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1 Washington University Medical School, Campus Box 8096, 660 S Euclid Avenue, St Louis, MO 63110, USA; vangelder@vision.wustl.edu
Drs Mainster and Sparrow have provided an excellent perspective on the relative merits and difficulties of extending intraocular lens (IOL) absorption into the blue portion of the spectrum.1
However, they have not considered an unintentional consequence of blockage of the blue portion of the spectrum—reducing the activity of intrinsically photosensitive retinal ganglion cells.2,3 These cells subserve several non-visual ocular photoreceptive tasks, most prominently the entrainment of the circadian clock to external light-dark cycles.4 Pupillary light responses in mice are also at least partially controlled by this system, which appears to use a novel opsin (melanopsin)5,6 and possibly also a flavoprotein (cryptochrome)7,8 as photopigments.
Experiments in mice have suggested that the action spectrum for these photopigments peak in the blue, at approximately 480 nm, but with substantial sensitivity to blue light to 430 nm.9 This system appears to be functional in humans as documented by the action spectrum for light suppression of the pineal hormone, melatonin.10,11
The clinical importance of these photoreceptors is presently unknown, although it appears that loss of retinal ganglion cells predisposes children and young adults to disorders of sleep timing that outer retinal disease does not.12 While, as the authors note, there may be substantial benefit in blocking blue light phototoxicity, particularly for patients with pre-existing outer retinal degeneration, these lenses may have unintended consequences with respect to the timing of sleep and wakefulness or levels of certain neurohormones.
References
Mainster MA, Sparrow JR. How much blue light should an IOL transmit? Br J Ophthalmol 2003;87:1523–9.
Berson DM. Strange vision: ganglion cells as circadian photoreceptors. Trends Neurosci 2003;26:314–20.
Berson DM, Dunn FA, Takao M. Phototransduction by retinal ganglion cells that set the circadian clock. Science 2002;295:1070–3.
Freedman MS, Lucas RJ, Soni B, et al. Regulation of mammalian circadian behavior by non-rod, non-cone, ocular photoreceptors. Science 1999;284:502–4.
Panda S, Provencio I, Tu DC, et al. Melanopsin is required for non-image-forming photic responses in blind mice. Science 2003;301:525–7.
Hattar S, Lucas RJ, Mrosovsky N, et al. Melanopsin and rod-cone photoreceptive systems account for all major accessory visual functions in mice. Nature 2003;424:75–81.
Van Gelder RN, Wee R, Lee JA, et al. Reduced pupillary light responses in mice lacking cryptochromes. Science 2003;299:222.
Selby CP, Thompson C, Schmitz TM, et al. Functional redundancy of cryptochromes and classical photoreceptors for nonvisual ocular photoreception in mice. Proc Natl Acad Sci USA 2000;97:14697–702.
Lucas RJ, Douglas RH, Foster RG. Characterization of an ocular photopigment capable of driving pupillary constriction in mice. Nat Neurosci 2001;4:621–6.
Brainard GC, Hanifin JP, Greeson JM, et al. Action spectrum for melatonin regulation in humans: evidence for a novel circadian photoreceptor. J Neurosci 2001;21:6405–12.
Thapan K, Arendt J, Skene DJ. An action spectrum for melatonin suppression: evidence for a novel non-rod, non-cone photoreceptor system in humans. J Physiol (Lond) 2001;535:261–7.
Wee R, Van Gelder RN. Sleep disturbances in young subjects with visual dysfunction. Ophthalmology. (in press).
Author’s reply
M A Mainster2
2 University of Kansas Medical School, 3901 Rainbow Boulevard, MS3009, Kansas City, KS 66160-7379, USA; mmainste@kumc.edu
I appreciate Van Gelder’s thoughtful comments regarding the potential consequences of a ultraviolet + blue light absorbing intraocular lens (IOL) on circadian rhythmicity. I agree that the clinical importance of retinal ganglion photoreceptors is currently unknown and that decreasing the amount of blue light reaching them might affect their function. Conversely, if photosensitive ganglia respond to circadian changes in their blue light exposure rather than just the magnitude of that exposure, a ultraviolet + blue light absorbing IOL may not impair ganglion function.
Van Gelder re-emphasises our finding that IOL chromophore selection balances the potential loss of useful visual function against a reduction in the risk of acute ultraviolet-blue phototoxicity. Our paper did not state, however, that ultraviolet + blue absorbing IOLs were desirable for people with outer retinal degeneration. Indeed, blue light is more important in scotopic than photopic vision. Individuals with age related macular degeneration have greater night-time visual problems than their peers without it, and these scotopic problems may be exacerbated if a significant amount of blue light is blocked by an IOL.