Purpose:To develop diffusion-based fundus fluorescein angiography (DiFFA), a noninvasive method for generating high-quality FFA images from color fundus (CF) photographs using diffusion models, addressing the limitations of invasive FFA examinations in detecting diabetic microvascular complications. Methods:DiFFA was trained on paired CF and FFA images from 4032 patients across 3 hospitals, with external validation using 2000 CF images from the UK Biobank. Four systematic evaluations were conducted: (1) objective image quality assessment using the mean absolute error, peak signal-to-noise ratio, structural similarity index measure, and Fréchet inception distance metrics, (2) subjective authenticity evaluation by ophthalmologists, (3) diagnostic efficiency assessment, and (4) automated classification accuracy for diabetic retinopathy and diabetic kidney disease using VGG16 with and without synthetic FFA images. Results:DiFFA achieved strong objective performance (mean absolute error, 109.25,; peak signal-to-noise ratio, 27.677; Fréchet inception distance, 38.466; structural similarity index measure, 0.694). Ophthalmologists showed limited ability to distinguish synthetic from real FFA images (area under the curve, 0.52 ± 0.06 for junior ophthalmologists and 0.57 ± 0.05 for senior ophthalmologists), with no significant quality score differences (P > 0.05). Combining synthetic FFA with CF images improved automated classification, achieving an area under the curve of 0.933 for diabetic retinopathy and 0.849 for diabetic kidney disease internally, compared with 0.891 and 0.792 using CF photographs alone. External validation confirmed improvements (diabetic retinopathy, 0.858 to 0.879; diabetic kidney disease, 0.731 to 0.814). Conclusions:DiFFA successfully generates clinically authentic FFA images from non-invasive CF photographs, enhancing diagnostic accuracy while overcoming the invasiveness limitations of traditional FFA examinations. Translational Relevance:Diffusion-based fundus fluorescein angiography enables noninvasive early detection of diabetic microvascular complications, improving patient compliance and diagnostic accessibility while reducing examination risks in diabetes screening and monitoring.

To assess the association between serum uric acid (SUA) level and the prevalence of diabetic retinopathy (DR) and chronic kidney disease (CKD) in patients with long-term diabetes. A cross-sectional analysis was conducted involving diabetic patients from Shanghai General hospital during October 2018 and October 2021. Participants underwent measurements of SUA, renal function test and DR assessments via fundus photography. Multivariable ordinal logistic regression models assessed odd ratios (ORs) and 95

To explore the associations between renal function and retinal/choroidal microvascular characteristics as well as structure through swept-source optical coherence tomographic angiography (SS-OCTA). This cross-sectional study recruited diabetic patients without diabetic retinopathy (DR) who visited the National Metabolic Management Center (MMC) in Shanghai General Hospital, Shanghai, China. The 6 mm×6 mm fundus images obtained by SS-OCTA were divided into three rings: a central ring (C, 1 mm), an inner ring (I, 3 mm), and an outer ring (O, 6 mm). The perfusion and vessel length density of the superficial and deep capillary plexus (SCP-PD, SCP-VLD, DCP-PD, DCP-VLD), foveal avascular zone (FAZ), macular thickness (MT), choroid thickness (CT), choroid volume (CV) and choroidal vascularity index (CVI) were evaluated. Renal function was reflected by the urinary microalbumin‒creatinine ratio (UACR), estimated glomerular filtration rate (eGFR), blood urea nitrogen (BUN) and the renin‒angiotensin‒aldosterone system (RAAS). Pearson correlation coefficients, multivariate analyses and interaction analyses were used to analyse the correlations between OCTA parameters and renal function. eGFR was positively correlated with the SCP-PD (Average, C, I, O), SCP-VLD (Average, C, I), DCP-PD (C, I), DCP-VLD (C, I), CT (C, I, O, Overall) and CV (C, I, O, Overall). BUN was negatively correlated with the SCP-PD (C), SCP-VLD (C), DCP-PD (C, I), DCP-VLD (C), FAZ circulation. UACR was negatively correlated with the SCP-PD (C) and SCP-VLD (C). Angiotensin was negatively correlated with the SCP-PD (C), MT (C, I). According to the multivariate analysis, as chronic kidney impairment progressed, the SCP-PD (C) and SCP-VLD (C) decreased. There are significant correlations between renal function and retinal/choroidal structural and microvascular characteristics in diabetic patients without DR. These findings suggest that OCTA-derived parameters may serve as potential early biomarkers for diabetic microvascular complications.

PURPOSE:To compare the computation of the choriocapillaris flow deficit obtained from three different optical coherence tomography angiography devices in healthy subjects. METHODS:Twenty-six healthy subjects were included in this post hoc analysis of data from a prospective healthy subject optical coherence tomography angiography study. Fovea-centered 6 × 6 optical coherence tomography angiography volume scans were obtained by all three devices: Heidelberg Spectralis spectral domain optical coherence tomography angiography (Heidelberg, Germany) using a full spectrum probabilistic algorithm (512 × 512 pixels); Zeiss Cirrus 5000 AngioPlex (Zeiss Meditec, Dublin, CA) (spectral domain-optical coherence tomography angiography) using the optical microangiography algorithm (350 × 350 pixels); Zeiss PLEX Elite 9000 swept source optical coherence tomography angiography (Zeiss Meditec, Dublin, CA) using the optical microangiography algorithm (500 × 500 pixels). Choriocapillaris slabs were binarized using Image J (Bethesda, MD) and the choriocapillaris flow deficit % was measured applying a Phansalkar radius of ∼20 µm, adjusted for each device based on the size and resolution of the images. RESULTS:Twenty-six healthy eyes of 26 subjects with no ocular or systemic disease were included in this analysis. The mean age of the subjects was 47.60 ± 13.00 (range, 26-69) years and 46.15% were females. The choriocapillaris flow deficit % measured by the devices varied significantly from each other (p < .01). The mean choriocapillaris flow deficit % measured by the Spectralis (Heidelberg, Germany) was the highest at 57.00% (±13.21%), followed by the Angioplex at 25.70% (±9.00%), and the Plex Elite at 7.62 (±3.06%). There was a significant positive correlation between choriocapillaris flow deficit % measured by swept source-optical coherence tomography angiography and spectral domain-optical coherence tomography angiography devices (Angioplex and PLEX Elite) using the optical microangiography algorithm (r = 0.78, p < .01). Of note, this correlation was better than the correlation between two spectral domain-optical coherence tomography angiography devices using different algorithms (Spectralis, Heidelberg, Germany, full spectrum probabilistic algorithm and Angioplex optical microangiography) (r = 0.389, p = .04). CONCLUSION:The correlation between swept source and spectral domain optical coherence tomography angiography devices using the same optical coherence tomography angiography algorithm is better than between spectral domain-optical coherence tomography angiography devices using different algorithms.

Purpose:To describe and evaluate the multimodal imaging findings in retinal microvascular ischemia associated with COVID-19 infection. Methods:Patients with COVID-19 associated retinal microvascular ischemia and visiting the outpatient Department of Ophthalmology, Shanghai General Hospital from December 2022, to February 2023, were documented and their multimodal images were retrospectively reviewed. Retinal microvascular ischemia was defined as the presence of isolated or multiple focal retinal whitening(s) on color fundus images. Patients with retinal vessel occlusion or retinopathies secondary to systematic disorders diagnosed before infection were excluded. Results:A total of 32 eyes from 21 patients were included, 24 (75.00 %) eyes with multiple retinal whitenings, while 8 (25.00 %) eyes with isolated lesions. When divided by the types of ischemia, 9 (28.13 %) eyes had only inner retinal involvement (known as cotton wool spot, CWS), 4 (12.50 %) eyes had only middle retinal involvement (known as paracentral acute middle maculopathy, PAMM), and 19 (59.38 %) eyes had both. In addition, 4 (12.50 %) eyes had coincident angular sign of Henle fiber layer hyperreflectivity (ASHH). Patients with hypertension tended to have multiple lesions rather than isolated lesion of retinal microvascular ischemia (P = 0.008). Transient uncontrolled high blood pressure or acute kidney injury was simultaneously detected in some cases. Conclusions:Ocular manifestation of COVID-19 associated microvascular ischemia can be variable, including CWS, PAMM and ASHH. Multimodal fundus imaging technologies are useful tools to reveal involved retinal layers, extent, and severity. Moreover, ocular manifestations may serve as a window of COVID-19 related microcirculation in other systems throughout the body.

Objective In diabetes mellitus patients, hyperuricemia may lead to the development of diabetic complications, including macrovascular and microvascular dysfunction. However, the level of blood uric acid in diabetic patients is obtained by sampling peripheral blood from the patient, which is an invasive procedure and not conducive to routine monitoring. Therefore, we developed deep learning algorithm to detect noninvasively hyperuricemia from retina photographs and metadata of patients with diabetes and evaluated performance in multiethnic populations and different subgroups. Materials and methods To achieve the task of non-invasive detection of hyperuricemia in diabetic patients, given that blood uric acid metabolism is directly related to estimated glomerular filtration rate(eGFR), we first performed a regression task for eGFR value before the classification task for hyperuricemia and reintroduced the eGFR regression values into the baseline information. We trained 3 deep learning models: (1) metadata model adjusted for sex, age, body mass index, duration of diabetes, HbA1c, systolic blood pressure, diastolic blood pressure; (2) image model based on fundus photographs; (3)hybrid model combining image and metadata model. Data from the Shanghai General Hospital Diabetes Management Center (ShDMC) were used to develop (6091 participants with diabetes) and internally validated (using 5-fold cross-validation) the models. External testing was performed on an independent dataset (UK Biobank dataset) consisting of 9327 participants with diabetes. Results For the regression task of eGFR, in ShDMC dataset, the coefficient of determination (R2) was 0.684±0.07 (95% CI) for image model, 0.501±0.04 for metadata model, and 0.727±0.002 for hybrid model. In external UK Biobank dataset, a coefficient of determination (R2) was 0.647±0.06 for image model, 0.627±0.03 for metadata model, and 0.697±0.07 for hybrid model. Our method was demonstrably superior to previous methods. For the classification of hyperuricemia, in ShDMC validation, the area, under the curve (AUC) was 0.86±0.013for image model, 0.86±0.013 for metadata model, and 0.92±0.026 for hybrid model. Estimates with UK biobank were 0.82±0.017 for image model, 0.79±0.024 for metadata model, and 0.89±0.032 for hybrid model. Conclusion There is a potential deep learning algorithm using fundus photographs as a noninvasively screening adjunct for hyperuricemia among individuals with diabetes. Meanwhile, combining patient's metadata enables higher screening accuracy. After applying the visualization tool, it found that the deep learning network for the identification of hyperuricemia mainly focuses on the fundus optic disc region.

AIM: To describe the practice patterns of intravitreal injections (IVIs) among ophthalmologists in China. METHODS: This was a cross-sectional online survey. Ophthalmologists who had performed accumulated more than 100 injections were contacted by the Brightness Center, a hospital-based national network, to complete an anonymous, 24-question, internet-based survey. They were surveyed on practices in injection techniques, pre-, and post-injections procedures. RESULTS: A total of 333 ophthalmologists from 28 provinces/municipalities/autonomous regions responded to the survey (50.68% response rate). The 91.29% of the respondents evaluated systemic risk factors by medical history, electrocardiogram (ECG) and blood test. All the respondents used pre-injection prophylactic antibiotics. Most checked intraocular pressure (IOP, 99.1%) and blood pressure (96.1%) before injections. A majority of the respondents performed injections in the operating room (98.8%), wore masks (99.7%), gloves (99.4%) and sterile surgical clothing (96.1%), performed topical anesthetics (97.9%), and applied povidone-iodine (95.8%) pre-injection. The 61.26% of the respondents dilated pupil. About half of the respondents (51.05%) performed bilateral injections in the same setting. Superior temporal quadrant (40.54%) was the most frequent site of injection. Around three quarters used 30-gauge needles. Most respondents (97.9%) measured the site of injection from limbus. More than half (53.45%) performed conjunctiva displacement prior to injection. The 32.43% of the respondents checked IOP post-injection and 87.99% physicians checked hand motion (HM) or counting fingers (CF) after injection, while 36.94% observed optic nerve perfusion. All participants used topical antibiotics post-injections. Most physicians (91.89%) reviewed patients on the following day. CONCLUSION: This study provides a description of the real-world practice patterns in IVIs in China and offers critical information regarding education and training of ophthalmologists and amendment of local society guidelines.

Abstract Background Ciliary body tumor is extremely rare and treatment is challenging. The aim of this study is to present our experience in treating this rare entity, especially large tumors with more than 5 clock hours of involvement, and to evaluate the surgical outcomes and complications of local resection via partial lamellar sclerouvectomy in four cases of ciliary body tumors in China. Methods Four patients with ciliary body tumors underwent partial lamellar sclerouvectomy between October 2019 and April 2023 in Shanghai General Hospital, China. Tumor features, histopathologic findings, complications, visual acuity, and surgical outcomes were reviewed at a mean follow-up of 20.8 months. Results Four patients with a mean age of 31.8 years were included in this study. The histopathological diagnosis was adenoma of non-pigmented ciliary epithelium (ANPCE), schwannoma, and multiple ciliary body pigment epithelial cysts. The mean largest tumor base diameter was 6.00 mm (range: 2.00–10.00) and the mean tumor thickness was 3.50 mm (range: 2.00–5.00). Preoperative complications included cataract in 3 (75%) eyes, lens dislocation in 2 (50%), and secondary glaucoma in 1 (25%). Temporary ocular hypotonia was observed in one case and no other postoperative complications were observed. At a mean follow-up of 20.8 months, the best corrected visual acuity increased in 3 eyes and was stable in 1 eye. Tumor recurrence was absent in all eyes. All patients were alive at the end of follow-up. Conclusions Local tumor resection via PLSU is useful in the treatment of ciliary body tumors, including large tumors occupying more than five clock hours of pars plicata. Surgery-related complications were manageable with adequate preoperative assessment and careful operation during surgery.

Chen, Chong MD; Liu, Kun MD, PhD; Gong, Yuanyuan MD; Yu, Suqin MD; Xu, Xun MD; Su, Li MD, PhDEditor(s): Grewal, Dilraj; Valikodath, Nita; Justin, Grant A. Author Information

Purpose: To correlate baseline spectral-domain optical coherence tomography characteristics with the number of as-needed intravitreal injections of ranibizumab over a 24-month follow-up period in eyes with neovascular age-related macular degeneration. Methods: Two hundred thirty-six eyes of 236 subjects with neovascular age-related macular degeneration treated with ranibizumab 0.5 mg pro re nata in the HARBOR study were enrolled. Baseline spectral-domain optical coherence tomography images were evaluated by certified reading center graders for specific morphologic features of the macular neovascularization lesion and surrounding retina. Baseline optical coherence tomography features and patient demographics correlated with the number of injections over the next 2 years. Results: The mean number of injections in the 0.5 mg pro re nata group was 8.07 (median 8, 3–12) after 12 months and 14.25 (median 14, 3–24) after 24 months of treatment. After multivariate, linear, regression analysis, the only baseline parameter that was independently associated with a higher injection frequency at both 12 and 24 months was a greater baseline subretinal fluid thickness. Conclusion: A greater subretinal fluid thickness at baseline was associated with a higher frequency of pro re nata injections over 12 and 24 months in eyes treated with ranibizumab for neovascular age-related macular degeneration. These findings may be of value in counseling patients who are about to initiate therapy for macular neovascularization.

PURPOSE:To report a case of programmed cell death receptor-1 (PD-1) inhibitor induced panuveitis.METHOD:Observational case report of a 13-year-old Chinese girl presented as panuveitis. The clinical course, imaging performance, laboratory examination, differential diagnosis, treatment and prognosis were described.RESULT:Patient presented with bilateral anterior granulomatous uveitis, vitritis, papillitis, and various creamy yellow nodular lesions in the mid-peripheral fundus. She had a history of biopsy proven alveolar soft tissue sarcoma on the chest wall and pulmonary metastasis, and a PD-1 inhibitor (sintilimab) was intravenously administered. Blood tests, magnetic resonance imaging of the cranium and the orbit, aqueous humor assay of inflammatory cytokines and microbial DNA were performed to distinguish infectious and non-infectious uveitis, choroidal metastases, and intravenous injection-related endophthalmitis. The oncologist evaluated that the sarcoma was stable and terminated sintilimab dosage. After sintilimab withdrawal, the blurred vision improved. Then, the patient received oral corticosteroids, resulted in resolution of the panuveitis. A diagnosis of PD-1 inhibitor induced panuveitis was made.CONCLUSION:For patients taking PD-1 inhibitors, the major diagnostic challenge is to identify whether the cause of the uveitis is due to the antitumor treatment or not. It is suggested to be screened by eye care specialist and timely referral to uveitis specialist with any suspicion of intraocular inflammation for these patients.

BACKGROUND:Diabetic retinopathy (DR) is the most common retinal microvascular disease caused by diabetes. Previous studies indicated that Pentraxin 3 (PTX3), an acute phase reactant, was closely related to the development of DR. But the exact effect of PTX3 in diabetic retinopathy needs more investigations. METHODS:Real-time fluorescence quantitative polymerase chain reaction (qRT-PCR) analysis and western blot (WB) were used to detect the expression of PTX3 in vitro. The Ki67 immunofluorescent staining, scratch-wound migration assay, and tube formation experiments were performed to detect the effect of PTX3 knockdown and overexpression on the fibroblast growth factor (FGF)-induced proliferation, migration and tube-forming ability of human retinal microvascular endothelial cells (HRMECs). The phosphorylation levels of extracellular regulated protein kinases (ERK) and fibroblast growth factor receptor (FGFR) in HRMECs were detected by WB. RESULTS:In vitro, the mRNA and protein expressions of PTX3 in the high-concentration glucose condition group were upregulated compared with the normal group (p < 0.05). The proliferation, migration and tube-forming abilities of HRMECs exposed to high-concentration glucose were enhanced (p < 0.01, p < 0.01, p < 0.05 respectively), and the phosphorylation of FGFR and ERK1/2 were increased (p < 0.01, p < 0.05 respectively) compared with the normal condition group. Compared with the high glucose condition group, the proliferation, migration and tube-forming abilities of HRMECs in the high glucose + PTX3 siRNA condition group were further strengthened (p < 0.001, p < 0.0001, p < 0.05 respectively), and the phosphorylation of FGFR and ERK1/2 were increased (p < 0.001, p < 0.01 respectively). Compared with the high glucose condition group, the proliferation, migration and tube-forming abilities of HRMECs in the high glucose + PTX3 overexpression condition group were compromised (p < 0.001, p < 0.05, p < 0.01 respectively), and the phosphorylation of FGFR and ERK1/2 were inhibited (p < 0.001, p < 0.0001 respectively). Neither the scramble siRNA condition group nor the blank plasmid condition group showed significant difference on the proliferation, migration and tube-forming abilities of HRMECs compared with the high glucose condition group (p > 0.05). CONCLUSIONS:The upregulated expression of PTX3 may play a protective role on pathological angiogenesis in DR. PTX3 may serve as a new target for the treatment of DR.

Purpose To characterize changes in retinal perfusion during pregnancy and the postpartum period using optical coherence tomography angiography (OCTA). Methods A nonmydriatic OCTA camera was used to image healthy women who were pregnant or in the postpartum period along with nonpregnant controls. Perfusion density (PD) and vessel length density (VLD) in the superficial capillary plexus (SCP), intermediate capillary plexus (ICP), and deep capillary plexus (DCP) were evaluated. Results A total of 16, 15, and 13 eyes from nonpregnant, pregnant, and healthy postpartum subjects, respectively, were evaluated. When compared to controls, there were significant increases in ICP PD during the second and third trimester of pregnancy, along with significant decreases in both PD and VLD in SCP, ICP, and DCP up to 14 weeks postpartum. Conclusions During pregnancy, vascular changes consistent with retinal vasodilation were noted in the ICP. During the postpartum period, changes in retinal vasculature suggest relative vasoconstriction involving all three layers when compared to both the pregnant and nonpregnant states. Translational Relevance Detecting postpartum changes in retinal vasculature could offer important insights into postpartum physiology throughout the body.

Objective To investigate the differences in amino acid metabolism in aqueous humor of patients with cataract, according to diabetes status, using a 1 H-nuclear magnetic resonance approach. Methods Aqueous humor samples from patients with age-related cataract, with or without diabetes, were collected during cataract surgery. All samples underwent nuclear magnetic resonance spectra analysis to characterize their metabolic function. Potential metabolic pathways were analyzed via MetaboAnalyst 3.0. Results This study included eight aqueous humor samples from patients with cataract and diabetes and eight aqueous humor samples from age- and sex-matched patients with cataract alone. Four metabolites were found to significantly differ in the aqueous humor of patients with cataract and diabetes, relative to patients with cataract alone; these metabolites were glucose (higher in patients with diabetes), valine, lysine, and tyrosine (all lower in patients with diabetes). Aminoacyl-tRNA biosynthesis was presumed to be involved in the metabolic differences observed in patients with cataract, according to diabetes status. Conclusions The amino acid metabolic profile in the aqueous humor differed among patients with cataract, according to diabetes status. Disturbance of amino acid metabolism in the aqueous humor may be related to cataract formation in patients with diabetes.

Purpose To study the choroid in uncomplicated pregnant women using advanced optical coherence tomography (OCT) imaging and analysis. Methods Women with uncomplicated pregnancy in the third trimester (>28 weeks gestational age) and age-matched nonpregnant women were enrolled in this prospective study. All subjects underwent spectral-domain OCT with enhanced depth imaging mode and spectral-domain optical coherent tomography angiography (OCTA). Main outcomes were subfoveal choroidal thickness (SFCT), choroidal vascularity index (CVI), and choriocapillaris flow deficits (CC FD). Results Twenty-two eyes of 12 uncomplicated pregnant women and 23 eyes of 15 nonpregnant, female controls were included. The mean age was 32.27 ± 6.96 years for the pregnant group and 30.08 ± 5.49 years for control group (P > 0.05). Mean SFCT was 238.70 ± 82.96 µm in the pregnant group, and 277.40 ± 61.79 µm in the control group. CVI was 67.58% ± 2.45% in the pregnant group and 67.31% ± 2.62% in the control group. The CC FD% was 54.06 ± 3.95 in the pregnant group, and 55.02 ± 3.78 in the control group. There was no significant difference between the pregnant and control groups (P > 0.05) in SFCT, CVI or CC FD. Conclusions Although extensive hemodynamic changes occurred with pregnancy, choroidal measurements by OCT and OCTA demonstrated no differences in uncomplicated third-trimester pregnant women compared with nonpregnant controls. Translational Relevance The unaltered choroid in uncomplicated third-trimester pregnancy we described allows clinicians to determine whether abnormal choroidal measurements could be used as a biomarker for complications of pregnancy.

Retinal neovascularization is a hallmark pathological process of numerous ocular diseases which comprise the most common causes of blindness and affect millions of people from infants to the elderly. Compared to large proteins, small peptides have advantages for therapeutic application in ocular diseases, especially for retinal diseases. In this study, we investigated a small peptide derived from human tissue-type plasminogen kringle 2 (t-PA kringle 2), named TKII-12, and investigated the effect of TKII-12 on various aspects of vascular endothelial growth factor (VEGF)-induced angiogenesis in vitro and in vivo. Our results showed that TKII-12 effectively inhibited VEGF-induced human retinal microvascular endothelial cell proliferation, migration and tube formation on Matrigel dose-dependently as well as sequence-dependently. TKII-12 inhibited VEGF-induced formation of actin stress fibers and focal adhesions in vascular endothelial cells. Moreover, TKII-12 effectively inhibited retinal neovascularization in a mouse oxygen-induced retinopathy (OIR) model. Our study demonstrated that TKII-12 could effectively inhibit retinal angiogenesis in vitro and in vivo by eliminating the formation of focal adhesion complexes and the organization of actin stress fibers. TKII-12 can serve as a prototype for retinal angiogenesis inhibitory drug development.

The advent of optical coherence tomography angiography (OCTA) has allowed a qualitative and quantitative analysis of the retinal vasculature and the choriocapillaris. With the use of OCTA, several studies evaluated the changes in the choriocapillaris showing how this vascular structure plays a significant role in the pathogenesis of different conditions. This article reviews the current methods of analysis of the choriocapillaris and the relevant findings in different chorioretinal diseases.

PURPOSE: To evaluate the impact of processing technique and slab selection on the repeatability of choriocapillaris (CC) flow deficit (FD) measurements as assessed using optical coherence tomography angiography (OCTA) DESIGN: Prospective, cross-sectional study. METHODS: Healthy subjects were imaged with 4 consecutive 3 3 3-mm OCTA using a swept-source OCT (PLEX elite 9000; Carl Zeiss Meditec). OCTA images were generated using the Max projection, and three 10-mu m-thick slabs starting 11, 21, and 31 mu m posterior to the automatically segmented retinal pigment epithelial band. The resultant images were binarized using the Phansalkar method with a 43.94-mu m radius and then the CCFD% was computed. The intraclass correlation coefficient (ICC) and coefficient of variation (CV) were computed for the 4 acquisitions to assess the repeatability of the CCFD%. This entire analysis was repeated after separately modulating several parameters: (1) Sum instead of the Max projection, (2) retinal pigment epithelial fit instead of the retinal pigment epithelial band as the offset reference, (3) 14.65 and 87.88 mu m radius values instead of 43.94 mu m. RESULTS: Twenty-four healthy eyes (mean age; 36.4 years) were enrolled. The CCFD% in the 11-21-, 2131-, and 31-41-mu m slabs generated by the Max algorithm and the retinal pigment epithelial band showed high repeatability values (ICCs = 0.963, 0.975, and 911; CVs = 0.05, 0.05, and 0.05, respectively). As most of the cases were confounded with the hypointense region when the 11-21-mu m slab was used, however, this slab could not be included in the subsequent analyses. Those values in the 21-31- and 31-41-mu m slabs were higher than those of the corresponding slabs by the Sum algorithm (ICC = 0.916 and 0.776; CV = 0.15 and 0.19, respectively) or by the retinal pigment epithelial fit (ICC = 0.907 and 0.802; CV = 0.06 and 0.06, respectively). The Phansalkar radius of 43.94 mu m had the highest ICC numerically, but this was not statistically significantly greater than for a radius of 14.65 mu m (ICC = 0.960 and 0.911, respectively) or a radius of 87.88 mu m (ICC = 0.958 and 0.897, respectively). Regardless of which parameter was modulated, the 21-31-mu m slab was the most repeatable. CONCLUSIONS: In normal eyes, en face CC OCTA images generated using the Max projection and a 10-mu m-thick slab offset of 21 mu m below the instrumentgenerated retinal pigment epithelial band yielded the most repeatable CCFD%. These findings have implications for the design of standardized processing algorithms for quantitative CC assessment. (C) 2020 Elsevier Inc. All rights reserved.

To study the retinal capillary microvasculature and the choriocapillaris (CC) in myopic eyes using swept-source optical coherence tomography angiography (SS-OCTA). Patients with high myopia (≥ − 6D; axial length ≥ 26.5 mm), moderate myopia (≥ − 3D, < − 6D), and age-matched healthy subjects presenting to the Shanghai General Hospital and Doheny-UCLA Eye Centers were enrolled in this prospective, multicenter study. Any subjects with evidence of macular abnormalities suggestive of pathologic myopia were excluded. SS-OCTA at both sites was performed using a Zeiss PLEX Elite instrument with a 6 × 6 mm scan pattern centered on the fovea. Two repeated volume scans were acquired for image averaging. The instrument pre-defined en face slab of the superficial and deep retinal capillary microvasculature was used to isolate and display the superficial and deep retinal capillaries. A slab spanning from 21 to 31 μm deep to the RPE fit line was used to isolate and display the CC. The OCTA images were exported for averaging using Image J. Littmann’s method and the Bennett formula were applied to adjust for the impact of magnification in the high and moderate myopia groups. The resultant images were then binarized. Though projection artifact removal software was used, regions below the large superficial retinal vessels were excluded for quantitative analyses of the deep retinal capillary plexus and the CC. Vessel density (VD) and vessel length density (VLD) of the superficial and deep retinal capillary plexus (SCP, DCP) and CC flow deficit (FD) were analyzed, quantified, and compared between different groups. Twenty-five eyes of 25 patients with high myopia, 25 eyes of 25 patients with moderate myopia, and 25 eyes of 25 normal age-matched controls were included in this study. The VD of the SCP was lower in the high myopia group compared with the emmetropic control groups (p < 0.05), but the VD of the DCP demonstrated no significant difference among the three groups (p > 0.05). The VLDs of the SCP were lower in the high and moderate myopia groups compared with the control group (p < 0.05), while the VLD of the DCP was lower in the high myopia group compared with the moderate myopia and emmetropic control group (p < 0.05). The CC FD% in the high myopia group was significantly greater than both the control and moderate myopia subjects (p < 0.05). Of note, the severity of the CC flow deficit was not correlated with choroidal thickness (p > 0.05). The retinal microvasculature may demonstrate alterations in highly myopia eyes. The CC in macular regions shows greater impairment in eyes with high myopia compared with eyes with lesser degrees of myopia, and these deficits are already present in the absence of features of pathologic or degenerative myopia. The threshold of CC FD leading to myopic maculopathy remains to be defined.

Purpose: To study maternal retinal changes in pregnancies that resulted in a small for gestational age (SGA) infant. Methods: Pregnant women with SGA infants at birth and age-matched pregnant women with appropriate for gestational age (AGA) infants at birth (controls) were enrolled. All subjects underwent spectral domain optical coherent tomography angiography (OCTA) imaging using a 10 degrees x 10 degrees scan pattern centered on the fovea. Vessel density (VD) and vessel length density (VLD) of the superficial capillary plexus (SCP), intermediate capillary plexus (ICP), and deep capillary plexus (DCP) were analyzed and compared between the two groups. Results: Twelve eyes of eight subjects with SGA infants and 64 eyes of 44 age-matched subjects with AGA infants were included in this study. There was no significant difference in chronic hypertension (P = 1.0), gestational hypertension (P = 1.0), type 1/2 diabetes (P = 1.0), gestational diabetes (P = 0.97), or preeclampsia (P = 0.50) between the SGA group and AGA group. There were significant increases in both VD and VLD in the SCP and ICP layers when comparing the SGA group with the AGA group (P < 0.05). Conclusions: In this pilot study, subjects with SGA infants had increases in selective retinal vasculature layers that may represent systemic perfusion changes compensating for placental insufficiency. Translational Relevance: Additional assessment of maternal retinal changes in pregnancy using OCTA could prove the technology useful as a biomarker of fetal morbidity.