Retinal Pigment Epithelial Adenoma: Initial Treatment Outcomes following Episcleral Brachytherapy.

Introduction: We aim to explore the safety and efficacy of episcleral brachytherapy as a primary management option for eyes with retinal pigment epithelial (RPE) adenoma. Methods: Retrospective chart review of the demographic, clinical, ancillary, and postoperative outcome data of patients with RPE adenoma in 2 tertiary referral centers. Tumor regression, final visual acuity, and complications were assessed. Results: Five patients (3 females and 2 males) were included. Four of the 5 eyes had peripheral and mid-peripheral lesions, while one tumor was juxtapapillary. Three eyes were treated with ruthenium-106 (100 Gray), and 2 received iodine-125 episcleral plaques (85 Gray). All eyes showed clinical and imaging-based evidence of regression. Four eyes had stable or improved visual acuity, while 1 eye exhibited one line loss of visual acuity due to radiation retinopathy. Local recurrence was not observed in any eye over a median follow-up of 24 (range 6-112) months. Conclusions: Episcleral brachytherapy is an effective management option for select cases of RPE adenoma that is capable of achieving tumor regression while maintaining favorable visual acuity. The initial safety profile of brachytherapy is good without significant vision-compromising complications.

LncRNA ANRIL Promotes Glucose Metabolism and Proliferation of Colon Cancer in a High-Glucose Environment and is Associated with Worse Outcome in Diabetic Colon Cancer Patients.

BACKGROUND: The potential involvement of type 2 diabetes mellitus (T2DM) as a risk factor for colon cancer (CC) has been previously reported. Epigenetic changes, such as deregulation of long non-coding RNA (lncRNA) and microRNA (miR), have been linked to the advancement of CC; however, the effects of high glucose levels on their deregulation and, in turn, colon cancer remain unexplored. METHODS: Fifty patients had a dual diagnosis of CC and T2DM, and 60 patients with CC without diabetes mellitus were included in the study. qRT-PCR was used to examine the expression of lncRNA ANRIL and miR-186-5p in tissue samples. ANRIL, miR-186-5p, and their downstream target genes HIF-1α, PFK, HK, Bcl-2, and Bax were also determined in CC cell lines under various glucose conditions. Glucose uptake, lactate production and cells proliferation were estimated in CC cell lines. RESULTS: A significant upregulation of ANRIL expression levels (p<0.001) and a significant downregulation of miR-186-5p expression (p<0.001) in diabetic colon cancer specimens compared to those in non-diabetic colon cancer group were observed. MiR-186-5p expression levels were inversely correlated with ANRIL expression levels, blood glucose levels and HbA1c%. Concerning in vitro model, a significant upregulation of ANRIL, downregulation of miR-186-5p, upregulation of HIF-1α, glycolytic enzymes and activation of antiapoptotic pathway was detected in higher glucose concentrations than lower one. There was a significant increase of glucose uptake, lactate accumulation and proliferation of the Caco2 and SW620 cell lines in a dose dependent manner of glucose concentrations. Moreover, a significant positive correlation between glucose uptake and ANRIL expression was shown. CONCLUSIONS: A high-glucose environment can increase the tumor-promoting effect of ANRIL. ANRIL can promote glucose metabolism and colon cancer proliferation by downregulating miR-186-5p with subsequent upregulation of glycolysis enzymes expression and inhibition of apoptosis.

Retinal vasculature of different diameters and plexuses exhibit distinct vulnerability in varying severity of diabetic retinopathy.

OBJECTIVES: To study the changes in vessel densities (VD) stratified by vessel diameter in the retinal superficial and deep vascular complexes (SVC/DVC) using optical coherence tomography angiography (OCTA) images obtained from people with diabetes and age-matched healthy controls. METHODS: We quantified the VD based on vessel diameter categorized as <10, 10-20 and >20 µm in the SVC/DVC obtained on 3 × 3 mm2 OCTA scans using a deep learning-based segmentation and vascular graph extraction tool in people with diabetes and age-matched healthy controls. RESULTS: OCTA images obtained from 854 eyes of 854 subjects were divided into 5 groups: healthy controls (n = 555); people with diabetes with no diabetic retinopathy (DR, n = 90), mild and moderate non-proliferative DR (NPDR) (n = 96), severe NPDR (n = 42) and proliferative DR (PDR) (n = 71). Both SVC and DVC showed significant decrease in VD with increasing DR severity (p < 0.001). The largest difference was observed in the <10 µm vessels of the SVC between healthy controls and no DR (13.9% lower in no DR, p < 0.001). Progressive decrease in <10 µm vessels of the SVC and DVC was seen with increasing DR severity (p < 0.001). However, 10-20 µm vessels only showed decline in the DVC, but not the SVC (p < 0.001) and there was no change observed in the >20 µm vessels in either plexus. CONCLUSIONS: Our findings suggest that OCTA is able to demonstrate a distinct vulnerability of the smallest retinal vessels in both plexuses that worsens with increasing severity of DR.

Synthetic Optical Coherence Tomography Angiographs for Detailed Retinal Vessel Segmentation Without Human Annotations.

Optical coherence tomography angiography (OCTA) is a non-invasive imaging modality that can acquire high-resolution volumes of the retinal vasculature and aid the diagnosis of ocular, neurological and cardiac diseases. Segmenting the visible blood vessels is a common first step when extracting quantitative biomarkers from these images. Classical segmentation algorithms based on thresholding are strongly affected by image artifacts and limited signal-to-noise ratio. The use of modern, deep learning-based segmentation methods has been inhibited by a lack of large datasets with detailed annotations of the blood vessels. To address this issue, recent work has employed transfer learning, where a segmentation network is trained on synthetic OCTA images and is then applied to real data. However, the previously proposed simulations fail to faithfully model the retinal vasculature and do not provide effective domain adaptation. Because of this, current methods are unable to fully segment the retinal vasculature, in particular the smallest capillaries. In this work, we present a lightweight simulation of the retinal vascular network based on space colonization for faster and more realistic OCTA synthesis. We then introduce three contrast adaptation pipelines to decrease the domain gap between real and artificial images. We demonstrate the superior segmentation performance of our approach in extensive quantitative and qualitative experiments on three public datasets that compare our method to traditional computer vision algorithms and supervised training using human annotations. Finally, we make our entire pipeline publicly available, including the source code, pretrained models, and a large dataset of synthetic OCTA images.

COVID-19 VACCINE-INDUCED ACUTE EXUDATIVE POLYMORPHOUS VITELLIFORM MACULOPATHY: CASE REPORTS.

BACKGROUND: Acute exudative polymorphous vitelliform maculopathy is a presumed retinal pigment epithelium abnormality that has been reported in patients with neoplasms and under certain classes of drugs. The pathophysiology remains unclear, despite the typical clinical features. PURPOSE: To report two cases of acute exudative polymorphous vitelliform maculopathy occurring after vaccination with a COVID-19 vaccine. CASE REPORTS: Two adult patients presented with visual disturbance after inoculation with a COVID-19 vaccine. The patients were otherwise healthy and have no family history of retinal dystrophies. Both cases exhibited the following features on multimodal imaging: multifocal hyporeflective lesions involving the macula, elongated photoreceptors, accumulated vitelliform material exhibiting autofluorescence, and lack of fluorescein dye leakage. Evidence of retinal pigment epithelium dysfunction was confirmed by electrooculography. CONCLUSION: Two cases of acute exudative polymorphous vitelliform maculopathy occurring after COVID-19 vaccination were reported. A relationship between the vaccine and the retinal pigment epithelial abnormality development that led to acute exudative polymorphous vitelliform maculopathy was postulate, possibly through autoantibodies against the severe acute respiratory syndrome coronavirus 2 virus structural surface glycoprotein antigens that cross react with the normal retinal pigment epithelial cells.

Diminished choroidal blood flow in hypertensive and preeclamptic third trimester pregnancies using optical coherence tomography angiography.

PURPOSE: The aim of this study was to compare choroidal adjusted flow index (AFI) in healthy, hypertensive & preeclamptic pregnancies using optical coherence tomography angiography (OCTA). METHODS: In this prospective study, healthy, hypertensive & preeclamptic third trimester pregnant women underwent OCTA imaging. 3x3 & 6x6 mm choriocapillaris slabs were exported and the parafoveal area was marked by two concentric ETDRS circles at 1 & 3 mm, centered on the foveal avascular zone. Parafoveal AFI was calculated as a parameter of choroidal blood flow. RESULTS: Fifteen eyes of fifteen women per group were recruited (45 eyes). AFI was significantly lower in the preeclamptic compared to the healthy & hypertensive groups (Tukey HSD: <0.001 in both groups on 3x3 mm, and 0.02 & 0.04 in 6x6 mm scans), and in the hypertensive compared to the healthy group (0.005 & 0.03 in 3x3 & 6x6 mm scans respectively). CONCLUSIONS: Pregnancies complicated with preeclampsia revealed the lowest choroidal blood flow on OCTA followed by pregnancies with systemic hypertension compared to healthy pregnancies. We provide in-vivo documentation of choroidal ischemia, highlighting its culpability in hypertensive and preeclamptic retinochoroidal pathology, and the possibility of utilizing choroidal blood flow on OCTA as a precursor for disease progression.

Case Report: Acquired Brown Syndrome after COVID-19 Vaccination.

SIGNIFICANCE: Brown syndrome, or superior oblique tendon sheath syndrome, is characterized by limitation of elevation on adduction. The disorder is thought to involve the trochlea/superior oblique tendon complex through traumatic, surgical, and inflammatory mechanisms. It could be an indication of multiple underlying immunological or rheumatological disorders. PURPOSE: This study aimed to report an unusual strabismus after receiving the first dose of a live attenuated coronavirus disease 2019 (COVID-19) vaccine. CASE REPORT: A 31-year-old female patient presented with painful vertical diplopia and tenderness of the left trochlear area 3 days after the first dose of COVID-19 vaccination. She had a compensatory chin elevation and face turn to the right, as well as a left 10-prism-diopter hypotropia in the primary position, which increased to 15 prism diopters in the right gaze and disappeared in the left gaze. Ocular motility revealed the limitation of elevation on adduction. The patient denied any history of ocular trauma and was consequently investigated for dysthyroid disease and various immunological and rheumatological disorders, which were excluded. A Hess chart was obtained to document the motility disorder. CONCLUSIONS: We report a case of acquired Brown syndrome in a 31-year-old otherwise healthy woman shortly after COVID-19 vaccination. It is possible that the patient may have developed trochleitis and/or superior oblique tenosynovitis brought on by cross-reacting antibodies generated by the immune response to the vaccine. In the age of the widest vaccination campaign in human history, it is highly likely that we will continue to observe many unexpected potential adverse effects of these vaccines in our clinical practice.

Temporary Vitelliform Regression After Intravitreal Ranibizumab Injection for Macular Neovascularization Complicating Best Disease.

Background: In this report, we present a case of a 12-year-old boy with Best vitelliform macular dystrophy (BVMD) complicated by macular neovascularization (MNV) and treated with two intravitreal ranibizumab injections. We document an unusual temporary regression of his vitelliform deposits and describe a 2-year follow-up course through multimodal imaging. Case Presentation: A 12-year-old boy complaining of metamorphopsia presented with bilateral yellowish subfoveal deposits, suggestive of BVMD, which was confirmed by fundus autofluorescence and electrooculography. The left eye showed an inferior juxtafoveal complicating MNV, for which the patient was treated with two intravitreal ranibizumab injections. In addition to demonstrating a remarkable response to injection, both clinically and through various multimodal imaging modalities, optical coherence tomography (OCT) showed a surprising temporary resolution of the subfoveal hypopreflective space denoting a regression in the lipofuscin deposits accumulating at the RPE and the subfoveal space. Within 2 months, there was a subsequent build-up of the subfoveal space and lipofuscin reaccumulation through serial imaging despite the clear regression of the MNV. The patient remained stable over a course of 2 years. Conclusion: Our findings cast light on a rather unusual response to intravitreal anti-VEGF injections that has not been previously reported in literature in the form of a temporary disappearance of the subfoveal vitelliform deposits, which later began to reaccumulate. This process may reflect a temporary relief of the RPE dysfunction or decreased photoreceptor damage with regression of the complicating MNV, leading to decreased vitelliform deposition. Adding to other reports, our findings also provide a 2-year-long follow-up with serial multimodal documentation of the response to injection and suggest a favorable long-term prognosis for intravitreal anti-VEGF injections in eyes with BVMD presenting with early complicating MNVs.

OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY REVEALS PARADOXICALLY DECREASING CHOROIDAL THICKNESS AND INCREASING BLOOD FLOW IN REMITTING VOGT-KOYANAGI-HARADA SYNDROME.

PURPOSE: To assess changes in choroidal thickness and blood flow in active Vogt-Koyanagi-Harada syndrome and after remission using optical coherence tomography angiography. METHODS: This was a prospective study of patients with active early uveitis secondary to Vogt-Koyanagi-Harada syndrome. They underwent optical coherence tomography angiography imaging twice: at baseline and after remission on treatment. 3- × 3- and 6- × 6-mm choriocapillaris slabs were used to evaluate parafoveal adjusted flow index as a marker for choroidal blood flow. Mean choroidal thickness of 3 points (subfoveally and 2 points 300 µ m parafoveally) was also measured. RESULTS: Thirty-nine eyes of 25 patients were initially recruited. After excluding eyes with media opacity, submacular fibrosis, and choroidal neovascularization, 23 eyes of 14 patients were included. The mean follow-up period was 8.7 ± 2.5 months. Mean choroidal thickness in activity and remission was 581.65 ± 108.29 µ m and 318.34 ± 72.85 µ m respectively ( P < 0.01). Mean adjusted flow index in the 3- × 3-mm slabs activity and remission were 0.495 ± 0.027 and 0.519 ± 0.0336 ( P = 0.011), and the 6- × 6-mm slabs were 0.487 ± 0.037 and 0.517 ± 0.052 respectively ( P = 0.025). CONCLUSION: We demonstrate decreasing choroidal thickness with paradoxically increasing choroidal flow on optical coherence tomography angiography in remitting Vogt-Koyanagi-Harada syndrome. This may reflect inflammatory infiltrations or granulomas increasing choroidal thickness during activity and causing sluggish circulation of the choriocapillaris, and a reversal of this process with remission. These findings shed more light on the relationship between Vogt Koyanagi Harada syndrome and its underlying choroidal disturbances. Larger studies are needed to evaluate the efficacy of adjusted flow index in evaluating and predicting disease activity.

Prognostic value of NOTCH1 and OCT4 in gastric carcinoma.

Background: NOTCH1 pathway activation has been recently described to be a key player in gastric carcinogenesis, enhance the survival and proliferation of cancer stem cells (CSCs) and mediate chemoresistance in several malignancies. Aim: This study investigated the correlation between NOTCH1 and CSC marker OCT4 (octamer binding transcription factor-4) expression and the clinicopathological properties, survival and treatment outcome in patients with gastric carcinoma (GC) receiving adjuvant chemotherapy. Materials and. Methods: NOTCH1 and OCT4 were immunohistochemically detected in 50 post-operated specimens of GC. Patients' data regarding disease-free survival (DFS), overall survival (OS), and the response to the chemotherapy was statistically analyzed. Results: NOTCH1 and OCT4 overexpression was detected in 60% and 52% of GC tissues, respectively, and that was significantly higher than the rates in adjacent non-neoplastic gastric mucosa (P < 0.05). A significant correlation was detected between overexpression of NOTCH1 and OCT4 in GC and aggressive clinicopathological features; poor differentiation (P = 0.021, P = 0.037, respectively), depth of tumor invasion (P < 0.001 for both), TNM stage (P < 0.001 for both), lymph node metastasis (P = 0.002, P = 0.003, respectively) and distant metastasis (P < 0.001 for both). NOTCH1 was positively correlated with OCT4 (P = 0.002). Survival analysis disclosed that upregulation of NOTCH1 and OCT4 was associated with worse DFS (P = 0.013, P < 0.001, respectively) and OS (P < 0.001 for both). Overexpression of NOTCH1 and OCT4 correlated with poor response to chemotherapy (P = 0.013, P = 0.005, respectively) and worse clinical outcome. Conclusion: Combined detection of these proteins might disclose even better predictive value for shorter survival and resistance to chemotherapy.

Masking of macular neovascular membranes by subretinal hyperreflective material on optical coherence tomography angiography.

PURPOSE: The purpose of this study was to determine whether subretinal hyperreflective material (SHRM) may mask the detection of macular neovascular membranes (MNV) on optical coherence tomography angiography (OCTA). METHODS: In this observational study, eyes with active neovascular age-related macular degeneration (nAMD), co-existing SHRM & intraretinal or subretinal fluid or hemorrhage on structural OCT, underwent OCTA & fundus fluorescein angiography (FFA) imaging. 6 × 6 mm choriocapillaris and outer retinal slabs on OCTA were examined to determine the presence of MNV underneath the SHRM. The corresponding area on FFA was used as a reference arm to confirm activity. RESULTS: Thirty eyes of thirty patients with SHRM and active nAMD were recruited. All eyes failed to show a MNV in the choriocapillaris & avascular slabs of the OCTA underneath the SHRM, but showed active hyperfluorescent MNVs that increased in size and intensity in the late stages of FFA. In one eye, parts of a MNV under the SHRM were undetectable due to signal attenuation, while parts extending beyond the SHRM were detected on the choriocapillaris en face slab with flow on the B scan. CONCLUSIONS: SHRM may act as a reflecting surface that limits the passage of light waves in OCTA, creating areas of signal attenuation and diminishing its ability to detect underlying MNVs.

Unique presentations of aspergillosis endogenous endophthalmitis in two hospitalized patients with severe COVID-19.

We present two ICU-hospitalized patients with coronavirus disease-19 (COVID-19) presenting with endogenous endophthalmitis in one eye and variable manifestations of chorioretinitis in the fellow eye. Two diabetic patients (57 and 62 years old) showed anterior uveitis and yellowish-white subretinal infiltrations. The fellow eye of one patient showed patches of choroiditis, while the other showed full retinal thickness infiltrations. A workup yielded high serum titers of galactomannan, diagnostic of aspergillosis. The widespread use of high doses of corticosteroids in the management of COVID-19 may predispose to various secondary fungal opportunistic infections and may manifest in different forms of chorioretinal infiltration.

Choriocapillaris Island: an optical coherence tomography angiography finding observed in central serous chorioretinopathy.

PURPOSE: To report the observation of the choriocapillaris island (CCI) on optical coherence tomography angiography (OCTA) in eyes with active central serous chorioretinopathy (CSCR), and to investigate its associated clinical features. DESIGN: Retrospective observational study. METHODS: Patients diagnosed with active CSCR underwent OCTA imaging (Optovue Inc, Fremont, California, USA), and the software built-in en face choriocapillaris slab was examined to demonstrate CCI, defined as an area of detectable choriocapillaris flow surrounded by an area of undetectable or diminished flow. Electronic medical records (EMR) were reviewed for demographics, clinical data, other imaging modalities and any intervention, and these parameters were correlated with CCI findings. RESULTS: 25 eyes of 25 patients were recruited. CCI was detected in all examined eyes and was best elucidated on the en face choriocapillaris density maps. 24 eyes had focal retinal pigment epithelium (RPE) alterations overlying CCI. All 14 eyes with simultaneous fundus fluorescein angiography (FA) showed actively leaking point(s) well corresponding to the CCI location. Resolution of sub-retinal fluid in 4 eyes was associated with disappearance of CCI on follow-up OCTA scans. 1 eye showed complicating neovascularization 5 months after the initial presentation at the same location of the CCI. CONCLUSION: We demonstrate the observation of the "choriocapillaris island" an OCTA finding in eyes with active CSCR underneath the area of neurosensory detachment. CCI may constitute an angiographic representation of the focal area of choriocapillaris structural and functional affection, with secondary RPE alteration jeopardizing its barrier function. Larger longitudinal studies are needed to further elucidate this finding.

Bilateral Morning Glory Syndrome with Bilateral Persistent Fetal Vasculature in a Patient with Joubert's Syndrome.

Purpose. We report a case of a 1-year-old girl who was referred to us with a cerebellar anomaly and delayed growth and development for bilateral ptosis and poor fixation. Based on our ophthalmologic examination, we concluded that she has bilateral persistent fetal vasculature (PFV) with morning glory syndrome (MGS). A closer look into her neurologic condition revealed that she has Joubert's syndrome. Observations. External examination revealed bilateral symmetrical ptosis with syndromic facies and her fundus examination revealed a large dysplastic optic disc with anomalous radiating vessels and a fibrous tissue tuft originating from the disc. The left eye showed similar findings in addition to a central excavation and a fibrovascular stalk extending from the optic disc. These findings were consistent with bilateral MGS and bilateral PFV. The brain imaging included a computed tomography scan and magnetic resonance imaging, both of which revealed a "molar tooth appearance" of the midbrain and an anomalous cerebellum suggestive of Joubert's syndrome. Conclusions and Importance. This is the first case report of a case of bilateral MGS and bilateral PFV associated with Joubert's syndrome. This case report documents the associated optic nerve disease in these patients, not previously described, which are additive causes of visual compromise in addition to the brain insult.

Optical coherence tomography angiography reveals progressive worsening of retinal vascular geometry in diabetic retinopathy and improved geometry after panretinal photocoagulation.

PURPOSE: To quantify vessel tortuosity and fractal dimension of the superficial capillary plexus (SCP) of the macula in different stages of diabetic retinopathy (DR), and following panretinal photocoagulation (PRP) using optical coherence tomography angiography (OCTA). METHODS: 75 eyes of 75 subjects were divided into five groups; healthy controls, diabetes with no clinical DR, non-proliferative diabetic retinopathy (NPDR), proliferative diabetic retinopathy (PDR) and patients who received PRP for PDR (PDR+PRP).For vessel tortuosity, SCP slabs from 3x3 mm macular OCTA scans were processed using imageJ (NIH, USA), where large perifoveal vessels were traced and their length was measured with tortuosity calculated as the ratio between the actual length and the straight Euclidean length. For fractal dimension, SCP slabs were processed and imported to Fractalyse (ThéMA, France), where box-counting analyses produced fractal dimension values. RESULTS: We found a significant difference in vessel tortuosity and fractal dimension between the five groups (one-way ANOVA, p < 0.001both). NPDR and PDR had significantly more tortuous vessels and lower fractal dimension compared to healthy controls (Tukey HSD: p = 0.02, 0.015,0.015 and <0.001, respectively). Fractal dimension was also significantly lower in NPDR and PDR compared to eyes with no clinical DR (p <0.001 both), and in PDR compared to NPDR (p = 0.014). Following PRP, vessel tortuosity was significantly lower and fractal dimension was higher in PDR+PRP compared to PDR (p = 0.001 and 0.031, respectively). CONCLUSIONS: We used macular OCTA scans to demonstrate significantly higher perifoveal large vessel tortuosity, and lower fractal dimension in NPDR and PDR compared to healthy controls. Vessel tortuosity shows more dramatic normalization than fractal dimension and could be explored as a sensitive marker for successful PRP.

Effect of KRAS mutational status on disease behavior and treatment outcome in patients with metastatic colorectal cancer: intratumor heterogeneity and mutational status.

BACKGROUND: Nowadays, the outcomes of metastatic colorectal cancer (mCRC) have considerably improved. Genetic studies evaluating KRAS mutational status are important in the personalized therapy era to understand disease heterogeneity, disease behaviors, and treatment outcomes. METHODS: This multicenter retrospective study evaluated 360 patients with mCRC treated at three oncology centers in Saudi Arabia and Egypt between February 2011 and December 2015. Patients were treated with bevacizumab and cetuximab according to guidelines. Therapy outcome, time to progression, and disease-associated death were assessed. KRAS mutational status was evaluated by testing exons 12 and 13. RESULTS: Approximately 220 (61.1%) cases were of wild-type KRAS, whereas KRAS mutation was noted in 38.9%. KRAS mutation was common in the descending colon, whereas a low incidence of the KRAS mutation was observed in the ascending colon (P<0.001). Among patients with KRAS mutation, 64.3% initially presented as emergency cases with obstruction/perforation (P=0.002), and 62.9% had hepatic or pulmonary metastasis. The progression-free survival (PFS) was 10.7 months. Cases without KRAS mutation showed a higher PFS than did those with KRAS mutation (mean PFS: 11.5 vs. 9.6 months, P=0.001). The overall survival was 23.2 months. The survival varied considerably according to KRAS type: patients without mutation survived for 25.0 months and those with mutation survived for 19.6 months (P<0.001). Disease-related death occurred in 132 (36.7%) cases, approximately 57.1% of them (80 cases) had KRAS mutations (P=0.001). CONCLUSIONS: A major association between KRAS mutational status and both disease behavior and treatment outcomes was found in this study. Patients with KRAS mutation show advanced disease presentation, with lower PFS and overall survival.

Exploring the relationship between collaterals and vessel density in retinal vein occlusions using optical coherence tomography angiography.

PURPOSE: To characterize the types of collaterals in eyes with retinal vein occlusion (RVO) and further investigate their correlations with vessel densities of the superficial (SCP) and the deep capillary plexus (DCP) using optical coherence tomography angiography (OCTA). METHODS: This cross-sectional study included 25 eyes of 23 patients with RVO. 3 x 3 mm2 OCTA macular scans were used to quantify the parafoveal vessel density (VD) of the SCP and DCP, and to classify the collaterals into one of four types (true superficial, true deep, superficial diving, and foveal collateral). Generalized estimating equation (GEE) regression analysis was performed to identify significant associations between parafoveal VD and collaterals. We further compared parafoveal VD between subgroups classified by the presence of specific collateral types based on the results of a clustering algorithm. RESULTS: 16 of 25 eyes (64%) developed collaterals. Of the 43 collateral vessels analyzed, 12/19 (63%) true superficial collaterals developed in eyes with central RVO, while all 10 superficial diving collaterals (100%) developed in eyes with branch RVO. Located exclusively in the SCP, true superficial collaterals were all arteriovenous (A-V), while diving collaterals were all veno-venular (V-V). We found a significant negative correlation between SCP VD and the total number of collaterals (P < 0.001) for the entire study cohort. Furthermore, BRVO eyes that developed superficial diving collaterals and CRVO eyes that developed true superficial collaterals demonstrated significantly lower SCP VD (P-value = 0.014) and DCP VD (P-value = 0.030), respectively, as compared to the eyes without collaterals in the respective RVO group. CONCLUSION: Our data shows that decreased capillary perfusion in RVO is associated with the development of collaterals, while the RVO type largely dictates the type of collateral that ultimately develops.

Projection resolved optical coherence tomography angiography to distinguish flow signal in retinal angiomatous proliferation from flow artifact.

PURPOSE: To investigate whether hyperreflective foci (HRF) exhibit flow projection artifact on OCTA, and study the efficacy of commercial projection artifact removal software (PAR-OCTA, Optovue, Inc), and a custom projection resolved OCTA (PR-OCTA) in distinguishing artifacts from true flow in retinal angiomatous proliferation (RAP). METHODS: The study included five eyes with HRF representing pigment migration in dry age-related macular degeneration (AMD), five eyes with leaking treatment-naïve RAP, and ten eyes with diabetic hard exudates. We examined flow signal on OCTA cross-sections using PAR, and performed PR-OCTA to study the effect of increasingly stringent projection removal thresholds. Flow signal intensity was analyzed and quantified using imageJ (NIH, Bethesda, MD, USA), by calculating the percentage of red pixels (R) representing flow, compared to green (G) and blue (B) pixels. RESULTS: PAR-OCTA cross sections revealed persistent flow signal in all HRF, including RAP, hard exudates and pigment migration. In RAP, PR-OCTA detected intransigent flow, irrespective of the flow removal threshold. Mean R in the five RAP lesions remained higher than mean G and B at the most stringent PR-OCTA threshold (40.96% vs 29.52 and 29.52%, respectively), denoting persistence of flow. In contrast, increasing the PR-OCTA threshold in pigment migration and hard exudates removed the flow signal, with a statistically significant decrease in mean R with increasing threshold. (p = 0.017 and 0.0029, respectively). CONCLUSION: Commercial PAR-OCTA is not completely effective at removing artifactual flow in hard exudates and HRF related to pigment migration. Custom built PR-OCTA, using a sliding scale of threshold, allowed us to distinguish true flow in RAP from artifactual flow in avascular HRF. Further studies are needed to validate the optimum threshold for projection artifact removal, which would preserve true flow in RAP and the small intraretinal capillaries.

Improved Macular Capillary Flow on Optical Coherence Tomography Angiography After Panretinal Photocoagulation for Proliferative Diabetic Retinopathy.

PURPOSE: This study evaluated the macular microvascular changes in eyes with proliferative diabetic retinopathy (PDR) following panretinal photocoagulation (PRP). DESIGN: Using optical coherence tomographic angiography (OCTA), we prospectively studied 10 eyes of 10 subjects with high-risk PDR immediately before, at 1 month, and at 3-6 months following PRP, using a 3- × 3-mm OCTA scan at each visit. METHODS: The following parameters were calculated for the superficial (SCP), middle (MCP), and deep capillary plexuses (DCP): parafoveal vessel density (VD), adjusted flow index (AFI), and percent area of nonperfusion (PAN). Parafoveal SCP vessel-length density (VLD) was also evaluated. We performed univariate and multivariable statistics, adjusting for age and signal strength. To model the hemodynamic effect of PRP, we also present a mathematical model based on electrical circuits. RESULTS: We found no significant difference for the vascular density parameters following PRP, except for decreased density at the MCP at the latest timepoint in the adjusted multivariable model. PAN, a metric of nonperfusion adjusted for noise, and AFI, a surrogate metric of blood flow, showed significant increases at all capillary levels in the adjusted model. Our mathematical model explained how PRP would increase macular blood flow. CONCLUSIONS: Using OCTA, we found an overall increase in the flow metrics of all capillary layers in the macula following PRP, unrelated to macular edema or thickening, in line with the mathematical model. Our results suggest an overall redistribution of blood flow to the posterior pole following PRP, adding a new dimension to our understanding of the complex biologic effects of PRP in PDR. NOTE: Publication of this article is sponsored by the American Ophthalmological Society.

Hemodynamic Response of the Three Macular Capillary Plexuses in Dark Adaptation and Flicker Stimulation Using Optical Coherence Tomography Angiography.

Purpose: To assess retinal microvascular reactivity during dark adaptation and the transition to ambient light and after flicker stimulation using optical coherence tomography angiography (OCTA). Methods: Fifteen eyes of 15 healthy participants were dark adapted for 45 minutes followed by OCTA imaging in the dark-adapted state. After 5 minutes of normal lighting, subjects underwent OCTA imaging. Participants were then subjected to a flashing light-emitting diode (LED) light and repeat OCTA. Parafoveal vessel density and adjusted flow index (AFI) were calculated for superficial (SCP), middle (MCP), and deep capillary plexuses (DCP), and then compared between conditions after adjusting for age, refractive error, and scan quality. SCP vessel length density (VLD) was also evaluated. Between-condition capillary images were aligned and subtracted to identify differences. We then analyzed images from 10 healthy subjects during the transition from dark adaptation to ambient light. Results: SCP vessel density was significantly higher while SCP VLD was significantly lower during ambient light and flicker compared to dark adaptation. There was a significant positive mean value for DCP "flicker minus dark or light," suggesting more visible vessels during flicker due to changes in flow, dilation, or vessel recruitment. We found a significant, transient increase in SCP and decrease in both MCP and DCP vessel density during the transition from dark to light. Conclusions: We show evidence suggesting constriction of deeper vessels and dilation of large SCP vessels during the transition from dark to light. This contrasts to redistribution of blood flow to deeper layers during dark adaptation and flicker stimulation.