Article Text
Abstract
Myopia is rapidly increasing in Asia and around the world, while it is recognised that complications from high myopia may cause significant visual impairment. Thus, imaging the myopic eye is important for the diagnosis of sight-threatening complications, monitoring of disease progression and evaluation of treatments. For example, recent advances in high-resolution imaging using optical coherence tomography may delineate early myopic macula pathology, optical coherence tomography angiography may aid early choroidal neovascularisation detection, while multimodal imaging is important for monitoring treatment response. However, imaging the eye with high myopia accurately has its challenges and limitations, which are important for clinicians to understand in order to choose the best imaging modality and interpret the images accurately. In this review, we present the current imaging modalities available from the anterior to posterior segment of the myopic eye, including the optic nerve. We summarise the clinical indications, image interpretation and future developments that may overcome current technological limitations. We also discuss potential biomarkers for myopic progression or development of complications, including basement membrane defects, and choroidal atrophy or choroidal thickness measurements. Finally, we present future developments in the field of myopia imaging, such as photoacoustic imaging and corneal or scleral biomechanics, which may lead to innovative treatment modalities for myopia.
- imaging
- optics and refraction
- sclera and episclera
- optic nerve
- diagnostic tests/investigation
Statistics from Altmetric.com
Introduction
The reported prevalence of myopia has increased in recent years, the highest currently being in East Asia with up to 70%–90% of young adults in countries such as Singapore and China.1 Furthermore, the prevalence of pathological changes from high myopia where myopic degeneration of the macula occurs with axial elongation, that is, pathological myopia (PM), is also expected to increase.2 PM is a cause of low vision and blindness in 4.5%–7.8% in European populations and up to 12.2%–31.3% in East Asian populations such as China, Hong Kong and Japan.2 While PM in older generations is probably due to genetic factors, high myopia in younger persons is likely to be associated with environmental factors.3 Nonetheless, myopia has been recognised as an important public health problem in the future that needs to be addressed today.4
High myopia is associated with axial length elongation and various complications such as cataract formation; retinal complications such as retinal detachment from peripheral retinal tears; macula complications such as choroidal neovascularisation (CNV); and optic nerve-related degeneration leading to glaucoma.5 Thus, imaging of the myopic eye has become extremely important for the early detection of complications associated with PM and may help identify prognostic factors for progression of the disease. For example, high-resolution imaging of the macula may reveal subtle changes not detectable on clinical examination, such as macular schisis or early macular holes, to identify eyes at risk of developing macular hole retinal detachments.6 In eyes with PM, myopic CNV is a leading cause of visual impairment,7 and early detection of atrophy and defects in the basement membrane may help to predict the risk of CNV development.8 Imaging may also help to monitor posterior staphyloma and geographic atrophy progression, which lead to visual impairment in older patients.9 Furthermore, optic nerve imaging to assess myopic changes, such as tilting of the optic disc, peripapillary atrophy (PPA) and pitting of the optic disc,10 could help detect factors associated with optic nerve damage.11 12 Serial imaging may be important to monitor the development of open-angle, normal-tension glaucoma.13
The purpose of this review is to summarise the importance of imaging the myopic eye and its challenges, from the optic nerve to the posterior segment and anterior segment. We also discuss potential future clinical applications and novel developments in the field of imaging in myopia.
Challenges with imaging the myopic eye
The main challenges of imaging an eye with myopia are related to (1) the difficulty with direct visualisation due to optical imperfections within the eye, affecting modalities such as fundus photography and angiography; (2) abnormal structural changes and elongation of the eye hindering imaging techniques such as optical coherence tomography (OCT); and (3) irregular changes to the shape of the eye which lead to difficulties with biometric measurements or inaccurate imaging of the structure of the eye, for example, ultrasound. As the optical system of the eye essentially consists of two positive lenses, that is, the cornea and the crystalline lens, any image of structures within the eyes is critically dependent on the optical properties of these media. Factors that may affect image quality include diffraction of the light in the pupil, optical aberrations and intraocular scattering. In patients with high myopia, any imaging modality, including fundus photography, may have degradation in quality due to an interaction between low-order and high-order aberrations.14 15 It may even be simply affected by limitations of the focus in the device; for example, in cases of very high myopia (eg, more than –12.0 dioptres), the dioptre compensation of the image capture may not be sufficient. Furthermore, in PM the elongation of the eye is associated with irregularities in the scleral or corneal curvature, and disproportionate alterations in structural properties within the eye, for example, cataract leading to loss of clarity, or retinal thinning leading to unusual image projections.15 16 Gross structural irregularities leading to issues with accurate imaging are exemplified by the alterations in optic nerve head morphology, leading to the challenges associated with image interpretation, which will be covered in a subsequent part of this review.
Given these challenges, imaging modalities used in myopia include photography, dye-based angiography, ultrasound (including biomicroscopy) and MRI. As in other fields of ophthalmology, OCT has now become the most frequently used tool for characterising alterations in ocular tissues due to myopia.17 The development of enhanced depth imaging (EDI) and swept-source OCT (SS-OCT) with its higher wavelength in the order of 1050 nm now allows for improved penetration into deeper layers, while the speed of capture and software enhancements enable for wider field of scans. More recently the introduction of OCT angiography (OCTA) has yet added another dimension to imaging the vasculature within the eye.18–20 However, there are still many limitations and scope for improvement (eg, even with wide-field OCT [WF-OCT], the depth range may be insufficient to capture the entire anterior-posterior extent of the posterior pole, leading to issues with segmentation in the periphery) (figure 1). Another issue relates to the normative database found in OCT systems, as the reference cohort should ideally be selected from the same population as patient cohort in order to optimally reflect comorbidities.21 Usually stratification is required for covariates that affect measurements such as age, ethnicity and refractive error. For myopia, this is a challenge because of the large regional variation in refractive error prevalence.22 As such the normative database in OCT systems will not optimally reflect the patient population in regions where myopia and PM are highly prevalent, such as in East Asia.
Imaging the retina in myopia
Before the advent of modern imaging techniques, the myopic retina posed several challenges to diagnosis. First, the lack of contrast between the retinal tissue and underlying choroid made it difficult to diagnose conditions like myopic foveoschisis based on clinical examination or fundus photography. Second, posterior staphyloma, a key feature of PM,23 is difficult to discern from two-dimensional (2D) fundus photographs alone. Finally, peripheral retinal lesions such as lattice degeneration and retinal breaks are difficult to capture on traditional 50° fundus photographs.
OCT revolutionised the diagnosis and management of the retinal complications of PM by enabling high-resolution, in vivo examination of the retinal layers. The splitting of retinal layers that characterise myopic traction maculopathy can be seen in great detail on cross-sectional OCT scans of the retina, which is further improved with retromode fundus imaging.24 These features include inner or outer retinal schisis, foveal detachment, lamellar or full-thickness macular hole and/or macular detachment (figure 2A).25 Myopic maculopathy, another common retinal complication of PM, can be clearly characterised with OCT: in areas of patchy chorioretinal atrophy, absence of the retinal pigment epithelium (RPE) can be clearly identified as areas of increased transmission of signal and may be associated with loss of the outer retina (figure 2B). OCT imaging has also revealed choroidal thickness to be a possible biomarker for myopic maculopathy severity and progression.26
Furthermore, OCT imaging is invaluable in the diagnosis of posterior staphyloma, a key lesion of PM, and provides a greater level of detail on its nature because the change in contour at the staphyloma edge is not always apparent on non-stereoscopic fundus photographs, but can be readily visualised with an OCT scan.27 28 Shinohara et al 28–30 compared the utility of WF-OCT in detecting posterior staphyloma with three-dimensional (3D) MRI and found no difference in the detectability of staphyloma with either technique. While there was a high concordance in the classification of staphyloma, ultra-wide-field OCT (UWF-OCT) had the advantage in its ability to visualise the spatial relationship of the staphyloma with the optic nerve and macula.29 30
Conventional fundus imaging can typically image up to 50° of the retina. In contrast, UWF retinal imaging can image 200° of the retina and is particularly useful in highly myopic eyes due to the high prevalence of peripheral retinal lesions such as lattice degeneration and retinal breaks (figure 3A). In addition, the margins of wide posterior staphylomata can be captured easily on UWF retinal imaging but are often missed on traditional fundus photography.31 32 UWF fluorescein angiography (FA) and indocyanine green angiography (ICGA) have been applied to the study of peripheral retinal circulation33 and the choroidal outflow system, respectively, adding new insights into the pathogenesis of PM (figure 3B).34
Multimodal imaging is crucial for the assessment of myopic choroidal neovascularisation (mCNV), a sight-threatening retinal disease in high myopes that is difficult to diagnose and monitor based on clinical examination alone (figure 4A,B). The diagnosis is confirmed on fundus FA where the lesion demonstrates hyperfluorescence that increases in size and intensity with time, indicating leakage.35 Furthermore, wide-field fundus FA may reveal retinal avascularity in the 360° of the periphery, which is a feature of PM.33 OCTA has emerged as a useful modality for identifying the neovascular membranes non-invasively, differentiating between the different causes of subretinal exudation in high myopes, that is, simple lacquer crack haemorrhage, inflammatory lesions and mCNV.36 37 However, OCTA has lower sensitivity compared with FA and cannot replace the latter as the diagnostic gold standard.38 Another limitation of OCTA is the lack of information on disease activity, as the flow signal may persist in an inactive mCNV, thus still requiring FA to monitor the level of activity (figure 4D,F).37–39 OCT appearance is helpful to determine the stage of mCNV, such as signs of activity, that is, ill-defined margins40 and disruption of the external limiting membrane,41 with variable amount of intraretinal or subretinal fluid (figure 4C). With treatment, the hyper-reflective lesion consolidates and acquires a distinct border (figure 4E). Studies using OCT have revealed that macular atrophy developing after mCNV may be the result of the rupture of the Bruch’s membrane.42 Nonetheless, recent multimodal imaging combining OCTA and SS-OCT suggests that mCNV may not be supplied by choroidal vasculature but instead directly from the short posterior ciliary artery.43
Imaging the choroid and sclera in myopia
Techniques currently available for imaging the choroid include ICGA, ultrasonography (US) and OCT. Imaging the choroid remains a challenge given its anatomical position between the sclera and the RPE, and in PM the choroid is often too thin to measure, with further multiple factors disrupting the ability to properly image the choroid in the myopic eye.
The emission spectra of fluorescein, as used in angiography, is blocked by melanin and thus is rendered less effective for choroid visualisation. Additionally, RPE pigment and choroidal blood cause light absorption and scattering. Alternatively, angiography via indocyanine green (ICG) has an emission spectrum within near-infrared and is less affected by RPE pigment and choroidal blood.44 ICG has potential utility in assessing a variety of choroidal vasculopathies and inflammatory diseases.45 However, ICGA is less practical in clinical settings when compared with the more widely used OCT and autofluorescence imaging. OCTA could also be used to assess choroidal vascularity and its structure.46–48 B-scan US may also be used to image the choroid with better penetration, but suffers from poor resolution, which is exacerbated as the choroid gets thinner with PM.49 Despite this, US remains useful in determining staphylomas and globe contours.
Currently, EDI, which is a function of spectral domain OCT instruments, is able to visualise the choroid specifically.50 However, OCT imaging of the choroid remains challenging since a key limitation is that its sensitivity is inversely proportionate with deeper tissues imaged. In the choroid the signal obtained is weak because of the high attenuation coefficient of the RPE. Yet imaging the full thickness of the choroid in high myopes is still achievable, given thinner choroids and relative depigmentation. However, these high myopes also tend to have staphylomas and abnormal eyewall contours, further distorting OCT imaging. In comparison SS-OCT suffers less from decreased sensitivities in relation to increased tissue depth.51 Ultimately, regardless of the method, OCT faces constraints in imaging high myopia, due to the extreme axial length of highly myopic eyes, exaggerations of curvature deformities on OCT and the production of imaging artefacts.52
Staphylomatous changes are a common feature in highly myopic eyes, which makes imaging the posterior segment and the sclera even more challenging. Techniques such as OCT are unable to clearly delineate the posterior scleral boundary, and the choroid (unless extremely thin) tends to attenuate signals and decrease scleral image quality. Adaptive compensation (based on direct application of pixel intensity exponentiation) can enhance scleral boundaries using ‘Reflectivity’ software, to allow more accurate assessment of scleral thickness.53 54 Thus, in terms of imaging the scleral contour and characterisation of staphyloma, 3D MRI and US are preferred. Moreover, both quantitative US and super-resolution 3D MRI have been used to localise areas of scleral weakness and pliability in both guinea pigs ex vivo and human in vivo. These modalities have the potential to detect scleral weakness prior to staphyloma formation and determine which highly myopic eyes are headed down the path towards staphyloma and MM formation, and would be critical in research endeavours focused on scleral reinforcement (such as macular buckling55 or scleral collagen cross-linking56 57).
Anterior segment imaging in myopia
The studies attempting to define the relationship between the anterior segment characteristics and high myopia have been variable, with contradicting studies suggesting that myopia could be associated with flatter or steeper corneal curvatures, while some have suggested an association of myopia with thinner corneal thicknesses and deeper anterior chamber depths.58 However, many of these reported associations have been inconsistent, as they have been confounded by varying patient selection, variability in definitions of myopia and the use of different imaging techniques.59 Although most of the refractive error associated with myopia comes from the axial length, it is increasingly recognised that changes of the anterior segment in high myopia lead to significant optical and higher order aberrations.60 A potentially interesting aspect is the study of biomechanical changes associated with corneal thickness in high myopia, which may affect the evaluation of intraocular pressure61 and diagnosis of glaucoma—elaborated further later in this review.62 However, current studies have variable results due to the different imaging techniques and the technological limitations in measuring on the biomechanical changes of the cornea associated with increasing myopia.63
Nonetheless, imaging of the cornea and anterior segment is important in the clinical evaluation of patients with high myopia when planning for various surgical procedures. For example, accurate corneal imaging is important before offering corneal refractive procedures such as laser in situ keratomileusis,64 or even newer forms such as refractive lenticule extraction,65 as such eyes are at higher risk of developing ectasia with greater amounts of corneal ablation.66 Precise anterior segment imaging is also required for planning safe phakic lens implantation, which are more likely to be performed in high myopes that are unsuitable for laser refractive correction.67 As presenile cataracts are associated with high myopia, choosing accurate intraocular lens implantation after cataract surgery in high myopes presents a challenge as accurate formulae, precise anterior segment imaging and corneal topography are required to prevent refractive surprises.68 Recent advances in biometry incorporating anterior segment OCT technology69 with next-generation formulae have improved intraocular lens calculation and refractive prediction in high myopes.68
Imaging the optic nerve in myopia
Identification of optic disc changes associated with glaucoma in highly myopic eyes is notoriously difficult.70 71 Optic disc tilt, PPA and abnormally large or small optic discs confound delineation of optic disc margins in these eyes and are one of the earliest known changes occurring even in young highly myopic adults and may precede the development of PM.72 73 Eyes with myopic maculopathy pose an additional challenge by confounding visual field findings.74 Imaging of deep optic nerve structure in highly myopic eyes has emerged as a potential modality to diagnose glaucoma accurately in these eyes (figure 5).
Optic disc tilt in highly myopic eyes deform the lamina cribrosa (LC) and may obstruct axoplasmic flow within the optic nerve head, thus promoting glaucomatous optic nerve damage.75 Imaging of the LC integrity in these eyes may yield information on the risk of glaucoma.11 Sawada et al 75 evaluated LC defects in myopic eyes with and without open-angle glaucoma using enhanced depth OCT and found these defects to be related to the optic disc tilt angle and were associated with glaucomatous visual field defects in both location and severity.
Bruch’s membrane opening (BMO) is the anatomical exit site of the optic nerve and can be clearly identified on OCT. Malik et al 76 assessed the diagnostic performance of using the BMO as a landmark for neuroretinal rim measurements compared with the conventional disc margin-based measurements and found BMO minimum rim width (BMO-MRW) to be significantly more sensitive (71% vs 30%) than disc margin rim area (DM-RA) for the diagnosis of glaucoma. Enders et al 77 further showed that a 2D neuroretinal rim parameter based on the BMO, the BMO minimum rim area, outperformed BMO-MRW, retinal nerve fibre layer thickness and DM-RA in the diagnostic power for glaucoma. However, the diagnostic performance of this parameter has not been validated in myopic eyes.
Besides BMO, the border tissue of Elschnig is another deep optic nerve head structure of interest that can be visualised with enhanced depth OCT. The border tissue is a cuff of collagenous tissue arising from the sclera that joins the Bruch’s membrane at the optic disc margin.75 Han et al 78 evaluated the externally oblique border tissue length, optic nerve head tilt angle and optic canal obliqueness, and observed that temporally located maximal values for these parameters were independently associated with the presence of myopic normal-tension glaucoma, and were consistent with the location of retinal nerve fibre layer defects.
The circumpapillary retinal nerve fibre layer (cp-RNFL) thickness is a good indicator of glaucoma in non-myopic eyes but is difficult to interpret in the presence of PPA in high myopes. An alternative parameter, the macular ganglion cell complex (GCC) thickness, has shown diagnostic power similar to cp-RNFL measurements for detecting glaucoma in non-myopes and could be a potential substitute parameter in high myopes.79–82 To this end, Zhang et al 83 demonstrated the superior diagnostic power of macular GCC parameters compared with cp-RNFL parameters for diagnosing glaucoma in high myopes. Among these macular parameters, the focal loss volume on the RTVue-OCT and the minimum ganglion cell-inner plexiform layer on the Cirrus HD-OCT had the greatest diagnostic power. Two challenges remain for the use of macular GCC measurements to diagnose glaucoma in high myopes, that is, lack of a normative database in highly myopic eyes and chorioretinal atrophy from myopic maculopathy that can confound these measurements. Recent emerging reports suggested OCTA of the optic nerve as a potential adjunctive tool for assessment of glaucomatous changes in the myopic disc. Suwan et al 84 measured the perfused capillary density (PCD) as measured on a 4.5×4.5 mm OCTA scan centred on the optic nerve head and demonstrated the lowest PCD in eyes with both myopia and open-angle glaucoma compared with eyes with glaucoma only and control eyes.
Future of imaging in myopia
The pathological elongation of the eye may be related to remodelling of the sclera associated with alterations of the biomechanical properties.85 One regulator of scleral extracellular matrix remodelling is the choroid.86 As such the focus on imaging in myopia needs to be directed towards these tissues and their biomechanical properties. Imaging the choroid and the sclera with optical technology is, however, difficult because the RPE and choroid are highly scattering.87 As such the choroid may be imaged with OCT systems working at wavelengths around 1060 nm,88 but the resolution is not sufficient to visualise details of the microvasculature or the cellular structure. As such it is currently difficult to classify choroidal layers and the choroidal scleral interface,88 but there is considerable need for a standardisation of choroidal segmentation and OCT-based definition of the layers to allow for comparison of existing data. Furthermore, the sclera is usually not visible using OCT and cannot be studied well in conjunction with the choroid in myopia.69
The limitations mentioned above for OCT-based choroidal imaging also hold true for OCTA. No standardised protocol has been established for segmentation. In addition, outcome parameters for OCTA have not clearly been defined. Some authors used analysis of flow voids or signal voids in the choriocapillaris to quantify the area that is covered by the microvasculature,89 90 but data in patients with myopia are limited.91 Different authors used, however, different image analysis approaches to quantify signal voids and no common protocol is currently available. Nonetheless, emerging reports suggest that understanding the blood supply and changes in vasculature from the anterior to the posterior segment of the myopic eye92–94 is important in understanding the disease.95
Higher ultrasound frequencies that are used in US biomicroscopy of the anterior segment do not have sufficient penetration depth to image the posterior pole of the eye.96 A future alternative may be photoacoustic imaging, which detects the waves generated by the absorption of pulsed laser light in tissue.97 In contrast to other optical imaging techniques, the contrast is solely based on absorption. The technique is of interest because it may fill the gap between OCT and US in terms of penetration depth. Indeed, photoacoustic imaging systems have been described that image the posterior pole of the eye in vitro and in animal models in vivo, which can also be used for angiography, measurement of oxygen saturation and pigment imaging.98 Disadvantages of photoacoustic imaging include moderate depth resolution, pure optical absorption sensing, need for contact detection with the ultrasound sensor and relatively long acquisition time. A photoacoustic imaging for posterior pole imaging in humans has not yet been realised.
Visualising and measuring the biomechanical properties of the eye in vivo are challenging. Several studies have proposed measurements of ocular rigidity based on non-invasive measurements,99 100 but none of these techniques have been used in patients with myopia. In the recent years there is a focus towards elastography approaches to study the biomechanical properties of ocular tissues either with OCT101 or with ultrasound.102 The principle of elastography is that an internal or an external force induces motion of tissue that is detected using imaging devices; thus, most in vivo work was directed towards the biomechanical properties of the cornea.103 104 In vivo imaging was so far only achieved by using the ocular pulse as internal excitation source, but extraction of biomechanical parameters was not achieved,105 106 while some in vitro work has been done using acoustic radiation force optical coherence elastography.107
Conclusion
In summary, as the prevalence of myopia and PM increases around the world, the need for accurate imaging and clinical interpretation will continue to intensify for the diagnosis, prognostication and evaluation of treatment modalities. It is important for clinicians to understand the current limitations and challenges of imaging the myopic eye, which affect clinical interpretation. The myopic eye in itself represents challenges with an irregular shape and anatomical distortion of the posterior segment layers, which affect evaluation of the images produced. Fortunately, recent advances especially in the field of 3D MRI and OCT now enhance the depth and provide wide-field imaging, vastly improving the imaging of the posterior segment and optic nerve even in PM. This may lead to better understanding of the pathogenesis of myopic degeneration and its sight-threatening complications such as mCNV and maculopathy. Improvements in ocular imaging in myopia may lead to further investigation in studying potential biomarkers for myopic progression or development of complications, for example, wide-field imaging detecting early peripheral retinal changes to prognosticate for retinal detachments, detailed OCT imaging of the macula to detect early macula changes to anticipate macula hole detachments or myopic CNV, or early myopic disc changes and peripapillary choroidal atrophy which may predict the risk of developing pathological changes in myopia. Newer technologies such as OCTA now allow for visualisation of choroidal vasculature with structure, giving new insights into the diseases, while OCT elastography may improve our understanding of the biomechanics in the cornea and sclera, which play a role in myopic progression and evaluating new modalities of treatment such as scleral cross-linking.
References
Footnotes
Correction notice Since this article was first published online, the author Donny V Hoang has been updated to Quan V Hoang.
Contributors All authors met the ICMJE criteria: (1) substantial contributions to conception and design, acquisition of data, or analysis and interpretation of data; (2) drafting the article or revising it critically for important intellectual content; and (3) final approval of the version to be published.
Funding This study was funded by Singapore Imaging Eye Network (SIENA) from the Singapore National Medical Research Council (NMRC).
Competing interests GCMC serves on the speaker bureau for Topcon and Zeiss. MA is a speaker for Zeiss, Nidek, Allergan, Santen and Johnson & Johnson Vision.
Patient consent for publication Not required.
Provenance and peer review Not commissioned; externally peer reviewed.
Data sharing statement Additional data can be obtained from the corresponding author.