Macular optical coherence tomography angiography analysis in diabetes mellitus patients with a history of Covid-19.

PURPOSE: There is evidence of decreased vessel density in optical coherence tomography angiography (OCTA) after Covid-19. We aimed to investigate whether the outcome of retinal vasculopathy would be worse if patients with diabetes mellitus (DM) were infected with coronavirus using OCTA to assess retinal vessels. METHODS: One eye of each subject was included in the study. Diabetic patients without retinopathy and non-diabetic controls were divided into four groups according to their Covid-19 history: group 1=DM(-)Covid-19(-); group 2=DM(+)Covid-19(-); group 3=DM(-)Covid-19(+); and group 4=DM(+)Covid-19(+). All Covid-19 patients were not hospitalised. Macular OCTA scans were performed in a 6 × 6 mm area. RESULTS: Diabetes had no effect on the area of the foveal avascular zone (FAZ), but Covid-19 caused an increase in FAZ area. Diabetes and Covid-19 had an effect on both the superficial capillary plexus (SCP) and the deep capillary plexus (DCP) in the fovea. Eta squared (ƞ2) is a measure of effect size. The effect size of Covid-19 (ƞ2=0.180) was found to be greater than that of diabetes (ƞ2=0.158) on the SCP, whereas the effect size of diabetes (ƞ2=0.159) was found to be greater than that of Covid-19 (ƞ2=0.091) on the DCP. CONCLUSIONS: The percentage of vessel density was lower in the fovea and the FAZ area was enlarged in the diabetic patients who recovered from Covid-19. In diabetic patients Covid-19 may lead to deterioration of vascular metrics.

Classification of Diabetic Retinopathy Severity in Fundus Images Using the Vision Transformer and Residual Attention.

Diabetic retinopathy (DR) is a common retinal vascular disease, which can cause severe visual impairment. It is of great clinical significance to use fundus images for intelligent diagnosis of DR. In this paper, an intelligent DR classification model of fundus images is proposed. This method can detect all the five stages of DR, including of no DR, mild, moderate, severe, and proliferative. This model is composed of two key modules. FEB, feature extraction block, is mainly used for feature extraction of fundus images, and GPB, grading prediction block, is used to classify the five stages of DR. The transformer in the FEB has more fine-grained attention that can pay more attention to retinal hemorrhage and exudate areas. The residual attention in the GPB can effectively capture different spatial regions occupied by different classes of objects. Comprehensive experiments on DDR datasets well demonstrate the superiority of our method, and compared with the benchmark method, our method has achieved competitive performance.

How does Covid-19 affect the choroidal structures at the early post-infectious period?

PURPOSE: To evaluate choroidal thickness (CT) and choroidal vascularity index (CVI) in patients recovered from COVID-19 using enhanced depth imaging optical coherence tomography in the early postinfectious period. METHODS: Sixty-five patients recovered from COVID-19 and 72 healthy subjects were included in the study. A full ophthalmic examination including best-corrected visual acuity (BCVA), slit lamp biomicroscopy, and dilated fundus examination was performed. CT was measured at 3 points as follows: subfoveal, 1000µm nasal and temporal to the fovea. The total choroidal area (TCA), luminal area (LA), stromal area (SA), and CVI were measured with Image-J. RESULTS: The mean age was 39.09±11.27 years in the COVID-19 group and 39.61±11.43 years in the control group. The mean time from the first positive RT-PCR was 49.54±26.82 days (range 18-120) in the COVID-19 group. No statistically significant difference was detected between the groups with regard to axial length, spherical equivalent, and BCVA (all P>0.05). CT was found to be lower in the COVID-19 group compared to the control group in all quadrants, but this difference was not significant (all P>0.05). The mean TCA, LA, and CVI were statistically significantly reduced in the COVID-19 group (all P<0.001); however, SA showed no statistically significant difference (P=0.064). CONCLUSIONS: In asymptomatic or mild COVID-19, CVI and LA decrease significantly, while CT thins in the early postinfectious period but not significantly.

POSTERIOR SEGMENT OCULAR FINDINGS IN CRITICALLY ILL PATIENTS WITH COVID-19.

PURPOSE: To describe ophthalmological fundoscopic findings in patients with COVID-19 admitted to the intensive care unit of the largest third-level referral center for COVID-19 in Mexico City. METHODS: In this cross-sectional single-center study, consecutive patients admitted to the intensive care unit with a diagnosis of COVID-19 underwent fundus examination with an indirect ophthalmoscope. Clinical photographs were taken using a posterior-pole camera. We explored the association between ocular manifestations and demographic characteristics, inflammatory markers, hemodynamic factors, and comorbidities. RESULTS: Of 117 patients examined, 74 were men; the median age was 54 years (range: 45-63 years). Forty-two patients had ophthalmological manifestations (unilateral in 23 and bilateral in 19), and 10 of these patients had more than one ophthalmological manifestation. Ocular findings were papillitis (n = 13), cotton wool spots (n = 12), retinal hemorrhages (n = 5), retinal nerve fiber layer edema (n = 8), macular whitening (n = 5), retinal vascular tortuosity (n = 4), papillophlebitis (n = 3), central retinal vein occlusion (n = 1), and branch retinal vein occlusion (n = 1). Ocular fundus manifestations were not associated with demographic characteristics, inflammatory markers, hemodynamic factors, or comorbidities. CONCLUSION: More than one-third of patients with severe COVID-19 had ophthalmological manifestations. The most frequent fundoscopic findings were optic nerve inflammation, microvasculature occlusion, and major vascular occlusions. We recommend long-term follow-up to prevent permanent ocular sequelae.

Unilateral Purtscher-like retinopathy post-COVID-19.

A 32-year-old male with no known systemic illness presented with unilateral Purtscher-like retinopathy in his left eye 2 weeks after recovering from a severe COVID-19 infection. Fundus examination revealed areas of intraretinal whitening and few cotton wool spots. Multimodal imaging findings were consistent with embolic occlusion of capillaries seen in Purtscher-like retinopathy. The case highlights the effect of virus-directed coagulation cascade activation leading to unilateral microvasculopathy in our patient. The case adds to the spectrum of COVID-19 retinopathy and presses that retina screening strategies should be established for patients suffering from or recovering from severe COVID-19 infection.

Retinal microvascular morphology versus COVID-19: What to anticipate?

BACKGROUND: To investigate retinal microvascular morphological changes in previously COVID-19 infected patients using optical coherence tomography angiography (OCTA), and compare the findings to age- and gender-matched healthy subjects. METHODS: In this cross-sectional study, OCTA findings (6.0 × 6.0 mm scan size and scan quality index ≥7/10) from previously COVID-19 infected patients (group 1, 32 patients, 64 eyes) with ≥1 month of complete recovery were compared to healthy subjects (group 2, 33 subjects, 66 eyes) with no history of COVID-19 infection. A positive real-time reverse transcription-polymerase chain reaction test on a naso-pharyngeal swab sample confirmed the diagnosis. The AngioVueAnalytics, RTVue-XR 2017.1.0.155 software measured and recorded OCTA parameters. RESULTS: Group 1 had significantly lower superficial capillary plexus vessel densities in all foveal regions than group 2 (P<0.05). Foveal deep capillary plexus vessel density in group 1 was also significantly lower than in group 2 (P=0.009); however, no significant differences were found in other regions (P>0.05). All foveal avascular zone (FAZ) parameters were higher in group 1 than in group 2, with significant differences in FAZ area (P=0.019) and foveal vessel density 300 µm area around FAZ (P=0.035), but not FAZ perimeter (P=0.054). The outer retina and choriocapillaris flows were significantly lower in group 1 than in group 2 (P<0.05). CONCLUSIONS: Prior COVID-19 infection seems to be associated with significant changes in retinal microvascular density, as well as FAZ and flow parameters, which may be attributed to different pathogenic mechanisms that lead to SARS-CoV-2 infection, such as thrombotic microangiopathy and angiotensin-converting enzyme 2 disruption.

A case of neuro retinitis in association with COVID-19.

A 36-year-old female presented with blurring of vision in one eye for 10 days after 1 month of an episode of COVID-19 infection. Her fundus showed disc edema with blurring of margins along with exudation around the fovea. Her C-reactive protein levels were raised. She responded well to oral steroids. A likely association with COVID-19 infection and its associated immune response was suspected.

Vogt Koyanagi Harada disease following a recent COVID-19 infection.

A 23-year-old female presented with a 3-day history of bilateral (OU) diminution of vision 3 weeks after COVID-19 infection. Best corrected visual acuity (BCVA) was 20/30 in right eye and 20/40 in left eye. Anterior segment showed OU 1+ cells in anterior chamber and anterior vitreous face. Fundus OU showed disc hyperemia and multiple pockets of subretinal fluid (SRF), confirmed on optical coherence tomography. Fundus fluorescein angiography showed multiple pin point leaks suggestive of Vogt Koyanagi Harada disease. Oral corticosteroids 1 mg/kg/day were started. At 2-months' follow-up, her BCVA improved to 20/25 OU with complete resolution of SRF.

Multitarget microangiopathy in a young healthy man with COVID-19 disease: A case report.

A 41-year-old man presented to the emergency department complaining of decrease of vision in his left eye. Initial examination was consistent with retrobulbar optic neuritis, and an intravenous drip of methylprednisolone was started. On the third day, the fundus examination revealed the appearance of multiple Purtscher-like cotton-wool spots in the posterior pole and nasally to the optic disc, slight retinal whitening around the fovea, and cherry-red spot. The patient reported flu-like symptoms, and he tested positive at PCR (polymerase chain reaction) test for 2019-nCoV (2019 novel coronavirus) infection. Assuming possible 2019-nCoV-related vascular damage, we prescribed low-molecular-weight heparin. The lesions were regressing at follow-up, and we registered a complete visual recovery.

Retinal Vessel Extraction via Assisted Multi-Channel Feature Map and U-Net.

Early detection of vessels from fundus images can effectively prevent the permanent retinal damages caused by retinopathies such as glaucoma, hyperextension, and diabetes. Concerning the red color of both retinal vessels and background and the vessel's morphological variations, the current vessel detection methodologies fail to segment thin vessels and discriminate them in the regions where permanent retinopathies mainly occur. This research aims to suggest a novel approach to take the benefit of both traditional template-matching methods with recent deep learning (DL) solutions. These two methods are combined in which the response of a Cauchy matched filter is used to replace the noisy red channel of the fundus images. Consequently, a U-shaped fully connected convolutional neural network (U-net) is employed to train end-to-end segmentation of pixels into vessel and background classes. Each preprocessed image is divided into several patches to provide enough training images and speed up the training per each instance. The DRIVE public database has been analyzed to test the proposed method, and metrics such as Accuracy, Precision, Sensitivity and Specificity have been measured for evaluation. The evaluation indicates that the average extraction accuracy of the proposed model is 0.9640 on the employed dataset.

Nonmydriatic Ultra-Widefield Fundus Photography in a Hematology Clinic Shows Utility for Screening of Sickle Cell Retinopathy.

PURPOSE: To determine the feasibility and accuracy of nonmydriatic ultra-widefield (UWF) fundus photographs taken in a hematology clinic setting for screening of sickle cell retinopathy (SCR) DESIGN: Prospective cohort study. METHODS: This single-site study took place at the Johns Hopkins Sickle Cell Center for Adults and the Wilmer Eye Institute. The study population was 90 eyes of 46 consecutive adults with sickle cell disease (SCD). Bilateral nonmydriatic fundus photos taken by clinic personnel during the participants' routine hematology appointment were graded by 2 masked retina specialists at the Wilmer Eye Institute for the presence of nonproliferative SCR (NPSR) and proliferative sickle retinopathy (PSR). A third retina specialist adjudicated in cases of grader disagreement. All participants underwent the standard dilated fundus examination (DFE) within 2 years of acquisition of UWF photographs. The main outcome measure was the sensitivity and specificity of nonmydriatic UWF images for the detection of NPSR and PSR RESULTS: PSR was noted in 19 of 90 eyes that underwent DFE and in 9 of 67 gradable UWF images. Interrater agreement between the 2 graders was moderate, with κ = 0.65 (range 0.43-0.87) for PSR. For gradable UWF photos, the sensitivity and specificity of detecting SCR using the nonmydriatic photos compared with the DFE were 85.2% and 62.5% for NPSR, respectively, and 69.2% and 100% for detection of PSR, respectively. One participant required ophthalmic therapy in both eyes for active sea-fan neovascularization. CONCLUSIONS: UWF imaging shows utility in screening for SCR and may help identify patients with PSR who require a DFE and who may benefit from treatment.

RF-GANs: A Method to Synthesize Retinal Fundus Images Based on Generative Adversarial Network.

Diabetic retinopathy (DR) is a diabetic complication affecting the eyes, which is the main cause of blindness in young and middle-aged people. In order to speed up the diagnosis of DR, a mass of deep learning methods have been used for the detection of this disease, but they failed to attain excellent results due to unbalanced training data, i.e., the lack of DR fundus images. To address the problem of data imbalance, this paper proposes a method dubbed retinal fundus images generative adversarial networks (RF-GANs), which is based on generative adversarial network, to synthesize retinal fundus images. RF-GANs is composed of two generation models, RF-GAN1 and RF-GAN2. Firstly, RF-GAN1 is employed to translate retinal fundus images from source domain (the domain of semantic segmentation datasets) to target domain (the domain of EyePACS dataset connected to Kaggle (EyePACS)). Then, we train the semantic segmentation models with the translated images, and employ the trained models to extract the structural and lesion masks (hereafter, we refer to it as Masks) of EyePACS. Finally, we employ RF-GAN2 to synthesize retinal fundus images using the Masks and DR grading labels. This paper verifies the effectiveness of the method: RF-GAN1 can narrow down the domain gap between different datasets to improve the performance of the segmentation models. RF-GAN2 can synthesize realistic retinal fundus images. Adopting the synthesized images for data augmentation, the accuracy and quadratic weighted kappa of the state-of-the-art DR grading model on the testing set of EyePACS increase by 1.53% and 1.70%, respectively.

[Bilateral central serous chorioretinopathy post-COVID-19]. / Choriorétinopathie séreuse centrale bilatérale post-COVID-19.

Coronavirus disease (COVID-19) can result in many ocular manifestations. We report a rare case of bilateral central serous chorioretinopathy post-infection with COVID-19 in a 38-year-old woman who presented with bilateral blurred vision 1 month after infection with COVID-19. She reported fever, cough, and shortness of breath and was COVID-PCR positive. During her 10-day hospital stay, she received oxygen, antibiotics, heparin and corticosteroids intravenously and then orally. After her recovery from COVID-19, the patient developed progressive visual loss in both eyes: her corrected visual acuity was 3/10 in both eyes, the anterior segment was normal, and the vitreous was clear. Fundus examination, optical coherence tomography and fluorescein angiography showed bilateral serous retinal detachments. Her course was characterized by improvement in visual acuity and regression of the retinal detachments. Central serous chorioretinopathy can occur after COVID-19 infection due to the administration of corticosteroids; thus, ophthalmologic examination is essential to detect ocular involvement as early as possible.

Optical coherence tomography angiography of retinal vasculature in recovered COVID-19 patients compared to age and ethnic matched controls.

CLINICAL RELEVANCE: Understanding the impact of the COVID-19 virus on the retinochoroidal vasculature can provide valuable information regarding potential multi-organ ischaemic sequelae in COVID-19 patients, and can thus be a useful tool for optometrists, ophthalmologists, pulmonologists, infectious disease specialists and others. BACKGROUND: Assessment of retinochoroidal vasculature alterations in recovered mild COVID-19 patients using optical coherence tomography angiography (OCTA) when compared to age and ethnic matched controls. METHODS: Multimodal imaging was performed using OCTA, spectral domain (SD)-OCT (Optovue RTVue XR Avanti; Optovue, Inc, Fremont, CA), and colour fundus photography (Compass; iCare Inc, Raleigh, NC). Vessel flow density, foveal avascular zone, foveal perimeter circumference and retinal thickness were calculated automatically by the OCTA software on 6 × 6mm angiograms. Morphologic changes in the retinochoroidal vasculature on OCTA were assessed and compared with the findings on fundoscopy, SD-OCT and fundus photography and were evaluated by two trained graders. RESULTS: Mean vessel parafoveal density, superior and inferior hemispheric vessel density and perifoveal temporal vessel density on 6 × 6 angiograms of the superficial capillary plexus were lower among the COVID-19 patients when compared to their age and ethnic matched controls. Vessel flow density of the deep capillary plexus, foveal avascular zone size and circumference and retinal thickness did not illustrate statistical significance between the groups. CONCLUSION: OCTA provides non-invasive high-resolution imaging of the retinochoroidal vascular network. Compared with conventional imaging, OCTA can demonstrate precise microvascular structural alterations in the retinal vessels before visible on SD-OCT or fundus examination. When matched for age and ethnicity, patients with a history of mild COVID illness manifested alterations in vessel density.

Selfie fundus imaging for diabetic retinopathy screening.

BACKGROUND: Regular screening for retinopathy and timely intervention reduces blindness from diabetes by 90%. Screening is currently dependent on the interpretation of images captured by trained technicians. Inherent barriers of accessibility and affordability with this approach impede widespread success of retinopathy screening programs. Herein, we report our observations on the potential of a novel approach, Selfie Fundus Imaging (SFI), to enhance diabetic retinopathy screening. METHODS: The study was undertaken over a two-month period during COVID 19 lockdown. 60 diabetic patients participated in the study. Retinal images were captured using three different approaches, handheld smartphone-based photographs captured by patients themselves after a short video-assisted training session (SFI group), and smartphone-based photographs captured by a trained technician and photographs taken on desktop conventional digital fundus camera (Gold standard). Sensitivity and kappa statistics was determined for retinopathy and macular oedema grading. FINDINGS: Mean age of the study participants was 52.4 years ± 9.8 years and 78% were men. Of 120 images captured using SFI, 90% were centred-gradable, 8% were decentred-gradable and 2% were ungradable. 82% patients captured the image within a minute (majority by 31-45 s). The sensitivity of SFI to detect diabetic retinopathy was 88.39%. Agreement between SFI grading and standard fundus photograph grading was 85.86% with substantial kappa (0.77). For the detection of diabetic macular oedema, the agreement between SFI images and standard images was 93.67, with almost perfect kappa (0.91). CONCLUSION: Fundus images were captured by patients using SFI without major difficulty and were comparable to images taken by trained specialist. With greater penetrance, advances, and availability of mobile photographic technology, we believe that SFI would positively impact the success of diabetic retinopathy screening programs by breaking the barriers of availability, accessibility, and affordability. SFI could ensure continuation of screening schedules for diabetic retinopathy, even in the face a highly contagious pandemic.

Diagnostic accuracy of current machine learning classifiers for age-related macular degeneration: a systematic review and meta-analysis.

BACKGROUND AND OBJECTIVE: The objective of this study was to systematically review and meta-analyze the diagnostic accuracy of current machine learning classifiers for age-related macular degeneration (AMD). Artificial intelligence diagnostic algorithms can automatically detect and diagnose AMD through training data from large sets of fundus or OCT images. The use of AI algorithms is a powerful tool, and it is a method of obtaining a cost-effective, simple, and fast diagnosis of AMD. METHODS: MEDLINE, EMBASE, CINAHL, and ProQuest Dissertations and Theses were searched systematically and thoroughly. Conferences held through Association for Research in Vision and Ophthalmology, American Academy of Ophthalmology, and Canadian Society of Ophthalmology were searched. Studies were screened using Covidence software and data on sensitivity, specificity and area under curve were extracted from the included studies. STATA 15.0 was used to conduct the meta-analysis. RESULTS: Our search strategy identified 307 records from online databases and 174 records from gray literature. Total of 13 records, 64,798 subjects (and 612,429 images), were used for the quantitative analysis. The pooled estimate for sensitivity was 0.918 [95% CI: 0.678, 0.98] and specificity was 0.888 [95% CI: 0.578, 0.98] for AMD screening using machine learning classifiers. The relative odds of a positive screen test in AMD cases were 89.74 [95% CI: 3.05-2641.59] times more likely than a negative screen test in non-AMD cases. The positive likelihood ratio was 8.22 [95% CI: 1.52-44.48] and the negative likelihood ratio was 0.09 [95% CI: 0.02-0.52]. CONCLUSION: The included studies show promising results for the diagnostic accuracy of the machine learning classifiers for AMD and its implementation in clinical settings.

The Impact of Coronavirus Disease 2019 (COVID-19) on Retinal Microcirculation in Human Subjects.

BACKGROUND: The aim of the study was to assess retinal microcirculation in patients with coronavirus disease 2019 (COVID-19) through the use of optical coherence tomography angiography (OCT-A) and compare the results with those obtained in healthy controls. METHODS: The study enrolled 39 patients who had fully recovered from COVID-19 and 40 healthy controls. OCT-A image acquisitions were obtained using AngioVue software (version 2017.1.0.151) and the RTVue XR Avanti imaging system (Optovue Inc., Fremont, CA, USA). Nonflow area in the superficial capillary plexus (SCP), foveal avascular zone (FAZ) area in the whole retinal vasculature, FAZ perimeter, acircularity index of FAZ, and foveal density were automatically obtained with the FAZ assessment tool. Vessel density (VD) at the SCP and deep capillary plexus were also measured. RESULTS: Compared to the control group, the nonflow area and the FAZ area in the whole retina was greater in the COVID-19 group; however no statistically significant difference was observed (p > 0.05 respectively). As for vessel densities, all superficial parafoveal VD parameters were considerably higher in the COVID-19 group compared to the control group (p < 0.05 respectively). Despite the fact that the vessel densities in the remaining zones were lower in the COVID-19 group, those differences were not statistically significant (p > 0.05 respectively). CONCLUSION: VD at the parafoveal area of the SCP was significantly higher among patients in the late post-recovery period of COVID-19 disease compared to healthy controls. These findings show the impact of COVID-19 on the retinal microvasculature and its possible role as a risk factor for the development of ocular diseases.