Cataract Surgeon Perspectives on the Acrysof Natural IOL
Thousands of Patients are Satisfied with Their Vision
BY ROBERT CIONNI, M.D.

Even in childhood, the human crystalline lens filters a great deal of light in the blue wavelength spectrum. As we age, our crystalline lens gradually yellows, further decreasing the amount of blue light that can reach the retina¹. Removing the crystalline lens significantly increases the amount of blue light reaching the retina, and UV-blocking IOLs do not filter any of this blue light energy.

A study published in 1996 by Pollack and colleagues showed that the incidence of progression from dry to wet AMD was more than four times greater in the eyes with UV blocking IOLs than in eyes left phakic ². Recently, Wang et al. published a follow-up on approximately 6,000 eyes over 5 years and concluded that the risk of developing late-stage AMD was increased significantly in eyes that had undergone cataract surgery compared with phakic eyes ³.

Research clearly demonstrates that blue light can damage retinal tissues and suggests that blue light may be a risk factor in causing the progression of AMD ^4,5. The lipofuscin fluorophore A2E, which has an excitation maximum in the blue wavelength region, appears to be a mediator in this destructive process. As we age, the retinal pigment epithelium (RPE) accumulates higher concentrations of lipofuscin laden with A2E. Blue light is absorbed by and excites A2E, which causes the formation of free radicals. These free radicals may initiate RPE cell death ⁶.

In fact, more data exists regarding the potential dangers of blue light to the retina than the dangers of UV light ^7-23. However, today it has become the standard of care to implant UV absorbing IOLs and ignore the mounting evidence of blue light danger.

The AcrySof Natural IOL replaces both the UV and blue light filtering characteristics of the crystalline lens that are lost following cataract surgery. Results from the FDA clinical trial demonstrate that there is no difference between the AcrySof Natural lens and the AcrySof Single-Piece lens in terms of visual acuity, color perception or contrast sensitivity under photopic and mesopic conditions. Additionally, in a quality of life questionnaire regarding color perception, driving ability, and other vision-specific tasks, both groups demonstrated an improvement over baseline, and there was no difference between the two groups.

We recently completed an FM-100 color perception study comparing patients with bilateral implantation of either the AcrySof Natural or the AcrySof Single-Piece lens. The results also indicate that there is no difference in terms of color perception between these patient populations ²⁴.

Do AcrySof Natural patients view the world similar to someone wearing Blublocker sunglasses? No! These sunglasses block much more blue light than does the AcrySof Natural IOL. Additionally, the natural crystalline lens is already filtering blue light, so double filtration occurs when someone is wearing Blublocker sunglasses, creating an abnormally yellow hue.

Might blue light filtering IOLs decrease scotopic vision (moonless night)? Although blocking all blue light from the retina may decrease scotopic vision, the AcrySof Natural does not block all blue light. AcrySof Natural approximates the blue-light filtering capability of a healthy, human crystalline lens.

Our Patients Have Had No Complaints

I have implanted more than 1,000 AcrySof Natural IOLs, including in patients who have a standard UV blocking IOL in the fellow eye. None have complained of abnormal color perception or trouble driving, day or night. In fact, we don't hear complaints of cyanopsia (caused by increased levels of blue light reaching the retina) from these patients like we hear from our patients after cataract surgery with standard UV blocking IOLs.

Furthermore, the AcrySof Natural IOL has been on the market internationally since September 2002. After more than 300,000 implants, there are no confirmed scotopic or color perception issues. Any claims that suggest patients implanted with the AcrySof Natural IOL will have abnormal color perception or decreased night driving vision are theoretic at best. The FDA study data, the recently completed FM-100 Hue study, and the extensive clinical experience we have with this IOL clearly demonstrate that there are no negative visual consequences to using the AcrySof Natural IOL.

AMD is one of the leading causes of blindness in the developed world ²⁵. Although there are additional risk factors for AMD, increased exposure to blue light following the removal of a cataract is one factor that can now be addressed. My patients are thrilled that I can provide them with more natural vision and increased retinal protection without any negative visual consequences following cataract surgery.

Dr. Cionni is medical director of the Cincinnati Eye Institute. He's also a consultant to Alcon.

IOL is Based on Incomplete Understanding
BY JACK HOLLADAY, M.D., M.S.E.E., F.A.C.S.

For the first 30 years of IOL development, the transmission spectrum of light reaching the retina through an IOL was similar to that of an aphakic patient. The cornea blocked light less than 300 nm, but most of the light above 320 nm was transmitted by the early polymethylmethacrylate (PMMA) IOLs¹. The crystalline lens normally transmits light only above 400 nm ². Calculations by Mainster suggested that the increased exposure to near UV light with IOLs compared to the crystalline lens increased the possibility of thermal retinal damage.

In addition, animal studies suggested an increase in non-thermal, phototoxic retinal damage with light of decreasing wavelengths, with the greatest damage occurring from wavelengths in the UV and near-blue portion of the spectrum^3-5.

In his 1978 article, Mainster suggested that intraocular lenses should be designed to mimic the transmission of the human crystalline lens. However, there is no one transmission curve for the human lens. The curve changes with age, decreasing the percent of light transmitted, particularly in the short-wavelength (blue) portion of the visible spectrum. Cataract surgery creates a rapid shift in the amount of blue light that reaches the patient's retina. Given that the transmission of the crystalline lens varies with age, how does that affect visual function, and what does it tell us in terms of designing intraocular lenses?

No Clear Link Between Blue Light and AMD

It has been suggested that an IOL should block blue as well as ultraviolet light to protect the retina against light-induced phototoxicity, and age-related macular degeneration (ARMD). There is no conclusive evidence linking blue light exposure to ARMD. Five of the seven large epidemiological studies found no correlation between light exposure and ARMD ^6-10.

Color discrimination matures from birth, reaches its peak at age 19 ^11-14 and then begins to decrease linearly with age. The decrease in color discrimination is primarily in the blue region of the visual spectrum, due to yellowing of the crystalline lens.

The transmission of blue light (range from 400 to 500 nm) through the crystalline lens decreases with age. It peaks at approximately age 20, and decreases steadily after age 40. When blue-yellow sensitivity on the FM-100 is plotted on a graph, we see a steady decrease in the ability to discriminate the color blue with age ¹¹. It is clear that the decrease in color vision with age is directly related to the yellowing of the crystalline lens.

Filtering Visible Blue Light is Inappropriate

Based on what we know today, phakic and pseudophakic patients benefit from wearing protective eyewear when outdoors in the sun. Liu et al. (1989) stated "The cheapest and most effective public health measure may be to encourage use of protective eyewear at early ages" ¹⁵.

Balanced nutrition must also be encouraged. Deficiencies in dietary antioxidants such as vitamins A, E, and C can accelerate a variety of components of senescence. In epidemiological studies, smoking is the one environmental factor consistently associated with ARMD ^16-19 and with cataracts ^20-21.

Blocking blue light will affect color vision and scotopic sensitivity. Several studies have shown that the yellowing of the aging lens goes hand in hand with decreased color discrimination to blue on color tests. To decrease the transmission of blue light to the retina is not physiologic, and is not supported by any direct or indirect evidence for cumulative light damage. In addition, the decreased transmission of visible light caused by blocking blue light decreases the overall luminance levels of the retina and significantly reduces scotopic sensitivity. This may be a particular problem in older individuals who have deficiencies in scotopic vision at the neural level, leading to difficulties with navigating safely in the dark ²².

Without conclusive data and a complete understanding of all of the complex interacting factors affecting the optics and sensory components of the visual system, blocking or filtering visible blue light is inappropriate. Reproducing the properties of the 20-year-old crystalline lens is appropriate and takes into account 150,000 years of development in our environment. This has been proven true with regard to spherical aberration, where designing an IOL to match the negative spherical aberration of the 20-year-old crystalline lens significantly improves retinal image contrast, contrast sensitivity, and night driving performance ²³.

The idea of replicating the 50-year-old lens because this is a "protective" phenomenon of the eye with age, as opposed to a simple aging process, is no different than suggesting 50-year-old skin damaged from UV is ideal and is protective against further UV damage. Re-creating the optical performance of the 20-year-old crystalline lens with regard to monochromatic and chromatic performance should be our goal until our knowledge and our ability to "improve" the system significantly increases.

Dr. Holladay is a clinical professor of ophthalmology at Baylor College of Medicine in Houston. He is also a consultant to Pfizer and Advanced Medical Optics, Inc.

Retina Specialist Perspectives on the Acrysof Natural IOL

Mounting Evidence Should Not Be Ignored
BY STANLEY CHANG, M.D.

The relationship between cataract surgery and the progression of age-related macular degeneration has been a subject of interest for retina specialists for two decades. Two recent reports pool data from several population-based studies and support the hypothesis that cataract surgery is associated with an increased risk for developing late AMD ^1-2. While analysis of each of the individual population-based study groups may not have shown this association, combining the data sets consistently showed the association between cataract surgery and increased prevalence of late AMD.

Freeman and associates ¹ had data from 11,690 subjects; 471 had cataract surgery on 718 eyes. They found an odds ratio of 1.7 that patients with previous cataract surgery developed late AMD. This was statistically significant. Wang and associates ² had 8,580 subjects at baseline, and 6,019 were re-examined after 5 years. 315 eyes were non-phakic. Multivariate-adjusted odds ratios were estimated. The relative risk for the progression to late AMD ranged from 2.8-3.7 at 5 years following cataract surgery. When adjusted for gender and smoking, those eyes that had drusen or pigmentary abnormalities at baseline had a substantially greater risk for developing late stage AMD compared with phakic eyes (odds ratio 5.7). These findings were also statistically significant.

Looking Deeper

Evidence is also mounting that the accumulation of aging pigments in the retinal pigment epithelium (RPE) cells may contribute to the development of AMD. Lipofuscin, a product of the phototransduction cascade, accumulates in RPE cells with age. It is believed that at age 80, up to 20% of the cell's cytoplasmic volume contains lipofuscin. The major component of lipofuscin is A2E, a fluorophore that exhibits autofluorescence, and has its peak absorption in the blue light region. Work from the laboratories of Drs. Janet Sparrow and Koji Nakanishi at Columbia University, has shown that human RPE cells that were fed A2E and exposed to blue light for brief periods of time underwent oxidative damage and subsequently apoptosis3. When cells contained larger amounts of A2E and were exposed to blue light for longer periods of time, the rate of cell death was increased. Similar cells exposed to green light for the same time did not undergo apoptosis.

Using the same model, they also compared the effect of the Acrysof Natural blue-blocking IOL with conventional IOLs, by placing the lens in the pathway of the blue light illuminated on the cells. Compared with conventional IOLs, the blue-blocking IOL reduced cell death by 80% ⁴.

Studies of retinal autofluorescence in AMD have also shown that areas of geographic atrophy in AMD may be preceded by areas exhibiting autofluorescence ^5-6. Spaide ⁷ found that fellow eyes of patients with exudative AMD had more intense areas of autofluorescence than eyes with non-exudative AMD. These studies indicate that lipofuscin accumulation is probably related to the development of age-related changes in the macula.

Despite these observations that provide strong circumstantial evidence, a carefully designed clinical study will be necessary to prove that a blue-blocking IOL such as Acrysof Natural will protect against the risk of visual loss from progression of AMD. Such a study may require several hundred patients followed for up to 5 years.

In the late 1980s when the first IOL with ultraviolet filtration was introduced, the concept was met with reluctance. Based on a few clinical studies supporting the relationship between macular degeneration and cataract surgery, this concept was adopted into all IOLs on the market today. Blue light is less hazardous than ultraviolet rays, but more research on the effects of chronic light exposure in our aging population is needed. It is expected that patients of my generation will probably live to an average age of 100 years (a frightening thought). We are being subjected to increased levels of blue light in our environment: the increasing use of mercury halide and xenon lights, brighter illumination in the workplace, and a more active outdoor lifestyle on the golf course or tennis court. Our visual demands are increasing, and cataract surgery is done earlier, which mean we will probably remain pseudophakic for longer periods of our lives.

If They Were My Eyes

Thus, based on current knowledge, if I personally were about to undergo cataract surgery, my preference would be for an Acrysof Natural IOL. If I already had early changes of AMD, I would definitely want a blue-blocking lens. In addition to the type of implant selected, I would also wear sunglasses while outdoors and take antioxidant oral supplements.

Dr. Chang is director of the department of ophthalmology at the Edward S. Harkness Eye Institute (Columbia Univeristy College of Physicians and Surgeons) in New York. He's also a consultant to Alcon on retinal tamponades.

A Vision Trade-Off for Uncertain Protection
BY MARTIN A. MAINSTER, PH.D., M.D., F.R.C.OPHTH

Many of our older patients complain of problems seeing with dim illumination ^1-4. They often curtail nighttime activities such as driving ^5-6. Their scotopic (dim light) visual problems have been studied carefully.

Scotopic vision declines with aging, even in 20/20 eyes. It decreases twice as fast with aging as photopic sensitivity ⁷. This decline is worst in the blue part of the spectrum ⁸. Rod-mediated dark adaptation slows progressively with aging⁹.The fact is that older adults have progressively increasing difficulty seeing at night or in dim environments, even when they don't have cataract or age-related macular degeneration (AMD). All these and other measures of scotopic vision are even worse in people with AMD ^10-11.

Older adults expect cataract surgery to improve their vision, particularly their night vision. Unfortunately, current blue light blocking IOLs trade off scotopic visual performance for limited protection against one of the two types of acute retinal photoxicity.

Applying the Science

Here's how: Scotopic visual sensitivity peaks at 506 nm in the blue-green part of the visible spectrum, whereas photopic (bright light) sensitivity peaks at 555 nm in the yellow-green part of the spectrum. Thus, blue light is much more important for scotopic than photopic vision.

In 1966, Werner Noell discovered a blue-green type of photic retinopathy that had the same action spectrum as scotopic sensitivity ¹². It occurred in experimental animals at light levels far too low for retinal photocoagulation. Blue-green phototoxicity may be involved in AMD, but it's a huge stretch to go from acute animal experiments to human aging. Furthermore, epidemiological studies relating lifelong light exposure to AMD have been inconclusive. The Chesapeake Bay Waterman study found that severe AMD was associated with higher estimated sunlight exposure over the previous two decades ¹³. The Beaver Dam study found a similar result ¹⁴. Nonetheless, three large epidemiological studies found no relationship between AMD and sunlight exposure, including a study involving Hugh Taylor who was a Waterman study investigator ^15-17.

In 1976, Bill Ham demonstrated a second type of photic retinopathy that increased with decreasing wavelength ¹⁸. This UV-blue damage peaked at 440 nm in phakic eyes, so it's sometimes called the "blue light hazard." UV-blue phototoxicity is responsible for solar, welder's and operating microscope macular injuries. It requires higher irradiances in shorter exposures than blue-green phototoxicity.

The cornea protects the retina from UV radiation below 300 nm ¹⁹. The crystalline lens blocks UV radiation between 300 and 400 nm ¹⁹.This crystalline lens protection is potentially lost in cataract surgery.

In 1978, I discovered that clear PMMA IOLs transmitted UV radiation between 330 and 400 nm to the retina, and cautioned clinicians and manufacturers about this hazard ^20-21. When I revisited the subject in 1986, I found that manufacturers had listened and that most IOLs being manufactured throughout the world had UV blocking chromophores to protect patients ²².

In the same 1986 AJO paper, I recommended blocking violet light up to 430 nm to reduce the risk of acute retinal phototoxicity ²². In comparison with a UV-only blocking IOL, however, the AcrySof Natural IOL blocks violet, blue and even some green light up to and above 500 nm ²³.

I recently examined how much a particular crystalline or intraocular lens decreased scotopic sensitivity and the risk of acute retinal phototoxicity. My calculations showed that the AcrySof Natural IOL provided better acute UV-blue phototoxicity protection but roughly 25% worse scotopic sensitivity than UV-only blocking IOLs. These results were presented in the December issue of the British Journal of Ophthalmology, in a paper that I co-authored with Janet Sparrow ²³. Decreased scotopic vision with blue-blocking spectacle filters has been reported previously by Eero Aarnisalo ²⁴.

It's important to remember that UV-blue phototoxicity is only one of the two types of retinal phototoxicities that are known currently. Blue-green phototoxicity takes place at lower light levels over longer exposures than UV-blue phototoxicity. Thus, if light is a factor in retinal aging, blue-green phototoxicity may play a key role ²⁵. It's currently unknown if either, neither, or both types of acute experimental phototoxicities are involved in AMD.

Blue-green phototoxicity has the same spectrum as scotopic sensitivity, so IOLs can't protect patients against it without causing an equivalent decrease scotopic sensitivity. No IOL provides significant protection against acute blue-green photic retinopathy, so sunglasses should be worn in very bright environments regardless of IOL chromophores. With a UV-only blocking IOL, however, patients can take off their sunglasses and have optimal night vision. With an AcrySof Natural lens, blue light blocking chromophores are still there to decrease scotopic vision when patients remove their sunglasses.

Substantial Concerns Require Our Attention

I have two primary concerns about the AcrySof Natural lens. First, we need to be sure that we aren't sacrificing the improved night vision that our patients want for an unproven hypothetical connection between AMD and acute UV-blue phototoxicity in experimental animals. Second, patients may be misled into thinking that sunglasses are unnecessary in bright environments. Anyone who believes as I do that light may be a factor in AMD should wear sunglasses in very bright environments because of blue-green retinal phototoxicity.

To summarize the facts: There's no conclusive evidence that lifelong light exposure causes AMD in susceptible people; acute laboratory light experiments don't simulate lifelong human light exposure; blue light absorbing IOLs trade off scotopic vision for limited protection against UV-blue phototoxicity; they're an especially poor choice for AMD patients whose scotopic vision is worse than their peers without it; there's no definitive data on how much blue light, if any, an IOL should block; and sunglasses should be worn in bright environments because no IOL provides protection against acute blue-green phototoxicity.

The bottom line is that if I had to have cataract surgery and choose from the IOLs currently available in the United States, I'd choose a UV-only blocking IOL, and wear sunglasses in bright environments that I could remove for optimal vision in dim illumination.

Dr. Mainster is vice chairman, professor of ophthalmology and director of the macular and retinal vascular service at the University of Kansas Medical School. He also serves as a consultant for Advanced Medical Optics, Inc.