Of course it is not guttae themselves but reduced endothelial cell density (ECD) and secondary loss of pump-function that is the primary cause for visual loss in FCED.
In the majority, bilateral guttae become clinically detectable in middle age, more frequently in women.
In bilateral disease, the clinical presence of corneal guttae is diagnostic.
Corneal endothelial specular microscopy (see Figure 3) or confocal microscopy can confirm reduced ECD and the presence of guttae, but such imaging is usually difficult in an already oedematous cornea.
The few studies that have screened for the presence of corneal guttae in general populations suggest relatively high prevalence of up to 5% in the over 60s age group.
Although the severity of FECD was usually graded clinically on the basis of the area and confluence of guttae, and the presence of edema [15, 28], we divided eyes with FECD in our study into stages with and without the presence of corneal edema only, which were correlated to grades 0-4 and grade 5 in Krachmer's grading system, respectively.
Parameters as mean AD, DM/AD, and CCT were compared with GEE analysis for 99 eyes, including 53 normal eyes and 46 FECD with guttae alone eyes.
Parameters as mean AD, DM/AD, and CCT were compared for all 53 diseased eyes in the study group, which were further separated by clinical examination into guttae alone group (46 eyes in 24 patients) and edema group (7 eyes in 4 patients).
Our findings were similar to the higher reflectivity, or "Camel sign," on the densitograms of FECD patients reported by Renato Ambrosio et al.,  who indicated that the second hump corresponded to corneal guttae at DM level.
We also compared normal eyes with FECD eye with guttae alone to exclude the effect of corneal edema in severe FECD eyes in causing the difference.
We found that DM/AD failed to show significant difference between guttae alone group and edema group.