16
16.1
Blue-Light-Filtering Intraocular Lenses
Robert J. Cionni
Introduction
The normal human crystalline lens filters not
only ultraviolet light, but also most of the
higher frequency blue wavelength light. However, most current intraocular lenses (IOLs)
filter only ultraviolet light and allow all blue
wavelength light to pass through to the retina. Over the past few decades, considerable
literature has surfaced suggesting that blue
light may be one factor in the progression of
age-related macular degeneration (AMD) [1].
In recent years, blue-light-filtering IOLs have
been released by two IOL manufacturers. In
this chapter we will review the motivation for
developing blue-filtering IOLs and the relevant clinical studies that establish the safety
and efficacy of these IOLs.
16.2
Why Filter Blue Light?
Even at the early age of 4 years, the human
crystalline lens prevents ultraviolet and much
of the high-energy blue light from reaching
the retina (Fig. 16.1). As we age, the normal
human crystalline lens yellows further, filtering out even more of the blue wavelength
light [2]. In 1978, Mainster [3] demonstrated
that pseudophakic eyes were more susceptible to retinal damage from near ultraviolet
light sources. Van der Schaft et al. conducted
postmortem examinations of 82 randomly
selected pseudophakic eyes and found a sta-
tistically significant higher prevalence of
hard drusen and disciform scars than in agematched non-pseudophakic controls [4].
Pollack et al. [5] followed 47 patients with bilateral early AMD after they underwent extracapsular cataract extraction and implantation of a UV-blocking IOL in one eye, with the
fellow phakic eye as a control for AMD
progression. Neovascular AMD developed in
nine of the operative versus two of the control
eyes, which the authors suggested was linked
to the loss of the “yellow barrier” provided by
the natural crystalline lens.
Data from the Age-Related Eye Disease
Study (AREDS), however, suggest a heightened risk of central geographic retinal atrophy rather than neovascular changes after
cataract surgery [6, 7]. There were 342 patients in the AREDS study who were observed
to have one or more large drusen or geographic atrophy and who subsequently had
cataract surgery. Cox regression analysis was
used to compare the time to progression of
AMD in this group versus phakic control cases matched for age, sex, years of follow-up,
and course of AMD treatment. This analysis
showed no increased risk of wet AMD after
cataract surgery. However, a slightly increased risk of central geographic atrophy
was demonstrated.
The retina appears to be susceptible to
chronic repetitive exposure to low-radiance
light as well as brief exposure to higher-radiance light [8–11]. Chronic, low-level exposure
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Fig. 16.1. Light transmission spectrum of a 4-year-old and 53-year-old human crystalline lens com-
pared to a 20-diopter colorless UV-blocking IOL [37, 42]
(class 1) injury occurs at the level of the photoreceptors and is caused by the absorption
of photons by certain visual pigments with
subsequent destabilization of photoreceptor
cell membranes. Laboratory work by Sparrow
and coworkers has identified the lipofuscin
component A2E as a mediator of blue-light
damage to the retinal pigment epithelium
(RPE) [12–15]; although the retina has inherent protective mechanisms from class 1 photochemical damage, the aging retina is less
able to provide sufficient protection [16, 17].
Several epidemiological studies have concluded that cataract surgery or increased
exposure of blue-wavelength light may be associated with progression of macular degeneration [18, 19]. Still, other epidemiologic
studies have failed to come to this conclusion
[20–22]. Similarly, some recent prospective
trials have found no progression of diabetic
retinopathy after cataract surgery [23, 24],
while other studies have reported progression [25]. These conflicting epidemiological
results are not unexpected, since both diabetic and age-related macular diseases are complex, multifactorial biologic processes. Certainly, relying on a patient’s memory to recall
the amount of time spent outdoors or in specific lighting environments over a large portion of their lifetime is likely to introduce error in the data. This is why experimental work
in vitro and in animals has been important in
understanding the potential hazards of blue
light on the retina.
The phenomenon of phototoxicity to the
retina has been investigated since the 1960s.
But more recently, the effects of blue light on
retinal tissues have been studied in more detail [8, 26–30]. Numerous laboratory studies
have demonstrated a susceptibility of the
RPE to damage when exposed to blue light
[12, 31]. One of the explanations as to how
blue light can cause RPE damage involves the
accumulation of lipofuscin in these cells as
we age. A component of lipofuscin is a compound known as A2E, which has an excitation
maximum in the blue wavelength region
(441 nm). When excited by blue light, A2E
generates oxygen-free radicals, which can
lead to RPE cell damage and death.At Columbia University, Dr Sparrow exposed cultured
human retinal pigment epithelial cells laden
with A2E to blue light and observed extensive
cell death. She then placed different UV-
Chapter 16
Fig. 16.2. Cultured human RPE cells laden with
A2E exposed to blue wavelength light. Cell death is
significant when UV-blocking colorless IOLs are
blocking IOLs or a blue-light-filtering IOL in
the path of the blue light to see if the IOLs
provided any protective effect. The results of
this study demonstrated that cell death was
still extensive with all UV-blocking colorless
IOLs, but very significantly diminished with
the blue-light-filtering IOL [32] (Fig. 16.2).
Although these experiments were laboratory
in nature and more concerned with acute
light damage rather than chronic long-term
exposure, they clearly demonstrated that by
filtering blue light with an IOL, A2E-laden
RPE cells could survive the phototoxic insult
of the blue light.
Blue-Light-Filtering Intraocular Lenses
placed in the path of the light, yet is markedly reduced when the AcrySof Natural IOL is placed in
the light path [32]
16.3
IOL Development
As a result of the mounting information on
the effects of UV exposure on the retina [1,
33], in the late 1970s and early 1980s IOL
manufacturers began to incorporate UVblocking chromophores in their lenses to
protect the retina from potential damage.
Still, when the crystalline lens is removed
during cataract or refractive lens exchange
surgery and replaced with a colorless UVblocking IOL, the retina is suddenly bathed in
much higher levels of blue light than it has
ever known and remains exposed to this increased level of potentially damaging light
ever after. Yet, until recent years, the IOLmanufacturing 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
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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
waves in efforts to incorporate blue-light protection into IOLs, although these efforts have
not all been documented in the peer-reviewed literature. Recently, two IOL manufacturers have developed stable methods to incorporate blue-light-filtering capabilities into
IOLs without leaching or progressive discoloration of the chromophore.
16.4
Hoya IOL
Hoya released PMMA blue-light-filtering
IOLs in Japan in 1991 (three-piece model
HOYA UVCY) and 1994 (single-piece model
HOYA UVCY-1P). Clinical studies of these yellow-tinted IOLs (model UVCY, manufactured
by Hoya Corp., Tokyo, and the Meniflex NV
type from Menicon Co., Ltd., Nagoya) have
been carried out in Japan [16, 17, 34]. One
study found that pseudophakic color vision
with a yellow-tinted IOL approximated the vision of 20-year-old control subjects in the
blue-light range [35]. Another study found
some improvement of photopic and mesopic
contrast sensitivity, as well as a decrease in the
effects of central glare on contrast sensitivity,
in pseudophakic eyes with a tinted IOL versus
a standard lens with UV-blocker only [36].
Hoya also introduced a foldable acrylic bluelight-filtering IOL with PMMA haptics to
some European countries in late 2003.
16.5
AcrySof Natural IOL
In 2002, the AcrySof Natural, a UV- and bluelight-filtering IOL, was approved for use in
Europe, followed by approval in the USA in
2003. The IOL is based on Alcon’s hydrophobic acrylic IOL, the AcrySof IOL. In addition
to containing a UV-blocking agent, the
AcrySof Natural IOL incorporates a yellow
chromophore cross-linked to the acrylic molecules. Extensive aging studies have been performed on this IOL and have shown that the
chromophore will not leach out or discolor
[37]. This yellow chromophore allows the IOL
not only to block UV light, but selectively to
filter varying levels of light in the blue wavelength region as well. Light transmission assessment demonstrates that this IOL approximates the transmission spectrum of the
normal human crystalline lens in the blue
light spectrum (Fig. 16.3). Therefore, in addi-
Chapter 16
Blue-Light-Filtering Intraocular Lenses
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
retina to blue light, color perception should
seem more natural to these patients as opposed to the increased blueness, clinically
known as cyanopsia, reported by patients
who have received colorless UV-blocking
IOLs [38].
16.6
FDA Clinical Study
In order to gain approval of the Food and
Drug Administration (FDA), a multi-centered, randomized prospective study was
conducted in the USA. It involved 300 patients randomized to bilateral implantation
of either the AcrySof Natural IOL or the clear
AcrySof Single-Piece IOL. One hundred and
fifty patients received the AcrySof Natural
IOL and 147 patients received the AcrySof
Single-Piece IOL as a control. Patients with
bilateral age-related cataracts who were willing and able to wait at least 30 days between
cataract procedures and had verified normal
preoperative color vision were eligible for the
study. In all bilateral lens implantation cases,
the same model lens was used in each eye.
Postoperative parameters measured included
visual acuity, photopic and mesopic contrast
sensitivity, and color perception using the
Farnsworth D-15 test. Results showed that
there was no difference between the AcrySof
Natural IOL and the clear AcrySof IOL in
any of these parameters [39] (Figs. 16.4, 16.5,
16.6 and 16.7). More substantial color perception testing using the Farnsworth–Munsell 100 Hue Test has also demonstrated no
difference in color perception between the
AcrySof Natural IOL and the clear AcrySof
IOL [39].
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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
Fig. 16.8. Blue-light transmission spectrum showing low transmission of 441 nm light and high trans-
mission of 507 nm light with the AcrySof Natural IOL
16.7
Blue-Light-Filtering IOLs
and Low Light Conditions
Both mesopic vision and scotopic vision refer
to vision with low-light conditions. Wyszecki
and Stiles point out that mesopic vision begins at approximately 0.001 cd/m2 and extends up to 5 cd/m2 for a 3° diameter centrally fixated target; however, the upper range
could extend up to 15 cd/m2 for a 25° diameter target [40]. Nevertheless, 3 cd/m2 is the
most often cited upper limit for mesopic vision. One can liken this to the low light conditions on a cloudless night with a full moon.
The contrast sensitivity tests performed under mesopic conditions in the FDA trials
demonstrated that the AcrySof Natural IOL
does not negatively affect mesopic vision.
Scotopic refers to light levels below the
mesopic range, which can be likened to a
moonless, starry night. Since blue wavelength
light is imperative for scotopic vision, some
are worried that attenuating blue light will
negatively affect scotopic vision. Certainly, if
all blue light were blocked, one might expect
some decrease in scotopic vision. However,
the AcrySof Natural IOL does not block all
blue light. Indeed, the most important wavelength for scotopic vision is at and around
507 nm [41]. The AcrySof Natural allows
transmission of approximately 85% of light
at 507 nm. In comparison, a UV-blocking colorless IOL transmits only 5% more. The normal human crystalline lens at any age transmits significantly less light at and near
507 nm than does the AcrySof Natural IOL
and therefore, patients implanted with the
AcrySof Natural IOL should have enhanced
scotopic vision. It would be counterintuitive
to believe that scotopic vision would be diminished instead of enhanced (Fig. 16.8).
16.8
Clinical Experience
Having implanted more than 1,000 AcrySof
Natural IOLs over the past year, I have had the
opportunity to gain insight into the quality of
vision provided by this unique IOL. The IOL
behaves identically to the clear AcrySof IOL
in all aspects. It also has the advantage of being easier to visualize during folding, loading
and implantation due to its yellow coloration.
The visual results in my patients have been
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excellent without any complaints of color
perception or night vision problems. I have
implanted this blue-light-filtering IOL in the
fellow eye of patients previously implanted
with colorless UV-filtering IOLs. When asked
to compare the color of a white tissue paper,
70% do not see a difference between the two
eyes. Of the 30% that could tell a difference,
none perceived the difference before I
checked and none felt the difference was
bothersome.With more than 1,000,000 AcrySof
Natural IOLs implanted worldwide by the
time of this writing, there are no confirmed
reports of color perception or night vision
problems.
16.9
Summary
Given the growing body of evidence implicating blue light as a potential factor in the worsening of AMD and the positive collective clinical experience with this new IOL, the AcrySof
Natural has become the lens of choice in
cataract surgery patients for many ophthalmologists worldwide. When performing refractive lens exchange, especially in the
younger patient, one should ponder the potential consequences of exposing the retina to
higher levels of blue light for the rest of that
patient’s life. I believe that blue-light-filtering
IOLs will become the lens of choice for these
patients as well.
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