesion on anti-VEGF therapy for retinal vein occlusion using machine learning

Vitreomacular adhesion (VMA) represents a prognostic biomarker in the management of exudative macular disease using anti-vascular endothelial growth factor (VEGF) agents. However, manual evaluation of VMA in 3D optical coherence tomography (OCT) is laborious and data on its impact on therapy of retinal vein occlusion (RVO) are limited. The aim of this study was to (1) develop a fully automated segmentation algorithm for the posterior vitreous boundary and (2) to study the effect of VMA on anti-VEGF therapy for RVO. A combined machine learning/graph cut segmentation algorithm for the posterior vitreous boundary was designed and evaluated. 391 patients with central/branch RVO under standardized ranibizumab treatment for 6/12 months were included in a systematic post-hoc analysis. VMA (70%) was automatically differentiated from non-VMA (30%) using the developed method combined with unsupervised clustering. In this proof-of-principle study, eyes with VMA showed larger BCVA gains than non-VMA eyes (BRVO: 1512 vs. 1111 letters, p=0.02; CRVO: 1814 vs. 913 letters, p<0.01) and received a similar number of retreatments. However, this association diminished after adjustment for baseline BCVA, also when using more fine-grained VMA classes. Our study illustrates that machine learning represents a promising path to assess imaging biomarkers in OCT.(VLID)460644

Multivendor Spectral-Domain Optical Coherence Tomography Dataset, Observer Annotation Performance Evaluation, and Standardized Evaluation Framework for Intraretinal Cystoid Fluid Segmentation

Development of image analysis and machine learning methods for segmentation of clinically significant pathology in retinal spectral-domain optical coherence tomography (SD-OCT), used in disease detection and prediction, is limited due to the availability of expertly annotated reference data. Retinal segmentation methods use datasets that either are not publicly available, come from only one device, or use different evaluation methodologies making them difficult to compare. Thus we present and evaluate a multiple expert annotated reference dataset for the problem of intraretinal cystoid fluid (IRF) segmentation, a key indicator in exudative macular disease. In addition, a standardized framework for segmentation accuracy evaluation, applicable to other pathological structures, is presented. Integral to this work is the dataset used which must be fit for purpose for IRF segmentation algorithm training and testing. We describe here a multivendor dataset comprised of 30 scans. Each OCT scan for system training has been annotated by multiple graders using a proprietary system. Evaluation of the intergrader annotations shows a good correlation, thus making the reproducibly annotated scans suitable for the training and validation of image processing and machine learning based segmentation methods. The dataset will be made publicly available in the form of a segmentation Grand Challenge

Journal of Ophthalmology / Impact of B-Scan Averaging on Spectralis Optical Coherence Tomography Image Quality before and after Cataract Surgery

Background and Objective. To determine optimal image averaging settings for Spectralis optical coherence tomography (OCT) in patients with and without cataract. Study Design/Material and Methods. In a prospective study, the eyes were imaged before and after cataract surgery using seven different image averaging settings. Image quality was quantitatively evaluated using signal-to-noise ratio, distinction between retinal layer image intensity distributions, and retinal layer segmentation performance. Measures were compared pre- and postoperatively across different degrees of averaging. Results. 13 eyes of 13 patients were included and 1092 layer boundaries analyzed. Preoperatively, increasing image averaging led to a logarithmic growth in all image quality measures up to 96 frames. Postoperatively, increasing averaging beyond 16 images resulted in a plateau without further benefits to image quality. Averaging 16 frames postoperatively provided comparable image quality to 96 frames preoperatively. Conclusion. In patients with clear media, averaging 16 images provided optimal signal quality. A further increase in averaging was only beneficial in the eyes with senile cataract. However, prolonged acquisition time and possible loss of details have to be taken into account.(VLID)486394