Dear Editor

Drs Mainster and Sparrow have provided an excellent perspective on the relative merits and difficulties of extending 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 IOLS lenses may have unintended consequences with respect to the timing of sleep and wakefulness or levels of certain neuro-hormones.

References

1. Mainster MA, Sparrow JR. How much blue light should an IOL transmit? Br. J. Ophthalmol. 2003;87:1523-9.

2. Berson DM. Strange vision: ganglion cells as circadian photoreceptors. Trends Neurosci. 2003;26:314-20.

3. Berson DM, Dunn FA, Takao M. Phototransduction by retinal ganglion cells that set the circadian clock. Science. 2002;295:1070-3.

4. 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.

5. 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.

6. 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.

7. Van Gelder RN, Wee R, Lee JA, Tu DC. Reduced pupillary light responses in mice lacking cryptochromes. Science. 2003;299:222.

8. Selby CP, Thompson C, Schmitz TM, Van Gelder RN, Sancar A. Functional redundancy of cryptochromes and classical photoreceptors for nonvisual ocular photoreception in mice. Proc. Natl. Acad. Sci. U. S. A. 2000;97:14697-702.

9. Lucas RJ, Douglas RH, Foster RG. Characterization of an ocular photopigment capable of driving pupillary constriction in mice. Nat. Neurosci. 2001;4:621-6.

10. 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.

11. 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.

12. Wee R, Van Gelder RN. Sleep disturbances in young subjects with visual dysfunction. Ophthalmology. In press.