Richard Rosen

Sickle cell disease (SCD) exists on a phenotypic spectrum with variable genetic expressivity, making it difficult to assess an individual patient’s risk of complications at any particular point in time. Current and emerging SCD treatments, including CRISPR-based gene editing, result in a variable proportion of affected red blood cells (RBCs) still vulnerable to sickling. Clinical serological indicators of disease such as hemoglobin, indirect bilirubin, and reticulocyte count and clinical metrics including number of emergency department visits and hospitalizations over time often fall short in their ability to objectively quantify ischemic disease activity and efficacy of treatments. Clearly, better clinical biomarkers are needed. The rapidly developing field of oculomics leverages the transparent nature of the ocular tissue to directly study the retinal microvasculature in order to characterize the status of systemic diseases. In this case report, we demonstrate the ability of optic...

While plasmapheresis is well known to significantly improve both retinal findings and systemic manifestations associated with Waldenstrom macroglobulinemia, few reports exist documenting changes in optical coherence tomography angiography (OCT-A). The authors present a case of a patient with Waldenstrom macroglobulinemia who had resolution of white-centered peripheral retinal lesions and parafoveal outer nuclear layer hyperreflective material following plasmapheresis. Applying image analysis software to before and after OCT-A images, the authors were able to show an objective decrease in retinal capillary and large vessel density following plasmapheresis. This technique can be used to guide treatment and surveillance for patients with hyperviscosity-related retinopathy.

Retinal surface macrophages play key roles in the regulation of immune response, maintenance of vitreous clarity, and tissue repair. We examined the variation of parafoveal surface macrophages in a thyroid eye disease (TED) patient before and after treatment with teprotumumab (Tepezza, Horizon therapeutics). Pre- and posttreatment parafoveal surface macrophages were imaged using clinical en face OCT, and their density was assessed using a novel cell density mapping technique. Pretreatment, surface macrophage cell density was high. Macrophages had a nonuniform spatial distribution, and their appearance was round with few protrusions, consistent with an “activated” state. Posttreatment, cell density decreased. The macrophages were regularly spaced and had a ramified appearance and filopodia-like processes, consistent with a “quiescent” state. Surface macrophage density decreased as the Clinical Activity Score (CAS) decreased with teprotumumab treatment, suggesting a potential associat...

Purpose Fundus albipunctatus is an inherited cause of congenital stationary night blindness. The objective of this report is to describe structural changes occurring in a macular phenotype of a novel RDH5 mutation producing fundus albipunctatus using high-resolution in vivo imaging. A 62-year-old male with longstanding night blindness underwent imaging and genetic evaluation. High-resolution images of the photoreceptor mosaic were compared to those of a healthy subject. Results of a comprehensive ophthalmic evaluation and genetic testing with imaging including fundus photography, spectral-domain optical coherence tomography (OCT), fluorescein angiography (FA), OCT angiography (OCT-A), and adaptive optics scanning light ophthalmoscopy (AOSLO) are described. Observations The patient presented with visual acuity of 20/25 in both eyes and longstanding poor dark adaptation. Anterior segment examination was unremarkable. Fundoscopy revealed well circumscribed bilateral perifoveal mottling...

Scanning laser ophthalmoscopy (SLO) and optical coherence tomography (OCT) have substantially advanced ophthalmic imaging by improving the transversal resolution and axial resolution beyond that which can be achieved by the fundus camera. SLO improved the transversal resolution by using a small aperture in front of the photodetector and OCT improved the axial resolution by employing principles of coherence gating. Combining the two technologies into a single instrument produces an OCT instrument with the transversal resolution of an SLO but the finer axial resolution afforded by OCT principles, typically 5-10 um or less. Transversal resolution of both SLO and OCT instruments is limited by the aberrations of the eye to more than 15 um with a pupil size of less than 3 mm. Transversal resolution in both instruments can, in principle, be improved to less than 3 um resolution by enlarging the beam diameter. In practice, this often fails due to imperfections in the crystalline lens, corne...

The molecular signaling cascades that regulate angiogenesis and microvascular remodeling are fundamental to normal development, healthy physiology, and pathologies such as inflammation and cancer. Yet quantifying such complex, fractally branching vascular patterns remains difficult. We review application of NASA’s globally available, freely downloadable VESsel GENeration (VESGEN) Analysis software to numerous examples of 2D vascular trees, networks, and tree-network composites. Upon input of a binary vascular image, automated output includes informative vascular maps and quantification of parameters such as tortuosity, fractal dimension, vessel diameter, area, length, number, and branch point. Previous research has demonstrated that cytokines and therapeutics such as vascular endothelial growth factor, basic fibroblast growth factor (fibroblast growth factor-2), transforming growth factor-beta-1, and steroid triamcinolone acetonide specify unique “fingerprint” or “biomarker” vascula...

ABSTRACTPurposeSoft drusen and subretinal drusenoid deposits (SDD) aka reticular macular disease (RMD) characterize two pathways to advanced age-related macular degeneration (AMD). We propose these pathways are distinct diseases, with distinct genetic risks, serum risks and associated systemic diseases.Methods126 Subjects with AMD had: retinal imaging for RMD status, serum risks, genetic testing, and histories of cardiovascular disease (CVD) and stroke.Results62 subjects had RMD, 64 were nonRMD (drusen only), 51 had CVD or Stroke. RMD correlated significantly with: ARMS2 risk allele (p= 0.019); lower mean serum HDL (61±18 vs. 69±22 mg/dl, p= 0.038, t test); CVD and troke (34/51 RMD, p= 0.001).NonRMD correlated/trended with APOE2 (p= 0.032) and CETP (p= 0.072) risk alleles. 97 subjects total had some drusen, which correlated with CFH risk (p= 0.016). Multivariate independent risks for RMD were: CVD and Stroke (p= 0.008), and ARMS2 homozygous risk (p= 0.038).ConclusionThe RMD and soft...

ABSTRACTImportanceHigh-risk vascular diseases (HRVs) may remain undetected until catastrophe ensues. Detection from non-invasive retinal imaging would be highly significant.ObjectiveTo demonstrate that certain lesions of Age-Related Macular Degeneration (AMD) found on retinal imaging correlate with co-existing HRVs.DesignCross-sectional cohort study. Two years. Retinal image graders blinded to HRV status.Setting2 retina referral clinics.Participants151 consecutive AMD patients, ages 50-90, 97 females, 54 males, with lesions of soft drusen and/or subretinal drusenoid deposits (SDD). 12 others approached, 10 refused, 2 excluded.MethodsPatients were classified by retinal imaging into SDD (SDD present, +/- drusen) or nonSDD (soft drusen only), and by history into HRV (cardiac pump defect (myocardial infarction (MI), coronary artery bypass grafting (CABG), congestive heart failure (CHF)), valve defect, and carotid stroke) or nonHRV, with serum risk factors and medical histories.Main Outc...

Introduction. We present a case of serpiginous choroidopathy (SC) with novel OCTA and en face OCT reflectance findings which help identify subclinical disease progression. Case Presentation. En face OCT reflectance images demonstrated outer retinal tubules (ORT) at the serpiginous lesion margins of affected and unaffected retina on multimodal imaging. OCTA findings demonstrate variable dropout of choriocapillaris in “normal” retina beyond lesion borders which was not visible on standard imaging and which demonstrated a clear transition zone beyond the ORT. Discussion. This is the first report of choriocapillaris atrophy identified on OCTA not identified on traditional multimodal imaging in serpiginous choroidopathy. Damage to vasculature only visible with OCTA may help characterize the distribution of inflammation, aiding in monitoring of suppression not illustrated by traditional imaging and which may threaten the central macula. ORT in SC suggest death and reorganization of outer ...

PurposeTo investigate the progression characteristics of ellipsoid zone (EZ) loss in eyes with macular telangiectasia type 2 (MacTel) as reflected by area and linear measurements, and their relevance for visual acuity.MethodsParticipants were selected from the MacTel Study cohort. Linear and area measurements of EZ loss were performed in Spectral‐Domain Optical Coherence Tomograph (SD‐OCT) volume scans. Progression characteristics and correlations between linear and area measurements were analysed using linear mixed effects models.ResultsA total of 134 eyes of 70 patients were included (85 eyes with follow‐up, mean 4.7 years, range: 1.4–8 years). Ellipsoid zone (EZ) loss significantly progressed at a mean annual increment of 0.057 mm2 (p = 0.005). The progression rate was non‐linear and interacted significantly with initial EZ lesion size indicating an exponential growth before reaching a plateau. There was a strong heterogeneity in area sizes between fellow eyes. EZ break length ha...

PURPOSE To develop a consensus nomenclature for reporting optical coherence tomography angiography (OCTA) findings in retinal vascular disease (e.g., diabetic retinopathy, retinal vein occlusion) by international experts. DESIGN Delphi-based survey SUBJECTS, PARTICIPANTS AND/OR CONTROLS: Twenty-five retinal vascular disease and OCTA imaging experts METHODS, INTERVENTION, OR TESTING: A Delphi method of consensus development was used, comprising two rounds of online questionnaires, followed by a face-to-face meeting conducted virtually. Twenty-five experts in retinal vascular disease and retinal OCTA imaging were selected to constitute the OCTA Nomenclature in Delphi Study Group for retinal vascular disease. The four main areas of consensus were: definition of parameters of "widefield (WF)" OCTA, measurement of decreased vascular flow on conventional and WF-OCTA, nomenclature of OCTA findings, and OCTA in retinal vascular disease management and staging. The study endpoint was defined by the degree of consensus for each question: "strong consensus" was defined as ≥ 85% agreement, "consensus" as 80-84% and "near consensus" as 70-79%. MAIN OUTCOME MEASURES Consensus and near-consensus on OCTA nomenclature in retinal vascular disease RESULTS: A consensus was reached that a meaningful change in percentage of flow on WF-OCTA imaging should be an increase or decrease ≥30% of the absolute imaged area of flow signal and that a "large area" of WF-OCTA reduced flow signal should also be defined as ≥ 30% of absolute imaged area. The presence of new vessels (NV) and intra-retinal microvascular abnormalities (IRMAs), the foveal avascular zone (FAZ) parameters, the presence and amount of "no flow" area and the assessment of vessel density in various retinal layers should be added for the staging and classification of DR. Decreased flow ≥ 30% of the absolute imaged area should define an ischemic central retinal vein occlusion (CRVO). Several other items did not meet consensus requirements or were rejected in the final discussion round. CONCLUSIONS This study provides international consensus recommendations for reporting OCTA findings in retinal vascular disease, which may help to improve the interpretability and description in clinic and clinical trials. Further validation in these settings is warranted and ongoing. Efforts are continuing to address unresolved questions.

Copyright © 2015 Xiaoliang L. Xu et al.This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Uvealmelanoma cells were inoculated into the choroid of nudemice and treatedwith orwithout intraocular injection of zeaxanthin. After 21 days, mice were sacrificed and the eyes enucleated. Histopathological analysis was performed in hematoxylin and eosin stained frozen sections. Melanoma developed rapidly in the control group (without treatment of zeaxanthin). Tumor-bearing eye mass and tumor mass in the control group were significantly greater than those in zeaxanthin treated group. Melanoma in the controlled eyes occupied a large part of the eye, was epithelioid in morphology, and was with numerous mitotic figures. Scleral perforation and extraocular extension were observed in half of the eyes. Melanomas in zeaxanthin treated eyes ...

Copyright © 2015 Chunyan Xue et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Zeaxanthin and lutein are two carotenoid pigments that concentrated in the retina, especially in the macula. The effects of lutein and zeaxanthin on the prevention and treatment of various eye diseases, including age-related macular degeneration, diabetic retinopathy and cataract, ischemic/hypoxia induced retinopathy, light damage of the retina, retinitis pigmentosa, retinal detachment, and uveitis, have been studied in different experimental animal models. In these animal models, lutein and zeaxanthin have been reported to have beneficial effects in protecting ocular tissues and cells (especially the retinal neurons) against damage caused by different etiological factors. The mechanisms responsible for these effects of lutein and zeaxa...

Pathophysiology of sickle cell disease (SCD) features intermittent vaso-occlusion of microcirculatory networks that facilitate ischemic damage. Past research has, however, relied on static images to characterize this active disease state. This study develops imaging metrics to more fully capture dynamic vascular changes, quantifying intermittent retinal capillary perfusion in unaffected controls and SCD patients using sequential optical coherence tomography angiography (OCT-A) scans. The results reveal significant dynamic variation of capillary perfusion in SCD patients compared to controls. This measurement of vaso-occlusive burden in patients would provide utility in monitoring of the disease state and in evaluating treatment efficacy.

Purpose: To report a case of release of vitreomacular traction (VMT) in a patient with a full thickness macular hole (FTMH) immediately following pneumatic vitreolysis (PV) combined with head bobbing movements. Methods: A 71-year-old female with VMT and an FTMH presented with blurred vision for 2 months to the level of 20/400. At her 1-month follow-up visit, PV was performed using C3F8 gas and she was instructed to perform the drinking bird technique for ten minutes. Results: Optical coherence tomography performed ten minutes after PV with head bobbing showed VMT release and a smaller FTMH. Visual acuity improved to 20/150 immediately afterwards and to 20/80 two months later. Conclusions: Using the drinking bird technique for a continuous period of time immediately following PV may encourage rapid VMT release. PV may be a feasible option for patients with VMT and FTMH who do not want surgery.

To investigate the capability of the prototype AC Cornea OCT (Ophthalmic Technologies Inc., Toronto, Ontario, Canada) for imaging eyes with opaque corneas. More than 50 eyes of patients were included in the study. The density of opacification influenced the ability of OCT to reveal anterior segment details. Imaging was limited by shadows cast by abnormal pigmentation or vascularity within the cornea. However, the system's unique coronal perspective capability was helpful in revealing occult spatial relationships. The AC Cornea OCT is valuable for examining eyes with opaque corneas and provides cross-sectional and coronal views helpful in formulating specific management strategies.

Wide-field handheld high frequency ultrasonography using a variable high frequency ultrasound system is an imaging modality in the frequency range of 35 to 50 MHz. Using a water bath immersion technique, high-resolution digital movies obtained from a variety of anterior segment ocular conditions were particularly helpful in establishing the diagnosis in each case. Images taken with the wide-field limbus-to-limbus mode provided a comprehensive picture of large and extensive lesions, whereas the focal mode was for small to medium lesions or specific areas of interest.

Twenty-three normal eyes were examined with the Intensity Profiling technique of 3D I-Scan and 52 normal eyes with the Automated technique of OTI-Scan 1000 ultrasound systems (Ophthalmic Technologies Inc., Toronto, Ontario, Canada). With the eye looking straight, the probe was applied on the temporal sclera. Scanning generated 3D image files. Coronal optic nerve measurements were obtained 3 mm behind the globe. The mean optic nerve sheath diameter was 4.8 mm (standard deviation = 0.6; range, 3.9 to 5.9 mm) with the Intensity Profiling technique, and 5.4 mm (standard deviation = 0.4; range, 4.4 to 6.0 mm) with the Automated technique. 3D ultrasound imaging can be used to obtain optic nerve measurements in vivo. Both the Intensity Profiling and the Automated techniques yielded measurements similar to current magnetic resonance imaging and computed tomography scan reports. Coronal "C-scan" sectioning can be used as a screening tool to measure optic nerve diameter prior to magnetic resonance imaging or computed tomography.

To assess mitochondrial dysfunction in vivo in ocular hypertension (OHT) and primary open-angle glaucoma (POAG) using retinal metabolic analysis. This was an observational, cross-sectional study performed from November 2015 to October 2016 at the New York Eye and Ear Infirmary of Mount Sinai. Thirty-eight eyes with varying stages of POAG, 16 eyes with OHT, and 32 control eyes were imaged on a custom fundus camera modified to measure full retinal thickness fluorescence at a wavelength optimized to detect flavoprotein fluorescence (FPF). Optical coherence tomography was used to measure the retinal ganglion cell-plus layer (RGC+) thickness. Macular FPF and the ratio of macular FPF to RGC+ thickness were the primary outcome variables and were compared among the three groups using an age-adjusted linear regression model. A mixed-effects model was used to assess correlations between FPF variables and clinical characteristics. Both macular FPF and the macular FPF/RGC+ thickness ratio were ...

Solar retinopathy is a rare form of retinal injury that occurs after direct sungazing. To enhance understanding of the structural changes that occur in solar retinopathy by obtaining high-resolution in vivo en face images. Case report of a young adult woman who presented to the New York Eye and Ear Infirmary with symptoms of acute solar retinopathy after viewing the solar eclipse on August 21, 2017. Results of comprehensive ophthalmic examination and images obtained by fundus photography, microperimetry, spectral-domain optical coherence tomography (OCT), adaptive optics scanning light ophthalmoscopy, OCT angiography, and en face OCT. The patient was examined after viewing the solar eclipse. Visual acuity was 20/20 OD and 20/25 OS. The patient was left-eye dominant. Spectral-domain OCT images were consistent with mild and severe acute solar retinopathy in the right and left eye, respectively. Microperimetry was normal in the right eye but showed paracentral decreased retinal sensiti...

To use fractal dimensional analysis to investigate retinal vascular disease patterns in patients with diabetic retinopathy using spectral domain optical coherence tomography angiography. A retrospective study was conducted which included 49 eyes from 26 control subjects and 58 eyes from 35 patients known to have diabetic retinopathy. Of the 58 eyes with known retinopathy, 31 were categorized as nonproliferative diabetic retinopathy (13 mild, 9 moderate, and 9 severe) and 27 were categorized as proliferative diabetic retinopathy. Optical coherence tomography angiography images were acquired using the RTVue XR Avanti (Optovue, Inc). Automated segmentation was obtained through both the superficial and deep capillary plexuses for each eye. Grayscale optical coherence tomography angiography images were standardized and binarized using ImageJ (National Institutes of Health). Fractal box-counting analyses were conducted using Fractalyse (ThéMA). Fractal dimensions (FDs) and correlation coe...

Epiretinal membranes (ERM) are a collection of glial or RPE cells and collagenous cells that can form a contractile fibrocellular scaffold. This contractile scaffold can lead to reduced vision and metamorphopsia. Epiretinal membranes can occur idiopathically or may be associated with uveitis, posterior vitreous detachments, retinal tears, retinal detachments, and vitreous hemorrhage. ERMs have been called by a variety of different names including macular pucker, cellophane maculopathy, preretinal macular fibrosis, epimacular membranes, and preretinal gliosis. Ocular coherence tomography (OCT) can help identify the presence of an ERM and elucidate characteristics of retinal thickening or distortion and the extent of the ERM. Prior to a surgical intervention, it is important to establish that the ERM is in fact the cause of the patient’s visual disturbance.

Our ability to visualize has often limited our ability to conceptualize, in medicine as well as technology, science, and mathematics. Before we were able to see the retina, our perspective of ocular disease was largely confined to disorders of the anterior segment, such as strabismus, corneal disease, conjunctivitis, and cataracts. Our understanding of blindness and amaurosis was hidden behind the seemingly impenetrable pupillary curtain.

In vivo microvascular imaging was performed on healthy and diseased retinas using an adaptive optics scanning light ophthalmoscope (AOSLO) employed with fluorescein angiography and non-confocal imaging techniques. With qualitative and quantitative image analyses, AOSLO provides a platform for characterizing retinal microvascular changes cross-sectionally and longitudinally due to disease progression or response to treatment.