Retinal vein occlusion and macular edema – critical evaluation of the clinical value of ranibizumab

Retinal vein occlusions (RVOs) constitute the second most common cause of retinal vascular disease after diabetic retinopathy, with a prevalence of between 1% and 2% in persons older than 40 years of age. Despite the existence of numerous potential therapeutic options, none is entirely satisfactory, and many patients with RVO suffer irreversible visual loss. Fortunately however, the recent introduction of antivascular endothelial growth factor (VEGF) agents, such as ranibizumab (Lucentis®, Genentech, South San Francisco, CA) and bevacizumab (Avastin®, Genentech), offers a potentially new treatment approach for clinicians managing this disorder. The results of the BRAVO and CRUISE trials have provided the first definitive evidence for the efficacy and safety of ranibizumab in the treatment of RVO. As a result, ranibizumab has recently been approved by the US Food and Drug Administration for the treatment of RVO-associated macular edema. In this review, we provide a critical evaluation of clinical trial data for the safety and efficacy of ranibizumab, and address unresolved issues in the management of this disorder

Development of Anti-VEGF Therapies for Intraocular Use: A Guide for Clinicians

Angiogenesis is the process by which new blood vessels form from existing vessel networks. In the past three decades, significant progress has been made in our understanding of angiogenesis; progress driven in large part by the increasing realization that blood vessel growth can promote or facilitate disease. By the early 1990s, it had become clear that the recently discovered “vascular endothelial growth factor” (VEGF) was a powerful mediator of angiogenesis. As a result, several groups targeted this molecule as a potential mediator of retinal ischemia-induced neovascularization in disorders such as diabetic retinopathy and retinal vein occlusion. Around this time, it also became clear that increased intraocular VEGF production was not limited to ischemic retinal diseases but was also a feature of choroidal vascular diseases such as neovascular age-related macular degeneration (AMD). Thus, a new therapeutic era emerged, utilizing VEGF blockade for the management of chorioretinal diseases characterized by vascular hyperpermeability and/or neovascularization. In this review, we provide a guide for clinicians on the development of anti-VEGF therapies for intraocular use

Optical Coherence Tomography Angiography of the Optic Disc; an Overview.

Different diseases of the optic disc may be caused by or lead to abnormal vasculature at the optic nerve head. Optical coherence tomography angiography (OCTA) is a novel technology that provides high resolution mapping of the retinal and optic disc vessels. Recent studies have shown the ability of OCTA to visualize vascular abnormalities in different optic neuropathies. In addition, quantified OCTA measurements were found promising for differentiating optic neuropathies from healthy eyes

Agreement, repeatability, and reproducibility of quantitative retinal layer assessment using swept-source and spectral-domain optical coherence tomography in eyes with retinal diseases

PurposeTo evaluate the agreement and precision of retinal thickness measurements obtained using swept-source optical coherence tomography (SS-OCT) and spectral-domain OCT (SD-OCT) in healthy eyes and eyes with retinopathy.MethodsThis cross-sectional prospective study involved three DRI-OCT Triton (SS-OCT) and three 3D-OCT-1 Maestro (SD-OCT) devices. One of each device (Maestro and Triton) was paired with a single operator. Healthy subjects and patients with retinal diseases were recruited, with study eye and testing order randomized. At least 3 scans per eye were captured for wide scan (12 mm × 9 mm-Triton and Maestro) and macular cube scan (7 mm × 7 mm-Triton, 6 mm × 6 mm-Maestro). Thickness of the full retina, ganglion cell layer + inner plexiform layer (GCL+), and ganglion cell complex (GCL++) were obtained from wide scan and cube scans. Agreement of the measurements between the Triton and Maestro was evaluated by Bland–Altman analysis and Deming regression for each group. Repeatability and reproducibility were assessed using a two-way random effect analysis of variance (ANOVA) model for each parameter by group.ResultsTwenty-five healthy subjects (25 eyes) and 26 patients with retinal diseases (26 eyes), including, but not limited to, age-related macular degeneration, macular hole, and diabetic retinopathy were recruited. Overall, the measurement differences between Triton and Maestro were <6 μm (mean differences of full retina, GCL++, and GCL+ thickness were ≤5.5 μm, 1.3 μm, and 2.8 μm, respectively) and not statistically significant across the parameters. The repeatability and reproducibility estimates indicate high precision in both devices and groups. Across all the parameters, the repeatability limit was ≤7.6 μm for Triton and ≤12.7 μm for Maestro; reproducibility limit was ≤9.2 μm for Triton and ≤14.4 μm for Maestro. In eyes with retinal pathology, the repeatability coefficient of variation (CV)% was ≤2.6% for Triton and ≤3.4% for Maestro; reproducibility CV% was ≤3.3% for Triton and ≤3.5% for Maestro.ConclusionBoth Triton SS-OCT and Maestro SD-OCT provide reliable measurements of retinal thickness in healthy eyes and eyes with retinal diseases. Excellent agreement between the two devices indicates interoperability when testing healthy eyes or eyes with retinal pathology. These findings support the use of thickness measurements from Triton SS-OCT and Maestro SD-OCT in clinical practice

Alterations in the Choriocapillaris in Intermediate Age-Related Macular Degeneration.

Purpose The purpose of this study was to compare the choriocapillaris plexus in eyes with intermediate AMD (iAMD), with or without neovascular AMD in the fellow eye, using optical coherence tomography angiography (OCTA). Methods We collected data from 42 eyes with iAMD from 42 patients who had obtained OCTA. This cohort was divided into two subgroups according to the status of the fellow eye, yielding a group of 20 cases with bilateral intermediate AMD (bilateral iAMD group) and 22 cases with neovascular AMD in the fellow eye (unilateral iAMD group). An additional control group of 20 eyes from 20 healthy subjects was included for comparison. Main outcome measures were: (1) the percent of nondetectable perfused choriocapillaris area and (2) the average choriocapillaris signal void size. Results No differences in the percent of nondetectable perfused choriocapillaris area were found among the three groups (2.3 ± 1.4% in the unilateral iAMD group, 1.5 ± 0.9% in the bilateral iAMD group, and 1.7 ± 1.4% in the control group, respectively). The average choriocapillaris signal void size, however, was significantly increased in unilateral iAMD eyes (293.7 ± 71.2 μm2) compared to both bilateral iAMD (241.5 ± 51.6 μm2, P = 0.031) and control (212.7 ± 48.6 μm2, P = 0.001) eyes. Conclusions Intermediate AMD eyes of patients with neovascular AMD in the fellow eye have an increased average choriocapillaris signal void size compared to eyes without neovascular AMD in the fellow eye. If replicated in future studies, choriocapillaris signal void size may prove to be a useful parameter for evaluating eyes with AMD

Computational aberration compensation by coded-aperture-based correction of aberration obtained from optical Fourier coding and blur estimation

We report a novel generalized optical measurement system and computational approach to determine and correct aberrations in optical systems. The system consists of a computational imaging method capable of reconstructing an optical system’s pupil function by adapting overlapped Fourier coding to an incoherent imaging modality. It recovers the high-resolution image latent in an aberrated image via deconvolution. The deconvolution is made robust to noise by using coded apertures to capture images. We term this method coded-aperture-based correction of aberration obtained from overlapped Fourier coding and blur estimation (CACAO-FB). It is well-suited for various imaging scenarios where aberration is present and where providing a spatially coherent illumination is very challenging or impossible. We report the demonstration of CACAO-FB with a variety of samples including an in vivo imaging experiment on the eye of a rhesus macaque to correct for its inherent aberration in the rendered retinal images. CACAO-FB ultimately allows for an aberrated imaging system to achieve diffraction-limited performance over a wide field of view by casting optical design complexity to computational algorithms in post-processing

EyeArt + EyePACS: Automated Retinal Image Analysis For Diabetic Retinopathy Screening in a Telemedicine System

Telemedicine frameworks are key to screening the large, ever-growing diabetic population for preventable blindness due to diabetic retinopathy (DR). Integrating fully-automated screening systems in telemedicine frameworks will make DR screening more efficient, cost-effective, reproducible, and accessible. In this paper, we present the integration of EyeArt, an automated DR screening system, into EyePACS, a telemedicine system for DR screening used in diverse screening settings. EyeArt in- corporates novel image processing and analysis algorithms for assessing image gradability; enhancing images based on median filtering; detecting interest regions and localizing lesions based on multi-scale morphological analysis; and DR screening and thus achieves robustness to the large image variability seen in a telemedicine system such as EyePACS. EyeArt is implemented as a scalable, high-throughput cloud-based system to enable large-scale DR screening. We evaluate the safety and performance of EyeArt on a dataset with 434,023 images from 54,324 patient cases obtained from EyePACS. On this dataset, EyeArt’s screening sensitivity is 90% at specificity 60.8% and the area under the receiver operating characteristic curve (AUROC) is 0.883. In a setup where trained human graders review patient cases recommended for referral by EyeArt with low confidence, a workload reduction of 62% is possible. Therefore, EyeArt can be safely integrated into large real world telemedicine DR screening programs such as EyePACS helping reduce workload and increase efficiency and thus help in reducing vision loss due to DR through early detection and treatment

Subretinal Fluid in Eyes with Active Ocular Toxoplasmosis Observed Using Spectral Domain Optical Coherence Tomography

Purpose To describe the clinical finding of subretinal fluid (SRF) in the posterior pole by spectral domain optical coherence tomography (SD-OCT) in eyes with active ocular toxoplasmosis (OT). Design Retrospective case series. Participants Thirty-eight eyes from 39 patients with active OT. Methods Eyes with active OT which underwent SD-OCT were reviewed. SRFs in the posterior pole were further analyzed. Main Outcome Measures Presence of SRF; its accompanying features, e.g. retinal necrosis, cystoid macular edema (CME), choroidal neovascularization (CNV); and longitudinal changes of SRF, including maximum height and total volume before and after treatment. Results SRF presented in 45.5% (or 15/33) of eyes with typical active OT and in 51.3% (or 20/39) of eyes with active OT. The mean maximum height and total volume of SRF were 161.0 (range: 23–478) µm and 0.47 (range: 0.005–4.12) mm3, respectively. For 12 eyes with SRF related to active retinal necrosis, SRF was observed with complete absorption after conventional anti-toxoplasmosis treatment. The mean duration for observation of SRF clearance was 33.8 (range: 7–84) days. The mean rate of SRF clearance was 0.0128 (range: 0.0002–0.0665) mm3/day. Conclusions SRF (i.e., serous retinal detachment) is a common feature in patients with active OT when SD-OCT is performed. The majority of SRF was associated with retinal necrosis and reacted well to conventional therapy, regardless of total fluid volume. However, SRF accompanying with CME or CNV responded less favorably or remained refractory to conventional or combined intravitreal treatment, even when the SRF was small in size