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Nawash B, Ong J, Driban M, Hwang J, Chen J, Selvam A, Mohan S, Chhablani J. Prognostic Optical Coherence Tomography Biomarkers in Neovascular Age-Related Macular Degeneration. J Clin Med 2023; 12:jcm12093049. [PMID: 37176491 PMCID: PMC10179658 DOI: 10.3390/jcm12093049] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2023] [Revised: 04/13/2023] [Accepted: 04/19/2023] [Indexed: 05/15/2023] Open
Abstract
Optical coherence tomography has revolutionized the diagnosis and management of neovascular age-related macular degeneration. OCT-derived biomarkers have the potential to further guide therapeutic advancements with anti-vascular endothelial growth factor; however, the clinical convergence between these two tools remains suboptimal. Therefore, the aim of this review of literature was to examine the current data on OCT biomarkers and their prognostic value. Thirteen biomarkers were analyzed, and retinal fluid had the strongest-reported impact on clinical outcomes, including visual acuity, clinic visits, and anti-VEGF treatment regimens. In particular, intra-retinal fluid was shown to be associated with poor visual outcomes. Consistencies in the literature with regard to these OCT prognostic biomarkers can lead to patient-specific clinical decision making, such as early-initiated treatment and proactive monitoring. An integrated analysis of all OCT components in combination with new efforts toward automated analysis with artificial intelligence has the potential to further improve the role of OCT in nAMD therapy.
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Affiliation(s)
- Baraa Nawash
- Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA
| | - Joshua Ong
- Michigan Medicine, University of Michigan, Ann Arbor, MI 48104, USA
| | - Matthew Driban
- Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA
| | - Jonathan Hwang
- Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA
| | - Jeffrey Chen
- Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA
| | - Amrish Selvam
- Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA
| | - Sashwanthi Mohan
- Ophthalmology, Medcare Hospital LLC, Dubai P.O. Box 215565, United Arab Emirates
- Education and Research, Rajan Eye Care Hospital Pvt Ltd., Chennai 600042, India
| | - Jay Chhablani
- Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA
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2
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Blasiak J, Sobczuk P, Pawlowska E, Kaarniranta K. Interplay between aging and other factors of the pathogenesis of age-related macular degeneration. Ageing Res Rev 2022; 81:101735. [PMID: 36113764 DOI: 10.1016/j.arr.2022.101735] [Citation(s) in RCA: 32] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2022] [Revised: 08/03/2022] [Accepted: 09/12/2022] [Indexed: 01/31/2023]
Abstract
Age-related macular degeneration (AMD) is a complex eye disease with the retina as the target tissue and aging as per definition the most serious risk factor. However, the retina contains over 60 kinds of cells that form different structures, including the neuroretina and retinal pigment epithelium (RPE) which can age at different rates. Other established or putative AMD risk factors can differentially affect the neuroretina and RPE and can differently interplay with aging of these structures. The occurrence of β-amyloid plaques and increased levels of cholesterol in AMD retinas suggest that AMD may be a syndrome of accelerated brain aging. Therefore, the question about the real meaning of age in AMD is justified. In this review we present and update information on how aging may interplay with some aspects of AMD pathogenesis, such as oxidative stress, amyloid beta formation, circadian rhythm, metabolic aging and cellular senescence. Also, we show how this interplay can be specific for photoreceptors, microglia cells and RPE cells as well as in Bruch's membrane and the choroid. Therefore, the process of aging may differentially affect different retinal structures. As an accurate quantification of biological aging is important for risk stratification and early intervention for age-related diseases, the determination how photoreceptors, microglial and RPE cells age in AMD may be helpful for a precise diagnosis and treatment of this largely untreatable disease.
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Affiliation(s)
- Janusz Blasiak
- Department of Molecular Genetics, University of Lodz, Pomorska 141/143, 90-236, Lodz, Poland.
| | - Piotr Sobczuk
- Emergency Medicine and Disaster Medicine Department, Medical University of Lodz, Pomorska 251, 92-209 Lodz, Poland; Department of Orthopaedics and Traumatology, Polish Mothers' Memorial Hospital - Research Institute, Rzgowska 281, 93-338 Lodz, Poland
| | - Elzbieta Pawlowska
- Department of Pediatric Dentistry, Medical University of Lodz, Pomorska 251, 92-216 Lodz, Poland
| | - Kai Kaarniranta
- Department of Ophthalmology, Institute of Clinical Medicine, University of Eastern Finland, P.O. Box 1627, FI-70211, Kuopio, Finland; Department of Ophthalmology, Kuopio University Hospital, KYS, P.O. Box 100, FI-70029 Finland
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3
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Lu Y, Zhou H, Zhou X, Chen Y, Wang RK. Correlation Between Laser Speckle Flowgraphy and OCT-Derived Retinal and Choroidal Metrics in Healthy Human Eye. Transl Vis Sci Technol 2022; 11:15. [PMID: 35704328 PMCID: PMC9206497 DOI: 10.1167/tvst.11.6.15] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2022] [Accepted: 05/17/2022] [Indexed: 12/02/2022] Open
Abstract
Purpose To investigate the correlation between laser speckle flowgraphy (LSFG) signals and the quantitative metrics derived from optical coherence tomography (OCT) in normal eyes. Methods LSFG, OCT, and OCT angiography (OCTA) imaging were performed on normal participants using a custom-designed LSFG system and a commercial swept-source OCT system. Mean (PWM) and amplitude (PWA) of the LSFG pulse waveform were selected to quantify the LSFG signals. Retinal and choroidal maps were obtained using the standard 6 × 6 mm OCT and OCTA scans. Structural and vascular metrics maps, including thickness, vessel area density, vessel skeleton density, and vessel diameter index of the retina, and choroidal thickness (CT), choroidal vessel volume (CVV) and choroidal vessel index (CVI), were employed to quantify the retinal and choroidal properties. Correlation analysis was then performed between the LSFG, retinal, and choroidal metrics maps. Results Twelve healthy participants aged 23 to 36 years were enrolled in this study. The spatial distribution of the PWM and PWA values was highly correlated with that of the CT and CVV metrics. On average, Spearman correlation coefficients (ρ) were 0.80 and 0.78 (all P < 0.001) for the correlations between PWM and CT and CVV, respectively, and were 0.61 and 0.63 (all P < 0.05) for the correlations between PWA and CT and CVV, respectively. In comparison, both PWM and PWA were generally weak or not correlated with all the retinal metrics and CVI. Conclusions LSFG signals were positively correlated with the choroidal thickness and vessel volume, suggesting choroidal blood flows dominate the LSFG signals at the area absent of large retinal vessels. Translational Relevance This study illustrates the dominant source of the LSFG signals in the eye.
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Affiliation(s)
- Yiming Lu
- Department of Bioengineering, University of Washington, Seattle, WA, USA
| | - Hao Zhou
- Department of Bioengineering, University of Washington, Seattle, WA, USA
| | - Xiao Zhou
- Department of Bioengineering, University of Washington, Seattle, WA, USA
| | - Yuxuan Chen
- Department of Bioengineering, University of Washington, Seattle, WA, USA
| | - Ruikang K. Wang
- Department of Bioengineering, University of Washington, Seattle, WA, USA
- Karalis Johnson Retina Center, Department of Ophthalmology, University of Washington, Seattle, WA, USA
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4
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Chiu YH, Huang JY, Huang YP, Pan SL. Osteoarthritis Is Associated With an Increased Risk of Age-Related Macular Degeneration: A Population-Based Longitudinal Follow-Up Study. Front Med (Lausanne) 2022; 9:854629. [PMID: 35620721 PMCID: PMC9127570 DOI: 10.3389/fmed.2022.854629] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2022] [Accepted: 04/20/2022] [Indexed: 11/26/2022] Open
Abstract
Aims To investigate the long-term risk of age-related macular degeneration (AMD) in persons with osteoarthritis (OA). Methods This retrospective cohort study first enrolled 71,609 subjects diagnosed with OA, and 236,169 without such a diagnosis between January 1, 2002 and December 31, 2005, from the Longitudinal Health Insurance Database 2005. All were aged 40–69. After excluding subjects who had pre-existing AMD and/or who had missing socioeconomic data, frequency matching by sex and age was performed. This resulted in there being 60,274 subjects in each of the final matched OA and non-OA groups. The study participants were followed up to the occurrence of AMD, death, or the end of 2011. We used Cox proportional-hazards regression to estimate the impact of OA on the risk of developing AMD, and performed subgroup analyses stratified by sex and age. Results The median follow-up time was 8.9 years, with an interquartile range of 1.4 years. The incidence rate of AMD in the OA group was 2.77 per 1,000 person-years [95% confidence interval (CI), 2.62–2.92], and in the non-OA group, 2.06 per 1,000 person-years (95% CI, 1.94–2.19). The adjusted hazard ratio (HR) of AMD for the OA group was therefore 1.30 (95% CI, 1.20–1.41). In the subgroup analysis stratified by sex for the OA group, the adjusted HRs of AMD were 1.29 in the women's stratum and 1.31 in the men's. When stratified by age, the adjusted HRs of AMD for the younger (40–54 years) and older (55–69 years) strata were 1.28 and 1.31, respectively. Conclusions Persons with OA have an increased risk of developing AMD, regardless of age and sex.
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Affiliation(s)
- Yi-Hsiang Chiu
- Department of Physical Medicine and Rehabilitation, National Taiwan University Hospital, Taipei, Taiwan
| | - Jehn-Yu Huang
- Department of Ophthalmology, National Taiwan University Hospital, Taipei, Taiwan
| | - Ya-Ping Huang
- Department of Physical Medicine and Rehabilitation, College of Medicine, National Taiwan University, Taipei, Taiwan.,Department of Physical Medicine and Rehabilitation, National Taiwan University Hospital, Yun-Lin Branch, Yun-Lin County, Taiwan
| | - Shin-Liang Pan
- Department of Physical Medicine and Rehabilitation, National Taiwan University Hospital, Taipei, Taiwan.,Department of Physical Medicine and Rehabilitation, College of Medicine, National Taiwan University, Taipei, Taiwan
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Raimondi R, Zollet P, De Rosa FP, Tsoutsanis P, Stravalaci M, Paulis M, Inforzato A, Romano MR. Where Are We with RPE Replacement Therapy? A Translational Review from the Ophthalmologist Perspective. Int J Mol Sci 2022; 23:ijms23020682. [PMID: 35054869 PMCID: PMC8775975 DOI: 10.3390/ijms23020682] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2021] [Revised: 12/28/2021] [Accepted: 12/30/2021] [Indexed: 02/06/2023] Open
Abstract
The retinal pigmented epithelium (RPE) plays a pivotal role in retinal homeostasis. It is therefore an interesting target to fill the unmet medical need of different retinal diseases, including age-related macular degeneration and Stargardt disease. RPE replacement therapy may use different cellular sources: induced pluripotent stem cells or embryonic stem cells. Cells can be transferred as suspension on a patch with different surgical approaches. Results are promising although based on very limited samples. In this review, we summarize the current progress of RPE replacement and provide a comparative assessment of different published approaches which may become standard of care in the future.
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Affiliation(s)
- Raffaele Raimondi
- IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089 Rozzano–Milan, Italy; (P.Z.); (M.S.); (M.P.); (A.I.)
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20072 Pieve Emanuele–Milan, Italy; (F.P.D.R.); (P.T.); (M.R.R.)
- Correspondence:
| | - Piero Zollet
- IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089 Rozzano–Milan, Italy; (P.Z.); (M.S.); (M.P.); (A.I.)
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20072 Pieve Emanuele–Milan, Italy; (F.P.D.R.); (P.T.); (M.R.R.)
| | - Francesco Paolo De Rosa
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20072 Pieve Emanuele–Milan, Italy; (F.P.D.R.); (P.T.); (M.R.R.)
| | - Panagiotis Tsoutsanis
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20072 Pieve Emanuele–Milan, Italy; (F.P.D.R.); (P.T.); (M.R.R.)
| | - Matteo Stravalaci
- IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089 Rozzano–Milan, Italy; (P.Z.); (M.S.); (M.P.); (A.I.)
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20072 Pieve Emanuele–Milan, Italy; (F.P.D.R.); (P.T.); (M.R.R.)
| | - Marianna Paulis
- IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089 Rozzano–Milan, Italy; (P.Z.); (M.S.); (M.P.); (A.I.)
- Institute of Genetic and Biomedical Research (IRGB), UOS of Milan, National Research Council of Italy, 20138 Milan, Italy
| | - Antonio Inforzato
- IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089 Rozzano–Milan, Italy; (P.Z.); (M.S.); (M.P.); (A.I.)
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20072 Pieve Emanuele–Milan, Italy; (F.P.D.R.); (P.T.); (M.R.R.)
| | - Mario R. Romano
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20072 Pieve Emanuele–Milan, Italy; (F.P.D.R.); (P.T.); (M.R.R.)
- Eye Center, Humanitas Gavazzeni-Castelli, 24128 Bergamo, Italy
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Verticchio Vercellin AC, Harris A, Chiaravalli G, Sacco R, Siesky B, Ciulla T, Guidoboni G. Physics-based modeling of Age-related Macular Degeneration-A theoretical approach to quantify retinal and choroidal contributions to macular oxygenation. Math Biosci 2021; 339:108650. [PMID: 34197878 DOI: 10.1016/j.mbs.2021.108650] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2021] [Revised: 06/23/2021] [Accepted: 06/23/2021] [Indexed: 10/21/2022]
Abstract
We developed a mathematical model to characterize how macular oxygenation may be affected by abnormalities in the retinal and choroidal oxygen supplies. The macular region is modeled as a layered structure including: ganglion cell and nerve fiber layers, inner plexiform layer, inner nuclear layer, outer plexiform layer, outer nuclear layer, inner segment of photoreceptors layer and retinal pigmented epithelium. Each layer is characterized by specific levels of oxygen consumption. The vitreous and the choroid are located at the macula boundary and provide oxygen via boundary conditions of Dirichlet type. The three capillary plexi (superficial, intermediate, and deep) of the retinal circulation pierce the macular layers and provide oxygen via a volumetric source that depends on the retinal blood flow. Oxygen profiles through the macular tissue are calculated by simulating the balance among oxygen supply, consumption and diffusion in: (a) physiological baseline conditions; (b) retinal blood flow reduced by 10%, 30% and 50% with respect to baseline; (c) choroidal oxygen level diminished by 10%, 30% and 50% with respect to baseline. Model simulations predict that: (1) the oxygenation of the foveal avascular zone is not affected by reduction in retinal blood flow; (2) a reduction in choroidal oxygen supply significantly affects the outer layers, especially the photoreceptors and outer nuclear layers; (3) the impact of reduction in choroidal oxygen supply is larger in the region more proximal to the macular center; (4) the impact of reduction in retinal blood flow is larger in the region more proximal to the macular periphery. The proposed mathematical model suggests that changes in retinal and choroidal oxygen supplies impact the oxygenation of the macular tissue differentially. These results may help better understand the pathogenesis of macular degeneration.
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Affiliation(s)
| | - Alon Harris
- Department of Ophthalmology, Icahn School of Medicine at Mount Sinai, New York, NY, United States of America.
| | - Greta Chiaravalli
- Italian Institute of Technology, Milano, Italy; Dipartimento di Fisica, Politecnico di Milano, Italy
| | - Riccardo Sacco
- Dipartimento di Matematica, Politecnico di Milano, Italy
| | - Brent Siesky
- Department of Ophthalmology, Icahn School of Medicine at Mount Sinai, New York, NY, United States of America
| | - Thomas Ciulla
- Vitreoretinal Medicine and Surgery, Midwest Eye Institute, Indianapolis, IN 46290, United States of America
| | - Giovanna Guidoboni
- Department of Electrical Engineering and Computer Science, Department of Mathematics, University of Missouri, Columbia, MO, United States of America
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7
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Wei X, Balne PK, Meissner KE, Barathi VA, Schmetterer L, Agrawal R. Assessment of flow dynamics in retinal and choroidal microcirculation. Surv Ophthalmol 2018; 63:646-664. [DOI: 10.1016/j.survophthal.2018.03.003] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2017] [Revised: 03/19/2018] [Accepted: 03/19/2018] [Indexed: 01/08/2023]
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8
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Burkemper B, McKean-Cowdin R, Choudhury F, Klein R, Gauderman WJ, Jiang X, Hsu C, Torres M, Varma R. Factors Associated with Age-Related Macular Degeneration in Chinese American Adults: The Chinese American Eye Study (CHES). Ophthalmol Retina 2018; 2:209-216. [PMID: 31047588 DOI: 10.1016/j.oret.2017.07.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2017] [Revised: 06/29/2017] [Accepted: 07/03/2017] [Indexed: 10/18/2022]
Abstract
OBJECTIVE To assess associations between age-related macular degeneration (AMD) and multiple factors comprising a conceptual model of AMD risk in a population of Chinese Americans, and to draw comparisons with a similar risk assessment of a Latino population. DESIGN A cross-sectional population-based study. PARTICIPANTS We enrolled 4582 Chinese Americans aged ≥50 residing in Monterey Park, California. METHODS Participants completed a comprehensive eye examination, including stereoscopic fundus photography and ocular biometric measurements. Fundus images were graded using a modified version of the Wisconsin Age-Related Maculopathy Grading System. MAIN OUTCOMES AND MEASURES Odds ratios for factors significantly modifying the risk of AMD and its related retinal lesions. RESULTS Of the eligible participants, 4172 (72%) had fundus photographs gradable for AMD. Early AMD was present in 375 eyes (4.6%), and late AMD was present in 17 (0.2%). Shorter axial length, male sex, older age, and family history of AMD were identified as independent risk factors for prevalent AMD and its characteristic retinal lesions using a conceptual model of potential AMD risk factors. Of 4 AMD risk factors identified for Latinos, 3 (older age, male sex, shorter axial length) overlapped with those identified for Chinese Americans, with an association similar in magnitude and direction. Lower levels of education were a risk factor specific to Latinos. Based on a multivariable logistic regression model, the predicted probability of early AMD was 31% lower among Chinese Americans relative to Latinos (95% confidence interval [CI], 17%-43%). Chinese Americans also had statistically significantly lower odds of any AMD and 2 types of early retinal lesions symptomatic of AMD. CONCLUSIONS Factors associated with prevalent AMD are similar for Chinese Americans and Latinos. Chinese Americans who were older, were male, had a family history of AMD, and had a shorter axial length were at an increased risk for AMD compared with those without these risk factors. We observed a significantly lower predicted prevalence of AMD among Chinese Americans compared with Latinos, even after controlling for all relevant covariates, suggesting that additional genetic or lifestyle differences may play an important role in determining AMD risk.
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Affiliation(s)
- Bruce Burkemper
- USC Roski Eye Institute, Department of Ophthalmology, Keck School of Medicine of the University of Southern California, Los Angeles, California
| | - Roberta McKean-Cowdin
- Department of Preventive Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, California
| | - Farzana Choudhury
- USC Roski Eye Institute, Department of Ophthalmology, Keck School of Medicine of the University of Southern California, Los Angeles, California
| | - Ronald Klein
- Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
| | - W James Gauderman
- Department of Preventive Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, California
| | - Xuejuan Jiang
- USC Roski Eye Institute, Department of Ophthalmology, Keck School of Medicine of the University of Southern California, Los Angeles, California
| | - Chunyi Hsu
- USC Roski Eye Institute, Department of Ophthalmology, Keck School of Medicine of the University of Southern California, Los Angeles, California
| | - Mina Torres
- USC Roski Eye Institute, Department of Ophthalmology, Keck School of Medicine of the University of Southern California, Los Angeles, California
| | - Rohit Varma
- USC Roski Eye Institute, Department of Ophthalmology, Keck School of Medicine of the University of Southern California, Los Angeles, California.
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Farnoodian M, Sorenson CM, Sheibani N. Negative Regulators of Angiogenesis, Ocular Vascular Homeostasis, and Pathogenesis and Treatment of Exudative AMD. J Ophthalmic Vis Res 2018; 13:470-486. [PMID: 30479719 PMCID: PMC6210860 DOI: 10.4103/jovr.jovr_67_18] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Angiogenesis, the formation of new blood vessels from pre-existing capillaries, is very tightly regulated and normally does not occur except during developmental and reparative processes. This tight regulation is maintained by a balanced production of positive and negative regulators, and alterations under pathological conditions such as retinopathy of prematurity, diabetic retinopathy, and age-related macular degeneration can lead to growth of new and abnormal blood vessels. Although the role of proangiogenic factors such as vascular endothelial growth factor has been extensively studied, little is known about the roles of negative regulators of angiogenesis in the pathogenesis of these diseases. Here, we will discuss the role of thrombospondin-1 (TSP1), one of the first known endogenous inhibitors of angiogenesis, in ocular vascular homeostasis, and how its alterations may contribute to the pathogenesis of age-related macular degeneration and choroidal neovascularization. We will also discuss its potential utility as a therapeutic target for treatment of ocular diseases with a neovascular component.
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Affiliation(s)
- Mitra Farnoodian
- Department of Ophthalmology and Visual Sciences, University of Wisconsin, School of Medicine and Public Health, Madison, WI, USA
| | - Christine M Sorenson
- Department of Pediatrics, University of Wisconsin, School of Medicine and Public Health, Madison, WI, USA.,McPherson Eye Research Institute, University of Wisconsin, School of Medicine and Public Health, Madison, WI, USA
| | - Nader Sheibani
- Department of Ophthalmology and Visual Sciences, University of Wisconsin, School of Medicine and Public Health, Madison, WI, USA.,McPherson Eye Research Institute, University of Wisconsin, School of Medicine and Public Health, Madison, WI, USA.,Department of Biomedical Engineering, University of Wisconsin, School of Medicine and Public Health, Madison, WI, USA.,Department of Cell and Regenerative Biology, University of Wisconsin, School of Medicine and Public Health, Madison, WI, USA
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10
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Saravia M, Zeman L, Ingolotti M, Schlaen A. The VEGF paradox: Does diabetic retinopathy protect from age related macular degeneration? Med Hypotheses 2017; 109:156-161. [DOI: 10.1016/j.mehy.2017.10.001] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2017] [Revised: 09/19/2017] [Accepted: 10/01/2017] [Indexed: 10/18/2022]
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11
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Ischemic Optic Neuropathy in Cardiac Surgery: Incidence and Risk Factors in the United States from the National Inpatient Sample 1998 to 2013. Anesthesiology 2017; 126:810-821. [PMID: 28244936 DOI: 10.1097/aln.0000000000001533] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2023]
Abstract
BACKGROUND Ischemic optic neuropathy is the most common form of perioperative visual loss, with highest incidence in cardiac and spinal fusion surgery. To date, potential risk factors have been identified in cardiac surgery by only small, single-institution studies. To determine the preoperative risk factors for ischemic optic neuropathy, the authors used the National Inpatient Sample, a database of inpatient discharges for nonfederal hospitals in the United States. METHODS Adults aged 18 yr or older admitted for coronary artery bypass grafting, heart valve repair or replacement surgery, or left ventricular assist device insertion in National Inpatient Sample from 1998 to 2013 were included. Risk of ischemic optic neuropathy was evaluated by multivariable logistic regression. RESULTS A total of 5,559,395 discharges met inclusion criteria with 794 (0.014%) cases of ischemic optic neuropathy. The average yearly incidence was 1.43 of 10,000 cardiac procedures, with no change during the study period (P = 0.57). Conditions increasing risk were carotid artery stenosis (odds ratio, 2.70), stroke (odds ratio, 3.43), diabetic retinopathy (odds ratio, 3.83), hypertensive retinopathy (odds ratio, 30.09), macular degeneration (odds ratio, 4.50), glaucoma (odds ratio, 2.68), and cataract (odds ratio, 5.62). Female sex (odds ratio, 0.59) and uncomplicated diabetes mellitus type 2 (odds ratio, 0.51) decreased risk. CONCLUSIONS The incidence of ischemic optic neuropathy in cardiac surgery did not change during the study period. Development of ischemic optic neuropathy after cardiac surgery is associated with carotid artery stenosis, stroke, and degenerative eye conditions.
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12
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Linsenmeier RA, Zhang HF. Retinal oxygen: from animals to humans. Prog Retin Eye Res 2017; 58:115-151. [PMID: 28109737 DOI: 10.1016/j.preteyeres.2017.01.003] [Citation(s) in RCA: 166] [Impact Index Per Article: 20.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2016] [Revised: 01/13/2017] [Accepted: 01/17/2017] [Indexed: 10/20/2022]
Abstract
This article discusses retinal oxygenation and retinal metabolism by focusing on measurements made with two of the principal methods used to study O2 in the retina: measurements of PO2 with oxygen-sensitive microelectrodes in vivo in animals with a retinal circulation similar to that of humans, and oximetry, which can be used non-invasively in both animals and humans to measure O2 concentration in retinal vessels. Microelectrodes uniquely have high spatial resolution, allowing the mapping of PO2 in detail, and when combined with mathematical models of diffusion and consumption, they provide information about retinal metabolism. Mathematical models, grounded in experiments, can also be used to simulate situations that are not amenable to experimental study. New methods of oximetry, particularly photoacoustic ophthalmoscopy and visible light optical coherence tomography, provide depth-resolved methods that can separate signals from blood vessels and surrounding tissues, and can be combined with blood flow measures to determine metabolic rate. We discuss the effects on retinal oxygenation of illumination, hypoxia and hyperoxia, and describe retinal oxygenation in diabetes, retinal detachment, arterial occlusion, and macular degeneration. We explain how the metabolic measurements obtained from microelectrodes and imaging are different, and how they need to be brought together in the future. Finally, we argue for revisiting the clinical use of hyperoxia in ophthalmology, particularly in retinal arterial occlusions and retinal detachment, based on animal research and diffusion theory.
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Affiliation(s)
- Robert A Linsenmeier
- Biomedical Engineering Department, Northwestern University, 2145 Sheridan Road, Evanston 60208-3107, IL, USA; Neurobiology Department, Northwestern University, 2205 Tech Drive, Evanston 60208-3520, IL, USA; Ophthalmology Department, Northwestern University, 645 N. Michigan Ave, Suite 440, Chicago 60611, IL, USA.
| | - Hao F Zhang
- Biomedical Engineering Department, Northwestern University, 2145 Sheridan Road, Evanston 60208-3107, IL, USA; Ophthalmology Department, Northwestern University, 645 N. Michigan Ave, Suite 440, Chicago 60611, IL, USA.
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Bringmann A, Hollborn M, Kohen L, Wiedemann P. Intake of dietary salt and drinking water: Implications for the development of age-related macular degeneration. Mol Vis 2016; 22:1437-1454. [PMID: 28031693 PMCID: PMC5178186] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2016] [Accepted: 12/20/2016] [Indexed: 10/26/2022] Open
Abstract
PURPOSE Systemic hypertension is a risk factor of age-related retinal diseases such as diabetic retinopathy and age-related macular degeneration. High intake of dietary salt and low intake of water increase extracellular osmolality resulting in hypertension, in particular in salt-sensitive individuals. This review summarizes the present knowledge regarding the impact of salt and water intake on the regulation of blood pressure, retinal function, and the development of age-related retinal diseases. METHODS A literature search of the Medline database and a summary of recent studies that used human RPE cells. RESULTS The salt sensitivity of the blood pressure and plasma osmolality increase with age, and body water deficits are common in older individuals. High plasma osmolality has adverse effects in the retina. In RPE cells, high osmolality induces expression and secretion of angiogenic factors, such as vascular endothelial growth factor (VEGF), placental growth factor, and basic fibroblast growth factor, and expression of aquaporin-5, a water channel implicated in transepithelial water transport. The transcriptional activities of hypoxia-inducible factor-1 (HIF-1) and nuclear factor of activated T cell 5 (NFAT5) are critical for the production of VEGF in response to salt-induced osmotic stress. Salt-induced osmotic stress also induces priming of the NLRP3 inflammasome and activates inflammatory enzymes in RPE cells. CONCLUSIONS Raised plasma osmolality may aggravate age-related retinal diseases by stimulation of local inflammation and angiogenic factor production in the RPE. Alterations in salt and water consumption, and of minerals that stimulate renal salt excretion, may offer nutritional approaches to prevent age-related retinal disorders, in particular in salt-sensitive individuals and individuals who show signs of body dehydration.
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Affiliation(s)
- Andreas Bringmann
- Department of Ophthalmology and Eye Hospital, University of Leipzig, Leipzig, Germany
| | - Margrit Hollborn
- Department of Ophthalmology and Eye Hospital, University of Leipzig, Leipzig, Germany
| | - Leon Kohen
- Department of Ophthalmology and Eye Hospital, University of Leipzig, Leipzig, Germany,Helios Klinikum Aue, Aue, Germany
| | - Peter Wiedemann
- Department of Ophthalmology and Eye Hospital, University of Leipzig, Leipzig, Germany
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Holappa M, Vapaatalo H, Vaajanen A. Ocular renin-angiotensin system with special reference in the anterior part of the eye. World J Ophthalmol 2015; 5:110-124. [DOI: 10.5318/wjo.v5.i3.110] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2015] [Revised: 03/21/2015] [Accepted: 06/16/2015] [Indexed: 02/06/2023] Open
Abstract
The renin-angiotensin system (RAS) regulates blood pressure (BP) homeostasis, systemic fluid volume and electrolyte balance. The RAS cascade includes over twenty peptidases, close to twenty angiotensin peptides and at least six receptors. Out of these, angiotensin II, angiotensin converting enzyme 1 and angiotensin II type 1 receptor (AngII-ACE1-AT1R) together with angiotensin (1-7), angiotensin converting enzyme 2 and Mas receptor (Ang(1-7)-ACE2-MasR) are regarded as the main components of RAS. In addition to circulating RAS, local RA-system exists in various organs. Local RA-systems are regarded as tissue-specific regulatory systems accounting for local effects and long term changes in different organs. Many of the central components such as the two main axes of RAS: AngII-ACE1-AT1R and Ang(1-7)-ACE2-MasR, have been identified in the human eye. Furthermore, it has been shown that systemic antihypertensive RAS- inhibiting medications lower intraocular pressure (IOP). These findings suggest the crucial role of RAS not only in the regulation of BP but also in the regulation of IOP, and RAS potentially plays a role in the development of glaucoma and antiglaucomatous drugs.
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Told R, Palkovits S, Boltz A, Schmidl D, Napora KJ, Werkmeister RM, Haslacher H, Frantal S, Popa‐Cherecheanu A, Schmetterer L, Garhöfer G. Flicker-induced retinal vasodilatation is not dependent on complement factor H polymorphism in healthy young subjects. Acta Ophthalmol 2014; 92:e540-5. [PMID: 24863099 PMCID: PMC4225479 DOI: 10.1111/aos.12433] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2013] [Accepted: 03/17/2014] [Indexed: 02/02/2023]
Abstract
Purpose The complement factor H (CFH) tyrosine 402 histidine (Y402H, rs1061170) variant is known to be significantly associated with age-related macular degeneration (AMD). Whether this genetic variant may impact retinal blood flow regulation is largely unknown. This study investigated whether flicker-induced vasodilation, an indicator for the coupling between neural activity and blood flow, is altered in subjects carrying the rs1061170 risk allele. Methods One hundred healthy subjects (aged between 18 and 45 years) were included in this study. Retinal blood flow regulation was tested by assessing retinal vessel calibres in response to stimulation with diffuse flicker light. Retinal vascular flicker responses were determined with a Dynamic Vessel Analyzer (DVA). In addition, genotyping for rs1061170 was performed. Results Eighteen subjects were homozygous for the risk allele C, 50 were homozygous for the ancestral allele T, and 31 subjects were heterozygous (CT). One subject had to be excluded from data evaluation, as no genetic analysis could be performed due to technical difficulties. Baseline diameters of retinal arteries (p = 0.39) and veins (p = 0.64) were comparable between the three groups. Flicker-induced vasodilation in both retinal arteries (p = 0.38) and retinal veins (p = 0.62) was also comparable between the three studied groups. Conclusions Our data indicate that homozygous healthy young carriers of the C risk allele at rs1061170 do not show abnormal flicker-induced vasodilation in the retina. This suggests that the high-risk genetic variant of CFH polymorphism does not impact neuro-vascular coupling in healthy subjects.
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Affiliation(s)
- Reinhard Told
- Department of Clinical Pharmacology Medical University of Vienna Vienna Austria
- Center for Medical Physics and Biomedical Engineering Medical University of Vienna Vienna Austria
| | - Stefan Palkovits
- Department of Clinical Pharmacology Medical University of Vienna Vienna Austria
| | - Agnes Boltz
- Department of Clinical Pharmacology Medical University of Vienna Vienna Austria
- Center for Medical Physics and Biomedical Engineering Medical University of Vienna Vienna Austria
| | - Doreen Schmidl
- Department of Clinical Pharmacology Medical University of Vienna Vienna Austria
| | - Katarzyna J. Napora
- Department of Clinical Pharmacology Medical University of Vienna Vienna Austria
- Center for Medical Physics and Biomedical Engineering Medical University of Vienna Vienna Austria
| | - René M. Werkmeister
- Center for Medical Physics and Biomedical Engineering Medical University of Vienna Vienna Austria
| | - Helmuth Haslacher
- Department of Laboratory Medicine Medical University of Vienna Vienna Austria
| | - Sophie Frantal
- Center for Medical Statistics Informatics and Intelligence Systems Medical University of Vienna Vienna Austria
| | | | - Leopold Schmetterer
- Department of Clinical Pharmacology Medical University of Vienna Vienna Austria
- Center for Medical Physics and Biomedical Engineering Medical University of Vienna Vienna Austria
| | - Gerhard Garhöfer
- Department of Clinical Pharmacology Medical University of Vienna Vienna Austria
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McKeague C, Margrain TH, Bailey C, Binns AM. Low-level night-time light therapy for age-related macular degeneration (ALight): study protocol for a randomized controlled trial. Trials 2014; 15:246. [PMID: 24965385 PMCID: PMC4227140 DOI: 10.1186/1745-6215-15-246] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2013] [Accepted: 05/23/2014] [Indexed: 12/11/2022] Open
Abstract
Background Age-related macular degeneration (AMD) is the leading cause of blindness among older adults in the developed world. The only treatments currently available, such as ranibizumab injections, are for neovascular AMD, which accounts for only 10 to 15% of people with the condition. Hypoxia has been implicated as one of the primary causes of AMD, and is most acute at night when the retina is most metabolically active. By increasing light levels at night, the metabolic requirements of the retina and hence the hypoxia will be considerably reduced. This trial seeks to determine whether wearing a light mask that emits a dim, green light during the night can prevent the progression of early AMD. Methods/design ALight is a Phase I/IIa, multicentre, randomized controlled trial. Sixty participants (55 to 88 years old) with early AMD in one eye and neovascular AMD (nAMD) in the fellow eye will be recruited from nAMD clinics. They will be randomized (in the ratio 1:1), either to receive the intervention or to be in the untreated control group, stratified according to risk of disease progression. An additional 40 participants with healthy retinal appearance, or early AMD only, will be recruited for a baseline cross-sectional analysis. The intervention is an eye mask that emits a dim green light to illuminate the retina through closed eyelids at night. This is designed to reduce the metabolic activity of the retina, thereby reducing the potential risk of hypoxia. Participants will wear the mask every night for 12 months. Ophthalmologists carrying out monthly assessments will be masked to the treatment group, but participants will be aware of their treatment group. The primary outcome measure is the proportion of people who show disease progression during the trial period in the eye with early AMD. A co-primary outcome measure is the rate of retinal adaptation. As this is a trial of a CE-marked device for an off-label indication, a further main aim of this trial is to assess safety of the mask in the cohort of participants with AMD. Trial registration International Standard Randomised Controlled Trials Register: ISRCTN82148651
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Affiliation(s)
| | | | | | - Alison M Binns
- School of Optometry and Vision Sciences, Cardiff University, Cardiff CF24 4 LU, UK.
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Huang EJC, Wu SH, Lai CH, Kuo CN, Wu PL, Chen CL, Chen CY, King YC, Wu PC. Prevalence and risk factors for age-related macular degeneration in the elderly Chinese population in south-western Taiwan: the Puzih eye study. Eye (Lond) 2014; 28:705-14. [PMID: 24625378 PMCID: PMC4058619 DOI: 10.1038/eye.2014.55] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2013] [Accepted: 02/07/2014] [Indexed: 01/30/2023] Open
Abstract
AIM This study aimed to ascertain the prevalence of and the risk factors associated with early and late age-related macular degeneration (AMD) among Chinese individuals aged ≥65 years residing in Puzih, Taiwan. METHODS This population-based cross-sectional study graded digital colour photographs of the ocular fundus of 673 individuals using the Wisconsin Age-Related Maculopathy Grading System. We compared the characteristics of individuals with early and late AMD using χ(2)-analyses and described risk factors for early and late AMD using odds ratios and 95% confidence intervals. RESULTS Individuals with late AMD were significantly older and more likely to have hypertension. Further, their sunlight exposure time was longer than that of those with early AMD, only drusen, or no AMD lesions (P<0.01). A history of hyperlipidaemia for >10 years was a significant risk factor for early AMD, while old age, hypertension for >10 years, and exposure to sunlight for >8 h per day were associated with late AMD. CONCLUSIONS The prevalence rate of early AMD in the present study was 15.0%, which is similar to that reported for Caucasians and Japanese included in the European Eye Study and the Hisayama Study, respectively. The late AMD prevalence rate of 7.3% found among our study participants was comparable to that reported by the Greenland Inuit Eye Study and Reykjavik Study, but considerably lower than that reported for Caucasians, indicating that late AMD might be less prevalent among Asians than Caucasians.
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Affiliation(s)
- E J-C Huang
- Department of Ophthalmology, Chang Gung Memorial Hospital- Chiayi, Chiayi, Taiwan
- Chang Gung University College of Medicine, Tao-Yuan, Taiwan
| | - S-H Wu
- Department of Ophthalmology, Chang Gung Memorial Hospital- Chiayi, Chiayi, Taiwan
- Chang Gung University College of Medicine, Tao-Yuan, Taiwan
| | - C-H Lai
- Department of Ophthalmology, Chang Gung Memorial Hospital- Chiayi, Chiayi, Taiwan
- Chang Gung University College of Medicine, Tao-Yuan, Taiwan
- Department of Nursing, Chang Gung University of Science and Technology, Chiayi, Taiwan
| | - C-N Kuo
- Department of Ophthalmology, Chang Gung Memorial Hospital- Chiayi, Chiayi, Taiwan
- Chang Gung University College of Medicine, Tao-Yuan, Taiwan
| | - P-L Wu
- Department of Ophthalmology, Chang Gung Memorial Hospital- Chiayi, Chiayi, Taiwan
- Chang Gung University College of Medicine, Tao-Yuan, Taiwan
| | - C-L Chen
- Department of Ophthalmology, Chang Gung Memorial Hospital- Chiayi, Chiayi, Taiwan
- Chang Gung University College of Medicine, Tao-Yuan, Taiwan
| | - C-Y Chen
- Department of Ophthalmology, Chang Gung Memorial Hospital- Chiayi, Chiayi, Taiwan
- Chang Gung University College of Medicine, Tao-Yuan, Taiwan
| | - Y-C King
- Department of Ophthalmology, Chang Gung Memorial Hospital- Chiayi, Chiayi, Taiwan
| | - P-C Wu
- Department of Ophthalmology, Chang Gung Memorial Hospital- Chiayi, Chiayi, Taiwan
- Chang Gung University College of Medicine, Tao-Yuan, Taiwan
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Boddu S, Lee MD, Marsiglia M, Marmor M, Freund KB, Smith RT. Risk factors associated with reticular pseudodrusen versus large soft drusen. Am J Ophthalmol 2014; 157:985-993.e2. [PMID: 24491417 DOI: 10.1016/j.ajo.2014.01.023] [Citation(s) in RCA: 49] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2013] [Revised: 01/22/2014] [Accepted: 01/23/2014] [Indexed: 10/25/2022]
Abstract
PURPOSE To investigate genetic, environmental, and systemic risk factors in prospectively identified subjects with the age-related macular degeneration (AMD) phenotypes of (1) reticular pseudodrusen without large soft drusen and (2) large soft drusen without reticular pseudodrusen. DESIGN Prospective case-case comparison. METHODS In a clinical practice setting, patients with AMD were sequentially screened using clinical examination and scanning laser ophthalmoscopy imaging to prospectively identify subjects (n = 73) with the phenotypes of (1) reticular pseudodrusen without large soft drusen (n = 30) or (2) large soft drusen without reticular pseudodrusen (n = 43). Subjects were genotyped for 2 alleles associated with AMD, age-related maculopathy susceptibility 2 (ARMS2) and complement factor H (CFH). A questionnaire was administered to collect history of smoking, hypertension, diabetes, and hyperlipidemia, as well as personal and family history of AMD. RESULTS The reticular pseudodrusen group was older (median age 87 vs 81 years, P = .04) and had more female subjects (83.3% vs 48.8%, P = .003), later ages of AMD onset (83 vs 70 years, P = .0005), and a greater frequency of hypertension (76.7% vs 55.8%, P = .08). No significant differences were found in the distribution of the ARMS2 risk allele (P = .4) between the reticular pseudodrusen (homozygous = 20.0%; heterozygous = 56.7%) and large soft drusen (homozygous = 19.0%; heterozygous = 42.9%) phenotypes, or in the distribution of the CHF risk allele (P = .7) between the reticular pseudodrusen (homozygous = 26.7%; heterozygous = 56.7%) and large soft drusen (homozygous = 21.4%; heterozygous = 66.7%) phenotypes. CONCLUSIONS The reticular pseudodrusen phenotype was associated with increased age, later age of AMD onset, and female sex.
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Wickremasinghe SS, Chong EWT, Guymer RH. Lifestyle and age-related macular degeneration. EXPERT REVIEW OF OPHTHALMOLOGY 2014. [DOI: 10.1586/17469899.4.1.79] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
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Türkcü FM, Yüksel H, Sahin A, Cinar Y, Cingü K, Arı S, Sahin M, Altındağ S, Caça I. Effects of smoking on visual acuity of central serous chorioretinopathy patients. Cutan Ocul Toxicol 2013; 33:115-9. [PMID: 23841829 DOI: 10.3109/15569527.2013.810633] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
BACKGROUND The aim of this study was to evaluate the differences, in terms of visual outcome and treatment needs, between smokers and non-smokers central serous chorioretinopathy (CSCR) patients. METHODS The files of 252 patients diagnosed with CSCR who had presented to the Retina Unit of the Ophthalmology Clinic at Dicle University Medical School in Turkey were retrospectively evaluated. Eighty-four smokers, with a known history of smoking of at least one pack-year, and 133 non-smokers were included, whereas 35 patients with additional pathologies were excluded from the study. RESULTS Of the patients, 192 (88.5%) were male and 25 (11.5%) were female. The mean patient age was 38.8 ± 8.1 years (range: 20-68 years). Visual acuity (VA) of the smoker and non-smoker groups was measured as 0.45 ± 0.35 and 0.24 ± 0.28 logarithm of the minimum angle of resolution (logMar), respectively, at the first visit; 0.19 ± 0.29 and 0.06 ± 0.14 logMar at the sixth month; and 0.07 ± 0.14 and 0.02 ± 0.05 logMar at the ninth month. VA measurements at presentation and during all examinations (1th, 6th and 9th month) were significantly different for the two groups. VA was lower in the smoker group. In 27 patients (12.4%), an additional treatment modality was needed. Of the 27 patients, only 8 (6%) were non-smokers, whereas 19 (22.6%) were smokers. There was no difference between groups in the recurrence rate during follow-up (p = 0.907); 14 (16.7%) smokers and 8 (19.0%) non-smokers experienced a recurrence. CONCLUSION This study has shown that patients selected and who are current smokers have poorer vision and need longer treatment.
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Affiliation(s)
- Fatih Mehmet Türkcü
- Department of Ophthalmology, Dicle University Faculty of Medicine , Diyarbakir , Turkey
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Gopinath B, Flood VM, Rochtchina E, Wang JJ, Mitchell P. Homocysteine, folate, vitamin B-12, and 10-y incidence of age-related macular degeneration. Am J Clin Nutr 2013; 98:129-35. [PMID: 23636242 DOI: 10.3945/ajcn.112.057091] [Citation(s) in RCA: 66] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
Abstract
BACKGROUND Epidemiologic evidence of a relation between serum total homocysteine (tHcy), vitamin B-12, and folate and age-related macular degeneration (AMD) is inconsistent and unresolved. OBJECTIVE In this cohort study, we aimed to investigate associations between intakes and serum concentrations of folate and vitamin B-12 or serum tHcy and 10-y AMD incidence. DESIGN Serum folate, vitamin B-12, and tHcy were determined from blood samples drawn in 1997-1999 from cohort members aged ≥55 y. AMD was assessed in 1760 survivors from retinal photographs taken in 2002-2004 and 2007-2009. Total intakes of folate and vitamin B-12 were assessed by using a food-frequency questionnaire. RESULTS After adjustment for age, sex, current smoking, white blood cell count, and fish consumption, each 1-SD increase in serum tHcy was associated with increased risk of incident early and any AMD [ORs (95% CIs): 1.33 (1.09, 1.63) and 1.33 (1.11, 1.60), respectively]. Participants with a serum vitamin B-12 deficiency (<185 pmol/L) had higher risk of incident early and late AMD [ORs (95% CIs): 1.58 (1.06, 2.36) and 2.56 (1.38, 4.73), respectively]. Folate deficiency (<11 nmol/L) was associated with 75% and 89% increased risk of incident early and any AMD, respectively, 10 y later. Participants who reported supplementary vitamin B-12 intake had 47% reduced risk of incident any AMD (OR: 0.53; 95% CI: 0.33, 0.85). CONCLUSION Elevated serum tHcy and folate and vitamin B-12 deficiencies predicted increased risk of incident AMD, which suggests a potential role for vitamin B-12 and folate in reducing AMD risk.
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Affiliation(s)
- Bamini Gopinath
- Centre for Vision Research, Department of Ophthalmology and Westmead Millennium Institute, University of Sydney, Sydney, Australia
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Told R, Palkovits S, Haslacher H, Frantal S, Schmidl D, Boltz A, Lasta M, Kaya S, Werkmeister RM, Garhöfer G, Schmetterer L. Alterations of choroidal blood flow regulation in young healthy subjects with complement factor H polymorphism. PLoS One 2013; 8:e60424. [PMID: 23596508 PMCID: PMC3626650 DOI: 10.1371/journal.pone.0060424] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2013] [Accepted: 02/26/2013] [Indexed: 11/18/2022] Open
Abstract
A common polymorphism in the complement factor H gene (rs1061170, Y402H) is associated with a high risk of age-related macular degeneration (AMD). In the present study we hypothesized that healthy young subjects homozygous for the high-risk haplotype (CC) show abnormal choroidal blood flow (ChBF) regulation decades before potentially developing the disease. A total of 100 healthy young subjects were included in the present study, of which 4 subjects were excluded due to problems with genotyping or blood flow measurements. ChBF was measured continuously using laser Doppler flowmetry while the subjects performed isometric exercise (squatting) for 6 minutes. The increase in ChBF was less pronounced than the response in ocular perfusion pressure (OPP), indicating for some degree of choroidal blood flow regulation. Eighteen subjects were homozygous for C, 47 subjects were homozygous for T and 31 subjects were heterozygous (CT). The increase in OPP during isometric exercise was not different between groups. By contrast the increase in ChBF was more pronounced in subjects homozygous for the high risk C allele (p = 0.041). This was also evident from the pressure/flow relationship, where the increase in ChBF in homozygous C carriers started at lower OPPs as compared to the other groups. Our data indicate that the regulation of ChBF is abnormal in rs1061170 CC carriers. So far this polymorphism has been linked to age related macular degeneration (AMD) mainly via inflammatory pathways associated with the complement system dysfunction. Our results indicate that it could also be related to vascular factors that have been implicated in AMD pathogenesis.
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Affiliation(s)
- Reinhard Told
- Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria
- Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, Vienna, Austria
| | - Stefan Palkovits
- Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria
| | - Helmuth Haslacher
- Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria
| | - Sophie Frantal
- Center for Medical Statistics, Informatics and Intelligence Systems, Medical University of Vienna, Vienna, Austria
| | - Doreen Schmidl
- Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria
| | - Agnes Boltz
- Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria
- Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, Vienna, Austria
| | - Michael Lasta
- Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria
| | - Semira Kaya
- Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria
| | - René M. Werkmeister
- Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, Vienna, Austria
| | - Gerhard Garhöfer
- Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria
| | - Leopold Schmetterer
- Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria
- Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, Vienna, Austria
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Perivascular mural cells of the mouse choroid demonstrate morphological diversity that is correlated to vasoregulatory function. PLoS One 2013; 8:e53386. [PMID: 23308209 PMCID: PMC3537675 DOI: 10.1371/journal.pone.0053386] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2012] [Accepted: 11/27/2012] [Indexed: 01/17/2023] Open
Abstract
Objective Perivascular mural cells of the choroid have been implicated in physiological functioning as well as in retinal disease pathogenesis. However details regarding their form and function are not well understood. We aim to characterize choroidal mural cells in the adult mouse choroid in terms of their distribution and morphology, and correlate these to their contractile behavior. Methods Sclerochoroidal flat-mounted explants were prepared from albino transgenic mice in which the α-smooth muscle actin (α-SMA) promoter drives the expression of green fluorescent protein (GFP). α-SMA-expressing smooth muscle cells and pericytes in the living choroid were thereby rendered fluorescent and imaged with confocal microscopy and live-cell imaging in situ. Results Choroidal perivascular mural cells demonstrate significant diversity in terms of their distribution and morphology at different levels of the vasculature. They range from densely-packed circumferentially-oriented cells that provide complete vascular coverage in primary arteries to widely-spaced stellate-shaped cells that are distributed sparsely over terminal arterioles. Mural cells at each level are immunopositive for contractile proteins α-SMA and desmin and demonstrate vasoconstrictory contractile movements in response to endothelin-1 and the calcium ionophore, A23187, and vasodilation in response to the calcium chelator, BAPTA. The prominence of vasoregulatory contractile responses varies with mural cell morphology and density, and is greater in vessels with dense coverage of mural cells with circumferential cellular morphologies. In the choriocapillaris, pericytes demonstrate a sparse, horizontal distribution and are selectively distributed only to the scleral surface of the choriocapillaris. Conclusions Diversity and regional specialization of perivascular mural cells may subserve varying requirements for vasoregulation in the choroid. The model of the α-SMA-GFP transgenic albino mouse provides a useful and intact system for the morphological and functional study of choroidal mural cells.
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Kur J, Newman EA, Chan-Ling T. Cellular and physiological mechanisms underlying blood flow regulation in the retina and choroid in health and disease. Prog Retin Eye Res 2012; 31:377-406. [PMID: 22580107 DOI: 10.1016/j.preteyeres.2012.04.004] [Citation(s) in RCA: 486] [Impact Index Per Article: 37.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2012] [Revised: 04/17/2012] [Accepted: 04/22/2012] [Indexed: 02/06/2023]
Abstract
We review the cellular and physiological mechanisms responsible for the regulation of blood flow in the retina and choroid in health and disease. Due to the intrinsic light sensitivity of the retina and the direct visual accessibility of fundus blood vessels, the eye offers unique opportunities for the non-invasive investigation of mechanisms of blood flow regulation. The ability of the retinal vasculature to regulate its blood flow is contrasted with the far more restricted ability of the choroidal circulation to regulate its blood flow by virtue of the absence of glial cells, the markedly reduced pericyte ensheathment of the choroidal vasculature, and the lack of intermediate filaments in choroidal pericytes. We review the cellular and molecular components of the neurovascular unit in the retina and choroid, techniques for monitoring retinal and choroidal blood flow, responses of the retinal and choroidal circulation to light stimulation, the role of capillaries, astrocytes and pericytes in regulating blood flow, putative signaling mechanisms mediating neurovascular coupling in the retina, and changes that occur in the retinal and choroidal circulation during diabetic retinopathy, age-related macular degeneration, glaucoma, and Alzheimer's disease. We close by discussing issues that remain to be explored.
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Affiliation(s)
- Joanna Kur
- Department of Neuroscience, University of Minnesota, Minneapolis, MN 55455, USA
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Grisanti S, Lueke J, Lueke M, Rudolf M, Peters S. Current and future strategies for nonexudative age-related macular degeneration. EXPERT REVIEW OF OPHTHALMOLOGY 2011. [DOI: 10.1586/eop.11.26] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
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Çekiç O, Bardak Y, Yeşildağ A. Color Doppler Imaging of Ocular Blood Flow after Combined Photodynamic Therapy with Intravitreal Triamcinolone in Age-Related Macular Degeneration. Curr Eye Res 2010; 36:149-53. [DOI: 10.3109/02713683.2010.533809] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
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Abstract
Ischemia and hypoxia have been implicated in the pathophysiology of age related macular degeneration (AMD). This has mostly been based on studies on choroidal perfusion, which is not the only contributor to retinal hypoxia found in AMD eyes. Other features of AMD may also interfere with retinal oxygen metabolism including confluent drusen, serous or hemorrhagic retinal detachment, retinal edema and vitreoretinal adhesion. Each of these features contributes to retinal hypoxia: the drusen and retinal elevation by increasing the distance between the choriocapillaris and retina; vitreoretinal adhesion by reducing diffusion and convection of oxygen towards and vascular endothelial growth factor (VEGF) away from hypoxic retinal areas. Hypoxia-inducible-factor is known to exist in subretinal neovascularization and hypoxia is the main stimulus for the production of VEGF. Each feature may not by itself create enough hypoxia and VEGF accumulation to stimulate wet AMD, but they may combine to do so. Choroidal ischemia in AMD has been demonstrated by many researchers, using different technologies. Choroidal ischemia obviously decreases oxygen delivery to the outer retina. Confluent drusen, thickening of Bruch's membrane and any detachment of retina or retinal pigment epithelium, increases the distance between the choriocapillaris and the retina and thereby reduces the oxygen flux from the choroid to the outer retina according to Fick's law of diffusion. Retinal elevation and choroidal ischemia may combine forces to reduce choroidal oxygen delivery to the outer retina, produce retinal hypoxia. Hypoxia leads to production of VEGF leading to neovascularization and tissue edema. A vicious cycle may develop, where VEGF production increases effusion, retinal detachment and edema, further increasing hypoxia and VEGF production. Adhesion of the viscous posterior vitreous cortex to the retina maintains a barrier to diffusion and convection currents in the vitreous cavity according to the laws of Fick's, Stokes-Einstein and Hagen-Poiseuille. If the vitreous is detached from the surface of the retina, the low viscosity fluid transports oxygen and nutrients towards an ischemic area of the retina, and cytokines away from the retina, at a faster rate than through attached vitreous gel. Vitreoretinal adhesion can exacerbate retinal hypoxia and accumulation of cytokines, such as VEGF. Vitreoretinal traction can also cause hypoxia by retinal elevation. Conceivably, the basic features of AMD, drusen, choroidal ischemia, and vitreoretinal adhesion are independently determined by genetics and environment and may combine in variable proportions. If the resulting hypoxia and consequent VEGF accumulation crosses a threshold, this will trigger effusion and neovascularization.
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Affiliation(s)
- Einar Stefánsson
- University of Iceland, National University Hospital, 101 Reykjavík, Iceland.
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Roller AB, Mahajan VB, Boldt HC, Abramoff MD, Russell SR, Folk JC. Effects of vitrectomy on age-related macular degeneration. Ophthalmology 2010; 117:1381-6. [PMID: 20176401 DOI: 10.1016/j.ophtha.2009.11.007] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2009] [Revised: 10/09/2009] [Accepted: 11/03/2009] [Indexed: 01/29/2023] Open
Abstract
PURPOSE To determine whether vitrectomy alters the long-term progression of age-related macular degeneration (AMD). DESIGN Retrospective case-control study. PARTICIPANTS Forty-four eyes of 22 patients with AMD who underwent vitrectomy in 1 eye were included in the study. The progression of AMD at follow-up in the 22 eyes that underwent vitrectomy was compared with the 22 fellow, nonvitrectomized eyes. METHODS The charts and photographs of subjects with Age-Related Eye Disease Study category 3 AMD in both eyes who previously underwent vitrectomy surgery for an epiretinal membrane or macular hole were reviewed. Subjects were excluded if they had had a vitrectomy in both eyes, had <2 years of follow-up, had previous choroidal neovascularization (CNV), retinal detachment, diabetic retinopathy, angioid streaks, high myopia, vascular occlusions, or extensive macular scarring in either eye, or insufficient hospital records or photographs to determine the extent of AMD. Clinical notes throughout the follow-up interval were reviewed. Two vitreoretinal specialists independently graded pre- and postvitrectomy fundus photographs of all eyes in a masked fashion. MAIN OUTCOME MEASURES The development or progression of geographic atrophy of the retinal pigment epithelium and the development of CNV. RESULTS Twenty-two patients were included. The average follow up interval was 5.5 years (range, 2-15). Choroidal neovascularization developed in 5 control eyes and in 2 vitrectomized eyes, and atrophy developed in 7 control and 4 vitrectomized eyes. The difference between vitrectomized eyes and fellow eyes for the combined end points of RPE geographic atrophy or CNV was significant (P = 0.02). CONCLUSIONS In this pilot study, we did not detect that vitrectomy increased the progression of AMD. In fact, it was associated with a reduced progression to geographic atrophy or CNV. Additional studies are needed to confirm or refute this association. FINANCIAL DISCLOSURE(S) The authors have no proprietary or commercial interest in any of the materials discussed in this article.
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Affiliation(s)
- A Brock Roller
- Vitreoretinal Service, Department of Ophthalmology and Visual Sciences, The University of Iowa Hospitals & Clinics, Iowa City, Iowa 52242, USA.
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Tosi J, Janisch KM, Wang NK, Kasanuki JM, Flynn JT, Lin CS, Tsang SH. Cellular and molecular origin of circumpapillary dysgenesis of the pigment epithelium. Ophthalmology 2009; 116:971-80. [PMID: 19410955 PMCID: PMC2717946 DOI: 10.1016/j.ophtha.2008.10.032] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2008] [Revised: 10/31/2008] [Accepted: 10/31/2008] [Indexed: 11/29/2022] Open
Abstract
PURPOSE We studied clinical phenotyping and TEAD1 expression in mice and humans to gain a better understanding of the primary origin in the pathogenesis of circumpapillary dysgenesis of the pigment epithelium. DESIGN Observational case series and experimental study. PARTICIPANTS Three female patients from an affected family were included for phenotypic study. Mice and human tissues were used for biochemistry and immunohistochemistry studies. METHODS We performed genetic analyses and longitudinal clinical, imaging, and electrophysiologic studies in a 3-generation family. Western blotting and immunohistochemistry were used to detect TEAD1 expression in mice and human retinal tissues. MAIN OUTCOME MEASURES Autofluorescence and optical coherence tomography (OCT) imaging were compared and reviewed from 3 patients. TEAD1 expression was compared in different tissues from mice and human samples. RESULTS A point mutation at T1261 in TEAD1 was detected in the mother. Autofluorescence and OCT imaging studies revealed choroid is involved earlier than retinal pigment epithelium (RPE). From immunoblot analysis, we discovered that TEAD1 and its cofactors YAP65 and FOXA2 are expressed in the choroid. Immunohistochemical analysis on frozen sections of mouse retina supports immunoblot results. CONCLUSIONS The primary cellular origin of circumpapillary dysgenesis of the pigment epithelium is within the choroid instead of the pigment epithelium. The loss of the RPE and photoreceptors in later stages of the disease is a secondary consequence of choroidal degeneration. Studies of the downstream targets of TEAD1 in choroidal cells will provide promising new research opportunities for the development of treatments for choroidal diseases. FINANCIAL DISCLOSURE(S) The author(s) have no proprietary or commercial interest in any materials discussed in this article.
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Affiliation(s)
- Joaquin Tosi
- Bernard and Shirlee Brown Glaucoma Laboratory, Department of Pathology and Cell Biology, Columbia University, 160 Fort Washington Ave., New York, NY 10032, USA
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Interobserver Repeatability of Heidelberg Retinal Flowmetry Using Pixel-by-Pixel Analysis. J Glaucoma 2009; 18:280-3. [DOI: 10.1097/ijg.0b013e318181544a] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Christen WG, Glynn RJ, Chew EY, Albert CM, Manson JE. Folic acid, pyridoxine, and cyanocobalamin combination treatment and age-related macular degeneration in women: the Women's Antioxidant and Folic Acid Cardiovascular Study. ARCHIVES OF INTERNAL MEDICINE 2009; 169:335-41. [PMID: 19237716 PMCID: PMC2648137 DOI: 10.1001/archinternmed.2008.574] [Citation(s) in RCA: 104] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
BACKGROUND Observational epidemiologic studies indicate a direct association between homocysteine concentration in the blood and the risk of age-related macular degeneration (AMD), but randomized trial data to examine the effect of therapy to lower homocysteine levels in AMD are lacking. Our objective was to examine the incidence of AMD in a trial of combined folic acid, pyridoxine hydrochloride (vitamin B(6)), and cyanocobalamin (vitamin B(12)) therapy. METHODS We conducted a randomized, double-blind, placebo-controlled trial including 5442 female health care professionals 40 years or older with preexisting cardiovascular disease or 3 or more cardiovascular disease risk factors. A total of 5205 of these women did not have a diagnosis of AMD at baseline and were included in this analysis. Participants were randomly assigned to receive a combination of folic acid (2.5 mg/d), pyridoxine hydrochloride (50 mg/d), and cyanocobalamin (1 mg/d) or placebo. Our main outcome measures included total AMD, defined as a self-report documented by medical record evidence of an initial diagnosis after randomization, and visually significant AMD, defined as confirmed incident AMD with visual acuity of 20/30 or worse attributable to this condition. RESULTS After an average of 7.3 years of treatment and follow-up, there were 55 cases of AMD in the combination treatment group and 82 in the placebo group (relative risk, 0.66; 95% confidence interval, 0.47-0.93 [P = .02]). For visually significant AMD, there were 26 cases in the combination treatment group and 44 in the placebo group (relative risk, 0.59; 95% confidence interval, 0.36-0.95 [P = .03]). CONCLUSIONS These randomized trial data from a large cohort of women at high risk of cardiovascular disease indicate that daily supplementation with folic acid, pyridoxine, and cyanocobalamin may reduce the risk of AMD.
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Affiliation(s)
- William G Christen
- Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 900 Commonwealth Avenue E, Boston, MA 02215-1204, USA.
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Ehrlich R, Harris A, Kheradiya NS, Winston DM, Ciulla TA, Wirostko B. Age-related macular degeneration and the aging eye. Clin Interv Aging 2008; 3:473-82. [PMID: 18982917 PMCID: PMC2682379 DOI: 10.2147/cia.s2777] [Citation(s) in RCA: 77] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023] Open
Abstract
Age-related macular degeneration (AMD) is an ocular disease that causes damage to the retinal macula, mostly in the elderly. Normal aging processes can lead to structural and blood flow changes that can predispose patients to AMD, although advanced age does not inevitably cause AMD. In this review, we describe changes that occur in the macular structure, such as the retinal pigment epithelium and Bruch's membrane, with advancing age and in AMD. The role of genetics in AMD and age-related changes in ocular blood flow that may play a role in the pathogenesis of AMD are also discussed. Understanding the pathophysiology of AMD development can help guide future research to further comprehend this disease and to develop better treatments to prevent its irreversible central vision loss in the elderly.
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Affiliation(s)
- Rita Ehrlich
- Indiana University School of Medicine, Department of Ophthalmology, Indianapolis, IN 46202, USA
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Fong AMY, Koh A, Lee K, Ang CL. Bietti's crystalline dystrophy in Asians: clinical, angiographic and electrophysiological characteristics. Int Ophthalmol 2008; 29:459-70. [PMID: 18854949 DOI: 10.1007/s10792-008-9266-7] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2007] [Accepted: 09/22/2008] [Indexed: 11/28/2022]
Abstract
This article describes nine Chinese patients with Bietti's crystalline dystrophy, including two families, one consisting of three siblings and the other a pair of sisters. All patients had the classic refractile deposits located in all layers of the retina, with varying degrees of pigment epithelium atrophy. However, paralimbal crystals were not seen in the anterior corneal stroma. We describe clinical, angiographical and electrophysiological characteristics, and also review the literature on Bietti's crystalline dystrophy. All patients had full eye examination, including best corrected visual acuity, biomicroscopy, applanation tonometry and dilated funduscopy. Fluorescein angiography and indocyanine green angiography were performed, together with visual fields and electrophysiologic studies. All nine of our patients were phenotypically heterogeneous, with varying age and symptoms at presentation, as well as different degrees of progression. Age was not found to be a predictor of severity. The differences in disease severity, even within sibling groups, suggested that perhaps other factors were at play in phenotypic expression. We found that in early ICGA, all stages of BCD had delayed choroidal filling, which has not been previously described. We also observed a relative derangement of inner choroidal circulation as evidenced by late hypofluorescence on the ICGA. However, it is as yet unclear whether this circulatory disturbance is due to primary involvement of the posterior ciliary arteries, or secondary to choroidal and/or retinal pigment epithelial atrophy. While the FA and ICGA findings were similar, we found that the true extent of the atrophic areas was better delineated by ICGA. ICGA was also superior in outlining the degree and extent of choroidal vascular compromise.
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Pemp B, Schmetterer L. Ocular blood flow in diabetes and age-related macular degeneration. Can J Ophthalmol 2008; 43:295-301. [PMID: 18443612 DOI: 10.3129/i08-049] [Citation(s) in RCA: 116] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
The 2 leading causes of blindness in adults in the industrialized nations, diabetic retinopathy and age-related macular degeneration, have been investigated thoroughly with respect to their pathogenesis. In recent years, it has been discovered that dysfunctional ocular microcirculation appears to play a part in the development of both diseases. In diabetic retinopathy, it has been shown that the disease is associated with early retinal vascular dysregulation. In the later states of the disease, retinal tissue hypoxia is a major trigger of sight-threatening neovascularization. In age-related macular degeneration, there is increasing evidence that reduced blood flow in the choroid is associated with the development and progression of the disease. Knowledge of the pathophysiological vascular states underlying these diseases is essential for the assessment and development of future therapies.
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Affiliation(s)
- Berthold Pemp
- Department of Clinical Pharmacology, Medical University of Vienna, Währinger Gürtel 18-20, Vienna, Austria
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37
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Riva CE, Schmetterer L. Microcirculation of the Ocular Fundus. Microcirculation 2008. [DOI: 10.1016/b978-0-12-374530-9.00018-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/20/2023]
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Metelitsina TI, Grunwald JE, DuPont JC, Ying GS, Brucker AJ, Dunaief JL. Foveolar choroidal circulation and choroidal neovascularization in age-related macular degeneration. Invest Ophthalmol Vis Sci 2008; 49:358-63. [PMID: 18172113 PMCID: PMC3077130 DOI: 10.1167/iovs.07-0526] [Citation(s) in RCA: 114] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022] Open
Abstract
PURPOSE To investigate in a longitudinal study whether foveolar choroidal blood flow changes are associated with the development of choroidal neovascularization (CNV) in AMD. METHODS Relative foveolar choroidal blood velocity (ChBVel), volume (ChBVol), and flow (ChBFlow) were assessed in 135 patients with AMD, at baseline and then annually with laser Doppler flowmetry. All study eyes had visual acuity of 20/40 or better and no CNV at the time of enrollment. Comparison of foveolar choroidal circulatory measurements at baseline and their change before the development of CNV was made between eyes that had CNV and those that did not. RESULTS CNV developed in 28 eyes during the study. Baseline average foveolar ChBVol and ChBFlow in these eyes were 24% (P < 0.0001) and 20% (P = 0.0007) lower than that observed in the 165 eyes in which CNV did not develop. In the eyes with CNV, foveolar ChBVol and ChBFlow decreased by 9.6% and 11.5% before the formation of CNV, whereas in the eyes that did not, they increased by 6.7% (P = 0.006) and 2.8% (P = 0.004), respectively. Eyes with lower baseline foveolar ChBFlow were more likely (risk ratio = 3.47, 95% CI: 1.24-8.70) to show visual loss of three or more lines than were eyes with a higher baseline ChBFlow (P = 0.005). CONCLUSIONS The development of CNV and visual loss are associated with lower choroidal circulatory parameters at baseline. In addition, the results suggest that decreases in the foveolar choroidal circulation precede the development of CNV in AMD and may play some role in its development.
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Affiliation(s)
- Tatyana I Metelitsina
- Department of Ophthalmology, Scheie Eye Institute, School of Medicine, University of Pennsylvania, 51 North 39th Street, Philadelphia, PA 19104, USA
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Koizumi H, Iida T, Saito M, Nagayama D, Maruko I. Choroidal circulatory disturbances associated with retinal angiomatous proliferation on indocyanine green angiography. Graefes Arch Clin Exp Ophthalmol 2007; 246:515-20. [DOI: 10.1007/s00417-007-0705-3] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2007] [Revised: 09/06/2007] [Accepted: 10/01/2007] [Indexed: 02/03/2023] Open
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Rechtman E, Harris A, Siesky B, Kagemann L, Danis RP, Sines D, Ciulla TA. The Relationship Between Retrobulbar and Choroidal Hemodynamics in Non-Neovascular Age-Related Macular Degeneration. Ophthalmic Surg Lasers Imaging Retina 2007; 38:219-25. [PMID: 17552388 DOI: 10.3928/15428877-20070501-06] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
BACKGROUND AND OBJECTIVE To evaluate the relationship between retrobulbar and choroidal hemodynamics in non-neovascular age-related macular degeneration. PATIENTS AND METHODS Thirteen patients with age-related macular degeneration were assessed by both color Doppler imaging and scanning laser ophthalmoscope indocyanine green (ICG) angiography. Color Doppler imaging was used to measure peak systolic and end diastolic velocity (from which the resistance index, a measure of the resistance to flow downstream, was calculated) in the retrobulbar vessels. Scanning laser ophthalmoscope ICG angiograms were analyzed by area dilution analysis for quantitative choroidal fluorescence intensity assessment. Color Doppler imaging parameters were correlated with scanning laser ophthalmoscope ICG area dilution analysis parameters. RESULTS A good correlation was found between the posterior ciliary arteries resistance index and scanning laser ophthalmoscope ICG area dilution analysis fluorescence duration. CONCLUSIONS Scanning laser ophthalmoscope ICG area dilution analysis "duration" may serve as an alternative to color Doppler imaging in assessing the resistance to blood flow in the posterior ciliary arteries.
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Zhu L, Zheng Y, von Kerczek CH, Topoleski LDT, Flower RW. Feasibility of extracting velocity distribution in choriocapillaris in human eyes from ICG dye angiograms. J Biomech Eng 2006; 128:203-9. [PMID: 16524331 DOI: 10.1115/1.2165692] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
Indocyanine green (ICG) dye angiography has been used by ophthalmologists for routine examination of the choroidal vasculature in human eyes for more than 20 years. In this study, a new approach is developed to extract information from ICG dye angiograms about blood velocity distribution in the choriocapillaris and its feeding blood vessels. ICG dye fluorescence intensity rise and decay curves are constructed for each pixel location in each image of the choriocapillaris in an ICG angiogram. It is shown that at each instant of time the magnitude of the local instantaneous dye velocity in the choriocapillaris is proportional to both the slope of the ICG dye fluorescence intensity curve and the dye concentration. This approach leads to determination of the absolute value of blood velocity in the choriocapillaris, assuming an appropriate scaling, or conversion factor can be determined. It also enables comparison of velocities in different regions of the choriocapillaris, since the conversion factor is independent of the vessel location. The computer algorithm developed in this study can be used in clinical applications for diagnostic purposes and for assessment of the efficacy of laser therapy in human eyes.
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Affiliation(s)
- L Zhu
- Department of Mechanical Engineering, University of Maryland, Baltimore County, Baltimore, MD 21250, USA.
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Figueroa M, Schocket LS, DuPont J, Metelitsina TI, Grunwald JE. Long-term effect of laser treatment for dry age-related macular degeneration on choroidal hemodynamics. Am J Ophthalmol 2006; 141:863-7. [PMID: 16527229 DOI: 10.1016/j.ajo.2005.11.049] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2005] [Revised: 11/25/2005] [Accepted: 11/30/2005] [Indexed: 11/30/2022]
Abstract
PURPOSE To determine whether laser treatment applied according to the complications of age-related macular degeneration prevention trial (CAPT) has an effect on the choroidal circulation. DESIGN Randomized controlled trial. METHODS This study included 30 CAPT patients with bilateral drusen. Laser Doppler flowmetry was used to measure relative choroidal blood flow (Ch(flow)) in the fovea. Measurements were obtained through dilated pupils in both eyes of each patient before photocoagulation was applied in one eye. Measurements were repeated at three months (30 patients) and 28 months (23 patients). RESULTS Average Ch(flow) at baseline, three months, and 28 months was 7.2 +/- 2.1 (+/-1 SD), 7.3 +/- 2.5, and 6.8 +/- 2.7 arbitrary units (AU) in the control eyes and 6.6 +/- 1.6, 7.0 +/- 2.3, and 7.8 +/- 3.0 AU in the treated eyes. In comparison to control eyes, there was no significant change in Ch(flow) in the treated eyes at three months after treatment. At 28 months, however, there was a 5.6% drop in Ch(flow) in control eyes and an 18.2% increase in Ch(flow) in treated eyes from baseline. The average difference of 23.8% between the percentage changes in Ch(flow) observed in the control and treated eyes was statistically significant (paired two-tailed Student t test; P = .05). CONCLUSIONS Our results suggest an increase in choroidal blood flow 28 months after laser treatment according to the CAPT protocol. This increase may play a role in the mechanism leading to the disappearance of drusen after photocoagulation. Whether removal of drusen after photocoagulation is beneficial to the patients is not known at this time.
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Affiliation(s)
- Mauricio Figueroa
- Department of Ophthalmology, Scheie Eye Institute, School of Medicine, University of Pennsylvania, 51 North 39th Street, Philadelphia, PA 19104, USA
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Metelitsina TI, Grunwald JE, DuPont JC, Ying GS. Effect of systemic hypertension on foveolar choroidal blood flow in age related macular degeneration. Br J Ophthalmol 2006; 90:342-6. [PMID: 16488959 PMCID: PMC1856936 DOI: 10.1136/bjo.2005.082974] [Citation(s) in RCA: 37] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Abstract
AIM To investigate the effect of systemic hypertension (SH) on the foveolar choroidal circulation in patients with age related macular degeneration (AMD). METHODS This study included 163 study eyes with early AMD characteristics of 124 AMD patients. Study eyes had visual acuity of 20/40 or better, drusen > or =63 microm, and/or RPE hypertrophy. 56 of the AMD patients had a history of SH and 47 of these patients were receiving antihypertensive medications. Laser Doppler flowmetry (Oculix) was used to assess relative choroidal blood velocity (ChBVel), volume (ChBVol), and flow (ChBFlow) in the centre of the fovea of the study eyes. Differences in the mean haemodynamic parameters between groups of eyes were assessed using analysis of variance (ANOVA) and a test of linear trend, with adjustment for the correlation between eyes of the same patient. RESULTS AMD patients with SH showed decreased ChBFlow in comparison with those without SH (ANOVA, p = 0.02). This association was maintained after adjustments for multiple factors (p = 0.04). CONCLUSIONS AMD patients with SH have lower ChBFlow than those without SH. This decrease in choroidal blood circulation may help explain the mechanism by which systemic hypertension may contribute to the progression of AMD and the development of choroidal neovascularisation.
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Affiliation(s)
- T I Metelitsina
- Department of Opthalmology, Scheie Eye Institute, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
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Thornton J, Edwards R, Mitchell P, Harrison RA, Buchan I, Kelly SP. Smoking and age-related macular degeneration: a review of association. Eye (Lond) 2006; 19:935-44. [PMID: 16151432 DOI: 10.1038/sj.eye.6701978] [Citation(s) in RCA: 348] [Impact Index Per Article: 18.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022] Open
Abstract
PURPOSE Age-related macular degeneration (AMD) is the leading cause of severe and irreversible vision loss in the Western world. As there is no effective treatment for all types of AMD, identifying modifiable risk factors is of great importance. This review evaluates the epidemiological evidence associating smoking with AMD. METHODS Systematic review of published epidemiological studies evaluated against established criteria for evidence of a causal relationship. RESULTS In total, 17 studies (cross-sectional studies, prospective cohort studies, and case-control studies) were included in the review. A total of 13 studies found a statistically significant association between smoking and AMD with increased risk of AMD of two- to three-fold in current-smokers compared with never-smokers. Five studies found no association between smoking and AMD. There was also evidence of dose-response, a temporal relationship and reversibility of effect. CONCLUSION The literature review confirmed a strong association between current smoking and AMD, which fulfilled established causality criteria. Cigarette smoking is likely to have toxic effects on the retina. In spite of the strength of this evidence, there appears to be a lack of awareness about the risks of developing eye disease from smoking among both healthcare professionals and the general public.
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Affiliation(s)
- J Thornton
- Evidence for Population Health Unit, Division of Epidemiology and Health Sciences, University of Manchester, Manchester, UK
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Harris A, Bingaman D, Ciulla TA, Martin B. Retinal and Choroidal Blood Flow in Health and Disease. Retina 2006. [DOI: 10.1016/b978-0-323-02598-0.50011-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/23/2023]
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Walsh AC, Updike PG, Sadda SR. Quantitative Fluorescein Angiography. Retina 2006. [DOI: 10.1016/b978-0-323-02598-0.50058-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
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Abstract
This review presents a new unified view of the pathogenesis of three common causes of acquired retinal degenerative disease-diabetic retinopathy, age related macular degeneration, and retinopathy of prematurity. In these three conditions, angiogenesis has a predominant role in the development of sight threatening pathology. Angiogenesis is controlled by among other factors the expression of vascular endothelial growth factor (VEGF), which in turn is regulated by absolute and relative lack of oxygen. The severe pathological manifestations of these three conditions are not part of a general underlying disease process because they are peculiar to the eye, and the profound hypoxia that develops in normal retina during dark adaptation (rod driven hypoxia) is an adequate and elegant additional factor to explain their pathogenesis. A large number of experimental reports support this conclusion, although rod driven anoxia is not generally considered as a causal factor in ocular disease. However, the hypothesis can be critically tested, and also suggests novel methods of treatment and prevention of these conditions that may be simpler and more inexpensive than current therapies and that have a smaller potential for adverse effects.
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Affiliation(s)
- G B Arden
- Henry Wellcome Laboratories, Applied Vision Research Centre, Department of Optometry and Visual Science, City University, Northampton Square, London EC1V 0HB, UK.
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Mori K, Gehlbach PL, Ito YN, Yoneya S. DECREASED ARTERIAL DYE-FILLING AND VENOUS DILATION IN THE MACULAR CHOROID ASSOCIATED WITH AGE-RELATED MACULAR DEGENERATION. Retina 2005; 25:430-7. [PMID: 15933588 DOI: 10.1097/00006982-200506000-00006] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
PURPOSE To compare the angioarchitecture of choroidal arteries and veins in patients with age-related macular degeneration (AMD) to the angioarchitecture of age-matched normal subjects using indocyanine green (ICG) angiography. METHODS ICG angiography was performed in 35 consecutive AMD patients and 18 normal age-matched volunteers with a fundus ICG camera. ICG video images, including the arterial and venous phases, were quantitatively analyzed using image analyzing software. RESULTS In patients with AMD, the choroidal arterioles are dilated, fewer, run a straighter course, and possess fewer bifurcations. The number of choroidal arteries and the macular fluorescent intensity in the arterial phase of choroidal filling was significantly less in patients with AMD as compared to age-matched normal controls (P = 0.008). The mean and maximum caliber of choroidal veins in the macula was dilated in AMD eyes than in age-matched normal control eyes (P < 0.001). There was no statistically significant difference in arterial dye filling or venous caliber observed in AMD eyes, with or without choroidal neovascular membrane (CNV). CONCLUSION Choroidal arterial perfusion in the macula was significant decreased in eyes with AMD with and without CNV, and was associated with choroidal venous dilation. These observations implicate poor choroidal perfusion of the macula in the pathogenesis of AMD.
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Affiliation(s)
- Keisuke Mori
- Department of Ophthalmology, Saitama Medical School, Iruma, Saitama, Japan.
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Comer GM, Ciulla TA, Heier JS, Criswell MH. Future pharmacological treatment options for nonexudative and exudative age-related macular degeneration. Expert Opin Emerg Drugs 2005; 10:119-35. [PMID: 15757408 DOI: 10.1517/14728214.10.1.119] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
Age-related macular degeneration (AMD) is the leading cause of irreversible vision loss in the industrialised world. Within the past decade, researchers have introduced many promising prevention and treatment options in an attempt to minimise the central vision loss imparted from AMD. Based on large-scale, randomised, prospective, placebo-controlled trials, a specially formulated combination of the antioxidants vitamin C, vitamin E, beta-carotene, copper and zinc is the only proven means of AMD prophylaxis. Thermal laser photocoagulation and photodynamic therapy with verteporfin are the only standard treatment options. However, efficacy is limited and treatment is only applicable to a minority of AMD patients. Thus, alternative pharmacological interventions are in all phases of clinical development. Researchers are guardedly optimistic that these advances may change the entire approach to AMD management in the near future. This review article will detail the currently accepted treatment options, as well as describe several of the more promising investigational pharmacological approaches to AMD.
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Affiliation(s)
- Grant M Comer
- Indiana University School of Medicine, Department of Ophthalmology, 702 Rotary Circle, Indianapolis, IN 46202, USA.
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Guymer RH, Chiu AWI, Lim L, Baird PN. HMG CoA reductase inhibitors (statins): do they have a role in age-related macular degeneration? Surv Ophthalmol 2005; 50:194-206. [PMID: 15749309 DOI: 10.1016/j.survophthal.2004.12.002] [Citation(s) in RCA: 44] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
Age-related macular degeneration is a progressive late onset disease affecting central vision. It is the leading cause of irreversible blindness in developed countries, and with the aging population the problem is increasing. Current treatment options are limited to the late stage of the disease when central vision is already under great threat, and even new treatments make little impact on the rate of blindness. Intervention earlier in the disease may prove more rewarding, but to date little progress has been made with this approach. Epidemiologic, genetic, and pathological evidence continues to accumulate, suggesting a possible link between risk factors for cardiovascular diseases and age-related macular degeneration. This article reviews the evidence and discusses the rationale behind the recent suggestions that cholesterol-lowering agents may be useful in the treatment of early age-related macular degeneration. The cholesterol-lowering family of drugs called statins are 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) inhibitors with pleiotropic actions. Their therapeutic effects in cardiovascular disease and dyslipidaemia have been well proven. In this review we will outline the known actions of statins and discuss possible ways that they may impact on age-related macular degeneration.
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Affiliation(s)
- Robyn Heather Guymer
- Centre for Eye Research Australia, Department of Ophthalmology, University of Melbourne, East Melbourne, Australia
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