Clinical Factors for Early and Late Endothelial Cell Loss After Corneal Transplantation
- 25 Downloads
Purpose of Review
To consider the relative importance of factors associated with post-keratoplasty endothelial cell loss.
Lamellar keratoplasty continues to supplant penetrating keratoplasty. When host endothelium is healthy, retaining it with deep anterior lamellar keratoplasty significantly reduces long-term endothelial cell loss. Endothelial keratoplasty and penetrating keratoplasty differ fundamentally in relative rates of early and late central endothelial cell loss, yet at 10 years, their cumulative cell loss is similarly substantial. The greatest risk factor for post-keratoplasty endothelial decompensation is prior glaucoma filtration surgery, particularly an aqueous shunt. Interestingly, vital dye staining and sophisticated imaging software suggest that the actual viable endothelial cell density of donor corneas is often overestimated by specular microscopy, inflating estimates of early cell loss.
Corneal graft longevity is often determined by endothelial cell survival. Adoption of new surgical techniques has improved graft survival, and new imaging techniques allow more accurate preoperative endothelial cell evaluation.
KeywordsPenetrating keratoplasty Endothelial keratoplasty Anterior lamellar keratoplasty Endothelial cell loss Specular microscopy Eye bank
Compliance with Ethical Standards
Conflict of Interest
The authors declare that they have no conflict of interest.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
- 8.Huang J, Maram J, Tepelus TC, Modak C, Marion K, Sadda SR, et al. Comparison of manual and automated analysis methods for corneal endothelial cell density measurements by specular microscopy. J Optom 2017;S1888–4296(17):30049–30043.Google Scholar
- 12.•• Bhogal M, Lwin CN, Seah XY, Murugan E, Adnan K, Lin SJ. Real-time assessment of corneal endothelial cell damage following graft preparation and donor insertion for DMEK. PLoS One. 2017;12:e0184824. This study reported methods of vital dye staining and image analysis for more accurate assessment of cell loss associated with different keratoplasty techniques. CrossRefPubMedPubMedCentralGoogle Scholar
- 13.•• Bhogal M, Balda MS, Matter K, Allan BD. Global cell-by-cell evaluation of endothelial viability after two methods of graft preparation in Descemet membrane endothelial keratoplasty. Br J Ophthalmol. 2016;100:572–8. This study showed that eye bank estimations of central endothelial cell density overestimate the actual viable cell density after EK tissue preparation. CrossRefPubMedPubMedCentralGoogle Scholar
- 14.• AS G, Garcin T, Thuret G, He Z, Jullienne R, Trone MC, et al. Very early endothelial cell loss after penetrating keratoplasty with organ-cultured corneas. Br J Ophthalmol. 2017;101:1113–8. Using vital dye staining and sophisticated imaging software, this study showed that the viable endothelial cell density of the donor graft was substantially less than the specular microscopy reading reported by the eye bank. CrossRefGoogle Scholar
- 15.• Kitazawa K, Inatomi T, Tanioka H, Kawasaki S, Nakagawa H, Hieda O, et al. The existence of dead cells in donor corneal endothelium preserved with storage media. Br J Ophthalmol. 2017;101:1725–30. This study found mean dead cell rate was 5% in donor corneas stored in cold storage media. CrossRefPubMedGoogle Scholar
- 18.Price MO, Calhoun P, Kollman C, Price FW Jr, Lass JH. Descemet stripping endothelial keratoplasty: ten-year endothelial cell loss compared with penetrating keratoplasty. Ophthalmology. 2016;123:1421–7. This study used sophisticated statistical methods to model 10-year endothelial cell loss after DSEK and compared the results with 10-year cell loss after penetrating keratoplasty procedures performed in the multi-center Cornea Donor Study for similar indications. CrossRefPubMedGoogle Scholar
- 25.•• Sugar A, Gal RL, Kollman C, Raghinaru D, Dontchev M, Croasdale C, et al. Factors predictive of corneal graft survival in the Cornea Donor Study. JAMA Ophthalmol. 2015;133:246–54. This multi-center study assessed the factors predictive of penetrating keraotplasty survival for treatment of Fuchs’ dystrophy and pseudophakic or aphakic corneal edema. CrossRefPubMedPubMedCentralGoogle Scholar
- 30.Rose-Nussbaumer J, Alloju S, Chamberlain W. Clinical outcomes of Descemet membrane endothelial keratoplasty during the surgeon learning curve versus Descemet stripping endothelial keratoplasty performed at the same time. J Clin Exp Ophthalmol 2016;7(5).pii:599.Google Scholar
- 34.Heinzelmann S, Bohringer D, Eberwein P, Reinhard T, Maier P. Outcomes of Descemet membrane endothelial keratoplasty, Descemet stripping automated endothelial keratoplasty and penetrating keratoplasty from a single centre study. Graefes Arch Clin Exp Ophthalmol. 2016;254:515–22.CrossRefPubMedGoogle Scholar
- 48.Ruzza A, Parekh M, Ferrari S, Salvalaio G, Nahum Y, Bovone C, et al. Preloaded donor corneal lenticules in a new validated 3D printed smart storage glide for Descemet stripping automated endothelial keratoplasty. J Ophthalmol. 2015;99:1388–95.Google Scholar
- 51.• Hos D, Tuac O, Schaub F, Stanzel TP, Schrittenlocher S, Hellmich M, et al. Incidence and clinical course of immune reactions after Descemet membrane endothelial keratoplasty: retrospective analysis of 1000 consecutive eyes. Ophthalmology. 2017;124:512–8. This large single-center study confirmed that DMEK has a remarkably low rate of immunologic rejection. CrossRefPubMedGoogle Scholar
- 53.• Price MO, Feng MT, Scanameo A, Price FW Jr. Loteprednol etabonate 0.5% gel vs. prednisolone acetate 1% solution after Descemet membrane endothelial keratoplasty: prospective randomized trial. Cornea. 2015;34:853–8. This randomized study showed that topical corticosteroid strength can be reduced 1 month after DMEK to reduce the risk of intraocular pressure elevation without increasing the risk of immunologic graft rejection. CrossRefPubMedGoogle Scholar
- 54.• Price MO, Scanameo A, Feng MT, Price FW Jr. Descemet’s membrane endothelial keratoplasty: risk of immunologic rejection episodes after discontinuing topical corticosteroids. Ophthalmology. 2016;123:1232–6. This study showed that continued once-daily use of a low-dose topical corticosteroid is protective against immunologic rejection episodes after DMEK. CrossRefPubMedGoogle Scholar
- 57.• Nahum Y, Mimouni M, Busin M. Risk factors predicting the need for graft exchange after Descemet stripping automated endothelial keratoplasty. Cornea. 2015;34:876–9. This study confirmed that prior trabeculectomy or aqueous shunt was a major risk factor for post-keratoplasty endothelial decompensation. CrossRefPubMedGoogle Scholar
- 59.• Kang JJ, Ritterband DC, Lai K, Liebmann JM, Seedor JA. Descemet stripping endothelial keratoplasty in eyes with previous glaucoma surgery. Cornea. 2016;35:1520–5. This study confirmed that the post-keratoplasty risk of endothelial decompensation was increased significantly in eyes with previous aqueous shunt implantation. CrossRefPubMedGoogle Scholar
- 60.• Yagi-Yaguchi Y, Yamaguchi T, Higa K, Suzuki T, Yazu H, Aketa N, et al. Preoperative aqueous cytokine levels are associated with a rapid reduction in endothelial cells after penetrating keratoplasty. Am J Ophthalmol. 2017;181:166–73. This study showed that higher preoperative aqueous levels of certain cytokines were associated with increased post-keratoplasty endothelial cell loss. CrossRefPubMedGoogle Scholar
- 61.• Yazu H, Yamaguchi T, Aketa N, Higa K, Suzuki T, Yagi-Yaguchi Y, et al. Preoperative aqueous cytokine levels are associated with endothelial cell loss after Descemet’s stripping automated endothelial keratoplasty. Invest Ophthalmol Vis Sci. 2018;59:612–20. This study showed that higher preoperative aqueous levels of certain cytokines were associated with increased post-keratoplasty endothelial cell loss. CrossRefPubMedGoogle Scholar
- 62.• Feng MT, Price FW Jr, McKee Y, Price MO. Memantine-associated corneal endothelial dysfunction. JAMA Ophthalmol. 2015;133:1218–20. This study showed that post-keratoplasty endothelial dysfunction can be associated with recipient use of N -methyl- d -aspartate receptor antagonists for Alzheimer’s disease. CrossRefPubMedGoogle Scholar
- 66.• Birbal RS, Parker J, Dirisamer M, Janicijevic A, Baydoun L, Dapena I, et al. Descemet membrane endothelial transfer: ultimate outcome. Cornea. 2018;37:141–4. This study showed that endothelial cell migration can result in central corneal clearance despite significant detachment of an endothelial keratoplasty graft, but that ultimately, the cornea decompensates and a regraft is required. CrossRefPubMedGoogle Scholar
- 68.Zygoura V, Baydoun L, Ham L, Bourgonje VJA, van Dijk K, Lie JT, et al. Quarter-Descemet membrane endothelial keratoplasty (Quarter-DMEK) for Fuchs endothelial corneal dystrophy: 6 months clinical outcome. Br J Ophthalmol. 2018 ePub ahead of print; https://doi.org/10.1136/bjophthalmol-2017-311398.
- 71.• Rosenfeld C, Price MO, Lai X, Witzmann FA, Price FW Jr. Distinctive and pervasive alterations in aqueous humor protein composition following different types of glaucoma surgery. Mol Vis. 2015;25:911–8. This study showed that different types of glaucoma surgery produce distinctive and pervasive alterations in aqueous humor protein concentrations. Google Scholar
- 72.• Ishii N, Yamaguchi T, Yazu H, Satake Y, Yoshida A, Shimazaki J. Factors associated with graft survival and endothelial cell density after Descemet’s stripping automated endothelial keratoplasty. Sci Rpt. 2016;6:25276. This study showed that preexisting iris damage can significantly impact corneal endothelial survival. Google Scholar
- 73.• Price MO, Lisek M, Feng MT, Price FW Jr. Effect of donor and recipient diabetes status on Descemet membrane endothelial keratoplasty adherence and survival. Cornea. 2017;36:1184–8. This study found that recipient diabetes was associated with a higher rate of chronic post-keratoplasty endothelial cell loss. PubMedGoogle Scholar
- 75.•• Lass JH, Benetz BA, Verdier DD, Szczotka-Flynn LB, Ayala AR, Liang W, et al. Corneal endothelial cell loss 3 years after successful Descemet stripping automated endothelial keratoplasty in the Cornea Preservation Time Study: a randomized clinical trial. JAMA Ophthalmol. 2017;135:1394–400. This randomized, multi-center study evaluated the effect of donor preservation time on cell loss after DSEK. CrossRefPubMedGoogle Scholar
- 76.• Rodriguez-Calvo de Mora M, Groeneveld-van Beek EA, Frank LE, van der Wees J, Oellerich S, Bruinsma M, et al. Association between graft storage time and donor age with endothelial cell density and graft adherence after Descemet membrane endothelial keratoplasty. JAMA Ophthalmol. 2016;134:91–4. This study found that longer donor preservation time in culture medium was associated with increased cell loss after DMEK. CrossRefPubMedGoogle Scholar
- 79.•• Price DA, Price MO, Kelley M, Price FW Jr. DMEK vs. DSEK: 5-year graft survival, endothelial cell loss and rejection episode rates, and the effect of donor sex-matching. Ophthalmology. 2018; in press. This study assessed outcomes of over 2000 endothelial keratoplasty procedures; the rejection episode rate was significantly lower with DMEK, but the 5-year graft survival rates were comparable with DMEK and DSEK. Neither donor sex nor donor/recipient sex matching significantly influenced EK outcomes. Google Scholar