Abstract
Visual function improves with oxygen inhalation in people with diabetes even in the absence of visible retinopathy. Rods consume the most oxygen in the retina due to the high metabolic activity required to maintain the dark current. Therefore, Arden hypothesized that in diabetes where oxygen supply may also be affected due to the changes in retinal vasculature, prevention of dark adaptation may be a viable option to prevent or decrease the rate of progression of diabetic retinopathy. Animal experiments have proven that the absence of rods decreases the development of retinal neovascularisation. The same principle applies to panretinal photocoagulation, an established treatment for proliferative diabetic retinopathy. Recently, a few clinical studies have also shown that preventing dark adaptation by suppressing rods with 500-nm light source at night decreases the rate of progression of early diabetic retinopathy and maculopathy in the short-term. We await the results of a large two-year multi-centre trial (CLEOPATRA trial) to evaluate the long-term effects of decreasing dark adaptation by applying a 500nm light source as a mask over eyes with non-central diabetic macular oedema.
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
References
Stem MS, Gardner TW . Neurodegeneration in the pathogenesis of diabetic retinopathy: molecular mechanisms and therapeutic implications. Curr Med Chem 2013; 20 (26): 3241–3250.
Stitt AW, Curtis TM, Chen M, Medina RJ, McKay GJ, Jenkins A et al. The progress in understanding and treatment of diabetic retinopathy. Prog Retin Eye Res 2015 e-pub ahead of print 18 August 2015 doi:10.1016/j.preteyeres.2015.08.001.
Arden GB, Wolf JE, Tsang Y . Does dark adaptation exacerbate diabetic retinopathy? Evidence and a linking hypothesis. Vision Res 1998; 38: 1723–1729.
Arden GB . The absence of diabetic retinopathy in patients with retinitis pigmentosa: implications for pathophysiology and possible treatment. Br J Ophthalmol 2001; 85 (3): 366–370.
Arden GB, Sidman RL, Arap W, Schlingemann RO . Spare the rod and spoil the eye. Br J Ophthalmol 2005; 89 (6): 764–769.
Ramsey DJ, Arden GB . Hypoxia and dark adaptation in diabetic interactions, consequences, and therapy. Curr Diab Rep 2015; 15 (12): 118.
Kern TS, Engerman RL . Capillary lesions develop in retina rather than cerebral cortex in diabetes and experimental galactosemia. Arch Ophthalmol 1996; 114: 306–310.
de Gooyer TE, Stevenson KA, Humphries P, Simpson DA, Gardiner TA, Stitt AW . Retinopathy is reduced during experimental diabetes in a mouse model of outer retinal degeneration. Invest Ophthalmol Vis Sci 2006; 47 (12): 5561–5568.
Ames A, Li YY, Heher EG, Kimble CR . Energy metabolism of rabbit retina as related to function: high cost of Na transport. J Neurosci 1992; 12: 840–853.
Linsenmeier RA, Braun RD . Oxygen distribution and consumption in the cat retina during normoxia and hypoxemia. J Gen Physiol 1992; 99 (2): 177–197.
Braun RD, Linsenmeier RA, Goldstick TK . Oxygen consumption in the inner and outer retina of the cat. Invest Ophthalmol Vis Sci 1995; 36 (3): 542–554.
Haugh LM, Linsenmeier RA, Goldstick TK . Mathematical models of the spatial distribution of retinal oxygen tension and consumption, including changes upon illumination. Ann Biomed Eng 1990; 18 (1): 19–36.
Ahmed J, Braun RD, Dunn R Jr, Linsenmeier RA . Oxygen distribution in the macaque retina. Invest Ophthalmol Vis Sci 1993; 34 (3): 516–521.
Wangsa-Wirawan ND, Linsenmeier RA . Retinal oxygen: fundamental and clinical aspects. Arch Ophthalmol 2003; 121 (4): 547–557.
Lau JC, Linsenmeier RA . Oxygen consumption and distribution in the Long-Evans rat retina. Exp Eye Res 2012; 102: 50–58.
Wang S, Birol G, Budzynski E, Flynn R, Linsenmeier RA . Metabolic responses to light in monkey photoreceptors. Curr Eye Res 2010; 35 (6): 510–518.
Birol G, Wang S, Budzynski E, Wangsa-Wirawan ND, Linsenmeier RA . Oxygen distribution and consumption in the macaque retina. Am J Physiol Heart Circ Physiol 2007; 293 (3): H1696–H1704.
Okawa H, Sampath AP, Laughlin SB, Fain GL . ATP consumption by mammalian rod photoreceptors in darkness and in light. Curr Biol 2008; 18 (24): 1917–1921.
Haugh-Scheidt LM, Griff ER, Linsenmeier RA . Light-evoked oxygen responses in the isolated toad retina. Exp Eye Res 1995; 61: 73–81.
Muir ER, RenterÃa RC, Duong TQ . Reduced ocular blood flow as an early indicator of diabetic retinopathy in a mouse model of diabetes. Invest Ophthalmol Vis Sci 2012; 53 (10): 6488–6494.
Cao J, McLeod S, Merges CA, Lutty GA . Choriocapillaris degeneration and related pathologic changes in human diabetic eyes. Arch Ophthalmol 1998; 116 (5): 589–597.
Bailey CC, Sparrow JM . Visual symptomatology in patients with sight-threatening diabetic retinopathy. Diabet Med 2001; 18 (11): 883–888.
Drasdo N, Chiti Z, Owens DR, North RV . Effect of darkness on inner retinal hypoxia in diabetes. Lancet 2002; 359: 2251–2253.
Harris A, Arend O, Danis RP, Evans D, Wolf S, Martin BJ . Hyperoxia improves contrast sensitivity in early diabetic retinopathy. Br J Ophthalmol 1996; 80: 209–213.
Kurtenbach A, Mayser HM, Jagle H, Fritsche A, Zrenner E . Hyperoxia, hyperglycemia, and photoreceptor sensitivity in normal and diabetic subjects. Vis Neurosci 2006; 23: 651–661.
Takamura Y, Tomomatsu T, Matsumura T, Arimura S, Gozawa M, Takihara Y et al. The effect of photocoagulation in ischemic areas to prevent recurrence of diabetic macular edema after intravitreal bevacizumab injection. Invest Ophthalmol Vis Sci 2014; 55 (8): 4741–4746.
Nguyen QD, Shah SM, Van Anden E, Jennifer U, Sung JU, Vitale S et al. Supplemental oxygen improves diabetic macular edema: a pilot study. Invest Ophthalmol Vis Sci 2004; 45: 617–624.
West SD, Nicoll DJ, Stradling JR . Prevalence of obstructive sleep apnoe men with type 2 diabetes. Thorax 2006; 61 (11): 945–950.
Leong WB, Jadhakhan F, Taheri S, Chen YF, Adab P, Thomas GN . Effect of obstructive sleep apnoea on diabetic retinopathy and maculopathy: a systematic review and meta-analysis. Diabet Med 2015 e-pub ahead of print 29 May 2015doi:10.1111/dme.12817.
Nannapaneni S, Ramar K, Surani S . Effect of obstructive sleep apnea on type 2 diabetes mellitus: a comprehensive literature review. World J Diabetes 2013; 4: 238–244.
Mason RH, West SD, Kiire CA, Groves DC, Lipinski HJ, Jaycock A et al. High prevalence of sleep disordered breathing in patients with diabetic macular edema. Retina 2012; 32 (9): 1791–1798.
Nishimuraa A, Kasai T, Tamura H, Yamato A, Yasuda D, Nagasawa K et al. Relationship between sleep disordered breathing and diabetic retinopathy. Analysis of 136 patients with diabetes. Diabetes Res Clin Pract 2015; 109: 306–311.
Arden GB, Gündüz MK, Kurtenbach A, Völker M, Zrenner E, Gündüz SB et al. A preliminary trial to determine whether prevention of dark adaptation affects the course of early diabetic retinopathy. Eye (Lond) 2010; 24 (7): 1149–1155.
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 (12): 1546–1554.
Sivaprasad S, Arden G, Prevost AT, Crosby-Nwaobi R, Holmes H, Kelly J et al. A multicentre phase III randomised controlled single-masked clinical trial evaluating the clinical efficacy and safety of light-masks at preventing dark-adaptation in the treatment of early diabetic macular oedema (CLEOPATRA): study protocol for a randomised controlled trial. Trials 2014; 15: 458.
Kern TS, Berkowitz BA . Photoreceptors in diabetic retinopathy. J Diabetes Investig 2015; 6 (4): 371–380.
Yagi T, MacLeish PR . Ionic conductances of monkey solitary cone inner segments. J Neurophysiol 1994; 71: 656–665.
Hoang QV, Linsenmeier RA, Chung CK, Curcio CA . Photoreceptor inner segments in monkey and human retina: mitochondrial density, optics, and regional variation. Vis Neurosci 2002; 19: 395–407.
Lucas RJ, Peirson SN, Berson DM, Brown TM, Cooper HM, Czeisler CA et al. Measuring and using light in the melanopsin age. Trends Neurosci 2014; 37 (1): 1–9.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Competing interests
SS is the Chief Investigator of the CLEOPATRA study. The other author declares no conflict of interest.
Rights and permissions
About this article
Cite this article
Sivaprasad, S., Arden, G. Spare the rods and spoil the retina: revisited. Eye 30, 189–192 (2016). https://doi.org/10.1038/eye.2015.254
Received:
Accepted:
Published:
Issue date:
DOI: https://doi.org/10.1038/eye.2015.254
This article is cited by
-
Retinal and choroidal thickness measurements in obstructive sleep apnea: impacts of continuous positive airway pressure treatment
Graefe's Archive for Clinical and Experimental Ophthalmology (2021)
-
Effects of emixustat hydrochloride in patients with proliferative diabetic retinopathy: a randomized, placebo-controlled phase 2 study
Graefe's Archive for Clinical and Experimental Ophthalmology (2021)
-
Measurement of dark adaptometry during ISCEV standard flash electroretinography
Documenta Ophthalmologica (2017)