Download Age-Related Macular Degeneration

Volume 1, Issue 6
2014
A Learning Resource for Optometrists from the School of Optometry & Vision Science, University of Waterloo, and the School of Optometry, University of Montreal
Age-Related Macular Degeneration:
From Diagnosis to Treatment
By Julie Brûlé, OD, MSc, FAAO, Julie-Andrée Marinier, OD, MSc,
and Judith Renaud, OD, PhD
Age-related macular degeneration (AMD) is the most common cause of legal blindness in adults
living in developed countries. It is associated with significant functional, quality of life, and psychological implications. While the atrophic (“dry”) form is more common, exudative or neovascular
(“wet”) AMD is responsible for up to 90% of the cases of significant vision loss related to AMD.
This issue of Optometry Rounds outlines the clinical evaluation and management for the patient
with AMD, including the latest data on nutritional supplements and pharmacotherapy.
Age-related macular degeneration (AMD) is the leading cause of legal blindness (corrected visual
acuity [VA] ≤6/60 or greatest diameter of the visual field ≤20° in each eye) among adults in developed
countries.1 In Canada, an estimated 1 million adults aged ≥40 years have early AMD and a further
250 000 have more advanced forms.2 These amounts are projected to double by 2030.3
AMD is associated with significant negative functional and psychosocial effects. Social roles and
daily activities, particularly those requiring central vision, may be significantly affected.4-7 For example,
AMD patients may need to prematurely stop working or modifying their work tasks. They also often
have difficulty recognizing faces and facial expressions, which hinders social interactions.8 Many
leisure activities can be restricted.6,7 To adapt to these changes, the person will have several significant
adjustments to make and will need assistance, technological as well as human.6,9
The traumatic experience of visual loss associated with AMD frequently has significant emotional
and psychological consequences. Quality of life in individuals with AMD is comparable to that of
those suffering from serious systemic diseases such as cancer, ischemic heart disease, and stroke.10 Fears
of going blind and loss of independence often lead to anxiety and depression.11,12 Older individuals
with visual disabilities are at particularly high risk for depression; the prevalence of depression in this
population is 7%–25%,13,14 and 25%–45% experience depressive symptoms.15-17 Given the increased
risk of suicide in the depressed elderly, this mental health problem cannot be overlooked.
Clinical Classification
AMD is divided into 2 types: atrophic (“dry”) and exudative or neovascular (“wet”). The dry
form is the most common, affecting approximately 85% of AMD patients. 18 In its early stages,
dry AMD is characterized by the presence of fatty deposits under the retinal pigmented epithelium
(RPE), called drusen, as well as regions of irregular RPE pigment (Figures 1A, 1B). Drusen may
coalesce and progress towards a detachment of the RPE and, eventually, form atrophic regions. This
atrophy can be focal or extensive; the latter, called geographic atrophy, is the advanced form of dry
AMD and may cause significant visual loss (Figure 1C).18,19 Some cases of dry AMD may progress to
the wet form.
Exudative (“wet”) AMD is characterized by the development of neovascular choroidal vessels.
These new vessels can leak and cause bleeding or accumulation of intraretinal fluid. Exudative AMD
often presents with retinal fibrosis (Figure 1D).18,19 Despite its markedly lower occurrence than the dry
form, wet AMD accounts for up to 90% of cases of significant AMD-related vision loss.20-22
Paul Murphy, FCOptom, PhD, FAAO
Professor and Director
Thomas F. Freddo, OD, PhD, FAAO
Professor and Co-Editor, Optometry Rounds
Contributing Faculty Authors:
Sarah MacIver, OD, FAAO
Clinical Lecturer
C. Lisa Prokopich, OD, MSc
Clinical Lecturer
Michelle Steenbakkers, OD, FAAO
Clinical Lecturer
École d’Optométrie
School Administration:
Christian Casanova, PhD
Director and Professor
Neurophysiology and Imaging
Danielle de Guise, OD, MSc
Associate Director of Cycle 1 Studies
Binocular Vision and Orthoptics
Jocelyn Faubert, PhD, FAAO
Associate Director of Research and Advanced Studies
Professor, Psychophysiology and Visual Perception
Jacques Gresset, OD, PhD, FAAO
Secretary and Professor
Epidemiology and Low Vision
Editorial Committee:
Jean-François Bouchard, BPharm, PhD
Associate Professor, Neuropharmacology
Pierre Forcier, OD, MSc
Associate Professor, Ocular Health
Langis Michaud, OD, MSc, FAAO (Dipl.)
Associate Professor, Contact Lenses
Co-Editor, Optometry Rounds
Judith Renaud, OD, PhD
Assistant Professor, Low Vision
Risk Factors
University of Waterloo
School of Optometry & Vision Science
200 University Avenue West, Waterloo, ON N2L 3G1
Although the pathological processes leading to the onset and progression of AMD have yet to be
fully understood, several risk factors for the disease have been identified.
Université de Montréal
École d’Optométrie
3744 Jean-Brillant, Montreal, QC H3T 1P1
Available online at www.optometryrounds.ca
The editorial content of Optometry Rounds is determined
solely by the School of Optometry & Vision Science,
University of Waterloo, and the School of Optometry,
University of Montreal.
Figures 1A-D: Age-Related Eye Disease Study (AREDS)
categories for age-related macular degeneration (AMD)
1A. Category 2: intermediate confluent drusen and
abnormalities in the retinal pigmented epithelium (RPE)
Non-modifiable risk factors
Age. Population-based studies indicate that the incidence,
prevalence, and severity of AMD increase significantly with
age.20-26
Family history. The presence of AMD within the family is
associated with an increased risk of its development.24,27 This
association is consistent with the increasingly important role
of several predisposing genetic factors.19
Ethnicity has long been identified as a major risk factor
for AMD. Studies have suggested that Caucasians are more
affected by AMD than other races.20,28,29 Despite this fact, a
recent meta-analysis attributed a low level of risk to this
factor.24
Sex. Women may be at a slightly greater risk than men for
developing AMD;20,25 however, this factor remains controversial.21,24
Systemic conditions. AMD appears to be associated with a
positive history of cardiovascular disease, hypertension, or
diabetes.24,29,30
Ocular risk factors. Patients with lighter iris pigmentation
are at a greater risk of developing AMD,24,31 as are those who
are hyperopic.20 A history of cataract surgery is also a risk factor for the development of advanced AMD, 24,32 although a
randomized, controlled clinical trial did not report any effect
of cataract surgery on the course of AMD.33
Modifiable risk factors
1B. Category 3: intermediate and large drusen that
coalesce with RPE abnormalities
1C. Category 4: geographic atrophy involving the fovea
Smoking (current and ex-smokers) is the most important
modifiable risk factor for AMD. It is strongly associated with a
markedly increased risk of developing AMD and of evolving
towards the more advanced stages.20,21,24,29,34
Alcohol. Moderate daily alcohol consumption (2 standard
drinks per day) has been linked to an elevated risk of AMD,35
and high alcohol consumption (>3 drinks per day) is associated with a significantly increased risk of early AMD development.36
Medication. Regular and long-term ingestion of acetylsalicylic acid may raise the risk of developing neovascular AMD,
depending on the dose;37 however, it should be noted that the
standard dose prescribed for the prevention of cardiovascular
disease (81 mg) was not studied.
Obesity. Although some data support an association
between obesity and AMD,24,38,39 the effect of weight loss in the
prevention or slowing down of AMD remains to be determined.40
Sun exposure. The role of sun exposure in the development of AMD is a longstanding controversy.20,22,31,41,42 A recent
meta-analysis43 reveals that individuals who had greater exposure to the sun are at an increased risk of developing AMD.
The optometric and ophthalmological communities thus consider exposure to sun as a risk factor, especially since it is easily
modifiable.44
Clinical Evaluation
1D. Category 4: exudative AMD with retinal fibrosis
2
Clinical examination of patients living with AMD
includes the assessment of numerous visual functions as well
as a mandatory fundus examination with pupillary dilation.
Disease staging (Figure 2) is an essential element for decision
making regarding management, including timing of optometric follow-up and determination of whether referral to an
ophthalmologist and/or low vision services is indicated.
Figure 2: Clinical follow-up of AMD
Category 1*
Category 2*
Category 3*
• Management of
risk factors
• Management of risk
factors
• Amsler grid
(home use)
• Follow-up: 1 year
• Management of risk
factors
• Amsler grid
(home use)
• Follow-up:
6-12 months
• Amsler grid
(home use)
• Nutritional
supplements
• Follow-up:
6-12 months
• Referral as
needed to an
ophthalmologist or
vision rehabilitation
Category 4*
Dry AMD:
geographic atrophy
• Management of risk factors
• Nutritional supplements
• Referral to an
ophthalmologist
• Vision rehabilitation
• Follow-up: 6 months
Wet (exudative) AMD
• Referral to an
ophthalmologist
• Vision rehabilitation
• Follow-up: 6 months
* According to AREDS
Management
Inform patients about the importance of regular examinations, even in the absence of symptoms, and instruct them to
seek prompt consultation with an optometrist or ophthalmologist following the emergence of any new visual symptoms.
Patient history should include questions about the known
risk factors for AMD, recent visual changes, or symptoms
relating to the onset or progression of AMD, such as meta-
morphopsia. It is also important to ask patients about the
functional impact of AMD on their daily life (Table 1).
Measurement of VA is essential to assess the progression
of AMD and in order to perform functional vision follow-up.
When there is a significant decrease in vision (VA <6/18), lowvision charts are more appropriate. These include the Feinbloom and Early Treatment Diabetic Retinopathy Study
Table 1: Examples of activities and roles affected by AMD
Nutrition
Meal preparation
Operating food-preparation appliances (eg, stove, microwave)
Reading restaurant menus
Personal care
Medication identification and dosing
Choice of clothing
Hair styling, makeup, and shaving
Communication
Reading and writing
Use of computer, telephone, and television
Housing
Housekeeping
Operating appliances (eg, washer, dryer, heating system)
Mobility
Safe ambulation inside and outside the home
Crossing streets
Loss of driver’s license (consult provincial/territory laws)
Use of public transit
Community life
Use of public services (bank, post office, library) and shops
Responsibilities
Payment of accounts
Distinguishing money (bills and coins)
Use of credit and bank cards
Interpersonal relationships
Recognition of faces and facial expressions
Work
Commuting to work
Performing job-related responsibilities
Leisure
Crafts and hobbies (eg, do-it-yourself projects, knitting)
Games (eg, bridge, bingo) and sports activities
Attending artistic or cultural events (eg, theatre)
3
(ETDRS) charts for distance vision. Options for near vision
include the reduced ETDRS and Lighthouse (single letter)
charts as well as reading charts such as the Minnesota Reading
Test (MNRead Card) or Colenbrander.45 During VA measurement, it is important to verify the presence of binocular summation (improvement) or inhibition (deterioration),
especially while measuring reading VA.46 Finally, the evaluation of contrast sensitivity, using specific scales such as PelliRobson for distance vision or the Mars for near vision, can
help to understand the patient’s functional complaints.47,48
Considering the modifications of the central visual field,
refraction should be tested with trial frames to allow eccentric
fixation. 49 In a patient receiving anti-vascular endothelial
growth factor (anti-VEGF) injections, it is possible to observe
a refraction variation. This underlines the need to verify the
prescription should a change in VA occur.
Evaluation of the peripheral and central visual fields will
determine whether metamorphopsia or a scotoma (relative or
absolute) are present. An automated Octopus or Goldmann
perimeter with a dome is typically used as a kinetic visual field
to measure the functional visual field. The Amsler grid helps to
verify the presence of metamorphopsia or central scotomas.
Use of reverse polarity, with white lines on a black background
with a marked X, is recommended. It should be noted that if
the Amsler grid is used by the patient at home (for monitoring
purposes), the optometrist cannot rely solely on these results
to determine the presence or absence of scotomas. Central
visual field testing, such as a 10-2 central field (Humphrey or
Octopus), should be included in the evaluation, assuming
there is sufficient central vision to maintain fixation.50
The complete eye examination performed under dilation
with fundus biomicroscopy and indirect binocular ophthalmoscopy will help to properly establish the stage of AMD
(Table 2). Fundus photography will document the progression
of AMD and will be useful for interdisciplinary references.
Additional assessments, such as optical coherence tomography (OCT) and microperimetry, are used with increasing
frequency. OCT identifies, among other things, the presence
of neovascularization, subretinal fluid, and retinal tears, helping to specify the stage of AMD (Figures 3A,B). 51 A recent
study52 concluded that the best predictor of VA improvement
following ranibizumab (anti-VEGF) injections was the pretreatment integrity of the outer retina on OCT. In addition,
Table 2: AREDS categories
Category
Signs
1
None or few small drusen
2
At least 1 of the following:
• several small drusen (≤63 µm)
• some intermediate drusen (62-124 µm)
• RPE anomalies
3
At least 1 of the following:
• several intermediate drusen
• 1 or more large drusen (≥125 µm)*
• geographic atrophy not involving the fovea
4
Geographic atrophy involving the fovea or
any sign of exudative AMD and visual loss
* 125 µm represents approximately the diameter of the retinal vein near the optic
nerve
4
Figures 3A,B: Retinal optical coherence tomography
sections
3A. Moderate dry AMD
3B. Wet AMD with intraretinal fluid and neovascularization
outer retinal thickness and OCT-determined integrity of the
RPE have been shown to be good predictors of AMD progression and central visual field narrowing, as measured by
microperimetry. 53 From a functional point of view, vision
rehabilitation experts study eccentric fixation with
microperimetry and scanning laser ophthalmoscopy (SLO)
combined with OCT. Recent studies show that a comprehensive assessment of functional vision allows effective and positive vision rehabilitation for patients receiving anti-VEGF
injections.53
New retinal imaging techniques (with the autofluorescence function) have reduced the use of fluorescein angiography in AMD treatment. However, a consensus of Canadian
ophthalmologists recently reported that angiography remains
important for the clinical monitoring of AMD, in particular to
determine the size of the lesion to be treated and to detect
geographic atrophy or early choroidal neovascularization.54
Management of AMD Patients
Managing risk/aggravating factors
The management of risk factors and aggravating factors is
essential in all patients with AMD and at all stages of the disease. Optometrists should educate the patient about modifiable risk/aggravating factors related to lifestyle and
recommend changes. The effects of smoking, the most important modifiable risk factor, are reversible: the risk begins to
decrease as soon as the patient stops smoking.55 It is therefore
important to question patients regarding their smoking status
and to encourage patients who smoke to begin their cessation
attempt and even refer them to specific resources like the panCanadian telephone helpline (iQuitnow 1-866-527-7383). It is
also important to advise patients with respect to adequate sun
protection, as well as to raise awareness regarding the importance of maintaining a healthy weight and limiting alcohol
consumption.
Nutritional supplements
The prescription of nutritional supplements can be useful
in some patients with AMD. The Age-Related Eye Disease
Study (AREDS) showed that a combination of high doses of
antioxidants and minerals (vitamins C and E, beta carotene,
and zinc) could delay the progression of dry AMD in patients
with moderate or advanced stages of the disease (ie, AREDS
category 3–4; Table 3).56 Patients who smoke or have recently
quit should receive formulas without beta-carotene; supplements containing high doses of beta-carotene have been associated with a higher risk of lung cancer in these populations.57
Despite the suggested benefit in some studies of dietary supplementation with antioxidants, minerals, and omega-3 in the
delay or prevention of AMD onset,35,58,59 there is insufficient
evidence to justify their recommendation to patients with no
disease evidence of AMD or only mild disease.35,56,60
Various studies suggest a protective effect of carotenoids
(lutein and zeaxanthin) throughout the progression of AMD
towards the advanced stages. AREDS-261 explored this question, in addition to the effect of omega-3 alone or in combination with carotenoids on a randomized, controlled
sample. There was no statistically significant effect of adding
omega-3 or carotenoids to the original AREDS formula,
whether on AMD progression to advanced stages or on
improvement of VA.
particular challenges faced with their social roles and activities is of paramount importance (Table 1). It is important to
maximize their independence and safety in their daily life. It
is also important to discuss the patient’s expectations and to
ensure that they are realistic. The patient’s goals should
guide the examination.
It is essential to recognize that patients’ psychological or
cognitive state may create a dichotomy between their daily
functioning and objective measures. For example, a depressive
state is associated with a reduced perception of functional
capacity, sometimes resulting in an inequality between measured visual functions and functioning in everyday life.62 Furthermore, studies have identified an association between the
signs of AMD and cognitive deficits.63,64 Conversely, cognitive
problems may affect visual skills.65 The optometrist must be
vigilant to these potential health problems and refer patients to
their family physicians or other healthcare professionals (geriatricians, neuropsychologists, psychiatrists, psychologists) for
appropriate treatment. It is also important to discuss potential
functional and psychosocial issues with the patient’s relatives.
Consideration of functional and psychosocial impacts
Patient resources
The functional impacts of AMD sometimes require multiple adjustments to ensure that patients can perform their
daily activities and social roles: adaptation to their environments, compensatory strategies, use of assistive devices
(optic and nonoptic; Table 4), and human assistance. In
assessing the needs of the individual, identification of the
A wide array of interventions exists to help AMD patients
in their adaptation process. In Canada, many resources are
available, varying from timely services to national programs.66
Specialized readaptation services exist through hospitals,
optometric/ophthalmological clinics, provincial government
centres, or organizations such as the Canadian National Institute for the Blind (www.cnib.ca). Some provinces reimburse
specialized examinations for low vision and offer loans or
grants for technical aids.
Several community organizations and associations provide both general assistance to the elderly and more specific
services for those with visual impairment, including AMD; eg,
disease information, support groups, psychological support,
cleaning services, and home meals. Optometrists should be
aware of the different resources in their community to better
inform their patients.
In addition, the federal and some provincial governments
provide a tax credit for people with legal blindness. For the
federal tax statement, this credit can be claimed under the
Disability Tax Credit Certificate (form T2201, http://www.
cra-arc.gc.ca/E/pbg/tf/t2201); optometrists are authorized to
fill out this form.
Carotenoids
Table 3: AREDS-recommended dose of nutritional
supplements to delay the progression of AMD according
to AREDS
Ingredients
Original AREDS Recommended
formula
AREDS-2* formula
Beta-carotene (mg)
15
0
Omega-3 (ester/
triglycerides; mg)
0
0
Vitamin C (mg)
500
500
Vitamin E (UI)
400
400
Copper (mg)
2
2
80 (O)
80 (O)
Lutein (mg)
0
10
Zeaxanthin (mg)
0
2
Moderate
AMD: prescribe
the formula
without betacarotene (formula "S") for
smokers and
ex-smokers
Moderate AMD
Zinc (oxide or
gluconate; mg)
When should they be
recommended?
(clinical target)
Medical Treatments
* The AREDS-2 formula is characterized by the absence of beta-carotene. According
to the results of the study, the combination of lutein and zeaxanthin replaces
beta-carotene while reducing the risk of side effects in smokers, ex-smokers or
those who have been exposed to second-hand smoke.
Since the advent of anti-VEGF agents for the treatment of
wet AMD, such as bevacizumab and ranibizumab, numerous
clinical trials have attempted to specify the efficacy and dosage
of these therapeutic agents.
Ranibizumab, a humanized monoclonal antibody fragment that binds with high affinity to all types of VEGF antigen isoforms (VEGF-A) and their associated degenerative
products, is approved by Health Canada for the treatment of
exudative AMD, as well as for the treatment of visual impairment due to diabetic macular edema and macular edema secondary to retinal vein occlusion. 67 The MARINA 68 and
ANCHOR69,70 studies have shown significantly greater efficacy
of ranibizumab compared to sham injection and verteporfin
5
Table 4: Activities, adaptation, and technical aids
Activities
Target VA according to activity
Suggested adaptation and technical aids
Reading prices in stores and
medication names, using postal
and bank services
For decoding, should see 1M (use near
VA cards such as reduced ETDRS or
Lighthouse charts)
llluminated hand-held magnifier, high-add
eyeglasses (>4.00D), microscopic eyeglasses
Reading, managing finances, and
mail
For reading, should see 0.8M (use
reading charts such as MNRead or
Colenbrander)
Adjust lighting, large-print materials, high-add
eyeglasses (>4.00D), microscopic eyeglasses,
illuminated stand magnifier, electro-optical
magnifying device, closed-circuit television
(CCTV)
Reading street names, addresses,
and notice boards
At distance, target VA of 6/12
Terrestrial telescopes, binoculars
Use of electronics, appliances,
remote controls, and telephone
Device labeling with contrasting or textured tags,
large-print devices
VA = visual acuity; ETDRS = Early Treatment Diabetic Retinopathy Study
therapy, respectively, over a period of 2 years. Improvements
in the best corrected VA were significantly higher than results
obtained with previous therapies used for AMD treatment.
For the first time, a treatment managed to maintain and even
significantly improve the VA in the treatment group in comparison with the control group. In addition to greater visual
function, monthly injections of ranibizumab also resulted in
an improvement of the retina’s anatomical architecture as
observed with angiography and OCT over a period of 24
months.71,72 A recent consensus among Canadian ophthalmologists recommended that an initial monthly intravitreal injection dose for the first 3 months be continued with monthly
injections until the neovascularization has stabilized.54
Bevacizumab, also administered by monthly intravitreal
injection, was studied for the treatment of exudative AMD.
This human monoclonal antibody binds and blocks the action
of all vascularization isotypes, similar to those covered by
ranibizumab. Several retrospective and prospective studies
have shown its efficacy for the treatment of exudative AMD,
with a low risk of complications.73-76 It is important to note,
however, that bevacizumab is not approved by Health Canada
for ocular use.77
In light of persistent clinical questions regarding whether
ranibizumab or bevacizumab is more effective for the treatment
of exudative AMD, the National Eye Institute of the United States
(US) from the National Institutes of Health (NIH) organized the
multicentre, prospective, randomized, controlled clinical Comparison of Age-related Macular Degeneration Treatments Trials
(CATT).78 In 2011, the CATT group published that bevacizumab
was not inferior to ranibizumab for the treatment of wet AMD.
As well, the rates of adverse events such as bacterial endophthalmitis, increased intraocular pressure, uveitis, and retinal
detachment were similar between the 2 agents in all of the
groups. However, patients receiving bevacizumab experienced
significantly more serious systemic adverse events and hospitalizations (risk ratio 1.29; 95% confidence interval 1.01 to 1.66).
Finally, on the same monthly injection basis over the period of 1
year, bevacizumab was much less costly than ranibizumab. These
results were supported by the 2-year CATT results.79 It is ultimately up to the ophthalmologist to weigh the clinical risks versus the benefits for each patient treated.
6
The most recent treatment for exudative AMD is intravitreal aflibercept, which recently received approval from Health
Canada. 80 In 2012, the VIEW 1 and VIEW 2 81 randomized
clinical trials showed that aflibercept, when administered
monthly or every 2 months following the first 3 initial
monthly injections, proved to be as effective and safe as
ranibizumab for the treatment of exudative AMD. The
administration of aflibercept every 2 months could reduce the
risks associated with monthly intravitreal injections.
Finally, collaboration between the optometrist and ophthalmologist is essential for preservation of vision for patients
receiving intravitreal treatment. Proper disease staging and
appropriate treatment will result in stabilization or even
improvement of the patient’s vision.
Emerging therapies
New therapies are emerging for the treatment of AMD,
particularly gene therapy and stem cell (RPE) transplantation
therapy. Knowing the genotype of the patient with AMD will
eventually make it possible to intervene and treat earlier in the
disease, especially in the first stage of atrophic AMD.82 Stem
cell transplantation therapy involves the replacement of damaged retinal cells with embryonic stem cells.83
Conclusion
Optometrists, as primary eye care professionals,
regularly encounter individuals with AMD in their practice.
AMD is classified under 2 forms: atrophic (dry) and exudative (wet). The evolution and the complications associated
with these 2 forms differ, requiring each a specific follow-up.
Fundus examination performed under pupil dilation as well
as other complementary tests, such as OCT, will help the
optometrist to determine the stage of AMD. Given that there
are numerous risk factors and treatment options for this
disease, the optometrist must be familiar with them in order
to educate and counsel patients. Finally, AMD can impact on
both functional and psychosocial levels. Vision rehabil itation services can minimize these impacts on patients’
daily activities and social roles. Actively collaborating with
AMD patients, the optometrist plays a key role in oculo visual health.
Dr. Brûlé is an Assistant Professor at the School of Optometry,
University of Montreal. Dr. Marinier is an Assistant Professor at
the School of Optometry, University of Montreal, and an
Optometrist at the Institut Nazareth et Louis-Braille.
Dr. Renaud is an Assistant Professor at the School of Optometry,
University of Montreal, and an Optometrist at the Institut
Nazareth et Louis-Braille. These authors contributed equally to
this article.
References
1. Resnikoff S, Pascolini D, Etya’ale D, et al. Global data on visual impairment
in the year 2002. Bull World Health Organ. 2004;82(11):844-851.
2. Burhmann R, Hodge W, Beardmore J, et al. Foundations for a Canadian
Vision Health Strategy. Toronto (ON). Prepared for the National Coalition
for Vision Health, January 2007.
3. Buhrmann R, Hodge WG, Gold D. Forecasting the vision loss epidemic in
Canada: current and projected estimates of age-related eye disease. Report submitted to the National Coalition for Vision Health. 2006 September 23, 2006.
4. Hassell JB, Lamoureux EL, Keeffe JE. Impact of age related macular degeneration on quality of life. Br J Ophthalmol. 2006;90(5):593-596.
5. Lamoureux EL, Pallant JF, Pesudovs K, et al. Assessing participation in daily
living and the effectiveness of rehabiliation in age related macular degeneration patients using the impact of vision impairment scale. Ophthalmic Epidemiol. 2008;15(2):105-113.
6. Desrosiers J, Wanet-Defalque M-C, Temisjian K, et al. Participation in daily
activities and social roles of older adults with visual impairment. Disabil
Rehabil. 2009;31(15):1227-1234.
7. Alma MA, van der Mei SF, Melis-Dankers BJM, van Tilburg TG, Groothoff
JW, Suurmeijer TPBM. Participation of the elderly after vision loss. Disabil
Rehabil. 2011;33(1):63-72.
8. Wong EYH, Guymer RH, Hassell JB, Keeffe JE. The experience of agerelated macular degeneration. J Vis Impair Blind. 2004;98(10):1-30.
9. Good GA, LaGrow S, Alpass F. An age-cohort study of older adults with and
without visual impairments: activity, independence, and life satisfaction.
J Vis Impair Blind. 2008;102(9):517-527.
10. Yuzawa M, Fujita K, Tanaka E, Wang EC. Assessing quality of life in the
treatment of patients with age-related macular degeneration: clinical
research findings and recommendations for clinical practice. Clin Ophthalmol. 2013;7:1325-32.
11. Casten R, Rovner B. Depression in age-related macular degeneration. J Vis
Impair Blind. 2008;102(10):591-599.
12. Berman K, Brodaty H. Psychosocial effects of age-related macular degeneration. Int Psychogeriatr. 2006;18(3):415-428.
13. Brody BL, Gamst AC, Williams RA, et al. Depression, visual acuity, comorbidity, and disability associated with age-related macular degeneration.
Ophthalmology. 2001;108(10):1893-1900.
14. Horowitz A, Reinhardt JP, Kennedy GJ. Major and subthreshold depression
among older adults seeking vision rehabilitation services. Am J Geriatr Psychiatry. 2005;13(3):180-187.
15. Burmedi D, Becker S, Heyl V, Wahl H-W, Himmelsbach I. Emotional and
social consequences of age-related low vision. Vis Impair Res. 2002;4(1):4771.
16. Hayman KJ, Kerse NM, La Grow SJ, Wouldes T, Robertson MC, Campbell
AJ. Depression in older people: visual impairment and subjective ratings of
health. Optom Vis Sci. 2007;84(11):1024-1030.
17. Mathew RS, Delbaere K, Lord SR, Beaumont P, Vaegan, Madigan MC.
Depressive symptoms and quality of life in people with age-related macular
degeneration. Ophthalmic Physiol Opt. 2011;31(4):375-380.
18. Haddad S, Chen CA, Santangelo SL, Seddon JM. The genetics of age-related
macular degeneration: a review of progress to date. Surv Ophthalmol.
2006;51(4):316-363.
19. Lim LS, Mitchell P, Seddon JM, Holz FG, Wong TY. Age-related macular
degeneration. Lancet. 2012;379(9827):1728-1738.
20. Age-Related Eye Disease Study Research Group. Risk factors associated with
age-related macular degeneration. A case-control study in the age-related
eye disease study: Age-Related Eye Disease Study Report Number 3. Ophthalmology. 2000;107(12):2224-2232.
21. Smith W, Assink J, Klein R, et al. Risk factors for age-related macular degeneration: Pooled findings from three continents. Ophthalmology. 2001;
108(4):697-704.
22. Hyman LG, Lilienfeld AM, Ferris FL 3rd, Fine SL. Senile macular degeneration: a case-control study. Am J Epidemiol. 1983;118(2):213-227.
23. Klein R, Klein BE, Knudtson MD, Meuer SM, Swift M, Gangnon RE. Fifteen-year cumulative incidence of age-related macular degeneration: the
Beaver Dam Eye Study. Ophthalmology. 2007;114(2):253-262.
24. Chakravarthy U, Wong TY, Fletcher A, et al. Clinical risk factors for agerelated macular degeneration: a systematic review and meta-analysis. BMC
Ophthalmol. 2010;10:31.
25. Rudnicka AR, Jarrar Z, Wormald R, Cook DG, Fletcher A, Owen CG. Age
and gender variations in age-related macular degeneration prevalence in
populations of European ancestry: a meta-analysis. Ophthalmology. 2012;
119(3):571-580.
26. Sin HP, Liu DT, Lam DS. Lifestyle modification, nutritional and vitamins
supplements for age-related macular degeneration. Acta Ophthalmol.
2013;91(1):6-11.
27. Shahid H, Khan JC, Cipriani V, et al; Genetic Factors in AMD Study Group.
Age-related macular degeneration: the importance of family history as a
risk factor. Br J Ophthalmol. 2012;96(3):427-431.
28. Friedman DS, Katz J, Bressler NM, Rahmani B, Tielsch JM. Racial differences in the prevalence of age-related macular degeneration: the Baltimore
Eye Survey. Ophthalmology. 1999;106(6):1049-1055.
29. Clemons TE, Milton RC, Klein R, Seddon JM, Ferris FL 3rd. Age-Related Eye
Disease Study Research G. Risk factors for the incidence of Advanced AgeRelated Macular Degeneration in the Age-Related Eye Disease Study
(AREDS) AREDS report no. 19. Ophthalmology. 2005;112(4):533-539.
30. Reynolds R, Rosner B, Seddon JM. Serum lipid biomarkers and hepatic
lipase gene associations with age-related macular degeneration. Ophthalmology. 2010;117(10):1989-1995.
31. Mitchell P, Smith W, Wang JJ. Iris color, skin sun sensitivity, and age-related
maculopathy. The Blue Mountains Eye Study. Ophthalmology. 1998;105(8):
1359-1363.
32. Cugati S, Mitchell P, Rochtchina E, Tan AG, Smith W, Wang JJ. Cataract
surgery and the 10-year incidence of age-related maculopathy: the Blue
Mountains Eye Study. Ophthalmology. 2006;113(11):2020-2025.
33. Chew EY, Sperduto RD, Milton RC, et al. Risk of advanced age-related macular degeneration after cataract surgery in the Age-Related Eye Disease
Study: AREDS report 25. Ophthalmology. 2009;116(2):297-303.
34. McCarty CA, Mukesh BN, Fu CL, Mitchell P, Wang JJ, Taylor HR. Risk factors for age-related maculopathy: the Visual Impairment Project. Arch Ophthalmol. 2001;119(10):1455-1462.
35. Adams MK, Chong EW, Williamson E, et al. 20/20 – Alcohol and agerelated macular degeneration: the Melbourne Collaborative Cohort Study.
Am J Epidemiol. 2012;176(4):289-298.
36. Chong EW, Kreis AJ, Wong TY, Simpson JA, Guymer RH. Alcohol consumption and the risk of age-related macular degeneration: a systematic
review and meta-analysis. Am J Ophthalmol. 2008;145(4):707-715.
37. Liew G, Mitchell P, Wong TY, Rochtchina E, Wang JJ. The association of
aspirin use with age-related macular degeneration. JAMA Intern Med.
2013;173(4):258-264.
38. Schaumberg DA, Christen WG, Hankinson SE, Glynn RJ. Body mass index
and the incidence of visually significant age-related maculopathy in men.
Arch Ophthalmol. 2001;119(9):1259-1265.
39. Seddon JM, Cote J, Davis N, Rosner B. Progression of age-related macular
degeneration: association with body mass index, waist circumference, and
waist-hip ratio. Arch Ophthalmol. 2003;121(6):785-792.
40. Cheung N, Wong TY. Obesity and eye diseases. Surv Ophthalmol. 2007;
52(2):180-195.
41. Cruickshanks KJ, Klein R, Klein BE. Sunlight and age-related macular degeneration. The Beaver Dam Eye Study. Arch Ophthalmol. 1993;111(4):514-518.
42. Delcourt C, Carriere I, Ponton-Sanchez A, Fourrey S, Lacroux A, Papoz L,
POLA Study Group. Light exposure and the risk of age-related macular
degeneration: the Pathologies Oculaires Liées à l’Age (POLA) study. Arch
Ophthalmol. 2001;119(10):1463-1468.
43. Sui GY, Liu GC, Liu GY, et al. Is sunlight exposure a risk factor for agerelated macular degeneration? A systematic review and meta-analysis. Br J
Ophthalmol. 2013;97(4):389-394.
44. Somani S, Hoskin-Mott A, Mishra A, et al. Managing patients at risk for
age-related macular degeneration: a Canadian strategy. Can J Optom.
2009;71(2):14-20.
45. Patel PJ, Chen FK, Da Cruz L, Rubin GS, Tufail A. Test-retest variability of
reading performance metrics using MNREAD in patients with age-related
macular degeneration. Invest Ophthalmol Vis Sci. 2011;52(6):3854-3859.
46. Tarita-Nistor L, Gonzalez EG, Markowitz SN, Steinbach MJ. Binocular
interactions in patients with age-related macular degeneration: acuity summation and rivalry. Vision Res. 2006;46(16):2487-2498.
47. Thayaparan K, Crossland MD, Rubin GS. Clinical assessment of two new
contrast sensitivity charts. Br J Ophthalmol. 2007;91(6):749-752.
48. Dougherty BE, Flom RE, Bullimore MA. An evaluation of the Mars Letter
Contrast Sensitivity Test. Optom Vis Sci. 2005;82(11):970-975.
7
49. DeCarlo DK, McGwin G Jr, Searcey K, et al. Trial frame refraction versus
autorefraction among new patients in a low-vision clinic. Invest Ophthalmol
Vis Sci. 2013;54(1):19-24.
50. Fletcher DC, Schuchard RA, Renninger LW. Patient awareness of binocular
central scotoma in age-related macular degeneration. Optom Vis Sci.
2012;89(9):1395-1398.
51. Sulzbacher F, Kiss C, Kaider A, et al. Correlation of SD-OCT features and
retinal sensitivity in neovascular age-related macular degeneration. Invest
Ophthalmol Vis Sci. 2012;53(10):6448-6455.
52. Mathew R, Richardson M, Sivaprasad S. Predictive value of spectraldomain optical coherence tomography features in assessment of visual
prognosis in eyes with neovascular age-related macular degeneration
treated with ranibizumab. Am J Ophthalmol. 2013;155(4):720-726.
53. Acton JH, Smith RT, Hood DC, Greenstein VC. Relationship between retinal layer thickness and the visual field in early age-related macular degeneration. Invest Ophthalmol Vis Sci. 2012;53(12):7618-7624.
54. Cruess AF, Berger A, Colleaux K, et al. Canadian expert consensus: optimal
treatment of neovascular age-related macular degeneration. Can J Ophthalmol. 2012;47(3):227-235.
55. Neuner B, Komm A, Wellmann J, et al. Smoking history and the incidence
of age-related macular degeneration – results from the Muenster Aging and
Retina Study (MARS) cohort and systematic review and meta-analysis of
observational longitudinal studies. Addict Behav. 2009;34(11): 938-947.
56. Age-Related Eye Disease Study Research Group. A randomized, placebocontrolled, clinical trial of high-dose supplementation with vitamins C and
E, beta carotene, and zinc for age-related macular degeneration and vision
loss: AREDS report no. 8. Arch Ophthalmol. 2001;119(10):1417-1436.
57. Evans JR, Lawrenson JG. Antioxidant vitamin and mineral supplements for
slowing the progression of age-related macular degeneration. Cochrane
Database Syst Rev. 2012;11:CD000254.
58. van Leeuwen R, Boekhoorn S, Vingerling JR, et al. Dietary intake of antioxidants and risk of age-related macular degeneration. JAMA. 2005;294(24):
3101-3107.
59. Tan JS, Wang JJ, Flood V, Mitchell P. Dietary fatty acids and the 10-year incidence of age-related macular degeneration: the Blue Mountains Eye Study.
Arch Ophthalmol. 2009;127(5):656-665.
60. Evans JR, Lawrenson JG. Antioxidant vitamin and mineral supplements for
preventing age-related macular degeneration. Cochrane Database Syst Rev.
2012;6:CD000253.
61. Age-Related Eye Disease Study 2 Research Group. Lutein + zeaxanthin and
omega-3 fatty acids for age-related macular degeneration: The Age-Related
Eye Disease Study 2 (AREDS2) randomized clinical trial. JAMA. 2013;
309(19):2005-2015.
62. Renaud J, Bedard E. Depression in the elderly with visual impairment and
its association with quality of life. Clin Interv Aging. 2013;8:931-943.
63. Clemons TE, Rankin MW, McBee WL; Age-Related Eye Disease Study
Research Group. Cognitive impairment in the Age-Related Eye Disease
Study: AREDS report no. 16. Arch Ophthalmol. 2006;124(4):537-543.
64. Baker ML, Wang JJ, Rogers S, et al. Early age-related macular degeneration,
cognitive function, and dementia: the Cardiovascular Health Study. Arch
Ophthalmol. 2009;127(5):667-673.
65. Rovner BW, Casten RJ, Massof RW, Leiby BE, Tasman WS; Wills Eye AMD
Study. Psychological and cognitive determinants of vision function in agerelated macular degeneration. Arch Ophthalmol. 2011;129(7):885-890.
66. Robillard N, Overbury O. Quebec model for low vision rehabilitation. Can J
Ophthalmol. 2006;41(3):362-366.
67. Novartis Pharmaceuticals Canada Inc. Lucentis® (ranibizumab injection)
Product Monograph. Date of authorization: December 13, 2011.
68. Rosenfeld PJ, Brown DM, Heier JS, et al; MARINA Study Group.
Ranibizumab for neovascular age-related macular degeneration. N Engl J
Med. 2006;355(14):1419-1431.
69. Brown DM, Kaiser PK, Michels M, et al; ANCHOR Study Group.
Ranibizumab versus verteporfin for neovascular age-related macular
degeneration. N Engl J Med. 2006;355(14):1432-1444.
70. Brown DM, Michels M, Kaiser PK, Heier JS, Sy JP, Ianchulev T; ANCHOR
Study Group. Ranibizumab versus verteporfin photodynamic therapy for
neovascular age-related macular degeneration: Two-year results of the
ANCHOR study. Ophthalmology. 2009;116(1):57-65.
71. Kaiser PK, Blodi BA, Shapiro H, Acharya NR; MARINA Study Group.
Angiographic and optical coherence tomographic results of the MARINA
study of ranibizumab in neovascular age-related macular degeneration.
Ophthalmology. 2007;114(10):1868-1875.
72. Sadda SR, Stoller G, Boyer DS, Blodi BA, Shapiro H, Ianchulev T. Anatomical benefit from ranibizumab treatment of predominantly classic neovascular age-related macular degeneration in the 2-year ANCHOR study. Retina.
2010;30(9):1390-1399.
73. Spaide RF, Laud K, Fine HF, et al. Intravitreal bevacizumab treatment of
choroidal neovascularization secondary to age-related macular degeneration. Retina. 2006;26(4):383-390.
74. Emerson MV, Lauer AK, Flaxel CJ, et al. Intravitreal bevacizumab (Avastin)
treatment of neovascular age-related macular degeneration. Retina. 2007;
27(4):439-444.
75. Pedersen R, Soliman W, Lund-Andersen H, Larsen M. Treatment of
choroidal neovascularization using intravitreal bevacizumab. Acta Ophthalmol Scand. 2007;85(5):526-533.
76. Aggio FB, Farah ME, Silva WC, Melo GB. Intravitreal bevacizumab for
exudative age-related macular degeneration after multiple treatments.
Graefes Arch Clin Exp Ophthalmol. 2007;245(2):215-220.
77. Hoffmann-La Roche Ltd. Avastin® (bevacizumab for injection) Product
Monograph. Date of authorization: February 23, 2012.
78. CATT Research Group; Martin DF, Maguire MG, Ying GS, Grunwald JE,
Fine SL, Jaffe GJ. Ranibizumab and bevacizumab for neovascular agerelated macular degeneration. N Engl J Med. 2011;364(20):1897-1908.
79. Comparison of Age-related Macular Degeneration Treatments Trials
(CATT) Research Group; Martin DF, Maguire MG, Fine SL, et al.
Ranibizumab and bevacizumab for treatment of neovascular age-related
macular degeneration: two-year results. Ophthalmology. 2012;119(7): 13881398.
80. Bayer Inc. Eylea® (aflibercept) Product Monograph. Date of approval:
November 8, 2013.
81. Heier JS, Brown DM, Chong V, et al; VIEW 1 and VIEW 2 Study Groups.
Intravitreal aflibercept (VEGF trap-eye) in wet age-related macular degeneration. Ophthalmology. 2012;119(12):2537-2548.
82. Priya RR, Chew EY, Swaroop A. Genetic studies of age-related macular
degeneration: lessons, challenges, and opportunities for disease management. Ophthalmology. 2012;119(12):2526-2536.
83. Schwartz SD, Hubschman JP, Heilwell G, et al. Embryonic stem cell trials for
macular degeneration: a preliminary report. Lancet. 2012;379(9817): 713720.
The authors stated that they have no disclosures to report in
association with the contents of this issue.
Change of address notices and requests for subscriptions
for Optometry Rounds are to be sent by mail to P.O.
Box 310, Station H, Montreal, Quebec H3G 2K8 or by fax to (514)
932-5114 or by e-mail to [email protected]. Please reference
Optometry Rounds in your correspondence. Undeliverable copies
are to be sent to the address above. Publications Post #40032303
A Partnership for Excellence in Continuing Optometry Education
Optometry Rounds is made possible through independent sponsorships from
Alcon Canada and Novartis Pharmaceuticals Canada Inc.
© 2014 School of Optometry & Vision Science, University of Waterloo, and School of Optometry, University of Montreal, which are solely responsible for the contents. The opinions expressed
in this publication do not necessarily reflect those of the publisher or sponsor, but rather are those of the authoring institution based on the available scientific literature. Publisher: SNELL
Medical Communication Inc. in cooperation with the School of Optometry & Vision Science, University of Waterloo, and School of Optometry, University of Montreal. All rights reserved.
The administration of any therapies discussed or referred to in Optometry Rounds should always be consistent with the approved prescribing information Canada.
149-006E