Fluorescein Angiography Images Research Articles

Multi-label classification of retinal lesions in diabetic retinopathy for automatic analysis of fundus fluorescein angiography based on deep learning.

To automatically detect and classify the lesions of diabetic retinopathy (DR) in fundus fluorescein angiography (FFA) images using deep learning algorithm through comparing 3 convolutional neural networks (CNNs). A total of 4067 FFA images from Eye Center at the Second Affiliated Hospital of Zhejiang University School of Medicine were annotated with 4 kinds of lesions of DR, including non-perfusion regions (NP), microaneurysms, leakages, and laser scars. Three CNNs including DenseNet, ResNet50, and VGG16 were trained to achieve multi-label classification, which means the algorithms could identify 4 retinal lesions above at the same time. The area under the curve (AUC) of DenseNet reached 0.8703, 0.9435, 0.9647, and 0.9653 for detecting NP, microaneurysms, leakages, and laser scars, respectively. For ResNet50, AUC was 0.8140 for NP, 0.9097 for microaneurysms, 0.9585 for leakages, and 0.9115 for laser scars. And for VGG16, AUC was 0.7125 for NP, 0.5569 for microaneurysms, 0.9177 for leakages, and 0.8537 for laser scars. Experimental results demonstrate that DenseNet is a suitable model to automatically detect and distinguish retinal lesions in the FFA images with multi-label classification, which lies the foundation of automatic analysis for FFA images and comprehensive diagnosis and treatment decision-making for DR.

Screening and Follow-Up of Acute ROP: Reproducibility of Fluorescein Angiography

Binocular indirect ophthalmoscopy (BIO) is fundamental for screening of retinopathy of prematurity (ROP). Digital retinal imaging devices with fluorescein angiography (FA) proved to be useful in screening and management of ROP. FA provides valuable additional information that is not detectable through ophthalmoscopy. FA images are relatively easy to interpret even by personnel without specific experience in ROP. The aim of this study is to evaluate reproducibility of FA for the screening and follow-up of ROP. A total of 106 pairs of FA images of 30 eyes of 15 premature infants with stage II ROP were evaluated by 5 ophthalmologists: 2 experts, 2 non-experts, and 1 expert in reading FA in adult patients. Each operator gave a score to each of following parameters: leakage, ischemic areas, peripheral plus disease and vascular anomalies. The images were reviewed twice. Intra- and inter-concordance between the readers of the FA findings was evaluated by the means of Cohen's kappa coefficient (κ). The intra-operator concordance was very good (κ > 0.81) for all FA findings. Inter-operator concordance was good (κ> 0.41) for all operators and all FA findings. Global concordance was: substantial (intra-inter readers: κ > 0.61) for leakage, ischemic areas, and plus disease; almost perfect (κ> 0.81) for vascular anomalies; and moderate (κ = 0.41-0.60) for continuity/discontinuity of the ischemic areas. Total FA score was directly correlated to the percentage of treatment: a score ≥ 7 was correlated with 100% treatment and a score ≤ 3 with no treatment. Treatment timing was inversely correlated to FA score: a score ≥ 8 was correlated with a timely treatment (≤ 6days), and a score ≤ 7 was correlated with a delayed treatment (< 10days). This study showed that FA represents a reproducible imaging technique. It is useful for detecting ROP progression, and to define the treatment timing and type.

RETINAL LEAKAGE INDEX DYNAMICS ON ULTRA-WIDEFIELD FLUORESCEIN ANGIOGRAPHY IN EYES TREATED WITH INTRAVITREAL AFLIBERCEPT FOR PROLIFERATIVE DIABETIC RETINOPATHY IN THE RECOVERY STUDY.

Characterization of leakage indices on ultra-widefield fluorescein angiography in proliferative diabetic retinopathy treated with intravitreal aflibercept. Prospective study enrolling subjects for treatment of proliferative diabetic retinopathy randomized 1:1 to receive 2-mg intravitreal aflibercept every 4 weeks (2q4) or every 12 weeks (2q12). Ultra-widefield fluorescein angiography images obtained at baseline, 24, and 48 weeks were analyzed using a semiautomated leakage segmentation platform. Panretinal and zonal leakage indices were calculated. Forty eyes of 40 subjects were included, and mean age was 48 ± 12.1 years. Mean number of injections was 11 ± 1.7 in the 2q4 arm and 4 ± 0.4 in the 2q12 arm. Median baseline leakage index in the 2q4 and 2q12 groups was 5.1% and 4.3%, respectively (P = 0.28). At 24 and 48 weeks, the 2q4 group significantly improved to 1.1% (-79%, P < 0.0001). At Week 24, the 2q12 group demonstrated nonsignificant improvement (3.4%; -21%, P = 0.47); by Week 48, improvement was significant (1.4%; -68%, P = 0.02). The 2q4 group resulted in lower leakage index compared with the 2q12 group at 24 weeks (1.1% vs. 3.4%, respectively; P = 0.008), but by 48 weeks, leakage index was similar between both groups (1.1% vs. 1.4%, respectively; P = 0.34). Proliferative diabetic retinopathy treated with intravitreal aflibercept demonstrated significant leakage index reductions at 1 year. Monthly dosing provided more rapid reduction in leakage index compared with quarterly dosing. RECOVERY study (NCT02863354); https://clinicaltrials.gov/ct2/show/NCT02863354.

A Novel Deep Learning Pipeline for Retinal Vessel Detection In Fluorescein Angiography.

While recent advances in deep learning have significantly advanced the state of the art for vessel detection in color fundus (CF) images, the success for detecting vessels in fluorescein angiography (FA) has been stymied due to the lack of labeled ground truth datasets. We propose a novel pipeline to detect retinal vessels in FA images using deep neural networks (DNNs) that reduces the effort required for generating labeled ground truth data by combining two key components: cross-modality transfer and human-in-the-loop learning. The cross-modality transfer exploits concurrently captured CF and fundus FA images. Binary vessels maps are first detected from CF images with a pre-trained neural network and then are geometrically registered with and transferred to FA images via robust parametric chamfer alignment to a preliminary FA vessel detection obtained with an unsupervised technique. Using the transferred vessels as initial ground truth labels for deep learning, the human-in-the-loop approach progressively improves the quality of the ground truth labeling by iterating between deep-learning and labeling. The approach significantly reduces manual labeling effort while increasing engagement. We highlight several important considerations for the proposed methodology and validate the performance on three datasets. Experimental results demonstrate that the proposed pipeline significantly reduces the annotation effort and the resulting deep learning methods outperform prior existing FA vessel detection methods by a significant margin. A new public dataset, RECOVERY-FA19, is introduced that includes high-resolution ultra-widefield images and accurately labeled ground truth binary vessel maps.

Multimodal Registration of Fundus Images With Fluorescein Angiography for Fine-Scale Vessel Segmentation

Background and objective: The analysis of retinal vessels in fundus images is vital in the diagnosis of retinal diseases and early diagnosis of chronic vascular diseases and diabetes. Automatic vessel segmentation relies on costly expert annotations that may have limitations in the level of detail. We develop an automatic method to generate highly-accurate vessel segmentation including fine-scale vessels. Methods: We present a new framework for fine-scale vessel segmentation from fundus images through registration and segmentation of corresponding fluorescein angiography (FA) images. We first register and aggregate the extracted vessels highlighted from the fluorescent dye in the FA frames. This FA vessel mask is then registered to the fundus image based on an initial fundus vessel mask. Post-processing is performed to refine the final vessel mask. Registration of the FA frames, and registration of FA vessel mask to the fundus image, are performed by similar coarse-to-fine hierarchical frameworks comprising both projective and deformable registration. Two convolutional neural networks with identical network structures, both trained on public datasets but with different configurations, are used for vessel segmentation of both the FA frames and the fundus images. Results: Qualitative examples support the robustness and accuracy of the proposed method. Quantitative evaluations, including the area-under-curve (AUC) of the receiver operating characteristic (ROC) curve are presented. Although fair comparisons cannot be made due to a lack of similar methods and adequate public datasets, we demonstrate that the proposed method with an AUC ROC of 0.979, outperforms a state-of-the-art automatic vessel segmentation method trained on publicly available datasets at 0.956. Conclusions: The proposed method generates accurate vessel segmentation results containing filamentary vessels that are virtually indiscernible to the naked eye in color retinal fundus images.

Coexistence of retinal angiomatous proliferation and pachychoroid phenotype.

Retinal angiomatous proliferation (RAP) is usually seen in the eye with thin choroid and drusen.[12] Pachychoroid is the morphological description of the thick choroid.[3] We herein report two cases of RAP noted in eyes with pachychoroid. Case 1 Fundus photograph of the right eye of a 48-years-old gentleman with 6/18, N8 vision showed RPE alterations [Fig. 1a and b]. Spectralis SDOCT line scan showed intraretinal edema, hyperreflective spot, subfoveal choroidal thickness (CT) of 436μ and dilated large choroidal vessels. Line scan through the area of thickening showed serous RPE detachment and edema [Fig. 1c and d]. Early phase fluorescein angiogram (FA) showed hyperfluorescence at fovea [Fig. 2a]. Indocyanine angiogram (ICGA) showed hot spot [Fig. 2b]. Late phase FA [Fig. 2c] showed a leak whereas ICGA [Fig. 2d] showed hypercyanescence at fovea amidst diffuse hypercyanescence due to choroidal hyperpermeability. A diagnosis of pachychoroid phenotype with RAP was made.Figure 1: (a) Color fundus photograph of the right eye shows retinal pigment epithelium (RPE) alterations (black arrow). (b) Confocal scanning laser ophthalmoscopy based multicolor image shows greenish hue (yellow arrow) owing to thickening. RPE atrophy is highlighted as reddish hue (black arrow). (c) Spectral domain optical coherence tomography (SDOCT) line scan through the fovea shows intraretinal thickening (yellow arrow) and hyperreflective spot (red arrow). Subfoveal choroidal thickness is 436 μ. Dilated Haller's layer vessels (yellow stars) are seen. (d) SDOCT line scan slightly above fovea shows serous RPE detachment (red arrow) and intraretinal edema (yellow arrow)Figure 2: (a) Early phase fluorescein angiography (FA) image of right eye shows hyperfluorescence at fovea. (b): Early phase indocyanine angiography (ICGA) shows hot spot at fovea. (c): Late phase FA image shows hyperfluorescence increasing in area and intensitiy suggestive of leak from retinal angiomatous proliferation (RAP). (d): Late phase ICGA image shows diffuse hypercyanescence at macula due to choroidal hyperpermeability in pachychoroid eyes. RAP is seen as focal increased hypercyanescence at foveaCase 2 Fundus photography of left eye of a 62 years old gentleman with 6/18, N10 vision revealed RPE alteration at fovea [Fig. 3a and b]. SDOCT scan through fovea showed hyperreflective spots, subretinal fluid, and CT of 336μ. Line scan above fovea showed prominent hyperreflective spot with dilated large choroidal vessel layer [Fig. 3c and d]. Early FA image showed hyperfluorescence corresponding to hyperreflective spot and leak in late phase [Fig. 4a and b] suggestive of RAP in an eye with pachychoroid phenotype.Figure 3: (a) Color fundus photograph of left eye shows RPE alterations (black arrow). (b) Multicolor image shows greenish hue nasal to fovea owing to thickening (yellow arrow). (c): SDOCT line scan through fovea shows hyperreflective spot (yellow arrow) at the level of outer plexiform layer. There is small subretinal fluid (red arrow). Subfoveal choroidal thickness is 336 μ. (d) SDOCT line scan superior to fovea shows well defined hyperreflective spot (yellow arrow) and shallow RPE detachment along with dilated Haller's layer vessels (yellow star)Figure 4: (a) Early FA image of left eye shows hyperfluorescence nasal to fovea. (b) Hyperfluorescence increased in size and intensity and corresponded to the hyperreflective spot seen on SDOCT, suggestive of RAPDiscussion Thickening of RPE and drusen in eyes with RAP hamper the diffusion of VEGF from RPE to choroid, which disturbs choroidal autoregulation leading to attenuation of choriocapillaris.[24] Thin choroid reduces the transport of metabolites back to retina, accentuating the retinal ischemia, and leading to RAP.[2] Attenuation of choriocapillaris is sine qua non of pachychoroid phenotype.[5] The pachychoroid neovasculopathy (PNV) in these eyes is a result of ischemic environment in sub-RPE space owing to attenuation of choriocapillaris.[3] Attenuation of choriocapillaris is common pathology between RAP and pachychoroid. It may be possible for eyes with pachychoroid to develop type 3 neovascularization or RAP in the manner in which they develop PNV. This plausible explanation for RAP in pachychoroid eyes needs to be substantiated in a larger case series. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.

Vascular Changes in the Retina and Choroid of Patients With EPAS1 Gain-of-Function Mutation Syndrome

Patients with the EPAS1 gain-of-function mutation syndrome (or Pacak-Zhuang syndrome) present with multiple paragangliomas or pheochromocytomas, duodenal somatostatinoma, polycythemia, headaches, and sometimes diminished visual acuity at an early age. The characteristic phenotype and known genetic cause of the syndrome provide an opportunity to study the role of hypoxia-inducible factor 2α (HIF-2α) in oxygen sensing, development in regions of physiologic hypoxia, and other pathological processes. To describe the ocular lesions in EPAS1 gain-of-function mutation syndrome and to establish whether early-onset diminished visual acuity is developmental or associated with long-term physiologic sequelae of the syndrome. This clinical case series with a transgenic murine model study was conducted from July 2013 to June 2019. Participants were 3 patients referred by their primary care physicians to the National Institutes of Health for evaluation of recurrent and metastatic paragangliomas or pheochromocytomas accompanied by polycythemia. The syndrome and somatic mosaicism in patients were confirmed by the identification of gain-of-function mutations in the EPAS1 gene in resected tumors and other tissues. Ocular findings in patients with EPAS1 gain-of-function mutation syndrome. A total of 3 patients (mean [SD] age, 29 [6.2] years) with confirmed ocular abnormalities were included in the study. Increased contrast accumulation at the posterior aspect of the globe was seen bilaterally on magnetic resonance imaging scans in all patients. Ophthalmoscopy images demonstrated fibrosis overlying the optic disc, tortuous and dilated retinal vessels, and retinal pigment epithelium changes. Optic disc edema and retinal exudates were also seen. Fluorescein angiography images showed leakage of dye from postcapillary venules surrounding the optic disc and highlighted aberrant retinal vascular patterns. Enhanced-depth imaging optical coherence tomography images showed substantial thickening of the choroid and dilation of choroidal vessels. The ocular features of the syndrome were confirmed with a transgenic model of mice with gain-of-function Epas1A529V mutation. In this case series, HIF-2α and hypoxia signaling was found to have a role in vessel development within the choroid and retina, indicating that the marked permanent choroidal thickening and tortuous and dilated veins seen in the choroid and retina in patients with EPAS1 gain-of-function mutation syndrome were suggestive of the persistence of venous elements within the developing mesenchyme. These findings may explain other eye and vascular abnormalities whose pathogenesis remains unclear.

Structural en face optical coherence tomography imaging for identification of leaky microaneurysms in diabetic macular edema.

To study the correspondence between fluorescein angiography (FA) and structural en face optical coherence tomography (OCT) in the identification of leaky microaneurysms in diabetic macular edema (DME). Fourteen eyes of eight patients with DME (6 males and 2 females, mean age 67.3 ± 8.5) were included. For all eyes, a 6 × 6mm structural en face image of the middle retina was obtained and superimposed on a FA image. The reflectivity, capsulation, and association with intraretinal cystic fluid (IRCF) of microaneurysms on en face were evaluated depending on their leaky status on FA. Out of the 320 leaky microaneurysms evaluated, 280 (89.0 ± 8.2%) coincided with those on en face OCT image. Twenty-nine (10.6 ± 6.9%) and 20 (6.5 ± 7.8%) out of all leaky microaneurysms were hyperreflective and demonstrated capsular appearance, respectively. A majority of leaky microaneurysms (97.9 ± 3.2%) were associated with IRCF. From 146 microaneurysms which were found only on en face images, 130 (88.2% ± 15.7%) were hyperreflective, 33 (23.9% ± 15.6%) demonstrated capsular structure, and 13 (9.2% ± 15.0%) demonstrated no associated IRCF. After exclusion of microaneurysms of the inner retina, 95.4 ± 5.4% of leaky microaneurysms were identified on en face image. En face imaging demonstrated 83.5% sensitivity and 89.4% specificity (the area under the curve 0.87) in the identification of leaky microaneurysms. Structural en face imaging is comparable to FA in identification of leaky microaneurysms in diabetic macular edema. Moderate reflectivity, the absence of capsular structure, and neighboring intraretinal cystic fluid indicate leaky microaneurysms.

Involvement of innate immunity in the course of choroidal neovascularization in mice

AbstractPurposeTo investigate the effect of retinal microglia depletion, and the effect of systemic lipopolysaccharide (LPS) exposure, in the course of laser‐induced choroidal neovascularization (CNV) in mice.MethodsFor microglia depletion, C57BL6/J mice were kept under a diet containing the colony‐stimulating factor 1 receptor (CSF‐1R) inhibitor PLX5622, for 1 week prior to CNV induction and until the end of the experiments. To evaluate the effect of systemic LPS challenge on the CNV course, LPS (1 mg/kg) was given intravenously in control‐fed mice for 1 or 4 consecutive days, immediately after CNV. Mice were imaged with optical coherence tomography (OCT) and fluorescein angiography (FA) at baseline, and at day 3, 7 and 14 after CNV. CNV lesions were measured in the FA images and flow cytometry was used to investigate the effects of PLX5622 on the innate immune cell populations in the retina and the choroid‐RPE of CNV‐subjected mice.ResultsPLX5622 led to microglia depletion in the retina, reduced numbers of dendritic cells, macrophages and leukocytes in the choroid‐RPE and a faster involution of CNV. Retinal swelling, vasodilation and accumulation of microglia/macrophages around retinal vessels were observed at day 4 after the first LPS challenge but not 1 day after a single LPS injection. Moreover, a single LPS injection led to exacerbation of the CNV lesion, while 4 consecutive LPS injections did not affect the CNV size compared to non‐injected mice.ConclusionsThe data suggest that suppression of the ocular innate immune response leads to a faster involution of CNV, while activation of innate immune cells with an acute systemic inflammatory stimulus results in increased CNV areas and slower involution. Moreover, chronic systemic LPS exposure do not affect the course of CNV. These findings highlight the importance of innate immunity in the course of experimental CNV and the different effects of acute and chronic systemic inflammation in the diseased retina.

Comparison of Automated versus Manually Modified OCT Angiography En Face Slabs for Detection of Choroidal Neovascularization

To evaluate the sensitivity and specificity for the detection of choroidal neovascularization (CNV) using automatically generated versus manually modified swept-source OCT angiography (SS-OCTA) en face images. Prospective cohort study. Consecutive patients with various chorioretinal diseases and subretinal hyperreflective material (SHRM) or pigment epithelial detachments (PEDs) on OCT possibly corresponding to CNV in at least 1 eye. A total of 102 eyes of 63 patients were included in this study. Fluorescein angiography (FA) and SS-OCTA imaging (PLEX Elite 9000, Carl Zeiss Meditec, Dublin, CA) were performed at the same day. OCTA en face images were generated using the "retina," "avascular," "choriocapillaris," and "outer retina to choriocapillaris (ORCC)" slabs automatically provided by the software. In addition, a custom slab was created by manual modification of the automatically provided boundary "retinal pigment epithelium fit" positioned at the level of Bruch's membrane and anterior to any SHRM or PED to ensure that a possible CNV was captured in its entirety. Two graders independently evaluated OCTA en face images for the presence of CNV masked to all other images of the patient. Sensitivity and specificity for detection of CNV using FA as the reference. In 40% of cases (41/102), a CNV was detected on FA. Automatically provided OCTA en face slabs revealed the highest sensitivity for the "ORCC" slab (46.3%), followed by the "retina" slab (22.0%), "avascular" slab (17.1%), and "choriocapillaris" slab (14.6%). Specificity ranged between 93.4% for "ORCC" and 100% for the "retina" and "avascular" slabs. Sensitivity could be increased to 78.1% using the custom slab with a specificity of 88.5%. Concordance between FA and OCTA en face slabs was moderate for the "ORCC" slab (κ = 0.43; range, 0.41-0.60) and substantial for the custom slab (κ = 0.67; range, 0.61-0.80). Segmentation artifacts and incomplete coverage of CNV on SS-OCTA en face images may impede identification of CNV. Manual modification of the position of automatically generated segmentation lines anterior and posterior to any suspected CNV (SHRM or PED) increases the sensitivity of CNV detection compared with automatically generated slabs.

Fluorescein Angiography Findings in Children With Congenital Zika Syndrome.

To evaluate the retinal and vasculature changes in infants with congenital Zika syndrome (CZS) using fluorescein angiography (FA). This consecutive case series included six infants with CZS. FA and color fundus imaging were performed under general anesthesia in both eyes of all infants using a contact widefield digital imaging system. All color fundus images were obtained using a 130° field of view lens, and the FA images were captured using either a 130° or 80° field of view lens. The immunoglobulin M antibody capture enzyme-linked immunosorbent assay was positive for Zika virus in the cerebrospinal fluid samples of all infants. Other congenital infections were ruled out. The mean ± standard deviation age of the infants at the time of examination was 1.4 years ± 0.1 years (range: 1.3 years to 1.5 years). Contact fundus photographs showed macular abnormalities in seven eyes (58%) and retinal vasculature changes in two eyes (17%). FA detected macular abnormalities in all 12 eyes (100%) and retinal vasculature changes in five eyes (42%). The main retinal vasculature changes were peripheral avascularity in five eyes (42%) and microvasculature abnormalities in three eyes (25%). FA may be an important tool for detecting subtle macular and retinal vasculature changes in CZS. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:702-708.].

Hypertensive choroidopathy, retinopathy and optic neuropathy in renal transplantation failure

A 32 year-old man who presented with severe elevation of blood pressure after failure of kidney transplant. The patient had multiple serous retinal detachments, venous dilation, arteriolar narrowing, retinal haemorrhages, as well as optic disc oedema. Due to the impossibility of performing a fluorescein angiography, an angiotomography and en-face optical coherence tomography images were used to identify the vascular alterations in the retina, choroid, and choriocapillaris. Angiotomography and en face-optical coherence tomography mode images are very useful in cases where it is not possible to perform fluorescein angiography.

DISTINGUISHING INTRARETINAL MICROVASCULAR ABNORMALITIES FROM RETINAL NEOVASCULARIZATION USING OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

With the increasing prevalence of diabetes, fast, noninvasive identification of proliferative diabetic retinopathy (PDR) becomes essential. This study evaluated the utility of optical coherence tomography angiography (OCTA) to characterize intraretinal microvascular abnormalities (IRMA) and retinal neovascularization (NV). Patients with severe non-PDR or PDR were imaged with fluorescein angiography and widefield swept-source OCTA (Zeiss Plex Elite 9000; Carl Zeiss Meditec, Dublin, CA). Regions suspicious for IRMA or retinal NV were identified and the OCTA, including flow overlay on the co-registered structural optical coherence tomography, and fluorescein angiography images were graded by two masked readers. Ninety-six foci of irregular vasculature were analyzed, comprised of 70 IRMA and 26 retinal NV lesions from 14 eyes. Compared with fluorescein angiography, OCTA with flow overlay demonstrated specificity of 99% and sensitivity of 92% in identifying IRMA and NV. Neovascularization differed from IRMA on OCTA by demonstrating supraretinal flow breaching the internal limiting membrane and posterior hyaloid (P < 0.001). Intraretinal microvascular abnormalities were distinguished from NV by outpouching of the internal limiting membrane (P = 0.035). Vascular flow was reduced in the presence of fibrosis. Optical coherence tomography angiography, through flow overlay, has utility to image and differentiate IRMA and NV, which are key features distinguishing severe non-PDR and PDR, respectively. Noninvasive widefield OCTA may be a useful tool to diagnose high-risk diabetic retinopathy eyes.

Spectral-Domain OCT–Based Prevalence and Progression of Macular Atrophy in the HARBOR Study for Neovascular Age-Related Macular Degeneration

Previous studies of macular atrophy (MA) in HARBOR analyzed color fundus photography and fluorescein angiography image data. This study performed a longitudinal assessment of monthly spectral-domain (SD) OCT scans to determine MA prevalence, incidence, and progression in HARBOR. Post hoc analysis of SD OCT images from HARBOR (ClincalTrials.gov identifier, NCT00891735), a phase 3 multicenter, prospective, randomized, double-blind, active treatment-controlled clinical trial. Patients (n= 1097) with subfoveal choroidal neovascularization secondary to neovascular age-related macular degeneration (nAMD) treated with ranibizumab 0.5 mg monthly (n= 275), 0.5 mg pro re nata (PRN) after 3 loading doses (n= 275), 2.0 mg monthly (n= 274), or 2.0 mg PRN (n= 273). Evaluable SD OCT macular cube scans from patients with 24 months of follow-up (N= 941) were examined by masked reading center-trained graders monthly from baseline to month 24. Atrophy diagnosis criteria were consistent with those proposed by the Classification of Atrophy Meetings (CAM) group: hypertransmission of light into the choroid, retinal pigment epithelium loss, and loss of outer retinal layers. Macular atrophy was considered Definite if all 3 criteria were met and Questionable if 2 were met. Study arms were compared for time to MA detection (log-rank test) and enlargement rates (time× arm interaction test). Prevalence, incidence, and enlargement rates of MA. At baseline, imbalance in MA rates across ranibizumab arms was evident (0.5 mg monthly, 19.1%; 0.5 mg PRN, 16.1%; 2.0 mg monthly, 10.1%; 2.0 mg PRN, 10.5%). At month 24, new MA development rates in eyes without baseline MA were similar between ranibizumab doses (0.5 mg, 25.9%; 2.0 mg, 25.4%) and treatment regimens (monthly, 26.4%; PRN, 25.0%). No significant differences in enlargement rate of new atrophy area (P= 0.479, square-root transformed) or time to detection of new MA (P= 0.997) were evident among study arms. In this analysis of a major nAMD trial using CAM atrophy criteria, no differences wereobserved in incidence or progression rates of new MA among study arms, ranibizumab doses, or treatment regimens. Monthly versus PRN treatment did not influence MA incidence or progression.

Solar maculopathy: prognosis over one year follow up

BackgroundTo document the visual acuity, spectral domain optical coherence tomography (SD-OCT) findings and prognosis in10 eyes of 6 patients with foveal damage from solar retinopathy in 1 year.MethodsThis was a prospective, observational case series of patients presented by solar maculopathy at Ophthalmology department, Sohag University. All patients underwent visual acuity (VA) testing, refraction, dilated fundus examination fluorescein angiography (FA) and SD-OCT (spectral Domain ocular coherence Tomography) imaging and follow up for 1 year.ResultsThe mean age was 16.5 years (range 9–27 years, both eyes are affected in 4 patients. The mean spherical equivalent (SE) was – 0.25 ± 0.50 D.The visual acuity of the affected eyes ranged from 0.4 to 0.9 on presentation. At presentation Significant foveal pathology was identified on SD-OCT in 10 eyes, All eyes showed disruption of the photoreceptor ellipsoid zone and the interdigitation zone on SD-OCT, Follow up of the cases continued for 1 year.100% of cases showed improvement in VA: 20% eyes regained 1, 50% eyes with VA of 0.9; two eyes 20% 0.8 and one eyes (10%) with 0.4. The improvement began after 1 week and reached its maximum and became stationary after the 6th month of follow up, the outer retinal hole persist in OCT in 80% of cases.ConclusionSolar maculopathy has a good prognosis yet shows no improvement after 6 months. Young age might pose as a risk factor.

Relationship Between Retinal Fractal Dimension and Nonperfusion in Diabetic Retinopathy on Ultrawide-Field Fluorescein Angiography

To correlate fractal dimension (FD) of the retinal vasculature with the extent of retinal nonperfusion area in diabetic retinopathy (DR) on ultrawide-field fluorescein angiography (FA). Cross-sectional study. Baseline Optos 200Tx ultrawide-field FA images of 80 eyes with DR from the DAVE (NCT01552408) and RECOVERY (NCT02863354) studies were stereographically projected at the Doheny Image Reading Center. The retinal vasculature was extracted from an early-phase FA frame by exploiting the elongated nature of the vessels and then skeletonized for calculation of FD using a box-counting method. The nonperfusion area was delineated by 2 independent, reading center-certified graders who were masked to the study groups and who were using a standardized protocol and then computed in millimeters squared. While no difference in FD was observed for the entire retina in DR compared with normal control subjects, a significantly smaller FD was found in the far-periphery of the DR eyes (P < .001). FD for the entire retina was negatively associated with global nonperfusion area (R=-0.44; P < .001), and this relationship was also present within the 3 concentric retinal zones (posterior: R=-0.31, P= .016; midperiphery: R=-0.35, P= .007; and far periphery: R=-0.31, P= .015). Peripheral FD on ultrawide-field FA is reduced in DR eyes compared with normal eyes and is correlated with severity of retinal nonperfusion. FD can be calculated automatically without the need for correction of peripheral distortion, and therefore it may prove to be a useful surrogate biomarker when precise quantification of nonperfusion is not feasible.

Coroidopatía, retinopatía y neuropatía óptica hipertensiva en un paciente con fracaso de trasplante renal

A 32 year-old man who presented with severe elevation of blood pressure after failure of kidney transplant. The patient had multiple serous retinal detachments, venous dilation, arteriolar narrowing, retinal haemorrhages, as well as optic disc oedema.Due to the impossibility of performing a fluorescein angiography, an angiotomography and en-face optical coherence tomography images were used to identify the vascular alterations in the retina, choroid, and choriocapillaris.Angiotomography and en face-optical coherence tomography mode images are very useful in cases where it is not possible to perform fluorescein angiography.

Acute Retinopathy in Pseudoxanthoma Elasticum

Acute retinopathy may partly explain variable disease manifestation and vision loss in patients with pseudoxanthoma elasticum (PXE). The diagnosis of this likely autoimmune process may inform patient counseling and treatment approaches. To characterize acute retinopathy in patients with PXE as a disease manifestation that may be associated with profound visual impairment. This single-center case series was conducted from May 2013 to October 2018. It used the patient database of the Department of Ophthalmology at the University of Bonn, a referral center for PXE in Germany. Patients at this center with genetically confirmed PXE and who met the inclusion criteria were included (n = 9). Patients underwent multimodal retinal imaging, including fundus photography, fundus autofluorescence (AF), optical coherence tomography (OCT), fluorescein angiography (FA), and indocyanine green angiography (ICGA); in select cases, electroretinography as well as antiretinal and anti-retinal pigment epithelium (RPE) antibody testing were also used. Clinical presentation and disease course. Nine patients (8 [89%] female; mean [range] age, 43 [19-55] years) with acute retinopathy were identified in a cohort of 167 consecutive patients with PXE (frequency of 5%). Symptoms ranged from light sensations or metamorphopsia to profound vision loss. Visual acuity was reduced in 6 patients (67%), ranging from a best-corrected visual acuity of 20/30 to perception of hand movements at manifestation. All patients revealed characteristic fundus features with temporary appearance of partly confluent outer retinal whitish dots at the posterior pole, which corresponded to areas of hyperautofluorescence on fundus AF, loss of the ellipsoid band on OCT, and associated scotomata. The FA and late-phase ICGA imaging showed associated hyperfluorescence and hypocyanescence. Electroretinography revealed a variable reduction of amplitudes. Changes were fully reversible within 1 month in 3 of 8 patients with available follow-up data. Of the remaining 5 patients, 3 had a prolonged and likely permanent vision loss (observation period, 1-64 months) mainly owing to central subretinal hyperreflective material originating from angioid streaks. In 4 (67%) of 6 tested, antiretinal and/or anti-RPE antibodies were detected. Acute retinopathy in patients with PXE may occur, with symptoms ranging from short-term, reversible alterations to irreversible vision loss; these findings contribute to understanding the variable ocular disease progression in PXE and provide insights into the autoimmune phenomena of the posterior pole.

Simulating vascular leakage on optical coherence tomography angiography using an overlay technique with corresponding thickness maps

BackgroundTo demonstrate a technique for using optical coherence tomography angiography (OCTA) to simulate leakage in eyes with diabetic macular oedema and determine the sensitivity and positive predictive value of detecting...

High-Resolution In Vivo Fundus Angiography using a Nonadaptive Optics Imaging System.

PurposeWe provide a proof of concept for the detailed characterization of retinal capillary features and surrounding photoreceptor mosaic using a customized nonadaptive optics angiography imaging system.MethodsHigh-resolution fluorescein angiography (FFA) and/or indocyanine green angiography (ICGA) images were obtained using a modified Heidelberg retina angiograph (HRA2) device with a reduced scan angle enabling 3° field of view. Colocalized images of the photoreceptor mosaic also were captured in vivo using the same instrument. Visibility of vascular subbranches were compared between high-resolution images and conventional fundus angiography (FA) with a 30° field of view.ResultsHigh-resolution angiographic and infrared images (3° × 3° field of view, a 10-fold magnification) were obtained in 10 participants. These included seven patients with various retinal diseases, including myopic degeneration, diabetic retinopathy, macular telangiectasia, and central serous chorioretinopathy, as well as three healthy controls. Images of the retinal vasculature down to the capillary level were obtained on angiography with the ability to visualize a mean 1.2 levels more subbranches compared to conventional FA. In addition, imaging of the photoreceptor cone mosaic, to a sufficient resolution to calculate cone density, was possible. Movement of blood cells within the vasculature also was discernible on infrared videography.ConclusionsThis exploratory study demonstrates that fast high-resolution angiography and cone visualization is feasible using a commercially available imaging system.Translational RelevanceThis offers potential to better understand the relationship between the retinal neurovascular system in health and disease and the timing of therapeutic interventions in disease states.