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Copyright of Arquivos Brasileiros de Oftalmologia is the property of Arquivos Brasileiros de Oftalmologia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Purpose: To investigate patterns of ancillary imaging testing among vitreoretinal specialists for patients with vitreoretinal disease in the United States (US).Methods: Optical coherence tomography (OCT), color fundus photography (CFP), and fluorescein angiography (FA), ordered by vitreoretinal specialists and documented within the American Academy of Ophthalmology IRIS® Registry (Intelligent Research in Sight) between 01 January 2018 and 31 December 2020, were retrospectively assessed. Trends in imaging modality choice were analyzed by payer type, geographic region, and practice type. Sub-analyses were conducted according to categorization of vitreoretinal specialists into those treating a high versus low volume of patients with neovascular age-related macular degeneration (nAMD).Results: OCT was the most common imaging modality used, followed by CFP and FA. Following normalization, the highest volume of OCT procedures performed were identified among Medicare Advantage and Medicare Fee-for-Service beneficiaries, within the South of the US, and at medium and large practices. Minimal differences were observed for CFP and FA volume across payer types and regions. Across practice types, the largest volume of CFP and FA procedures were identified in small and private equity owned practices, respectively. Vitreoretinal specialists with a high nAMD volume more frequently performed OCT than those with a low nAMD volume.Conclusion: Vitreoretinal specialists demonstrated a strong preference for OCT, with real-world associations according to payer type, geographic location, and practice type. Volume of nAMD patients seen impacted the likelihood of specialists ordering OCTs.Plain Language Summary: Optical coherence tomography (OCT), color fundus photography (CFP), and fluorescein angiography (FA) are key imaging modalities used by vitreoretinal specialists in routine eye care. This study aimed to uncover patterns of OCT, CFP, and FA usage in the United States from 2018 to 2020, and investigated the impact of volume of patients with neovascular age-related macular degeneration on these trends. Higher rates of OCT use, compared with CFP and FA, were identified in the US. [ABSTRACT FROM AUTHOR]

To characterize fluorescein angiography (FA) features in pediatric uveitis. A retrospective cross-sectional study of pediatric uveitis patients in Atlanta, GA, who had FA imaging between May 2009 and August 2020. A total of 137 eyes of 88 patients were evaluated. The mean FA score in anterior uveitis was lower than that in other categories (p =.0093). The mean FA score in the clinically active group was higher than that in the clinically inactive group (p =.0057). The mean FA score in eyes 20/40 or better was lower than that in other categories (p =.0292). Worse visual acuity was associated with retinal vascular staining/leakage, retinal staining/pooling, and neovascularization elsewhere. Non-infectious uveitis more often demonstrated optic disc hyperfluorescence, retinal vascular staining/leakage, capillary leakage, and pinpoint leaks, while infectious uveitis more often demonstrated retinal staining/pooling. A standardized quantitative FA scoring system can be useful in the characterization of uveitis in pediatric patients. [ABSTRACT FROM AUTHOR]

Will optical coherence tomography angiography (OCTA) replace invasive imaging techniques like fundus fluorescein angiography (FFA) and indocyanine green (ICG) angiography entirely? While OCTA is being increasingly applied in the field of medical retina, will we see this change in the subspeciality of uveitis? In this article, five uveitis specialists with renowned imaging expertise answer to 10 specific questions to address this issue. The final verdict based on the comments of the experts suggests that FFA and ICG cannot be replaced by OCTA in uveitis, at least for now. While OCTA can offer new insights into the pathogenesis of certain inflammatory conditions and help in the diagnosis of complications like inflammatory choroidal neovascularisation, multimodal imaging is still the preferred approach in the assessment of patients with uveitis. [ABSTRACT FROM AUTHOR]

Copyright of Die Ophthalmologie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Central retinal artery occlusion (CRAO) can result in devastating permanent vision loss. Presently, there is no evidence-based treatment for CRAO that is widely accepted. In the literature, multiple studies propose intravenous (IV) prostaglandin E1 (IV PGE1) as a potential treatment option for patients with CRAO. We illustrate 2 cases of CRAO successfully treated with IV PGE1. In both cases, our patients with vascular risk factors were diagnosed with CRAO of the left eye. They were started on twice daily IV 40 μg PGE1 in 100 mL normal saline, with each dose administered over 3 h. In the first case, we documented reperfusion of the retina on fluorescein angiography after administration of IV PGE1. In the second case, our patient improved from no light perception visual acuity (VA) to count fingers VA within 48 h of treatment with IV PGE1. Our study highlights the vasodilatory effect of IV PGE1. Due to its mechanism of action and safety profile, it should be considered a potential treatment option for CRAO. Further randomized controlled trials are necessary to determine the overall therapeutic effect of IV PGE1 for CRAO. [ABSTRACT FROM AUTHOR]

Sclerochoroidal calcification (SCC) is a rare disease which is characterized by calcium deposition in the sclera. The choroid is secondarily involved. Typical localization is in the midperipheral region, outside the vascular arcades. SCC is mostly located in the superotemporal quadrant. Often times, the patients are referred with the diagnosis of an amelanotic tumor. SCC may be dystrophic or metastatic. Metastatic SCC lesions are associated with conditions altering calcium and phosphate metabolism including primary and secondary hyperparathyroidism, vitamin D intoxication, renal failure, hyperphosphatemia, and destructive bony lesions. SCC lesions have a characteristic appearance and appear as distinct, ill-defined, yellow-white, elevated scleral/choroidal masses funduscopically. The purpose of this literature review is to review the current knowledge on SCC, highlight the imaging features, and discuss the differential diagnosis as well as management options. [ABSTRACT FROM AUTHOR]

Fluorescein angiography in retinopathy of prematurity is increasingly utilized over the past decade. The development of ultra-wide-field imaging combined with fluorescein angiography has allowed improved visualization of the peripheral retinal vasculature. Patient cooperation in the pediatric population is particularly challenging, but hand-held digital retinal photography has shown promise and can visualize the infant retina without the need for anesthesia and intravenous access. Many features of retinopathy of prematurity and its response to laser and anti-VEGF treatment can be either exclusively or better visualized on fluorescein angiography compared to indirect ophthalmoscopy or color fundus photography. Disease treatment is gradually shifting from laser photocoagulation to intravitreal anti-VEGF agents, the latter being associated with late-onset vision-threatening sequelae. The role of fluorescein angiography in retinopathy of prematurity monitoring will continue to increase with the longer follow-up required and different clinical behavior seen with anti-VEGF treatment. We highlight the utility, safety, and importance of fluorescein angiography in the diagnosis, treatment, and follow-up of retinopathy of prematurity. [ABSTRACT FROM AUTHOR]

Modern advances in diagnostic technologies offer the potential for unprecedented insight into ophthalmic conditions relating to the retina. We discuss the current landscape of artificial intelligence in retina with respect to screening, diagnosis, and monitoring of retinal pathologies such as diabetic retinopathy, diabetic macular edema, central serous chorioretinopathy, and age-related macular degeneration. We review the methods used in these models and evaluate their performance in both research and clinical contexts and discuss potential future directions for investigation, use of multiple imaging modalities in artificial intelligence algorithms, and challenges in the application of artificial intelligence in retinal pathologies. [ABSTRACT FROM AUTHOR]

Purpose: This study is to assess the possible correlation between findings on fundus autofluorescence (FAF) and fluorescein angiography (FA) in patients with chronic central serous chorioretinopathy (cCSC). Methods: This multicentre retrospective cohort study included 71 cCSC patients (92 eyes) with at least 6 months of follow-up, who had a FAF-FA imaging discrepancy larger than 0.5 optic disc diameters in size in the corresponding areas of hyperfluorescent abnormalities. A comparison was performed between progression in size of areas of hyperautofluorescent retinal pigment epithelium (RPE) abnormalities on FAF (HF-FAF) and the hyperfluorescent areas on FA (HF-FA) at first visit and last visit. The possible correlations were estimated between FAF-FA discrepancy and disease characteristics. Results: The median area of HF-FAF at first visit was 7.48 mm2 (1.41–27.9). The median area of HF-FA at first visit and last visit was 2.40 mm2 (0.02–17.27) and 5.22 mm2 (0.53–25.62), respectively. FAF-FA discrepancy was associated with follow-up duration and the area of HF-FAF at first visit. A mathematical algorithm for grading FAF-FA discrepancy in time was suggested, which predicted the enlargement of hyperfluorescent RPE abnormalities on FA in 82.6% of cases. Conclusion: There is a statistically significant relationship between the areas of HF-FAF and HF-FA in cCSC patients with FAF-FA imaging discrepancy at first presentation. Long-term changes in RPE alterations in cCSC on FA can be predicted based on baseline HF-FAF and follow-up duration. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the effect of sodium fluorescein on the choroidal vascularity index (CVI). In this cross-sectional study, a total of 27 eyes of 27 mild nonproliferative diabetic retinopathy patients (without maculopathy and any systemic disease) who performed fluorescein angiography (FA) procedure were included. Choroidal parameters such as choroidal thickness (CT), total choroidal area (TCA), luminal area (LA), stromal area (SA), LA/SA, and CVI were examined with the optical coherence tomography and binarization technique at baseline and 5th, 15th, and 30th minutes after FA. The values of the parameters before and after the procedure were compared. At baseline, the mean values of the TCA, LA, SA, LA/SA, and CVI were 0.44 ± 0.14mm2, 0.29 ± 0.09 mm2, 0.15 ± 0.05 mm2, 1.87 ± 0.19. Five minutes later to FA, the mean values of the TCA, LA, SA, LA/SA, and CVI were 0.43 ± 0.13 mm2, 0.28 ± 0.08 mm2, 0.15 ± 0.05 mm2, 1.82 ± 0.20, and 0.64 ± 0.03, respectively. There was a significant decrease in LA and CVI values 5 minutes after FA (p:0.002 and p:0.021, respectively). On the other hand, the mean, nasal, subfoveal, and temporal CT were 279.22 ± 93.40 μm, 289.78 ± 91.17 μm, 267.44 ± 95.71 μm before FA and 270.33 ± 90.34 μm, 279.67 ± 90.01 μm, 261.82 ± 95.82 μm 5 minutes after FA (p = 0.960, p = 0.952, and p = 0.991, respectively). Although there was a reduction in the value of CT, there was not a statistically significant difference between before and after FA. This study shows that there was a significant decrease in LA and CVI values 5 minutes after FA in patients with mild nonproliferative diabetic retinopathy. [ABSTRACT FROM AUTHOR]

PURPOSE: The purpose of this study was to characterize the phenotypic spectrum of ophthalmic findings in patients with Alagille syndrome. METHODS: We conducted a retrospective, observational, multicenter, study on 46 eyes of 23 subjects with Alagille syndrome. We reviewed systemic and ophthalmologic data extracted from medical records, color fundus photography, fundus autofluorescence, optical coherence tomography, visual fields, electrophysiological assessments, and molecular genetic findings. RESULTS: Cardiovascular abnormalities were found in 83% of all cases (of those, 74% had cardiac murmur), whereas 61% had a positive history of hepatobiliary issues, and musculoskeletal anomalies were present in 61% of all patients. Dysmorphic facies were present in 16 patients, with a broad forehead being the most frequent feature. Ocular symptoms were found in 91%, with peripheral vision loss being the most frequent complaint. Median (range) Snellen visual acuity of all eyes was 20/25 (20/20 to hand motion [HM]). Anterior segment abnormalities were present in 74% of the patients; of those, posterior embryotoxon was the most frequent finding. Abnormalities of the optic disc were found in 52%, and peripheral retinal abnormalities were the most frequent ocular finding in this series, found in 96% of all patients. Fifteen JAG1 mutations were identified in 16 individuals; of those, 6 were novel. CONCLUSIONS: This study reports a cohort of patients with Alagille syndrome in which peripheral chorioretinal changes were more frequent than posterior embryotoxon, the most frequent ocular finding according to a number of previous studies. We propose that these peripheral chorioretinal changes are a new hallmark to help diagnose this syndrome.

PrecisMacular superficial capillary plexus (SCP) vessel density is more informative than deep capillary plexus (DCP) vessel density for the detection of glaucoma.PurposeThe purpose of this study was to characterize optical coherence tomography angiography macular SCP and projection-resolved DCP vessel densities and compare their diagnostic accuracies with ganglion cell complex (GCC) thickness in healthy, glaucoma suspect, and glaucoma eyes.Materials and methodsSixty-eight eyes of 44 healthy subjects, 26 eyes of 16 preperimetric glaucoma suspects, and 161 eyes of 124 glaucoma patients from the Diagnostics Innovations in Glaucoma Study with good quality high-density 6×6 mm2 macula optical coherence tomography angiography images were included. The diagnostic accuracy of SCP vessel density, projection-resolved DCP vessel density and GCC thickness were compared among groups.ResultsMean whole image vessel density (wiVD; % of area occupied by vessels containing flowing blood) in the SCP layer was highest in healthy eyes (49.7%), followed by glaucoma suspect eyes (46.0%), and glaucoma eyes (40.9%) (P

Background/objectivesWe aim to describe the clinical and imaging characteristics of young children with dark without pressure- a well-defined area of dark retina in the mid periphery associated with attenuated hyperreflective outer segment bands on spectral domain OCT.Subjects/methodsRetrospective medical chart review. We reviewed the charts and retinal images of children with dark without pressure (DWP) seen in the paediatric eye clinic that had undergone retinal imaging.ResultsWe identified 6 children (3 males, 3 females) ranging in age from 3 to 13 years with DWP lesions. These were an incidental finding in children referred for other disorders. The lesions spared the macula and were typically in the mid-peripheral retina. In those children who could cooperate with detailed imaging, the DWP lesions were hypoautofluorecent on fundus autofluorescence imaging and OCT imaging showed reduced reflectance of the outer segments and EZ line as has been described in older children and adults. In two of the six subjects a DWP lesion appeared in an area of previously normal fundus; in no subjects did the lesion resolve over the period of follow up.ConclusionsThe clinical and imaging characteristics of DWP lesions are similar in young children to those described in adults. The site of dysfunction appears to be at the level of the outer retina, but the precise cause is unknown. Recognition of this benign disorder will prevent patient anxiety and unnecessary further investigation.

Abstract Purpose: To evaluate the effect of fluorescein dye usage on renal function in patients with diabetic retinopathy (DR) and chronic kidney disease (CKD). Methods: Diabetic patients with retinopathy who were candidate for fundus fluorescein angiography (FA) were evaluated for serum creatinine and urea levels within five days prior to performing the FA. Serum creatinine levels of 1.5 mg/dl or more in males and 1.4 mg/dl or more in females were both identified as CKD and were included in the study. An increase of 0.5 mg/dl or 25% in creatinine after FA was considered as contrast-induced acute kidney injury (AKI). Estimated glomerular filtration rate (eGFR) was also calculated for all patients using a CKD-Epi formula. CKD grading was determined based on eGFR values. Results: Forty-two patients agreed to participate, of which 23 (54.8%) were male. Seventeen patients were identified with grade 3a or lower CKD, 12 with grade 3b, 11 with grade 4, and two with grade 5 CKD. Considering all grades of CKD, the mean blood urea before and after angiography was 58.48 ± 26.7 and 57 ± 27.81 mg/dl, respectively (P = 0.475). The mean serum creatinine before and after the test was 1.89 ± 1.04 and 1.87 ± 0.99 mg/dl, respectively (P = 0.993). The mean eGFR before and after the test was 44.024 ± 23.5447 and 43.850 ± 21.8581 mL/min/1.73 m2 (P = 0.875). Conclusion: According to the findings of this study, FA does not seem to further deteriorate kidney function in patients with diabetic associated CKD.

Abstract Background Cerebral malaria (CM) continues to present a major health challenge, particularly in sub-Saharan Africa. CM is associated with a characteristic malarial retinopathy (MR) with diagnostic and prognostic significance. Advances in retinal imaging have allowed researchers to better characterize the changes seen in MR and to make inferences about the pathophysiology of the disease. The study aimed to explore the role of retinal imaging in diagnosis and prognostication in CM; establish insights into pathophysiology of CM from retinal imaging; establish future research directions. Methods The literature was systematically reviewed using the African Index Medicus, MEDLINE, Scopus and Web of Science databases. A total of 35 full texts were included in the final analysis. The descriptive nature of the included studies and heterogeneity precluded meta-analysis. Results Available research clearly shows retinal imaging is useful both as a clinical tool for the assessment of CM and as a scientific instrument to aid the understanding of the condition. Modalities which can be performed at the bedside, such as fundus photography and optical coherence tomography, are best positioned to take advantage of artificial intelligence-assisted image analysis, unlocking the clinical potential of retinal imaging for real-time diagnosis in low-resource environments where extensively trained clinicians may be few in number, and for guiding adjunctive therapies as they develop. Conclusions Further research into retinal imaging technologies in CM is justified. In particular, co-ordinated interdisciplinary work shows promise in unpicking the pathophysiology of a complex disease.

PurposeTo develop geometric perfusion deficits (GPD), an optical coherence tomography angiography (OCTA) biomarker based on oxygen diffusion, and to evaluate its utility in a pilot study of healthy subjects and patients with diabetic retinopathy (DR).DesignRetrospective cross-sectional study.MethodsCommercial spectral-domain optical coherence tomography angiography (OCTA) instruments were used to acquire repeated 3 × 3-mm2 and 6 × 6-mm2 motion-corrected macular OCTA volumes. En face OCTA images corresponding to the superficial capillary plexus (SCP), deep capillary plexus (DCP), and full retinal projections were obtained using automatic segmentation. For each projection, the GPD percentage and the vessel density percentage, the control metric, were computed, and their values were compared between the normal and DR eyes. The repeated OCTA acquisitions were used to assess the test-retest repeatability of the GPD and vessel density percentages.ResultsRepeated OCTA scans of 15 normal eyes and 12 DR eyes were obtained. For all en face projections, GPD percentages were significantly higher in DR eyes than in normal eyes; vessel density percentages were significantly lower in all but 1 projection (DCP). Large GPD areas were used to identify focal perfusion deficits. Test-retest analysis showed that the GPD percentage had superior repeatability than the vessel density percentage in most cases. A strong negative correlation between the GPD percentage and the vessel density percentage was also found.ConclusionsGeometric perfusion deficits, an OCTA biomarker based on oxygen diffusion, provides a quantitative metric of macular microvascular remodeling with a strong physiological underpinning. The GPD percentage may serve as a useful biomarker for detecting and monitoring DR.

PurposeTo study maternal retinal changes in pregnancies that resulted in a small for gestational age (SGA) infant.MethodsPregnant 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° × 10° 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.ResultsTwelve 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).ConclusionsIn 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 relevanceAdditional assessment of maternal retinal changes in pregnancy using OCTA could prove the technology useful as a biomarker of fetal morbidity.

Inflammation plays a key role in the induction of choroidal neovascularization (CNV). Inflammatory choroidal neovascularization (iCNV) is a severe but uncommon complication of both infectious and non-infectious uveitides. It is hypothesized that its pathogenesis is similar to that of wet age-related macular degeneration (AMD), and involves hypoxia as well as the release of vascular endothelial growth factor, stromal cell-derived factor 1-alpha, and other mediators. Inflammatory CNV develops when inflammation or infection directly involves the retinal pigment epithelium (RPE)–Bruch’s membrane complex. Inflammation itself can compromise perfusion, generating a gradient of retinal–choroidal hypoxia that additionally promotes the formation of choroidal neovascularization in the course of uveitis. The development of choroidal neovascularization may be a complication, especially in conditions such as punctate inner choroidopathy, multifocal choroiditis, serpiginous choroiditis, and presumed ocular histoplasmosis syndrome. Although the majority of iCNV cases are well defined and appear as the “classic” type (type 2 lesion) on fluorescein angiography, the diagnosis of iCNV is challenging due to difficulties in differentiating between inflammatory choroiditis lesions and choroidal neovascularization. Modern multimodal imaging, particularly the recently introduced technology of optical coherence tomography (OCT) and OCT angiography (noninvasive and rapid imaging modalities), can reveal additional features that aid the diagnosis of iCNV. However, more studies are needed to establish their role in the diagnosis and evaluation of iCNV activity.

This paper presents an innovative retinal imaging system tailored for in vivo fundus detection in small animals. This system integrates Scanning Laser Ophthalmoscopy (SLO) and optical Coherence Tomography (OCT) techniques, enabling the simultaneous generation of images from various modalities, including SLO reflectance, SLO fluorescein angiogram, OCT, and OCT angiogram. The existing multi-modal retinal imaging systems generally encounter limitations such as the inability to detect peripheral lesion areas attributed to small Field of View (FOV) design and susceptibility to sample motion due to slow data acquisition speed. To address these challenges, it’s essential to underscore that this proposed system offers a range of notable advantages, including its compact design, the capacity for widefield imaging with a FOV of up to 100°, and a rapid OCT A-scan rate of 250 kHz, notably exceeding the capabilities of pre-existing multi-modal retinal imaging systems. Validation of the system involved imaging the eyes of normal wild-type mice and diseased mice afflicted with retinal detachment and choroidal neovascularization (CNV). The favorable imaging results demonstrate the system’s reliability in identifying retinal lesions in small animals.

There are different retinal vascular imaging modalities widely used in clinical practice to diagnose different retinal pathologies. The joint analysis of these multimodal images is of increasing interest since each of them provides common and complementary visual information. However, if we want to facilitate the comparison of two images, obtained with different techniques and containing the same retinal region of interest, it will be necessary to make a previous registration of both images. Here, we present a weakly supervised deep learning methodology for robust deformable registration of multimodal retinal images, which is applied to implement a method for the registration of fluorescein angiography (FA) and optical coherence tomography angiography (OCTA) images. This methodology is strongly inspired by VoxelMorph, a general unsupervised deep learning framework of the state of the art for deformable registration of unimodal medical images. The method was evaluated in a public dataset with 172 pairs of FA and superficial plexus OCTA images. The degree of alignment of the common information (blood vessels) and preservation of the non-common information (image background) in the transformed image were measured using the Dice coefficient (DC) and zero-normalized cross-correlation (ZNCC), respectively. The average values of the mentioned metrics, including the standard deviations, were DC = 0.72 ± 0.10 and ZNCC = 0.82 ± 0.04. The time required to obtain each pair of registered images was 0.12 s. These results outperform rigid and deformable registration methods with which our method was compared. [ABSTRACT FROM AUTHOR]

Purpose: Secondary multiple evanescent white-dot syndrome (MEWDS) is an epiphenomenon that can occur during or following an underlying chorioretinal disease. In a 22-year-old male patient who presented blurred vision in the right eye for 10 days, a granuloma-like lesion located adjacent to inferotemporal optic disc and accompanying multiple, scattered and deep-seated white dots around the posterior pole were detected; thus, the patient underwent multimodal imaging methods. A combination of oral trimethoprim-sulfamethoxazole and azithromycin was administered empirically and systemic evaluation was performed at the same time. The infectious panel was found to be negative and the diagnosis of secondary MEWDS secondary to the unilateral granuloma was established. A month later, the final visual acuity improved to 10/10 from the baseline visual acuity of 4/10 in the patient. The granuloma site was recovered with a choroidal excavation. Secondary MEWDS is a relatively less known entity seen in many chorioretinal diseases in addition to the original lesion. Conclusion: Secondary MEWDS is observed in addition to the lesions associated with a great deal of chorioretinal diseases. It is a new entity with good visual results with targeted therapy with exclusion of infectious pathologies. [ABSTRACT FROM AUTHOR]

A 58-year-old otherwise healthy man received a diagnosis of choroidal malignant melanoma (CMM) in June 2021 and underwent a single session of (21 Gy) CyberKnife stereotactic radiotherapy (SRT). Eleven months later, we noticed 3+ anterior chamber cells with occasional vitreous cells in the left eye. Though the tumor looked regressed, there were mild optic disc leakage, early hypofluorescent and late hyperfluorescent punctate lesions scattered 360 degrees, and late staining of the mass on fluorescein angiogram. The findings were compatible with a unilateral multiple evanescent white dot syndrome (MEWDS)-like reaction that was most likely related to CyberKnife SRT-induced tumor necrosis, and a dexamethasone implant was administered intravitreally into the left eye together with topical steroids. A second intravitreal injection of dexamethasone was given three months later due to remittance of the angiographic features. As there are only a few reports on CyberKnife SRT for the treatment of CMM, we wanted to share our interesting observation of a post-treatment MEWDS-like reaction likely related to tumor necrosis syndrome with the ophthalmic community. [ABSTRACT FROM AUTHOR]

To investigate the features of macrophage-like cell (MLC) characterized by en face optical coherence tomography (OCT) in Behçet's uveitis (BU). The extent of fluorescein vascular leakage (FVL) was graded on a scale of 0-3 (0=none, 1=mild, 2=moderate, 3=severe) for the optic nerve head (ONH), macula and peripheral retina. The 3μm en face OCT slabs on inner limiting membrane of ONH or macular region was used to visualize the MLCs. The MLC densities of BU group in ONH and macular region were significantly higher than the control group (both p<0.001). The ONH and macular MLC density were significantly higher in eyes with higher FVL grade and they were positively correlated with FVL score (all p<0.001). MLC density was elevated in Behçet's uveitis and it may serve as a noninvasive indicator for the severity of fluorescein leakage and retinal inflammation in Behcet's uveitis. [ABSTRACT FROM AUTHOR]

Nonparaneoplastic autoimmune retinopathy is a rare, potentially blinding retinal disease which can present as pericentral retinal degeneration or may be secondary to retinal damage from retinal degeneration. Treatment with IV immunoglobulin can be effective in these patients. Purpose: To report a case of nonparaneoplastic autoimmune retinopathy with phenotypical features of pericentral retinal degeneration (PRD) who responded to IV immunoglobulin therapy. Methods: A case report. A 27-year-old man presented with recent subacute progressive nyctalopia and photopsia. Results: Dilated fundoscopy demonstrated confluent yellow–white patches along the main temporal vascular arcades with sparing of the central island in the posterior pole. Color vision, fundus autofluorescence, fluorescein angiography, static visual field, and electroretinographic studies were inconclusive for retinal degeneration. Subsequent genetic testing for known mutations was negative. Workup for paraneoplastic autoimmune retinopathy was negative. Antiretinal antibodies were positive. The patient was diagnosed with nonparaneoplastic autoimmune retinopathy and was treated with IV immunoglobulin, which resulted in objective and subjective improvement on electroretinography, visual field, and optical coherence tomography of the retina. Conclusion: Nonparaneoplastic autoimmune retinopathy may present in a patient with the clinical phenotype of PRD. It is essential to rule out nonparaneoplastic autoimmune retinopathy in patients with subacute changes in the natural course of pericentral retinal degeneration because treatment with IV immunoglobulin may be helpful. [ABSTRACT FROM AUTHOR]

Serpiginous choroiditis (SC) is a bilateral, asymmetrical choroid inflammation leading to the loss of choriocapillaris, overlying retinal pigment epithelium (RPE), and outer retina causing the severe decrease of vision. This condition was initially diagnosed in patients with tuberculosis and syphilis, while autoimmune disorders are now considered to underlie this entity. Optical coherence tomography angiography (OCTA) is comparable to other invasive methods such as fluorescein angiography (FA) and indocyanine green angiography (ICGA) in diagnosing and monitoring the severity of the pathology mentioned above. [ABSTRACT FROM AUTHOR]

Diabetic macular edema (DME) is a common cause of vision impairment in diabetic retinopathy. The aim of this study was to analyze the relationship between visual outcome and anatomic changes detected by traditional multimodal retinal imaging and optical coherence tomography angiography (OCTA) in DME eyes under treatment with Aflibercept. Methods: Sixty-six DME eyes of 62 patients under treatment with intravitreal Aflibercept and with one-year follow-up were enrolled. All participants underwent a full ophthalmic evaluation, including best correct visual acuity (BCVA) measurement, spectral-domain optical coherence tomography, fluorescein angiography and OCTA, both at baseline and final examination. Fractal OCTA analysis of the superficial and deep capillary plexus (SCP and DCP) was performed to estimate vascular perfusion density and lacunarity (LAC). Results: At the final examination, there was a significant improvement in terms of BCVA and central macular thickness (CMT). Furthermore, eyes with CMT <373 µm at baseline reached the higher BCVA at the last follow-up. Eyes with CMT ≥373 µm and DCP LAC <0.41 reached a higher final BCVA, if compared with eyes showing the same CMT but higher initial LAC. Conclusion: A 12-month treatment with intravitreal Aflibercept for DME resulted in significant visual and anatomic improvement. Multimodal retinal imaging, together with fractal OCTA analysis, may provide useful biomarkers, predictive of visual outcome in DME. [ABSTRACT FROM AUTHOR]

Ocular decompression retinopathy (ODR) is characterized by multiple retinal hemorrhages. It is a rare complication associated with rapid decrease of intraocular pressure (IOP). The course of ODR is usually asymptomatic and self-limiting, which was confirmed by the observation of our patient. In this study, we present a 5-month follow up of a 77-year-old woman with acute right eye (RE) filtration angle closure who developed symptoms of ODR. Clinical examination and multimodal imaging modalities, including color fundus photography, optical coherence tomography (OCT), OCT angiography (OCTA) and fluorescein angiography (FA), were used to confirm the diagnosis and performed regularly in monitoring the course of the disease. Fundus lesions in the RE included diffuse intraretinal hemorrhages in the posterior pole, which gradually resolved during follow-up time. The fundus of the left eye (LE) was normal. The patient underwent conservative therapy, laser therapy and surgery, achieving stabilization of the IOP and improvement of the local condition in the RE. Of the various multimodal imaging techniques, color fundus photography and OCT seemed to be the most specific and helpful in monitoring the patient with ODR. [ABSTRACT FROM AUTHOR]

Background: Retinal arterial macroaneurysm (RAM) is a common clinical disease leading to vision loss in elderly individuals. The appropriate interpretation of swept-source optical coherence tomographic angiography (SS-OCTA), a noninvasive examination, is easy and convenient for detecting the status of RAMs and guiding treatment. Methods: The objectives of this study were to describe the morphologic characteristics of RAMs using SS-OCTA and to observe whether there are differences in the morphologies of RAMs between SS-OCTA and fundus fluorescein angiography (FFA), before and after treatment. We retrospectively evaluated twenty-two eyes of 22 patients who were diagnosed with RAMs. All patients underwent a complete ophthalmologic examination, including a review of medical records, best-corrected visual acuity (BCVA), fundus photography, FFA and SS-OCTA. RAMs were recorded by SS-OCTA before any treatment or observation decisions were made. The morphologic findings of the RAMs on SS-OCTA were investigated. Results: On SS-OCTA, RAMs can show local dilatation or an irregular linear blood flow signal, and the dilated cystic lumen may show thrombosis with a low reflection signal. After treatment, the shape of the RAMs will show reactive changes. The findings on SS-OCTA are not very consistent with those on FFA. Conclusions: The same RAM may have different manifestations on OCTA and FFA, and OCTA can more conveniently reflect the changes in blood flow signals and treatment response of RAMs. [ABSTRACT FROM AUTHOR]

There has been a sharp rise of reported handheld laser-induced maculopathy (HLIM) cases over the past decade, a concerning trend that may continue due to unregulated online access to high power lasers. Though HLIM has distinct clinical features, not uncommonly it may masquerade as other retinal disorders. It is critical therefore to recognise the clinical and multimodal imaging characteristics of this important and potentially devastating condition. As HLIM patients are typically young, unique issues need to be considered, such as delayed presentation, difficult history, poor compliance and behavioural or psychiatric comorbidity. This article will review the clinical and diagnostic features of laser injury, with a special emphasis on the multimodal retinal findings. In addition, we present a unique case of HLIM, resembling the presentation of a placoid disease variant and illustrating choroidal ischaemia using advanced retinal imaging, that offers further insight into the mechanisms of laser injury and its complications. The issues addressed in this review aim to increase recognition of an increasingly important and trending condition with potentially profound visual complications.

PurposeTo analyze the effect of induced astigmatism on en-face spectral-domain optical coherence tomography angiography quantitative metrics.DesignProspective crossover study.MethodsNormal eyes without astigmatism and with 0.75, 1.75, and 2.75 diopters (D) of with-the-rule (WTR) astigmatism were imaged using a 3 × 3-mm scan pattern SD-OCTA CIRRUS 5000 HD-OCT with AngioPlex (Carl Zeiss Meditec, Dublin, CA, USA). Quantitative parameters, including foveal avascular zone metrics, parafoveal vessel length density (VD), and perfusion density (PD) were corrected for magnification secondary to axial length and analyzed. Univariate linear regressions were performed within each eye to correlate quantitative metrics to the level of an induced astigmatic cylinder.ResultsFifteen eyes from 15 patients were imaged. Every 1-D increase in induced WTR astigmatism was associated with a statistically significant decrease in VD and PD within all Early Treatment Diabetic Retinopathy Study inner ring quadrants; however, especially more so nasally (VD: 0.63; P < .001; PD: 0.0089; P = .001). For every 1-D increase in induced astigmatism, the resulting decrease in the inner ring superior quadrant was 12% greater for VD and 16% greater for PD versus that in the inferior quadrant. The resulting decrease in the inner ring nasal quadrant was 40% greater for VD and 48% greater for PD versus that in the temporal quadrant.ConclusionsIncreasing levels of induced WTR astigmatism correlated with globally diminishing VD and PD, was more symmetrical for vertical than horizontal quadrants, and was most pronounced nasally. This may be due to a high prevalence of horizontally oriented vessels nasally and the horizontal optical defocus induced by WTR astigmatism.

PRéCIS:: Small but significant decreases in optical coherence tomography angiography (OCTA)-measured circumpapillary capillary density (cpCD) were observed in healthy eyes dilated with 2.5% phenylephrine/0.5% tropicamide. Although likely clinically insignificant, ophthalmologists should consider these changes when interpreting OCTA results from dilated eyes.PurposeThe purpose of this study was to investigate the effect of pupil dilation using 2.5% phenylephrine and 0.5% tropicamide on quantitative assessment of retinal microvasculature using OCTA.MethodsOptoVue AngioVue high density (HD) and non-HD OCTA macula and optic nerve head (ONH) images were obtained at 15-minute intervals predilation and postdilation in 26 healthy participants (mean age: 40.0; 95% confidence interval=33.9, 46.1 y). Superficial macular vessel density (VD) was measured in the whole image VD and the parafoveal region VD. ONH capillary density was measured in the whole image capillary density and the cpCD region. Differences between predilation and postdilation densities were assessed using linear mixed effects models to account for within-patient correlation.ResultsInstillation of dilating drops resulted in a small but statistically significant reduction in non-HD ONH whole image capillary density of 0.6%, from a mean of 45.2% (95% confidence interval=41.9%, 48.4%) to 44.6% (41.4%, 47.8%) (P=0.046). A similar reduction in non-HD ONH cpCD of 0.8% also was observed, from a mean of 49.3% (45.3%, 53.3%) to 48.5% (44.5%, 52.4%) (P=0.025). No postdilation decreases in macular VD or HD ONH capillary density were observed.ConclusionsPupil dilation using topical 2.5% phenylephrine and 0.5% tropicamide results in a small but statistically significant reduction in non-HD ONH whole image and cpCD in healthy eyes. The observed reduction likely is not clinically significant because the observed reduction was within the previously reported range of measurement variability. Further studies should consider investigating these effects in nonhealthy eyes with glaucoma and media opacities, as well as older individuals.

PurposeTo compare optical coherence tomography angiography (OCTA)-measured capillary density of the optic disc among 4 glaucomatous optic disc phenotypes.DesignCross-sectional study.MethodsCircumpapillary capillary density (cpCD) of 4 glaucomatous optic disc phenotypes in 193 eyes of 141 glaucoma patients and cpCD in 92 eyes of 55 healthy subjects from the Diagnostic Innovations in Glaucoma Study (DIGS) were compared. Areas under the receiver operating characteristic (AUROC) curves were used to evaluate diagnostic accuracy among groups after adjusting for confounders.ResultsFour glaucoma phenotypes were assessed: focal ischemic (n = 45), generalized cup enlargement (n = 60), myopic glaucoma (n = 38), and senile sclerotic (n = 50). Sex, mean ocular perfusion pressure, intraocular pressure, mean deviation, and the quality score did not differ among phenotypes. However, there were differences in age (P = .050), race (P = .039), axial length (P = .033), and retinal nerve fiber layer thickness (P < .001) among the groups. After adjusting for confounders, senile sclerotic discs had the lowest cpCD (37.1% [95% confidence interval, 35.3-38.8]), followed by focal ischemic (41.8% [40.0-43.6]), myopic glaucoma (42.1% [40-44.2]), and generalized cup enlargement (45.5% [44-47]) (P < .001) discs. The adjusted AUROC curves of cpCD for discriminating between healthy and glaucomatous eyes were highest in senile sclerotic eyes (0.928) and lowest in generalized cup enlargement eyes (0.704).ConclusionsOCTA-measured vessel density differs among optic disc phenotypes. Clinicians should be aware that the performance of OCTA for glaucoma diagnosis may be influenced by the optic disc phenotype.

PurposeThe purpose of this study was to evaluate the ability to align two types of retinal images taken on different platforms; color fundus (CF) photographs and infrared scanning laser ophthalmoscope (IR SLO) images using mathematical warping and artificial intelligence (AI).MethodsWe collected 109 matched pairs of CF and IR SLO images. An AI algorithm utilizing two separate networks was developed. A style transfer network (STN) was used to segment vessel structures. A registration network was used to align the segmented images to each. Neither network used a ground truth dataset. A conventional image warping algorithm was used as a control. Software displayed image pairs as a 5 × 5 checkerboard grid composed of alternating subimages. This technique permitted vessel alignment determination by human observers and 5 masked graders evaluated alignment by the AI and conventional warping in 25 fields for each image.ResultsOur new AI method was superior to conventional warping at generating vessel alignment as judged by masked human graders (P < 0.0001). The average number of good/excellent matches increased from 90.5% to 94.4% with AI method.ConclusionsAI permitted a more accurate overlay of CF and IR SLO images than conventional mathematical warping. This is a first step toward developing an AI that could allow overlay of all types of fundus images by utilizing vascular landmarks.Translational relevanceThe ability to align and overlay imaging data from multiple instruments and manufacturers will permit better analysis of this complex data helping understand disease and predict treatment.

PurposeTo compare gradient-boosting classifier (GBC) analysis of optical coherence tomography angiography (OCTA)-measured vessel density (VD) and OCT-measured tissue thickness to standard OCTA VD and OCT thickness parameters for classifying healthy eyes and eyes with early to moderate glaucoma.DesignComparison of diagnostic tools.MethodsA total of 180 healthy eyes and 193 glaucomatous eyes with OCTA and OCT imaging of the macula and optic nerve head (ONH) were studied. Four GBCs were evaluated that combined 1) all macula VD and thickness measurements (Macula GBC), 2) all ONH VD and thickness measurements (ONH GBC), 3) all VD measurements from the macula and ONH (vessel density GBC), and 4) all thickness measurements from the macula and ONH (thickness GBC). ROC curve (AUROC) analyses compared the diagnostic accuracy of GBCs to that of standard instrument-provided parameters. A fifth GBC that combined all parameters (full GBC) also was investigated.ResultsGBCs had better diagnostic accuracy than standard OCTA and OCT parameters with AUROCs ranging from 0.90 to 0.93 and 0.64 to 0.91, respectively. The full GBC (AUROC = 0.93) performed significantly better than the ONH GBC (AUROC = 0.91; P = .036) and the vessel density GBC (AUROC = 0.90; P = .010). All other GBCs performed similarly. The mean relative influence of each parameter included in the full GBC identified a combination of macular thickness and ONH VD measurements as the greatest contributors.ConclusionsGBCs that combine OCTA and OCT macula and ONH measurements can improve diagnostic accuracy for glaucoma detection compared to most but not all instrument provided parameters.

PURPOSE: To characterize the change rate of ganglion cell complex (GCC) thickness and macular vessel density in healthy, preperimetric glaucoma and primary open-angle glaucoma (POAG) eyes. DESIGN: Prospective, longitudinal study. PARTICIPANTS: One hundred thirty-nine eyes (23 healthy eyes, 36 preperimetric glaucoma eyes, and 80 POAG eyes) of 94 patients who had at least 3 visits were included from the Diagnostic Innovations in Glaucoma Study. The mean follow-up was 2.0 years for healthy eyes, 2.6 years for preperimetric glaucoma eyes, and 2.6 years for POAG eyes. METHODS: OCT angiography (OCTA)-based vessel density and OCT-based structural thickness of the same 3×3-mm2 GCC scan slab were evaluated. The dynamic range-based normalized rates of vessel density and thickness change were calculated and compared within each diagnostic group. The association between the rates of thickness and vessel density change and potential factors were evaluated. MAIN OUTCOME MEASURES: The rates of GCC thinning and macular vessel density loss. RESULTS: Significant rates of GCC thinning and macular vessel density decrease were detectable in all diagnostic groups (all P < 0.05). In healthy eyes and preperimetric glaucoma eyes, the normalized rates of GCC thinning and macular vessel density decrease were comparable (all P > 0.1). In contrast, the normalized rate (mean, 95% confidence interval) of macular vessel density decrease in the POAG eyes (-7.12 [-8.36, -5.88]%/year) was significantly faster than GCC thinning (-2.13 [-3.35, -0.90]%/year; P < 0.001). In the POAG group, more than two thirds of the eyes showed faster macular vessel density decrease than GCC thinning; faster macular vessel density decrease rate was associated significantly with worse glaucoma severity (P = 0.037). The association between GCC thinning rate and glaucoma severity was not significant (P = 0.586). Intraocular pressure during follow-up significantly affected the rate of GCC thinning in all groups (all P < 0.05) but showed no association with the rate of macular vessel density decrease. CONCLUSIONS: Both GCC thinning and macular vessel density decrease were detectable over time in all diagnostic groups. In POAG eyes, macular vessel density decrease was faster than GCC thinning and was associated with severity of disease. Macular vessel density is useful for evaluating glaucoma progression, particularly in more advanced disease.

PurposeTo determine the abundance and multimodal visibility of drusen and basal linear deposit (BLinD) in early age-related macular degeneration.MethodsA 69-year-old white man was imaged by color fundus photography and red free photography, fundus autofluorescence, and optical coherence tomography. From en face images, we determined the drusen field, drusen area, and equivalent diameters of individual drusen. From high-resolution light-microscopic histology (6 months after the last clinic visit), we determined the area of drusen, BLinD, and pre-BLinD in a subretinal pigment epithelium-basal lamina lipid field.ResultsIn right and left eyes, respectively, BLinD covered 40% and 46% of the lipid field, versus 21% and 14% covered by drusen. The lipid field was covered 60% to 61% by Drusen + BLinD and 65% to 72% by BLinD + pre-BLinD. In the left eye, the drusen area on color fundus photography (0.18 mm) and red free (0.28 mm) was smaller than the drusen area on histology (1.16 mm). Among drusen confirmed by optical coherence tomography, 55.1% and 56.6% were observed on red free and fundus autofluorescence, respectively.ConclusionBasal linear deposit covered 1.9 and 3.4-fold more fundus area than soft drusen, silently increasing progression risk. Improved visualization of BLinD and readouts of the retinal pigment epithelium health over lipid will assist population surveillance, early detection, and trial outcome measures.

PurposeTo employ quantitative fundus autofluorescence (qAF) imaging in rhesus macaques to noninvasively assess retinal pigment epithelial (RPE) lipofuscin in nonhuman primates (NHPs) as a model of aging and age-related macular degeneration (AMD).MethodsThe qAF imaging was performed on eyes of 26 rhesus macaques (mean age 18.8 ± 8.2 years, range 4-27 years) with normal-appearing fundus or with age-related soft drusen using a confocal scanning laser ophthalmoscope with 488 nm excitation and an internal fluorescence reference. Eyes with soft drusen also underwent spectral-domain optical coherence tomography imaging to measure drusen volume and height of individual drusen lesions. The qAF levels were measured from the perifoveal annular ring (quantitative autofluorescence 8 [qAF8]) using the Delori grid, as well as focally over individual drusen lesions in this region. The association between qAF levels and age, sex, and drusen presence and volume were determined using multivariable regression analysis.ResultsMean qAF levels increased with age (P < 0.001) and were higher in females (P = 0.047). Eyes with soft drusen exhibited reduced mean qAF compared with age-matched normal eyes (P = 0.003), with greater drusen volume showing a trend toward decreased qAF levels. However, qAF levels are focally increased over most individual drusen (P < 0.001), with larger drusen appearing more hyperautofluorescent (R2 = 0.391, P < 0.001).ConclusionsIn rhesus macaques, qAF levels are increased with age and female sex, but decreased in eyes with soft drusen, similar to human AMD. However, drusen lesions appear hyperautofluorescent unlike those in humans, suggesting similarities and differences in RPE lipofuscin between humans and NHPs that may provide insight into drusen biogenesis and AMD pathogenesis.

PurposeTo describe the pathology of AMD in eyes with geographic atrophy (GA) using confocal scanning laser ophthalmoscopy (SLO) blue light autofluorescence (BAF), and near-infrared (IR) AF and to correlate it with the histology and immunohistochemistry analysis at the margins of the GA lesion.MethodsEnucleated, fixed eyes from seventeen donors with GA were imaged and analyzed by BAF-SLO, IRAF-SLO, and by fundus macroscopy (FM). Tissue from the margins of the GA lesions was cut and processed for resin embedding and histology or cryosectioning and fluorescence in the green and far-red channels, and immunohistochemistry to assess markers of inflammation. Isolated DNA from donors was genotyped for single nucleotide polymorphisms (SNPs) previously shown to be risk factors for the development and progression of AMD.ResultsAround the leading edge of the GA lesions we observed hypertrophic RPE cells with cytoplasm filled with granules fluorescent both in the far-red and green-red channels; abundant microglia and macrophage; deposition of complement factor H (CFH) in Bruch's membrane (BM) and increased membrane attack complex (MAC) on RPE cells.ConclusionsFluorescence imaging of cryosections of RPE cells around the leading edge of the GA lesions suggest that IRAF-SLO visualizes mostly melanin-related compounds. In addition, medium-size GA atrophy displayed the most significant changes in inflammation markers.

PurposeTo investigate the relationship between choriocapillaris (CC) flow void (FV) percentage and geographic atrophy (GA) growth rate, and study how variations in FV percentage surrounding GA predict regional GA growth.MethodsThis prospective, longitudinal study enrolled subjects with GA secondary to nonexudative age-related macular degeneration. Optical coherence tomography angiography imaged the CC and FV percentage was evaluated using a validated algorithm. GA growth rate was measured as the difference in the square root of GA area divided by the months between baseline and follow-up imaging.ResultsTwelve eyes from 7 subjects with a mean age of 80 ± 5 years (range 74-86) were studied once at baseline and 7 to 16 months later. GA expansion rate was positively correlated with increased CC FV percentage (Spearman rank correlation coefficient r = 0.69 [P = 0.038] and 0.76 [P = 0.013]) within the 6 x 6 mm scanned macular region and the 2° margin surrounding each GA lesion, respectively. Regions with CC FV at baseline located within 480 µm from the GA margin showed 33% greater chance of becoming atrophic compared with regions within 480 µm from the GA margin that did not show CC FV at baseline.ConclusionsGA expansion rate and CC FV density throughout the macular region and surrounding the GA margin were significantly correlated. The regional magnitude of FV immediately surrounding GA was associated with GA growth into that region.Translational relevanceCC FV analysis may facilitate prediction of GA growth over time for patients with advanced nonneovascular age-related macular degeneration.

PurposeTo map and measure the depths of corneal neovascularization (NV) using 3-dimensional optical coherence tomography angiography (OCTA) at 2 different wavelengths.MethodsCorneal NV of varying severity, distribution, and underlying etiology was examined. Average NV depth and vessel density were measured using 840-nm spectral-domain OCTA and 1050-nm swept-source OCTA. The OCTA results were compared with clinical slit-lamp estimation of NV depth.ResultsTwelve eyes with corneal NV from 12 patients were imaged with OCTA. Clinically "superficial," "midstromal," and "deep" cases had an average vessel depth of 23%, 39%, and 66% on 1050-nm OCTA, respectively. Average vessel depth on OCTA followed a statistically significant ordinal trend according to the clinical classification of vessel depth (Jonckheere-Terpstra test, P < 0.001). In 8 cases where both 840-nm OCTA and 1050-nm OCTA were acquired, there was excellent agreement in the mean vessel depth between the 2 systems (concordance correlation coefficient = 0.94, P < 0.001). The average vessel density measured by 840-nm OCTA was higher (average 1.6-fold) than that measured by 1050-nm OCTA.ConclusionsCorneal OCTA was able to map corneal NV in 3 dimensions and measure vessel depth and density. The depth of corneal NV varied between different pathologies in a manner consistent with previous pathologic studies. The measured vessel density appeared to be affected by the interscan time, which affects blood flow velocity sensitivity, and the wavelength, which affects the ability to penetrate through opacity. These findings suggest possible clinical applications of OCTA for the diagnosis of corneal pathology and quantitative monitoring of therapeutic response in patients with corneal NV.

PurposeTo determine whether quantitative OCT angiography (OCTA) parameters can be used to distinguish among eyes at various stages of diabetic retinopathy (DR) in an urban safety-net hospital population.DesignProspective cross-sectional study.ParticipantsThree hundred twenty-nine eyes from 329 patients were included in this study: 90 nondiabetic patients, 170 diabetic patients without DR, 57 diabetic patients with mild to moderate nonproliferative DR (NPDR), and 12 diabetic patients with severe NPDR to proliferative DR.MethodsPatients underwent OCTA imaging and ultra-widefield fundus photography at Zuckerberg San Francisco General Hospital and Trauma Center between April and October 2018. For participants with diabetes, imaging was classified according to DR severity by a telemedicine reading center. Eight OCTA parameters were analyzed. Perfusion density and vessel length density (VD) were examined from both the superficial capillary plexus (SCP) and deep capillary plexus. The other 4 parameters were examined only from the SCP. Total extrafoveal avascular area (tEAA) was based on the area of absent capillary vessels. Foveal avascular zone (FAZ)-related metrics consisted of FAZ area, FAZ circularity index, and FAZ acircularity index.Main outcome measuresArea under the receiver operating characteristic curve (AUC) for OCTA parameters to distinguish among groups according to DR severity.ResultsAll OCTA parameters demonstrated a significant relationship with DR severity (P < 0.05). No significant difference was found when comparing nondiabetic participants versus diabetic participants without retinopathy. The FAZ area was the only metric that demonstrated a significant difference between genders: mean of 0.29±0.12 mm2 in men and 0.34±0.13 mm2 in women (P < 0.001). Receiver operating characteristic curve analyses showed that tEAA had the highest AUC when comparing various stages of the disease.ConclusionsIn this urban, public hospital population, quantification of retinal vascular findings with OCTA imaging was a useful means of distinguishing patients according to DR severity. Because these results were similar to those of other tertiary referral centers, it would be reasonable to perform further DR-related OCTA studies in this population and expect generalizable results.

PurposeAlthough the choroid contributes to the pathogenesis of age-related macular degeneration (AMD), the role of retinal perfusion is unclear. We sought to compare retinal vascular measurements between eyes with nonexudative and exudative AMD using optical coherence tomography angiography (OCT-A).DesignRetrospective, cross-sectional study.MethodsOCT-A images were analyzed from 310 eyes of 182 patients (mean age ± standard deviation [SD], 78.8 ± 8.8 years) with nonexudative (54.2%) and exudative (45.8%) AMD to measure retinal vessel density (VD) from the superficial capillary plexus in the foveal, parafoveal, and full macular regions and foveal avascular zone (FAZ) area, perimeter, and circularity. Multivariate regressions were used to compare nonexudative and exudative AMD eyes and the impact of anti-vascular endothelial growth factor (anti-VEGF) treatments or geographic atrophy (GA).ResultsIn eyes with AMD, VD decreases with age in the foveal (β = -0.211, P < .001), parafoveal (β = -0.305, P < .001), and full macular regions (β = -0.295, P < .001). Eyes with exudative AMD demonstrated lower VD, especially in the parafoveal (29.8% ± 6.3% vs 33.0% ± 5.7%, P < .001) and full regions (27.9% ± 6.2% vs 31.2% ± 5.5%, P < .001) compared with nonexudative AMD. There were no differences in FAZ area, perimeter, or circularity between the 2 groups (P = .503-.907). In eyes with exudative AMD, previous anti-VEGF treatments did not impact retinal vascular measurements (P = .324-.986). Nonexudative AMD severity and presence of central GA also impacted retinal VD and FAZ morphology.ConclusionsRetinal VD is decreased in eyes with exudative AMD compared with nonexudative AMD but is unaffected by anti-VEGF treatments, suggesting a retinal vascular contribution to the pathogenesis of AMD.

PurposeTo determine clear-cut distinctions between tractional and exudative intraretinal cystoid spaces subtypes.DesignRetrospective, multicenter, observational case series.MethodsA cohort of patients diagnosed with intraretinal cystoid spaces and imaged with optical coherence tomography (OCT), fluorescein angiography (FA), blue fundus autofluorescence (BFAF), en face OCT, and OCT angiography (OCT-A) was included in the study. All images were qualitatively and quantitatively evaluated.ResultsIn this study were included 72 eyes of 69 patients. Exudative intraretinal cystoid spaces (36/72 eyes, 50%) displayed a "petaloid" morphology as seen with en face OCT, FA, and BFAF. Tractional intraretinal cystoid spaces (24/72 eyes, 33.3%), displayed a radial "spoke-wheel" en face OCT pattern. There was no leakage with FA and BFAF did not reveal specific patterns. Eyes with full-thickness macular hole (FTMH, 12/72 eyes, 16.7%) displayed a "sunflower" en face OCT appearance. FTMH showed OCT, OCT-A, and BFAF features of both exudative and tractional cystoid spaces, but without any FA leakage. Inner nuclear layer (INL) thickness was significantly lower in tractional cystoid spaces (P < .001). There were a greater number of INL cystoid spaces in both the exudative and FTMH subgroups (P = .001). The surface area of INL cystoid spaces was significantly lower in the tractional subgroup (P < .001). There was a significant reduction of the microvascular density in eyes with exudative vs tractional (P = .002) and FTMH (P < .001) subgroups.ConclusionsExudative and tractional intraretinal cystoid spaces displayed characteristic multimodal imaging features and they may represent 2 different pathologic conditions with equally different clinical implications.

PRéCIS:: There is diagnostic information in the outer region of optical coherence tomography angiography (OCT-A) macula scans not available in the inner region, and this information is especially useful in the early stages of glaucoma.PurposeThe aim of this study was to evaluate the diagnostic accuracy of 3×3 and 6×6 mm macula OCT-A scans for classifying healthy, mild glaucoma, and moderate to severe glaucoma eyes.MethodsParticipants enrolled in the Diagnostic Innovations in Glaucoma Study (DIGS) with good quality 3×3 and 6×6 mm OCT-A images of the macula acquired on the same day were included in this cross-sectional study. The area under the receiver operating characteristic (AUC) curves were calculated to assess the diagnostic accuracy of vessel density (VD) of both scan sizes for differentiating between 3 diagnostic groups.ResultsTwo hundred seventy-nine eyes (89 healthy, 127 with mild glaucoma, and 63 with moderate to severe glaucoma) from 190 subjects were included in this study. The VD of the outer area of the 6×6 mm scan size had higher diagnostic accuracy compared with the VD of the inner area of the 3×3 mm scan when differentiating between healthy and mild glaucoma (3×3 mm AUC=0.71 and 6×6 mm AUC=0.79, P=0.032). The VD of the outer area of the 6×6 mm scans had only similar diagnostic accuracy compared with the inner area of the 3×3 mm scan when differentiating between healthy and moderate to severe glaucoma eyes (AUC=0.90 for 3×3 mm and 0.92 for 6×6 mm, P=0.279). The VD of the inner area of the 6×6 mm scan size had similar diagnostic accuracy to the corresponding area of the 3×3 mm scan in both diagnostic categories.ConclusionThe diagnostic accuracy of VD using the 6×6 mm macula OCT-A scan was better than the 3×3 mm scan when differentiating between healthy and mild glaucoma eyes, and similar to the 3×3 mm scan when differentiating between healthy and moderate to severe glaucoma eyes.

PurposeTo characterize the evolution and structure of soft drusen in aged rhesus macaques using in vivo multimodal retinal imaging and ex vivo histologic and ultrastructural analyses as a nonhuman primate model of early age-related macular degeneration (AMD).MethodsMultimodal imaging including fundus photography, spectral domain optical coherence tomography (SD-OCT), and fundus autofluorescence (FAF) were used to characterize and track individual drusen lesions in 20 aged rhesus macaques (mean age 23.3 ± 2.7 years) with drusenoid lesions over 2 years, followed by semithin histologic analysis and transmission electron microscopy (TEM).ResultsAlthough most drusen gradually increased in size, a portion spontaneously regressed or collapsed over 2 years. Histologic analyses showed that soft drusen exhibit hypertrophy and dysmorphia of overlying retinal pigment epithelium (RPE), as seen in early and intermediate AMD, but do not exhibit RPE atrophy, RPE migration, or photoreceptor degeneration characteristic of advanced AMD. Ultrastructure of soft drusen showed abundant lipid particles within Bruch's membrane and AMD-related basal linear deposits (BlinD) resembling those in human drusen.ConclusionsThe dynamic remodeling, histologic findings, and ultrastructural features of soft drusen in aged rhesus macaques support nonhuman primates as an animal model of early AMD and reveal important insights into drusen biogenesis and AMD development.

Human CD34 + stem cells are mobilized from bone marrow to sites of tissue ischemia and play an important role in tissue revascularization. This study used a murine model to test the hypothesis that intravitreal injection of human CD34 + stem cells harvested from bone marrow (BMSCs) can have protective effects in eyes with diabetic retinopathy. Streptozotocin-induced diabetic mice (C57BL/6J) were used as a model for diabetic retinopathy. Subcutaneous implantation of Alzet pump, loaded with Tacrolimus and Rapamycin, 5 days prior to intravitreal injection provided continuous systemic immunosuppression for the study duration to avoid rejection of human cells. Human CD34 + BMSCs were harvested from the mononuclear cell fraction of bone marrow from a healthy donor using magnetic beads. The CD34 + cells were labeled with enhanced green fluorescent protein (EGFP) using a lentiviral vector. The right eye of each mouse received an intravitreal injection of 50,000 EGFP-labeled CD34 + BMSCs or phosphate buffered saline (PBS). Simultaneous multimodal in vivo retinal imaging system consisting of fluorescent scanning laser ophthalmoscopy (enabling fluorescein angiography), optical coherence tomography (OCT) and OCT angiography was used to confirm the development of diabetic retinopathy and study the in vivo migration of the EGFP-labeled CD34 + BMSCs in the vitreous and retina following intravitreal injection. After imaging, the mice were euthanized, and the eyes were removed for immunohistochemistry. In addition, microarray analysis of the retina and retinal flat mount analysis of retinal vasculature were performed. The development of retinal microvascular changes consistent with diabetic retinopathy was visualized using fluorescein angiography and OCT angiography between 5 and 6 months after induction of diabetes in all diabetic mice. These retinal microvascular changes include areas of capillary nonperfusion and late leakage of fluorescein dye. Multimodal in vivo imaging and immunohistochemistry identified EGFP-labeled cells in the superficial retina and along retinal vasculature at 1 and 4 weeks following intravitreal cell injection. Microarray analysis showed changes in expression of 162 murine retinal genes following intravitreal CD34 + BMSC injection when compared to PBS-injected control. The major molecular pathways affected by intravitreal CD34 + BMSC injection in the murine retina included pathways implicated in the pathogenesis of diabetic retinopathy including Toll-like receptor, MAP kinase, oxidative stress, cellular development, assembly and organization pathways. At 4 weeks following intravitreal injection, retinal flat mount analysis showed preservation of the retinal vasculature in eyes injected with CD34 + BMSCs when compared to PBS-injected control. The study findings support the hypothesis that intravitreal injection of human CD34 + BMSCs results in retinal homing and integration of these human cells with preservation of the retinal vasculature in murine eyes with diabetic retinopathy.

AimTo show the characteristics and outcomes of patients with neovascular age-related macular degeneration (nAMD) who had extended remission (ER) while on a pro re nata (PRN) treatment protocol.MethodsThis was a retrospective case-control study of a consecutive series of patients with nAMD treated with a PRN antivascular endothelial growth factor (anti-VEGF) drug regimen. ER was defined as the absence of haemorrhage, intraretinal/subretinal fluid on optical coherence tomography and leakage on fluorescein angiography for 52 weeks after cessation of anti-VEGF therapy. Matching patients with nAMD who did not achieve ER were included as control group. Cox regression analysis was fitted to identify predictors of time to achieve ER and time to recurrence. A logistic regression analysis of baseline characteristics was used to identify predictors of achieving ER.ResultsOf 830 eyes treated with anti-VEGF monotherapy, 77 (9.2%) eyes achieved ER during a median follow-up of 236 weeks (range 70-525 weeks). Cox regression analysis showed that ER was achieved earlier in eyes with isolated intraretinal fluid (HR, 2.05; 95% CI 1.929 to 4.520; p=0.045) at presentation. Logistic regression analysis showed that type 3 choroidal neovascularisation (OR, 0.090; 95% CI 0.021 to 0.382; p=0.001), thinner choroid (OR, 0.993; 95% CI 0.988 to 0.998; p=0.004) and absence of macular atrophy (OR, 0.233; 95% CI 0.065 to 0.839; p=0.026) at baseline increased the likelihood of achieving ER.ConclusionER is achievable in 9.2% of patients under PRN therapy for nAMD. At presentation with nAMD, anatomical features on retinal imaging may predict the likelihood of achieving ER and a shorter time to achieve ER.