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. 2026 Jul 8;26:614. doi: 10.1186/s12886-026-05108-w

Phototherapeutic Keratectomy for epithelial basement membrane dystrophy: long-term observation in Chinese patients

Manrong Yu 1,2,3,#, Minjie Chen 1,2,3,#, Jinhui Dai 4,✉
PMCID: PMC13628794  PMID: 42420929

Abstract

Objective

To evaluate the short-term and long-term efficacy of Phototherapeutic Keratectomy (PTK) in treating corneal epithelial basement membrane dystrophy (EBMD) and to investigate the factors that influence its outcomes.

Methods

This retrospective case series with prospective outcome evaluation analyzed all patients undergoing PTK for EBMD by a single surgeon at Eye & ENT hospital of Fudan University. Participants unresponsive to pharmacological therapy with recurrent ocular pain from epithelial erosions underwent PTK. Pre- and postoperative analysis included symptomatology, treatments, refractive status, visual acuity and corneal densitometry (CD).

Results

Medical records of 40 patients aged 42.0 ± 13.5 years old were analyzed, with a follow-up duration ranging from 12 to 150 months. The mean ablation depth was 23.1 ± 9.7 μm, with a range of 6–40 μm. PTK significantly alleviated erosion symptoms and reduced the need for medication in both the short and long term postoperatively. A single erosive event was observed in one patient, but no patient warrant reoperation. Best Corrected Visual Acuity (BCVA) improved significantly after surgery, with 87.5% of patients achieving a BCVA of 20/20. No significant hyperopia or myopic shift was observed. CD values at center of the anterior and central strata decreased significantly after PTK (p < 0.05).

Conclusion

PTK with ablation depth of around 25 μm is a simple and feasible surgical method that effectively mitigates discomfort symptoms in patients with EBMD, minimizes medication reliance, and demonstrates safety and efficacy in long-term follow-up.

Keywords: Phototherapeutic keratectomy, Epithelial basement membrane dystrophy, Corneal densitometry

Introduction

Epithelial basement membrane dystrophy (EBMD), also known as Map-Dot-Fingerprint Dystrophy (MDF), is one of the most prevalent forms of recurrent corneal erosions (RCE). Patients with EBMD frequently suffer from an acute onset of pain, irritation and photophobia. Additionally, most patients report symptoms such as lacrimation, blurred vision, and a foreign body sensation. Conventional treatments of EBMD, including the use of artificial tears or lubricants, therapeutic contact lens, epithelial debridement, or a combination of these methods, are often inadequate. Studies indicate that 18–40% of patients continue to experience recurrences [1].

The pathogenesis of RCE was reported to involve an abnormal adhesion between the corneal epithelium and stroma [2–4], resulting from defects in hemidesmosomes and poor anchoring of collagen fibrils [5, 6].

Phototherapeutic Keratectomy (PTK) has been used in the treatment of RCE for more than 20 years [4, 7]. The therapeutic principle behind the partial ablation of the Bowman’s layer in RCE treatment may involve the removal of basal membrane debris to create a clean surface for epithelium cell migration. This process also aims to facilitate the development of a new hemi-desmosome adhesion complex and new anchoring fibrils formation. As a result, this approach strengthens the adhesion of basal epithelial cells to the underlying tissue [8, 9].

When eyes with RCE do not respond to conventional treatments, surgical interventions become a consideration. The treatment of PTK involves the ablation of both basement membrane and Bowman’s layer, with the ablation depths ranging between 3 and 100 μm. However, complications are reported including haze, scar formation, hyperopic shift, and even keratectasia, with a positive correlation to the depth of corneal ablation [10–15]. Recently, less invasive methods have been developed, shallow ablation techniques that maintain tissue removal at a depth of approximately 5 μm [16], thereby leaving part of Bowman’s layer intact [17]. The reported success rates for shallow ablation PTK varied from 76.92% to 84.6%, with a significant reduction in complications [18–20]. As this method may not be effective for deep or dense lesions [21], the choice of surgical procedure ultimately depends on the nature of the lesion, its depth, and the corneal topography following a thorough evaluation.

Corneal densitometry (CD) value, as obtained using Scheimpflug tomography, is useful in assessing cornea health [22–24]. This method quantifies minimal changes in corneal shape and opacity by measuring the degree of light backscatter, providing insights into the visualization and evaluation of corneal pathologies such as keratoconus, post-surgical stromal reactions and haze [25–27].

In the current study, the main outcome measures included long-term outcomes of PTK in the treatment of EBMD, specifically visual acuity, recurrence rate, time to recurrence, refractive shift, and topical medication use. The secondary outcome was the analysis of CD measurements derived from Scheimpflug tomography before and after the treatment to demonstrate the corneal restoration.

Patients and methods

Participants

This retrospective study included 40 consecutive eyes (40 patients) with EBMD treated with PTK between April 2009 and March 2021. All patients were enrolled in the clinic at Eye and ENT Hospital of Fudan University, and all patients were treated by the same surgeon (JHD). All enrolled participants were aged 18 years or older. Written informed consent for the surgery and for publication of the data was obtained from all patients before surgery. All subjects were treated in accordance with the tenets of the Declaration of Helsinki and the protocol was approved by the Institutional Review Board of the Eye and ENT Hospital of Fudan University.

Patients diagnosed with EBMD exhibited symptomatic recurrent corneal erosions, characterized by painful episodes during sleep or on awakening, along with irritation and visual disturbances. Morphological examination via slit-lamp revealed characteristic findings such as epithelial irregularity, microcysts, or map-dot-fingerprint patterns. Due to technological limitations of the clinic in the early period, in vivo confocal microscopy (IVCM, HRT3-RCM, Heidelberg Engineering, Heidelberg, Germany) was performed in twenty-three patients who underwent PTK after 2015. Patients were included in the study if they failed to respond to conventional treatments for EBMD, including ocular lubricants, ophthalmic hyperosmotic agents, and/or therapeutic contact lens. Subjects with any other eye diseases were excluded from the study.

Pre- and post-operative examinations

All patients received comprehensive ophthalmic examinations before PTK and at 3 months and 1 year after PTK. This included assessments with a slit lamp, Fluorescein sodium corneal staining, uncorrected visual acuity (UCVA), refractive error, best corrected visual acuity (BCVA) and corneal tomography. The following information was collected for each patient: the etiology of recurrent corneal erosions, the duration of these erosions and the treatments administered prior to PTK, the frequency of pre-PTK recurrences, a comparison of preoperative and postoperative BCVA and spherical equivalent refractive error (SERE) at 3 months and one year post-surgery, and a subjective evaluation of ocular pain before and after the procedure on a scale of 1 to 10. Additionally, any complications arising from PTK were documented.

The criteria for defining a clinical recurrence included the first occurrence of symptomatic corneal erosion after PTK or necessitating a second PTK procedure. Patients were scheduled for follow-up visits at the clinic three months and one-year post-surgery, with subsequent appointments every two to three years. Each clinic visit involved a reexamination with a slit lamp to detect any signs of RCE or complications associated with PTK. Specific inquiries were made regarding any sudden ocular pain, discomfort upon waking, and any symptoms suggestive of a recurrence, as well as whether the patient had undergone a repeat PTK. Due to the COVID-19 pandemic, a number of follow-ups between 2020 and 2022 were conducted via telephone interview, which conducted only for long-term symptom assessment (≥ 1 year postoperatively). In total, seven patients (7/40) complete post-PTK symptom assessment via telephonic survey.

Corneal densitometry

Corneal tomography was performed using Rotating Scheimpflug imaging technology (Pentacam; Oculus, Wetzlar, Germany) as previously described [28]. Corneal tomography was performed before and 3 months after surgery. The Pentacam system provided a graphical map showing Cornea Densito Average across various corneal sectors (CD annulus and layer averages) in the form of arbitrary density units [29].

PTK procedure

The excimer laser treatment (Carl Zeiss Meditec AG, Jena, Germany) was performed adhering to a standardized ablation protocol. This procedure was initiated after the removal of the loosely adherent corneal epithelial flap with a crescent blade. The energy used was 250 kHz with a pulse energy of 150 nJ. A bandage contact lens (ACUVE OASYS, Johnson & Johnson, Inc) was placed for about a week until the corneal epithelium was intact. The ablation depth (AD) ranged from 6 to 40 μm, with more than half of the patients featuring an AD of 25 μm (as shown in Fig. 1). Moreover, the optical zone diameter of all patients was set at 8 mm.

Fig. 1.

Fig. 1

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The proportion of different ablation depth in all patients underwent Phototherapeutic Keratectomy

A routine postoperative medication consisted of topical fluorometholone 0.1%, used initially four times a day and tapered for a period of 20 days, topical levofloxacin 0.5%, used four times daily for seven days, and artificial tears used throughout the half year period postoperatively. To further promote epithelial healing, deproteinized Calf serum eye lubricant was used every night for 1 month. A standard postoperative follow-up schedule was established, with appointments scheduled at 1 day, 1 week, 1 month, 3 months, 6 months, and then on an annual basis thereafter.

Statistical analysis

All statistical analyses were performed using SPSS 20.0 software (SPSS, Inc., Armonk, NY), and the parameters are reported as mean ± standard deviation. Paired t test was used to compare the pre- and post-treatment refractive parameters, visual acuity and CD. A p value < 0.05 was considered to indicate a statistically significant difference.

Results

A total of 40 patients, with an average age of 42.0 ± 13.5 years old, were enrolled in the study. This cohort included 25 patients with long follow-up periods ranging from 37 to 150 months, and 15 patients with short follow-up time between 12 and 24 months. The average duration of follow-up for the entire study population was 4.4 ± 3.3 years. The average intended AD was 23.1 ± 9.7 μm (range, 6–40 μm), which was consistent with the central corneal thickness change measured 3 months post-operatively at 23.3 ± 17.8 μm. At the one-week follow-up, all patients achieved complete corneal re-epithelialization. Detailed characteristics of patients were listed in Table 1.

Table 1.

Demographics of patients before PTK

Mean±SD Range (min, max)
Age (years old) 42.0±13.5 25, 75
Sex (male: female) 16：24
Spherical Equivalence (Diopter, D) -1.75±2.57 -7.75, +2.25
Best Corrected Visual Acuity (LogMAR) 0.06±0.12 -0.08, 0.52
Intraocular Pressure (mmHg) 14.3±3.6 8.1, 21.7
Central Corneal Thickness (μm) 534±50 439, 597
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Symptoms and treatments

Figure 2 demonstrates one patient with EBMD and his anterior segment photograph, fluorescent corneal staining and IVCM image. IVCM images revealed enlarged basal cells, highly reflective granular/infiltrating cells, and activated stromal cells within the superficial stromal layer.

Fig. 2.

Fig. 2

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Imaging examination findings in a patient with Epithelial Basement Membrane Dystrophy. A, the anterior segment photograph shows a loosed epithelial (indicated by the arrow); B, photograph of the fluorescent corneal staining; C, Corneal confocal microscope image shows enlarged basal cells, highly reflective granular/infiltrating cells, and activated stromal cells within the superficial stromal layer (indicated by the arrow)

The average frequency of symptom onset among patients varied from every 2 days to every 2 months before PTK. Nearly one-third of the patients suffered from ocular pain and irritation every 1–2 weeks before PTK, as shown in Fig. 3A. Most of patients had been enduring these symptoms for a minimum of half a year before opting for PTK (Fig. 3B).

Fig. 3.

Fig. 3

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Symptoms and medication usage before and after Phototherapeutic Keratectomy (PTK). A, the frequency of ocular pain and irritation experienced by patients prior to PTK. B, symptoms duration before PTK. C, the medication used pre- and post-surgery. D, the specific symptoms reported by patients pre- and post-operatively

Prior to undergoing PTK, all patients had been treated with artificial lubricants or a bandage contact lens for a period ranging from 1 to 2 years since the onset of symptoms. Additionally, over half of the patients had received at least three types of treatment before opting for PTK (Fig. 3C). Six months post-PTK, almost all patients continued to use artificial tears for dry eye symptoms, with half of this group maintaining their use up to 3 years postoperatively. It is worth mentioning that one third of patients did not need any medication or bandage contact lens 3 years post-PTK. The remaining patients used only artificial tears or gel occasionally for dry eye symptoms. No patient required prolonged postoperative bandage lens use or medication beyond the initial healing period.

Almost all patients suffered from pain and irritation before surgery, and these subjective symptoms were significantly alleviated after surgery. Only one fifth of the patients reported dry eye and a foreign body sensation, with no patient suffering from ocular pain 6 months post- operatively. Two out of 25 patients continued to require long-term artificial tears but without foreign body sensation, but dry eye persisted in nearly a quarter of patients even 4 to 10 years post-surgery (Fig. 3D).

Recurrences after PTK

A single instance of repeated erosion was observed in one patient. Specifically, the initial episode of RCE in this case was not trauma-related. The ablation depth of this patient was 6 μm. Two months after PTK, ocular pain reoccurred following minor trauma, and slit-lamp examination revealed local corneal epithelial erosion. The patient was subsequently treated with artificial tears and gel for a one-month period, which successfully resolved the ocular pain with no subsequent recurrences. Notably, no patient in the study required a second surgery, and no major postoperative complications were observed.

Refractive status and visual acuity

At one-year follow-up, the average refractive change was − 0.08 ± 0.37D Diopters (D), showing stable postoperative refraction. Although 4 of 40 eyes showed a refractive shift > 0.5 D after PTK, 77.5% patients retained same spherical equivalent (within ± 0.25 D) post-operatively (Fig. 4A). Additionally, no surgical-induced astigmatism was found (Fig. 4B). There was a significant improvement in BCVA after surgery (p = 0.002), 87.5% of the patients achieved a BCVA of 20/20 at the final follow-up, and all patients reached a BCVA of 20/25 (Fig. 4C). Among the patients, one patient (2.50%) lost one line of Snellen BCVA, two patients gained 5 lines in BCVA, and nearly half of the patients maintained their preoperative BCVA post-operatively (Fig. 4D). No eyes had grade 2 or higher cornea haze (Fantes corneal haze grading score).

Fig. 4.

Fig. 4

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Visual outcomes of Phototherapeutic Keratectomy (PTK) in Epithelial Basement Membrane Dystrophy. (A) Spherical equivalent refractive change after PTK, (B) refractive astigmatism pre- and postoperative, (C) best corrected distance visual acuity (BCVA) pre- and postoperative; (D) change in BCVA after PTK

Corneal densitometry

Preoperative CD data were available for 39 eyes (all except the one operated in 2009). CD values at the central two annuli (0–2 mm and 2–6 mm) of both the anterior and center layers decreased significantly after PTK. Additionally, the CD values for the 0–2 and 2–6 mm regions of the total corneal thickness also significantly decreased at 3 months postoperatively (all p < 0.05) (Fig. 5A and B). We further correlated CD values with BCVA, and found that a 1-unit decrease in anterior central CD corresponds to an average 0.02 logMAR improvement (r=-0.74, p = 0.02, N = 39). In contrast, the CD values in the remaining peripheral corneal regions remained similar as pre-operative measurements. Notably, the patient with a corneal thickness of 439 μm had a history of LASIK surgery 10 years prior to PTK. Her corneal densitometry values were not significantly different from those of other patients in the cohort.

Fig. 5.

Fig. 5

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(A) Corneal densitometry (C, D) across the cornea from anterior to posterior layers pre- and post-operatively. (B) Corneal densitometry map of a patient before (top) and after (bottom) Phototherapeutic Keratectomy using the Pentacam Scheimpflug imaging system. * indicates p < 0.05 (statistical significance of CD change after PTK)

Discussion

In this study, we evaluated a total of 40 eyes with EBMD that were treated with PTK, with a follow-up period extending up to 150 months after surgery. Clinical recurrence was observed in a single patient following PTK, who subsequently alleviated ocular pain with the use of artificial tears and gel for one month. Notably, no patient required a second surgery throughout the entire follow-up period. Although autologous serum has been reported to be effective for recurrent corneal erosions, the strict storage, complicated preparation, risk of contamination, prolonged patient compliance and repeated costs restricted its application in clinic. To date, high-level comparative evidence between DCS and autologous serum remains limited, with only one Chinese-language clinical study directly evaluating DCS in the context of corneal epithelial healing [30]. Therefore, our institution’s preference for DCS is partly empirical, based on our extensive clinical experience observing good safety and efficacy with DCS over many years.

The underlying principle of PTK in the treatment of RCE is the creation of smooth plane for the migrating epithelial cells by ablation of the Bowman’s layer. This smooth surface facilitates the formation of a new hemidesmosome adhesion complex [31]. During PTK procedure, corneal epithelium of each patient was readily removed with a blade, suggesting an abnormal epithelium with a weakened attachment to the corneal stroma. This abnormality was further confirmed using confocal microscope, which revealed enlarged basal cells, highly reflective granular/infiltrating cells, and activated stromal cells within the superficial stromal layer. The laser ablation removes the pre-existing basement membrane, allowing the epithelium to come into direct contact with the anterior stroma, thereby stimulating the synthesis of new anchoring fibrils and hemidesmosomes [32]. After PTK, the basal layer of the corneal epithelium forms new hemidesmosomes and a basement membrane.

In this study, over 90% of eyes maintained their initial Snellen BCVA or experienced an improvement after PTK. Notably, 87.5% of eyes achieved a BCVA of 20/20 or better at the final follow-up, indicating the high success rate of PTK. All patients achieved BCVA ≥ 20/25 at final follow-up; one patient decreased from 20/20 to 20/25. The patient with a preoperative visual acuity of 20/66 (equivalent to 0.52 LogMAR) improved postoperatively to 20/25. This improvement in BCVA post-PTK has also been reported in previous studies [33, 34]. Vision, which can be diminished preoperatively due to epithelium irregularities or defects along the visual axis, was observed to improve rapidly and significantly after PTK. Additionally, refraction remained stable postoperatively. This stability is attributed to the uniform laser ablation across the cornea during PTK, where the ablation depth was controlled to avoid excess [35]. This finding aligns with a recent publication [36].

While the maintenance and improvement of BCVA is a significant benefit of PTK, alleviating symptoms and preventing recurrence are more important clinical objectives. Almost all patients suffered from RCE symptoms, including ocular pain and irritation before surgery. After PTK, 80% of patients were free from irritation, and ocular pain was alleviated in all eyes. One patient (1/40 eyes, 2.5%) experienced a single mild erosive event after PTK; no patient required reoperation. Published success rates for PTK in EBMD range from 46% to 100% [20], which likely reflects differences in study populations, recurrence definitions, and follow-up durations. Our data support a low recurrence rate (2.5%) and no reoperations in this cohort.

Pogorelov et al. reported no recurrences of erosions with a mean 4.8 years following PTK in 15 eyes [37]. Conversely, Germundsson et al. reported a 46% total recurrence rate with a mean follow-up of 3.6 years in 51 eyes [34]. Not only eyes with EBMD, but also trauma-related RCE cases can benefit from PTK [33, 36]. Baryla et al. reported that 25% eyes experienced a recurrence after 3 months and 36% after 9 months in a cohort of 33 patients, suggesting that the absence of recurrences in the short term following PTK indicates a likelihood of long-term success [11]. In this study, 15 patients with a short-term follow-up for 12 to 24 months are expected to remain recurrence-free for a long time. Table 2 provides a comprehensive overview of studies from the past decade that have reported on the efficacy and safety of PTK for the treatment of RCE, including the depth ablation during PTK surgery. Analysis of the data presented in the table reveals that the recurrence rate is significantly reduced when the depth of tissue ablation during PTK exceeds 15 μm, as compared to ablation depths of less than 10 μm.

Table 2.

Previous studies reporting the efficacy and safety of PTK for the treatment of RCE over the past decade

Study Etiology Patients/eyes Age (years) Follow-up duration (months) Recurrences (eyes) Complication AD(µm)
haze refractive shift BCVA loss
Our study EBMD 40/40 42.0 ± 13.5 12–150 1/40 0/40 4/40 1/40 23.1 ± 9.7
Bizrah et al.[38] (2024) TA, EBMD 555/593 50.9 ± 14.2 60.5 (5–127) 6/593 9/593 NA NA 15
Yang et al. [42] (2023) EBMD NA/30 53 ± 16 18.1 (1.7–113) 3/30 1/30 2/30 NA 5 ~ 10
Zhang et al. [36] (2022) TA 22/24 NA 13(12–32) 0/24 0/24 NA NA 75 (including epithelium)
Song et al.[43] (2020) TA, EBMD, ID 23/23 43.6 ± 13.2 19.75 ± 6.83 5/23 NA NA NA 10
Lee et al. [44] (2017) EBMD 51/58 52(31–84) 3-170 9/58 9/58 NA 8/58 5
Mehlan et al. [45] (2016) TA, EBMD 37/37 41 ± 11 12 ± 12 (3–70) 3/37 NA NA NA 15,20,25
Dedes et al.[46] (2015) TA, EBMD, ID 82/89 45.5 ± 11.6 51.6 ± 21.2 (24–91) 25/89 NA NA NA 8
Chan et al. [47] (2014) TA, EBMD, Other 16/16 47.9 17.3 ± 8.4 6/16 8/16 NA 0/16 9
Suri et al.[48] (2013) EBMD, Other NA/7 46.5 ± 14.6 9 (2–52) 2/7 2/7 NA NA 5–6
Nassaralla et al.[19] (2012) TA, EBMD, ID 23/26 45.1 ± 13.2 144 ± 18.2 6/26 (all EBMD) 2/26 NA 2/26 5
Germundsson et al.[34] (2011) EBMD 39/52 55(25–75) 43(7-100) 7/52 NA NA 1/52 15
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Edited from table published by Chen et al. [20]. AD, ablation depth; TA, trauma; EBMD, epithelial basement membrane dystrophy; ID, idiopathic; haze: refers only to clinically significant haze (grade ≥ 2); NA, not available

Notably, despite the established correlation between deeper ablation depths and increased risks of corneal haze development and refractive instability, neither clinically significant haze nor substantial hyperopic/myopic shifts were observed in this cohort. This may be attributed to standardized postoperative management with regular fluorometholone therapy (0.1%) and scheduled follow-ups, with protocol-driven corticosteroid intensification when indicated. In a large sample retrospective analysis, only 1.6% of eyes in Bizrah M et al.’s study developed grade 2 cornea haze [38], indicating that PTK is safe and effective in treating RCES. The absence of significant refractive changes in this study is consistent with the uniform anterior corneal ablation pattern of PTK, where shallow ablation depths minimally alter corneal curvature.

CD is a quantitative and objective parameter that describes corneal opacities, evaluated with the densitometry program within the Pentacam system using scattering light [39]. A recent study reported CD changes after PTK in EBMD [40]. In agreement with those findings, our study also observed a significant reduction in CD values at the central two annuli (0–2 mm and 2–6 mm) of both the anterior and mid-cornea layers after PTK, correlating with the improvement in visual acuity. Furthermore, a previous study reported that central CD values were associated with decreased BCVA in eyes with Fuchs endothelial corneal dystrophy [41]. In our own EBMD cohort, correlation analysis demonstrated a different numerical relationship: a 1-unit decrease in CD corresponded to a 0.02 logMAR improvement in BCVA. Although direct numerical extrapolation from FECD to EBMD is not justified, the reduction in CD observed after PTK likely associated with the removal of opaque corneal tissue, which may in turn contribute to the improvement in visual acuity. In this way, these values may serve as an objective measure of the therapy’s success. Notably, our study provides additional layer-specific CD data (anterior vs. mid cornea) and a quantitative link to visual function, complementing previous reports.

The main limitations of this study include its retrospective design with self-controlled data, which led to variability in the follow-up duration. In addition, the long recruitment period and the later introduction of IVCM may introduce some diagnostic heterogeneity, although the primary diagnosis remained clinical. Another limitation is that re-epithelialization was assessed only on postoperative days 1 and 7. Without intermediate time points (days 2–6), the exact closure time could not be determined, and only a binary outcome (healed by day 7) is reported. In addition, no formal power calculation was performed because this was a single‑arm descriptive series. Consequently, negative findings (e.g., the absence of significant changes in peripheral CD) should be interpreted cautiously, as the study may have been underpowered to detect small effect sizes. Future studies aimed at evaluating the effects of EBMD treatment should aim to collect prospective data to mitigate these limitations. Despite these limitations, our findings demonstrate that vision loss and corneal erosion associated with EBMD are likely to be responsive to PTK.

Conclusion

The results of this study showed that no significant complications were observed following PTK, and no patients warranted reoperation. In addition, there was a significant improvement in visual acuity, with the refractive status remaining stable postoperatively. In conclusion, PTK offers an effective and safe surgical method for patients with EBMD, and it is a simple and feasible treatment option that effectively alleviates the erosive symptoms associated with EBMD.

Author contributions

Conception and design (MY, MC & JD); analysis and interpretation of the data (MY, JD); drafting of the paper (MY), revising for intellectual content (MY, MC); final approval of the version (MY, MC & JD); all authors agree to be accountable for all aspects of the work.

Funding

This work was financially supported by the National Natural Science Foundation of China (Grant 82101175 and Grant 81970831). The sponsor or funding organization had no role in the design or conduct of this research.

Data availability

The data that support the findings of this study are available from the corresponding author, JD , upon reasonable request.

Declarations

Ethics approval and consent to participate

All subjects were treated in accordance with the tenets of the Declaration of Helsinki and the protocol was approved by the Institutional Review Board of the Eye and ENT Hospital of Fudan University, the Approval number was 2014012.

Consent for publication

Consent for publication was obtained from the individual person for using the images of the person.

Competing interests

The authors declare no competing interests.

Footnotes

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Manrong Yu and Minjie Chen contributed equally to this work and should be considered equal first authors.

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Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Data Availability Statement

The data that support the findings of this study are available from the corresponding author, JD , upon reasonable request.

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