The Impact of Image Processing Algorithms on Optical Coherence Tomography Angiography Metrics and Study Conclusions in Diabetic Retinopathy.

Purpose: The purpose of this study was to evaluate the impact of image processing on quantitative metrics in optical coherence tomography angiography (OCTA) images and study conclusions in patients with diabetes. Methods: This was a single center, retrospective cross-sectional study. OCTA imaging with the Cirrus HD-OCT 5000 AngioPlex of patients with diabetes was performed. The 8 × 8 mm superficial slab images underwent 4 different preprocessing methods (none, background subtraction [BGS], foveal avascular zone brightness adjustment, and contrast limited adaptive histogram equalization [CLAHE]) followed by 4 different binarization algorithms (global Huang, global Otsu, local Niblack, and local Phansalkar) in ImageJ. Vessel density (VD), skeletonized VD (SVD), and fractal dimension (FD) were calculated. Mixed-effect multivariate linear regressions were performed. Results: Two hundred eleven scans from 104 patients were included. Of these scans, 67 (31.8%) had no diabetic retinopathy (DR), 99 (46.9%) had nonproliferative DR (NPDR), and 45 (21.3%) had proliferative DR (PDR). Forty-eight of 211 (22.7%) scans had diabetic macular edema (DME). The image processing method used significantly impacted values of VD, SVD, and FD (all P -values < 0.001). On multivariate analysis, the image processing method changed the clinical variables significantly associated with VD, SVD, and FD. However, BGS and CLAHE yielded more consistent significant covariates across multiple binarization algorithms. Conclusions: The image processing method can impact the conclusions of any given study analyzing quantitative OCTA metrics. Thus, caution is urged in the interpretation of such studies. Background subtraction or CLAHE may play a role in the standardization of image processing. Translational Relevance: This work proposes strategies to achieve robust and consistent analysis of OCTA imaging, which is especially important for clinical trials.

Suprachoroidal Hemorrhage after XEN Gel Implant Requiring Surgical Drainage.

Aim: To describe a case of a patient on anticoagulation who underwent XEN45 (XEN) gel stent placement and subsequently developed kissing suprachoroidal hemorrhages (SCHs) requiring surgical drainage. Background: Minimally invasive glaucoma surgery (MIGS) aims to achieve effective control of intraocular pressure (IOP) while minimizing the complications associated with traditional glaucoma surgeries. Rarely, a severe complication of intraocular surgery is SCH, which can result from early postoperative hypotony. The XEN gel stent is a MIGS device that theoretically avoids the risk of hypotony due to its outflow resistance properties. However, cases of SCH associated with XEN gel stents have been reported. Case Description: A monocular 86-year-old Caucasian male with glaucoma and atrial fibrillation on rivaroxaban underwent routine XEN gel stent placement with mitomycin C in his only seeing eye. On postoperative day 3, he presented with severe eye pain and worsening vision. He was found to have a SCH that gradually progressed to kissing suprachoroidals that required surgical drainage. After extensive discussion, the decision was made to hold the patient's rivaroxaban given his monocular status. The patient subsequently had a cerebral vascular accident (CVA) 1 week after drainage, but his symptoms gradually resolved after restarting anticoagulation. Two months after drainage, the patient's SCH had completely resolved, and he had recovered baseline visual acuity with excellent IOP control-off medications. Conclusion: This case highlights the importance of quick and appropriate management of complications following glaucoma surgery, as well as discussion with patients regarding risks of treatments and return precautions. It also is a reminder that although many new surgical interventions are "minimally invasive," those like the XEN that are more effective at IOP control may have a similar risk profile to more traditional surgeries like trabeculectomy. As such, risk factors like anticoagulation use and older age should be considered in anticipation of surgical intervention. Clinical significance: The XEN gel stent is a new surgical option for glaucoma patients that asserts a better safety profile than traditional surgeries like trabeculectomy, but our case of kissing SCHs requiring surgical intervention following XEN placement reminds us that even minimally invasive surgeries can have devastating complications. How to cite this article: Wang K, Wang JC, Sarrafpour S. Suprachoroidal Hemorrhage after XEN Gel Implant Requiring Surgical Drainage. J Curr Glaucoma Pract 2022;16(2):132-135.

Repair of Rhegmatogenous Retinal Detachment in Choroideremia Secondary to Posterior Extramacular Retinal Hole.

Rhegmatogenous retinal detachment in choroideremia is a rare occurrence. The authors present a case of a 23-year-old man with choroideremia with a near-total rhegmatogenous retinal detachment. Fundus examination did not reveal any retinal breaks, but extensive preoperative optical coherence tomography detected a small posterior hole along the superior arcades. The retinal detachment was successfully managed with vitrectomy, perfluorooctane to confirm the absence of any peripheral breaks, endolaser, and 20% sulfur hexafluoride gas. Similar extramacular holes were found in the patient's other eye. Patients with choroideremia may develop posterior retinal breaks leading to retinal detachment.

Photoreceptor Layer Thinning Is an Early Biomarker for Age-Related Macular Degeneration: Epidemiologic and Genetic Evidence from UK Biobank OCT Data.

PURPOSE: Despite widespread use of OCT, an early-stage imaging biomarker for age-related macular degeneration (AMD) has not been identified. Pathophysiologically, the timing of drusen accumulation in relationship to photoreceptor degeneration in AMD remains unclear, as are the inherited genetic variants contributing to these processes. Herein, we jointly analyzed OCT, electronic health record data, and genomic data to characterize the time sequence of changes in retinal layer thicknesses in AMD, as well as epidemiologic and genetic associations between retinal layer thicknesses and AMD. DESIGN: Cohort study. PARTICIPANTS: Forty-four thousand eight hundred twenty-three individuals from the UK Biobank (enrollment age range, 40-70 years; 54% women; median follow-up, 10 years). METHODS: The Topcon Advanced Boundary Segmentation algorithm was used for retinal layer segmentation. We associated 9 retinal layer thicknesses with prevalent AMD (present at enrollment) in a logistic regression model and with incident AMD (diagnosed after enrollment) in a Cox proportional hazards model. Next, we associated AMD-associated genetic alleles, individually and as a polygenic risk score (PRS), with retinal layer thicknesses. All analyses were adjusted for age, age-squared (age2), sex, smoking status, and principal components of ancestry. MAIN OUTCOME MEASURES: Prevalent and incident AMD. RESULTS: Photoreceptor segment (PS) thinning was observed throughout the lifespan of individuals analyzed, whereas retinal pigment epithelium (RPE) and Bruch's membrane (BM) complex thickening started after 57 years of age. Each standard deviation (SD) of PS thinning and RPE-BM complex thickening was associated with incident AMD (PS: hazard ratio [HR], 1.35; 95% confidence interval [CI], 1.23-1.47; P = 3.7 × 10-11; RPE-BM complex: HR, 1.14; 95% CI, 1.06-1.22; P = 0.00024). The AMD PRS was associated with PS thinning (ß, -0.21 SD per twofold genetically increased risk of AMD; 95% CI, -0.23 to -0.19; P = 2.8 × 10-74), and its association with RPE-BM complex was U-shaped (thinning with AMD PRS less than the 92nd percentile and thickening with AMD PRS more than the 92nd percentile). The loci with strongest support for genetic correlation were AMD risk-raising variants Complement Factor H (CFH):rs570618-T, CFH:rs10922109-C, and Age-Related Maculopathy Susceptibility 2 (ARMS2)/High-Temperature Requirement Serine Protease 1 (HTRA1):rs3750846-C on PS thinning and SYN3/Tissue Inhibitor of Metalloprotease 3 (TIMP3):rs5754227-T on RPE-BM complex thickening. CONCLUSIONS: Epidemiologically, PS thinning precedes RPE-BM complex thickening by decades and is the retinal layer most strongly predictive of future AMD risk. Genetically, AMD risk variants are associated with decreased PS thickness. Overall, these findings support PS thinning as an early-stage biomarker for future AMD development.

Cilioretinal Artery Occlusion as the Presenting Manifestation of Left Atrial Myxoma.

Purpose: This work reports a case of left atrial myxoma presenting with cilioretinal artery occlusion. Methods: A case report is discussed. Results: A 57-year-old man was referred for acute vision loss in the left eye after a workup including electrocardiogram, magnetic resonance imaging of the brain without contrast, computed tomography angiography of the head and neck, erythrocyte sedimentation rate, and C-reactive protein had negative results. Examination revealed cilioretinal artery occlusion with visible emboli. Because an echocardiogram was not performed, the patient was referred to the emergency department. Echocardiogram revealed a large left atrial mass prolapsing into the left ventricle. The mass was excised, and pathology showed myxoma. Conclusions: This is the first case to our knowledge of isolated cilioretinal artery occlusion as the initial presentation of an atrial myxoma. Thorough and complete workup was crucial to averting further morbidity and mortality.

Management of Large Subretinal Gas Bubble After Pneumatic Retinopexy With Head-Positioning Maneuver.

Purpose: This work reports on the management of a large subretinal gas bubble after pneumatic retinopexy. Methods: A case report is discussed. Results: We report a case of subretinal gas after pneumatic retinopexy for rhegmatogenous retinal detachment that was managed with a series of head-positioning maneuvers to allow the subretinal gas to migrate into the vitreous cavity through the retinal break. Despite the subretinal bubbles being larger than the retinal break, this approach eliminated the subretinal gas and averted surgical intervention. Conclusions: Subretinal gas after pneumatic retinopexy can be successfully managed by head-positioning maneuvers in some cases, even if the subretinal gas bubble is larger than the retinal break.

Deep Learning of the Retina Enables Phenome- and Genome-Wide Analyses of the Microvasculature.

BACKGROUND: The microvasculature, the smallest blood vessels in the body, has key roles in maintenance of organ health and tumorigenesis. The retinal fundus is a window for human in vivo noninvasive assessment of the microvasculature. Large-scale complementary machine learning-based assessment of the retinal vasculature with phenome-wide and genome-wide analyses may yield new insights into human health and disease. METHODS: We used 97 895 retinal fundus images from 54 813 UK Biobank participants. Using convolutional neural networks to segment the retinal microvasculature, we calculated vascular density and fractal dimension as a measure of vascular branching complexity. We associated these indices with 1866 incident International Classification of Diseases-based conditions (median 10-year follow-up) and 88 quantitative traits, adjusting for age, sex, smoking status, and ethnicity. RESULTS: Low retinal vascular fractal dimension and density were significantly associated with higher risks for incident mortality, hypertension, congestive heart failure, renal failure, type 2 diabetes, sleep apnea, anemia, and multiple ocular conditions, as well as corresponding quantitative traits. Genome-wide association of vascular fractal dimension and density identified 7 and 13 novel loci, respectively, that were enriched for pathways linked to angiogenesis (eg, vascular endothelial growth factor, platelet-derived growth factor receptor, angiopoietin, and WNT signaling pathways) and inflammation (eg, interleukin, cytokine signaling). CONCLUSIONS: Our results indicate that the retinal vasculature may serve as a biomarker for future cardiometabolic and ocular disease and provide insights into genes and biological pathways influencing microvascular indices. Moreover, such a framework highlights how deep learning of images can quantify an interpretable phenotype for integration with electronic health record, biomarker, and genetic data to inform risk prediction and risk modification.

Epimacular Inverted Retinal Flap Simulating an Epiretinal Membrane.

A 66-year-old man was referred for management of a visually significant epiretinal membrane (ERM) with persistent cystoid macular edema after surgery for recurrent retinal detachment with proliferative vitreoretinopathy. The membrane was noted to be particularly thick and vascularized on preoperative optical coherence tomography. During the subsequent vitrectomy, the "membrane" was found to be an inverted retinal flap and successfully removed. The inverted retinal flap was thought to have been related to retinal slippage during prior surgery. This is the first report of an epimacular inverted flap simulating an ERM and highlights the importance of careful review of preoperative imaging. [Ophthalmic Surg Lasers Imaging Retina. 2021;52:293-295.].

Impact of contact versus non-contact wide-angle viewing systems on outcomes of primary retinal detachment repair (PRO study report number 5).

BACKGROUND/AIMS: Vitrectomy to repair retinal detachment is often performed with either non-contact wide-angle viewing systems or wide-angle contact viewing systems. The purpose of this study is to assess whether the viewing system used is associated with any differences in surgical outcomes of vitrectomy for primary non-complex retinal detachment repair. METHODS: This is a multicenter, interventional, retrospective, comparative study. Eyes that underwent non-complex primary retinal detachment repair by either pars plana vitrectomy (PPV) alone or in combination with scleral buckle/PPV in 2015 were evaluated. The viewing system at the time of the retinal detachment repair was identified and preoperative patient characteristics, intraoperative findings and postoperative outcomes were recorded. RESULTS: A total of 2256 eyes were included in our analysis. Of those, 1893 surgeries used a non-contact viewing system, while 363 used a contact lens system. There was no statistically significant difference in single surgery anatomic success at 3 months (p=0.72), or final anatomic success (p=0.40). Average postoperative visual acuity for the contact-based cases was logMAR 0.345 (20/44 Snellen equivalent) compared with 0.475 (20/60 Snellen equivalent) for non-contact (p=0.001). After controlling for numerous confounding variables in multivariable analysis, viewing system choice was no longer statistically significant (p=0.097). CONCLUSION: There was no statistically significant difference in anatomic success achieved for primary retinal detachment repair when comparing non-contact viewing systems to contact lens systems. Postoperative visual acuity was better in the contact-based group but this was not statistically significant when confounding factors were controlled for.

Widefield Swept-Source OCTA in Vogt-Koyanagi-Harada Disease.

Herein, the authors describe an initial case report of widefield swept-source optical coherence tomography angiography (SS-OCTA) in Vogt-Koyanagi-Harada (VKH) disease. When compared to fluorescent angiography, indocyanine green angiography, and enhanced-depth OCT - upon which the revised criteria for VHK are based - widefield SS-OCTA enables detection of vitreous inflammation, noninvasive identification of characteristic areas of flow void at the level of choriocapillaris in the acute phase and may be a novel valuable tool not only for noninvasive diagnosis and monitoring of disease progression, persistence, resolution, and recurrence to guide therapy in VKH disease in the future. [Ophthalmic Surg Lasers Imaging Retina. 2020;51:407-412.].

Detection of retinal microvascular changes in von Hippel-Lindau disease using optical coherence tomography angiography.

PURPOSE: Von Hippel-Lindau (VHL) disease is a hereditary disorder that can lead to ophthalmic manifestations, including retinal capillary hemangioma (RCH). The diagnosis of RCH is often guided by wide-field fluorescein angiography. In some cases, optical coherence tomography angiography (OCT-A) serves as a non-invasive alternative to FA. Herein, we used OCT-A to examine the macular microvasculature in patients with VHL disease. SUBJECTS: Subjects were selected from patients with a diagnosis of VHL. The control group included eyes without retinal diagnosis from patients with an episode of unilateral retinal detachment or trauma and age ≤ 50 years old. METHODS: Subjects were scanned on the Optovue RTVue-XR device to acquire 3mm x 3mm OCT-A images of the superficial (SCP) and deep capillary plexus (DCP). SCP and DCP vessel density (VD) were calculated after the images were binarized. Furthermore, for subjects with RCH, each OCT-A image was divided equally into four quadrants. SCP and DCP VD of quadrants with RCH were compared to those without RCH. T-tests were performed for statistical analysis. RESULTS: 67 eyes with a history of VHL disease were included as study subjects, while 16 eyes were included as controls. Significant increases in VD were found in patients with VHL disease for both the SCP (p = 0.0441) and DCP (p = 0.0344). When comparing quadrants with associated RCH development to those without, we found no significant difference in SCP VD (p = 0.160) or DCP VD (p = 0.484). CONCLUSIONS: OCT-A can detect changes in the retinal microvasculature in the macula of patients with VHL disease. OCT-A imaging may be an additional tool for screening and early detection of patients at risk of developing ocular complications of VHL disease. Future studies should explore subtle progression on OCT-A associated with the pathogenesis and development of RCH, particularly with larger scan patterns.

FACTORS ASSOCIATED WITH THE USE OF 360-DEGREE LASER RETINOPEXY DURING PRIMARY VITRECTOMY WITH OR WITHOUT SCLERAL BUCKLE FOR RHEGMATOGENOUS RETINAL DETACHMENT AND IMPACT ON SURGICAL OUTCOMES (PRO STUDY REPORT NUMBER 4).

PURPOSE: To determine factors associated with 360-degree laser retinopexy (360LR) during primary pars plana vitrectomy ± scleral buckle for rhegmatogenous retinal detachment (RRD) and its impact on surgical outcomes. METHODS: This is a multicenter, retrospective, interventional study. Patients undergoing primary pars plana vitrectomy or primary pars plana vitrectomy + scleral buckle for noncomplex primary RRD in 2015 were evaluated. Primary outcomes were single surgery anatomical success (SSAS) and final anatomical success. Secondary outcomes included final logarithm of the minimum angle of resolution visual acuity, epiretinal membrane formation, cystoid macular edema development, and number of subsequent vitrectomies. Multivariate regressions were performed. RESULTS: Two thousand two hundred and forty-eight surgeries by 61 surgeons were included; of which, 516 underwent 360LR. Younger age (P = 0.01), more retinal breaks (P = 0.01), more extensive RRD (P < 0.001), and surgeon ID (P < 0.001) were significantly associated with 360LR. No significant associations between 360LR and single surgery anatomical success (P = 0.44), epiretinal membrane formation (P = 0.14), cystoid macular edema development (P = 0.28), or number of subsequent vitrectomies (P = 0.41) were found. Controlling for case complexity, 360LR was significantly associated with lower final anatomical success (P < 0.001) and worse final logarithm of the minimum angle of resolution visual acuity (P < 0.001). CONCLUSION: Multiple factors influenced whether 360LR was performed during primary pars plana vitrectomy ± scleral buckle for RRD. However, 360LR was not associated with improved surgical outcomes, and in fact, it may be associated with poorer outcomes.

Myeloid sarcoma involving the greater wing of the sphenoid bone and additional skeletal sites presenting with unilateral proptosis and fevers.

We report a case of myeloid sarcoma with multifocal skeletal involvement, including the greater wing of the sphenoid bone. A 23-month-old boy presented with left-sided proptosis and fevers, and was found to have an infiltrative mass involving the left sphenoid bone on orbital imaging. Full body imaging further demonstrated multiple bony lesions in the pelvis, thoracic and lumbar vertebrae, bilateral femura, and left humerus, and biopsies of the humerus were consistent with myeloid sarcoma. The patient was started on a standard chemotherapy regimen and is responding well. Myeloid sarcoma presenting with proptosis due to sphenoid bone involvement with simultaneous multifocal skeletal involvement is very uncommon and highlights the importance of biopsy for establishing a definitive diagnosis.

Closure of Macular Hole Associated With Extreme High Myopia After Conventional Vitrectomy With ILM Peeling.

Macular hole associated with high myopia (MH-HM) and macular hole-associated retinal detachment (MH-RD) are two conditions found in eyes with pathologic myopia that often have poor postoperative outcomes. A discrepancy in size between the stretched retina and the posteriorly expanded sclera is a major factor in the pathogenesis. The authors report a case comprising both types of maculopathy, one in each eye. The eye with the MH-HM (right eye) represents the longest axial length ever reported to have successful macular hole closure by any technique. The authors conclude that traditional surgery can be an adequate treatment for such a challenging condition. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:e99-e101.].

Distinguishing White Dot Syndromes With Patterns of Choroidal Hypoperfusion on Optical Coherence Tomography Angiography.

BACKGROUND AND OBJECTIVE: To compare patterns of choroidal hypoperfusion in white dot syndromes (WDS) using optical coherence tomography angiography (OCTA). PATIENTS AND METHODS: Consecutive patients with WDS were imaged with either the Zeiss AngioPlex OCT Angiography (Carl Zeiss AG, Oberkochen, Germany) or the AngioVue OCT Angiography (Optovue, Fremont, CA) from February to November 2016. Four patients with acute posterior multifocal placoid pigment epitheliopathy (APMPPE), birdshot chorioretinopathy (BCR), presumed ocular histoplasmosis syndrome (POHS), and multiple evanescent white dot syndrome (MEWDS) were selected. This study was approved by the institutional review board at Massachusetts Eye and Ear. RESULTS: Unique patterns of choroidal hypoperfusion were observed. In POHS and MEWDS, areas of choroidal hypoperfusion correlated well with clinically observed pathology, but in APMPPE and BCR, they were more widespread. CONCLUSION: OCTA can identify different patterns of choroidal hypoperfusion in APMPPE, BCR, POHS, and MEWDS, which appears to be a shared feature of WDS. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:638-646.].