Unexpected findings: loss of corneal endothelial cells in Uygur patients with exfoliation syndrome

Exfoliation syndrome (XFS) is a condition wherein the extracellular matrix (ECM) undergoes changes, affecting individuals of various ages. It is marked by the continuous buildup of abnormal fibrils in intra and extraocular structures [1, 2]. This condition impacts 10–20% of the elderly population, leading to a higher incidence among the elderly and glaucoma patients [3]. In China, 5.1% of Kashi Uygur residents [4], and 2.2% and 9.5% of Kuche Uygur individuals aged 60 and 80 years or more, respectively, exhibit XFS [5].

XFS gives rise to eye complications, such as exfoliation glaucoma (XFG), and heightens the risk of unsuccessful intraocular surgery due to zonular weakness. XFS endotheliopathy is a gradually advancing condition affecting the corneal endothelial layer, resulting in early corneal endothelial cell decompensation and potentially leading to serious bullous keratopathy [6‐8]. Numerous studies have examined the clinical data of XFS cases, investigating the characteristics of their anterior segment parameters. However, there is no consensus in the existing literature. To enhance the quality of available data and consider the prevalence of this condition, we conducted an assessment of anterior segment characteristics in Uyghur XFS/XFG cases.

A total of 56 Uygur patients with XFS/XFG (112 eyes) were included, comprising 44 XFG and 60 XFS eyes (data unavailable for 8 eyes). Additionally, 100 Uygur control patients with age-related cataracts (200 eyes) were enrolled. The study and control group had mean ages of 71.92 ± 5.81, 71.20 ± 4.76, and 71.01 ± 0.80 years, respectively (P > 0.05). The case group exhibited a predominance of male patients (χ² = 17.45, P < 0.001), with 44 (78.57%) male and 12 (21.43%) female XFS/XFG patients. Meanwhile, the control group consisted of 44 (44%) male and 56 (56%) female participants (Table 1).

We conducted a statistical analysis of eye parameters, including AL, ACD, CCT, and ECD, in both groups. A statistically significant difference was observed in ECD between the XFS/XFG and the control group, whereas the remaining indices did not exhibit significant differences. Further analysis of ocular parameters in XFS and XFG patients, distinct from those with age-related cataracts, revealed consistent findings. Notably, there were no significant differences between XFS and XFG patients (Table 2).

XFS exerts a comprehensive impact on the entire eye, with a notable emphasis on the anterior segment due to the accumulation of exfoliation material (XFM). Independently, it is linked with various disorders, including a small pupil, cataract, and zonular laxity. XFG, as the most common and severe associated disease, demonstrates heightened aggressiveness in comparison to primary open-angle glaucoma (POAG) [10‐13]. These distinctive features render XFS patients particularly vulnerable to corneal endothelium-related complications during cataract phacoemulsification surgery. Our study represents the first exploration of the anterior segment parameters before operation in Xinjiang Uygur, China, for XFS/XFG patients. It reveals a statistically significant reduction in corneal ECD in Uyghur XFS/XFG patients compared to older cataract patients. This underscores the importance of assessing corneal status preoperatively and implementing intraoperative corneal endothelial protective measures.

Vaiciuliene et al. [14] conducted a review, noting that Tomaszewski et al. had previously used specular microscopy to assess ECD in individuals with 133 eyes with XFS syndrome (65 with glaucoma, 68 without glaucoma) and 84 eyes without XFS syndrome. In comparison to the control group, the XFS group exhibited a significantly lower ECD (2297 ± 359 cells/mm² vs. 2503 ± 262 cells/mm²). This study also examined the ECD change in the XFG group, revealing that although there was no statistically significant difference between the XFS and XFG groups, the ECD in the XFG group (2241 ± 363 cells/mm²) was significantly lower than that in the control group [15]. Kristianslund et al. indicated that, before surgery, there was no significant difference in ECDs between the XFS and control groups [16]. Ucar et al. [17] similarly found no difference in ECD between XFS and cataracts before their investigation.

Various studies have assessed anterior ocular segment parameters in both XFS and XFG patients, yielding diverse findings. Kaygisiz et al. [18] compared these parameters among XFS, XFG, and normal subjects, finding no differences in anterior segment indexes between the XFS and XFG groups. However, in another report, corneal biomechanical indexes, including corneal hysteresis (CH), corneal resistance factor (CRF), and CCT, differed in XFS cases compared to healthy controls, with more pronounced changes in XFG cases [19]. In Turkey patients, those with XFG and XFS exhibited greater lens thickness, increased ACD, and reduced CCT compared to normal subjects [18]. Contrarily, our study found no significant difference in CCT between XFS/XFG and control patients, while a clear and significant difference was observed in corneal ECD, without distinction between the XFS and XFG groups. ECD, being a crucial indicator reflecting corneal condition, warrants special consideration in individuals with chronic eye disorders like recurrent uveitis, glaucoma, and PEX. It is also noteworthy in cases of IOL dislocation, especially prior to ophthalmological interventions [14]. We hypothesize that factors such as the accumulation of XFM may influence anterior chamber indexes during the progression from XFS to XFG, altering anterior chamber structures.

The outcomes of these studies have shown less consistency, and our endeavor is to contribute additional data to the clinical profile of individuals affected by XFS/XFG. Another study suggested elevated incidence rates for glaucoma (77.4%), cornea guttata (45.2%), and XFG (16.1%) in cases with a short AL [20]. However, our data showed no difference in AL between XFS/XFG and cataract patients. There were also no differences in ACD and W–W distance. This may be attributed to the limited sample size, necessitating a broader case pool, balanced gender representation, and preferably multicenter clinical studies for more robust and convincing data. This study underscores the importance of careful patient selection and adequate sample size, with a preference for using the normal population as a reference for comparison.

In this study, corneal ECD was found to be reduced in patients with XFS and XFG when compared to age-related cataract subjects. Despite the lower ECD values observed, all participants maintained values greater than 2000/mm². Advancements in equipment and surgical techniques have significantly reduced the risk of corneal decompensation following cataract surgery in XFS patients. However, it is crucial to remain vigilant in order to enhance surgical safety in individuals with XFS/XFG and proactively address potential complications before they arise.