Introduction

Fuchs endothelial corneal dystrophy (FECD) is a progressive corneal disease characterized by endothelial cell loss and the accumulation of guttae on the inner corneal layer, leading to corneal edema and visual deterioration.¹ The disease is influenced by both genetic and environmental factors, particularly oxidative stress, which plays a central role in the progressive endothelial damage observed in FECD.¹ Most cases manifest in the fifth or sixth decade of life, with late-onset FECD being the predominant form.¹

While the prevalence of FECD varies significantly across different populations, this study did not aim to determine the prevalence. However, existing data suggests a higher prevalence in Caucasians compared to Asian populations, with significant variability even among different Asian ethnicities.^2,3 For example, Chinese Singaporeans show a higher prevalence of FECD (6.7%) compared to Japanese and Indian populations.^4–6 In Thailand, a previous study reported genetic differences in FECD patients compared to Caucasians, highlighting the ethnic variability in the disease’s manifestation.⁷

Corneal transplantation remains the definitive treatment for advanced FECD, with endothelial keratoplasty (EK) now preferred due to its faster recovery and lower complication rates compared to penetrating keratoplasty (PK).⁸ However, PK remains prevalent in some regions, including parts of Southeast Asia, where resource constraints and limited surgical expertise influence treatment options.^1,9 Understanding regional patterns in FECD management is crucial, particularly given the increasing demand for corneal transplants and the long waiting periods for corneal donors in Thailand.

This study, which involves one of the largest cohorts of FECD patients in Thailand, provides critical insights into the clinical characteristics and demographic profile of this population. The findings reflect trends in corneal transplantation and patient management in Southeast Asia, where corneal donor shortages and evolving surgical techniques play a key role in treatment decisions. By identifying key clinical features of FECD, this study aims to support decision-making in the allocation of corneal transplantation resources and improve the care of patients with this debilitating disease.

Materials and Methods

Study Design and Setting

This single-center, retrospective cohort study was conducted at the Department of Ophthalmology and the Excellence Center for Cornea and Limbal Stem Cell Transplantation, King Chulalongkorn Memorial Hospital, Bangkok, Thailand. The study was approved by the hospital’s Institutional Review Board (IRB No. 0590/66, Certificate of Approval No. 1238/2023) and adhered to the principles of the Declaration of Helsinki. The study collected the data from January 2017 to June 2023.

Study Population

Patients were identified from hospital-based electronic medical records (EMR) between January 2017 and June 2023.

The inclusion criteria were:

• All patients who received a definite diagnosis of FECD by a corneal specialist and presented in the outpatient clinic during the study period.

Exclusion criteria were:

• Eyes with a history of prior keratoplasty at the time of first presentation.
• Eyes with a history of topical medication that could affect corneal endothelial health, such as rho kinase inhibitors.
• Eyes with a history of intraocular surgery or intraocular laser, including laser iridotomy (only excluded from the corneal endothelial cell count analysis).

Operational Definitions

• FECD Diagnosis: The diagnosis of FECD was made based on slit-lamp biomicroscopy findings, specifically the presence of corneal guttae, and/or confirmed through specular microscopy. In cases where corneal edema or decompensation was present, diagnosis was confirmed if corneal guttae were detected in the contralateral eye or if histopathology supported the diagnosis.
• Disease Progression: Progression of FECD was defined by clinical indicators such as increased central corneal thickness (CCT) leading to significant visual impairment, the development of bullous keratopathy, or a marked reduction in endothelial cell density (ECD) that raised concerns for intraocular surgery.
• Candidates for Corneal: Transplantation: Eligibility for corneal transplantation required donor allocation from the Thai Red Cross Eye Bank (TRCEB), patient readiness for surgery, and consent for the procedure.

Data Collection

Approval to access and use data from the Thai Red Cross Eye Bank (TRCEB) and the Chulalongkorn Corneal Registration System (CUCRS) was obtained, ensuring adherence to data privacy and confidentiality protocols. No informed consent process was done as the study involved retrospective data collection. Data were collected and recorded in a manner that ensured subjects could not be identified. The collected data included demographic information (age, gender, systemic diseases) and clinical data from both eyes (visual acuity, intraocular pressure, lens status, central corneal thickness [CCT], endothelial cell density [ECD]). Disease severity was graded using the Adamis grading system (Table 1). In cases where the medical record used the modified Krachmer (MK) grading system, the severity was converted to align with the Adamis system for consistency.

Table 1 Adamis’ Grading of Fuchs Endothelial Corneal dystrophy

Table 2 Demographic Profiles and Systemic Comorbidities of FECD Patients

Table 3 Clinical Characteristics of FECD Patients at the Initial Visit

Table 4 Annual Changes in Central Corneal Thickness and Endothelial Cell Density by FECD Stage

Table 5 Surgical Interventions in Phakic and Pseudophakic Eyes with FECD

Details regarding corneal transplantation, such as the date of donor request, surgery type, and related data, were retrieved from the Thai Red Cross Eye Bank (TRCEB) and the Chulalongkorn Corneal Registration System (CUCRS).

Statistical Analysis

Descriptive statistics were used to summarize the demographic and clinical characteristics of FECD patients. Categorical variables were presented as frequencies and percentages, while continuous variables were summarized as means with standard deviations or medians with interquartile ranges (IQR), depending on the data distribution. Normality was assessed using visual inspection of histograms and descriptive statistics.

Comparisons between groups (such as different grades of disease severity or corneal transplantation status) were performed using chi-square tests for categorical variables and independent sample t-tests or Mann–Whitney U-tests for continuous variables, as appropriate. A p-value of <0.05 was considered statistically significant. Missing data were handled by excluding the affected variables from analysis, with the proportion of missing data reported where applicable.

Results

Demographics

A total of 900 patients (1,743 eyes) were included in the study. The mean age of the cohort was 63.94 years (±11.47), with an age range of 11 to 95 years. The sex distribution showed that 77.2% of patients were female (n=695) and 22.8% male (n=205). In terms of home location, 67.0% of patients (n=603) resided in Bangkok, while the remaining 33.0% (n=297) were from outside Bangkok. Systemic comorbidities included diabetes mellitus (17.4%) and hypertension (38.6%), as outlined in Table 2. A family history of FECD was reported in 9.1% of patients.

Baseline Clinical Characteristics

The baseline clinical characteristics were analyzed for the entire cohort of 1,743 eyes. The median best-corrected visual acuity (BCVA) was 0.2 LogMAR, with 81.23% of eyes having a BCVA of better than 20/63, while 5.06% had a BCVA worse than 20/200. The mean intraocular pressure (IOP) was 13.09 ± 3.38 mmHg. Glaucoma was present in 8.95% of eyes, and 27.83% had a history of prior intraocular surgery or laser procedures. Most eyes (83.71%) were classified as Adamis’ grade I. The mean central corneal thickness (CCT) was 565.04 ± 59.58 µm, and the mean endothelial cell density (ECD) was 2086.96 ± 639.99 cells/mm². Table 3 summarizes the clinical characteristics at baseline.

Clinical Course

Table 4 presents detailed annual changes in central corneal thickness (CCT) and endothelial cell density (ECD) over a 5-year follow-up period. Due to the high rate of surgical intervention, particularly cataract surgeries, only eyes without prior surgical interventions were included in this analysis to capture the natural progression of FECD. Most eyes classified as Adamis’ grade I showed stable ECD values over time, while Adamis’ grade II eyes exhibited a progressive decline in ECD, particularly after the first year. The percentage change in CCT and ECD for different stages of the disease is summarized in Table 4.

Disease Management

A total of 20.4% of phakic eyes (n=1,345) underwent cataract surgery during the follow-up period, with 6 eyes (2.2%) requiring corneal transplantation within five years. Pseudophakic eyes (n=394) had a higher rate of corneal transplantation (16.2%), with DMEK being the most common procedure (57.8%), followed by PK at 18.8%. Combined surgeries, particularly “Triple-DMEK” (corneal transplantation with DMEK), were performed in 96.5% of cases. The breakdown of surgical interventions for phakic and pseudophakic eyes is summarized in Table 5.

Cumulative Incidence of Corneal Transplantation

To evaluate the cumulative incidence of corneal transplantation, we focused on the 1,241 eyes diagnosed after 2017, for which complete follow-up data were available. A total of 8.1% of these eyes underwent corneal transplantation within the 5-year follow-up period. Among these, 26% received donor tissue from international sources, highlighting the reliance on imported donor tissue due to the limited availability of domestic donors. The cumulative incidence of corneal transplantation over time is shown in Figure 1.

Figure 1 Cumulative incidence of corneal transplantation over time.

Corneal Transplantation Trends

Between January 2017 and June 2023, 215 eyes underwent corneal transplantation at our institution, with 29 eyes (13.5%) receiving imported donor tissue. DMEK was the most common procedure, increasing from 26.3% of corneal transplants in 2017 to 90.9% in 2023, reflecting the growing preference for this less invasive method. The use of PK decreased from 15.8% to 9.1% during the same period, and Descemet stripping automated endothelial keratoplasty (DSAEK) was phased out entirely by 2023. Figures 2 and 3 illustrate the distribution of corneal transplantation procedures over time.

Figure 2 Annual distribution of corneal transplantation procedures by type.

Figure 3 Percentage of corneal transplantation procedures by type.

Corneal Transplantation Outcomes

A total of 215 corneal transplantations were performed. Graft survival rates were 94.8% at 6 months, 94.3% at 1 year, 91.8% at 2 years, 86.9% at 3 years, 83.6% at 4 years, and 76.2% at 5 years. These data are illustrated in Figure 4.

Figure 4 Graft survival rates over time following corneal transplantation.

The average post-operative ECD decreased progressively over time. At 6 months, the average ECD was 1,707.6 ± 603.9 cells/mm², reducing to 1,667.8 ± 668.0 cells/mm² at 1 year, and further declining to 1,140.7 ± 684.4 cells/mm² at 5 years. These trends are presented in Figure 5.

Figure 5 Average endothelial cell density over time after corneal transplantation.

Donor Registration Data

Among the 1,241 eyes included in the cumulative incidence analysis, 67.4% registered for a corneal donor request during the 5-year follow-up period. The majority of registrations occurred at the first presentation visit (84.8%). Despite this, 45.6% of eyes remained on the waiting list by the final follow-up visit, underscoring the challenges posed by corneal donor shortages. Figure 6 presents the percentage of donor registrations by year of follow-up.

Figure 6 Percentage of corneal donor registrations by year of follow-up since initial presentation.

Discussion

FECD is a bilateral, progressive disorder characterized by corneal endothelial cell loss, guttae formation, and eventual stromal edema, which can significantly impair vision.¹ Our study analyzed the demographic profiles, clinical characteristics, and treatment decisions in a cohort of 900 Thai FECD patients (1,743 eyes). This data is particularly valuable given the limited reports on FECD in Southeast Asian populations, and it provides new insights into the disease progression and management in this region.

Consistent with global findings, FECD was more prevalent in women, though the reasons behind this gender preference remain unclear.¹ The mean age of diagnosis in our cohort was 63.8 years, aligning with reports from other Asian populations, such as India (59–62 years) and Japan (62.8 years).^3,5,11,12 This supports the predominance of late-onset FECD, which typically begins in the fifth decade of life and progresses over subsequent decades.

One notable finding in our cohort was the high prevalence of systemic comorbidities. Diabetes mellitus (DM) affected 17.4% of patients, a higher rate than reported in Mexican (11.8%) and US (12%) studies.^13,14 Hypertension was also prevalent in 38.6% of our patients. These findings underscore the importance of monitoring systemic comorbidities in FECD patients, as conditions like DM and hypertension may exacerbate endothelial dysfunction and accelerate disease progression.^15,16

In terms of visual function, most eyes presented with early-stage FECD, as reflected by the high proportion of eyes classified as Adamis grade I (83.7%). The majority of FECD diagnoses were incidental, detected during routine check-ups or pre-operative cataract assessments. Early detection allows for appropriate planning of cataract surgery, a frequent intervention in this patient group. Only a small proportion of eyes were categorized as Adamis grade II or higher, and these more advanced cases were more likely to require corneal transplantation. Our data reinforces the importance of early detection and regular monitoring in managing FECD.

The progression of FECD was assessed through endothelial cell density (ECD) and central corneal thickness (CCT) over a five-year follow-up period. In early-stage FECD (Adamis grade I), a measurable decline in ECD was observed, but average ECD values remained above 2,000 cells/mm² after five years, indicating slow progression in many cases. However, more advanced disease (Adamis grade II or higher) was associated with lower baseline ECD and higher CCT, often leading to corneal transplantation. These findings align with previous studies that highlight the importance of ECD and CCT monitoring to determine the appropriate timing for surgical intervention.¹⁷

The rate of corneal transplantation in our study (8.1% over five years) was consistent with other studies reporting rates between 4.4% and 21%.^3,13,14,18 DMEK was the most common procedure, accounting for 69.3% of cases, reflecting the global shift toward endothelial keratoplasty (EK) due to its superior visual outcomes and quicker recovery time compared to PK.^19,20 This mirrors the global trend in regions such as the United States, Europe, and Singapore.^19–22

Cataract surgery was also a key intervention in our cohort, with 20.4% of phakic eyes undergoing the procedure. Only 2.2% of these eyes required corneal transplantation within five years, suggesting that cataract surgery can effectively delay the need for keratoplasty in early-stage FECD.²³ For more advanced cases, combined procedures, such as “Triple-DMEK” (corneal transplantation with DMEK and cataract surgery), were frequently performed, accounting for 73.1% of combined surgeries. Surgical decisions, as noted, depended on multiple factors, including cataract density, endothelial cell density, corneal thickness, graft waiting time, and both patient and surgeon preference. Patients with a preoperative central corneal thickness > 640 μm and/or an endothelial cell density < 1000 cells/mm² are at high risk of corneal decompensation following cataract surgery alone, as previously reported.²³ These thresholds are typically used to guide discussions with patients about surgical options. However, variability in decision-making among surgeons remains a study limitation. This approach offers several advantages, including reducing the number of surgeries and overall healthcare costs, particularly for patients with advanced disease.^24,25

Our study demonstrated a 5-year graft survival rate of 76.2%, which is lower than rates reported in other studies but reflects the inclusion of both PK and EK in our cohort.^26–29 Dunker et al reported better 2-year graft survival for PK (97%) and DSAEK (93%) compared to DMEK (71%) in the European Cornea and Cell Transplantation Registry, highlighting variability in outcomes among different techniques.²⁶ Similarly, Ang et al found superior 5-year survival for DSAEK over PK in Asian eyes with FECD and bullous keratopathy in the Singapore Corneal Transplant Registry.²⁷ These findings suggest that while PK remains a viable option, EK techniques like DSAEK and DMEK generally yield better long-term outcomes, particularly in developed settings with standardized surgical techniques. Our study’s lower survival rates may reflect our inclusion of PK cases and the limited number of patients with long-term follow-up. However, the increasing trend toward EK in our population is expected to enhance graft survival rates in future reports. Further research with larger cohorts and extended follow-up is essential to validate these observations and explore additional factors influencing survival outcomes.

The corneal tissue shortage in Thailand presents a significant challenge, with average waiting times for non-urgent corneal transplantation ranging from 3 to 4 years. In our cohort, only 8.8% of eyes that registered for donor tissue received a transplant within the five-year follow-up period. The long waiting times contribute to early registration for donation, even when immediate surgery is not necessary, potentially burdening the eye banking system. Refining the criteria for donor registration could help reduce unnecessary registrations and alleviate strain on the system.

This study has several limitations. Its retrospective nature may introduce selection bias, particularly if patients with different clinical outcomes did not return for follow-up. Additionally, missing data were excluded from the analysis, which could affect the generalizability of the findings if the data were not missing completely at random. Lastly, the study’s focus on a Southeast Asian population means that the findings may not be fully applicable to other populations with different genetic and environmental factors. Despite these limitations, the study provides important insights into the management and progression of FECD in Thailand.

Conclusion

This study provides a comprehensive analysis of the demographic profile and clinical characteristics of FECD in Thai patients. It highlights the high prevalence of systemic comorbidities and the predominance of early-stage FECD, allowing for conservative management in many cases. The increasing use of DMEK, mirroring global trends toward less invasive surgical interventions, emphasizes the evolving treatment landscape in Southeast Asia. These findings underscore the need for continued advancements in surgical techniques and improved eye banking practices to address corneal tissue shortages in the region.