Three-dimensional assessment of posterior polymorphous corneal dystrophy with swept-source optical coherence tomography

Introduction

Posterior polymorphous corneal dystrophy (PPCD), also known as Schlichting dystrophy, can present as either autosomal dominant or isolated unilateral cases, with a similar phenotype but without a hereditary pattern (1). PPCD usually presents during the first decade of life and follows a slowly progressive clinical course. Since the onset is insidious and the progress is slow, patients typically remain asymptomatic, with diagnosis frequently being incidental. The mild endothelial alterations of PPCD may progress gradually over an extended period, potentially resulting in visual impairment (2). The disease exhibits characteristic abnormalities in corneal endothelial cell morphology, with concomitant changes in the Descemet membrane (DM). The disease process involves the proliferation of metaplastic cells that form multiple cellular strata with epithelium-like features, ultimately contributing to the development of an anomalous collagenous layer (3). The distinguishing features include the presence of vesicular lesions, gray-white opacities, placoid lesions, and linear bands on the posterior corneal surface (1,4).

Descriptions of PPCD have primarily been based on slit-lamp findings and in vivo confocal microscopy (IVCM). Waring et al. (5) classified PPCD into three types based on the pathological morphology observed under slit-lamp microscopy. Type 1 is characterized by vesicular opacities in the corneal endothelium, which may appear alone or in clusters. Type 2 presents as translucent band-like lesions, typically with two parallel wavy or linear gray lesions. Type 3 exhibits partial or complete corneal posterior opacity and thickening. In IVCM, patients exhibited hypo-reflective vesicles and curvilinear or placoid hyper-reflective changes in the endothelium and DM, along with guttae-like dark spots (6-9).

Recent advancements in non-invasive corneal imaging techniques have demonstrated significant potential for clinical applications (10). Optical coherence tomography (OCT) enables non-contact, minimally invasive, real-time corneal imaging, providing visualization from the epithelial layer to the endothelial layer in vivo. Clinically, this technology has been applied to measure both anterior and posterior corneal parameters in patients diagnosed with corneal dystrophy (11-14). With its fast-tuning laser source and balance detection, swept-source optical coherence tomography (SS-OCT) can generate high-resolution images and detailed three-dimensional (3D) maps of the posterior cornea (15-19). This technique facilitates the more accurate assessment of endothelial alterations, which aids in the clinical diagnosis and follow-up of patients with PPCD.

To date, no published reports have documented 3D alterations of the inner corneal surface in PPCD. In this study, we analyzed the morphologic features of the inner corneal surface in patients with PPCD using SS-OCT. We present this article in accordance with the STROBE reporting checklist (available at https://qims.amegroups.com/article/view/10.21037/qims-2025-aw-2104/rc).

Methods

This retrospective study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the Ethics Committee of the Eye & ENT Hospital (No. EENT-IRB20220222). Informed consent was obtained from all participants involved in the study.

A total of 16 eyes of 10 patients (6 females and 4 males), aged 9 to 30 years, were identified retrospectively at the Department of Ophthalmology, Eye, Ear, Nose and Throat Hospital of Fudan University, China, between November 2021 and August 2022. The PPCD diagnosis was made clinically by two cornea specialists. The diagnosis of PPCD was established based on the IC3D Classification of Corneal Dystrophies (1). Specifically, to differentiate between PPCD and posterior corneal vesicles (PCVs), we considered the following: (I) morphology: while PCV typically presents as a solitary, non-progressive vesicle, the unilateral PPCD cases in this study exhibited multiple, clustered vesicles or band-like lesions, which are pathognomonic for PPCD; and (II) IVCM: while PCV shows only simple focal endothelial changes, the PPCD cases exhibited characteristic endothelial features on IVCM, including hyper-reflective bands (“railroad tracks”) and vesicular hypo-reflective areas with surrounding pleomorphism.

Slit-lamp examination and IVCM were performed on each eye to classify the examined corneas as either healthy or affected by PPCD. Patients were classified based on the predominant clinical features observed under slit-lamp biomicroscopy and IVCM. Type 1 (vesicular) was characterized by vesicular opacities and/or clustered lesions, while Type 2 (band-like) was characterized by parallel linear bands with scalloped edges. Notably, the placoid subtype was not observed in our study cohort during the inclusion period. Consequently, the statistical analysis was restricted to comparisons between the vesicular and band-like phenotypes.

Patient demographics and clinical characteristics, including age and sex, and anterior segment photographs, were collected. Endothelial specular microscopy was performed in all study eyes using a Tomey EM-3000 (Tomey, USA) to analyze endothelial cell density (ECD, cells/mm²) and hexagonality (HEX%). The IVCM images were captured using the Heidelberg Retina Tomograph (HRT III, Heidelberg Engineering GmbH, Heidelberg, Germany). The SS-OCT instrument used in this study was an SS-OCT system (VG200D, SVision Imaging, Henan, China), which operates at a wavelength of 1,050 nm and incorporates industry-leading specifications, including an ultrafast scanning speed of 200,000 A-scans per second, a wide field of 87 degrees, and an imaging depth of 12 mm (in tissue). Each participant fixated on a central target, and optimal centration was confirmed by visible specular reflection in all scan images. The SS-OCT was performed at the same visit as the IVCM in all patients. The same trained operator performed and analyzed both the IVCM and SS-OCT.

B-scans and the Anterior Segment Cube 16 mm × 16 mm scanning protocol were used for the pattern analysis. For en-face imaging, a custom segmentation strategy was used first to visualize the DM and corneal endothelium. The inner boundary followed the inner cornea, and the outer boundary was set 60–80 µm anterior to the posterior surface of the corneal stroma on the instrument. The segmentation boundaries were then manually adjusted by an experienced observer to optimally visualize the lesions. The en-face SS-OCT images were generated using built-in software (van Gogh; SVision Imaging, Henan, China) to investigate the 3D structure of the whole inner corneal structure. ImageJ (NIH, USA) was then used to analyze the SS-OCT images. A trained observer used ImageJ to measure the affected area of the cornea and calculate the percentage of the total corneal area, recording the presence of pupillary axis involvement of the affected area.

The statistical analysis was conducted using Graphpad Prism software (San Diego, CA, USA). Continuous data were summarized as the mean and standard deviation. Differences between the two subtypes were evaluated using the Welch’s t-test. Either Pearson’s or Spearman’s correlation test was used to assess the relationship between the affected corneal area and other variables.

Results

During the study period, 10 patients (16 eyes) were identified and included. The cohort comprised 6 females and 4 males, with a mean age of 17.7±7.8 years (range, 9–30 years). Four patients had unilateral involvement, while six patients had bilateral PPCD. In all patients, slit-lamp microscopy revealed characteristic endothelial findings. Among the 16 eyes, vesicular lesions were observed in 7 eyes (43.75%), and band-like patterns in 9 eyes (56.25%). Consistent with the rarity of the phenotype, no cases of placoid PPCD were observed.

Based on slit-lamp and IVCM features, the 16 eyes were classified into two subtypes. Type 1 (vesicular) presented as isolated or clustered endothelial vesicles. Type 2 (band-like) presented as translucent, parallel linear bands with scalloped edges. Specular microscopy was successfully performed in 10 patients. Table 1 summarizes the demographic, clinical, and en-face SS-OCT findings.

In Type 1 PPCD, 3D reconstruction of en-face SS-OCT (16 mm × 16 mm cube scan) revealed distinct, highly reflective, scattered, round lesions at the level of the posterior corneal surface. These lesions varied in size and distribution (center or periphery). Correspondingly, the IVCM images revealed hypo-reflective vesicular opacities (Figure 1). In Type 2 PPCD, classic band-like patterns were clearly visualized. The bands featured wavy margins and were oriented horizontally, obliquely, or circularly, either involving or sparing the central visual axis. IVCM revealed hyper-reflective “railroad track” appearances (Figure 2). The en-face SS-OCT images correlated well with the IVCM findings.

Figure 1 Changes in Type 1 (vesicular) lesions of PPCD. Slit-lamp biomicroscopy showing typical endothelial greyish opacities (A). In vivo confocal microscopic sections showing hypo-reflective, crater-like (B), hyper-reflective oval, and placoid lesions (C) at the level of the DM, and nucleated endothelial cells (D). White arrows indicate the typical PPCD-related lesions on the posterior corneal surface in (A-D). En-face images of a 16 mm × 16 mm cube scan at the level of the inner corneal surface showing scattered oval or round hyper-reflective lesions (E,F), which correspond to characteristics seen under slit-lamp microscopy and IVCM. The arrow (F) indicates the corneal layer corresponding to the en face image in (E). Vertical SS-OCT B-scan image showing hyper-reflective material and deposits (white arrow) on the posterior cornea, protruding into the anterior chamber (G). DM, Descemet membrane; IVCM, in vivo confocal microscopy; PPCD, posterior polymorphous corneal dystrophy; SS-OCT, swept-source optical coherence tomography.

Figure 2 Characteristics of Type 2 (band-like) lesions in PPCD. Right eye slit-lamp photograph showing a classic band-like structure at the DM (A), a characteristic of PPCD. In vivo confocal microscopic sections showing curvilinear, hyper-reflective lesions (B), guttae-like dark spots (C), and endothelial deposits (D) at the level of the DM. White arrows indicate the typical PPCD-related lesions on the posterior corneal surface in (A-D). En-face images of a 16 mm × 16 mm cube scan at the inner corneal surface showing a horizontal hyper-reflective band opacity (white arrows), extending from the inferior cornea toward the center (E,F). This feature corresponds to the lesions observed in the IVCM images. DM, Descemet membrane; IVCM, in vivo confocal microscopy; PPCD, posterior polymorphous corneal dystrophy.

The mean ECD of the affected eyes was 2,024.1±369.4 cells/mm² (range, 1,706–2,768 cells/mm²). en-face SS-OCT allowed for a comprehensive assessment of the corneal endothelium. The mean proportion of the corneal lesion area relative to the total corneal area was 3.57%±1.82% (range, 0.07–6.31%).

A comparison of the two PPCD subtypes (Type 1 vs. Type 2) revealed no significant differences in the proportions of the corneal lesion area, mean ECD, or hexagonality (Table 2).

No statistically significant correlation was observed between the proportion of the affected corneal area and ECD [r=−0.4808, P=0.059, 95% confidence interval (CI): −0.7886 to 0.01952] or hexagonality (r=−0.3648, P=0.165, 95% CI: −0.7288 to 0.1598). However, involvement of the central visual axis was significantly associated with worse endothelial status. Specifically, patients with visual axis involvement had lower ECD (r=−0.8044, P<0.001, 95% CI: −0.9316 to −0.5015) and reduced hexagonality (r=−0.5419, P=0.036, 95% CI: −0.8232 to −0.0472) compared to those without axis involvement (Figure 3).

Figure 3 Relationship between the affected corneal area, ECD, and hexagonality. No statistically significant correlation was observed between the proportion of the affected corneal area and ECD (r=−0.4808, P=0.059) (A) or hexagonality (r=−0.3648, P=0.165) (B). Patients with involvement of the central visual axis of the cornea exhibited lower ECD (r=−0.8044, P<0.001) (C) and reduced hexagonality (r=−0.5419, P=0.036) (D). ECD, endothelial cell density.

Discussion

In the present study, we analyzed structural alterations of the inner corneal surface in three-dimensions in the eyes of patients with different types of PPCD using SS-OCT, producing both cross-sectional and en-face images of the cornea. To the best of our knowledge, this study represents one of the first attempts to use wide-field (16 mm × 16 mm) en-face SS-OCT for the quantitative characterization of morphological features on the posterior corneal surface.

Anterior segment OCT is widely used in the diagnosis of corneal dystrophies (14). In this study, we focused on the additional information provided by SS-OCT via 3D imaging of the cornea. The results showed that en-face SS-OCT imaging clearly depicted the structure of the whole inner corneal surface, corresponding closely to the features observed with the slit-lamp microscopy and IVCM.

Corneal endothelial changes in PPCD may progress gradually over the years, resulting in visual disturbance. The ability to visualize the DM and endothelium is essential for diagnosing PPCD and monitoring its clinical course. Due to its high magnification and resolution of corneal structures, IVCM is of value in definitively identifying features characteristic of PPCD. However, IVCM is contact-based, more technically challenging, user-dependent, and especially unfavorable for follow up in children. Conversely, SS-OCT offers fast scanning rates and uses a light source with longer tunable wavelengths (20). It enables non-invasive in vivo imaging of corneal microstructure. Images were successfully obtained for all participants in this study.

Siebelmann et al. summarized the characteristics of corneal dystrophies and correlated them with anterior segment SD-OCT findings and B-scan images of patients with PPCD (14). Apart from this study, no other reports have described the performance of wide-field en-face SS-OCT in PPCD. On B-scan images, PPCD appears as a thickened DM, accompanied by patchy dense opacification of the posterior corneal layers, protruding into the anterior chamber. However, patients with PPCD typically exhibit multiple changes on the posterior cornea surface, whether continuous or unconnected, and B-scan images do not allow accurate or comprehensive visualization of these abnormalities. Due to the lack of comprehensive endothelial imaging, it has been challenging to determine the extent of the lesions and to monitor their progression. Based on SS-OCT B-scan transversal sections, reconstruction techniques can rebuild en-face images. Tahiri Joutei Hassani et al. explored the potential of spectral domain optical coherence tomography (SD-OCT) with en-face imaging for ocular surface diseases, establishing correlations with IVCM findings. They demonstrated that en-face imaging provides additional information and novel insights into various ocular surface conditions without requiring corneal contact (21). Iovino et al. found that 3D anterior segment SD-OCT was a valuable tool for investigating endothelial features and may provide valuable support in diagnosing and staging Fuchs endothelial corneal dystrophy (12).

However, conventional SD-OCT imaging has been limited by its smaller scan area. Generally, imaging is restricted to the central 1–8 mm of the cornea, as the telecentric probe shows reduced axial resolution and signal intensity in peripheral regions. This study sought to detect the posterior of the cornea in patients with PPCD using wide-field (16 mm × 16 mm) en-face images, which can be acquired in a few seconds. The SS-OCT visualization window is hundreds of times larger than the surface area analyzed by IVCM. Thus, we sought to visualize the inner corneal surface using 3D reconstruction of wide-field en-face SS-OCT. We showed that wide-field en-face SS-OCT accurately evaluates the inner corneal surface in patients with PPCD, providing complete visualization of corneal lesions. In addition, the characteristics observed were quite consistent with those in IVCM images. Moreover, this method enables the measurement of changes across the entire posterior corneal surface. As the method can be performed with a commercially available SS-OCT machine, it has potential for use in the quantitative morphologic analysis of posterior corneal surfaces.

Specular microscopy enables high-resolution imaging of characteristic PPCD findings in the DM and endothelial layer. However, it is primarily used to observe the central part of the cornea. When the ECD is low or the morphological data are inadequate, non-contact SS-OCT can be performed first. Based on the focus position and morphology of the DM and endothelium in the SS-OCT images, the need for further IVCM examination can then be determined.

This study had several limitations. First, due to the rarity of PPCD and the retrospective nature of this study, the sample size was inherently limited. Consequently, all statistical analyses presented herein should be considered exploratory and hypothesis-generating. We did not apply corrections for multiple comparisons, nor did we adjust for potential inter-eye correlations in bilateral cases due to the small sample size, so the statistical significance reported should be interpreted with caution. Second, given the retrospective design, long-term longitudinal changes in PPCD were not consistently followed up on or examined. Future prospective, multi-center studies with larger cohorts are necessary to validate these preliminary findings. Further, genetic testing was not routinely performed for all patients in this retrospective cohort. The diagnosis of PPCD was established based on characteristic slit-lamp biomicroscopy and IVCM findings. While clinical diagnosis is highly reliable for classic phenotypes, the lack of genotypic correlation remains a limitation of this study.

Conclusions

Our findings suggest that wide-field en-face SS-OCT is a valuable tool for investigating structural abnormalities of the inner corneal layers with high resolution and may have a potential role in monitoring the progression of PPCD. Further, this device may be valuable for future research on corneal endothelial diseases and for elucidating the pathogenesis and natural course of these corneal endothelial changes.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://qims.amegroups.com/article/view/10.21037/qims-2025-aw-2104/rc

Data Sharing Statement: Available at https://qims.amegroups.com/article/view/10.21037/qims-2025-aw-2104/dss

Funding: This work was supported by the National Natural Science Foundation of China (Nos. 81970766 and 82171102), the Shanghai Medical Innovation Research Program (No. 22Y21900900), and the Shanghai Key Clinical Research Program (No. SHDC2020CR3052B).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-2025-aw-2104/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the Ethics Committee of the Eye & ENT Hospital (No. EENT-IRB20220222). Informed consent was obtained from all participants involved in the study.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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