Characteristics of the fundus and optical coherence tomography angiography metrics in myopic patients with myelinated retinal nerve fibers

Abstract

Aims

To investigate the fundus characteristics and macular optical coherence tomography angiography (OCTA) metrics in patients with myelinated retinal nerve fibers (MRNF) and to identify the associations among myopic parameters, fundus metrics, and OCTA metrics.

Methods

The single-center case-control study included 15 patients with monocular MRNF and 15 patients without MRNF, matched for age, affected eyes’ spherical equivalent error (SER), and axial length (AL) between May 2021 and December 2021. Fundus features, including the entire MRNF area (Area1), the denser MRNF area (Area2), and the shortest distance from the fovea to the MRNF border (D_f−m), along with ocular parameters, including SER, AL, best corrected visual acuity (BCVA), and OCTA metrics at the fovea, including choroidal (ChT) and retinal (ReT) thicknesses at the fovea, the foveal avascular zone area (FAZ), foveal avascular zone perimeter (FAZP), FAZ-circularity index (FAZ-CI), and foveal vessel density in a 300-µm wide region (FD-300), were assessed.

Results

The SER, AL, and BCVA were significantly different, and the ChT was thinner in the affected eyes than in the contralateral eyes. Compared with matched eyes, affected eyes had reduced BCVA and thinner ReT. In the affected eyes, both Area1 and Area2 were negatively correlated with SER (r₁ = -0.84, r₂ = -0.65), △SER (r₁ = -0.86, r₂ = -0.61), ReT at the vertical superior 3 mm (VS) (r₁ = -0.78, r₂ = -0.67), and ChT_VS (r₁ = -0.64, r₂ = -0.62), and positively correlated with AL (r₁ = 0.82, r₂ = 0.52) and BCVA (r₁ = 0.54, r₂ = 0.59). D_f−m was negatively correlated with BCVA (r = -0.57).

Conclusion

The presence of MRNF affects BCVA and ReT at the fovea. The area of the MRNF, as well as the distance from the MRNF to the fovea, are closely associated with the affected eyes’ BCVA, SER, AL, and the degree of anisometropia.

Supplementary Information

The online version contains supplementary material available at 10.1186/s12886-024-03733-x.

Introduction

Myelinated retinal nerve fibers (MRNF) were first described in 1856 by Virchow [1]. They are congenital retinal lesions that present as grey or white patches with feathery edges in the inner retinal layer. Their prevalence has been reported as 0.02% [2], 0.4% [3], 0.57% [4], and 0.98% [5] in the general population.

Patients with MRNF and myopia often present with axial myopia [6]. Affected eyes tend to have a longer axial length (AL) and more severe myopia than eyes without MRNF [6]. MRNF have been postulated to affect visual development and stimulate axial elongation [7]. In addition, eyes with widespread MRNF may present higher degrees of myopia and decreased best corrected visual acuity (BCVA) [1, 8]. However, the associations between the area of MRNF and myopic parameters such as spherical equivalent error (SER), AL, and BCVA have not been adequately evaluated.

One proposed mechanism of myopia development involves the potential role of altered choroidal microvasculature and reduced choroidal blood flow in the development of myopia [9]. Myopia-related visual signals can reduce choroidal capillary patency and blood flow, reduce the supply of oxygen and nutrients to the neighbouring avascular sclera, and cause scleral extracellular matrix remodeling [9]. The dense and widespread MRNF may compress the retinal and choroidal vasculature, resulting in the development of myopia. Optical coherence tomography angiography (OCTA) is an advanced, non-invasive imaging technology capable of providing detailed information on the microvascular metrics of the retina and choroid. OCTA can visualize the macular microvasculature. OCTA is an instrument that can successfully visualize the retinal and choroidal microvascular network in many ocular and general diseases [10–13] Little is known about OCTA metrics in patients with MRNF.

We performed this study to investigate fundus and OCTA metrics and the associations among fundus metrics, OCTA metrics, and myopic parameters in patients with MRNF.

Methods

Study design

This was a single-center study. Written informed consent was obtained from all recruited participants or their guardians before their participation in the study. All patients were treated in accordance with the tenets of the Declaration of Helsinki. This study was conducted in accordance with the guidelines of the Ethics Committee of the Eye and ENT Hospital of Fudan University, Shanghai, China.

Participant selection

Fifteen consecutive patients with MRNF presenting between May 2021 and December 2021 at the Department of Ophthalmology of Fudan University Eye & ENT Hospital were included in this study. Fifteen participants without MRNF were matched based on age, SER, and AL of affected eyes.

The exclusion criteria were as follows: participants with a history of ocular surgery/trauma, smoking, or systemic diseases (hypertension, diabetes, etc.) that may affect retinal or choroidal blood flow.

Clinical examinations

Each patient underwent a comprehensive ophthalmic examination, which included slit-lamp evaluation, measurement of intraocular pressure (IOP), evaluation of uncorrected distance visual acuity (UDVA) and BCVA using standard logarithmic visual acuity charts, and manifest refraction. AL, corneal curvature, and anterior chamber depth (ACD) were measured in each eye using swept-source optical coherence tomography (IOL Master 700, Carl Zeiss Meditec AG, Jena, Germany). A cover test and alternating cover test were used to detect the presence of strabismus. Each patient underwent an interview, which included assessments of demographic data and medical history, when available.

Acquisition of fundus images

An ultra-wide-field fundus camera, Zeiss Clarus 500 (Carl Zeiss Meditec, Jena, Germany), which utilizes true colors, was used to acquire fundus images. The single wide-field mode, which achieves a 133-degree field, as well as the montage mode with four images that achieve an approximately 220-degree field, were used to obtain a full view of the MRNF. For eyes with MRNF, the border of MRNF on fundus images was delineated, and the area covered by MRNF was measured using the ImageJ Pro software (version 6.0.0.260, Media Cybernetics, Inc., Bethesda, USA) (Supplemental Fig. 1). The entire area of the MRNF was defined as Area1. Considering that MRNF thickness may affect myopic parameters and OCTA metrics, we further defined the area covering the denser MRNF as Area2. The shortest distance from the fovea to the border of the MRNF was defined as the D_f−m. The MRNF measurements were performed by two experienced doctors (WMY and RYW), and the average of the measurements was calculated.

Image acquisition of OCTA

The SS-OCT/OCTA system (VG100; SVision Imaging, Henan, China) was used; it functions near 1050 nm and features the following specifications: scan speed, 100,000 A-scans per second; wide-field, 56°; and imaging depth, 2.7 mm (in tissue). The axial and lateral resolutions were 5 μm and 13 μm, respectively. An eye-tracking system based on an integrated confocal scanning laser ophthalmoscope was used to eliminate eye-motion artifacts.

Structural OCT of the macular region was performed using 18 radial scan lines centered on the fovea. Each scan line, which was generated by 2048 A-scans, was 12 mm long. Sixteen B-scans were obtained on each scan line and automatically averaged to improve the signal-to-noise ratio [14]. Vertical scans were used to analyze the choroidal thickness. The choroid in the SS-OCT images was defined as the zone from the retinal pigment epithelium–Bruch’s membrane complex to the choroid-sclera interface. Each OCTA image was corrected for image magnification based on AL with Bennett’s formula using integral manufacturer-developed software.

After segmentation, the choroidal and retinal thicknesses at the fovea were defined as the ChT and ReT, respectively. Choroidal and retinal thicknesses at the vertical superior 3 mm centered on the fovea were defined as ChT_VS and ReT_VS, respectively. Similarly, choroidal and retinal thicknesses at the vertical inferior 3 mm were defined as ChT_VI and ReT_VI, respectively.

For angiography, a raster scan mode of 512 horizontal B-scans covering an area of 3 × 3 mm centered on the fovea was used. Each B-scan contained 512 A-scans, which were repeated four times and averaged. The foveal avascular zone (FAZ) area, foveal avascular zone perimeter (FAZP), FAZ-circularity index (FAZ-CI), and foveal vessel density in a 300-µm wide region (FD-300) were automatically analyzed.

Statistical analysis

Data were analyzed with Stata13.0 (StataCorp, Texas, USA) and reported as mean ± standard deviation (SD) or medians with interquartile ranges. The distribution was examined using the Shapiro–Wilk test. Paired t-tests or Wilcoxon signed-rank tests were used to evaluate the interocular differences between fellow eyes for ocular biometrics and OCTA parameters. Correlations among myopic variables (BCVA, SER, △SER [defined as the difference in SER between affected and contralateral eyes], and AL), fundus parameters, and OCTA parameters were examined using the Pearson correlation test and expressed as the Pearson correlation coefficient. Furthermore, we carried out univariate linear regression analysis, with the fundus metrics (Area1, Area2, and D_f−m) as independent variables and those myopic parameters and OCTA metrics that were significantly correlated with the fundus metrics in Pearson correlation analysis as dependent variables. The regression analysis results were expressed as the regression coefficient beta (β) and the 95% confidence interval (CI) of β. The statistical significance level was set at P < 0.05.

Results

Patient characteristics

Demographic characteristics are presented in Table 1. Fifteen participants with MRNF (male/female, 4/11) and 15 participants without MRNF (male/female, 7/8) were included in the study (P = 0.45). The mean age was 24.3 ± 13.1 years (range, 7 to 51 years) and 24.7 ± 12.5 years (range, 8 to 50 years), respectively (P = 0.17).

Table 1.

Characteristics of the study participants

	Eyes with MRNF (n = 15)	Contralateral eyes without MRNF (n = 15)	Control eyes (n = 15)	P #	P*
Spherical error	-9.17 ± 6.13	-3.33 ± 3.70	-9.37 ± 5.94	0.003	0.45
range	-20.75, 0.00	-12.00, 1.50	-21.00, 0.00
Cylindrical error	-2.00 (-2.25, -1.00) †	-1.13 ± 0.75	-1.55 ± 1.10	0.04	0.53
range	-5.50, 0.00	-2.50, 0.00	-4.25, -0.25
SER	-10.10 ± 6.36	-3.90 ± 3.94	-10.14 ± 6.11	0.002	0.80
range	-21.25, 0.00	-13.25, 0.75	-21.5, -0.13
BCVA, logMAR	0.40 (0, 0.7) †	-0.02 ± 0.05	0.04 ± 0.09	0.002	0.01
range	-0.08, 1.30	-0.18, 0.00	0.00, 0.30
IOP, mmHg	13.20 ± 2.80	13.36 ± 3.08	15.27 ± 2.79	0.74	0.05
range	10.0, 19.9	9.0, 19.0	12.0, 20.5
Axial length, mm	27.65 ± 2.64	25.22 ± 1.51	27.47 ± 2.42	0.003	0.58
range	23.39, 32.91	23.14, 28.33	24.38, 33.1
Corneal K readings, D	42.78 ± 1.76	42.87 ± 1.87	43.85 ± 1.53	0.46	0.11
range	39.68, 45.10	39.38, 45.55	41.45, 46.10
CCT, µm	560.5(517.0,566.0)†	545.5(511.8,564.5) †	530.5 ± 37.9	0.04	0.36
range	433, 584	430, 574	466, 588
ACD, mm	3.46 ± 0.26	3.49 ± 0.27	3.41 ± 0.26	0.11	0.69
range	2.88, 3.77	2.93, 3.84	2.99, 3.94
Area1, (pixel)×104	137.15 ± 152.04	-
Range	4.60, 441.22
Area2, (pixel)×104	43.86 ± 38.09	-
range	4.29, 142.83
Df−m, µm	399.77 ± 219.06	-
range	0, 728.87

#Comparison between eyes with MRNF and contralateral eyes without MRNF

*Comparison between eyes with MRNF and control eyes

†Median (P25–P75)

MRNF = Myelinated Retinal Nerve Fiber; BCVA = Best Corrected Visual Acuity; IOP = Intraocular Pressure; CCT = Central Corneal Thickness; ACD = Anterior Chamber Depth; SER = Spherical Equivalent Error

Each patient with MRNF had one affected eye and a contralateral unaffected eye. Four of the 15 affected eyes were right eyes. None of the patients had any other accompanying congenital systemic abnormalities. Among the 15 affected eyes, nine had amblyopia. All unaffected eyes had a BCVA of ≤ 0 logMAR. None of the patients had any concomitant strabismus.

Differences in manifest refraction and biometric parameters

Compared with the contralateral eyes, spherical error, cylindrical error, SER, and BCVA (logMAR) were worse in the affected eyes (all P < 0.05), while the AL was significantly greater (P = 0.003) and the CCT was significantly lower (P = 0.04). No statistically significant differences were found in anterior corneal K readings or ACD (P = 0.46, P = 0.11, respectively). (Table 1)

Compared with the matched eyes of control participants, eyes with MRNF had reduced BCVA (logMAR) (P = 0.01) and no statistically significant differences were detected in other parameters (all P > 0.05). (Table 1)

Characteristics of MRNF in fundus images

Data for Area1, Area2, and D_f−m are presented in Table 1. The MRNF in all eyes were directly connected to the optic disc (15/15 eyes, 100%). The MRNF involved four, three, two, and one quadrant in nine (60%), two (13.3%), three (20%), and one (6.7%) eye, respectively. In twelve eyes (80%), MRNF exhibited a greater area in two superior quadrants than in two inferior quadrants. Eight eyes (53.3%) had MRNF surrounding the optic disc. (Fig. 1).

Fig. 1.

Fundus images of the 15 eyes with myelinated retinal nerve fibers

Differences in OCTA metrics

The ChT, ChT_VS, ChT_VI, and ReT_VS were thinner in the affected eyes than in the unaffected eyes. No significant differences were found in the FAZ, FAZP, FAZ-CI, FD-300, ReT, or ReT_VI between the affected and unaffected eyes. (Table 2).

Table 2.

OCTA metrics of the study participants

	Eye with MRNF (n = 15)	Contralateral eyes without MRNF (n = 15)	Control eyes (n = 15)	P #	P*
FAZ, mm2	0.31 ± 0.14	0.35 ± 0.13	0.37 ± 0.19	0.21	0.19
FAZP, mm	2.36 ± 0.59	2.54 ± 0.44	2.51 ± 0.69	0.17	0.11
FAZ-CI	0.68 ± 0.09	0.68 ± 0.09	0.68 ± 0.11	0.98	0.84
FD-300	42.74 ± 5.39	44.01 ± 5.28	39.81 ± 4.41	0.42	0.06
ReT, µm	206.27 ± 26.93	216 ± 15.49	227.21 ± 27.50	0.08	0.04
ChT, µm	176 (149, 213)†	299.73 ± 84.18	221.64 ± 92.38	0.001	0.07
ReT_VI, µm	208 (162, 232) †	260.2 ± 12.59	242.86 ± 37.60	0.1	0.85
ChT_VI, µm	216.67 ± 79.24	281.87 ± 75.96	226.14 ± 95.51	0.008	0.23
ReT_VS, µm	161 (125, 264) †	287(275, 293) †	269.14 ± 15.08	0.01	0.04
ChT_VS, µm	203.87 ± 113.90	280(243, 331) †	252.21 ± 102.21	0.003	0.07

#Comparison between eyes with MRNF and contralateral eyes without MRNF

*Comparison between eyes with MRNF and control eyes

†Median (P25–P75)

FAZ = Foveal Avascular Zone; FAZP = Foveal Avascular Zone Perimeter;

FAZ-CI = FAZ-circularity index; FD-300 = Foveal vessel density in a 300 μm wide region around FAZ; ReT = Foveal Retinal Thickness; ChT = Foveal Choroidal Thickness; ReT_VI = Retinal Thickness at Vertical Inferior 3 mm around Fovea; ChT_VI = Choroidal Thickness at Vertical Inferior 3 mm around Fovea; ReT_VS = Retinal Thickness at Vertical Superior 3 mm around Fovea; ChT_VS = Choroidal Thickness at Vertical Superior 3 mm around Fovea

The ReT and ReT_VS were thinner in the eyes with MRNF than in the matched eyes in control participants. No significant differences were found in other parameters. (Table 2)

Correlations among myopic parameters, MRNF, and OCTA in eyes with MRNF

In the affected eyes, both Area1 and Area2 were negatively correlated with SER (r_area1 = -0.84, r_area2 = -0.65), △SER (r_area1 = -0.86, r_area2 = -0.61), ReT_VS (r_area1 = -0.78, r_area2 = -0.67), and ChT_VS (r_area1 = -0.64, r_area2 = -0.62), and positively correlated with AL (r_area1 = 0.82, r_area2 = 0.52) and BCVA (r_area1= 0.54, r_area2 = 0.59). D_f−m was negatively correlated with BCVA (r = -0.57). (Table 3).

Table 3.

Pearson’s correlations among the fundus metrics, myopic parameters, and OCTA metrics in the affected eyes

	Area1, (pixel)×103	Area2, (pixel)×103	Df−m
SER	-0.84‡	-0.65†	0.38
△SER	-0.86‡	-0.61*	0.10
AL	0.82‡	0.56*	-0.18
BCVA	0.54*	0.59*	-0.57*
FAZ, mm2	-0.03	-0.36	0.48
FAZP, mm	-0.31	-0.57	0.47
FAZ-CI	0.31	0.19	0.19
FD-300	-0.49	-0.34	0.01
ReT, µm	-0.09	0.06	-0.18
ChT, µm	-0.49	-0.45	0.39
ReT_VI, µm	-0.22	-0.25	-0.04
ChT_VI, µm	-0.37	-0.36	0.31
ReT_VS, µm	-0.78‡	-0.67†	0.41
ChT_VS, µm	-0.64*	-0.62*	0.50

*P < 0.05; ^†P < 0.01; ^‡P < 0.001

SER = Spherical Equivalent Error; AL = Axial Length; BCVA = Best Corrected Visual Acuity; FAZ = Foveal Avascular Zone; FAZP = Foveal Avascular Zone Perimeter; FAZ-CI = FAZ-circularity index; FD-300 = Foveal vessel density in a 300 μm wide region around FAZ; ReT = Foveal Retinal Thickness; ChT = Foveal Choroidal Thickness; ReT_VI = Retinal Thickness at Vertical Inferior 3 mm around Fovea; ChT_VI = Choroidal Thickness at Vertical Inferior 3 mm around Fovea; ReT_VS = Retinal Thickness at Vertical Superior 3 mm around Fovea; ChT_VS = Choroidal Thickness at Vertical Superior 3 mm around Fovea

Linear regression showed that larger Area1 and Area2 were significantly associated with worse SER (β_area1 = -0.035, 95% CI: -0.049, -0.022, P < 0.001; β_area2 = -0.109, 95% CI: -0.185, -0.033, P = 0.009), AL (β_area1 = 0.014, 95% CI: 0.008, 0.020, P < 0.001; β_area2 = 0.039, 95% CI: 0.005, 0.073, P = 0.029), and BCVA (β_area1 = 0.0016, 95% CI: 0.0001, 0.0031, P = 0.036; β_area2 = 0.0071, 95% CI: 0.0013, 0.0128, P = 0.020). (Table 4).

Table 4.

Univariate regression analysis of myopic parameters and fundus metrics in the affected eyes

	SER		AL		BCVA		ReT_VS		ChT_VS
	Correlation Coefficient (95%CI)	P Value	Correlation Coefficient (95% CI)	P Value	Correlation Coefficient (95% CI)	P Value	Correlation Coefficient (95% CI)	P Value	Correlation Coefficient (95% CI)	P Value
Area1	-0.035 (-0.049,-0.022)	< 0.001	0.014 (0.008, 0.020)	< 0.001	0.0016 (0.0001,0.0031)	0.036	-0.381 (-0.566, -0.195)	0.001	-0.477 (-0.823, -0.131)	0.011
Area2	-0.109 (-0.185,-0.033)	0.009	0.039 (0.005,0.073)	0.029	0.0071 (0.0013,0.0128)	0.020	-1.306 (-2.181, -0.430)	0.007	-1.858 (-3.262, -0.454)	0.013

SER = Spherical Equivalent Error; AL = Axial Length; BCVA = Best Corrected Visual Acuity; CI = Confidence Interval; ReT_VS = Retinal Thickness at Vertical Superior 3 mm around Fovea; ChT_VS = Choroidal Thickness at Vertical Superior 3 mm around Fovea; CI = Confidence In

Regarding the relationship between fundus metrics and OCTA, larger Area1 and Area2 were significantly associated with thinner ReT_VS (β_area1 =-0.381, 95% CI: -0.566, -0.195, P = 0.001; β_area2 =-1.306, 95% CI: -2.181, -0.430, P = 0.007) and ChT_VS (β_area1 = -0.477, 95% CI: -0.823, -0.131, P = 0.011; β_area2 = -1.858, 95%CI: -3.262, -0.454, P = 0.013). (Table 4) Additionally, shorter D_f−m was significantly associated with worse BCVA (β = -0.0012, 95% CI: -0.0022, -0.0002, P = 0.026).

Correlations among myopic parameters and OCTA metrics

In the affected eyes, SER was positively correlated with ChT (r = 0.64), ReT_VS (r = 0.75), and ChT_VS (r = 0.73). AL was negatively correlated with ChT (r = -0.67), ReT_VS (r = -0.72), and ChT_VS (r = -0.76). BCVA was negatively correlated with ChT (r = -0.54), ReT_VS (r = -0.64), and ChT_VS (r = -0.71). In the unaffected eyes, SER was positively correlated with ChT (r = 0.55) and ChT_VS (r = 0.64). AL was negatively correlated with ChT (r = -0.59) and ChT_VS (r = -0.69). (Supplemental Table 1)

Discussion

Myelination typically progresses from the chiasm to the optic nerve from the eighth month of gestation until birth and then stops at the lamina cribrosa [1]. The pathophysiology of MRNF remains unclear. Several factors, such as the structure of the lamina cribrosa and plasma proteins, have been proposed to inhibit myelination in the normal human retina [15, 16]. MRNF are usually present unilaterally in most cases [5]. Previous studies have reported the potential progression of these lesions [3, 17]; their findings on autofluorescence, fluorescein angiographic images [16], or OCT [17]; and their natural history [17]. With the advent of new examination equipment, doctors have more means of gaining a deeper understanding of such diseases. The present study is the first to investigate the fundus using true-color, ultra-wide-field fundus images and OCTA metrics, and to identify the associations among the area and location of MRNF with myopic parameters and OCTA metrics.

In this study, eyes with MRNF exhibited reduced BCVA compared to control eyes matched for age, SER, and AL. MRNF are often associated with high myopia, anisometropia, and amblyopia. Vision loss may occur due to anisometropia and amblyopia, or secondary to structural abnormalities of the retina and/or optic nerve [1]. In accordance with our study, Kee et al. [18] investigated the visual prognosis of amblyopia associated with anisometropia and MRNF in 12 children (mean age: 4.2 years, range: 2.1–8.6). They found that the amount of anisometropia and the area of myelination differed between groups with different BCVA. In addition, our study found that BCVA was strongly positively correlated with the area of MRNF and negatively correlated with D_f−m, indicating that the area of MRNF and the distance of the MRNF to the macula affect patients’ visual prognosis. This explains why, in some cases, although aggressive treatments were applied, many patients did not respond well to treatment [1]. These results suggest that doctors should set realistic expectations among patients for the final recovery of vision.

In addition to the new insights into the associations between MRNF and BCVA, our study also investigated the correlations between MRNF and △SER, SER, and AL. In the present study, the area and location of MRNF were also correlated with patients’ SER, AL, and △SER. The larger the area of the MRNF, the worse the SE, AL, and △SER. Regarding △SER, in contrast to our findings, Kee et al. [18] found no statistical correlation between the extent of myelination and the amount of anisometropia. The underlying reason contributing to these discrepancies may be that we used ultra-wide-field images to calculate the full area of MRNF, while Kee et al. used clock hours of retinal involvement. Clarus is an ultra-wide-field fundus camera that obtains approximately 133° in a single capture and 220° in a montage mode, which makes it possible to obtain a full view of MRNF in comparison with traditional fundus cameras.

The area of MRNF was also found to be associated with patients’ ReT_VS and ChT_VS, but not with foveal ReT, ChT, ReT_VI, or ChT_VI. The underlying reason may be that MRNF were more often distributed at the superior and inferotemporal areas of the optic disc rather than other areas. Consistent with our results, Straatsma et al. [5] reported a similar result of MRNF distribution in 42 patients with MRNF. The MRNF-involved retina tends to be thinner [16], which results in compression of the choroid and causes a reduction in choroid thickness.

Knowledge of the microvascular metrics of the retina and choroid can help differentiate it from other intraretinal lesions or elucidate the mechanism underlying the association of axial myopia with MRNF. Previous studies reported that there was no significant difference in FAZ between the myopia and the non-myopia groups in patients without MRNF [19, 20]. In the present study, we did not find any statistical difference in FAZ parameters, including FAZ, FAZP, FAZ-CI, and FD-300, between the eyes with and without MRNF. However, we did not evaluate microvessel density metrics other than FAZ parameters because thick MRNF could result in intense posterior shadowing with loss of structural and vascular information of the retina and choroid.

As for choroidal thickness, the foveal ChT, ChT_VI, and ChT_VS were significantly thinner in the affected eyes. Two reasons may have contributed to this finding. First, the thickened MRNF-involved retina compressed the choroid, resulting in a decrease in choroid thickness. Second, affected eyes tend to show axial high myopia, and the progression of myopia has been suggested to be associated with elongation of the eyeball, mechanically stretching the retina and causing a reduction in the retinal nerve fiber layer thickness, retinal microvascular density, and choroid thickness [19, 21]. Consistent with these findings, the SER and AL were closely correlated with ChT in the unaffected eyes in our study (mean SER: -3.90 ± 3.94 D; range, -13.25 to 0.75 D).(Table 3) Therefore, to distinguish the factor causing thinning of the choroid, the ideal study design would include other age-, sex-, and SER-matched controls. However, age- and sex-matched children with super-high myopia are rare in clinics, making them very difficult to recruit. Thus, further studies with better designs are necessary.

This study had two limitations. First, the sample size was small, which may have limited the precision of the results. However, the prevalence of patients with MRNF is very low; therefore, it is difficult to include a large number of patients. Second, MRNF could be isolated, or associated with myopia, anisometropia, amblyopia syndrome, optic nerve diseases [22, 23], and systemic diseases [1]. None of the patients in the present study had systemic diseases, so the findings of the present study could not be extrapolated to other situations.

In summary, the findings of the present study suggest that the presence of MRNF impacts BCVA and ReT at the fovea, especially ReT_VS. The area of MRNF, as well as the distance from the MRNF to the fovea, are closely associated with the affected eyes’ BCVA, SER, AL, the amount of anisometropia, ReT_VS, and ChT_VS. These findings could help doctors judge the visual prognosis of patients and elucidate the mechanism underlying axial myopia associated with MRNF in the future.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Author contributions

Weiming Yang and Xingtao Zhou had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysisConcept and design: Xingtao Zhou, Meiyan LiAcquisition, analysis, or interpretation of data: All authorsDrafting of the manuscript: Weiming Yang, Meiyan Li, Ruoyan WeiCritical revision of the manuscript for important intellectual content: All authorsStatistical analysis: Meiyan Li, Chen Huang, Ruoyan WeiObtained funding: Xingtao Zhou, Meiyan Li, Ruoyan WeiAdministrative, technical, or material support: Xingtao Zhou and Meiyan LiSupervision: Xingtao Zhou and Meiyan Li.

Funding

(1) Shanghai Rising-Star Program (21QA1401500); (2) National Natural Science Foundation of China (82371091, 82301251); (3) Construction of a 3D digital intelligent prevention and control platform for the whole life cycle of highly myopic patients in the Yangtze River Delta (21002411600); (4) Natural Science Foundation of Shanghai (23ZR1409200); (5) Project of Shanghai Xuhui District Science and Technology (2020-015, XHLHGG202104); (6) Shanghai Yangfan Project (23YF1445300).

Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request at doctzhouxingtao@163.com.

Declarations

Ethical approval

The study adhered to the Declaration of Helsinki and was approved by the Ethics Committee of the Eye and ENT Hospital of Fudan University (No.2013014). Written informed consent was obtained from all recruited participants or their guardians before their participation in the study.

Commercial relationships disclosures

None.

Competing interests

The authors declare no competing interests.