Speculation that light exposure is involved in the pathogenesis of age-related macular degeneration (AMD) remains unproven, despite almost a century of study, but it has prompted some manufacturers to introduce IOLs that restrict visible light as well as UV radiation. Blue-blocking IOLs attenuate substantial amounts of violet (400 nm to 440 nm) and blue (440 nm to 500 nm) light. It has been known for more than 50 years that blue light is important for vision in dim environments.1,2 A rapidly growing body of scientific evidence now documents that blue light is vital for optimal systemic and mental health.2,3 UV-blocking IOLs have provided pseudophakes with their best possible photoreception for more than 3 decades. Blue-blocking IOLs sacrifice rod and retinal ganglion photoreception for ineffective photoprotection against an unproven hazard. Here are the facts.
PHOTOTOXICITY AND AMD
AMD is a complex multifactorial process. Smoking and age are its only consistently documented risk factors. The phototoxicity-AMD hypothesis posits that photic retinopathy (ie, retinal phototoxicity) from repeated environmental light exposure causes AMD.2-4 Many mechanisms other than light have been postulated for AMD, including choroidal sclerosis, retinal pigment epithelium (RPE) dysfunction, genetic defects, retinoid deficiency, and inflammation.4
Acute retinal phototoxicity experiments and the phototoxicity-AMD hypothesis have been used to advocate blue-blocking IOLs, despite the fact that AMD is a chronic process, whereas photic retinopathy occurs only when retinal defenses are overwhelmed acutely by brilliant light exposures. The risk of UV-blue phototoxicity (ie, the blue light hazard) increases with decreasing wavelength (Figure 1).2,5 Thus, UV radiation is more hazardous than violet light, which is more hazardous than blue light. The international standard phototoxicity risk function5 Al (Figure 1) is based on experiments in which young dilated monkey eyes were exposed to intense light from lasers or powerful xenon lamps.6 Acute UV-blue photic retinopathy may injure the macula, but damage requires very high retinal irradiances such as those causing solar and welding arc macular injuries.7,8
Photic retinopathy and AMD both involve oxidative stress, but that does not mean that retinal phototoxicity causes AMD any more than it means that AMD causes photic retinopathy. A vitreous fluorophotometry study showed that blood-retinal barrier disruption was lower in eyes with UV-only or blue-blocking IOLs in comparison with UV-transmitting IOLs,9 but its significance is uncertain, because no retinal abnormalities were found, and differences in IOL chromophore light transmission may affect fluorophotometric measurements.
The Beaver Dam and Blue Mountain Eye studies found that cataract surgery was correlated with late AMD,10 but both the Age-Related Eye Disease Study and a recent Swiss study showed that pseudophakia is not a major risk factor in neovascular AMD.11,12 If there is a correlation between cataract surgery and AMD, it is probably due to shared risk factors and/or the physiological effects of intraocular surgery.2,10
The phototoxicity-AMD hypothesis' greatest weakness is its lack of support by nine of the 11 major epidemiological studies that examined it.2,3 These large studies should have confirmed the hypothesis—if environmental light exposure was linked closely with AMD. Their failure to do so suggests that (1) lifelong light exposure is not a significant risk factor in AMD, (2) it is inherently difficult to estimate a patient's cumulative light exposure, or (3) factors such as variable genetic susceptibility obfuscate a weak correlation.2,3
Lipofuscin phototoxicity increases with decreasing wavelength (Figure 1).13 Popularity of the phototoxicity-AMD hypothesis persists, despite its failures, because RPE lipofuscin accumulates with aging, hypothetically increasing an older adult's risk of retinal phototoxicity.3,4 Conversely, pupil area and crystalline lens transmittance decrease progressively with age, substantially reducing retinal illuminance and phototoxic risks.
Twenty- to 30-year-old phakic adults have the highest risk of retinal phototoxicity if age-related decreases in crystalline lens transmittance and pupil area and age-related increases in RPE cell phototoxicity risk are considered (Figure 2).3 This figure also shows that when phototoxic risks are compared for phakic and pseudophakic eyes, 65- and 75-year-old pseudophakes with a 20.00-D blue-blocking IOL have the equivalent ocular ages (EOAs) of 28- and 34-year-old phakic adults, respectively.3 Most AMD occurs in phakic individuals more than 60 years of age, so blue-blocking IOLs are less effective than much younger crystalline lenses that do not prevent AMD.2,3
Acute phototoxicity can injure the retina, but it cannot simulate AMD, just as solar retinopathy can scar the macula but it cannot simulate a lifetime of normal light exposure.2 In the United States, the Centers for Medicare and Medicaid Services (CMS) concluded that, "the relationship between blue light and AMD is speculative and not proven by available evidence."14 Blue-blocking IOLs have no proven efficacy, they do not represent evidence-based medicine, and there is no medical justification for permanently limiting blue light that is vital for photoreception.
SUNLIGHT AND MELANOMA
Blue-blocking IOLs have also been advocated using data from a study showing that decreasing violet and blue light reduces proliferation in uveal melanoma cell culture stimulated by intense 12-hour white light exposures.15 Conversely, several other reports in the literature show that blue light inhibits the growth of melanoma and leukemia cells in vitro.16,17
Regardless of the relative merits of these studies, the literature does not support a significant role for sunlight in the oncogenesis of uveal melanoma.18,19 Indeed, recent epidemiological evidence shows that the incidence of uveal melanoma actually increases with decreasing solar exposure,20 consistent with the long-reported inverse relationship between solar exposure and nonskin cancer mortality, which may be mediated by the beneficial effects of vitamin D.21
PHOTOPIC VISION
Standard D15 and Farnsworth-Munsell (FM) 100-hue tests do not detect differences between the color vision of pseudophakes with UV- or blue-blocking IOLs.22 Nonetheless, tritan defects can be demonstrated in pseudophakes with blue-blocking filters using a Moreland anomaloscope,23 and blue-blocking IOLs are not recommended for United States Air Force aircrew because of their need to perform operational color vision tasks.23 Additionally, color disparity problems required explantation of a blue-blocking IOL in one patient with a UV-blocking IOL in the contralateral eye.24,25 Blue-blocking IOLs also decrease photopic luminance contrast.26
Reduction of chromatic aberration has been mentioned as a possible benefit for blue-blocking IOLs,27 and chromatic dispersion does influence pseudophakic optical performance. Nonetheless, the photopic performance of pseudophakic eyes at medium- and high-spatial frequencies is determined primarily by wavelengths between 500 nm and 600 nm that are focused better on the retina than shorter or longer wavelengths.28,29 Thus, violet and blue wavelengths contribute little to modulation transfer at mid- or high-spatial frequencies,28 accounting for the failure of blue-blocking chromophores to improve pseudophakic contrast sensitivity.22,28
SCOTOPIC AND MESOPIC VISION
Blue light provides 7% of cone-mediated photopic vision and 35% of rod-mediated scotopic sensitivity.2 Thus, blue light is more important for vision in dim than bright environments. Cone photoreceptors image headlight-illuminated objects during night driving, but rods provide the remaining visual field.30 Driving, mobility, and peripheral vision problems are all associated with rod- but not cone-mediated dark adaptation parameters.31 When you get up at night and lighting is too dim to see color, you are using rod-mediated vision.
Scotopic vision and other rod-mediated visual functions decline progressively with age, due to decreasing pupil area32,33 and crystalline lens transmittance34 that reduce the amount of blue light available for retinal photoreception. These optical factors decrease effective scotopic retinal illuminances for 65- and 75-year-old eyes to only 37% and 26% of 10-year-old eyes, respectively.3 UV-blocking IOLs provide equivalent ocular ages for rod photoreception roughly 15 years younger than blue-blocking IOLs.3
Diminishing neural sensitivity causes additional age-related loss in rod photoreception.35 A recent study showed that pseudophakes with blue-blocking IOLs have decreased scotopic vision at violet and blue wavelengths,36 a loss previously correlated with night driving difficulties.37
Blue-blocking IOLs offer 14% to 21% less scotopic sensitivity than UV-blockers.2,38 This reduction is small compared with the broad range of visual sensitivity,38 but (1) it is a loss, (2) perimetric tests are poor surrogates for common tasks dim illumination, (3) rod deficits are worse in AMD and diabetic retinopathy, (4) reduced night vision causes older adults to curtail nighttime activities,39 and (5) impaired dark adaptation increases older adults' risk of falling, debilitating injury, long-term hospitalization, and death.2,40
CIRCADIAN PHOTOENTRAINMENT
Circadian photoreception is unconscious. It adjusts (ie, photoentrains) our body to match environmental day-night cycles, so it is essential for good physical and mental health.2,3,41 Circadian photoreception is mediated by blue-light sensitive retinal ganglion photoreceptors that were discovered in 2001. Approximately 1% of all human retinal ganglion cells are photoreceptors.42-44 The axons of most retinal ganglion cells mediating conscious vision synapse in the lateral geniculate nuclei of the thalamus, but most axons from retinal ganglion photoreceptors synapse in nonvisual nuclei including the paired suprachiasmatic nuclei of the hypothalamus.3 Suprachiasmatic nuclei are the human body's master biological clock. The advantage of circadian rhythmicity is that it permits our body to anticipate and prepare for essential daily activities. For example, it takes time to upregulate protein synthesis and increase blood sugar, heart rate, and blood pressure before arising.3,41 Suprachiasmatic nuclei have their own intrinsic periodicity, so the advantages of circadian rhythmicity would be lost without effective photoentrainment to external environmental diurnal rhythms.
Melatonin conveys timing information from the suprachiasmatic nuclei to synchronize peripheral clocks throughout the human body. Melatonin has important antioxidant, anticancer, and antiaging functions. Bright light suppresses melatonin secretion, increasing core temperature, alertness, and cognition.2,3,45 Effective blue-light exposure is crucial to synchronize melatonin secretion to environmental day-night cycles.
The spectral efficiency of melatonin suppression peaks at 460 nm in the blue part of the spectrum (Figure 3). This blue-light dependence arises because retinal ganglion photoreceptors express the blue-light–sensitive photopigment melanopsin.42,43 Blue light provides 55% of melatonin suppression (Figure 3),2 which is a well-defined widely used surrogate for retinal photic input to the suprachiasmatic nuclei.
Circadian rhythmicity is often disturbed in aging and in people with insomnia, depression, and memory loss.3,41 Circadian dysfunction occurs in coronary artery disease, hypertension, diabetes, Alzheimer's disease, and many cancers. Health risks are correlated with the degree and duration of circadian disruption. Numerous clinical studies have shown the risks of disturbed circadian photoentrainment and the benefits of optimal rhythmicity.
Circadian photoreception declines progressively with age because of decreasing crystalline lens transmittance34 and pupil area.32,33 These optical factors reduce the effective circadian retinal illuminance of 65- and 75-year-old eyes to only 27% and 17% of that of 10-year-old eyes, respectively.3 Diminishing neural sensitivity probably causes additional age-related loss in retinal ganglion photoreception. Blue-blocking IOLs decrease circadian photoreception by 27% to 38%, in comparison with UV-blocking IOLs.2 Less blue light is the likely cause of decreased melatonin suppression in older adults, and some elderly sedentary lifestyles provide only half the total daily luminance of young adults.46 If circadian photoreception is compared in phakic and pseudophakic eyes, UV-blocking IOLs provide equivalent ocular ages 15 years to 20 years younger than blue-blocking IOLs.3 For example, 75-year-old pseudophakes have equivalent phakic ocular ages of 54 years with a 30.00-D blue-blocking IOL; 50 years with a 20.00-D blue-blocking IOL; and 33 years with a 20.00- or 30.00-D UV-blocking IOL.3
Older adults cannot appreciate the decline of retinal ganglion cell photoreception directly, because it is not a conscious process. It has been shown, however, that cataract surgery with a standard IOL may decrease insomnia and daytime sleepiness.47 Therapy with light may also reduce insomnia and restore older adults' peak nocturnal melatonin to youthful levels.46
CONCLUSION
Advocates of blue-blocking IOLs insist that they have no downside and that approximately 1 million have been implanted without incident of confirmed negative visual disturbance.48 Yet, the incidence of visually significant cystoid macular edema is approximately 1%, so at least a transient visual disturbance should have been expected in a few thousand patients. Additionally, explantation of blue-blocking IOLs for color disparity problems is documented in the literature.24,25
Insomnia and night vision difficulties are common well-known aging problems. It is possible that many physicians are unaware that their patients have these problems. Nonetheless, philosophical analysis tells us that absence of evidence is not evidence of absence. Retinal ganglion photoreception is unconscious. Older and blind patients typically fail to inform even their internists about insomnia.3,41 They are far less likely to discuss it with their ophthalmologists, particularly in an era when open-ended questions are often shunned in patient interviews.
The medical literature documenting that blue light is important for good health grows rapidly. Withholding blue light does have its dark side.
Proponents of blue-blocking IOLs assert that it is better to be safe rather than sorry regarding retinal phototoxicity.49 Yet, hundreds of millions of people with UV-transmitting and -blocking IOLs implanted over the past 3 decades are not sorry that they had cataract surgery, and a new generation of IOL users should not be sorry because their best possible photoreception has been sacrificed for the illusion of being safe. If light is a risk factor for AMD in some people, then sunglasses should be worn in bright environments, because blue-blocking IOLs provide less photoprotection than crystalline lenses that do not prevent AMD (Figure 2).2,3,50 The big difference between sunglasses and blue-blocking IOLs, however, is that people have the freedom to remove their sunglasses for optimal photoreception whenever they choose to do so.
After 3.5 billion years of evolution, life on earth is well adapted to its blue sky. Blue light is essential for good vision and health. The purpose of cataract surgery is to improve vision and quality of life. Cataract surgery can provide older adults with better conscious vision in bright and dim environments. Increasing blue-light–dependent unconscious circadian photoreception extends the benefits of cataract surgery beyond image-based vision to improved health and longevity.
Martin A. Mainster, MD, PhD, FRCOphth, is the Luther L. Fry Endowed Professor of Ophthalmology at the University of Kansas Medical School, in Kansas City, Kansas. Dr. Mainster states that he is a paid consultant to Advanced Medical Optics, Inc. He may be reached at mmainste@kumc.edu.
Patricia L. Turner, MD, is an ophthalmologist in Leawood, Kansas. Dr. Turner states that she has no financial interest in the products or companies mentioned.
Up Front | May 2007
Blue Light: To Block or Not To Block
Cataract surgery should improve vision and health, and blue light is essential for both.
Martin A. Mainster, MD, PhD, FRCOphth, and Patricia L. Turner, MD
