Papers by Richard B Rosen
Ophthalmology, 2010
Objective-To describe the natural history of eyes with drusenoid pigment epithelial detachments (... more Objective-To describe the natural history of eyes with drusenoid pigment epithelial detachments (DPED) associated with age-related macular degeneration (AMD). Participants-Among 4757 participants enrolled in the Age-Related Eye Disease Study (AREDS), 255 were identified as having DPED in at least one eye and having 5 or more years of follow-up after the initial detection of the DPED. Methods-Baseline and annual fundus photographs were evaluated for the evolution of the fundus features and the development of advanced AMD in the forms of central geographic atrophy (CGA) or neovascular (NV) AMD. Kaplan-Meier analyses of progression to advanced AMD and of moderate vision loss (≥15 letters compared with baseline) were performed. Results-A total of 311 eyes (from 255 participants) with DPED were followed for a median follow-up time of 8 years subsequent to the initial detection of a DPED. Of the 282 eyes that did not have advanced AMD at baseline, advanced AMD developed within 5 years in 119 eyes (42%) (19% progressing to CGA and 23% to NV-AMD). In the remaining eyes that did not develop advanced AMD (n = 163), progressive fundus changes, typified by the development of calcified drusen and pigmentary changes, were detected. Visual decline was prominent among study eyes, with
Eye (London, England), 2014
To investigate the relationship between retinal sensitivity (RS) assessed by microperimetry (MP) ... more To investigate the relationship between retinal sensitivity (RS) assessed by microperimetry (MP) and retinal structural changes in patients with resolved central serous chorioretinopathy (CSC). Spectral domain optical coherence tomography (OCT) examination and MP tests were performed in patients with resolved CSC. Point-to-point correlation was performed between RS and corresponding retinal structural changes using Pearson's correlation analysis. In addition, in a 1-mm zone in the central fovea, a correlation was calculated between the mean RS and the mean central retinal thickness (CRT). Eighty-four eyes were analyzed. The total number of MP test points was 1092 (84 eyes × 13 points). The mean RS and retinal point thickness (RPT) of all test points were 13.53±3.84 dB and 208.6±48.0 μm, respectively. The RS and RPT were significantly decreased in the test points with loss of the ellipsoid portion of the inner segments (EPIS) (P<0.0001). Within the 1-mm foveal center zone, the...
Ophthalmology, 2011
Purpose-To determine the area and enlargement rate (ER) of geographic atrophy (GA) in patients wi... more Purpose-To determine the area and enlargement rate (ER) of geographic atrophy (GA) in patients with age-related macular degeneration (AMD) using the spectral-domain optical coherence tomography (SDOCT) fundus image. Design-Prospective longitudinal natural history study Participants-Eighty-six eyes of 64 patients with at least 6 months follow-up. Methods-Patients with GA secondary to AMD were enrolled in this study. Macular scans were performed using the Cirrus SDOCT (Carl Zeiss Meditec, Dublin CA). The areas of GA identified on the SDOCT fundus images were quantified using a digitizing tablet. Reproducibility of these measurements was assessed and the ER of GA was calculated. The usefulness of performing square root transformations of the lesion area measurements was explored. Main Outcome Measure-Enlargement rate of GA Results-At baseline, 27% of eyes had a single area of GA. The mean total area at baseline was 4.59mm 2 (1.8 disc areas (DA)). The mean follow up time was 1.24 years. Reproducibility, as assessed with the intraclass correlation coefficient (ICC), was excellent on both the original area scale (ICC = 0.995) and the square-root scale (ICC=0.996). Inter-grader differences were not an important source of variability in lesion size measurement (ICC=0.999, 0.997). On average, the ER of GA per year was 1.2 mm 2 (0.47 DA; range [0.01-3.61 mm 2 /year]. The ER correlated with the initial area of GA (r=0.45, p<0.001), but there were variable growth rates for any given baseline area. When the square root transformation of the lesion area measurements was used as a measure of lesion size, the enlargement rate (0.28 mm/yr
Investigative Ophthalmology & Visual Science, Apr 28, 2009
Background and aims: The aim was to correlate retinal sensitivity as determined by scanning laser... more Background and aims: The aim was to correlate retinal sensitivity as determined by scanning laser ophthalmoscope microperimetry (SLO-MP) in glaucomatous eyes with paracentral visual field (VF) defects detected by standard automated perimetry (SAP). Methods: Twenty eyes with glaucomatous optic neuropathy and an SAP VF defect involving the central 16 test points (at least one point with p<1% in the 24–2 VF) were enrolled. Eyes with diseases other than glaucoma were excluded. All patients underwent SLO-MP and SAP of the central 10°. Results from each eye were divided into four quadrants for analysis. Normal and abnormal quadrants by SAP were compared with the corresponding normal and abnormal quadrants by SLO-MP. Regression analysis was used to correlate the mean threshold values (dB) of SLO-MP and SAP in each quadrant. Macular optical coherence tomography (OCT) was performed when there was a disagreement between functional tests. Results: The mean age and VF mean deviation were 60.8 (13.4) years and −7.3 (6.1) dB, respectively. There was a significant correlation between SLO-MP and SAP results in all quadrants (r2⩾0.68, p<0.001). All abnormal SAP quadrants had a corresponding abnormal SLO-MP quadrant. However, 21% of the normal SAP quadrants had an abnormal corresponding microperimetry result; a corresponding significant reduction in total macular thickness measured by OCT was present in 75% of these quadrants. Conclusions: Macular sensitivity evaluated by SLO-MP correlates significantly with SAP paracentral VF defects. SLO-MP detected retinal sensitivity reduction in areas of OCT structural damage with normal SAP and suggests that subtle paracentral functional deficits may be present in many more eyes with established glaucoma than generally assumed.
Acta Ophthalmologica, 2019
PurposeTo investigate the progression characteristics of ellipsoid zone (EZ) loss in eyes with ma... more 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...
Investigative Ophthalmology & Visual Science, 2011
International Journal of Ophthalmology, 2020
• AIM: To test our hypothesis that activation of protein kinase A (PKA) signal pathway by β-adren... more • AIM: To test our hypothesis that activation of protein kinase A (PKA) signal pathway by β-adrenergic agonist plays an important role in the protecting of cultured retinal pigment epithelial (RPE) cells against the hydroxychloroquine (HCQ) toxicity. • METHODS: Cultured human RPE cells were treated with 1) HCQ, 2) HCQ with salbutamol (a β2-adrenergic receptor agonist), and 3) HCQ with salbutamol and a PKA inhibitor, and compared these to 4) untreated cells (controls). After treated for 24h, cell vacuolation, cells viability, PKA and PKA kinase activity levels were determined by the measurement of the size of vacuoles using Image J software, the cell counting with a dye-exclusion testing, Western blot and PKA kinase detection, respectively. • RESULTS: Cell vacuolation and cell death of cultured RPE cells were significantly increased by the treatment of HCQ. Salbutamol significantly elevated PKA and PKA activity levels and this was associated with the inhibition of the vacuolation and cell death. The PKA inhibitor significantly decreased the PKA levels and eliminated the protective effects of salbutamol on HCQ-treated RPE cells. • CONCLUSION: The PKA pathway plays an important role in the protective effects of β2-adrenergic agonist on the RPE cells against HCQ toxicity. These findings reveal a novel potential strategy against HCQ retinopathy by treatment with PKA activating medications.
Biomedical Optics Express, 2019
Computed tomography (CT), ultrasound, and magnetic resonance imaging have been used to image and ... more Computed tomography (CT), ultrasound, and magnetic resonance imaging have been used to image and diagnose diseases of the human heart. By gating the acquisition of the images to the heart cycle (gated imaging), these modalities enable one to produce 3D images of the heart without significant motion artifact and to more accurately calculate various parameters such as ejection fractions [1-3]. Unfortunately, these imaging modalities give inadequate resolution when investigating embryonic development in animal models. Defects in ...
We study the impact of higher dimension operators in the inflaton Lagrangian on the non-gaussiani... more We study the impact of higher dimension operators in the inflaton Lagrangian on the non-gaussianity of the scalar spectrum. These terms can strongly enhance the effect without spoiling slow-roll, though it is difficult to exceed f NL ∼ 1, because the scale which suppresses the operators cannot be too low, if we want the effective field theory description to make sense. In particular we explicitly calculate the 3-point function given by an higher derivative interaction of the form (∇φ) 4 , which is expected to give the most important contribution. The angular dependence of the result turns out to be quite different from the minimal case without higher dimension operators.
Nutrients, 2021
The study was designed to: (1) Analyze and create protocols of obtaining measurements using the M... more The study was designed to: (1) Analyze and create protocols of obtaining measurements using the Macular Pigment Reflectometry (MPR). (2) To assess the agreement of MPOD measurements obtained using the heterochromatic flicker photometry (MPS II) and MPR. (3) To obtain the lutein and zeaxanthin optical density obtained using the MPR in the central one-degree of the macula. The measurements were performed using the MPR and heterochromatic flicker photometry. The MPR measurements were performed twice without pupillary dilation and twice following pupillary dilation. The MPR measurements were performed for a 40-s period and the spectrometer signal was parsed at different time points: 10–20, 10–30, 10–40, 20–30, 20–40, and 30–40 s. The MPR analyzes the high-resolution spectrometer signal and calculates MPOD, lutein optical density and zeaxanthin optical density automatically. The MPR-MPOD data was compared with MPPS II-MPOD results. The MPR-MPOD values are highly correlated and in good ag...
Antioxidants, 2021
Age-related macular degeneration (AMD) remains a leading cause of modifiable vision loss in older... more Age-related macular degeneration (AMD) remains a leading cause of modifiable vision loss in older adults. Chronic oxidative injury and compromised antioxidant defenses represent essential drivers in the development of retinal neurodegeneration. Overwhelming free radical species formation results in mitochondrial dysfunction, as well as cellular and metabolic imbalance, which becomes exacerbated with increasing age. Thus, the depletion of systemic antioxidant capacity further proliferates oxidative stress in AMD-affected eyes, resulting in loss of photoreceptors, neuroinflammation, and ultimately atrophy within the retinal tissue. The aim of this systematic review is to examine the neuroprotective potential of the xanthophyll carotenoids lutein, zeaxanthin, and meso-zeaxanthin on retinal neurodegeneration for the purpose of adjunctive nutraceutical strategy in the management of AMD. A comprehensive literature review was performed to retrieve 55 eligible publications, using four datab...
Current Eye Research, 2021
ABSTRACT Purpose: Lipopolysaccharide (LPS) can activate Toll-like receptor 4 (TLR4) and increase ... more ABSTRACT Purpose: Lipopolysaccharide (LPS) can activate Toll-like receptor 4 (TLR4) and increase the expression of CXCL1 and CXCL2, the potent neutrophils chemoattractants, in various cell types. These effects have not been previously reported in the uveal melanocytes. This study was designed to investigate the effects of LPS on the activation of TLR4 and expression of CXCL1/CXCL2 in cultured human uveal melanocytes and the relevant signal pathways. Methods: Effects of LPS on the expression of TLR4 were tested using real-time PCR, flow cytometry and fluorescence immunostaining. Effects of LPS-induced expression/secretion of CXCL1/CXCL2 were studied using real-time PCR in cell lysates and ELISA in conditioned media of cultured uveal melanocytes. Activated NF-κB and phosphorylated MAPK signals were tested in cells with and without LPS treatment using flow cytometry. Effects of various signal inhibitors on p38, ERK1/2, JNK1/2 and NF-κB on the secretion of CXCL1/CXCL2 were tested by ELISA. The effects of neutralized antibodies of CXCL1/CXCL2 on the severity of LPS-induced uveitis were tested in a mouse model. Results: LPS stimulation increased the expression of TLR4 mRNA and protein in culture uveal melanocytes. Constitutive secretion of CXCL1/CXCL2 was detected in uveal melanocytes and was significantly increased dose- and time-dependently by LPS stimulation. LPS mainly increased the activated NF-κB and phosphorylated JNK1/2. LPS-induced expression of CXCL1/CXCL2 was blocked by NF-κB and JNK1/2 inhibitors. The severity of LPS-induced uveitis was significantly inhibited by neutralizing antibody to CXCL1/CXCL2 Conclusions: This is the first report on the LPS-induced expression of CXCL1 and CXCL2 by uveal melanocytes via the activation of TLR4. These results suggest that uveal melanocytes may play a role in the immune reaction that eliminates the invading pathogens. Conversely, an excessive LPS-induced inflammatory reaction may also lead to the development of inflammatory ocular disorders, such as non-infectious uveitis.
Ophthalmologica, 2018
Objective: To compare the anatomic and visual outcomes in primary rhegmatogenous retinal detachme... more Objective: To compare the anatomic and visual outcomes in primary rhegmatogenous retinal detachment repair involving combined pars plana vitrectomy (PPV)/scleral buckle (SB) using a sutureless belt loops technique versus a conventional sutured buckle technique. Methods: This is a retrospective, consecutive, interventional, comparative case series study using patients treated for primary retinal detachment who underwent the SB procedure in combination with PPV. Details regarding anatomic and visual outcome were analyzed. Results: Thirty-five eyes were included in this study: 18 eyes (18 patients) treated with combined PPV and SB performed using a sutureless belt loops technique (group A) and 17 eyes (17 patients) treated with combined PPV and SB sutured to the sclera (group B). Successful anatomic attachment and appropriate buckle height were achieved in all 35 cases. There was 1 case of redetachment in each group during the follow-up: 1/17 (5.9%) in group A and 1/18 (5.6%) in group B (p = 0.97). No cases of buckle infection, extrusion, or intrusion were noted during the follow-up period. Conclusion: SBs installed using a belt loops sutureless technique appear to be as safe and effective as those applied using conventional suturing for repair of retinal detachment, with similar anatomic and functional outcomes.
Journal of VitreoRetinal Diseases, 2018
Retinectomy can be complicated by recurrent retinal elevation and subretinal fluid (SRF) accumula... more Retinectomy can be complicated by recurrent retinal elevation and subretinal fluid (SRF) accumulation secondary to tractional chorioretinal adhesion band formation and contraction. Classically, this complication requires repeat vitrectomy with destruction of adhesion bands using the vitrectomy instrument. We present a novel, nonoperative technique utilizing neodymium-yttrium-aluminum-garnet (Nd:YAG) laser to address tractional retinal elevation of a retinectomy edge causing SRF accumulation secondary to peripheral chorioretinal adhesion formation after retinectomy. Nd:YAG laser was used to perform targeted adhesiolysis to release the tractional forces on the retina, after which argon laser retinopexy was performed. Retinal reattachment with resolution of SRF was achieved without the need for reoperation.
Operative Dictations in Ophthalmology, 2017
Panretinal photocoagulation (PRP) uses light energy to create thermal injury to the retinal tissu... more Panretinal photocoagulation (PRP) uses light energy to create thermal injury to the retinal tissue. When PRP is applied to areas of poorly perfused retina, pathologic levels of vascular endothelial growth factor (VEGF) are suppressed. PRP is an effective method of treating ischemic retinal vascular disease such as proliferative diabetic retinopathy (PDR). Fluorescein angiography should be performed to identify areas of neovascularization and retinal ischemia to guide application of PRP. A clear view of the fundus facilitates delivery of PRP. Effective delivery of PRP may be limited or delayed if the ocular media is obscured by corneal edema, cataract, and/or vitreous hemorrhage.
The British journal of ophthalmology, Sep 1, 2017
To assess peripapillary perfused capillary density (PCD) in primary open-angle glaucoma (POAG) ac... more To assess peripapillary perfused capillary density (PCD) in primary open-angle glaucoma (POAG) across stage of disease. In this observational, cross-sectional study, 60 eyes with varying stages of POAG and 24 control eyes were imaged on a spectral domain optical coherence tomography angiography system (AngioVue, Optovue, Fremont, California, USA) generating images centred on the optic nerve head. Major blood vessels were removed using custom automated software. PCD was calculated as a percentage as the ratio of pixels associated with perfused capillaries to the total number of pixels in the corresponding region-of-interest (ROI). Analysis of covariance was used to compare PCD among the subject groups and control for possible covariates. Area under the receiver operating characteristic curve (AROC) and sensitivity at 95% specificity were calculated to assess the capability of PCD to distinguish mild glaucoma from control. The Pearson's product-moment correlation coefficient was u...
Investigative ophthalmology & visual science, Jul 1, 2016
To compare perfused peripapillary capillary density in primary open-angle glaucoma (POAG), normal... more To compare perfused peripapillary capillary density in primary open-angle glaucoma (POAG), normal-tension glaucoma (NTG), and normal patients using optical coherence tomography angiography (OCT-A). A retrospective review of POAG, NTG, and normal patients imaged with OCT-A was performed. En face OCT angiograms identifying peripapillary vessels were obtained using a spectral-domain OCT system (Avanti RTVue-XR). A custom image analysis approach identified perfused peripapillary capillaries, quantified perfused capillary density (PCD), and generated color-coded PCD maps for 3.5- and 4.5-mm-diameter scans. We compared PCD values, PCD maps, standard automated perimetry (Humphrey visual field [HVF]) parameters, and OCT retinal nerve fiber layer (RNFL) thickness analyses across all groups. Forty POAG, 26 NTG, and 26 normal patients were included. Annular PCD in POAG (34.24 ± 6.76%) and NTG (37.75 ± 3.52%) patients was significantly decreased compared to normal patients (42.99 ± 1.81%) in 4....
Current diabetes reports, Dec 1, 2016
Diabetic retinopathy is a progressive microvascular disease that leads to increased vessel permea... more Diabetic retinopathy is a progressive microvascular disease that leads to increased vessel permeability, retinal ischemia, and retinal neovascularization. Optical coherence tomography angiography (OCTA) is a novel angiography technique that has the capability to advance our understanding of diabetic eye disease by providing high-resolution images of retinal and choroidal microvasculature blood flow and structure. Using OCTA, the vascular changes of diabetic retinopathy including microaneurysms, retinal non-perfusion, intraretinal microvascular abnormalities, and neovascularization can be clearly visualized. OCTA offers several advantages over fluorescein angiography (FA) in that it is faster, safer, and non-invasive, allows better visualization of retinal vessels in both the superficial and deep capillary layers, and can provide quantitative measurements of areas of non-perfusion of the macula and nerve. OCTA capillary perfusion density maps and average perfusion density values prov...
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Papers by Richard B Rosen