It is important to distinguish between cornea guttata (primary and secondary), Fuchs endothelial dystrophy, and pseudo-exfoliation syndrome. Primary central cornea guttata is characterized by irregular excrescences of collagenous basement membrane material produced by endothelial cells in the central cornea. On the other hand, the secondary guttata is associated with trauma, degenerative corneal disease, and inflammation; it tends to disappear after the removal of the cause. [18, 19]
The primary central cornea guttata is classified as Stage 1 of Fuchs endothelial corneal dystrophy, some patients remain in this stage and never progress further. It may advance to the subsequent grades: Stage 2 (endothelial decompensation and stromal edema), Stage 3 (bullous keratopathy), and Stage 4 (avascular subepithelial fibrosis and scarring between the epithelium and Bowman’s membrane). [5]
This entity differs from the pseudoexfoliation syndrome, in which small, white, and fluffy pseudoexfoliative deposits, are usually observed on the corneal endothelium, as well as, pigment deposition in the central cornea. In these patients, the damaged endothelium may cause corneal decompensation. This distinct endotheliopathy, may have been previously misdiagnosed as an ‘‘atypical non guttata Fuchs’ endothelial dystrophy.’’[20]
Corneal endothelial cells are essential for maintaining corneal transparency by keeping the corneal stroma in a state of partial dehydration. Such homeostatic status is accomplished by a delicate balance between the rate of water entering the hydrophilic stroma through the endothelial barrier and its active removal by the action of the metabolic Na/K ATPase endothelial pump [21].
After birth, the corneal endothelial cell density (ECD) reaches its peak at approximately 6000 cells/mm2 which starts to decline during the first years of life due initially to corneal growth [22]. Then, cell density continues its gradual decay over time, particularly between the ages of 20 to 80 years at an estimated annual rate of 0.6% [6]. This slowly progressive cell loss is accompanied by a proportional increase in polymorphism and polymegethism [23].
When aging, toxicity, trauma, inflammation, or disease produce an ECD drop below 500 cells/mm2, irreversible stromal edema occurs, and eventually the corneal loses its transparency [24]. For many years it was thought that corneal endothelial cells could not regenerate. However, recent investigations have shown that endothelial cells retain their capacity to divide and renew although they rarely do so [25]. A hypothesis that may help explain, at least in part such cellular behavior postulates that certain groups of dividing cells may enter a process of cellular senescence or replicative failure that limits their capacity to maintain their lifespan [26, 27] This hypothesis is supported by an age-related increase in the number of senescent cells in the human corneal endothelium [28–30]. Despite the relentless pursuit of a better understanding of the biologic mechanisms implicated in the gradual endothelial cell loss found during aging, there are still more questions than answers. Most probably, this phenomenon is multifactorial involving environmental, hormonal, biochemical and physiologic process related to aging [31].
There are several studies from diverse populations around the world analyzing the corneal endothelial cell density and morphology. Although investigators differ in their findings concerning the relationship between age and gender, and the corneal endothelial characteristics, the literature clearly shows a significant difference in corneal endothelial properties among races and ethnic groups [7–10].
In this study, MCD was found to be within normal values for healthy corneas [32]. Our mean number of cells studied per patient is higher than reported by other authors.
In table 3, the MCD among different elderly populations from different countries is portrayed. Although none of the authors studied exclusively elderly patients, a stratified calculation based on their age groups was performed. The MCD of 2268 cells/mm2 found in our study across all age groups is very similar to the Caucasian population in Lithuania (2366 cells/mm2) [1]. the Turkish population studied by Goktas et al. (2215 cells/mm2) [11] and distant from the findings of Hashemian et al. [12] in Iran (1681.61 cells/mm2) and also from Padilla et al. in the Philippines (2780.45cells/mm2) [7].
It is of interest to mention the results of Graue et al. [13] and Molina et al. [14] in Mexican population from Central Mexico where patients in the 60 to 89 years group of age showed a MCD of 1805.33 cells/mm2 and 1910.42 cells/mm2 respectively, contrasting with our findings and suggesting that corneal endothelial cells characteristics may differ with our counterparts in the center and south of the country.
Another study in population from Central Mexico showed a MCD of 1909 cells/mm2 in patients with a mean age of 71 years, interestingly, this cohort of patients had unilateral pseudophakic bullous keratopathy that developed after cataract surgery [33].
In our population, no difference was found in MCD as patients got older, suggesting that Hispanic patients who maintain ocular health after 65 years can also preserve a fair number of endothelial cells. The latter is supported by the fact that 77% of patients had a cell density over 2000 cells/mm2 and only 17% showed an MCD < 1500 cells/mm2. It has been shown in previous reports that as the mean population studied increases, there is also an increased spread in the range of MCD counts, making the endothelial cell density measurement an unreliable index for the evaluation of corneal aging. The same finding applies to other animal species studied, like the dog, cat, monkey, and rabbit where the density and morphology of endothelial cells change with age, but the adult MCD remains constant [30, 31, 34].
As for the endothelial cell size and shape, our population showed a high degree of polymegethism and pleomorphism (MCV of 42.04% and PHC 42.3%). This findings correlate with the fact that in most populations studied, pleomorphism and polymegethism tend to increase as patients age, [35–38] and suggests that elderly Hispanic patients could have more pleomorphism and polymegethism than other ethnicities [1, 7–14].. Surprisingly, the group of ≥ 85 years showed the lowest rate of polymegethism and pleomorphism (33% and 45%, respectively).
Regarding CCT 537 (95% CI 528 to 546), we find interesting that these values are similar to those reported in a previous study performed by our group in younger patients (Mean age: 32.54 ± 12.04 years and Mean CCT: 545.69 ± 36.88 µm). The findings reported in both studies support the idea that Mexican population could present a different mean CCT and “normal” CCT could be redefined for clinical purposes in our context. [39]
Albeit some authors have found differences between gender in endothelial cell parameters [7–10], we found those differences in our population to be minimal with no statistical significance, as resumed in table 2.
Although our results come from a small population, we believe this sets the basis for a prospective study with larger sample size and higher statistical power, which may be eased as specular microscopy becomes more available for the Mexican population.
In conclusion, the endothelial cell characteristics of elderly Mexican Northeastern patients differ from their counterparts from central and south Mexico and other nations. A high prevalence of polymegethism, pleomorphism, and guttata are present, but not in the > 85 year group, where within the sample size studied, the lowest rate of these characteristics was described.