AbstractWe aimed to assess long-term disease progression in patients with severe keratoconus (KC). Clinical records of 125 patients (201 eyes) with severe KC followed-up for > 12 months were retrospectively analyzed. From these, 28 patients (31 eyes) were included. Corneal topography parameters evaluated included thinnest corneal thickness (TCT), maximum keratometry (Kmax), anterior and posterior mean corneal radii of 3 mm (aKM, pKM), steep keratometry, and KC screening indices.

摘要我们旨在评估严重圆锥角膜（KC）患者的长期疾病进展。回顾性分析125例（201眼）严重KC患者随访12个月以上的临床记录。其中包括28名患者（31只眼）。评估的角膜地形图参数包括最薄的角膜厚度（TCT），最大角膜曲率（Kmax），前后平均角膜半径3 mm（aKM，pKM），陡峭角膜曲率和KC筛查指数。

All patients wore rigid gas permeable contact lenses (RGPCLs) for an extended period. The median patient age and follow-up period were 20 (interquartile range [IQR] 17–22) years and 25 (15–38) months, respectively. Compared to baseline, the aKM, Kmax, and KC screening indices on the anterior corneal surface were reduced at the final follow-up (P < 0.05).

所有患者均长期佩戴硬性透气性隐形眼镜（RGPCL）。患者的中位年龄和随访期分别为20（四分位间距[IQR]17-22）岁和25（15-38）个月。与基线相比，最终随访时角膜前表面的aKM，Kmax和KC筛查指数降低（P<0.05）。

No changes were observed in RGP-corrected visual acuity, TCT, pKM, or KC screening indices on the posterior corneal surface. The higher the baseline value, the greater the reduction in aKM and Kmax. Five patients (16%) experienced disease progression during follow-up. Patients with severe KC showed reduced anterior corneal surface curvature and no change in corneal thickness during an average follow-up period of 2–3 years while wearing RGPCLs..

角膜后表面的RGP矫正视力，TCT，pKM或KC筛查指数没有变化。基线值越高，aKM和Kmax的减少越大。五名患者（16%）在随访期间经历了疾病进展。严重KC患者佩戴RGPCLs后，平均随访2-3年，角膜前表面曲率降低，角膜厚度无变化。。

IntroductionKeratoconus (KC) is an eye disease characterized by corneal ectasia and thinning. It is accompanied by increased irregular corneal astigmatism and decreased vision, which affects a patient’s quality of life1,2. KC mostly occurs in young adults in their 20 s and is asymmetric and progressive3.

引言圆锥角膜（KC）是一种以角膜扩张和变薄为特征的眼病。。KC主要发生在20多岁的年轻人中，并且是不对称和渐进的3。

The disease progression varies in different age groups and may be rapid, slow, continuous, or intermittent until it stabilizes4,5,6,7.Corneal topography is an important tool in diagnosing KC and determining the severity of the disease1. Depending on the degree of corneal ectasia and visual impairment, patients with mild KC require glasses for vision correction, while those with moderate-to-severe KC require contact lenses or scleral lenses to correct their vision.

疾病进展在不同年龄组中有所不同，可能是快速，缓慢，连续或间歇性的，直到稳定4,5,6,7。角膜地形图是诊断KC和确定疾病严重程度的重要工具1。根据角膜扩张和视力障碍的程度，轻度KC患者需要眼镜进行视力矫正，而中度至重度KC患者需要隐形眼镜或巩膜镜来矫正视力。

In contrast, patients with severe KC, who cannot wear scleral lenses, require corneal transplant surgery8. The emergence of corneal cross-linking (CXL) has enabled the management of KC progression. This is beneficial because early diagnosis is crucial in controlling progression and improve prognosis9.

相比之下，不能佩戴巩膜镜片的严重KC患者需要进行角膜移植手术8。。这是有益的，因为早期诊断对于控制进展和改善预后至关重要9。

Despite the emergence and advancement of corneal tomography equipment and intelligent algorithms based on big data, which have enabled the early identification and diagnosis of KC, some patients do not seek medical treatment until a very severe stage due to neglect of symptoms or other reasons10. Moreover, patients with severe KC may lose the opportunity to undergo CXL because corneal thickness < 400 µm is a contraindication for this procedure11.

。此外，严重KC患者可能会失去接受CXL的机会，因为角膜厚度<400μm是该手术的禁忌症11。

Additionally, epidemiological surveys have shown that the prevalence of KC is higher in Asians than in other ethnic groups8.Therefore, understanding disease progression in KC can help physicians formulate effective treatment plans. However, long-term changes in the cours.

此外，流行病学调查显示，亚洲人KC的患病率高于其他种族8。因此，了解KC的疾病进展可以帮助医生制定有效的治疗计划。然而，课程的长期变化。

Table 1 Patient demographic data.Full size tableBaseline corneal topography findings showed that 24 of the 31 eyes with severe KC had common oval and papillary cones, whereas seven (22.6%) were slightly flat centrally with a raised peripheral ring-shaped cone; all seven patients had visible corneal scarring on tomography (Fig. 1).

表1患者人口统计数据。全尺寸表基线角膜地形图检查结果显示，严重KC的31只眼中有24只眼具有常见的椭圆形和乳头状视锥，而7只眼（22.6%）的中央稍平坦，周围环形视锥凸起；所有七名患者在断层扫描中都有可见的角膜瘢痕形成（图1）。

Figure 2 shows the tear distribution after fluorescent staining under rigid gas-permeable contact lens (RGPCL) in a patient with “ring-shaped” severe KC who underwent three-point contact fitting.Figure 1Special corneal morphology in three representative patients with severe keratoconus. The corneal topography reveals a flat cone center and steep mid-peripheral part forming a “ring-shaped” appearance in the upper images.

图2显示了在接受三点接触配件的“环形”严重KC患者中，在刚性透气性隐形眼镜（RGPCL）下进行荧光染色后的泪液分布。图1三名代表性的严重圆锥角膜患者的特殊角膜形态。角膜地形图显示扁平的圆锥体中心和陡峭的中间周边部分，在上图中形成“环形”外观。

Scheimpflug images show varying degrees of corneal scarring in the lower images.Full size imageFigure 2Distribution of fluorescein staining in tears of the eye with “ring-shaped” severe keratoconus wearing a rigid gas permeable contact lens using the three-point contact method.Full size imageFinal corneal topography measurements in 30 eyes with KC were obtained after RGPCL removal within 1 h; in one eye, it was obtained at the follow-up visit 6 months after the loss of the lens.

Scheimpflug图像在较低的图像中显示出不同程度的角膜瘢痕形成。全尺寸图像图2使用三点接触法佩戴刚性透气性隐形眼镜的“环形”严重圆锥角膜患者泪液中荧光素染色的分布。全尺寸图像在1小时内去除RGPCL后，获得了30只KC眼的最终角膜地形图测量结果；在一只眼睛中，它是在失去晶状体后6个月的随访中获得的。

The follow-up time between baseline and final corneal topography was 12–63 months, with a median of 25 (interquartile range [IQR] 15–38) months. The final comparison with baseline showed a decrease in anterior mean corneal radii of 3 mm (aKM), steep keratometry (Ks), and maximum keratometry (Kmax), but no change in RGPCL-corrected visual acuity (RGPVA), posterior mean corneal radii of 3 mm (pKM), or thinnest corneal thickness (TCT).

基线和最终角膜地形图之间的随访时间为12-63个月，中位数为25（四分位间距[IQR]15-38）个月。与基线的最终比较显示，前平均角膜半径（aKM），陡峭角膜曲率（Ks）和最大角膜曲率（Kmax）下降，但RGPCL矫正视力（RGPVA），后平均角膜半径（pKM）或最薄角膜厚度（TCT）没有变化。

Among the KC screening parameters, frontal surface curvature map (Sif), keratoconus vertex front (KVf), and Baiocchi–Calos.

在KC筛查参数中，有额叶表面曲率图（Sif），圆锥角膜顶点前缘（KVf）和Baiocchi-Calos。

Table 2 Baseline and final comparison of corneal topography parameters and corrected visual acuity.Full size tableDuring a median follow-up period of 25 (15–38) months, the 31 eyes with severe KC had a mean median 1.81 (0.06–3.46) D reduction in aKM, 2.37 (1.07–5.37) D reduction in Ks, and 5.92 (0.24–10.26) D reduction in Kmax.

表2角膜地形图参数和矫正视力的基线和最终比较。全尺寸表在中位随访25（15-38）个月期间，严重KC的31只眼的aKM平均中位数减少1.81（0.06-3.46）D，Ks平均减少2.37（1.07-5.37）D，Kmax平均减少5.92（0.24-10.26）D。

Factors influencing changes in aKM, Ks, and Kmax were analyzed separately by including age, sex, duration of follow-up, and baseline values as independent variables in the multivariate linear regression. The results indicated that higher baseline values of aKM and Kmax were associated with greater reductions during the follow-up period.

通过将年龄，性别，随访时间和基线值作为多元线性回归中的自变量，分别分析了影响aKM，Ks和Kmax变化的因素。结果表明，aKM和Kmax的较高基线值与随访期间的较大降低相关。

However, these independent variables had no effect on the change in Ks. The analysis results are presented in Table 3..

然而，这些自变量对Ks的变化没有影响。分析结果如表3所示。。

Table 3 Analysis of related factors of changes in the central mean curvature, steep curvature and maximum corneal curvature of the anterior corneal surface.Full size tableDuring the follow-up period, disease progression occurred in five (16.1%) of the 31 eyes with severe KC. Four patients experienced a Ks increase > 1.0 D/year, and four had a TCT decrease > 25 μm/year.

表3角膜前表面中央平均曲率，陡峭曲率和最大角膜曲率变化的相关因素分析。全尺寸表在随访期间，严重KC的31只眼中有5只眼（16.1%）发生疾病进展。四名患者的Ks增加>1.0 D/年，四名患者的TCT降低>25μm/年。

The specific changes in each patient are shown in Fig. 3. With the occurrence of disease progression as the dependent variable and age at diagnosis, sex, Kmax, TCT, and aKM as the independent variables and considering the duration of the follow-up period, Cox regression analysis was performed for the 31 KC cases and none of the above factors were found to be associated with KC progression (P > 0.05).

每个患者的具体变化如图3所示。以疾病进展的发生率为因变量，以诊断时的年龄、性别、Kmax、TCT和aKM为自变量，并考虑随访期的持续时间，对31例KC病例进行Cox回归分析，未发现上述因素与KC进展相关（P＞0.05）。

Statistical analysis results are available in Supplementary Table S1 online.Figure 3Changes of important parameters of corneal topography in patients with severe keratoconus at the beginning and end of follow-up. The upper graphs display changes in corneal topography parameters in five patients with progressive severe keratoconus.

统计分析结果可在线补充表S1中获得。图3随访开始和结束时严重圆锥角膜患者角膜地形图重要参数的变化。上图显示了5例进行性严重圆锥角膜患者角膜地形图参数的变化。

(a) is the change in astigmatism, (b) is the change in steep keratometry, and (c) is the change in thinnest corneal thickness. The lower graphs depict changes in corneal topography parameters in 26 patients with stable severe keratoconus (d) is the change in astigmatism, (e) is the change in steep keratometry, and (f) is the change in thinnest corneal thickness.Full size imageDiscussionIn this retrospective study, we analyzed the corneal topographic data of patients initially diagnosed with severe KC over the past 6 years, with a median followed up of 25 months, to observe changes in disease course.

（a） 是散光的变化，（b）是陡峭角膜曲率的变化，（c）是最薄角膜厚度的变化。下图描绘了26例稳定型严重圆锥角膜患者角膜地形图参数的变化（d）是散光的变化，（e）是陡峭角膜曲率的变化，（f）是最薄角膜厚度的变化。全尺寸图像讨论在这项回顾性研究中，我们分析了过去6年中最初诊断为严重KC的患者的角膜地形图数据，中位随访时间为25个月，以观察病程的变化。

All patients were RGPCL wearers with no history of ocular surgery, including corneal.

所有患者均为RGPCL佩戴者，无眼部手术史，包括角膜手术史。

Data availability

数据可用性

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

在当前研究期间生成和/或分析的数据集可根据合理要求从通讯作者处获得。

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Fuller, D. G. & Wang, Y. Safety and efficacy of scleral lenses for keratoconus. Optom. Vis. Sci. 97, 741–748 (2020).Article

Fuller，D.G。＆Wang，Y。巩膜镜片治疗圆锥角膜的安全性和有效性。光学。可见。科学。97741-748（2020）。文章

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Montalt, J. C., Porcar, E., España-Gregori, E. & Peris-Martínez, C. Visual quality with corneo-scleral contact lenses for keratoconus management. Cont. Lens Anterior Eye 41, 351–356 (2018).Article

Montalt，J.C.，Porcar，E.，España-Gregori，E。＆Peris Martínez，C。用于圆锥角膜管理的corneo巩膜隐形眼镜的视觉质量。Cont.晶状体前眼41351-356（2018）。文章

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Download referencesAcknowledgementsWe thank all patients who participated in this study.Author informationAuthors and AffiliationsThe First Affiliated Hospital of Zhengzhou University, Jianshe Road, Zhengzhou, 450000, ChinaXiaoDi Yang, YiRan Wang, YuYing Liu, Yong Lyu & WeiQun WangAuthorsXiaoDi YangView author publicationsYou can also search for this author in.

下载参考文献致谢我们感谢所有参与本研究的患者。作者信息作者和附属机构郑州大学第一附属医院，建设路，郑州，450000，中国杨小笛，王怡然，刘玉英，刘永柳和王伟群作者杨小笛观点作者出版物您也可以在中搜索这位作者。

PubMed Google ScholarYiRan WangView author publicationsYou can also search for this author in

PubMed Google ScholarYiRan WangView作者出版物您也可以在

PubMed Google ScholarYuYing LiuView author publicationsYou can also search for this author in

PubMed Google ScholarYuYing LiuView作者出版物您也可以在

PubMed Google ScholarYong LyuView author publicationsYou can also search for this author in

PubMed Google ScholarYong LyuView作者出版物您也可以在

PubMed Google ScholarWeiQun WangView author publicationsYou can also search for this author in

PubMed Google ScholarWeiQun WangView作者出版物您也可以在

PubMed Google ScholarContributionsX.Y. was responsible for data collection, editing, and manuscript writing; Y.W. contributed to data collection and English translation; Y.L. contributed to data statistical analysis; Y.L. and W.W. contributed to manuscript review and revision.

PubMed谷歌学术贡献x。Y、 负责数据收集，编辑和稿件撰写；Y、 W.为数据收集和英语翻译做出了贡献；Y、 L.有助于数据统计分析；Y、 L.和W.W.为稿件审查和修订做出了贡献。

All authors reviewed the manuscript.Corresponding authorsCorrespondence to.

所有作者都审阅了手稿。通讯作者通讯。

XiaoDi Yang or WeiQun Wang.Ethics declarations

杨小笛或王维群。道德宣言

Competing interests

相互竞争的利益

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Reprints and permissionsAbout this articleCite this articleYang, X., Wang, Y., Liu, Y. et al. Longitudinal assessment of the progression of severe keratoconus based on corneal topography.

转载和许可本文引用本文Yang，X.，Wang，Y.，Liu，Y。等人。基于角膜地形图的严重圆锥角膜进展的纵向评估。

Sci Rep 14, 19642 (2024). https://doi.org/10.1038/s41598-024-70084-4Download citationReceived: 17 June 2024Accepted: 12 August 2024Published: 23 August 2024DOI: https://doi.org/10.1038/s41598-024-70084-4Share this articleAnyone you share the following link with will be able to read this content:Get shareable linkSorry, a shareable link is not currently available for this article.Copy to clipboard.

Sci Rep 1419642（2024）。https://doi.org/10.1038/s41598-024-70084-4Downloadhttps://doi.org/10.1038/s41598-024-70084-4Share本文与您共享以下链接的任何人都可以阅读此内容：获取可共享链接对不起，本文目前没有可共享的链接。复制到剪贴板。

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KeywordsKeratoconusRetrospective studyRigid gas permeable corneal contact lens

关键词角膜接触镜回顾性研究GID透气性角膜接触镜

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Corneal diseasesEye manifestationsRefractive errors

角膜疾病表现屈光不正

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