Elsevier

Survey of Ophthalmology

Volume 67, Issue 2, March–April 2022, Pages 591-607
Survey of Ophthalmology

Review article
Associations of refractive errors and retinal changes measured by optical coherence tomography: A systematic review and meta-analysis

https://doi.org/10.1016/j.survophthal.2021.07.007Get rights and content

Highlights

  • High myopes show thinner retinal nerve fiber layer and pRNFL, except for temporal quadrants.

  • High myopes show thinner macular thickness, parafovea, perifovea, fovea and foveola.

  • Moderate myopes show thinner pRNFL in superior, inferior, and nasal quadrants.

  • Low myopes show thinner parafoveal and perifoveal macula, except for nasal quadrants.

  • Hyperopes show thicker average and inferior pRNFL.

Abstract

Studies reporting alteration in retinal thickness using optical coherence tomography (OCT) have been performed in different populations with various degrees of refractive error, producing inconsistent results. Therefore, we performed a meta-analysis to evaluate the alterations in retinal OCT measurements in myopic and hyperopic patients compared to controls. Evaluation of different retinal layers’ thickness may have significance for developing novel approaches for preventing, diagnosing, and treating refractive errors and their complications. We searched PubMed and EMBASE to identify articles that reported OCT measurements of different retinal layers and regions, including macular, foveal, parafoveal, perifoveal, foveolar, ganglion cell complex (GCC), retinal nerve fiber layer (RNFL), peripapillary retinal nerve fiber layer (pRNFL), and ganglion cell and inner plexiform layer (GC-IPL) thickness in addition to macular volume, and optic disc area in myopes and hyperopes comparing their differences with controls. We applied either a fixed-effects or random-effects model for the meta-analysis of these differences based on the assessed heterogeneity level. Furthermore, subgroup analyses and metaregression, as well as publication bias and quality assessment, were conducted for the eligible studies.

Forty-seven studies with a total of 12223 eyes, including 8600 cases and 3623 non-cases, are included in this meta-analysis. Our results showed that, in comparison to controls, highly myopic eyes had a significantly lower value for mean macular thickness, macular GCC, macular GC-IPL, parafoveal, perifoveal, foveal, foveolar, RNFL, and pRNFL thickness. Compared to controls, moderately myopic eyes showed a significantly thinner mean macular GCC layer and pRNFL. On the other hand, hyperopic eyes had significantly thicker average pRNFL than controls. Several other significant differences were also observed in various regional analyses. The findings of the current study affirm the retinal OCT measurement differences between myopic and hyperopic eyes compared to controls, emphasizing OCT measurements' advantages as potential biomarkers of ocular pathologies.

Introduction

Ranked as one of the leading causes of vision impairment across the globe by the World Health Organization (WHO), uncorrected refractive errors affect approximately 123 million individuals all over the world, of whom 4 million are blind.29,73 Almost all human eyes have some degree of refractive error, including myopia and hyperopia, which are known as spherical errors.29 As a global public health concern with the highest prevalence in Asian-Pacific high-income countries and the least in African and Oceanian population, myopia currently afflicts more than 1.4 billion people worldwide, especially young adults, and projections indicate that nearly half of the world population will be myopic by 2050.16,31 Unlike myopia, the prevalence of hyperopia increases with age and reaches 10 percent in those older than 60 years.93

Both genetic and environmental factors influencing the length of the eye or its optical power are responsible for developing refractive errors.53 In addition to causes of adult-onset refractive errors like changes in eye shape, diabetes, and cataracts, dysregulation in a developmental process called emmetropization also leads to the formation of myopia and hyperopia.47,71 An increase in axial length (AL) and reduction in scleral, choroidal, and retinal thickness are thought to be the prime causes of myopia.42,57 Although several animal studies on myopia and hyperopia imply that alteration in choroidal thickness precedes the scleral remodeling and changes in AL, other studies suggest that the progressive elongation of AL precedes scleral surface expansion and chorioretinal thinning and stretching.34,65,95 Collectively, these abnormalities in ocular structures prompt various pathophysiological consequences.70

Apart from the problems refractive errors create for daily functioning, multiple studies show that higher degrees of refractive errors are correlated with severe and sight-threatening ocular changes.13,37,80 Myopia with an AL greater than 26 mm or spherical equivalent refraction (SER) equal to or higher than 6 diopters (D) is referred to as high myopia or pathological myopia.12 High myopia is associated with choroidal neovascularization, patchy or diffuse chorioretinal atrophy, retinal detachment, macular retinoschisis, retinal vessel morphologic alterations, cataracts, and glaucoma.2,24,70,78 To a lesser extent, hyperopia is also related to specific pathologies such as macular atrophy, angle-closure glaucoma, and cataracts.36,92 Hence, detailed analysis of morphological changes in different retinal regions and layers and particularly their thickness may reveal underlying mechanisms for complications and comorbidities accompanying refractive errors and possibly allow the development of novel approaches for their prevention, diagnosis, and treatment.

Recently, the interest to study different retinal regions and layers in various ocular and non-ocular disorders has grown dramatically. Optical coherence tomography (OCT) is an in vivo noninvasive imaging modality that provides cross-sectional and high-resolution images of retinal components, as well as measurements of their thickness.5,10 Moreover, advancement in this imaging technology moving from time-domain (TD) to spectral-domain (SD) and swept-source (SS) OCTs enable researchers to assess the relationship between refractive status and retinal thickness more accurately.6,19 In this regard a number of studies have measured changes of retinal thickness in its various regions such as the macula, fovea, parafovea, perifovea, foveola, and optic nerve head (ONH) disc area, in addition to different cellular layers, specifically the ganglion cell complex (GCC) that consists of retinal nerve fiber layer (RNFL), ganglion cell layer (GCL), and inner plexiform layer (IPL) in diverse patients with different degrees of myopia and hyperopia.3,54,104 These measurements are often performed in high myopes because of the predictable influence that elongation of ocular length has on the thickness of the choroid and retina.15

These studies have been performed in different populations with different degrees of refractive errors, thus leading to varying and, even in some cases, contradictory results about retinal thickness alteration. For instance, Gupta and coworkers showed that high myopic patients have lower average RNFL thickness than controls, whereas a study by Hsu and coworkers had completely opposite results.27,33 In addition, several OCT measurements are thought to have promising applications in clinical practice. For instance, measuring pRNFL thickness could be used for diagnosis and monitoring of glaucoma in myopic patients instead of examining the optic disc's appearance as visual field defects in myopesare similar to those observed in glaucoma.56 No systematic review or meta-analysis has integrated these findings and reached a conclusion about the associations between refractive errors and retinal changes measured by OCT. Therefore, in this study, we performed a systematic review of the literature in order to pool the findings of the relationship between retinal thickness and spherical refractive errors. Furthermore, a comprehensive meta-analysis was conducted to evaluate the alterations in retinal OCT measurements in myopic and hyperopic patients as compared to controls.

Section snippets

Methods

The current systematic review and meta-analysis was conducted and reported in adherence to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) statement checklist.30 This 27-item checklist provides a plausible design for systematic reviews and meta-analyses. The study protocol was developed by two authors (MAS and SM) and registered at the International Prospective Register of Systematic Reviews (PROSPERO) (Registration No. CRD42020222280).

Study Selection

As demonstrated in Figure 1, the selection process identified 47 studies for the meta-analysis. The primary literature search detected 2794 articles (1269 in Pubmed and 1525 in EMBASE). After automatic and manual removal of the duplicate manuscripts (n=1089), the remaining 1705 articles were reviewed according to their title and abstract, which excluded 1484 records. In the next phase, detailed and thorough screening lead to the exclusion of 163 more studies that did not meet the eligibility

Discussion

The recent growing application of OCT has paved the way for researchers to more meticulously study the possible correlations between ocular refractive status and retinal thickness in its various regions. To summarize the results of the current meta-analysis on studies comparing OCT measurements between eyes with different refractive statuses and controls, results showed that, in comparison to controls, the eyes with high myopia had a significantly lower value in OCT measurements, including mean

Conclusion

In summary, the findings of the current study affirm the OCT measurement differences between myopic and hyperopic eyes in comparison to controls, emphasizing the advantages of evaluating OCT measurements as potential biomarkers of ocular pathologies that occur secondary to severe refractive errors, especially glaucoma. Furthermore, the possible association between refractive errors and OCT measurements of retinal layers possibly underlines a revision in the previously determined normative

Conflict of interest

• None of the authors of this paper has a financial or personal relationship with other people or organizations that could inappropriately influence or bias the content of the paper.

• It is to specifically state that “No Competing interests are at stake and there is No Conflict of Interest” with other people or organizations that could inappropriately influence or bias the content of the paper.

Funding

Not applicable

Conflict of interest

Authors declare no conflicts of interest.

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