The demographic profile, corneal morphometric characteristics, clinical course, and therapeutic outcome of Latin American patients with FECD have not been previously described. We analyzed 102 eyes from 51 Mexican-mestizo patients with FECD. Females predominated males by three to one, comparable to other Caucasian series showing a similar female predominance [4, 7, 8]. However, in a study performed in the United States, Rosenblum et al. reported a much larger female predominance (7.3:1) [17]. Another Caucasian study of 32 patients from Tangier found a female-to-male ratio of 2.6:1 [9], while data from Asians on predominantly corneal guttae stage I of FECD reported a ratio of 2.8:1 [11]. On the other hand, Lorenzzetti et al. found no significant differences in the incidence of corneal guttae between Caucasians and African-Americans [8].
Regarding the development of advanced FECD, female sex and age are the most significant risk factors for severe FECD requiring corneal transplantation [4, 18, 19]. Afshari et al. and Chan et al. reported a female prevalence of 77.6% and 61.8%, respectively, in FECD patient candidates for corneal transplantation [4, 18]. Contrary to these reports, only 17 eyes (16.67%) required corneal transplantation in our study. Of those, 64.7% were female patients. The reason for this gender-based disparity remains elusive. However, a recent murine study found that ultraviolet-A (UVA) light triggers estrogen-metabolizing enzymes and forms reactive estrogen metabolites and estrogen-DNA adducts in females but not male mice [20]. Moreover, UVA light also results in greater CEC loss and edema due to loss of tight-junction proteins (e.g., ZO-1) [16]. UVA exposure, however, might not fully explain the higher prevalence of FECD in women. In a study measuring the amount of ultraviolet radiation dose received by United States citizens, Godar et al. reported that males received higher doses [21]. Castanedo-Cazares et al. reported similar results in a Mexican-mestizo population [22]. The same author reported in another study that Mexicans disregard the potentially harmful effects of sun exposure, despite being aware of such effects [23]. Although UVA light damage seems a plausible explanation for the presence of FECD in our population, the gender-based disparity cannot be explained on this basis. More extensive studies are required to establish such a potential association.
Like previous studies, the average age of affected individuals was 65.35 years [11, 17]. Early-onset FECD, described as disease development before 40, occurred in only 3 (5.89%) of our patients. Such finding differs from other registries reporting a prevalence of up to 31.5% of FECD patients aged 10 to 39 [8]. So far, only the presence of the COL8A2 gene is associated with the early-onset form of FECD [24]. A variant presenting in the first decade of life has been described in patients with the COL8A2 gene mutations [25].
After excluding eyes with other potential causes of vision loss, the mean baseline BCVA in our study was 0.32 LogMAR (20/43 Snellen eq.), which differs from other studies reporting better visual acuities (0.08 LogMAR, 20/24 Snellen eq.) in patients with FECD at diagnosis [26]. Of those, 12 (23.01%) and 6 (11.54%) eyes were classified at presentation as FECD stage 2 and 3, respectively. Thirty-four eyes (65.4%) were classified as stage 1.
Although variable, a cutoff value ≥2,500 endothelial cells/mm2 has consistently been reported as normal [26-30]. In FECD patients, such values significantly decrease as the disease progresses. In a study performed in Asians, Kobashi et al. found a mean ECD of 1,893 cells/mm2 in patients with FECD [26]. In the present study, we report an even lower ECD (1,516.69 cells/mm2). Such difference might be explained by ethnicity but also by a delayed diagnosis. Previous studies have shown significant differences in the corneal ECD among different racial and ethnic groups and ages [27, 29]. McGlumphy et al. reported that, compared with Caucasians, African Americans and Asians had increased values of ECD, Hispanics had lower values [27]. A decrease in ECD occurred in our series with the increasing severity of FECD and age (Table 5). Corneal thickness represents an important parameter to measure disease progression and aid in surgical decision-making [16]. The mean CCT was 523.92 µm in stage-I, 564.08 µm in stage-II, and 607.40 µm in stage-III in our study population. Kopplin et al. evaluated the relationship between CCT and FECD severity [31]. They found that with the increasing severity of FECD, an increase in CCT occurred. Such findings were also observed in patients without clinically visible edema [31]. Moreover, a study of 259 eyes managed with PKP found that a preoperative corneal thickness of 775 µm or greater was a significant risk factor for a BCVA of 20/100 or worse, while below that level, BCVA was 20/60 [4].
Seventeen percent of eyes required corneal transplantation. Only two out of seven eyes (28.6%) managed with PKP or triple procedure achieved a BCVA better than 20/200. However, the two eyes managed with DMEK achieved a final BCVA of 20/20 and 20/40. A recent study performed by Castellucci et al. compared the visual outcomes and quality of life after bilateral ultrathin Descemet’s stripping automated endothelial keratoplasty (UT-DSAEK) with bilateral PKP for FECD [32]. Corneal high-order aberrations (HOAs), contrast sensitivity, BCVA, and quality of life were measured. After a mean follow-up of 32 months, all outcomes significantly favored UT-DSAEK. Only posterior HOAs were similar among groups. This study, however, was retrospective and included a small sample (13 in the UT-DSAEK group vs. 11 in the PKP group) [32]. Regarding graft clarity and ECD, Price et al. demonstrated that DSAEK and PKP were comparable after 3-years. Notwithstanding, a 3.2-mm DSAEK incision width was associated with significantly less ECD than a 5.0-mm incision [33].
The limitations to this study have to do with its retrospective nature, limiting the availability of standardized and complete clinical data and, a reasonable number of eyes analyzed had other ocular comorbidities that precluded an accurate analysis. Strengths include the fact that this is the first study evaluating the clinical profile of FECD patients in a Latin American population.