Background/aims To correlate visual acuity in highly myopic eyes without macular disease with retinal and choroidal thickness as measured by spectral-domain optical coherence tomography (OCT).
Methods 60 eyes of 46 highly myopic patients (spherical equivalent ≥−6 D or axial length ≥26 mm) were studied in a clinical setting. Eyes with any clinical evidence of maculopathy or amblyopia were excluded. Eyes were imaged using the 3D-2000 OCT (Topcon Corporation, Tokyo, Japan). Two independent investigators manually measured: choroidal thickness at 500-μm intervals up to 2500-μm nasal and temporal to the fovea, subfoveal choroidal thickness, foveal thickness, outer nuclear layer and photoreceptors in addition to retinal pigment epithelium (RPE). Statistical analysis was performed.
Results Mean age was 45.9±17.9 years (range 18–99), mean best-corrected visual acuity (BCVA) LogMAR was 0.11±0.19 (range 0–1), mean axial length was 28.2±2.4 mm (range 26–35.3) and mean spherical equivalent was −12.05±5.02 D (range −6 to −26). Mean macular choroidal thickness was 157±84.6 μm (range 16.7–426.5), mean subfoveal choroidal thickness was 166±88.7 μm (range 13.5–486.5), mean foveal thickness was 221.1±30.3 μm (range 157.5–296), mean outer nuclear layer was 121.3±22.6 μm (range 74–191.5) and mean photoreceptors in addition to RPE was 99.5±10.8 μm (range 71.5–115.5). BCVA (LogMAR) negatively correlated with macular choroidal thickness (r=−0.371, p=0.003), subfoveal choroidal thickness (r=−0.358, p=0.004) and photoreceptors and RPE aggregate (r=−0.346, p=0.006).
Conclusions Subfoveal choroidal thickness, mean macular choroidal thickness and outer retinal thickness are the most important predictive factors of visual acuity in highly myopic eyes without macular pathology. Outer nuclear layer and foveal thickness are not related to visual acuity.
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High myopia is one of the leading causes of low vision in the world.1 ,2 Both genetic and environmental factors are involved in its aetiology.3 Developing countries have significantly higher rates of myopia, especially Asian countries, but it is estimated that 1% of the global population exhibits high myopia.3 ,4
Pathological studies show that highly myopic eyes have a significantly thinner retina, choroid and sclera than age-matched controls without myopia.5 ,6 Thicker foveal thickness and thinner full macular thickness have been described in myopic and in highly myopic eyes using optical coherence tomography (OCT),7–9 although Lim et al10 could not find any differences between averaged macular thickness and varying degrees of myopia. Axial length has been positively correlated with foveal thickness8–10 and negatively correlated with choroidal thickness.11–13
There is a hypothesis that relates visual acuity and retinal structure in high myopia. Scleral expansion, and secondary retinal expansion, occurs in high myopia, resulting in an increase in cone spacing, a subsequent reduction in neural sampling density, and ultimately a negative influence on the visual acuity of these eyes.6 ,14 ,15 Outer retinal layers in the centre of the fovea, studied with OCT systems, comprise four hyper-reflective bands, external limiting membrane (ELM), the ellipsoid section of the photoreceptors and two additional bands in the area extending from the contact outer segments of the photoreceptors with the retinal pigment epithelium (RPE).16 Disruption in these outer layers on OCT is highly suggestive of photoreceptor dysfunction and such findings correlate with visual prognosis after macula-off retinal detachment and macular holes successfully closed with surgery.17–19 Some studies have correlated choroidal thickness and visual acuity in highly myopic patients.11 ,13 ,20 ,21 Hayashi et al2 associated enlarging posterior staphyloma with a higher incidence of myopic maculopathy.
The aim of this report was to analyse the correlation between visual acuity in highly myopic eyes, without any grade of maculopathy, and retinal and choroidal thickness as measured with spectral-domain OCT (SD-OCT).
Materials and methods
A retrospective analysis was performed on 60 eyes of 46 highly myopic patients. High myopia was defined as a negative spherical equivalent (SE) equal to or greater than 6 dioptres (D) or an axial length equal to or greater than 26 mm. Approval for data collection and analysis was obtained from the Institutional Review Board of Vissum Corporación Alicante. The research adhered to the tenets set forth in the Declaration of Helsinki.
Best-corrected visual acuity (BCVA) was performed by a trained optometrist with Early Treatment Diabetic Retinopathy Study (ETDRS) charts at 4 m. Highly myopic eyes without myopic maculopathy on dilated fundus examination were included in the study. Eyes with focal or diffuse chorioretinal atrophy in the macular area, a history of choroidal neovascularisation, photodynamic therapy, anti-vascular endothelial growth factor therapy, retinal detachment, scleral buckling, pars-plana vitrectomy, macular hole, epiretinal membrane, vitreomacular traction syndrome, foveoschisis, diabetic retinopathy, amblyopia, venous/artery occlusion, any type of glaucoma or posterior uveitis were excluded.
The patients were imaged with Topcon 3D-2000 OCT (Topcon Corporation, Tokyo, Japan) at Vissum Corporación Alicante from February 2011 to December 2011, by the same investigator (IFM). The patients were imaged as part of routine clinical ophthalmic care. The scan pattern used on 3D-2000 OCT was a 6-mm line consisting of 1024 A-scans, reference position ‘Choroid’ and image averaging of 50. The reference position moves the zero-delay line behind the RPE, which added to the averaged images make for better visualisation of the choroid. This pattern facilitates the visualisation of deeper ocular structures, similar to the enhanced depth imaging mode in Heidelberg Spectralis and Zeiss Cirrus OCT systems.
Two independent observers using the calliper system provided by the software manually measured: (1) choroidal thickness, perpendicularly from the outer edge of the hyper-reflective RPE to the choroid–scleral junction at 500 µm intervals up to 2500 µm nasal and temporal to the fovea, using the average of these 11 measurements as the mean macular choroidal thickness, (2) subfoveal choroidal thickness, (3) foveal thickness (R1), measured from the hyper-reflective line corresponding to the internal limiting membrane to the inner edge of the hyper-reflective RPE, (4) outer nuclear layer (R2), defined as the distance from the border of the hyper-reflective band corresponding to the outer plexiform layer and the line ascribed to the ELM and (5) photoreceptors in addition to RPE (R3), measured from the hyper-reflective line corresponding to the ELM to the outer border of the RPE. The image used for the measurements was the one crossing the centre of the fovea, with less foveal thickness, to measure equal meridians in each patient (figure 1).
ETDRS visual acuities were transformed into logarithm of the minimum angle of resolution (LogMAR). Statistical analysis was performed with SPSS software package V.17 (SPSS, Inc, Chicago, Illinois, USA). Pearson correlation was used to correlate variables. Intraclass correlation coefficient was performed to compare inter-observer measurements. Statistical significance was considered at p<0.05.
The mean age of our study group was 45.9±17.9 years (SD) (range 18–99), 57.7% were women. Mean BCVA (LogMAR) was 0.11±0.19 (range 0–1), mean axial length was 28.2±2.4 mm (range 26–35.3) and mean SE was −12.05±5.02 D (range 6–26). Mean macular choroidal thickness was 157±84.6 μm (range 16.7–426.5), mean subfoveal choroidal thickness was 166±88.7 μm (range 13.5–486.5), mean foveal thickness (R1) was 221.1±30.3 μm (range 157.5–296), mean outer nuclear layer (R2) was 121.3±22.6 μm (range 74–191.5) and mean photoreceptors in addition to RPE (R3) was 99.5±10.8 μm (range 71.5–115.5).
BCVA (LogMAR) negative correlated with mean macular choroidal thickness (r=−0.371, p=0.003), mean subfoveal choroidal thickness (r=−0.358, p=0.004), and mean photoreceptors and RPE aggregate (r=−0.346, p=0.006). No correlation was found between BCVA and foveal thickness and between BCVA and outer nuclear layer thickness (table 1).
Simple regression analysis showed a negative correlation between mean macular choroidal thickness and subfoveal choroidal thickness with age (r=−0.326, p=0.0109 and r=−0.328, p=0.0103, respectively), axial length (r=−0.700, p<0.001 and r=−0.565, p<0.001, respectively) and SE (r=−0.598, p<0.001 and r=−0.5178, p<0.001, respectively). Photoreceptors and RPE aggregate thickness had a negative correlation with axial length (r=−0.381, p=0.002) and SE (r=−0.366, p=0.013). Macular choroidal thickness showed a positive correlation with the photoreceptors and RPE aggregate (r=0.462, p<0.001). No correlation was found between age and photoreceptors and RPE aggregate. Foveal thickness and outer nuclear layer thickness were not correlated with any of the variables studied (table 1).
Inter-observer correlation was 0.818 for the mean macular choroidal thickness, 0.737 for the subfoveal choroidal thickness, 0.863 for the retinal thickness (R1), 0.808 for mean outer nuclear layer (R2) and 0.722 for mean photoreceptors in addition to RPE (R3) with the intraclass correlation coefficient. The sclera–choroid junction could be visualised in all patients.
In this study, best-corrected ETDRS visual acuity in high myopic eyes without myopic maculopathy or any other retinal disorder was correlated with subfoveal choroidal thickness, macular choroidal thickness and the distance from the ELM to the outer RPE band measured by SD-OCT. A previous study21 with similar variables was recently published using two different myopic populations—one from New York City in the USA (35 eyes) and the other from Japan (110 eyes). This study found mean BCVA (LogMAR) of 0.19 and 0.07, respectively, mean ages of 57 and 46.8 years, and mean SE −10.9 and −9.2 D, respectively. In the New York data group, the authors reported that subfoveal choroidal thickness was 113.8 μm and the mean foveal retinal thickness was 189.8 μm. In the Japanese cohort, subfoveal choroidal thickness was 172.9 μm, while mean foveal thickness was 240 μm. The Japan group data were very similar to the data in this report: subfoveal choroidal thickness was 166 μm and mean foveal thickness was 221.1 μm.
Upon further analysis of the OCT data herein, a negative correlation between subfoveal and mean macular choroidal thickness and BCVA (LogMAR) is shown in our study (r=−0.371, p=0.003 and r=−0.358, p=0.004, respectively). As other authors have published, thinner choroidal thickness is associated with poorer visual acuity in high myopic eyes.11 ,13 ,20 ,21
With regard to the outer retinal layer, defined as photoreceptor layer thickness plus RPE thickness, measured from the ELM to the outer border of the RPE, a negative correlation was found between BCVA (LogMAR) and this parameter (r=−0.346, p=0.006), as occurred with mean macular and subfoveal choroidal thickness correlation. In the study by Nishida et al, the Japanese group found significant correlation between visual acuity and the inner segment to RPE aggregate thickness (r=−0.227, p=0.017), as in our data, but this correlation was not found in the New York cohort.21 High myopia as well as macular hole and retinal detachment surgery are diseases wherein the outer retina layers, from ELM to the basal border of RPE, are the retinal main predictor factors for visual prognosis.17–19 From a pathological point of view, this measurement corresponds with the inner (including ellipsoid and myoid portion of the inner segments) and the outer segments of photoreceptors and RPE, structures that transform the light into nerve impulse.22
Photoreceptors and RPE aggregate thickness had a statistical correlation with all the variables measured, mean choroidal thickness, subfoveal choroidal thickness and foveal thickness, but not with age (table 1). The negative correlation with axial length (r=−0.381, p=0.002) and with SE (r=−0.366, p=0.013) makes us conclude that while axial enlargement of the high myopic eye implies an outer retinal stretching and subsequent thinning, we could not confirm this in our measurements of foveal and outer nuclear layer thickness.
Retinal thickness (defined from internal limiting membrane to the inner edge of the RPE) and outer nuclear layer thickness did not show a correlation with any other studied variable, even BCVA. The outer nuclear layer thickness did correlate with overall retinal thickness (r=0.8785, p<0.0001), but this finding has little import because this layer makes up the majority of the retinal foveal thickness. The outer nuclear layer includes the photoreceptors nucleus and it would be expected to have an important correlation in BCVA. These results are similar to the study by Nishida et al.21 On the other hand, other authors have correlated outer nuclear layer with visual acuity in age related macular degeneration and resolved central serous chorioretinopathy.23 ,24
As many other authors also report,11–13 ,20 ,21 ,25 ,26 our data show a negative correlation between mean macular and subfoveal choroidal thickness with age (r=−0.326, p=0.0109 and r=−0.328, p=0.0103, respectively), axial length (r=−0.700, p<0.001 and r=−0.565, p<0.001, respectively) and SE (r=−0.598, p<0.001 and r=−0.5178, p<0.001, respectively). Macular choroidal thickness and subfoveal choroidal thickness showed a positive correlation with the photoreceptors and RPE aggregate (table 1), so as the outer retina thickness increases the choroid is thicker. It remains to be established whether the outer retina determines a thicker choroid due to an increased energy consumption, or vice versa, a thicker choroid means more and better outer retinal metabolism and thus increased cellular survival.
This study has several limitations: its retrospective design, and manual measurements were made because there is no automated software commercially available to quantify choroidal thickness; however, the good level acquired in the intraclass correlation coefficient and the good reproducibility shown with Topcon devices and others systems27 ,28 make our measurements reliable; visual acuity has been compared with choroidal thickness only in a horizontal scan and not in a vertical one; we have not studied the RPE status. However, patchy or diffuse chorioretinal atrophy was an exclusion criterion. Futures studies comparing retinal/choroidal thickness and autofluorescence images would enhance these results.
In conclusion, this study demonstrates that subfoveal choroidal thickness, mean macular choroidal thickness and outer foveal thickness (at the same time dependent of the axial length), and not outer nuclear layer and foveal thickness, are the most important predictor factors for visual acuity in highly myopic eyes without macular pathology. The mechanism of how increasing axial length affects choroidal and external retinal thickness remains inadequately understood.
Contributors IFM, JRM, JSD, JMRM: Substantial contributions to conception and design, acquisition of data, or analysis and interpretation of data; drafting the article or revising it critically for important intellectual content; final approval of the version to be published.
Funding This study has been supported in part by a grant of the Spanish Ministry of Health, Instituto de Salud Carlos III, Red Temática de Investigación Cooperativa en Salud ‘Patología ocular del envejecimiento, calidad visual y calidad de vida’ (RD07/0062/0019). This study has been supported in part by a Research to Prevent Blindness. Unrestricted Grant to the New England Eye Center/Department of Ophthalmology, Tufts University School of Medicine and the Massachusetts Lions Clubs.
Competing interests Jay S Duker, MD, receives research support from Carl Zeiss Meditech, Inc., Optovue, Inc. and Topcon Medical Systems, Inc.
Patient consent Obtained.
Ethics approval Institutional Review Board of Vissum Corporación Alicante.
Provenance and peer review Not commissioned; externally peer reviewed.