We read with great interest the article by Kaufman et al.1 that describes a simple descemetorhexis to resolve corneal edema while at the same time not limiting future cataract extractions. Of most interest to us is this revolutionary technique to treat Fuchs endothelial dystrophy. These unanticipated cases of corneal clearing led us to publish a review concerning in vivo corneal endothelial regeneration, gathering all case reports of unexpected corneal clearing.2 Not only did we collect 47 patients who had such a descemetorhexis (65% clearing) but also 41 cases (80.5% clearing) with complicated endothelial keratoplasty and 12 cases of corneal clearing after troublesome cataract extraction (100% success).
We observed 2 findings recurring in this case report. First, we are convinced that removal of guttae is imperative for proper migration, which has also been shown by in vitro studies.3 The descemetorhexis was more successful in cases when the size was approximately 4.0 to 6.0 mm, suggesting this treatment is applicable for early-stage Fuchs endothelial dystrophy patients. Such a diameter removes all (central) guttae and leaves behind plenty of healthy cells.
The authors observed that “guttae surrounding the descemetorhexis…gradually increased and became confluent,” suggesting that the descemetorhexis might have been slightly too small, although we cannot argue with the result. We are curious as to their progression and whether they will accumulate over time, resulting in recurrent Fuchs endothelial dystrophy.
Second, we noted that corneal edema should resolve within a critical time period of approximately 3 months. Here, the patient's cornea cleared within 6 weeks, which indeed classifies this patient a (fast-)responder.4 If no initial clearing is detected within the first 2 months, we believe a salvage endothelial keratoplasty should be performed. All salvage surgeries reported were successful and performed within 4.0 to 8.5 months after descemetorhexis.2
Removal of the guttae, a limiting factor of migration, is not the only hurdle to overcome. In the cohort we studied, all cases with normal endothelium cleared, whereas only 65% of Fuchs endothelial dystrophy patients improved. We suspect that the migratory/proliferative capacity of the peripheral Fuchs endothelial dystrophy endothelium is further affected to different degrees, rendering outcomes unpredictable at present.
Regardless of migration, the authors mention that this phenomenon is mediated by an “unidentified intraocular chemical messenger.” Indeed, the mechanism in humans in vivo is not identified yet; however, we would like to mention that when looking to in vitro and neonatal animal studies, there are reasons to believe that an immature differentiation status of the peripheral endothelium and a process called contact inhibition in relation to upregulation of cyclin-dependent kinases are most likely involved.2,5
To conclude, we are excited about studies in this specific domain and hope to elucidate the intrinsic mechanism together with clinicians and scientists in the coming years. Once we succeed to fine-tune this therapy, corneal donor lists would be shortened significantly as the largest patient population now are Fuchs endothelial dystrophy patients, as Kaufman et al. indicated.
Kaufman AR, Nosé RM, Lu Y, Pineda R II. Phacoemulsification with intraocular lens implantation after previous descemetorhexis without endothelial keratoplasty. J Cataract Refract Surg
Van den Bogerd B, Ní Dhubhghaill S, Koppen C, Tassignon M-J, Zakaria N. (2018). A review of the evidence for in vivo corneal endothelial regeneration. Surv Ophthalmol, 63
, 22-31, Available at: http://www.surveyophthalmol.com/article/S0039-6257(17)30105-4/pdf
Rizwan M, Peh GS, Adnan K, Naso SL, Mendez AR, Mehta JS, Yim EKF. In vitro topographical model of Fuchs dystrophy for evaluation of corneal endothelial cell monolayer formation. Adv Healthc Mater
Rao R, Borkar DS, Colby KA, Veldman PB. Descemet membrane endothelial keratoplasty after failed Descemet stripping without endothelial keratoplasty. Cornea
Joyce NC. Proliferative capacity of corneal endothelial cells. Exp Eye Res