期刊论文详细信息
Trials
Low-level night-time light therapy for age-related macular degeneration (ALight): study protocol for a randomized controlled trial
Alison M Binns3  Clare Bailey1  Tom H Margrain2  Claire McKeague2 
[1] Bristol Eye Hospital, Lower Maudlin Street, Bristol BS1 2LX, UK;School of Optometry and Vision Sciences, Cardiff University, Cardiff CF24 4 LU, UK;Division of Optometry and Visual Science, School of Health Sciences, City University, London EC1V 0HB, UK
关键词: Randomized controlled trial;    Light mask;    Hypoxia;    Biomarker;    Age-related macular degeneration;   
Others  :  829454
DOI  :  10.1186/1745-6215-15-246
 received in 2013-12-13, accepted in 2014-05-23,  发布年份 2014
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【 摘 要 】

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

【 授权许可】

   
2014 McKeague et al.; licensee BioMed Central Ltd.

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【 参考文献 】
  • [1]Resnikoff S, Pascolini D, Etya’ale D, Kocur I, Pararajasegaram R, Pokharel GP, Mariotti SP: Global data on visual impairment in the year 2002. Bull World Health Organ 2004, 82:844-851.
  • [2]Bunce C, Xing W, Wormald R: Causes of blind and partial sight certifications in England and Wales: April 2007-March 2008. Eye (Lond) 2010, 24:1692-1699.
  • [3]The CATT Research group: Ranibizumab and Bevacizumab for Neovascular Age-Related Macular Degeneration. N Engl J Med 2011, 364:1897-1908.
  • [4]Economics A: Future Sight Loss UK (1): the Economic Impact of Partial Sight and Blindness in the UK Adult Population. London: Royal National Institute of Blind People; 2009.
  • [5]Cruess AF, Zlateva G, Xu X, Pauleikhoff D, Lotery A, Mones J, Buggage R, Schaefer C, Knight T, Goss TF: Economic burden of bilateral macular degeneration multi-country observational study. Pharmacoeconomics 2008, 26:57-73.
  • [6]Dargent-Molina P, Favier F, Grandjean H, Baudoin C, Schott AM, Hausherr E, Meunier PJ, Breart G: Fall-related factors and risk of hip fracture: the EPIDOS prospective study. Lancet 1996, 348:145-149.
  • [7]Margrain TH, Nollett C, Shearn J, Stanford M, Edwards RT, Ryan B, Bunce C, Casten R, Hegel MT, Smith DJ: The Depression in Visual Impairment Trial (DEPVIT): trial design and protocol. BMC Psychiatry 2012, 12:57.
  • [8]Feigl B: Age-related maculopathy - linking aetiology and pathophysiological changes to the ischaemia hypothesis. Prog Retin Eye Res 2009, 28:63-86.
  • [9]Stefánsson E, Geirsdóttir A, Sigurdsson H: Metabolic physiology in age related macular degeneration. Prog Retin Eye Res 2011, 30:72-80.
  • [10]Ciulla TA, Harris A, Martin BJ: Ocular perfusion and age-related macular degeneration. Acta Ophthalmol Scand 2001, 79:108-115.
  • [11]Ciulla TA, Harris A, Kagemann L, Danis RP, Pratt LM, Chung HS, Weinberger D, Garzozi HJ: Choroidal perfusion perturbations in non-neovascular age related macular degeneration. Br J Ophthalmol 2002, 86:209-213.
  • [12]Feigl B: Age-related maculopathy in the light of ischaemia. Clin Exp Optom 2007, 90:263-271.
  • [13]Metelitsina TI, Grunwald JE, DuPont JC, Ying G-S, Brucker AJ, Dunaief JL: Foveolar choroidal circulation and choroidal neovascularization in age-related macular degeneration. Invest Ophthalmol Vis Sci 2008, 49:358-363.
  • [14]Sarks S, Cherepanoff S, Killingsworth M, Sarks J: Relationship of basal laminar deposit and membranous debris to the clinical presentation of early age-related macular degeneration. Invest Ophthalmol Vis Sci 2007, 48:968-977.
  • [15]Ciulla TA, Harris A, Chung HS, Danis RP, Kagemann L, McNulty L, Pratt LM, Martin BJ: Color Doppler imaging discloses reduced ocular blood flow velocities in nonexudative age-related macular degeneration. Am J Ophthalmol 1999, 128:75-80.
  • [16]Ahmed J, Braun RD, Dunn R, Linsenmeier RA: Oxygen distribution in the macaque retina. Invest Ophthalmol Vis Sci 1993, 34:516-521.
  • [17]Wangsa-Wirawan ND, Linsenmeier RA: Retinal oxygen: fundamental and clinical aspects. Arch Ophthalmol 2003, 121:547-557.
  • [18]Hagins WA, Ross PD, Tate RL, Yoshikami S: Transduction heats in retinal rods: tests of the role of cGMP by pyroelectric calorimetry. Proc Natl Acad Sci USA 1989, 86:1224-1228.
  • [19]Witmer AN, Vrensen GFJM, Van Noorden CJF, Schlingemann RO: Vascular endothelial growth factors and angiogenesis in eye disease. Prog Retin Eye Res 2003, 22:1-29.
  • [20]Dunaief JL, Dentchev T, Ying G-S, Milam AH: The role of apoptosis in age-related macular degeneration. Arch Ophthalmol 2002, 120:1435-1442.
  • [21]Karakucuk S, Oner AO, Goktas S, Siki E, Kose O: Color vision changes in young subjects acutely exposed to 3,000 m altitude. Aviat Space Environ Med 2004, 75:364-366.
  • [22]Connolly DM, Barbur JL, Hosking SL, Moorhead IR: Mild hypoxia impairs chromatic sensitivity in the mesopic range. Invest Ophthalmol Vis Sci 2008, 49:820-827.
  • [23]Vingrys AJ, Garner LF: The effect of a moderate level of hypoxia on human color vision. Doc Ophthalmol 1987, 66:171-185.
  • [24]Connolly DM, Hosking SL: Aviation-related respiratory gas disturbances affect dark adaptation: a reappraisal. Vis Res 2006, 46:1784-1793.
  • [25]Brinchmann-Hansen O, Myhre K: The effect of hypoxia upon macular recovery time in normal humans. Aviat Space Environ Med 1989, 60:1183-1186.
  • [26]Connolly DM, Hosking SL: Oxygenation state and mesopic sensitivity to dynamic contrast stimuli. Optom Vis Sci 2009, 86:1368-1375.
  • [27]Tinjust D, Kergoat S, Lovasik JV: Neuroretinal function during mild systemic hypoxia. Aviat Space Environ Med 2002, 73:1189-1194.
  • [28]Feigl B, Stewart IB, Brown B, Zele AJ: Local neuroretinal function during acute hypoxia in healthy older people. Invest Ophthalmol Vis Sci 2008, 49:807-813.
  • [29]Pavlidis M, Stupp T, Georgalas I, Georgiadou E, Moschos M, Thanos S: Multifocal electroretinography changes in the macula at high altitude: a report of three cases. Ophthalmologica 2005, 219:404-412.
  • [30]Chen JC, Firzke FW, Pauleikhoff D, Bird AC: Functional loss in age-related Bruch’s membrane change with choroidal perfusion defect. Invest Ophthalmol Vis Sci 1992, 33:334-340.
  • [31]Remulla JF, Gaudio AR, Miller S, Sandberg MA: Foveal electroretinograms and choroidal perfusion characteristics in fellow eyes of patients with unilateral neovascular age-related macular degeneration. Br J Ophthalmol 1995, 79:558-561.
  • [32]Arden GB: The absence of diabetic retinopathy in patients with retinitis pigmentosa: implications for pathophysiology and possible treatment. Br J Ophthalmol 2001, 85:366-370.
  • [33]Arden GB, Gunduz MK, Kurtenbach A, Volker M, Zrenner E, Gunduz SB, Kamis U, Ozturk BT, Okudan S: A preliminary trial to determine whether prevention of dark adaptation affects the course of early diabetic retinopathy. Eye (Lond) 2010, 24:1149-1155.
  • [34]Arden GB, Jyothi S, Hogg CH, Lee YF, Sivaprasad S: Regression of early diabetic macular oedema is associated with prevention of dark adaptation. Eye (Lond) 2011, 25:1546-1554.
  • [35]Wyszechki G, Stiles WS: Colour Science: Concepts and Methods, Quantitative Data and Formulae. New York: John Wiley; 1982.
  • [36]Moseley MJ, Bayliss SC, Fielder AR: Light transmission through the human eyelid: in vivo measurement. Ophthalmic Physiol Opt 1988, 8:229-230.
  • [37]Robinson J, Bayliss SC, Fielder AR: Transmission of light across the adult and neonatal eyelid in vivo. Vis Res 1991, 31:1837-1840.
  • [38]Ando K, Kripke DF: Light attenuation by the human eyelid. Biol Psychiatry 1996, 39:22-25.
  • [39]Winn B, Whitaker D, Elliott DB, Phillips NJ: Factors affecting light-adapted pupil size in normal human subjects. Invest Ophthalmol Vis Sci 1994, 35:1132-1137.
  • [40]Age-Related Eye Disease Study Research Group: A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E, beta carotene, and zinc for age-related macular degeneration and vision loss: AREDS report no. 8. Arch Ophthalmol 2001, 119:1417-1436.
  • [41]Bjelakovic G, Nikolova D, Gluud LL, Simonetti RG, Gluud C: Antioxidant supplements for prevention of mortality in healthy participants and patients with various diseases. Cochrane Database Syst Rev 2012, 3:CD007176.
  • [42]Yehoshua Z, Wang F, Rosenfeld PJ, Penha FM, Feuer WJ, Gregori G: Natural history of drusen morphology in age-related macular degeneration using spectral domain optical coherence tomography. Ophthalmology 2011, 118(12):2434-2441.
  • [43]Neelam K, Hogg RE, Stevenson MR, Johnston E, Anderson R, Beatty S, Chakravarthy U: Carotenoids and co-antioxidants in age-related maculopathy: design and methods. Ophthalmic Epidemiol 2008, 15(6):389-401.
  • [44]Stelmack JA, Szlyk JP, Stelmack TR, Demers-Turco P, Williams RT, Moran D, Massof RW: Psychometric properties of the Veterans Affairs Low-Vision Visual Functioning Questionnaire. Invest Ophthalmol Vis Sci 2004, 45:3919-3928.
  • [45]Ferris FL, Davis MD, Clemons TE: A simplified severity scale for age-related macular degeneration: AREDS Report No. 18. Arch Ophthalmol 2005, 123:1570-1574.
  • [46]Chylack LT Jr, Wolfe JK, Singer DM, Leske MC, Bullimore MA, Bailey IL, Friend J, McCarthy D, Wu SY: The Lens Opacities Classification System III. The Longitudinal Study of Cataract Study Group. Arch Ophthalmol 1993, 111(6):831-836.
  • [47]Buysse DJ, Reynolds CF, Monk TH, Berman SR, Kupfer DJ: The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research. Psychiatry Res 1989, 28:193-213.
  • [48]O’Neill-Biba M, Sivaprasad S, Rodriguez-Carmona M, Wolf JE, Barbur JL: Loss of chromatic sensitivity in AMD and diabetes: a comparative study. Ophthalmic Physiol Opt 2010, 30:705-716.
  • [49]Dimitrov PN, Robman LD, Varsamidis M, Aung K-Z, Makeyeva GA, Guymer RH, Vingrys AJ: Visual function tests as potential biomarkers in age-related macular degeneration. Invest Ophthalmol Vis Sci 2011, 52:9457-9469.
  • [50]Gaffney AJ, Binns AM, Margrain TH: The topography of cone mediated dark adaptation in age-related maculopathy. Optom Vis Sci 2011, 88:1080-1087.
  • [51]British Standards Institution: BS EN ISO 15004-2:2007: Ophthalmic Instruments. Fundamental Requirements and Test Methods. Light Hazard Protection. London; 2007.
  • [52]Wong TY, Chakravarthy U, Klein R, Mitchell P, Zlateva G, Buggage R, Fahrbach K, Probst C, Sledge I: The natural history and prognosis of neovascular age-related macular degeneration: a systematic review of the literature and meta-analysis. Ophthalmology 2008, 115(1):116-126.
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