Refractive Error and Risk of Early or Late Age-Related Macular Degeneration: A Systematic Review and Meta-Analysis

Methodological quality of the review: Medium confidence

Author: Ying Li1, JiWen Wang, XiaoJing Zhong, Zhen Tian, Peipei Wu, Wenbo Zhao, Chenjin Jin

Region: Australia, India, France, Singapore, Norway, USA, China, Copenhagen, Netherlands

Sector: Refractive error

Subsector: Refractive error and risk of early or late age-related macular degeneration

Equity focus: No

Study population: Adults

Type of programme: Community based

Review type: Other review

Quantitative synthesis method: Systematic review and meta-analyses

Qualitative synthesis method: Not applicable

Background: Age-related macular degeneration (AMD) – a devastating disease affecting the macula – is the leading cause worldwide of irreversible central vision loss in people over 50 years old. As a major public health issue, the precise cause of AMD remains unknown, but ageing, smoking and positive family history increase the predisposition of an individual to develop AMD. Refractive error, especially hyperopia, has also been considered to be associated with AMD in previous studies. Prevention should be emphasised more strongly owing to the lack of effective treatments for AMD at present. It is therefore necessary to identify risk factors in an effort to prevent the development of AMD.

Objectives: The objective of this study was to summarise relevant evidence investigating the associations between refractive error and age-related macular degeneration (AMD).

Main findings: Fourteen studies, comprising 54,091 individuals, with 5,814 of whom had AMD were eligible. The scores awarded for study quality varied. The quality of 10 studies ranked as high, and the remaining three studies were ranked as moderate. No attempt was made to weight studies based on the quality score to avoid introducing subjective bias to the meta-analysis. Significant associations were found between hyperopia, myopia, per-diopter increase in SE, per-millimeter increase in AL and prevalent early AMD. The pooled ORs and 95% CIs were 1.13 (1.06-1.20), 0.79 (95% CI, 0.61-0.97), 1.10 (1.07-1.14), and 0.79 (0.73-0.85), respectively. The per-diopter increase in SE was also significantly associated with early AMD incidence (OR, 1.06; 95% CI, 1.02-–1.10). However, no significant association was found between hyperopia or myopia and early AMD incidence. Furthermore, neither prevalent nor incident late AMD was associated with refractive error. Considerable heterogeneity was found among studies investigating the association between myopia and prevalent early AMD (P=0.001, I²=72.2%). In addition, significant heterogeneity was found in studies investigating SE and late AMD prevalence (P=0.00, I²=85.6). No publication bias was found, with all P-values for results on the Egger’s and Begg’s tests .0.5. Geographic location might play a role; the heterogeneity became non-significant after stratifying these studies into Asian and non-Asian subgroups.

Methodology: Inclusion criteria consisted of studies that A) explored the associations between hyperopia, myopia, SE, AL and AMD; B) clearly reported the method used to assess AMD, which was limited to the Wisconsin Age-Related Maculopathy grading system or the International Classification and Grading system; C) reported an effect estimate, such as an odds ratio (OR) with 95% confidence interval (CI), or provided the raw data for calculation; D) in the case of multiple publications sharing the same sample, the study that best addressed our topic was included. Literature searches were done on Medline, Web of Science, and the Cochrane Library databases to identify all potentially relevant published studies by using the following combination of terms with no restrictions (MeSH terms were not used to search the Web of Science). The references cited in retrieved articles were also scanned for any additional relevant studies. Two authors independently conducted the search; any disagreements were solved by consensus. The current meta-analysis was conducted according to the guidelines in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Extracted information from each eligible study included: first author, publication year, study name, country in which the study was performed, age range or years of follow-up for patients with AMD, sample size (AMD patients/total population), response rate or follow-up rate, diagnostic standards for AMD, AMD type, adjusted confounders, definitions of hyperopia and myopia, and the effect estimates with corresponding 95% CIs. Study quality was ranked as high, moderate or low (score categories 7-9, 4-6, 3-0, respectively) by using the Newcastle-Ottawa Quality Assessment Scale (NOS). Two independent reviewers conducted the data extraction and quality assessment, and solved disagreements by discussion. All statistical analyses were performed using STATA software. The fully adjusted, study-specific ORs were combined using a random effects model, which accounts for both within- and between-study heterogeneities. Q and I² statistics were used to assess the presence and amount of between-study statistical heterogeneity. P,0.1 was used as the cut-off for significant heterogeneity. Publication bias was estimated using Egger’s linear regression test and Begg’s test.

Applicability/external validity: The authors emphasise the limitation of this study for proper interpretation. In total, the authors acknowledged six points of limitation which need to be considered.

Geographic focus: This review included studies from Europe, Asia, America and Pacific. This result can be applied within the countries of those regions. Unfortunately, the study did not investigate different levels of refractive error (low, moderate and high myopia or hyperopia) in relation to different subtypes or signs of AMD geographically.

Summary of quality assessment:

There is medium confidence in the conclusions about the effects of this study. Although authors used rigorous methods to analyse data of included studies, authors did not conduct a thorough search of the literature.