Towards standardising retinal OCT angiography image analysis with open-source toolbox OCTAVA.

Quantitative assessment of retinal microvasculature in optical coherence tomography angiography (OCTA) images is important for studying, diagnosing, monitoring, and guiding the treatment of ocular and systemic diseases. However, the OCTA user community lacks universal and transparent image analysis tools that can be applied to images from a range of OCTA instruments and provide reliable and consistent microvascular metrics from diverse datasets. We present a retinal extension to the OCTA Vascular Analyser (OCTAVA) that addresses the challenges of providing robust, easy-to-use, and transparent analysis of retinal OCTA images. OCTAVA is a user-friendly, open-source toolbox that can analyse retinal OCTA images from various instruments. The toolbox delivers seven microvascular metrics for the whole image or subregions and six metrics characterising the foveal avascular zone. We validate OCTAVA using images collected by four commercial OCTA instruments demonstrating robust performance across datasets from different instruments acquired at different sites from different study cohorts. We show that OCTAVA delivers values for retinal microvascular metrics comparable to the literature and reduces their variation between studies compared to their commercial equivalents. By making OCTAVA publicly available, we aim to expand standardised research and thereby improve the reproducibility of quantitative analysis of retinal microvascular imaging. Such improvements will help to better identify more reliable and sensitive biomarkers of ocular and systemic diseases.

Spatio-temporal optical coherence tomography provides full thickness imaging of the chorioretinal complex.

Despite the rapid development of optical imaging methods, high-resolution in vivo imaging with penetration into deeper tissue layers is still a major challenge. Optical coherence tomography (OCT) has been used successfully for non-invasive human retinal volumetric imaging in vivo, advancing the detection, diagnosis, and monitoring of various retinal diseases. However, there are important limitations of volumetric OCT imaging, especially coherent noise and the limited axial range over which high resolution images can be acquired. The limited range prevents simultaneous measurement of the retina and choroid with adequate lateral resolution. In this article, we address these limitations with a technique that we term spatio-temporal optical coherence tomography (STOC-T), which uses light with controlled spatial and temporal coherence and advanced signal processing methods. STOC-T enabled the acquisition of high-contrast and high-resolution coronal projection images of the retina and choroid at arbitrary depths.

Split-Window OCT biometry in pseudophakic eyes.

PURPOSE: To determine the utility of Split-Window optical coherence tomography OCT (SW-OCT) biometry in measuring ocular axial dimensions as well as imaging the intraocular lens (IOL) and posterior capsule in pseudophakic eyes. METHODS: Sixty-nine pseudophakic eyes of 69 subjects were enrolled in the study. The results of SW-OCT biometry implemented in the SD OCT device for posterior and anterior segment imaging (REVO NX, Optopol Technology) were compared with those obtained with the SS-OCT-based biometer IOLMaster 700 (Carl Zeiss Meditec). Differences in measurement values between the two biometers were determined using the paired t-test. Agreement was assessed through intraclass correlation coefficients (ICC) and Bland-Altman plots. RESULTS: The correlation between measurements obtained with SW-OCT and SS-OCT was very high (ICC for: axial length (AL) = 1.000; anterior chamber depth (ACD) = 0.997; IOL thickness (IOL LT) = 0.997; central corneal thickness (CCT) = 0.987). The mean AL measurement difference was 0.003 ± 0.021 mm (the 95% LoA ranged from -0.04 to 0.05); the mean ACD difference was -0.009 ± 0.025 mm (95% LoA, -0.06 to 0.04); mean LT difference was 0.001 ± 0.021 mm (95% LoA, -0.04 to 0.04); and mean CCT difference was 1.4 ± 5.4 µm (95% LoA, -9 to 12). CONCLUSION: The study shows small, non-significant differences between the biometric measurements obtained with REVO NX SW-OCT and IOLMaster 700 SS-OCT in pseudophakic eyes. However, SW-OCT offered significantly lower ACD and LT measurement failure rates. With high-resolution imaging, SW-OCT enables accurate assessment of IOL position relative to the posterior capsule and visualization of capsular fibrosis.

Simultaneous Corneal Topography and Epithelial Thickness Mapping from a Single Measurement Using Optical Coherence Tomography.

Purpose: To evaluate the performance of corneal epithelial thickness mapping (ETM) and demonstrate simultaneous measurement of ETMs and corneal topography using REVO NX (Optopol Technology, Zawiercie, Poland)-an OCT device for anterior and posterior segment imaging. Methods: One hundred thirty-seven eyes of 137 normal subjects and patients with corneal diseases were recruited to the study. Each subject was scanned with REVO NX. ETMs and corneal topography maps were reconstructed from a single measurement. Corneal topography was also carried out using Pentacam (Oculus, Wetzlar, Germany). One hundred twenty-eight eyes were qualified for the final analysis. Forty healthy eyes were used to evaluate the performance of ETM, and 88 eyes were used to compare ETMs and corneal topography. The repeatability and reproducibility of ETMs in healthy subjects were assessed on the basis of 17 spatial zones derived from an 8-mm diameter corneal scan using within-subject standard deviation, test-retest repeatability, within-subject coefficient of variation (CoV), and intraclass correlation coefficient (ICC). Results: The ICC for both repeatability and reproducibility of ETMs for the central sector was 0.95. The ICC value for the other sectors was only moderately lower. However, the CoV for repeatability (≤1.55%) was slightly higher than the value reported for the RTVue device (Optovue, Inc, Fremont, California, USA), for which a CoV in the central zone of 1.07% was reported in unoperated eyes. The superior quadrants were found to be the thinnest while the inferior ones were the thickest. ETMs and topography maps created from a single OCT measurement present a complementary image of the cornea. Conclusions: ETMs obtained using REVO NX show high levels of repeatability and reproducibility in normal eyes. Because the topographic and epithelial thickness analyses are performed using the same data, which means they are based on the exact same 3D corneal model, they do not require reciprocal centration and map matching. This ensures a complete point-to-point correlation between ETMs and corneal topography maps, which paints a fuller picture of a given pathology.

SAFETY AND THERAPEUTIC EFFECTS OF ORALLY ADMINISTERED AKST4290 IN NEWLY DIAGNOSED NEOVASCULAR AGE-RELATED MACULAR DEGENERATION.

PURPOSE: To evaluate the safety and therapeutic effects of orally administered AKST4290 (formerly BI 144807 and ALK4290) in treatment-naive patients with neovascular age-related macular degeneration. METHODS: In this prospective, multicenter, open-label Phase 2a pilot clinical study, 30 patients with newly diagnosed neovascular age-related macular degeneration self-administered AKST4290 (400 mg) orally twice daily for 6 weeks. Patients were examined weekly for safety, to measure best-corrected visual acuity (BCVA), and to perform exploratory morphologic assessments. The primary endpoint was the mean change in BCVA from baseline to end of treatment, and the secondary endpoint was safety. Exploratory endpoints investigated potential changes in macular morphology. RESULTS: Mean BCVA improved by +7.0 letters (95% CI, 2.2-11.7); 24 patients (82.8%) had stable or improved BCVA, with 6 (20.7%) gaining ≥15 letters. No patients experienced severe or serious adverse events. CONCLUSION: In this 6-week study, AKST4290 treatment was associated with improved BCVA scores in patients with treatment-naive neovascular age-related macular degeneration. All adverse events were mild or moderate in severity and no safety issues were identified. Treatment of neovascular age-related macular degeneration with AKST4290 warrants further investigation in randomized, placebo-controlled trials.

Multimode fiber as a tool to reduce cross talk in Fourier-domain full-field optical coherence tomography.

Fourier-domain full-field optical coherence tomography (FD-FF-OCT) is an emerging tool for high-speed eye imaging. However, cross-talk formation in images limits the imaging depth. To this end, we have recently shown that reducing spatial coherence with a fast deformable membrane can suppress the noise but over a limited axial range and with substantial data processing. Here, we demonstrate that a multimode fiber with carefully chosen parameters enables cross-talk-free imaging over a long axial range and without significant artifacts. We also show that it can be used to image the human retina and choroid in vivo with exceptional contrast.

In vivo imaging of the human eye using a 2-photon-excited fluorescence scanning laser ophthalmoscope.

BackgroundNoninvasive assessment of metabolic processes that sustain regeneration of human retinal visual pigments (visual cycle) is essential to improve ophthalmic diagnostics and to accelerate development of new treatments to counter retinal diseases. Fluorescent vitamin A derivatives, which are the chemical intermediates of these processes, are highly sensitive to UV light; thus, safe analyses of these processes in humans are currently beyond the reach of even the most modern ocular imaging modalities.MethodsWe present a compact, 2-photon-excited fluorescence scanning laser ophthalmoscope and spectrally resolved images of the human retina based on 2-photon excitation (TPE) with near-infrared light. A custom Er:fiber laser with integrated pulse selection, along with intelligent postprocessing of data, enables excitation with low laser power and precise measurement of weak signals.ResultsWe demonstrate spectrally resolved TPE fundus images of human subjects. Comparison of TPE data between human and mouse models of retinal diseases revealed similarity with mouse models that rapidly accumulate bisretinoid condensation products. Thus, visual cycle intermediates and toxic byproducts of this metabolic pathway can be measured and quantified by TPE imaging.ConclusionOur work establishes a TPE instrument and measurement method for noninvasive metabolic assessment of the human retina. This approach opens the possibility for monitoring eye diseases in the earliest stages before structural damage to the retina occurs.FundingNIH, Research to Prevent Blindness, Foundation for Polish Science, European Regional Development Fund, Polish National Agency for Academic Exchange, and Polish Ministry of Science and Higher Education.

In vivo imaging of the human cornea with high-speed and high-resolution Fourier-domain full-field optical coherence tomography.

Corneal evaluation in ophthalmology necessitates cellular-resolution and fast imaging techniques that allow for accurate diagnoses. Currently, the fastest volumetric imaging technique is Fourier-domain full-field optical coherence tomography (FD-FF-OCT), which uses a fast camera and a rapidly tunable laser source. Here, we demonstrate high-resolution, high-speed, non-contact corneal volumetric imaging in vivo with FD-FF-OCT that can acquire a single 3D volume with a voxel rate of 7.8 GHz. The spatial coherence of the laser source was suppressed to prevent it from focusing on a spot on the retina, and therefore, exceeding the maximum permissible exposure (MPE). The inherently volumetric nature of FD-FF-OCT data enabled flattening of curved corneal layers. The acquired FD-FF-OCT images revealed corneal cellular structures, such as epithelium, stroma and endothelium, as well as subbasal and mid-stromal nerves.

Comparison of Advanced Threshold and SITA Fast Perimetric Strategies.

PURPOSE: To compare the results obtained with two threshold strategies of visual field assessment: Humphrey SITA Fast (SFA) (Carl Zeiss Meditec) and PTS 2000 Advanced Threshold (ADV) (Optopol Technology) in healthy subjects and patients with glaucoma. METHODS: The study sample comprised of 53 healthy volunteers and 69 patients with glaucoma. One eye of each patient was examined with the SFA and ADV strategies. The quantitative comparisons of test duration and global indices were made using correlation coefficients. The sensitivity and specificity of the algorithms were evaluated based on the GHT results and the adjusted Anderson-Patella (A&P) criteria. RESULTS: The ADV test duration was shorter both in healthy subjects (by 5%) and patients with glaucoma (by 18%). The mean differences in MS values between the SFA and the ADV strategies were 1.06 ± 1.13 dB (MSSFA-MSADV) in healthy subjects and 1.00 ± 1.92 dB (MSSFA-MSADV) in patients with glaucoma. The MD index of ADV tests was lower than the SFA in the healthy (-0.74 ± 1.09 dB) (MSSFA-MSADV) and glaucoma group (-0.85 ± 2.19 dB) (MSSFA-MSADV). The mean differences in PSD values determined using both methods were -0.86 ± 0.67 dB (PSDSFA-PSDADV) and -0.53 ± 1.48 dB (PSDSFA-PSDADV) in healthy subjects and patients with glaucoma, respectively. Analysis of receiver operating characteristic curves built from MD and PSD indices show bigger area under curve in SFA than in ADV (0.983 vs.0.968 and 0.986 vs. 0.938, respectively). The GHT-based sensitivity and specificity for the ADV strategy were 92.75% and 77.36%, respectively, as compared to 92.75% and 90.57%, respectively, for the SFA strategy. CONCLUSIONS: Both SFA and ADV enable effective identification of glaucomatous defects within 5 minutes. The ADV strategy, however, is significantly faster. The correlation between the global indices of SFA and ADV is very high. Both strategies offer very high sensitivity when using both GHT and A&P criteria.

OCT Biometry (B-OCT): A New Method for Measuring Ocular Axial Dimensions.

PURPOSE: To present a new method of measuring ocular axial dimensions, termed OCT biometry (B-OCT). DESIGN: Observational cross-sectional study and evaluation of new diagnostic technology. METHODS: B-OCT was implemented in the spectral domain OCT device for posterior and anterior segment imaging (REVO NX, Optopol Technology). A total of 349 eyes (214 of healthy subjects, 115 of patients with cataract, and 20 with severe macular diseases) were enrolled in the study. The results of B-OCT were compared to swept source OCT-based IOLMaster 700 (Carl Zeiss Meditec). Differences in measurement values between the two biometers were determined using the paired t-test. Agreement was assessed through intraclass correlation coefficients (ICCs) and Bland-Altman plots. RESULTS: B-OCT obtained with REVO NX provides excellent interobserver reproducibility (ICC for: axial length (AXL) = 1.000; central corneal thickness (CCT) = 0.933; anterior chamber depth (ACD) = 0.933; lens thickness (LT) = 0.985) and intraobserver repeatability (ICC for: AXL = 1.000; CCT ≥ 0.994; ACD = 0.998; LT ≥ 0.993). The correlation between measurements made using both devices was outstanding (ICC for: AXL, healthy = 1.000; AXL, cataractous = 1.000; ACD, healthy = 0.998; ACD, cataractous = 0.997; LT, healthy = 0.998; LT, cataractous = 0.997; CCT, healthy = 0.989; CCT, cataractous = 0.979). The mean AXL measurement difference in healthy eyes was -0.001 ± 0.016 mm (the 95% LoA ranged from -0.034 to 0.031); mean ACD difference was 0.000 ± 0.024 mm (95% LoA, -0.047 to 0.047); mean LT difference was -0.002 ± 0.024 mm (95% LoA, -0.050 to 0.046); and mean CCT difference was -0.8 ± 5.1 µm (95% LoA, -10.81 to 9.26). The mean AXL measurement difference in cataractous eyes was -0.003 ± 0.022 mm (95% LoA, -0.046 to 0.039); mean ACD difference was 0.003 ± 0.029 mm (95% LoA, -0.054 to 0.059); mean LT difference was -0.002 ± 0.025 (95% LoA, -0.051 to 0.048); and mean CCT difference was 2.7 ± 6.4 µm (95% LoA, -9.80 to 15.7). CONCLUSION: The study shows small, nonsignificant differences between the biometric measurements obtained with REVO NX B-OCT and IOLMaster 700, which is of high significance for IOL power selection. As B-OCT utilizes a conventional OCT device, the measurements of the ocular axial dimensions are combined with high-resolution macular scans for the simultaneous assessment of central retina as a part of screening for macular pathology. The presented method is the first spectral domain OCT-based biometry technique and the only one integrated into a standard OCT device. Thus, it brings novel functionality to OCT technology.

Quality improvement of OCT angiograms with elliptical directional filtering.

We present a method of OCT angiography (OCTA) data filtering for noise suppression and improved visualization of the retinal vascular networks in en face projection images. In our approach, we use a set of filters applied in three orthogonal axes in the three-dimensional (3-D) data sets. Minimization of artifacts generated in B-scan-wise data processing is accomplished by filtering the cross-sections along the slow scanning axis. A-scans are de-noised by axial filtering. The core of the method is the application of directional filtering to the C-scans, i.e. one-pixel thick sections of the 3-D data set, perpendicular to the direction of the scanning OCT beam. The method uses a concept of structuring, directional kernels of shapes matching the geometry of the image features. We use rotating ellipses to find the most likely local orientation of the vessels and use the best matching ellipses for median filtering of the C-scans. We demonstrate our approach in the imaging of a normal human eye with laboratory-grade spectral-domain OCT setup. The "field performance" is demonstrated in imaging of diabetic retinopathy cases with a commercial OCT device. The absolute complex differences method is used for the generation of OCTA images from the data collected in the most noise-wise unfavorable OCTA scanning regime-two frame scanning.

Optical coherence tomography in diagnosis and monitoring multiple sclerosis.

This paper presents application of optical coherence tomography (OCT) for diagnosis and monitoring of multiple sclerosis (MS). The peripapillary retinal nerve fibre layer thinning and the reduced total macular volume analysis are shown. With the course of the MS, the severity of these abnormalities increases which reflects the progressive degeneration of retinal ganglion cells and nerve fibres. The OCT parameters are sensitive, non-invasive indicators useful in assessing the progression of inflammation and neurodegeneration in MS.

Pseudophakic cystoid macular edema: update 2016.

Pseudophakic cystoid macular edema (PCME) is the most common complication of cataract surgery, leading in some cases to a decrease in vision. Although the pathogenesis of PCME is not completely understood, the contribution of postsurgical inflammation is generally accepted. Consequently, anti-inflammatory medicines, including steroids and nonsteroidal anti-inflammatory drugs, have been postulated as having a role in both the prophylaxis and treatment of PCME. However, the lack of a uniformly accepted PCME definition, conflicting data on some risk factors, and the scarcity of studies comparing the role of nonsteroidal anti-inflammatory drugs to steroids in PCME prevention make the problem of PCME one of the puzzles of ophthalmology. This paper presents an updated review on the pathogenesis, risk factors, and use of anti-inflammatory drugs in PCME that reflect current research and practice.

Photoreceptor Inner and Outer Segment Junction Reflectivity after Vitrectomy for Macula-Off Rhegmatogenous Retinal Detachment.

Purpose. To evaluate the spatial distribution of photoreceptor inner and outer segment junction (IS/OS) reflectivity changes after successful vitrectomy for macula-off retinal detachment (PPV-mOFF) using spectral domain optical coherence tomography (SdOCT). Methods. Twenty eyes after successful PPV-mOFF were included in the study. During a mean follow-up period of 15.3 months, SdOCT was performed four times. To evaluate the IS/OS reflectivity a four-grade scale was used. Results. At the first follow-up visit the IS/OS had very similar reflectivity in entire length of the central scan with total average value of 1,05. At the second visit the most significant increase of the reflectivity was observed in temporal and nasal parafovea with average values of 2,17 and 2,22, respectively. The third region of increased reflectivity of an average value of 2,33 appeared during the third follow-up visit and was located in the foveola. At the last follow-up visit in entire central cross section the IS/OS reflectivity exceeded grade 2 reaching the highest average values in nasal and temporal parafovea and foveola. Conclusions. A gradual increase of the IS/OS reflectivity was observed in eyes after PPV-mOFF. The process is not random and starts independently in the peripheral and central part of the macula which may be attributed to the variable regenerative potential of cones and rods.

OCT angiography by absolute intensity difference applied to normal and diseased human retinas.

We compare four optical coherence tomography techniques for noninvasive visualization of microcapillary network in the human retina and murine cortex. We perform phantom studies to investigate contrast-to-noise ratio for angiographic images obtained with each of the algorithm. We show that the computationally simplest absolute intensity difference angiographic OCT algorithm that bases only on two cross-sectional intensity images may be successfully used in clinical study of healthy eyes and eyes with diabetic maculopathy and branch retinal vein occlusion.

Current trends in the monitoring and treatment of diabetic retinopathy in young adults.

The diagnosis and treatment of diabetic retinopathy (DR) in young adults have significantly improved in recent years. Research methods have widened significantly, for example, by introducing spectral optical tomography of the eye. Invasive diagnostics, for example, fluorescein angiography, are done less frequently. The early introduction of an insulin pump to improve the administration of insulin is likely to delay the development of diabetic retinopathy, which is particularly important for young patients with type 1 diabetes mellitus (T1DM). The first years of diabetes occurring during childhood and youth are the most appropriate to introduce proper therapeutic intervention before any irreversible changes in the eyes appear. The treatment of DR includes increased metabolic control, laserotherapy, pharmacological treatment (antiangiogenic and anti-inflammatory treatment, enzymatic vitreolysis, and intravitreal injections), and surgery. This paper summarizes the up-to-date developments in the diagnostics and treatment of DR. In the literature search, authors used online databases, PubMed, and clinitrials.gov and browsed through individual ophthalmology journals, books, and leading pharmaceutical company websites.

The diagnostic function of OCT in diabetic maculopathy.

Diabetic maculopathy (DM) is one of the major causes of vision impairment in individuals with diabetes. The traditional approach to diagnosis of DM includes fundus ophthalmoscopy and fluorescein angiography. Although very useful clinically, these methods do not contribute much to the evaluation of retinal morphology and its thickness profile. That is why a new technique called optical coherence tomography (OCT) was utilized to perform cross-sectional imaging of the retina. It facilitates measuring the macular thickening, quantification of diabetic macular oedema, and detecting vitreoretinal traction. Thus, OCT may assist in patient selection with DM who can benefit from treatment, identify what treatment is indicated, guide its implementing, and allow precise monitoring of treatment response. It seems to be the technique of choice for the early detection of macular oedema and for the followup of DM.

Drusen with accompanying fluid underneath the sensory retina.

PURPOSE: To investigate whether confluent drusen may be accompanied by fluid accumulation underneath the sensory retina and to determine if the detection of subretinal fluid on spectral-domain optical coherence tomography (OCT) in patients with coalescent drusen is indicative of choroidal neovascularization (CNV). DESIGN: Prospective, noncomparative case series. PARTICIPANTS: Seventy-four eyes of 57 patients with large, confluent drusen. METHODS: The retinal structure of patients with coalescent drusen was studied by spectral-domain OCT. Optical coherence tomography reflectivity and outer retina topography maps were created and compared with fluorescein angiography (FA) and indocyanine green angiography (ICGA) images as well as with microperimetry. MAIN OUTCOME MEASURES: Optical coherence tomography-derived retinal morphologic features. RESULTS: What appears to be fluid beneath the sensory retina was found on spectral-domain OCT in 8 eyes of 7 patients. The outer retina topography maps demonstrated that fluid accumulates only in the concavity between clustering soft drusen, not on their outward slopes. The maps also revealed a reduced distance between the retinal pigment epithelium (RPE) and the photoreceptor inner/outer segment (IS/OS) junction over large drusen and tiny elevations of the IS/OS junction around drusen of all sizes. Microperimetry showed decreased retinal light sensitivity at the site of diminished distance between the RPE and the IS/OS junction. Seven eyes of 6 patients who were followed up were found to have no retinal changes other than confluent drusen along with subretinal fluid during the entire observational period (12-27 months). There was no evidence of CNV on FA or ICGA in any of the patients. CONCLUSIONS: Large, confluent drusen may be accompanied by subretinal spaces that appear to be filled with fluid. Specific distribution of the fluid limited to the depression between adjacent drusen may indicate that the cluster of coalescent drusen produces mechanical strain to the outer retinal layers that locally pulls the sensory retina away from its normal position. Consequently, the appearance of fluid within subretinal compartment between coalescent drusen in OCT cross-sectional images may not be a reliable marker for the presence of CNV.

A study of macular hole formation by serial spectral optical coherence tomography.

BACKGROUND: The purpose of this paper is to evaluate changes of the vitreoretinal interface in fellow eyes of eyes with a macular hole and to study early stages of macular hole formation by spectral optical coherence tomography (SOCT). METHODS: A prospective study of 131 consecutive patients with history of macular hole. Serial SOCT examinations were performed on the fellow eyes four times during a 6-month observation period. Progression of foveal changes and formation of macular hole in the fellow eyes were studied. RESULTS: Seven distinct abnormalities in the foveal region were noted in 70 of the fellow eyes (53.4%). Additionally in 18 patients (13.6%) other defects typical for the older population were noted. Gradual evolution to full-thickness macular holes during the 6-month observation period was noted in five eyes. One of these eyes had a previously detected cyst, and four eyes had elevation of the photoreceptor layer. CONCLUSIONS: The high prevalence of macular abnormalities in the fellow eyes particularly epiretinal membranes and vitreous traction with schizis as well as the evolution of these abnormalities over time suggest that diseases of the vitreomacular interface may have similar pathogenesis. Macular hole formation often starts as a triangular elevation of the photoreceptor layer. In some cases, a cyst in the inner retinal layers can be an early step in macular hole formation.