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To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Download ; Lipids are implicated in the pathogenesis of age-related macular degeneration (AMD). The relationship between systemic lipids and AMD has not been well characterized. The objective was to investigate the relationship between serum lipids and AMD in older adults using a lipidomic approach. In a case-control study, 240 adults, aged ≥66 years, a third each having geographic atrophy, neovascular AMD, or no signs of AMD, were selected from a population-based sample of participants in the Age Gene/Environment Susceptibility-Reykjavik Study. The exposure was serum lipids and risk factors for AMD. The outcome was late AMD, assessed through fundus images taken through dilated pupils using a 45-degree digital camera and grading for neovascular AMD and geographic atrophy using the modified Wisconsin Age-Related Maculopathy Grading System. Of 177 serum lipid species measured, there were no significant differences in serum lipids between controls and those with geographic atrophy or neovascular AMD, respectively. Adults with neovascular AMD had higher total serum lysophosphatidylcholine (LPC) (P = 0.004) and serum LPC 18:0 (P = 0.0002) compared to those with geographic atrophy. Late AMD was not characterized by alterations in systemic lipids compared with normal controls. These findings suggest that there may be differences in the LPC pathway between adults with neovascular AMD and geographic atrophy. ; National Institutes of Health National Institute on Aging National Eye Institute Iceland Heart Association Icelandic Parliament University of Iceland Research Fund

Publisher's version (útgefin grein) ; Background: Lipids are implicated in the pathogenesis of age-related macular degeneration (AMD). The relationship between systemic lipids and AMD has not been well characterized. The objective was to investigate the relationship between serum lipids and AMD in older adults using a lipidomic approach. Methods: In a case-control study, 240 adults, aged ≥66 years, a third each having geographic atrophy, neovascular AMD, or no signs of AMD, were selected from a population-based sample of participants in the Age Gene/Environment Susceptibility-Reykjavik Study. The exposure was serum lipids and risk factors for AMD. The outcome was late AMD, assessed through fundus images taken through dilated pupils using a 45-degree digital camera and grading for neovascular AMD and geographic atrophy using the modified Wisconsin Age-Related Maculopathy Grading System. Results: Of 177 serum lipid species measured, there were no significant differences in serum lipids between controls and those with geographic atrophy or neovascular AMD, respectively. Adults with neovascular AMD had higher total serum lysophosphatidylcholine (LPC) (P = 0.004) and serum LPC 18:0 (P = 0.0002) compared to those with geographic atrophy. Conclusion: Late AMD was not characterized by alterations in systemic lipids compared with normal controls. These findings suggest that there may be differences in the LPC pathway between adults with neovascular AMD and geographic atrophy. ; This work was supported by National Institutes of Health grants R01 AG027012 and R01 EY017362, the Intramural Research Programs of the National Institute on Aging and the National Eye Institute (ZIAEY00401 and National Institutes of Health contract numbers N01-AG-1-2100 and HHSN271201200022C), the Iceland Heart Association, the Icelandic Parliament, and the University of Iceland Research Fund. The National Eye Institute was involved in the design and conduct of the study in regard to collection of fundus photographs. The funders had no role in data collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. ; Peer Reviewed

Abstract
Age-related macular degeneration (AMD) is a progressive degenerative eye disease. Neovascular age-related macular degeneration (nAMD) is the advanced form of AMD characterised by abnormal growth of newly formed blood vessels in chorioidea which typically involves fluid accumulation in the retina or retinal haemorrhage, retinal epithelial detachments, hard exudate or subretinal scars. The process of angiogenesis is controlled by ocular angiogenic factors, which have enabled the development of different treatment options aimed at these factors. This review aims to compile the available information about the most commonly identified ocular angiogenic factors, uncovering their role in the pathogenesis of nAMD and assessing their application possibilities as biomarkers of disease identification and treatment.

In the developed world, age-related macular degeneration (AMD) is one of the major causes of irreversible blindness in the elderly. Although management of neovascular AMD (wet AMD) has dramatically progressed, there is still no effective treatment for nonneovascular AMD (dry AMD), which is characterized by retinal pigment epithelial (RPE) cell death (or dysfunction) and microenvironmental disruption in the retina. Therefore, RPE replacement and microenvironmental regulation represent viable treatments for dry AMD. Recent advances in cell biology have demonstrated that RPE cells can be easily generated from several cell types (pluripotent stem cells, multipotent stem cells, or even somatic cells) by spontaneous differentiation, coculturing, defined factors or cell reprogramming, respectively. Additionally, in vivo studies also showed that the restoration of visual function could be obtained by transplanting functional RPE cells into the subretinal space of recipient. More importantly, clinical trials approved by the US government have shown promising prospects in RPE transplantation. However, key issues such as implantation techniques, immune rejection, and xeno-free techniques are still needed to be further investigated. This review will summarize recent advances in cell transplantation for dry AMD. The obstacles and prospects in this field will also be discussed.

Supanji Supanji,1– 4 Dewi Fathin Romdhoniyyah,1,2 Muhammad Bayu Sasongko,1,2,4 Angela Nurini Agni,1,2,4 Firman Setya Wardhana,1,2,4 Tri Wahyu Widayanti,1,2,4 Muhammad Eko Prayogo,1,2,4 Ayudha Bahana Ilham Perdamaian,1,2 Aninditta Dianratri,1,2 Masashi Kawaichi,5 Chio Oka5 1Department of Ophthalmology, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia; 2Department of Ophthalmology, Dr. Sardjito General Hospital, Yogyakarta, Indonesia; 3Ophthalmology Clinic, Military Air Force Central Hospital Dr. Suhardi Hardjolukito, Yogyakarta, Indonesia; 4Ophthalmology Clinic, Dr YAP Eye Hospital, Yogyakarta, Indonesia; 5Laboratory of Gene Function in Animals, Nara Institute of Science and Technology, Ikoma, Nara, JapanCorrespondence: Supanji SupanjiDepartment of Ophthalmology, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Jalan Farmako Sekip Utara, Yogyakarta, 55281, IndonesiaTel +62 274 560300Fax +62 274 581 876Email supanji@ugm.ac.idPurpose: This study aimed to determine the association of ARMS2 A69S, ARMS2 del443ins54, and CFH Y402H polymorphisms with neovascular age-related macular degeneration (nAMD) for the first time in an Indonesian population.Patients and Methods: Our case–control study involved 104 nAMD and 100 control subjects. AMD diagnosis was evaluated by retinal specialists based on color fundus photography and optical coherence tomography. The polymorphisms on CFH Y402H and ARMS2 A69S were analyzed by PCR-restriction fragment length polymorphism (PCR-RFLP), whereas ARMS2 del443ins54 was evaluated by PCR-based assay.Results: Significant allelic associations with nAMD were detected on all polymorphisms (P< 0.05), with stronger association with the ARMS2 A69S (OR 3.13; 95% CI 2.08– 4.71; P< 0.001) and ARMS2 del443ins54 (OR 3.28; 95% CI 2.17– 4.95; P< 0.001) polymorphisms than with CFH Y402H (OR 2.08; 95% CI 1.08– 3.99; P=0.028). Genotype analysis showed a statistical difference between nAMD and the control group for all polymorphisms (P< 0.05). However, the association with nAMD was weaker for CFH Y402H (P=0.043) than for ARMS2 A69S and ARMS2 del443ins54 (P< 0.001). A significant interaction between ARMS2 A69S and hypertension was documented (OR 9.53; 95% CI 3.61– 25.1; P< 0.001).Conclusion: Our findings indicate that ARMS2 A69S and ARMS2 del443ins54 polymorphisms are strongly associated with the risk of nAMD for the first time in an Indonesian population. The risk of nAMD increased when the presence of risk alleles from ARMS2 A69S was combined with the presence of hypertension.Keywords: age-related macular degeneration, ARMS2, CFH, polymorphism

PURPOSE: To present the evolution of intravitreal therapy for retinal diseases and its impact on clinical practice. DESIGN: Retrospective literature review and personal perspective. METHODS: Retrospective literature review and personal perspective. RESULTS: Pharmacotherapeutic advances in retinal disease have been remarkable over the last 25 years. Almost all of the new drugs developed have required intravitreal administration to be highly effective, leading to an exponential increase in the annual number of intravitreal injections given. The use of intravitreal antibiotic injections to treat endophthalmitis, usually on a one-time basis, first familiarized ophthalmologists with this method of drug delivery. Ganciclovir was the first widely available, relatively inexpensive, compounded drug that was used for repeat intravitreal injection to treat a chronic retinal disease, followed by triamcinolone for diabetic macular edema and bevacizumab for neovascular AMD. Ganciclovir was formulated for sustained-release drug delivery to avoid frequent intravitreal injections, a goal that has been more elusive for anti-VEGF drugs. Political obstacles encountered while conducting some of the trials to evaluate these treatments were substantial. Addressing the issues they raised led to important national policy changes that will impact the conduct of future clinical trials. The first comparative efficacy trial of intravitreal therapies was the Comparison of AMD Treatments Trials (CATT). The primary results from CATT and the many publications that followed continue to shape the use of intravitreal therapy today. CONCLUSION: Intravitreal therapy has proven highly effective for the treatment of many retinal diseases. The treatment burden for patients from numerous injections, the cost to health care systems, and the impact on workflows in clinical practice have been substantial. Efforts to develop effective intravitreal therapies with reduced treatment burden and cost are ongoing.

Intro -- Foreword -- Foreword -- Preface -- Contents -- About the Editor -- 1: Choroidal Neovascular Membrane: Historical Perspectives -- 1.1 Introduction -- 1.2 Historical Perspectives of Choroidal Neovascularization -- 1.3 Early Epidemiological Studies of Choroidal Neovascularization -- 1.4 Beaver Dam Eye Study -- 1.5 Blue Mountain Eye Study -- 1.6 Summary -- References -- Part I: Basic Science -- 2: Pathogenesis of Choroidal Neovascularization -- 2.1 Choroidal Neovascularization in Other Diseases -- 2.2 What Do These Patients Have in Common? -- 2.3 What Do We Know from Animal Models? -- References -- 3: Histopathology of Choroidal Neovascularization -- 3.1 General Histopathology of CNV -- 3.2 Inflammatory Associated CNV -- 3.2.1 Non-granulomatous Inflammation -- 3.2.1.1 Presumed Ocular Histoplasmosis Syndrome (POHS) -- 3.2.1.2 Punctate Inner Choroidopathy (PIC) -- 3.2.1.3 Serpiginous Choroiditis (SC) -- 3.2.1.4 Acute Posterior Multifocal Placoid Pigment Epitheliopathy (APMPPE) -- 3.2.1.5 Behçet's Disease -- 3.2.1.6 Pars Planitis -- 3.2.2 Granulomatous Inflammation -- 3.2.2.1 Toxoplasmosis -- 3.2.3 Tuberculosis -- 3.2.4 Vogt-Koyanagi-Harada (VKH) Syndrome -- 3.2.5 Sarcoidosis -- 3.3 Degeneration Associated CNV -- 3.3.1 Neovascular Age-Related Macular Degeneration (AMD) -- 3.3.2 Myopic Neovascular Maculopathy -- 3.3.3 Pachychoroid Related CNV -- 3.3.4 Polypoidal Choroidal Vasculopathy (PCV) -- 3.3.5 Macular Telangiectasia -- 3.3.6 CNV Secondary to Angioid Streaks -- 3.3.7 Best Associated CNV -- 3.4 Traumatic Associated CNV -- 3.4.1 Post-trauma CNV -- 3.4.2 LASER Induced CNV -- 3.5 Tumoral Associated CNV -- 3.5.1 Choroidal Osteoma -- 3.5.2 Choroidal Nevus -- 3.6 Development Alterations or Malformations Associated CNV -- 3.6.1 Coloboma -- 3.7 Unknown: Idiopathic CNV -- References.

Objectives: To examine the feasibility of automatically segmented choroidal vessels in three-dimensional (3D) 1060-nmOCT by testing repeatability in healthy and AMD eyes and by mapping Haller's and Sattler's layer thickness in healthy eyes Methods: Fifty-five eyes (from 45 healthy subjects and 10 with non-neovascular age-related macular degeneration (AMD) subjects) were imaged by 3D-1060-nmOCT over a 36°x36° field of view. Haller's and Sattler's layer were automatically segmented, mapped and averaged across the Early Treatment Diabetic Retinopathy Study grid. For ten AMD eyes and ten healthy eyes, imaging was repeated within the same session and on another day. Outcomes were the repeatability agreement of Haller's and Sattler's layer thicknesses in healthy and AMD eyes, the validation with ICGA and the statistical analysis of the effect of age and axial eye length (AL) on both healthy choroidalsublayers. Results: The coefficients of repeatability for Sattler's and Haller's layers were 35% and 21% in healthy eyes and 44% and 31% in AMD eyes, respectively. The mean±SD healthy central submacular field thickness for Sattler's and Haller's was 87±56 µm and 141±50 µm, respectively, with a significant relationship for AL (P<.001). Conclusions: Automated Sattler's and Haller's thickness segmentation generates rapid 3D measurements with a repeatability correspondingto reported manual segmentation. Sublayers in healthy eyes thinnedsignificantly with increasing AL. In the presence of the thinned Sattler's layer in AMD, careful measurement interpretation is needed. Automatic choroidal vascular layer mapping may help to explain if pathological choroidal thinning affects medium and large choroidal vasculature in addition to choriocapillaris loss. ; Macular Vision Research Foundation ; Medical University of Vienna ; European Union (project FUN OCT (FP7 HEALTH, contract no. 201880)) ; European Union (FAMOS (FP7 ICT 317744)) ; European Union (FWF-NFN 'Photoacoustic imaging in biology and Medicine', Oesterreichische Nationalbank Jubilaumsfonds projekt (14294)) ; National Institutes of Health (U.S.) (NIH R01-EY011289-27) ; Deutsche Forschungsgemeinschaft (DFG-GSC80-SAOT) ; Deutsche Forschungsgemeinschaft (DFG-GSC80-SAOT, DFG-HO-1791/11-1) ; Carl Zeiss Meditec, Inc. ; FEMTOLASERS (Firm) ; Christian Doppler Society

BACKGROUND: Age-related macular degeneration (AMD) is the leading cause of visual loss in older people. Advanced AMD takes two forms, neovascular (wet) and atrophic (dry). Stargardt disease (STGD) is the commonest form of inherited macular dystrophy. OBJECTIVE: To carry out a systematic review of treatments for dry AMD and STGD, and to identify emerging treatments where future NIHR research might be commissioned. DESIGN: Systematic review. METHODS: We searched MEDLINE, EMBASE, Web of Science and The Cochrane Library from 2005 to 13 July 2017 for reviews, journal articles and meeting abstracts. We looked for studies of interventions that aim to preserve or restore vision in people with dry AMD or STGD. The most important outcomes are those that matter to patients: visual acuity (VA), contrast sensitivity, reading speed, ability to drive, adverse effects of treatment, quality of life, progression of disease and patient preference. However, visual loss is a late event and intermediate predictors of future decline were accepted if there was good evidence that they are strong predictors of subsequent visual outcomes. These include changes detectable by investigation, but not necessarily noticed by people with AMD or STGD. ClinicalTrials.gov, the World Health Organization search portal and the UK Clinical Trials gateway were searched for ongoing and recently completed clinical trials. RESULTS: The titles and abstracts of 7948 articles were screened for inclusion. The full text of 398 articles were obtained for further screening and checking of references and 112 articles were included in the final report. Overall, there were disappointingly few good-quality studies (including of sufficient size and duration) reporting useful outcomes, particularly in STGD. However we did identify a number of promising research topics, including drug treatments, stem cells, new forms of laser treatment, and implantable intraocular lens telescopes. In many cases, research is already under way, funded by industry or governments. LIMITATIONS: In AMD, the main limitation came from the poor quality of much of the evidence. Many studies used VA as their main outcome despite not having sufficient duration to observe changes. The evidence on treatments for STGD is sparse. Most studies tested interventions with no comparison group, were far too short term, and the quality of some studies was poor. FUTURE WORK: We think that the topics on which the Health Technology Assessment (HTA) and Efficacy Mechanism and Evaluation (EME) programmes might consider commissioning primary research are in STGD, a HTA trial of fenretinide (ReVision Therapeutics, San Diego, CA, USA), a visual cycle inhibitor, and EME research into the value of lutein and zeaxanthin supplements, using short-term measures of retinal function. In AMD, we suggest trials of fenretinide and of a potent statin. There is epidemiological evidence from the USA that the drug, levodopa, used for treating Parkinson's disease, may reduce the incidence of AMD. We suggest that similar research should be carried out using the large general practice databases in the UK. Ideally, future research should be at earlier stages in both diseases, before vision is impaired, using sensitive measures of macular function. This may require early detection of AMD by screening.

Vascular endothelial growth factor (VEGF) inhibitor medications such as ranibizumab, pegaptanib and bevacizumab are in use for the treatment of neovascular age-related macular degeneration (AMD) and other retinal conditions, although only ranibizumab and pegaptanib are approved for these conditions. In contrast, bevacizumab was developed for the intravenous systemic treatment of colorectal cancer and is not formulated for intravitreal use, but is commonly used off-label in ophthalmology. European Union legislation permits the use of drugs outside the terms of their licence ('off-label') only under certain circumstances, such as during clinical trials, compassionate/named patient use in the absence of a licensed alternative, emergency scenarios (e.g., pandemics) or at the discretion of a treating physician. In such cases, patients should be fully informed regarding their treatment and any potential risks involved. Off-label drug use can be an important tool to provide patients with treatment in cases of unmet medical need. However, the use of an unlicensed medicinal product, when a suitable licensed alternative is available, puts prescribing physicians at risk of liability if safety issues arise. Emerging clinical evidence suggests safety differences exist between ranibizumab and bevacizumab.