Cataract and age-related macular degeneration (AMD) are both common causes of impaired visual acuity and blindness in the elderly population worldwide. Cataract progression is the most widespread cause of blindness worldwide [
In the past decades, it has become apparent that vision is not sufficient as a criterion for judging whether and when a cataract surgery should be performed on a patient. Concern has been raised that cataract surgery may increase the risk of incident AMD or progression of preexisting AMD. Early histological examinations [
Cataract and AMD often coexist in patients. The presence of AMD may adversely affect the visual outcome after cataract surgery. However, deferring surgery for visually significant cataract in patients with AMD will also negatively influence the visual function of patients. At the same time, case reports and cohort studies have raised the concern that cataract surgery may increase the risk of progression of AMD. So, how do we advise a patient with visually significant cataract and AMD?
The effect of cataract surgery on progression of AMD was previously evaluated by a review [
This meta-analysis was conducted following the PRISMA guidelines [
Type of study: we only included cohort studies comparing the visual performance of AMD patients with and without cataract surgery. Object of study: patients with age-related cataract who had phacoemulsification or with both cataract and AMD were included; patients with a history of surgery that may affect postoperative vision outcomes may be excluded. Outcome measures: describe whether cataract surgery will increase the risk (relative risk (RR)) of AMD progression.
Two independent reviewers used the same standardized form to extract data. The reviewers applied the Newcastle-Ottawa scale to assess risk of bias in nonrandomized studies [
Each study estimated the relationship between cataract surgery and the progression of AMD. Considering the low prevalence of AMD, we can generally ignore the distinctions among the various measures of relative risk (e.g., odds ratios, hazard ratio. and risk ratios) [
A total of 2,346 documents from multiple databases and 5 documents identified manually were retrieved, and 2,037 documents remained after the duplicates were deleted. After deleting the documents which were unrelated to cataract surgery and AMD progression based on the titles and abstracts, there were remaining 100 articles. All trials describing whether cataract surgery will increase the risk of AMD progression can be included. After reading the full text, 26 articles were selected, of which 1 was RCT, were case control trials, 10 were cross-sectional trials, and the rest were cohort trials. We only chose the cohort trials in quantitative synthesis (meta-analysis). To reduce duplicate synthesis in the same control group, for the same study population, we select the most recently published literature. The trials selection process is shown in Figure
The trials selection process.
The characteristics of the trials included in the current meta-analysis are shown in Table
Characteristics of articles included in this meta-analysis.
Author | Publish year | Study design | No. of cases/control | Location | Adjustment/match | AMD classification | Follow-up | OR/RR/HR | CI | Age | |
---|---|---|---|---|---|---|---|---|---|---|---|
Pollack | 1996 | Cohort | 47/47 | Asia | — | Early AMD | 1 year | RR = 4.500 | 1.027–19.726 | 0.054 | 80.4 (67–94) |
Lintje Ho | 2008 | Cohort | 6032 | Europe | Age, sex, follow-up time, and the correlation between eyes | AMD | 5.7 (2.8–9.7) | OR = 1.26 | 0.85–1.86 | — | ≥55 |
Early AMD | OR = 1.31 | 0.88–1.95 | |||||||||
Dry AMD | OR = 3.44 | 1.68–7.08 | |||||||||
Wet AMD | OR = 0.93 | 0.35–2.49 | |||||||||
Jie Jin Wang | 2003 | Cohort | 6019 | Oceania and North America (BDES and BMES) | Baseline age, gender, smoking status (current, past, and never), and preexisting early-stage ARM lesions at baseline | Late AMD | 5 years | OR = 5.7 | 2.4–13.6 | — | — |
Dry AMD | OR = 4.5 | 1.4–14.7 | |||||||||
Wet AMD | OR = 4.9 | 1.9–12.4 | |||||||||
North America (BDES) | Late AMD | OR = 7.3 | 2.6–20.4 | ||||||||
Dry AMD | OR = 4.7 | 1.4–16.1 | |||||||||
Wet AMD | OR = 6.8 | 1.9–24.3 | |||||||||
Oceania (BMES) | Late AMD | OR = 4.2 | 1.0–17.5 | ||||||||
Dry AMD | OR = 7.6 | 1.1–55.0 | |||||||||
Wet AMD | OR = 3.1 | 0.7–13.2 | |||||||||
Sudha Cugati | 2006 | Cohort | 1952 | Oceania (BMES) | Age, gender, smoking | Early AMD | 10 years | OR = 1.25 | 0.69–2.25 | — | ≥49 |
Age, gender, smoking, and presence of early ARM lesions | Late AMD | OR = 3.31 | 1.11–9.87 | ||||||||
Dry AMD | OR = 2.34 | 0.51–10.8 | |||||||||
Wet AMD | OR = 3.42 | 1.07–10.91 | |||||||||
Jau-Der Ho | 2018 | Cohort | 3465/10395 | Asia | Patient’s geographical location, urbanization level, monthly income, diabetes, hypertension, and cardiovascular and hyperlipidaemia | Wet AMD | 5 years | HR = 2.68 | 1.55–4.66 | <0.01 | 70.2 ± 9.6 |
Helena Buch | 2005 | Cohort | 359 | Europe | Age, sex | AMD | 14 years | OR = 1.3 | 0.7–2.4 | — | 82.4 ± 4.63 (75–95) |
Late AMD | OR = 1.6 | 0.8–3.2 | |||||||||
Emily Y. Chew | 2009 | Cohort | 6037 | America (AREDS) | Age, gender, race, smoking, AREDS treatment group, and eye-specific AMD severity status | Wet AMD | 5 years | OR = 0.76 | 0.44–1.30 | 0.31 | 55–80 |
Dry MD | OR = 0.55 | 0.31–0.99 | 0.047 | ||||||||
Jie Jin Wang | 2012 | Cohort | 1178 | Oceania (CSAMD) | Baseline early AMD in models for late AMD outcome (paired comparison) | Late AMD | 3 years | OR = 0.74 | 0.23–2.36 | ≥65 | |
Early AMD | OR = 1.07 | 0.74–1.65 | |||||||||
Jie Jin Wang | 2016 | Cohort | 2029 | Baseline early AMD in models for late AMD outcome (paired comparison) | Late AMD | 5 years | OR = 0.7 | 0.4–1.2 | |||
Early AMD | OR = 0.7 | 0.5–1.1 | |||||||||
Ronald Klein | 2002 | Cohort | 2764 | North America (BDES) | Age, sex, vitamin use, smoking, drinking, and systolic blood pressure | AMD | 10 years | RR = 1.97 | 1.29–3.02 | <0.01 | 43–86 |
Early AMD | RR = 1.36 | 0.82–2.23 | 0.23 | ||||||||
Late AMD | RR = 3.81 | 1.89–7.69 | <0.01 | ||||||||
Wet AMD | RR = 4.31 | 1.71–10.9 | <0.01 | ||||||||
Dry AMD | RR = 3.18 | 1.33–7.60 | <0.01 | ||||||||
Klein, B. E. | 2012 | Cohort | 3275 | North America (BDES) | Age, sex, education, smoking, drinking, cardiovascular disease, diabetes, and diastolic blood pressure | Early AMD | 20 years | OR = 1.06 | 0.81–1.38 | 0.7 | 43–86 |
3585 | Late AMD | OR = 1.96 | 1.28–3.02 | 0.002 | |||||||
Ronald Klein | 1998 | Cohort | 3684 | North America (BDES) | Age, smoking, beer consumption, drinking, pulse pressure, hypertension, and vitamin use | Early AMD | 5 years | OR = 1.73 | 0.93–3.21 | 0.08 | 43–86 |
Late AMD | OR = 2.80 | 1.03–7.63 | 0.04 | ≥65 | |||||||
Wet AMD | OR = 1.67 | 0.39–7.18 | 0.49 | ≥65 | |||||||
Dry AMD | OR = 3.49 | 0.80–15.16 | 0.1 | ≥65 | |||||||
AMD | OR = 2.57 | 1.61–4.11 | <0.001 | 43–86 |
Table
Evaluation of the quality of cohort studies included in the meta-analysis.
Author | Publish year | Study design | Selection | Comparability | Outcome | Score | |||||
---|---|---|---|---|---|---|---|---|---|---|---|
Representativeness of the exposed cohort | Selection of the nonexposed cohort | Ascertainment of exposure | Demonstration that outcome of interest was not present at start of study | Comparability of cohorts on the basis of the design or analysis | Assessment of outcome | Was follow-up long enough for outcomes to occur? | Adequacy of follow-up of cohorts | ||||
Pollack | 1996 | Cohort | 1 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 8 |
Lintje Ho | 2008 | Cohort | 1 | 1 | 1 | 1 | 2 | 1 | 1 | 1 | 10 |
Jie Jin Wang | 2003 | Cohort | 1 | 1 | 1 | 1 | 2 | 1 | 1 | 1 | 10 |
Sudha Cugati | 2006 | Cohort | 1 | 1 | 1 | 1 | 2 | 1 | 1 | 1 | 10 |
Jau-Der Ho | 2018 | Cohort | 1 | 1 | 1 | 1 | 2 | 1 | 1 | 1 | 10 |
Helena Buch | 2005 | Cohort | 1 | 1 | 1 | 1 | 2 | 1 | 1 | 1 | 10 |
Emily Y. Chew | 2009 | Cohort | 1 | 1 | 1 | 1 | 2 | 1 | 1 | 1 | 10 |
Jie Jin Wang | 2012 | Cohort | 1 | 1 | 1 | 1 | 2 | 1 | 1 | 1 | 10 |
Jie Jin Wang | 2016 | Cohort | 1 | 1 | 1 | 1 | 2 | 1 | 1 | 1 | 10 |
Ronald Klein | 2002 | Cohort | 1 | 1 | 1 | 1 | 2 | 1 | 1 | 1 | 10 |
Klein | 2012 | Cohort | 1 | 1 | 1 | 1 | 2 | 1 | 1 | 1 | 10 |
Ronald Klein | 1998 | Cohort | 1 | 1 | 1 | 1 | 2 | 1 | 1 | 1 | 10 |
We use the Stata/12.0 to integrate the data that was extracted from the articles. Eight studies with data from different study populations were included. We use RR to indicate the relationship between cataract surgery and AMD progression. Some studies have reported that cataract surgery can aggravate the progression of AMD, although the intensity of associations varies from study to study, and some small studies report a particularly strong inverse association. It can be seen from the visual inspection of the funnel plot that there is no publication bias (Egger’s test Pr > |
The funnel plot in Egger’s test and Begg’s test.
The filled funnel plot.
The RR for cataract surgery and AMD in the random effects model.
Sensitivity analysis.
It can be divided into four groups according to the locations, which are Asia, Europe, Oceania, and America. For those grouped according to the location, the RR for Asia was 2.855 (95% CI 1.704–4.781), Europe was 1.271 (95% CI 0.914–1.769), Oceania was 1.017 (95% CI 0.607–1.703), and America was 0.997 (95% CI 0.621–1.601). As shown in Figure
Subgroup analysis on different regions.
According to the records of different data in different documents, they can be divided into three groups according to the classification of AMD, which are, respectively, early AMD, late AMD, and AMD. For those grouped according to the classification of AMD, the RR for early AMD was 1.059 (95% CI 0.706–1.591), late AMD (including wet AMD and dry AMD) was 1.254 (95% CI 0.705–2.232), and AMD was 1.271 (95% CI 0.914–1.769). As shown in Figure
Subgroup analysis on different AMD classification.
According to the follow-up time classification, they can also be divided into 2 groups. For those grouped according to the follow-up year (Figure
Subgroup analysis on follow-up time.
Many large epidemiologic studies do not provide a clear indication of whether cataract surgery is associated with an increased risk of AMD progression. The aim of our meta-analysis was to determine the effect of cataract surgery on the progression of AMD and provide evidence-based recommendation on the care of patients with coexisting AMD and cataract. Only a small number of publications could be included in the article. It needs to be mentioned that randomizing patients to not undergo cataract surgery when their vision is poor enough to affect their daily life would neither be ethical nor practicable.
From the results in this article, it can be found that Asians are more likely to develop AMD after surgery. This is similar to the study in South Korea [
For this meta-analysis, AMD severity was classified as early AMD and late AMD (including wet AMD and dry AMD). Thus, the classification could be applied to all included studies, enabling a reasonable comparison of the individual studies. From the results of subgroups classified by AMD type, we could not conclude that cataract surgery can aggravate all types of AMD (RR: 1.271; 95% CI 0.914–1.769), and there is a high degree of heterogeneity in early and late AMD, and the results are not statistically significant. The included studies showed noticeable differences in the duration of the follow-up and did not present reasons for the chosen duration. When the follow-up time is longer than 5 years, there is an exact relationship between cataract surgery and AMD, and the RR is 1.372 (95% CI 1.062–1.772). Many studies have found that different clinical subtypes of AMD have different risks for developing neovascular AMD. Combining the results of Beaver Dam and Blue Mountain, it was found that cataract surgery was related to five-year incidence of neovascular AMD [
Although we did not find a clear link between cataract surgery and AMD, some studies have found that cataract and AMD may have the same risk factors epidemiologically [
Cataract surgery accelerates the progress of AMD, and the following mechanisms may exist. First, the elderly’s lens effectively absorbs short wavelengths thereby providing protection against short-wavelength irradiation. The natural lens is removed and replaced with an artificial intraocular lens (IOL) that provides less protection against short wavelengths [
Second, cataract surgery may directly impact progression of early AMD, such as photic retinal injuries caused by the operating microscope [
The third possible factor is cataract surgery-related, intraocular inflammation is common after cataract surgery. As early as 1994, Van der Van der Schaft et al. [
Fourth, theoretical link between AMD progression and cataract surgery is related to the immune system and inflammatory response induced by cataract surgery. Increasing evidence points towards imbalance in inflammatory regulation as a hallmark in the pathogenesis of AMD [
Last, there may be a genetic factor that is also a mechanism for the development of AMD after cataract surgery [
This meta-analysis also has some limitations. First, there were no trials at the highest level of evidence, which are randomized controlled trials (RCT) or systematic reviews of RCT, because there are a series of obstacles [
There is no firm conclusion as to whether cataract surgery can promote the progress of AMD. On the one hand, surgeons are concerned about serious visual impairment caused by neovascular AMD after removing the opaque lens. On the other hand, cataract patients with early AMD cannot be excluded from cataract surgery, as there have been quite a few studies [
We could draw out such a conclusion that there is still a positive correlation between cataract surgery and the progression of AMD and that cataract surgery increases the progression of early AMD to late AMD as follow-up years increase. The previously mentioned results show that a temporal sequence of cataract surgery and subsequent AMD development or progression would be necessary to conclude a causal relationship. However, according to the current results, it is not possible for us to draw out conclusions from existing studies on the impact of cataract surgery on the development of AMD. Overall, the included studies showed considerable differences concerning study population and study period; hence, their comparability was limited. Therefore, additional clinical trials (with sufficient statistical power) are needed to demonstrate this hypothesis by adequate control of confounding variables such as age and cataract severity. Research hypotheses and possible influencing factors, such as lens type and type of surgery, need to be clearly stated for a comprehensive assessment.
No data were used to support this study.
The authors declare that there are no conflicts of interest related to this published work.