Blue-Light-Filtering Intraocular Lenses Robert J

16 Blue-Light-Filtering Intraocular Lenses Robert J. Cionni

16.1 Introduction tistically significant higher prevalence of hard drusen and disciform scars than in age- The normal human crystalline lens filters not matched non-pseudophakic controls [4]. only ultraviolet light, but also most of the Pollack et al. [5] followed 47 patients with bi- higher frequency blue wavelength light.How- lateral early AMD after they underwent extra- ever, most current intraocular lenses (IOLs) capsular cataract extraction and implanta- filter only ultraviolet light and allow all blue tion of a UV-blocking IOL in one eye,with the wavelength light to pass through to the reti- fellow phakic eye as a control for AMD na. Over the past few decades, considerable progression. Neovascular AMD developed in literature has surfaced suggesting that blue nine of the operative versus two of the control light may be one factor in the progression of eyes, which the authors suggested was linked age-related macular degeneration (AMD) [1]. to the loss of the “yellow barrier” provided by In recent years, blue-light-filtering IOLs have the natural crystalline lens. been released by two IOL manufacturers. In Data from the Age-Related Eye Disease this chapter we will review the motivation for Study (AREDS), however, suggest a height- developing blue-filtering IOLs and the rele- ened risk of central geographic retinal atro- vant clinical studies that establish the safety phy rather than neovascular changes after and efficacy of these IOLs. cataract surgery [6, 7]. There were 342 patients in the AREDS study who were observed to have one or more large drusen or geo- 16.2 Why Filter Blue Light? graphic atrophy and who subsequently had cataract surgery. Cox regression analysis was Even at the early age of 4 years, the human used to compare the time to progression of crystalline lens prevents ultraviolet and much AMD in this group versus phakic control cas- of the high-energy blue light from reaching es matched for age, sex, years of follow-up, the retina (Fig. 16.1). As we age, the normal and course of AMD treatment. This analysis human crystalline lens yellows further, filter- showed no increased risk of wet AMD after ing out even more of the blue wavelength cataract surgery. However, a slightly in- light [2]. In 1978, Mainster [3] demonstrated creased risk of central geographic atrophy that pseudophakic eyes were more suscepti- was demonstrated. ble to retinal damage from near ultraviolet The retina appears to be susceptible to light sources. Van der Schaft et al. conducted chronic repetitive exposure to low-radiance postmortem examinations of 82 randomly light as well as brief exposure to higher-radi- selected pseudophakic eyes and found a sta- ance light [8–11]. Chronic, low-level exposure 152 R.J. Cionni

Fig. 16.1. Light transmission spectrum of a 4-year-old and 53-year-old human crystalline lens compared to a 20-diopter colorless UV-blocking IOL [37, 42]

(class 1) injury occurs at the level of the pho- the amount of time spent outdoors or in spe- toreceptors and is caused by the absorption cific lighting environments over a large por- of photons by certain visual pigments with tion of their lifetime is likely to introduce er- subsequent destabilization of photoreceptor ror in the data.This is why experimental work cell membranes.Laboratory work by Sparrow in vitro and in animals has been important in and coworkers has identified the lipofuscin understanding the potential hazards of blue component A2E as a mediator of blue-light light on the retina. damage to the retinal pigment epithelium The phenomenon of phototoxicity to the (RPE) [12–15]; although the retina has inher- retina has been investigated since the 1960s. ent protective mechanisms from class 1 pho- But more recently, the effects of blue light on tochemical damage, the aging retina is less retinal tissues have been studied in more de- able to provide sufficient protection [16, 17]. tail [8, 26–30]. Numerous laboratory studies Several epidemiological studies have con- have demonstrated a susceptibility of the cluded that cataract surgery or increased RPE to damage when exposed to blue light exposure of blue-wavelength light may be as- [12, 31]. One of the explanations as to how sociated with progression of macular degen- blue light can cause RPE damage involves the eration [18, 19]. Still, other epidemiologic accumulation of lipofuscin in these cells as studies have failed to come to this conclusion we age. A component of lipofuscin is a com- [20–22]. Similarly, some recent prospective pound known as A2E,which has an excitation trials have found no progression of diabetic maximum in the blue wavelength region retinopathy after cataract surgery [23, 24], (441 nm). When excited by blue light, A2E while other studies have reported progres- generates oxygen-free radicals, which can sion [25]. These conflicting epidemiological lead to RPE cell damage and death.At Colum- results are not unexpected, since both diabet- bia University, Dr Sparrow exposed cultured ic and age-related macular diseases are com- human retinal pigment epithelial cells laden plex, multifactorial biologic processes. Cer- with A2E to blue light and observed extensive tainly, relying on a patient’s memory to recall cell death. She then placed different UV- Chapter 16 Blue-Light-Filtering Intraocular Lenses 153

Fig. 16.2. Cultured human RPE cells laden with placed in the path of the light, yet is markedly re- A2E exposed to blue wavelength light. Cell death is duced when the AcrySof Natural IOL is placed in significant when UV-blocking colorless IOLs are the light path [32] blocking IOLs or a blue-light-filtering IOL in 16.3 IOL Development the path of the blue light to see if the IOLs provided any protective effect. The results of As a result of the mounting information on this study demonstrated that cell death was the effects of UV exposure on the retina [1, still extensive with all UV-blocking colorless 33], in the late 1970s and early 1980s IOL IOLs, but very significantly diminished with manufacturers began to incorporate UV- the blue-light-filtering IOL [32] (Fig. 16.2). blocking chromophores in their lenses to Although these experiments were laboratory protect the retina from potential damage. in nature and more concerned with acute Still, when the crystalline lens is removed light damage rather than chronic long-term during cataract or refractive lens exchange exposure, they clearly demonstrated that by surgery and replaced with a colorless UV- filtering blue light with an IOL, A2E-laden blocking IOL,the retina is suddenly bathed in RPE cells could survive the phototoxic insult much higher levels of blue light than it has of the blue light. ever known and remains exposed to this increased level of potentially damaging light ever after. Yet, until recent years, the IOL- manufacturing community had not provided the option of IOLs that would limit the exposure of the retina to blue light. Since the early 1970s, IOL manufacturers have researched 154 R.J. Cionni

Fig. 16.3. Light transmission spectrum of the AcrySof Natural IOL compared to a 4-year-old and 53-year-old human crystalline lens and a 20-diopter colorless UV-blocking IOL [37, 42]

methods for filtering blue-wavelength light in pseudophakic eyes with a tinted IOL versus waves in efforts to incorporate blue-light pro- a standard lens with UV-blocker only [36]. tection into IOLs, although these efforts have Hoya also introduced a foldable acrylic blue- not all been documented in the peer-re- light-filtering IOL with PMMA haptics to viewed literature. Recently,two IOL manufac- some European countries in late 2003. turers have developed stable methods to incorporate blue-light-filtering capabilities into IOLs without leaching or progressive discol- 16.5 AcrySof Natural IOL oration of the chromophore. In 2002, the AcrySof Natural, a UV- and blue- light-filtering IOL, was approved for use in 16.4 Hoya IOL Europe, followed by approval in the USA in 2003. The IOL is based on Alcon’s hydropho- Hoya released PMMA blue-light-filtering bic acrylic IOL, the AcrySof IOL. In addition IOLs in Japan in 1991 (three-piece model to containing a UV-blocking agent, the HOYA UVCY) and 1994 (single-piece model AcrySof Natural IOL incorporates a yellow HOYA UVCY-1P).Clinical studies of these yel- chromophore cross-linked to the acrylic mol- low-tinted IOLs (model UVCY, manufactured ecules.Extensive aging studies have been per- by Hoya Corp., Tokyo, and the Meniflex NV formed on this IOL and have shown that the type from Menicon Co., Ltd., Nagoya) have chromophore will not leach out or discolor been carried out in Japan [16, 17, 34]. One [37].This yellow chromophore allows the IOL study found that pseudophakic color vision not only to block UV light, but selectively to with a yellow-tinted IOL approximated the vi- filter varying levels of light in the blue wave- sion of 20-year-old control subjects in the length region as well. Light transmission as- blue-light range [35]. Another study found sessment demonstrates that this IOL approx- some improvement of photopic and mesopic imates the transmission spectrum of the contrast sensitivity,as well as a decrease in the normal human crystalline lens in the blue effects of central glare on contrast sensitivity, light spectrum (Fig. 16.3). Therefore, in addi- Chapter 16 Blue-Light-Filtering Intraocular Lenses 155

Fig. 16.4. Data from Alcon’s FDA study showing no significant difference in best corrected visual acuity between the AcrySof colorless IOL and the AcrySof Natural IOL tion to benefiting from less exposure of the Single-Piece IOL as a control. Patients with retina to blue light, color perception should bilateral age-related cataracts who were will- seem more natural to these patients as op- ing and able to wait at least 30 days between posed to the increased blueness, clinically cataract procedures and had verified normal known as cyanopsia, reported by patients preoperative color vision were eligible for the who have received colorless UV-blocking study. In all bilateral lens implantation cases, IOLs [38]. the same model lens was used in each eye. Postoperative parameters measured included visual acuity, photopic and mesopic contrast 16.6 FDA Clinical Study sensitivity, and color perception using the Farnsworth D-15 test. Results showed that In order to gain approval of the Food and there was no difference between the AcrySof Drug Administration (FDA), a multi-cen- Natural IOL and the clear AcrySof IOL in tered, randomized prospective study was any of these parameters [39] (Figs. 16.4, 16.5, conducted in the USA. It involved 300 pa- 16.6 and 16.7). More substantial color per- tients randomized to bilateral implantation ception testing using the Farnsworth–Mun- of either the AcrySof Natural IOL or the clear sell 100 Hue Test has also demonstrated no AcrySof Single-Piece IOL. One hundred and difference in color perception between the fifty patients received the AcrySof Natural AcrySof Natural IOL and the clear AcrySof IOL and 147 patients received the AcrySof IOL [39]. 156 R.J. Cionni

Fig. 16.5. Data from Alcon’s FDA study showing no significant difference in photopic contrast sensitivity between the AcrySof colorless IOL and the AcrySof Natural IOL

Fig. 16.6. Data from Alcon’s FDA study showing no significant difference in mesopic contrast sensitivity between the AcrySof colorless IOL and the AcrySof Natural IOL

Fig. 16.7. Data from Alcon’s FDA study showing no significant difference in color perception using the Farnsworth D-15 test between the AcrySof colorless IOL and the AcrySof Natural IOL Chapter 16 Blue-Light-Filtering Intraocular Lenses 157

Fig. 16.8. Blue-light transmission spectrum showing low transmission of 441 nm light and high transmission of 507 nm light with the AcrySof Natural IOL

16.7 Blue-Light-Filtering IOLs blue light. Indeed, the most important wave- and Low Light Conditions length for scotopic vision is at and around 507 nm [41]. The AcrySof Natural allows Both mesopic vision and scotopic vision refer transmission of approximately 85% of light to vision with low-light conditions. Wyszecki at 507 nm. In comparison, a UV-blocking col- and Stiles point out that mesopic vision be- orless IOL transmits only 5% more. The nor- gins at approximately 0.001 cd/m2 and ex- mal human crystalline lens at any age trans- tends up to 5 cd/m2 for a 3° diameter central- mits significantly less light at and near ly fixated target; however, the upper range 507 nm than does the AcrySof Natural IOL could extend up to 15 cd/m2 for a 25° diame- and therefore, patients implanted with the ter target [40]. Nevertheless, 3 cd/m2 is the AcrySof Natural IOL should have enhanced most often cited upper limit for mesopic vi- scotopic vision. It would be counterintuitive sion. One can liken this to the low light condi- to believe that scotopic vision would be di- tions on a cloudless night with a full moon. minished instead of enhanced (Fig. 16.8). The contrast sensitivity tests performed un- der mesopic conditions in the FDA trials demonstrated that the AcrySof Natural IOL 16.8 Clinical Experience does not negatively affect mesopic vision. Scotopic refers to light levels below the Having implanted more than 1,000 AcrySof mesopic range, which can be likened to a Natural IOLs over the past year,I have had the moonless, starry night. Since blue wavelength opportunity to gain insight into the quality of light is imperative for scotopic vision, some vision provided by this unique IOL. The IOL are worried that attenuating blue light will behaves identically to the clear AcrySof IOL negatively affect scotopic vision. Certainly, if in all aspects. It also has the advantage of be- all blue light were blocked, one might expect ing easier to visualize during folding, loading some decrease in scotopic vision. However, and implantation due to its yellow coloration. the AcrySof Natural IOL does not block all The visual results in my patients have been 158 R.J. Cionni

excellent without any complaints of color 4. Van der Schaft TL, Mooy CM, de Bruijn WC, perception or night vision problems. I have Mulder PG, Pameyer JH, de Jong PT (1994) implanted this blue-light-filtering IOL in the Increased prevalence of disciform macular fellow eye of patients previously implanted degeneration after cataract extraction with implantation of an intraocular lens. Br J Oph- with colorless UV-filtering IOLs.When asked thalmol 78:441–445 to compare the color of a white tissue paper, 5. Pollack A et al (1996) Age-related macular de- 70% do not see a difference between the two generation after extracapsular cataract extrac- eyes. Of the 30% that could tell a difference, tion with intraocular lens implantation. Oph- none perceived the difference before I thalmology 103:1546–1554 checked and none felt the difference was 6. Ferris FL (2002) The new AREDS findings. Pa- bothersome.With more than 1,000,000 AcrySof per presented at annual meeting of the Ameri- can Academy of Ophthalmology, 21 Oct 2002, Natural IOLs implanted worldwide by the Orlando, FL time of this writing, there are no confirmed 7. Age-Related Eye Disease Study Group (2000) reports of color perception or night vision Risk factors associated with age-related macu- problems. lar degeneration. A case-control study in the Age-Related Eye Disease Study: Age-Related Eye Disease Study report number 3. Ophthal- 16.9 Summary mology 107:2224–2232 8. Marshall J (1991) The effects of ultraviolet radiation and blue light on the eye. In: Cronly- Given the growing body of evidence implicat- Dillon J (ed) Susceptible visual apparatus. ing blue light as a potential factor in the wors- Macmillan Reference Ltd, London (Vision and ening of AMD and the positive collective clin- visual dysfunction, vol 16) ical experience with this new IOL,the AcrySof 9. Marshall J, Mellerio J, Palmer DA (1971) Dam- Natural has become the lens of choice in age to pigeon retinae by commercial light cataract surgery patients for many ophthal- sources operating at moderate levels. Vision mologists worldwide. When performing re- Res 11:1198–1199 10. Sperling HG, Johnson C, Harwerth RS (1980) fractive lens exchange, especially in the Differential spectral photic damage to primate younger patient, one should ponder the po- cones.Vision Res 20:1117–1125 tential consequences of exposing the retina to 11. Sykes SM, Robison WG Jr,Waxler M,Kuwabara higher levels of blue light for the rest of that T (1981) Damage to the monkey retina by patient’s life. I believe that blue-light-filtering broad-spectrum fluorescent light. Invest Oph- IOLs will become the lens of choice for these thalmol Vis Sci 20:425–434 patients as well. 12. Sparrow JR, Cai B (2001) Blue light-induced apoptosis of A2E-containing RPE: involvement of caspase-3 and protection by Bcl-2. Invest Ophthalmol Vis Sci 42:1356–1362 References 13. Ben-Shabat S, Parish CA, Vollmer HR, Itagaki Y, Fishkin N, Nakanishi K, Sparrow JR (2002) 1. Ham WT, Mueller A, Sliney DH (1976) Retinal Biosynthetic studies of A2 E, a major fluoro- sensitivity to short wavelength light. Nature phore of retinal pigment epithelial lipofuscin. 260:153–155 J Biol Chem 277:7183–7190 2. Lerman S (1980) Biologic and chemical effects 14. Liu J, Itagaki Y, Ben-Shabat S, Nakanishi K, of ultraviolet radiation. In: Radiant energy and Sparrow JR (2000) The biosynthesis of A2 E, a the eye. Macmillan, New York, pp 132–133 fluorophore of aging retina, involves the for- 3. Mainster MA (1978) Spectral transmittance of mation of the precursor, A2-PE, in the photo- intraocular lenses and retinal damage from receptor outer segment membrane. J Biol intense light sources. Am J Ophthalmol 85: Chem 275:29354–29360 167–170 Chapter 16 Blue-Light-Filtering Intraocular Lenses 159

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