In a population-based cohort of patients newly diagnosed with clinical, often symptomatic type 2 diabetes, 6.3% were visually impaired. Among those patients with reduced sight, 76% had cataract and 58% retinopathy, usually AMD, although many of these eye pathologies are not closely related to diabetes and metabolic control. During the first 6 years after diabetes diagnosis, the incidence of blindness was relatively high, 40 per 10,000 person-years. The baseline predictors of both the level of and speed of progressive visual impairment after diagnosis were AMD, cataract, age at diagnosis, and living alone. The level of visual acuity over 6 years was lower in patients who had a low self-rated health or a sedentary life-style. The rate of the 6-year visual loss increased if the patient had DR or high fasting triglycerides at diabetes diagnosis.
Strengths and limitations of the study
Our patients are likely to be representative of Danish patients with newly diagnosed, clinical, often symptomatic diabetes in this age group because of the well-defined background population in each general practice, the unchanged inclusion activity during the inclusion period, the small number of primary exclusions, and the acceptable participation in the eye examinations . Furthermore, data from studies including patients with known diabetes may be misleading because of selective survival of patients with a more favourable risk factor profile . Our results, however, cannot be generalised to all countries because of marked disparities in causes of reduced vision across the world .
Our patient sample was established in the early 90's and since then both surgical treatment of eye pathologies and pharmacological treatment of hyperglycaemia, hypertension and dyslipidaemia have been intensified, as has screening for diabetes. These initiatives to improve diabetes care and to identify patients earlier in the natural history of diabetes have probably decreased the variability of measures of treatment quality, so if a similar follow up study were to be made today, the associations between variables would perhaps be harder to identify. There is, however, no reason to suppose that the causal patterns underlying the associations that we have identified would be substantially different.
By presenting results from the best seeing eye only, we are underestimating the prevalence of eye pathologies in this patient group. This is because our main purpose is to estimate the change in visual acuity and its predictors, and eye pathologies are important in this study only insofar they are predictors of visual loss. In most studies the main pathology in the better eye is considered the cause of visual impairment [6, 7]. We analysed predictors of vision impairment prospectively. Furthermore, to improve statistical strength we chose to analyse visual acuity as a continuous outcome.
Our ability to detect a true clinical change in visual acuity is inversely related to the measurement error, i.e. the test-retest variability, of the test used [30, 31]. Unlike logMAR charts, the Snellen chart, which we had to rely on in this nationwide primary care study, has a large-scale increment resulting in a relatively high measurement error. Another factor contributing to the test-retest variability was differing routines for taking account of visual field loss . The lower precision of the outcome, visual acuity, will however only tend to lessen the strength of the association between the outcome and a predictor.
On the other hand, the true incidence of vision impairment may be underestimated if those patients who missed an eye examination experienced a relatively rapidly declining vision. However there is no reason to suppose that the possible imprecision and error introduced were associated with any of the possible predictors of visual loss that were examined. Comparison of visual acuity between studies, even when categorised, is in any case not feasible , and our prevalence and incidence figures for visual impairment should be interpreted in this light.
Almost all Danish ophthalmologists contributed to the study increasing the inter-rater variability, and their screening by funduscopy may have overlooked 10-40% of sight-threatening eye disease . Such measurement errors in the predictor variables will tend to reduce a true association between e.g. an eye pathology and the outcome, i.e. visual acuity, but it does not invalidate the associations that we actually find. It can be assumed that the detection rate for eye disease was higher in patients with low visual acuity. This may have biased the cross-sectional associations between eye disease and visual acuity in Table 2 and 5, but it does not to the same extent compromise the estimation of the predictive power of the eye pathologies at diagnosis for the change in visual acuity during the following 6 years. Therefore, our non-standardized estimation of eye pathologies at diabetes diagnosis only diminishes our ability to detect an effect of these variables on changes in visual acuity.
Comparison with existing literature
Predictors of 6-year visual loss
In Table 2 and in most studies [3–9, 34–36] the main eye pathology is assigned as the cause of visual impairment. We analysed prospectively 26 possible ocular and non-ocular predictors of vision loss (Table 1). It is striking that, besides age and triglycerides, only DR, AMD, and cataract, many of which are surgically modifiable, were associated with declining vision over 6 years. This was observed even though the measurement error in the estimation of these eye pathologies is considered to be greater than for many of the other possible predictors. In follow up studies, the association between baseline DR or AMD and later impaired vision is well documented [14–16, 19], and AMD may cause deterioration in visual acuity earlier in diabetic patients than in non-diabetic people though the prevalence of AMD does not seem to differ markedly between the two groups . Furthermore, diabetic subjects have a 2 to 4 times greater risk of developing cataract than non-diabetic people .
As our way of collecting information about glaucoma may underestimate the true prevalence of glaucoma in our patients, we were not able to analyse the predictive effect of glaucoma for visual loss. The possible importance of eye pressure for the change in eye sight over 6 years is, however, indicated by the non-significant tendency reported in Table 1.
Only a few prospective studies have assessed non-ocular predictors of visual loss other than age and sex [14, 16, 19–23]. The only study including more than a few possible predictors used a subjective measure of visual dysfunction , while the most comprehensive study until now using measured visual acuity examined the effect of HbA1c, blood pressures, proteinuria and smoking as well as age and sex . Among many candidate predictors we found only relatively high age, living alone and high triglycerides to be associated with worsening of visual acuity over 6 years, while high age, living alone, low self-rated health, and low level of physical activity were associated with a low level of visual acuity. Presumably the three last-mentioned relations are cases of reverse causation where poor vision affects living conditions. Marital status has similarly been found to predict vision loss in men with older-onset diabetes , but the association was reversed in a study of patients with advanced DR .
In UKPDS the incidence of visual impairment was slightly lower in the tight vs. the less tight blood pressure control group . Similarly, blood pressure, HbA1c and proteinuria have been shown to be indicative of visual loss in follow up studies [16, 19, 23], but none of these non-ocular patient variables was associated with visual loss in the present study. This could be due to measurement error and above all regression dilution bias , which is particularly relevant for biochemical and clinical variables in the dysmetabolic state of newly diagnosed clinical diabetes. In studies including patients with known diabetes [16, 19, 23], the measured risk factor levels are supposedly closer to an average steady state level, a kind of set point which is typical for the patient in question. In the present study, however, high level of triglycerides, which has been identified as a risk factor for proliferative DR , was a significant predictor of declining vision. In line with this finding, the FIELD study showed a promising reduction in the need for laser treatment for DR after treatment with fenofibrate but this did not affect worsening of visual acuity . It is possible that DR mediates the effect of triglycerides on visual acuity in a slow, progressive pathophysiological process. The strong counter-intuitive inverse univariate relation between smoking and visual acuity disappeared after age and sex adjustment (Table 1) while a similar association between smoking and DR persisted after adjustment in UKPDS .
Prevalence and incidence of blindness and moderate visual impairment
In population-based studies of patients with known type 2 diabetes the prevalence of blindness is between 1% and 3% [6, 7, 34, 41–43], lowest in populations offered regular eye screening. The prevalence increases markedly with diabetes duration [14, 23, 42, 43], in the present study from 0.9% at diagnosis to 2.4% six years later (Table 3).
With the gradual implementation of systematic eye screening the incidence of blindness among diabetic patients has declined . In the Nordic countries the incidence per 10,000 person-years has declined from the range of 200-500 [15, 45] in the early 1980s to more recent figures of about 15 [23, 46] among persons with known type 2 diabetes. Our patient sample included many old patients and both the prevalence [2, 4, 41] and the incidence [14, 16, 19] of visual impairment increases curvelinearly with age as in the background population [2, 36, 47]. This may partially explain why the incidence rate was as high as 40 per 10,000 person-years in the present study.
In studies of patients with known type 2 diabetes, which are to some extent population-based, the prevalence of 7-11% for moderate visual impairment [22, 34, 42, 43] is similar to the 6.7% observed 6 years after diagnosis in the present study. Of the 54 patients with moderate visual impairment at this point, however, 48 had normal vision at diagnosis, but the prevalence rate increased only modestly because of the over-mortality of patients with low vision .
Implications for clinical practice and future research
It is evident that even in Denmark where patients can refer themselves to free eye examinations, treatable eye pathologies such as DR and cataract predict further visual loss. Our results underline the importance of eliminating barriers to efficient eye care by facilitating access to eye examination, increasing the understanding of patients and primary care practitioners of the need for regular screening and early surgical treatment, and, in some countries, addressing patients' financial burdens . It should be easy to motivate a thoroughly informed patient to have regular eye examinations as many patients fear visual loss as the worst consequence of diabetes [10, 13]. The fact that almost all Danish primary care eye doctors participated in the present study demonstrates the commitment of ophthalmologists to preventive diabetes care.
In primary care, future intervention studies to reduce visual impairment in patients with diabetes may be designed primarily to overcome barriers to effective eye care, and such trials should preferably distinguish between the effect on visual acuity of changes in biological age on retina and of the interventions targeting treatable eye pathologies.