Download blue light - College of Optometrists

BLUE LIGHT
A review of the evidence on the
potential benefits and harms of
blue-filtering lenses
• Thierry Villette PhD, Essilor International
• Prof. John Lawrenson FCOptom, City U. London
LECTURE. Monday 13 March. 11:30 am
Blue-light – Part II
AGENDA
01
​BLUE-CUT TRADE-OFF
02
​PHOTOBIOLOGY
03
​LENS TECHNOLOGY & CRITERIA
Blue-cut lenses: their promise
Short-term benefits claimed:
Long-term benefits claimed:
reduces visual fatigue, digital eyestrain, glare
better contrast, depth perception
visual comfort, relaxed vision,
ideally suited for digital world, for indoor activities
…
protects against harmful blue light, prevents retinal
ageing, AMD, neurodegenerative process
visual health, protects visual capital
…
Europe
Amera
US / CA
…
Latin America
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Blue-light – Part II
AGENDA
01
​BLUE-CUT TRADE-OFF
02
​PHOTOBIOLOGY
03
​LENS TECHNOLOGY & CRITERIA
PHOTORECEPTION
VISUAL
VA, CS
scotopic, color
…
NON VISUAL
sleep, mood, alertness,
cognition,
pupil reflex
…
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PHOTOTOXICITY
photochemical damage
oxidative stress
inflammation
 tissue dysfunction
 eye diseases
Photoreception
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Photoreception – Light is essential for vision…
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Photoreception - … but also for non visual functions
Light is the main synchronizer of our biological clock.
New photoreceptor identified in 2002: ip-RGC (1 – 3% of RGCs)
LOCOMOTOR ACTIVITY
COGNITION
MOOD
PUPIL REFLEX
SLEEP
Blue-Turquoise
480 nm
BODY TEMPERATURE
ipRGC
Melanopsin
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Without light, the biological clock drifts in phase
Sleep hours
Jours consécutifs dans le gouffre
1
Michel Siffre, 24 yo
Summer 1962
62 days in French alps
10
20
30
40
33h shift
50
8
16
24
8
16
24
8
16
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Consequences of a poor light synchronization
•
Fatigue
•
Alertness disorders
•
Difficulties of concentrating
•
Memory disorders
•
Mood disorders
•
Sleepiness
•
Fragmented sleep
•
Poor sleep efficiency
•
Metabolic troubles
•
Muscular troubles
•
Digestive troubles
•
Cardiovascular troubles
Nature reviews, Neurosciences
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Phototoxicity
State of
the art
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Light & the eye, multiple risk parameters
Spectrum Eye absorption
Radiance
Genetics
Orientation
Ethnics
Distance
Time
Light
environment
Individual
risk
profiling
Patient
Season
Altitude
Latitude
Luminance
ratios
Age
Gender
Lifestyle
(food, smoking…)
Surface reflectances
Protections
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Acute phototoxicity
Rapid, bright light & short duration exposure
13
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Chronic / cumulative phototoxicity
Long-term, moderate light & long duration exposure / repetitions /
wavelength-dependent (photochemical reactions)
14
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Our light exposure behaviours are rapidly evolving
15 | CONFIDENTIAL | ESSILOR© and Paris Vision Institute –R&D Disruptive, Thierry Villette
Artificial light sources vs Sunlight
Daylight
Halogen
(sun)
Incandescent
Fluorescent
Cold white LED
Over 90% of light sources worldwide based
on LEDs by 2020.
16 | CONFIDENTIAL | ESSILOR© and Paris Vision Institute –R&D Disruptive, Thierry Villette
Fluorescent
Photoreception VS Phototoxicity
a threatened equilibrium
PHOTORECEPTION
PHOTOTOXICITY
Vision /
Well-being
Pathology
17 | CONFIDENTIAL | ESSILOR© and Paris Vision Institute –R&D Disruptive, Thierry Villette
Blue light, an identified risk factor for AMD
• The Chesapeake Bay study, 1992
(Taylor et al., Arch Ophthalmol, 1992)
• 838 watermen
• Significant correlation (p=0.05) between blue light exposure during the previous 20
years and severe AMD.
• Compared with age-matched controls, AMD patients were significantly higher
exposed to blue light but equally exposed to UV.
• The Beaver Dam Eye Study, 2004
• 5000 individuals, 43 – 84 yo
• The amount of time spent outdoors between 13 and 19 and between 30 and 39 yo
was significantly associated with development of both early and late AMD.
• The EUREYE study, 2008
• Correlation between blue exposure and wet AMD for patients with lower antioxidant
level
• Sui et al., Br J Ophthalmol, 2012,
Meta-analysis, 14 pooled studies. 12 studies
concluded to an increased risk of AMD with greater sunlight exposure (OD 1.379).
6 studies reported significant risks.
• Higher prevalence of AMD after cataract surgery
(loss of natural blue filtering)
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YELLOW IOL’s & RETINAL PROTECTION
Wang JJ, Klein R, Klein BE, Mitchell P et al. Increased risk (OR 5.7) for developing
Ophthalmology 2003
late-stage ARM, particularly wet AMD, after 5-year of cataract surgery
>6000 subjects; Pooled data from Beaver Dam Eye & Blue Mountains studies
110(10):1960-7
Nagai H et al.
Henderson BA, Grimes KJ (2010)
Survey Ophthalmol (55) 284-9
•
Photoreception
•
•
•
•
•
•
•
•
•
Transmission
Scotopic vision
VA
VA low contrast
contrast sensitivity
color vision
Sleep/circadian
Photoprotection
good ++
•
•
•
•
•
•
•
•
Low
•
superior
good
good
good
good
good
good
good
•
•
•
•
•
•
•
•
typically similar to 53 y.o.
may be altered in some subjects
good
good (save in low light)
good (> in mesopic)
good (except blue nuances)
good (Mind the spectrum!)
High
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25% blue-filtering IOLs
(54% in the USA)
TREND:
Blue-light – Part II
AGENDA
01
​BLUE-CUT TRADE-OFF
02
​PHOTOBIOLOGY
03
​LENS TECHNOLOGY & CRITERIA
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Phototoxicity mechanism in outer retina - AMD
Retinal Pigment Epithelium (RPE) cells
ensure
SURVIVAL, FUNCTIONING and RENEWAL
of photoreceptor
degenerate in maculopathies such as AMD
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Phototoxicity mechanism in outer retina - AMD
(2/2)
RPE
RPE
AND / OR
AND / OR
ATR
hν
O2
Reactive
oxygen
species
hν
Lipofuscin
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Lipofuscin:
pathological photosensitizer in aging and AMD
Delori et al., IOVS, 2012
Wing et al., IOVS; 1978
Fast lipofuscin accumulation in early age and after 45 yo
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Mains in vivo studies
Increasing dose
Blue light: lower thresholds for photochemical damages – Photoreceptor action spectra
van Norren & Gorgels, PP, 2011
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Putting et al., IOVS, 1994
Model
in vivo, rabbits
Spectral band
12 nm-wide blue bands 408, 418, 439, 455 and 485 nm
Exposure duration
1 to 6 h
Light level
35 - 208 mW/cm² - high level
Analysis
Conclusion
Fluorescein
(permeability damage)
439 nm is the most toxic wavelength for permeability damage in rabbits.
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Sparrow et al., IOVS, 2000
Model
in vitro, ARPE-19 cell line treated with A2E (100 µM)
Spectral band
1/ Blue light ; 2/ Green light
Exposure duration
60 s
Light level
1/ 75 mW/mm² ; 2/ 200 mW/mm² - high level (acute)
Analysis
Conclusion
No phototoxicity without photosensitizer.
The higher the concentration in photosensitizers, the higher the phototoxicity.
Blue light is 6.5 to 7.5 x more toxic than green light for RPE cells.
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Godley et al., JBC, 2005
Model
in vitro, RPE cells treated with lipofuscin
Spectral band
Blue-green light [390 nm – 550 nm]
Exposure duration
1 to 6 h
Light level
2,8 mW/cm² - low level (chronic)
Analysis
v
Conclusion
Blue light at chronic light levels induces DNA lesions, espacially for RPE cells loaded
with the age photosensitizer lipofuscin.
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Chamorro, Sanchez-Ramos et al., PP, 2013
Model
in vitro, cell line RPE cells
Spectral band
LEDs - blue-468 nm, green-525 nm, red-616 nm and white light
Exposure duration
3 light–darkness 12 h/12 h cycles
Light level
5 mW/cm²
Analysis
Apoptosis
Viability
Conclusion
LED radiations decrease 75–99% cellular viability, and increase 66–89% cellular
apoptosis. Higher toxicity for cold-white and blue LEDs.
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Phototoxicity
refined
spectral
data
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Collaborative research program since 2009
Custom-made
cell illumination
systems
in vitro
models of
eye diseases
Biomarker
analysis
30
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in vitro
photoprotection
Cell model of retinal photoageing and AMD
A2E
A2E
Primary RPE cell
cultures
Major component of
lipofuscin
31
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Tight junctions
Nucleus
photometry & illumination model
LED-based fibered system, 14 narrow illumination bands (10 nm)
from 390 to 520 nm + 630 nm, adjustable irradiances
Moderate irradiances normalized to retinal sunlight irradiances
18h light exposure, n≥ 6
E e,retina (λ ) =
A
pupil
u '²
×L
e , source
(λ ) × τ (λ )
Calculated irradiances reaching the A2E-loaded RPE cells (mW/cm²)
UNIT 2
1,42
1,35
1,40
1,30
1,42
1,36
1,60
1,40
1,47
1,50
1,23
1,09
1,20
1,00
0,82
0,80
0,59
0,60
0,35
0,40
0,20
0,11
0,04
0,00
380
UNIT 1
430
480
530
Wavelength (nm)
56
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580
630
680
The phototoxicity action spectrum on RPE cells
(outer retina): 415-455nm
*
*
*
8
1,8
*
*
*
7
*
*
*
1,6
*
*
*
1,4
6
1,2
5
1,0
4
0,8
3
0,6
2
0,4
1
0,2
0
0,0
Dark 390
410
430
450
470
Eclairements (mW/cm²)
Mort cellulaire – apoptose 40 µM A2E
9
490
510
630
Longueur d’onde (nm)
•
Toxicity not strictly correlated to irradiances
•
Toxicity not strictly correlated to the photon energy
•
Very significant increase of cell death 415 – 455 nm
33
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PLOS ONE paper.
August 2013
PLoS ONE (www.plosone.org). August 2013. 8(8). e71398
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↑ SOD clustering
activity but ⇊ functioning
⇈ peri-nuclear
for nucleus protection +
⇈ ROS (reactive
⇈ ROS (reactive
globular
shape
oxygen species)
oxygen species)
****
****
⇊ catalase
activity and
functioning
****
0
0
3
6
0
4
8
4
0
4
0
rk
a
D
****
****
4
*
**
*
**
*
BV light
induces…
****
* ***
* ***
* ***
* ***
****
**
***
****
***
****
0
0
63
0
48
44
40
D
ar
k
0
*
BV light at 430 nm
Darkness /Red light
02.⇈ cell death
GPX
1,6
1,4
0,2
0
0,0
D
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0
1
↑ glutathione activity
but ⇊ functioning
3
0,4
0
2
6
0,6
8
3
0
0,8
4
4
****
H20 + 02
4
1,0
0
5
4
1,2
a
6
0
7
H 20
+ 02
1,8
4
8
** *
** *
** * *
*
*
CAT
H 2 02
rk
9
SOD
Conclusion - Blue-light induced retinal damage
•
Blue-violet toxicity action spectrum on RPE cells confirmed with
oxidative stress biomarkers (415 – 455 nm).
•
Blue-violet light induces high ROS production (H2O2, O2.-).
•
Blue-violet light acts as a strong inhibitor of antioxidant
mechanisms (glutathione, SOD, catalase).
•
Blue-violet light directly impacts mitochondria: peri-nuclear
clustering, globular shape, decreased respiration rate.
•
Low-irradiance blue-violet light induces apoptotic cell death.
•
… Accelerated retinal photo-ageing and AMD.
36
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BLUE LIGHT HAZARD FUNCTION
should be revised to a B2(λ) curve for cumulative hazard
B (λ) = [Ham et al’s 1976] acute action spectrum on monkey eyes (acute)
X spectral transmittance of the human crystalline lens
Blue hzard function - relative spectral effectiveness weighting
function B (normalized to 1)
1
1997
0.9
0.8
0.7
0.6
0.5
B1
0.4
B2
0.3
0.2
0.1
0
380
400
420
440
460
480
500
Wavelength (nm)
Ham W.T., Mueller H.A. and Sliney D.H. (1976)
Retinal sensitivity to damage from short wavelength light. Nature. 260(5547):153-5
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Photoprotection
potency
in vitro
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Photoprotection benefits
A complete protection on front AND back sides
1
A 20% cut of noxious Blue-Violet light
in vitro quantification of protective effect
Decrease of 25% in average of the target retinal cell death
over [400 nm ; 455 nm] compared to the naked eye
Apoptose 40 µM A2E
6,00
5,00
Crizal Prevencia
4,00
Naked eye
3,00
Crizal Prevencia
2,00
Naked eye
1,00
0,00
Noir 400 410 420 430 440 450 460 480 490 500
Longueur d’onde (nm)
The UV protection on back side
2
A 25x higher protection compared to the naked eye
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in vitro photoprotective potency (% decrease in
cell death)
in vitro photoprotection potency model
100%
y = 6.5008x3 - 6.3084x2 + 2.3115x
R² = 0.9196
80%
60%
40%
20%
0%
0%
20%
40%
60%
80%
BVC (%)
The first biological quantification of the
effect of blue-cut optical filters in vitro
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100%
Blue-light – Part II
AGENDA
01
​BLUE-CUT TRADE-OFF
02
​PHOTOBIOLOGY
03
​LENS TECHNOLOGY & CRITERIA
CONFIDENTIAL © 2016 ESSILOR - All rights reserved – Do not copy
LENS TECHNOLOGIES for BLUE-VIOLET FILTERING
interferential vs absorption … or combined
Antireflective
coating
HMC system
HC system
Absorber
in coating
Additional
layer
Nanostructure
technologies
Absorber
in MASS
Substrate
interferential
Filtering % (efficacy)
Narrow band (selectivity)
low w. thin films
absorption
high
++
--
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Spectral selectivity
narrow-band ‘gutter profile’
SELECTIVITY of a BLUE-CUT LENS
Blue cut filter concepts
Target λ selectivity
cut the bad, leave the good
100
90
Transmission (%)
80
70
60
50
40
30
retina cell protection
20
chronobiology light
10
0
400
410
420
430
440
450
460
470
480
490
500
Wavelenghts (nm)
1. The selectivity of the filter
for the Blue-Violet light cut [415-455] nm
2. The selectivity of the filter
for the chronobiological light [465-495]nm
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Product performances:
toward next generations of blue-cut lenses
AR efficacy
0.6
(Rv >2,5= not AR)
1
T blue-turquoise%
Visible transmission
[465-495]nm
100%
100% (Tv% <80%=Class 1)
92%
92%
>2,5
80%
+ Yellow index (b*)
80%
20%
+ lens aesthetics
Product A
25
Product B
Product C
40%
Blue-violet cut
[400-455]nm
50%
50
ESPF: UV protection
+ in vitro photoprotection potency
44 | CONFIDENTIAL | ESSILOR© and Paris Vision Institute –R&D
– AprilDisruptive,
2013 - R&D
Thierry
Disruptive
Villette
Coralie Barrau, Thierry Villette
CONCLUSIONS
• Blue-violet light 380-455nm is a recognized risk factor in retinal
ageing and maculopathies
• Opportunity and filtering level of blue-cut lenses to be discussed
with ophthalmologists and optometrists:
 advice vs individual risk and environmental exposure level
 trade-off photoprotection vs photoreception
• Adopting relevant criteria for a blue-filtering lens:




45
blue-violet light filtering: T% in [380-455nm], T% in [415-455nm]
in vitro photoprotection potency (RPE cell model of AMD) – biology QC
chronobiology blue T% [465-495nm]
Tv(%), yellow index (b*), aesthetics
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FUTURE RESEARCH NEEDED
• Prospective and controled clinical studies to assess the benefit
of blue-cut lenses to slow down retinal ageing and AMD
 target population / filtering level / endpoint / follow-up 3+ years
• To what extent does blue-violet light contribute
to pathogenesis? to disease progression?
• Blue-cut lenses and immediate benefits
 what spectral determinant / what filtering dose-effect on
eye fatigue, digital eye strain, glare, photosensitivity …
46
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A review of the evidence on the
potential benefits and harms of
blue-filtering lenses
Professor John Lawrenson
City University London
Declarations of Interest
• John Lawrenson has no prorietary interests
in the development or marketing of any
product mentioned in this lecture
ASA Ruling
‘Boots did not provide evidence that a modest 20% reduction in the amount of harmful blue
light entering the eye would lead to a significant reduction in the amount of retinal damage
caused by exposure, as implied by the ad. In the context of an ad which purported that
harmful blue light was damaging to retinal cells and implied that the majority, if not all,
harmful blue light was filtered out by Boots’ lens coating before it reached the retina, we did
not consider the evidence was adequate to support the implied claim made. We therefore
concluded the ad was misleading.’
https://www.asa.org.uk/Rulings/Adjudications/2015/10/Boots-Professional-ServicesLtd/SHP_ADJ_293200.aspx#.Vt62ueaHuFt
Questions for the Optometrist
• Should we worry about exposure to blue
light in our natural visual environment?
• Do computers, tablets and smartphones
pose a serious risk to ocular health ?
• Is there a case for photo-protection and if so
how can this be achieved?
Is blue light harmful?
Radiance
Radiant power emitted into a
solid angle
Wm− 2 sr − 1
Luminance
Luminous power as perceived by
a human standard observer
cd m-2
http://www.icnirp.org/cms/upload/publications/ICNIRPVisible_Infrared2013.pdf
Is blue light harmful?
http://www.crizalusa.com/content/dam/crizal/us/en/pdf/bl
ue-light/Blue-Light-Roundtable_White-Paper.pdf
Is blue light harmful?
Is blue light harmful?
http://www.icnirp.org/cms/upload/publications/ICNIRPVisible_Infrared2013.pdf
Role of the Pupil
http://www.icnirp.org/cms/upload/publications/ICNIRPVisible_Infrared2013.pdf
Natural protective filter
Lens transmission aged 5, 50, 80 years
http://www.ncbi.nlm.nih.gov/pubmed/16445433
Natural protective filter
http://www.sciencedirect.com/science/article/pii/S1350946
215000865
Sunlight and AMD
Sunlight and AMD
http://bjo.bmj.com/content/97/4/389.abstract
Sunlight and AMD
In the low exposure group 20 people out of 1000
developed late AMD over 75 years, compared to 27 (95%
CI 22 to 34) out of 1000 for the high exposure group
Sunlight and AMD
The number
needed to harm
(NNH) indicates
how many patients
on average need to
be exposed to a
risk-factor over a
specific period to
cause harm in a
patient who would
otherwise not
have been harmed.
NNH=135
In the low exposure group 20 people out of 1000
developed late AMD over 75 years, compared to 27 (95%
CI 22 to 34) out of 1000 for the high exposure group
Cataract Extraction and AMD
http://www.ncbi.nlm.nih.gov/pubmed/16445433
Cataract Extraction and AMD
Relative Risk =3.05; CI 2.05 - 4.55
http://www.ncbi.nlm.nih.gov/pubmed/21144031
Cataract Extraction and
AMD
Benefits versus side effects of blue-filtering IOLs
http://www.ncbi.nlm.nih.gov/pubmed/16445433
Benefits of Blue Light
http://www.abbottmedicaloptics.com/products/cataract/m
onofocal-iols/tecnis-1-piece-iol
Based on the evidence the authors of this perspective disagreed on the IOL
they would choose should they need cataract surgery in the future!
• MAM opted for a UV-only blocking IOL to provide maximal UV protection
and to wear sunglasses in bright environments, which can be removed for
optimal vision in dim environments
• JRS opted for a UV+ blue blocking IOL to provide the same protection
against phototoxicity and scotopic sensitivity as a 50 year old crystalline
lens and to wear sunglasses in bright environments , which can be
removed for optimal vision in dim environments
Dr John O’Hagan
Group Leader, Laser and Optical
Radiation Dosimetry Group
Public Health England
http://www.ncbi.nlm.nih.gov/pubmed/26768920
The International Commission on Non-Ionizing Radiation Protection (ICNIRP) ‘rule of
thumb’ is that detailed risk assessments within spectral range 380-780 are not required for
luminance values <104 cd m-2
The ICNIRP blue light weighted radiance exposure limit for long-term viewing in range
300-700nm is 100Wm− 2 sr − 1
http://www.ncbi.nlm.nih.gov/pubmed/26768920
Blue light weighted spectral radiance:
• clear day in June = 10.4 Wm−2 sr −1
• cloudy day in December = 3.4 Wm− 2 sr − 1
These exposures represent 10.4% and 3.4% of the exposure limit.
http://www.ncbi.nlm.nih.gov/pubmed/26768920
Filtering the Blue
Blue light hazard peaks at 440nm
10%
40%
5 yr old versus 50 yr old lens
https://www.2020mag.com/ce/TTViewTest.aspx?LessonId=10865
4
http://www.ncbi.nlm.nih.gov/pubmed/10701805
Filtering the Blue
50%
UV versus blue filtering IOL
http://www.ncbi.nlm.nih.gov/pubmed/10701805
Filtering the Blue
50%
Filtering the Blue
http://www.ncbi.nlm.nih.gov/pubmed/10701805
Summary
• Blue light has the potential to cause retinal
phototoxicity although blue light also plays a role in
scotoptic sensitivity and circadian entrainment
• Blue light sources encountered indoors are unlikely
to approach exposure limits, even for extended
viewing times
• The eye possesses natural defences to mitigate blue
light damage
• Photoprotection could be considered in ‘at risk’
individuals