Routine Eye Examinations for Persons 20-64 Years of Age: An Evidence-Based Analysis

Medical Advisory Secretariat

. 2006 Jul 1;6(15):1–81.

Routine Eye Examinations for Persons 20-64 Years of Age

An Evidence-Based Analysis

Medical Advisory Secretariat

PMCID: PMC3379534 PMID: 23074485

Executive Summary

Objective

The objective of this analysis was to determine the strength of association between age, gender, ethnicity, family history of disease and refractive error and the risk of developing glaucoma or ARM?

Clinical Need

A routine eye exam serves a primary, secondary, and tertiary care role. In a primary care role, it allows contact with a doctor who can provide advice about eye care, which may reduce the incidence of eye disease and injury. In a secondary care role, it can via a case finding approach, diagnose persons with degenerative eye diseases such as glaucoma and or AMD, and lead to earlier treatment to slow the progression of the disease. Finally in a tertiary care role, it provides ongoing monitoring and treatment to those with diseases associated with vision loss.

Glaucoma is a progressive degenerative disease of the optic nerve, which causes gradual loss of peripheral (side) vision, and in advanced disease states loss of central vision. Blindness may results if glaucoma is not diagnosed and managed. The prevalence of primary open angle glaucoma (POAG) ranges from 1.1% to 3.0% in Western populations, and from 4.2% to 8.8% in populations of African descent. It is estimated up to 50% of people with glaucoma are aware that they have the disease. In Canada, glaucoma disease is the second leading cause of blindness in people aged 50 years and older. Tonometry, inspection of the optic disc and perimetry are used concurrently by physicians and optometrists to make the diagnosis of glaucoma. In general, the evidence shows that treating people with increased IOP only, increased IOP and clinical signs of early glaucoma or with normal-tension glaucoma can reduce the progression of disease.

Age-related maculopathy (ARM) is a degenerative disease of the macula, which is a part of the retina. Damage to the macula causes loss of central vision affecting the ability to read, recognize faces and to move about freely. ARM can be divided into an early- stage (early ARM) and a late-stage (AMD). AMD is the leading cause of blindness in developed countries. The prevalence of AMD increases with increasing age. It is estimated that 1% of people 55 years of age, 5% aged 75 to 84 years and 15% 80 years of age and older have AMD. ARM can be diagnosed during fundoscopy (ophthalmoscopy) which is a visual inspection of the retina by a physician or optometrist, or from a photograph of the retina. There is no cure or prevention for ARM. Likewise, there is currently no treatment to restore vision lost due to AMD. However, there are treatments to delay the progression of the disease and further loss of vision.

The Technology

A periodic oculo-visual assessment is defined “as an examination of the eye and vision system rendered primarily to determine if a patient has a simple refractive error (visual acuity assessment) including myopia, hypermetropia, presbyopia, anisometropia or astigmatism.” This service includes a history of the presenting complaint, past medical history, visual acuity examination, ocular mobility examination, slit lamp examination of the anterior segment, ophthalmoscopy, and tonometry (measurement of IOP) and is completed by either a physician or an optometrist.

Review Strategy

The Medical Advisory Secretariat conducted a computerized search of the literature in the following databases: OVID MEDLINE, MEDLINE, In-Process & Other Non-Indexed Citations, EMBASE, INAHTA and the Cochrane Library. The search was limited to English-language articles with human subjects, published from January 2000 to March 2006. In addition, a search was conducted for published guidelines, health technology assessments, and policy decisions. Bibliographies of references of relevant papers were searched for additional references that may have been missed in the computerized database search. Studies including participants 20 years and older, population-based prospective cohort studies, population-based cross-sectional studies when prospective cohort studies were unavailable or insufficient and studies determining and reporting the strength of association or risk- specific prevalence or incidence rates of either age, gender, ethnicity, refractive error or family history of disease and the risk of developing glaucoma or AMD were included in the review. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) system was used to summarize the overall quality of the body of evidence.

Summary of Findings

A total of 498 citations for the period January 2000 through February 2006 were retrieved and an additional 313 were identified when the search was expanded to include articles published between 1990 and 1999. An additional 6 articles were obtained from bibliographies of relevant articles. Of these, 36 articles were retrieved for further evaluation. Upon review, 1 meta-analysis and 15 population-based epidemiological studies were accepted for this review

Primary Open Angle Glaucoma

Age

Six cross-sectional studies and 1 prospective cohort study contributed data on the association between age and PAOG. From the data it can be concluded that the prevalence and 4-year incidence of POAG increases with increasing age. The odds of having POAG are statistically significantly greater for people 50 years of age and older relative to those 40 to 49 years of age. There is an estimated 7% per year incremental odds of having POAG in persons 40 years of age and older, and 10% per year in persons 49 years of age and older. POAG is undiagnosed in up to 50% of the population. The quality of the evidence is moderate.

Gender

Five cross-sectional studies evaluated the association between gender and POAG. Consistency in estimates is lacking among studies and because of this the association between gender and prevalent POAG is inconclusive. The quality of the evidence is very low.

Ethnicity

Only 1 cross-sectional study compared the prevalence rates of POAG between black and white participants. These data suggest that prevalent glaucoma is statistically significantly greater in a black population 50 years of age and older compared with a white population of similar age. There is an overall 4-fold increase in prevalent POAG in a black population compared with a white population. This increase may be due to a confounding variable not accounted for in the analysis. The quality of the evidence is low.

Refractive Error

Four cross-sectional studies assessed the association of myopia and POAG. These data suggest an association between myopia defined as a spherical equivalent of -1.00D or worse and prevalent POAG. However, there is inconsistency in results regarding the statistical significance of the association between myopia when defined as a spherical equivalent of -0.5D. The quality of the evidence is very low.

Family History of POAG

Three cross-sectional studies investigated the association between family history of glaucoma and prevalent POAG. These data suggest a 2.5 to 3.0 fold increase in the odds having POAG in persons with a family history (any first-degree relative) of POAG. The quality of the evidence is moderate.

Age-Related Maculopathy

Age

Four cohort studies evaluated the association between age and early ARM and AMD. After 55 years of age, the incidence of both early ARM and AMD increases with increasing age. Progression to AMD occurs in up to 12% of persons with early ARM. The quality of the evidence is low

Gender

Four cohort studies evaluated the association between gender and early ARM and AMD. Gender differences in incident early ARM and incident AMD are not supported from these data. The quality of the evidence is lows.

Ethnicity

One meta-analysis and 2 cross-sectional studies reported the ethnic-specific prevalence rates of ARM. The data suggests that the prevalence of early ARM is higher in a white population compared with a black population. The data suggest that the ethnic-specific differences in the prevalence of AMD remain inconclusive.

Refractive Error

Two cohort studies investigated the association between refractive error and the development of incident early ARM and AMD. The quality of the evidence is very low.

Family History

Two cross-sectional studies evaluated the association of family history and early ARM and AMD. Data from one study supports an association between a positive family history of AMD and having AMD. The results of the study indicate an almost 4-fold increase in the odds of any AMD in a person with a family history of AMD. The quality of the evidence, as based on the GRADE criteria is moderate.

Economic Analysis

The total population of Ontarians aged 50 to 64 years is estimated at 2.6 million based on the April 2006 Ontario Ministry of Finance population estimates. The range of utilization for a major eye examination in 2006/07 for this age group is estimated at 567,690 to 669,125, were coverage for major eye exams extended to this age group. This would represent a net increase in utilization of approximately 440,116 to 541,551.

The percentage of Ontario population categorized as black and/or those with a family history of glaucoma was approximately 20%. Therefore, the estimated range of utilization for a major eye examination in 2006/07 for this sub-population is estimated at 113,538 - 138,727 (20% of the estimated range of utilization in total population of 50-64 year olds in Ontario), were coverage for major eye exams extended to this sub-group. This would represent a net increase in utilization of approximately 88,023 to 108,310 within this sub-group.

Costs

The total cost of a major eye examination by a physician is $42.15, as per the 2006 Schedule of Benefits for Physician Services.(1) The total difference between the treatments of early-stage versus late-stage glaucoma was estimated at $167. The total cost per recipient was estimated at $891/person.

Current Ontario Policy

As of November 1, 2004 persons between 20 years and 64 years of age are eligible for an insured eye examination once every year if they have any of the following medical conditions: diabetes mellitus type 1 or 2, glaucoma, cataract(s), retinal disease, amblyopia, visual field defects, corneal disease, or strabismus. Persons between 20 to 64 years of age who do not have diabetes mellitus, glaucoma, cataract(s), retinal disease, amblyopia, visual field defects, corneal disease, or strabismus may be eligible for an annual eye examination if they have a valid “request for major eye examination” form completed by a physician (other than that who completed the eye exam) or a nurse practitioner working in a collaborative practice. Persons 20-64 years of age who are in receipt of social assistance and who do not have one of the 8 medical conditions listed above are eligible to receive an eye exam once every 2 years as a non-OHIP government funded service. Persons 19 years of age or younger and 65 years of age or older may receive an insured eye exam once every year.

Considerations for Policy Development

As of July 17, 2006 there were 1,402 practicing optometrists in Ontario. As of December 31, 2005 there were 404 practicing ophthalmologists in Ontario. It is unknown how many third party payers now cover routine eye exams for person between the ages of 20 and 64 years of age in Ontario.

Objective

The objective of this analysis was to determine the strength of association between age, gender, ethnicity, family history of disease and refractive error and the risk of developing glaucoma or ARM?

Background

Clinical Need: Target Population and Condition

Glaucoma

Glaucoma is a progressive degenerative disease of the optic nerve which causes gradual loss of peripheral (side) vision, and in advanced disease states loss of central vision.(6) There are two main types of glaucoma, primary open angle (POAG) and angle-closure glaucoma (ACG) of which POAG is the most common type. The earliest symptom of POAG is loss of peripheral vision, which can often go unnoticed. (7;8). Blindness may results if glaucoma is not diagnosed and managed (7). POAG is diagnosed by assessing characteristic degenerative changes in the optic disc and damage to visual fields (9)

Epidemiology

The prevalence of POAG ranges from 1.1% to 3.0% in Western populations, and from 4.2% to 8.8% in populations of African descent (10). The disease process can begin as early as 40 years of age and it is estimated that in developed countries, only 50% of people with glaucoma are aware they have the disease. (11) In Canada, glaucoma disease is the second leading cause of blindness in people aged 50 years and older, with POAG accounting for 90% of all cases.(12). It is estimated that 10% of people with POAG go blind in 1 eye and 4% go blind in both eyes. (Personal communication, clinical expert, July 6, 2006). The rate of progression to blindness has been difficult to determine with some studies reporting visual field loss rates of 2%-3% per year.(13). However, quantifying the lifetime risk of blindness for patients is difficult (14)

Some but not all people with POAG have increased intraocular pressure (IOP), which is the pressure of the fluid inside the eye. However, an estimated 25% to 50% of people with POAG have normal IOP. Those people with POAG whose IOP falls within the normal range (10-21mmHG) are said to have normal-tension or low-tension glaucoma (15). Risk factors for glaucoma include an increase in IOP, a family history of glaucoma, older age and being of African descent (9). Because the natural history of PAOG is not well-defined, some people with POAG who experience no disease progression will not experience a huge change in their vision, while others with more rapid progression may experience some loss of vision within 10 years of diagnosis. It is difficult to predict how fast the disease will progress. However, it is thought that people with higher IOP levels, poorer baseline visual field integrity and those who are older are at greater risk for rapid disease progression. Population studies indicate that approximately 50% of people with glaucoma have been diagnosed and treated (16). Prevalence and incidence are measures of burden of disease as is the patient perspectives on the impact of vision loss on functionality. (17) The degree of functional loss associated with glaucoma has not been adequately described. (6)

Diagnostic Tests for POAG

There are three methods of detecting POAG: tonometry, inspection of the optic disc and perimetry. All 3 tests are used concurrently to make the diagnosis of glaucoma.

Tonometry

Tonometry is a test that measures IOP. Because normal IOP has a diurnal fluctuation of as much as 5 mmHG if used alone to diagnose glaucoma, tonometry may not accurately detect the presence or absence of disease (7). Furthermore, as previously mentioned not everyone with glaucoma has an increased IOP. It is estimated that up to half of people with glaucoma have increases in IOP above normal in a random measurement. The positive predictive value for diagnosing glaucoma with tonometry has been reported to be 2% to 5% (7). IOP measurements above the upper limit of normal (21mmHG) have an estimated sensitivity of 47% and specificity of 92% for diagnosing POAG. The sensitivity of the classical cut-off for IOP of greater than 21mmHG is less than 50%. Furthermore, there is no IOP level where a reasonable balance of sensitivity and specificity is obtained.(6)

Inspection of the optic disc

Inspection or visualization of the optic disc called a fundoscopy (ophthalmoscopy) can be done by a physician or optometrist to determine if there is damage to the optic nerve. A dilated eye exam with direct ophthalmoscopy by an ophthalmologist has an estimated sensitivity of 59% and specificity of 73% for detecting glaucomatous-associated optic disc changes (15). Characteristic changes in the structure of the optic nerve have been used as diagnostic indicators of glaucoma. However, the ability of these parameters to accurately classify people into disease and non-disease states is relatively poor. Similar to tonometry, there is no cut-point that achieves an adequate sensitivity and specificity balance.

Perimetry

Perimetry is a test that evaluates the visual fields. The integrity of the visual fields determines where a person perceives visual stimuli. It is estimated that up to 30% to 50% of the optic nerve fibres must be lost before a classic glaucomatous visual field defect occurs with any consistency. Perimetry has been used as a screening test for glaucoma however the equipment is costly and not generally available to family physicians. The specificity and sensitivity of perimetry will vary depending on the method used as well as the cut-off point for defining visual field defects and the reference standard employed (15). To establish the presence of visual field defects, several visual field measurements are needed (9). Perimetry can be done by an automated instrument (Humphrey’s automated perimitry) or using a Goldmann perimetry device and a perimetrist (7). Measurement of visual fields can be difficult and the reliability of a single measurement may be low. Currently there is no defined standard of progression of visual field defects (9).

Treatments for POAG

Treatment for POAG is aimed at reducing IOP with topical agents often used as first-line therapy including pilocarpine, beta-adrenergic blockers such as timolol and betaxolol and systemic agents such as acetazolamide.(18). Surgery (laser trabeculoplasty or trabeculectomy) has also been used, usually when medical treatment has failed (18). In general, the evidence shows that treating people with increased IOP (16), increased IOP and clinical signs of early glaucoma (19) and normal-tension glaucoma (20) can reduce the progression of disease.

The Early Manifest Glaucoma Trial (19) evaluated the effectiveness of reducing IOP in patients 50 to 80 years of age with newly detected and previously untreated open-angle glaucoma (POAG, normal-tension glaucoma or exfoliation glaucoma) Patients were randomized to receive either a full 360 degree trabeculoplasty plus betaxolol hydrochloride eye drops at a dose of 5mg/ml twice daily (treatment group) or no treatment (control group). After a median follow-up time of 6 years, 58/129 (45%) of the treated patients compared with 78/126 (62%) of the controls showed disease progression (risk difference [RD], -17%, 95% confidence interval [CI], -.29, -.05, number-needed-to- treat [NNT] = 5.9) which was defined by progression of either glaucomatous visual field defects or optic disc cupping. The median time to progression was 48 months in the control group and 66 months in the treatment group (statistical significance not reported).

The Ocular Hypertension Treatment Study (16) determined the safety and efficacy of topical ocular hypotension medication (bextaxolol hydrochloride eye drops) in delaying or preventing the onset of POAG (evidenced by visual field defects or optic disc deterioration) in people 40 to -80 years of age with increased IOP (≥21mmHg) and no evidence of glaucomatous damage. At 60 months follow- up, the cumulative probability of developing POAG was 4.4% in the treatment group compared with 9.5% in the control (untreated) group (hazard ratio, 0.40; 95% CI, 0.27-0.59). The authors concluded that treatment with topical ocular hypotensive medication effectively delays the onset of POAG in people with increased IOP and that treatment should be considered for persons with ocular hypertension who are at moderate or high risk for developing POAG (16).

The Collaborative Normal-Tension Glaucoma Study (20) group determined the effect of treatment on disease progression in persons with normal-tension glaucoma (IOP ≤20mmHg). Disease progression was determined by glaucomatous optic disc progression or visual field loss. One eye of each participant was randomized to either no treatment (control) or treatment (topical medication or surgical treatment) in order to lower IOP by 30% from baseline values. Using the protocol definition of progression (deepening of an existing scotoma, the expansion of an existing scotoma, a new or expanded threat to fixation, or a fresh scotoma in a previously normal area of the visual field) and baseline values in the treatment group that were obtained after a 30% reduction in IOP had been achieved, 28/79 (35%) eyes in the control group showed disease progression compared with 7/61 (11.5%) of the treatment group eyes (P<.0001 survival curve analysis). Cataracts developed in 11 (14%) control group eyes and 23 (38%) treatment group (P=.0011) eyes. Of the 23 cataracts that developed in the treatment group 16 (26%) had been treated surgically and 7 (11%) received medical treatment. In a subsequent intention-to-treat analysis, where the outcomes of treatment managements were compared to the baseline values obtained at the time of randomization (before 30% reduction in IOP was achieved), 31/79 (39%) eyes in the control group progressed compared with 22/66 (33%) eyes in the treatment group (P=.21). However, the power to detect a difference in these observed rates with a 5% (two-sided) level of statistical significance was 11%. (9;20). In a subsequent analysis which censored the data from eyes that developed cataracts, the benefit of IOP reduction on the progression of visual field defects was statistically significant (P=.0018). This suggests that if IOP is reduced with treatments that do not cause adverse visual effects such as cataracts, a reduction in the progression of disease can be achieved in patients with normal-tension glaucoma. (20)

The major harms to glaucoma treatment include an increased risk of cataract formation associated with surgical intervention (15). The magnitude of any treatment in reducing impairment in vision-related function and quality of life is uncertain (9;15).

Age-Related Maculopathy

Age-related maculopathy (ARM) is a degenerative disease of a specific part of the retina called the macula (21). The macula is the central 25mm² of the retina that is responsible for visual acuity (sharpness of vision) and central vision (seeing objects straight ahead) (21). Damage to the macula causes loss of central vision affecting the ability to read, recognize faces and to move about freely (21). Degeneration of the macula is thought to occur because of a breakdown of the retinal pigment epithelium (RPE), which is the lining underneath the retina responsible for supplying the retina with oxygen and nutrients. ARM can be divided into an early- stage (early ARM) and a late-stage ARM (referred to as AMD) (21).

In early ARM, yellow spots under the retina called drusen are seen by a doctor during opthalmosocopy (22). Drusen are thought to be abnormal extracelluar deposits that range in size, shape and consistency from small well-defined hard drusen, to large ill-defined soft drusen. (23) Drusen may also be crystalline or calcific in nature. The size and shape of drusen determine in part how far the disease has progressed (24). In general, vision loss is not usually associated with early ARM. However, it is estimated that 0.5% to 50% of people with early ARM will develop AMD within 5 years (24).

There are 2 main types of AMD: dry and wet (7;22). Dry AMD, also called geographic atrophy, atrophic or non-neovascular AMD is characterized by well-defined areas of RPE atrophy (thinning out) (21;22). The most common symptom of dry AMD is blurred central vision which gradually worsens (25). If only one eye is affected, symptoms may not be noticeable (25). In wet AMD, also called exudative, neovascular (meaning forming new blood vessels) or disciform macular degeneration, abnormal blood vessels begin to grow and leak underneath the retina causing scarring and distortion of the retina. This type of AMD can lead to rapid and severe vision loss. A common symptom of wet AMD is that straight lines will appear wavy. Central vision can deteriorate rapidly in wet AMD (25).

Dry AMD comprises approximately 90% of all AMD cases. However, while less frequent, the wet form of AMD can be more devastating because of the risk of severe and sudden vision loss due to retinal detachment (7). Because of this, wet AMD accounts for the majority of cases of blindness caused by AMD (26).

Epidemiology

AMD is the leading cause of blindness in developed countries (21). The prevalence of AMD is estimated at 1% in people who are 55 years of age, increasing with increasing age to 5% in person aged 75 to 84 years, (21) and 15% in those 80 years of age and older (7). The prevalence of AMD is estimated to be higher in Caucasians than among people of African descent. Some of the other reported risk factors include age, family history of AMD, smoking, hypertension, atherosclerosis (hardening of the arteries), obesity, and chronic infection (24).

Diagnostic Test for ARM

ARM can be diagnosed during fundoscopy (ophthalmoscopy) which is a visual inspection of the retina by a physician or optometrist, or from a photograph of the retina (fundus photography) (21). During this examination, pale yellow spots called drusen can be seen many years before a person’s vision is affected. Detecting the presence of drusen during an eye exam can help identify people with this eye disease. The size, number and consistency (hard, soft, and crystalline) of the drusen as well as changes in the retina (loss and/or hypertrophy of RPE, retinal thickening and/or bleeding) indicate the advancement of the disease. Advanced disease is associated with severe vision loss. Fluorscein angiography can evaluate the vascularity (blood supply) of the retina to determine if the blood vessels are leaking (wet AMD). The Amsler chart (Figures 1 and 2) has also been used for patient self-monitoring. It is a 10x10 cm grid with twenty 5-mm squares drawn with white lines on a black background (opposite to figures 1 and 2). The grid is viewed periodically to check for metamorphopsia, or distortion of straight lines, which is one of the earliest symptoms associated with wet AMD.

Amsler Grid

Treatments

There is no cure or prevention for ARM. Likewise, there is currently no treatment to restore vision lost due to AMD. However, there are treatments to delay the progression of the disease and further loss of vision.

Antioxidants

The Age-Related Eye Disease Study (AREDS), a randomized controlled clinical trial (RCT), evaluated the efficacy of antioxidants compared with placebo in 3640 people aged 55 to 80 years of age who had either no AMD, mild, moderate or advanced AMD. Study participants were randomized to 1 of 4 treatment groups: antioxidant group (500 mg vitamin C, 400IU vitamin E, 15mg of beta-carotene); zinc group (80mgs of zinc oxide and 2 mg cupric (copper) oxide; antioxidants plus zinc group; or placebo group and followed for an average of 6.3 years. The outcome measure was the proportion of eyes developing advanced AMD in 5 years. Results showed that those people without AMD or with mild AMD did not benefit from antioxidant and/or zinc treatment. Those with moderate and advanced AMD however did benefit from treatment, showing a lower risk of progression to advanced AMD and preservation of visual acuity compared with people treated with a placebo at 7 years follow-up. People with the highest risk of AMD progression who were treated with antioxidants plus zinc had an odds ratio (OR) of 0.66 [99% CI, 0.47-0.91] and an absolute risk reduction (ARR) of 0.06 for the proportion of eyes developing advanced AMD in 5 years, equal to a NNT of 17. Those in the zinc treatment group had an OR of 0.71 [99% CI, 0.52-0.99] and an ARR of 0.36, equal to an NNT of 27. However, those treated with antioxidants only had an OR of 0.76 [99% OR CI, 0.55-1.05] which was not statistically significant (24). The authors concluded that all individuals older than 55 years of age should have a dilated fundoscopy examination of both eyes to determine if they have moderate AMD and if found should consider treatment with vitamin E, C, and beta-carotene plus zinc. (24). Adverse effects of treatment included a skin color change associated with beta-carotene and an increased risk of hospitalization due to genitourinary disease in men (26). Beta-carotene supplementation has also been connected to an increased risk of lung cancer in patients who smoke. (Numbers needed to harm [NNH] to produce 1 case of lung cancer in 3 years, 1190, and 294 in 6 years) (24). In other studies, high-dose vitamin E (≥ 400 IU/d) has been associated with a significant increase in the rate of heart failure in people with heart disease or diabetes (RR 1.13 [95% CI, 1.01-1.26] (24).

Laser Photocoagulation

Thermal laser photocoagulation has been used to coagulate the leaking capillaries of wet AMD. Results of RCTs indicate that in approximately 15% of the population with wet AMD (those with well-defined choroidal neovascularization [CNV]), treatment with thermal laser photocoagulation significantly reduced the relative risk (RR) of severe vision loss over 5 years (24). CNV can recur within 2 years of treatment in approximately 50% of patients treated (24). In 1995 the Canadian Task Force on the Periodic Health Examination stated that “the benefits of photocoagulation offer a rational for early detection and observation of AMD” (7). Photocoagualation will not restore vision already lost (24). Likewise, if retinal detachment has occurred photocoagulation will not be effective (7). Photocoagulation treatment is most beneficial for patients with a visual acuity of 20/60 or better and re-intervention may be required as some vessels may reopen(7). The earlier a person seeks treatment after the onset of symptoms, the greater chance of treating AMD (7). It is estimated that up to 50% of patients with wet AMD may benefit from treatment if the condition is identified early enough (7). Laser photocoagulation therapy is not indicated if the lesion is located directly under the fovea (centre of the macula) (personal communication with clinical expert Sept. 20, 2006).

Photodynamic Therapy

Photodynamic therapy has been investigated as a treatment for wet AMD. It involves the intravenous injection (into a vein) of photosensitive dye (verteporfin [Visudyne]) followed by the use of a laser to activate the photosensitive dye. The activated dye clots the leaking blood vessels underneath the retina (24). Unlike laser photocoagulation, photodynamic therapy targets the deleterious new growth of blood vessels while avoiding damage to the retina (26).

Pharmacological Treatment

Vascular endothelial growth factor (VEGF) inhibitors block the neovascularization process of AMD (24). Pegaptanib (Macugen) is the first VEGF inhibitor drug for the treatment of wet AMD to be approved by the United States Food and Drug Administration (FDA). It is also approved by Health Canada. (27). The long-term complications associated with chronic treatment with VEGF inhibitors are unknown (24).

Biological Treatment

On June 30, 2006, the FDA announced that it had approved Lucentis (ranibizumab injection), a new biologic treatment for wet AMD. Lucentis is injected into the eye once a month. It is the first treatment which can maintain the vision of more than 90% of patients with wet AMD (28;29). Lucentis contains an active substance which until now has never been approved for marketing in any form in the United States. (30) Intravitreal injections of Avastin (Bevacizumab), an anticancer drug, have been shown anecdotally to reverse vision loss in some patients with wet AMD. It is presently being used off label for this indication (31).

Visual Acuity

Visually Acuity is the term used to describe how clearly or sharply a person sees. Many people are familiar with the standard visual acuity measurement of 20/20 (meaning 20feet/20feet) or in metric 6/6 (meaning 6 meters /6meters), which is a measure of a person’s visual acuity; the larger the denominator the worse a person’s vision. Therefore, someone with 20/30 (6/9) vision cannot see as well as someone with 20/20 (6/6) vision. Visual acuity can be improved by wearing corrective lenses (glasses or contact lenses). Visual impairment is defined as a visual acuity of less than 20/60 (6/18) in the better eye with the best correction. Legal blindness is defined by visual acuity as well and is different in different jurisdictions. In Canada, legal blindness is defined as a visual acuity of less than 20/200 (6/60). This means that if a person with 20/20 vision can read a sign 30 feet away, a person with 20/200 vision will need to be 3 feet away from the sign to read it. Put another way, a person with 20/200 vision will see at 20 feet what a person with 20/20 vision will see at 200 feet. Table 1 reports the classification of severity of visual impairment recommended by the World Health Organization Study Group on the Prevention of Blindness, Geneva, 1972. Low vision comprises categories 1 and 2. Blindness comprises categories 3, 4 and 5 as well as category 9, unqualified visual loss.

Table 1: *Categories of Visual Impairment defined by Visual Acuity.

Category of Visual Impairment	Visual Acuity with Best Possible Correction
	Maximum less than	Minimum equal to or better than
1	20/70	20/200
2	20/200	20/400
3	20/400	20/1200
4	20/1200	Light perception
9	undetermined

Study Design	Level of Evidence	Number of Eligible Studies
Large RCT,^* systematic reviews of RCT	1
Large RCT unpublished but reported to an international scientific meeting	1(g)^†
Small RCT	2
Small RCT unpublished but reported to an international scientific meeting	2(g)
Non-RCT with contemporaneous controls	3a
Non-RCT with historical controls	3b
Non-RCT presented at international conference	3(g)
Surveillance (database or register)	4a
Case series (multisite) Meta-analysis of cross-sectional studies	4b	1
Case series (single site) Population based Prospective Cohort Population based Cross-sectional	4c	5 10
Retrospective review, modeling	4d
Case series presented at international conference	4(g)

Study Name	Design	Years Study Conducted	Sample Size ^* (Participation rate %)	Population	Mean Age (SD), years [range]
Chennai Glaucoma Study Southern India (36)	Cross-sectional	2001-2003	3934/4800 (82%)	≥ 40 years East Indian	53.8 (10.7)
Aravind Comprehensive Eye survey Southern India (5)	Cross-sectional	1995-1997	5150/5539 (93%)	≥40 years East Indian	Median 51.0 [40-90]
Blue Mountains Study Australia(37-39)	Cross-sectional	1992-1994	3654/4433 (82.4%)	≥49 years Predominately Caucasian	Males: 75.9 [49-97] Females: 65.9 [52-96]
Barbados Eye Study Barbados, West Indies(35;40;41)	Prospective Cohort	1992-1997 (4- year followup of cross sectional sample)	^†3427/4040 (85%)	40-84 years 93.1% Black 4.0% mixed race 2.9% Caucasian	57.5 (11.5)
	Cross-sectional	1988-1992	^‡4123/4314 (95.5%)		No POAG: 57.8 (11.8) POAG: 69.2 (10.4)
Baltimore Eye Study USA(42;43)	Cross-sectional	1985-1988	5308/6702 (79.2%)	≥40 years 45% Black 55% Caucasian
Beaver Dam Study USA (44;45)	Cross sectional	1987-1990	4926/5924 (83.1%)	43-84 years 99% Caucasian	60.6 (11.3)

Study	Sampling Method	Sample Size Calculation a priori	Standardized measurements	Reliability Assessments
Chennai Glaucoma Study Southern India (36)	Multistage sampling	Yes	Yes	Inter-rater reliability
Aravind Comprehensive Eye survey Southern India (5)	3 stage cluster sampling	Not reported	Yes	Study ophthalmologists were standardized to each other and to a senior ophthalmologist considered the reference standard. Standardization was repeated during the study.
Blue Mountains Study Australia(37-39)	census	Not reported	Yes	Inter- and Intra-rater reliability
Barbados Eye Study Barbados, West Indies(35;40;41)	Simple Random Sampling	Not reported	Yes	Inter- and intra-rater reliability
Baltimore Eye Study USA(42;43)	Stratified Multistage sampling	Not reported	Yes	Intra-rater reliability
Beaver Dam Study USA (44;45)	census	Not reported	Yes	Consensus of ¾ raters on 94.8% of visual field tests.

Study Name,	Diagnostic criteria for POAG	Definition of POAG
Chennai Glaucoma Study Southern India (36)	Diagnosed using the 3 categories of the International Society of Geographical and Epidemiologic Ophthalmology classification. Category 1: structural and functional evidence. ^CDR or CDR asymmetry ≥97.5^th percentile of the normal population or a neuroretinal rim width reduced to ≤ 0.1 CDR (between 11-10 or 5-7 o’clock) with a definite visual field defect on automated perimetry consistent with glaucoma Category 2:* advanced structural damage + unproven visual field loss for cases where visual fields could not be assessed or had a CDR and CDR asymmetry ≥ 99.5^th percentile for the normal population. Category 3: Optic disc not seen; visual field testing impossible. Visual acuity <3/60 and IOP ≥ 99.5^th percentile of normal population or visual acuity <3/60 and the eye shows evidence of glaucoma filtering surgery, or medical record were available confirming glaucomatous visual morbidity.	Definite POAG: 1 of the 3 categories + an open and normal appearing angle on gonioscopy. (Only 1 case was diagnosed based on IOP criterion in this study)
Aravind Comprehensive Eye survey Southern India (5)	Optic nerve damage: ^†VCDR>0.8 or a narrowest neuro-retinal rim width <0.2 (including classic notching) or asymmetry >0.2 between eyes coupled with a visual field defect on automated perimetry in the matching location In cases where visual fields were not available: Presence of significant optic disc excavation compatible with glaucoma, or end-stage glaucoma with severe central vision loss, or total optic disc cupping	Evidence of glaucomatous optic nerve damage which included either glaucomatous change in the appearance of the optic nerve head and/or nerve fiber bundle pattern perimetric defects typical of glaucomatous damage. Definition did not rely on IOP
Blue Mountains Study Australia (37-39)	Matching optic disc cupping with rim thinning (CDR ≥0.7 or cup-disc asymmetry ≥0.3) and characteristic visual field loss on automated perimetry.	Optic disc defects and visual field loss on automated perimetry. Definition did not rely on IOP.
Barbados Eye Study Barbados, West Indies (35;40;41)	Optic disc criteria: At least 2 signs of optic disc damage including either a HCDR or VCDR of ≥ 0.7, narrowest remaining neuroretinal rim of 0.1 disc diameters or less, notching asymmetry in CDR between eyes of > 0.2 and disc hemorrhages.	Criteria for definite PAOG were based on the presence of both visual field defects (Humphrey automated perimetery) and optic disc damage in at least 1 eye. Definition did not rely on IOP
Baltimore Eye Study USA (42;43)	Glaucomatous optic nerve damage and visual field defects on automated perimetry or Goldmann perimetry if automated was not possible in the presence of normal angles and in the absence of other likely causes. 97% of all cases were diagnosed using the following criteria:	A final classification of definite, probable and uncertain-unknown was made after considering glaucomatous optic nerve damage based on appearance of visual fields, optic disc, and nerve fiber layer, angle grade based on slit-lamp examination and gonioscopy.
	1. ≥ 2 abnormal visual fields with excellent congruence between fields	Definition did not rely on IOP
	2. End-stage disease with visual acuity ≤ 20/200 and 100% cupping
	3. ≥ 1 abnormal visual field with some but not perfect confluence between fields and a CDR ≥ 0.8 or a difference between the 2 eyes of ≥ 0.3/
	4. ≥ 1 abnormal visual field with some but not perfect congruence between fields
	5. 1 visual field performed with typical field defects.
	6. 1 visual field either typically abnormal or compatible with glaucoma and cupping or nerve-fiber layer loss
	7. asymmetric cupping with a difference between the 2 eyes of ≥ 0.4
Beaver Dam Study USA (44;45)	1. Visual field defects with suprathreshold static perimetry using multiple stimulus patterns.	Definite glaucoma: having at least 2 of the first 3 criteria.
	2. CDR ≥ 0.8 or difference in CDR of 0.2 or more in involved eye.	Probable glaucoma: criterion 4 and fewer than 2 of the other 3 criteria in the same eye.
	3. IOP ≥ 22 mmHg
	4. History of taking drops or having surgery for glaucoma

Study	Diagnostic Methods	Number of Prevalent cases in study sample	Crude Prevalence of POAG % (95% CI)	Rate of undiagnosed prevalent POAG (%)	Number of Incidence Cases in study sample	Crude Incidence of POAG % (95% CI)
Chennai Glaucoma Study Southern India (36)	^*I, VFD, T	^†64/3924	1.6 (1.4-1.8)	98.5	not applicable (N/A)	N/A
Aravind Comprehensive Eye survey Southern India (5)	I, VFD	64/5150	1.2 (0.9-1.5)	93	N/A	N/A
Blue Mountains Study Australia(37-39)	I, VFD	108/3654	2.4 (not reported) ^‡3.0 (2.5-3.6)	51	N/A	N/A
Barbados Eye Study Barbados, West Indies(35;40;41)	I, VFD	302/4314	7.0 (not reported)	51	67/2989	2.2 (1.7-2.8)
Baltimore Eye Study USA (42;43)	I, VFD	100/2395 32/2913	Black population: 4.2 (3.4-5.0) Caucasian population: 1.1 (0.7-1.6)	50
Beaver Dam Study USA (44;45)	I, VFD, T	104/4926	2.1 (not reported)	Not reported

Age (Years)	Odds Ratio (95% CI)
	^*Chennai Glaucoma Study (36) ≥ 40 years	^†Aravind Eye Study (5) ≥ 40 years	^‡Blue Mountains Study (39) ≥49 years	^§Barbados Eye Study (41) 40-84 years	^\|\|Beaver Dam Eye Study (44) 43-84 years
40-49	1.0	1.0
50-59	2.59 (1.17-5.73)	4.5 (1.6-12.2)
60-69	4.15 (1.97-8.76)	4.0 (1.4-11.3)
(70-79)	5.26 (2.34-11.80)	7.2 (2.3-22.4) (≥ 70 years)
≥ 80	Not reported	Not reported
Age (per year)			1.10 (1.08-1.13)	1.07 (1.05-1.08)
Age (per 10 year increment)					1.74 (1.45-2.09)

Study	Number of Incident Cases (%, 95% CI)
	40-49 years	50-59 years	60-69 years	≥ 70 years	Crude Incidence
Barbados Eye Study (35)	12/980 (1.2; 0.6-2.1)	12/821 (1.5; 0.8-2.5)	22/682 (3.2; 2.0-4.8)	21/506 (4.2; 2.6-6.3)	67/2989 (2.2;1.7-2.8)

Quality Assessment						Summary of Findings
Studies	Design	Quality	Consistency	Directness	Other modifying factors	Number of Subjects POAG/Total Study Sample Total	Quality
Chennai Aravind Blue Mtns. Barbados Beaver Dam	Cross sectional	No Issues	Yes, consistency in direction of association amongst studies	None	Strong evidence of association with increasing age s(OR > 2.0)	64/3924 64/5150 108/3654 302/4314 104/4926 642 / 21968	Moderate
GRADE	Low	Low	Low	Low	Moderate		Moderate

		^*OR 95% CI
Study	Males	Females
Chennai Glaucoma Study (36)		^§0.98 (0.58-1.62)
Aravind Comprehensive Eye Survey (5)	^‡2.60 (1.5-4.6)
Blue Mountains Eye Study (37)		^\|\| 1.55 (1.03-2.32)
Barbados Eye Study (41)	^†1.66 (1.24-2.24)
Beaver Dam (44)	Not statistically significant Point estimate not Reported

Age (years)	Number of POAG Cases	Number of cases/1000	Observed Prevalence Rate	^†Adjusted Prevalence Rate % (95% CI)	^‡OR (95% C.I.)
40-49
^*W	1/543	1.8	0.18 (0.02-1.03)	0.92 (0-2.72)	1.0
^*B	6/632	9.5	0.95 (0.35-2.07)	1.23 (0.23-2.24)	5.2 (0.6-43.4)
50-59
W	2/618	3.2	0.32 (0.03-1.17)	0.41 (0-098)	1.0
B	25/699	35.8	3.58 (2.32-5.26)	4.05 (2.47-5.63)	11.4 (2.7-48.4)
60-69
W	7/915	7.7	0.77 (0.31-1.57)	0.88 (0.14-1.62)	1.0
B	31/614	5.05	5.05 (3.4-7.2)	5.51 (3.57-7.46)	6.9 (3.0-15.8)
70-79
W	18/631	28.5	2.85 (1.70-4.50)	2.89 (1.44-4.34)	1.0
B	27/349	77	7.74 (4.9-10.5)	9.15 (5.83-12.48)	2.85 (1.5-5.3)
≥80
W	4/206	19.4	1.94(0.49-4.95)	1.29(0.80-1.78)	1.0
B	11/101	109	10.89 (4.8-16.9)	11.26 (4.52-17.00)	6.21 (1.9-19.9)
Overall
W	32/2913	11	1.10 (0.75-1.55)	1.29 (0.80-1.78)	1.0
B	100/2395	42	4.18 (3.38-4.98)	4.74 (3.81-5.67)	3.9 (2.6-5.9)

Study	OR (95% CI)
Blue	^*3.2 (1.8-5.6)
Mountains
Eye Study (39)
Barbados	^†2.43 (1.43-4.15)
Eye Study (41)	^‡3.15 (1.38-7.18)
Baltimore	^§2.85 (1.8-4.5)
Eye Study	¶B: 3.11 (1.86-5.19)
(43)	^\|\|W: 2.18 (.84-5.67)

Study	Diagnostic Methods	Follow-up years	Number of Incidence Cases in study sample/number at risk	Overall Crude Incidence Rates % (95% CI)
Barbados Incidence Eye Study II (47)	Fundus Photography and/or clinical evaluation	9	Early ARM: 260/2070 AMD: 21/3045	Early AMD: 12.6 (11.0-14.1) AMD: 0.7 (0.4-1.1)
Rotterdam Study (48)	Fundus Photography	6.5	Early ARM:413/5836 413/25,113 person-years	Early ARM:7.1 ^*16.4 (14.9-18.1) 5-year risk: 7.9
			AMD: 47/6312 47/26,592 person-years	AMD: 0.74 ^*1.8 (1.3-2.4) 5-year risk:0.9
The Beaver Dam Eye Study (49)	Fundus Photography	5	Early ARM: 232/2834 AMD: 32/3502	Early ARM: 8.2 AMD: 0.9
Blue Mountains Study (50)	Fundus Photography	5	Early ARM: 191/2198 AMD: 25/2313	Early ARM: 8.7 (^†NR) AMD: 1.1 (^†NR)

43-54 years		55-64 years		65-74 years		≥75 years
Number at risk	%	Number at risk	%	Number at risk	%	Number at risk	%
1254	0.0	1033	0.3	901	1.3	314	5.4

<60 years		60-69 years		70-79 years		≥80 years
Number at risk	%	Number at risk	%	Number at risk	%	Number at risk	%
721	0	940	0.6	541	2.4	111	5.4

Study	Age (years) Mean (SD)[Range]	OR (95% CI)	Definition of Myopia (Spherical Equivalent, S.E.)	Dose Response Effect Found?
Chennai Glaucoma Study (36)	53.8(10.7)	^*0.68 (0.40-1.17)	S.E. worse than -0.5 D in phakic eye	Not assessed
Aravind Comprehensive Eye Survey (5)	Median:51.0 [40-90]	^†Mild:2.9 (1.3-6.9) ^†Moderate:2.1 (1.0-4.6) ^†Severe3.9 (1.6-9.5)	S.E. worse than -0.5D in either phakic eye No definitions of mild, moderate or severe reported in study.	No
Beaver Dam Eye Study (45)	60.6(11.3)	^‡1.6 (1.1, 2.4) (2 eyes) ^‡1.6 (0.9-2.6) (right eyes only)	S.E. of -1.00D or worse	No
Blue Mountains Eye Study(38)	Males: 75.9 [49-97] Females: 65.9 [52-96]	^§2.1 (1.2-3.8) ^\|\|2.3 (1.3-4.1)	S.E. of -1.00D or worse	Yes as assessed in people ≥ 60 years of age
		^\|\|^¶2.3(1.3-4.1)	Low: S.E ≥-1.00 to < -3.0 D
		^\|\|^¶3.3(1.7-6.4)	Moderate to High: S.E. ≥ -3.00 D

Study Name	Design	Follow up (years)	Years Study Conducted	Sample Size (^*Response rate %)	Population	Mean Age (SD), years [range]
Barbados Incidence Study of Eye Disease II (BISED II)(47)	Population based cohort	9	1997-2003	2612/3448 (81)	93% black 40-84 years of age 60% female	55 (10.3)
The Rotterdam Study(48)	Population based cohort	6.5	1997-1999	3636/5109 (71.2)	The Netherlands ≥55 years of age	51.0 (not reported) [not reported]
The Beaver Dam Eye Study(49)	Population based cohort	5	1993-1995	3583/4541 (79)	United States 99% Caucasian 43-86 years of age	^†60.1 [43-86]
The Blue Mountains Study(50)	Population Based cohort	5	1997-1999	2311/3111 (74)	Australia ≥49 years of age	64.5 (not reported)

Study	Sampling Method	Sample Size Calculation a Prior	Standardized measurements	Reliability Assessments
Barbados Incidence Study of Eye Diseases Study Barbados, West Indies (47)	Simple Random Sampling	Not reported	Yes	Photographs were graded independently by 2 graders and discrepancies were resolved by consensus. When agreement could not be reached a third party (study retinal specialist) determined the final grading.
Rotterdam Study (48)	Cluster sampling	Not reported	Yes	Photographs were graded by 3 graders. Graders were trained according to the Wisconsin ARM grading system. Consensus sessions and inter-rater comparisons were completed at regular intervals throughout the course of the study.
Beaver Dam Study USA (49)	Census, the total population of Beaver Dam Wisconsin, USA was canvassed	Not reported	Yes	Two gradings were performed for each eye. A preliminary masked grading was done by 1 of 2 senior graders. Right and left eyes of the same subject were done consecutively. A second grading was then completed by 1 of 3 experienced graders. Results of the first and second gradings were compared for inconsistencies. Disagreements between gradings were resolved by a third grader.
Blue Mountains (50)	Census, the total population from 2 postcode areas west of Sydney, Australia was canvassed	Not reported	Yes	Photographs were assessed by 2 graders. Inter and intra-rater reliability of photographic grading was assessed on a random sample of eyes.

Study Name,	Diagnostic Methods	Definitions
Barbados Incidence Study of Eye Disease II (47)	30 degree color stereoscopic fundus photographs of the disc and macula and/or clinical evaluations of macula-related features.	Early ARM: any medium or large drusen or >20 small drusen with retinal pigment epithelium atrophy and/or pigment in at least one eye.
	Grading: Graded at the Fundus Photography Reading Center in Baltimore using a standardized grading protocol.	AMD: presence of 1 or more of the following in at least one eye: geographic atrophy; exudative features such as fluid, lipid, or hemorrhage; disciform scar.
The Rotterdam Study (48)	35 degree stereoscopic color photographs centered on the fovea and a standard eye exam and stereoscopic Grading: Photographs were graded according to the International Classification and Grading System for ARM and AMD	Early ARM as the presence of either soft distinct drusen (≥ 63μm) with hyperpigmentation and/or hypopigmentation of the RPE or soft indistinct or reticular drusen with or without pigmentary irregularities.
		AMD: Atrophic AMD defined as any sharply demarcated round or oval area of apparent absence of the retinal pigment epithelium, larger than 175 μm, with visible choroidal vessels and no neovascular AMD.
		Neovascular AMD was defined as the presence of a serous or a hemorrhagic retinal pigment epithelium detachment and/or a sub-retinal neovascular membrane and/or a sub-retinal hemorrhage and/or a peri-retinal fibrous scar.
		Progression: Progression of ARM was studied by stratifying the ARM fundus signs into 5 mutually exclusive stages
Beaver Dam (49)	30 degree stereoscopic color fundus photographs (96.9% of participants) centered on the disc, macula and a non-stereoscopic color fundus photograph including the fovea.	Early ARM: the presence of any type of drusen associated with retinal pigment epithelial depigmentation or increased retinal pigment
	2.3% of participants had 45 degree non-stereoscopic fundus photographs.	AMD: the appearance of either exudative macular degeneration or pure geographic atrophy
	Grading: Photographs were graded using the Wisconsin ARM Grading System
Blue Mountains Study (50)	30 degree stereoscopic retinal photographs (96.9% of participants) of the macula and other retinal fields of both eyes were taken. Grading: Photographs were graded using the Wisconsin ARM grading system.	Early ARM was defined as the presence of either: (1) large (>125µm diameter) indistinct soft or reticular drusen, or (2) both large distinct soft drusen and retinal pigmentary abnormalities (hyperpigmentation or hypopigmentation) and the absence of late stage ARM lesions (geographic atrophy and neovascular ARM.
		AMD: included geographic atrophy involving the fovea and neovascular AMD

	% Progression
Study	Unilateral ARM (%, 95% CI)	Bilateral Early ARM (%, 95% CI)
Barbados Study of Incidence Eye Disease (47)
Any AMD	1.7 (0.7-2.8)	2.2 (.04-4.5)
Dry AMD	0.7 (.01-1.4)	1.2 (0.0-2.9)
Wet AMD	1.0 (0.2-1.8)	1.0 (0.0-2.4)
The Beaver Dam Eye Study(49)
Any AMD	Not Reported	11.7 (NR)
Dry AMD		4.6 (NR)
Wet AMD		7.1 (NR)

	5-year Absolute Risk by Stage
Rotterdam study	Stage 0: 0.0
	Stage 1: 0.9
	Stage 2: 7.8
	Stage 3: 28.0
	Stage 4: 0.9

Incidence % (95 % C.I)
Study	Early ARM		AMD
	Men	Women	Men	Women
Barbados Incidence Study of Eye Disease II (47) (9-year incidence)	12.5 (10.1-14.9)	12.6 (10.7-14.6)	0.70 (0.3-1.2)	0.70 (0.3-1.2)
Rotterdam Study (48) (6.5 year incidence)	^*17.1/1000 (^†NR)	^*16.0/1000 (NR)	^*2/1000 (NR)	^*1.6/1000 (NR)
The Beaver Dam Eye Study(49) (5-year incidence)	7.1(NR)	9.0 (NR)	0.5(NR)	1.3 (NR)
Blue Mountains Study(50) (5-year incidence)	7.9 (NR)	9.4 (NR)	0.7 (NR)	1.4 (NR)

	Incident Early ARM (RR and 95% CI)	Incident AMD (RR and 95% CI)
Myopia	1.0 (0.7-1.3)	0.5 (0.2-1.5)
Hyperopia	0.9 (0.7-1.1)	1.2 (0.6-2.3)

Study Name	Risk Factor Assessed	Design	Years study Conducted	Sample Size (^*Response rate %)	Population	Mean Age (SD), years [range]
Blue Mtns. Eye Study (56)	Family History	Population based cross-sectional	1992-1994	3582/4433 (81)	Australia ≥ 49 years of age	Not reported
Los Angeles Latino Eye Study Fraser-Bell, 2005 (55)	Family History	Population based cross-sectional	2000-2003	5875/7789 (75)	Latino population ≥40 years 42% male	54.9 (NR)
^†The Eye Diseases Prevalence Research Group (54)	Ethnicity	Meta-analysis of 7 population based cross-sectional studies	2004	29658 (>80 each study)	≥40 years black 19.7% white 79.3%	Not reported
Atherosclerosis Risk in Communities (ARIC) Study (57)	Ethnicity	Population based cross-sectional	1993-1995	11532/12849(89.7)	United States 48 years-72 years 43.3% male 36.9% black	59.7 (10.7)
Multi-ethnic Study of Atherosclerosis (MESA) Klein, 2006(58)	Ethnicity	Population based cross-sectional	2002-2004	5887/6176 (95%)	United States Caucasian 39% Black 27% Hispanic 22% Chinese 12%	Caucasian 63 (10.2) Black 62.4 (9.9) Hispanic 61.6 (10.2) Chinese 62.4 (10.2

Study	Sampling Method	Sample Size Calculation a Prior	Standardized measurements	Reliability Assessments
Blue Mountains Study Australia (56)	A total sample of a population from 2 postcode areas west of Sydney.	Not reported	Yes	Inter and Intra-rater reliability
Los Angeles Latino Eye Study (55)	A total sample of a population in 6 census tracts in and around the city of La Puente, Los Angeles County	Yes	Yes	Inter and intra rater reliability
Atherosclerosis Risk in Communities (ARIC) Study (57)	Probability Sample		Yes	Inter rater and intra rater reliability
Multi-ethnic Study of Atherosclerosis (MESA) (58)	Probability Sampling	Yes	Yes	Inter and intra-rater reliability was assessed among the 9 graders on a random subset of images of 25 eyes

PERMALINK

Routine Eye Examinations for Persons 20-64 Years of Age

Executive Summary

Objective

Clinical Need

The Technology

Review Strategy

Summary of Findings

Primary Open Angle Glaucoma

Age-Related Maculopathy

Economic Analysis

Costs

Current Ontario Policy

Considerations for Policy Development

Objective

Background

Clinical Need: Target Population and Condition

Glaucoma

Epidemiology

Diagnostic Tests for POAG

Tonometry

Inspection of the optic disc

Perimetry

Treatments for POAG

Age-Related Maculopathy

Epidemiology

Diagnostic Test for ARM

Figure 1: Normal Vision.

Figure 2: Distortion of Straight Lines.

Treatments

Antioxidants

Laser Photocoagulation

Photodynamic Therapy

Pharmacological Treatment

Biological Treatment

Visual Acuity

Table 1: *Categories of Visual Impairment defined by Visual Acuity.

Vision Standards for Driving in Ontario

Technology Being Reviewed

Literature Review

Research Question

Methods

Inclusion Criteria

Exclusion criteria

Clinical Outcomes

Study Eligibility

Data Extraction

Assessment of Study Methodological Quality

Summarizing the Quality of the Body of Evidence

Quality of Evidence

Summary of Medical Advisory Secretariat Review

Table 2: Quality of Evidence of Included Studies.

Glaucoma

Table 3: Study Characteristics.

Internal Validity of Studies

Table 4: Internal Validity of Studies.

Diagnostic Methods

Table 5: Diagnostic Criteria for POAG used in Studies.

Prevalence and Incidence

Table 6: Crude Prevalence and Incidence of POAG (definite POAG where otherwise indicated) in Studies.

Multivariate Statistics

Cross-Sectional Design

Results

Age and POAG

Cross-Sectional Studies

Table 7: Association of Age and Prevalent POAG in Cross-Sectional Studies.

Prospective Cohort Studies

Figure 3: Age Specific Incidences of POAG in Barbados Eye Study.

Table 8: Age Specific Incidence of Definite POAG.

Conclusion

Table 9: GRADE Profile Question: Does prevalent POAG increase with age?

Gender and POAG

Table 10: Association of POAG and Gender with by Multivariate Analysis.

Conclusion

Table 11: GRADE Profile Question: What is the association between gender and prevalent POAG?

Ethnicity and POAG

Table 12: Prevalence of Definite POAG by Age and Race.

Conclusion

Table 13: GRADE Profile Question: What is the association between ethnicity and prevalent POAG?

Refractive Error and POAG

Study Name,	Diagnostic Methods	Definitions
Blue Mtns. Eye Study (56)	30 degree stereoscopic retinal photographs of the macula and other retinal fields of both eyes Grading: The Wisconsin age-related grading system was used to grade individual ARM lesions developed by Klein et al. (58)	Early ARM: was defined as the presence of either indistinct soft or reticular drusen or both distinct soft drusen and retinal pigmentary abnormalities in the absence of late AMD in either eye. AMD: includes neovascular AMD and geographical atrophy. Neovascular AMD was defined with serous or hemorrhagic detachment of the retinal pigment epithelium or sensory retina, the presence of subretinal or sub-retinal pigment epithelium hemorrhages or subretinal fibrous scars. Geographical atrophy was defined as discrete retinal depigmentation at least 175 μm in diameter with a sharp border and visible choroidal vessels.
Los Angeles Latino Eye Study(55)	30-degree stereoscopic color retinal photographs Grading: grading was completed at the Wisconsin Ocular Epidemiology Reading Center using the Wisconsin Age-related Maculopathy Grading System developed by Klein et al. (58)	Early ARM: absence of signs of advanced disease and the presence of soft indistinct or reticular drusen or hard or soft distinct drusen with pigmentary abnormalites (depigmentation or increased retinal pigment). AMD: presence of geographic atrophy or exudative AMD.
Atherosclerosis Risk in Communities (ARIC) Study (57)	45 degree retinal photograph was taken of 1 eye, centered on the region of the optic disc and the macula. Pupillary dilatation was achieved after the participant spent 5 minutes in a dark room. No pharmacological mydriatic drops were used. Grading: grading was completed using the Wisconsin Age-Related Maculopathy grading system developed by Klein et al. (58) Photographs were evaluated at the Fundus Photographic Reading Center in Madison Wisconsin.	Early ARM was defined as the presence of soft drusen alone, retinal pigment epithelium depigmentation alone, or a combination of soft drusen with increased retinal pigment and/or depigmentation in the absence of AMD. AMD was defined as the presence of signs of exudative ADM degeneration or pure geographic atrophy.
Multi-ethnic Study of Atherosclerosis (MESA)(58)	45 degree 6.3 megapixel digital nonmydriatic camera. Two photographic fields were taken of each eye, the first entered on the optic disc and the second on the fovea. Grading: grading was completed the Wisconsin Age-Related Maculopathy Grading scheme developed by Klein et al. (58)	Early ARM was defined by either the presence of any soft distinct or indistinct drusen and pigmentary abnormalities or the presence of a large soft drusen ≥ 125 μm in diameter, soft instinct drusen in the absence of signs of AMD. AMD was defined by the presence of any of the following: geographic atrophy or pigment epithelial detachment, sub-retinal hemorrhage or visible sub-retinal new vessel, or sub-retinal fibrous scar or laser treatment scar for AMD

Study	Diagnostic Methods	Number of Prevalent Cases in study sample/study sample	Overall Crude Prevalence Rates % (95% CI)
Blue Mtns. Eye Study (56)	Retinal Photography	Early AMD: 240/3582 AMD: 72/3582	Early AMD: 6.7 AMD: 2.0
Los Angeles Latino Eye Study (55)	Retinal Photography	Early ARM: 551/5875 AMD: 25/5875	Early ARM:9.4 AMD: 0.42
Atherosclerosis Risk in Communities (ARIC) Study (57)	Retinal Photography	Early ARM:581/11532 AMD:15/11532	Early ARM:5.0 AMD:0.13
Multi-ethnic Study of Atherosclerosis (MESA) (58)	Retinal Photography	Early ARM:221/5884 AMD:27/5884:	Early ARM:3.7 AMD:0.46:

Family History of AMD		Odds ratio (95% CI)
	^*Blue Mountains Eye Study	^†Los Angeles Latino Eye Study
None	1.00	1.00
Early ARM	2.17 (1.04-4.55)	Not reported
Any AMD	3.9 (1.3-11.5)	Not reported
Wet AMD only	4.3 (1.4-13.5)	Not reported
Dry AMD only	Sample too small	18.83 (2.02-175.7)

Variable	Baltimore Eye Survey	Barbados Eye Study	Beaver Dam Eye Study	Blue Mountains Eye Study	Rotterdam Study	Salisbury Eye Evaluation	Melbourne Vision Impairment Project
Sample size	n=4361	n=3413	n=4752	n=3632	n=6774	n=2387	n=4339
Years study conducted	1985-1988	1988-1992	1988-1990	1992-1994	1990-1993	1993-1995	1991-1998
Ages of Participants (years)	≥40	≥40	≥40	≥50	≥55	≥65	≥40
Ethnicity Distribution (%)	Black 42.3 White 57.7	Black 100	White 100	White 100	White 100	Black 23.7 White 74.3	White 100

Age (years)	Number of Early ARM Cases	Per 1000 persons	Prevalence Rates %
48-54
White (W)	54/1874	28	2.9
Black (B)	19/763	25	2.5
55-59
W	100/2460	41	4.1
B	25/761	33	3.3
60-64
W	136/2307	59	5.9
B	26/552	33	4.7
65-72
W	196/2343	84	8.4
B	23/472	49	4.9
Overall
W	486/8984	54	5.4
B	93/2548	36	3.6

Age (years)	Number of Early ARM Cases	Per 1000 persons	Prevalence Rates %
48-54
White (W)	2/1874	1	0.1
Black (B)	0/763	0	0
55-59
W	0/2460	0	0
B	0/761	0	0
60-64
W	2/2307	1	0.1
B	1/552	2	0.2
65-72
W	9/2343	4	0.4
B	0/472	0	0
Overall
W	13/8984	1.4	0.14
B	1/2548	.4	0.04

Early ARM			AMD
Ethnic Group	Crude Prevalence (%)	Age-gender adjusted Odds Ratio (95% CI)	Crude Prevalence (%)	Age-gender adjusted Odds Ratio (95% CI)
White	4.8	1.0	0.6	1.0
Black	2.1	0.45 (0.30-0.67)	0.3	0.52 (0.17-1.60)
Hispanic	4.0	0.88 (0.63-1.25)	0.2	0.48 (0.14-1.70)
Chinese	3.6	0.76 (0.49-1.19)	1.0	1.91 (0.75-4.87)

Province	Policy
British Columbia	Routine eye examinations are a benefit only for those 18 years of age and under and 65 years of age and over. Medically required eye examinations are a benefit for all Medical Service Plan beneficiaries when there is a medical necessity (such as eye diseases, trauma or injury, or health conditions associated with significant risk to the eyes such as diabetes.)
Alberta	Basic Medical Services include: Routine eye exams for children up to and including 19 year olds and seniors 65 and over Eye exams for adults when health risk is assessed by an ophthalmologist (medical doctor specializing in eye diseases). An ophthalmologist must perform the eye exam.
Saskatchewan	Routine Eye exams are limited to: 1 per 24 months period if you are between 18 and 64 years of age 1 per 12 months period if you are any other age partial eye examinations (except when your optometrist provides the service within 90 days of a routine eye examination) glaucoma testing (when your optometrist provides it during a routine eye examination, and you are 40 years of age or older).
Manitoba	If you are under 19 years of age or 65 and over you may receive one complete routine eye exam every two years. Exams for all ages will be covered if deemed medically necessary by your physician or optometrist. Routine eye exams for people 19-64 are not insured.
Quebec	Persons under 18 and 65 years of age and older are covered. People of any age on welfare are covered.
Nova Scotia	Provincial coverage for persons 10 years and younger and 65 years and older once every 2 years.
New Brunswick	Refractions for prescription eye glasses and optometrist services are not insured by either the New Brunswick Medicare or the province's hospital services. Persons of any age may have a provincially insured eye exam by an ophthalmologist for conditions other than refraction.
PEI	Optometrists' services are not covered for any persons of any age. With a referral from a family physician, services rendered by an ophthalmologist are covered by the province's Medicare plan.
Newfoundland	Routine eye examinations are not insured

High:	Further research is very unlikely to change our confidence in the estimate of effect.
Moderate:	Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low:	Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low:	Any estimate of effect is very uncertain.