## 4 Discussion
However, such proposals must be considered with caution since this observation is limited to a single study with a relatively low number of samples, requiring further studies and confirmation for greater certainty of the evidence. Eusol-C, one of the main preservation media used in Europe, presents a similar composition of Cornea Cold, including a high concentration of dextran and the absence of ascorbic acid and chondro sulfate. Dextran is an osmotically active agent present in most commercial preservation preparations that penetrates the cornea during preservation [36]. Despite the similar composition between Eusol-C and Cornea Cold, these media performed differently when compared with Optisol-GS, as no statistical difference was found between Eusol-C and Optisol-GS solutions up to 7 days [25; 42]. [PERSON] et al. [42] reported that the endothelial cell density of the corneas preserved for one week in Optisol-GS was the same as that of the corneas kept in Eusol-C for 1-2 days. Nevertheless, these results cannot be interpreted directly due to a lack of difference between the preservative preparations since the comparisons were not carried out under similar time conditions. Furthermore, other quantitative and qualitative endpoints related to cornea integrity were not evaluated [42]. The presence of 2 mM glutamine as a basic supplement in the Eusol-C medium, was proposed as compensating for the absence of the additives present in OptisolGS, causing the same final effect on cornea preservation [43]. The findings reported by [PERSON] et al. [27] suggest that, in eye banks that operate with a short interval between preservation and transplantation (7 days), Eusol-C would be a proper substitute for Optisol-GS. A recent issue has brought attention to the relevance of comparing the performance of Optisol-GS and Eusol-C, as a shortage of Optisol in the US reported by the American Academy of Ophthalmology by April 2022 [44], due to supply chain difficulties, led to the Eye Bank Association of America (EBAA) arranging for the importation of Eusol-C, mainly marketed in Europe. In this context, the literature provides evidence of similar performances on donor tissue preservation for keratoplasty [27; 42]. Furthermore, Eusol has been reported as presenting lower operational costs outside of the US [27]. One of the main limitations of the literature assessed in the present review was the restricted number of corneas enrolled in the selected studies due to a high demand for donor corneas and short preservation-to-transplantation times [27]. In addition, there are probably other available outcomes of the use of different cold corneal storage media compared with Optisol-GS that may not have been assessed in this review. Preliminarily, the intent of this review included the conduction of meta-analyses comparing such results, depending on the methodological heterogeneity across studies, by calculating the mean difference or relative risk corresponding to the outcomes reported as continuous or categorical data, respectively. However, the assessment of the available data showed the impossibility of this kind of analysis due to: (i) a considerable methodological heterogeneity between the studies, mainly related to differences in the composition of the media compared with Optisol-GS, preservation conditions, and follow-up periods; and (ii) the variation in the type of data reported for the outcomes assessed. Therefore, this review focused on the mainly employed corneal integrity parameters, for which more data are available to establish comparisons between studies. Regarding the limitations of the review process, it is also important to point out that four papers could not be retrieved as full texts and there is a risk that they could become eligible for this review.