New Therapies for Corneal Endothelial Diseases: 2020 and Beyond.

ABSTRACT: Penetrating keratoplasty used to be the only surgical technique for the treatment of end-stage corneal endothelial diseases. Improvements in surgical techniques over the past decade have now firmly established endothelial keratoplasty as a safe and effective modality for the treatment of corneal endothelial diseases. However, there is a worldwide shortage of corneal tissue, with more than 50% of the world having no access to cadaveric tissue. Cell injection therapy and tissue-engineered endothelial keratoplasty may potentially offer comparable results as endothelial keratoplasty while maximizing the use of cadaveric donor corneal tissue. Descemet stripping only, Descemet membrane transplantation, and selective endothelial removal are novel therapeutic modalities that take this a step further by relying on endogenous corneal endothelial cell regeneration, instead of allogenic corneal endothelial cell transfer. Gene therapy modalities, including antisense oligonucleotides and clustered regularly interspaced short palindromic repeats-based gene editing, offer the holy grail of potentially suppressing the phenotypic expression of genetically determined corneal endothelial diseases at the asymptomatic stage. We now stand at the crossroads of exciting developments in medical technologies that will likely revolutionize the way we treat corneal endothelial diseases over the next 2 decades.

Endothelial Keratoplasty Update 2020.

ABSTRACT: Endothelial keratoplasty has revolutionized the treatment of corneal endothelial dysfunction and lowered the threshold for treatment by providing rapid visual rehabilitation and setting a high standard for safety and efficacy. Over time, endothelial keratoplasty techniques have evolved toward the use of thinner tissue to optimize visual outcomes; refinements have facilitated donor tissue preparation, handling, and attachment; and adaptations have expanded utilization in eyes with challenging ocular anatomy. Despite early concerns about graft longevity, emerging 10-year endothelial cell loss and graft survival data have been encouraging. A shortage of human donor corneas restricts utilization in many areas of the world and is driving a search for keratoplasty alternatives. Further work is needed to expand the donor supply, minimize impediments to adoption, optimize graft survival, and improve refractive predictability.

Trends in corneal transplantation in a single center in Barcelona, Spain. Transitioning to DMEK.

PURPOSE: To observe trends in surgical techniques for corneal transplantation and main indications in our hospital over the past five years. METHODS: Retrospective descriptive study, including all keratoplasties performed at the Hospital Clinic of Barcelona, Spain, between January 2014 and December 2018. RESULTS: In total, 332 keratoplasties were performed. In total, 127 (38.25%) were penetrating keratoplasties (PK), and 205 (61.75%) were lamellar keratoplasties (LK). In 2014, a total of 48 keratoplasties were carried-out, whereas in 2018, the total was 93, which represents a 93.75% increase in corneal transplantation surgeries. Eye bank-delivered precut tissue for DMEK was introduced in 2016, and 3 cases (6.25%), were carried out that year. In 2018, DMEK became the leading technique with 56 cases (60.22%). Fuchs' dystrophy was the leading indication for corneal transplant (37.63%) in 2018. CONCLUSION: Introduction of DMEK in a single center can be implemented in a relatively short period of time, becoming the most popular surgical procedure in corneal transplantation. A possible factor encouraging this change is the availability of eye bank-delivered precut tissue, and standardization of donor preparation and host surgical steps, optimizing surgical time in the operating room. This trend should lead to better visual outcomes, faster recovery times, and eventually to a higher surgical volume per year.

Trends in corneal transplantation at the University Eye Hospital in Tübingen, Germany over the last 12 years: 2004 - 2015.

PURPOSE: This study aimed to investigate the trends in the surgical methods and leading indications for corneal transplantations carried out over the last 12 years. METHODS: The data from the corneal graft waiting list and from all keratoplasties carried out between 2004 and 2015 at the University Eye Hospital in Tübingen were retrospectively analyzed. RESULTS: A total of 1,185 keratoplasties were performed between 2004 and 2015 at this hospital. The most common surgical indications for corneal transplantation were Fuchs' endothelial corneal dystrophy (35.2%) and keratoconus (18.9%) with keratoconus being the leading cause during early years (from 2004 to 2009) and Fuch's dystrophy being the leading cause from 2010 to 2015. Overall, the total count of performed keratoplasties increased, from 385 corneal transplantations during the first 6-year period to 800 corneal transplantations during the second 6-year period (P = 0.008, using Mann-Whitney test). The Descemet's membrane endothelial keratoplasty has become the favored surgical method for endothelial disorders with the number of Descemet's membrane endothelial keratoplasties increasing significantly from 2008 to 2015. This increasing trend was statistically significant (P < 0.001 using multivariate adaptive regression splines (MARS). A decreasing trend was also noted for the rate of penetrating keratoplasty since 2008 (P < 0.001 using MARS). CONCLUSIONS: This research showed major changes in the preferred corneal transplantation techniques and leading indications for keratoplasty over the last 12 years. More importantly, it seems that the rapid development and implementation of endothelial keratoplasty, especially the Descemet's membrane endothelial keratoplasty, has had a profound effect on and begun a new era in corneal transplantation.

How Much Progress Has Been Made in Corneal Transplantation?

To assess the benefits of component lamellar corneal surgery, we investigated the surgical outcomes of deep anterior lamellar keratoplasty (DALK) for keratoconus and Descemet stripping automated endothelial keratoplasty (DSAEK) for laser iridotomy-induced bullous keratopathy (LI-BK). The results were compared with the surgical outcomes of penetrating keratoplasty (PKP). Seventy-nine eyes with keratoconus treated with DALK and 81 eyes with LI-BK treated with DSAEK were studied, and the graft clarity rate, best spectacle-corrected visual acuity, endothelial cell density (ECD), and surgical complications were compared with 273 eyes with keratoconus and 98 eyes with LI-BK all treated with PKP. Keratoconus eyes showed excellent visual outcomes with DALK and PKP, but graft survival was higher for PKP (100%, 98.9%, and 96.3% vs. 98.6%, 90.6%, and 86.1%, at 1, 3, and 5 years after surgery, respectively; P < 0.0001). There were no significant differences in the ECD up to 1 year after surgery. Greater ECD decline was observed for PKP at 3 and 5 years after surgery. Descemet membrane microperforation was observed in 49 eyes treated with DALK. Postoperative complications in eyes treated with PKP were increased incidence of immunological rejection and secondary glaucoma compared with eyes treated with DALK. LI-BK graft survival rates were excellent in both groups (DSAEK: 89.6% and 86.1%; PKP: 100% and 98.6%, 1- and 2-year rates, respectively; P = 0.17). Best spectacle-corrected visual acuity was better in the DSAEK group, and ECD showed a higher rate of decrease with DSAEK than with PKP. DALK and DSAEK considerably improved surgical outcomes in eyes with keratoconus and those with LI-BK, respectively. However, several key areas require further work, including development of safe surgical methods in DALK and prevention of early postoperative ECD loss in DSAEK.

Keratoplasty in the United States: A 10-Year Review from 2005 through 2014.

PURPOSE: To report evolving indications and preferred techniques of corneal transplantation in the United States. DESIGN: Retrospective review. METHODS: Annual reports from the Eye Bank Association of America on corneal graft distribution in the United States from 2005 through 2014 were reviewed. MAIN OUTCOME MEASURES: Number and percentage of corneal grafts distributed for various types of keratoplasty and their surgical indications in the United States. RESULTS: The total number of corneal transplants increased from 44 277 in 2005 to 46 513 in 2014. In the past decade, penetrating keratoplasty dramatically decreased (from 95% to 42%) and largely has been replaced by various lamellar keratoplasty (LK) techniques (from 5% to 58%). Descemet stripping (automated) endothelial keratoplasty was the most common (50%) type of corneal transplantation performed in the United Stated in 2014. The volume of Descemet membrane endothelial keratoplasty (DMEK) has been doubling every year since 2011 and accounted for 11% of total endothelial keratoplasties in 2014. There was a significant shift in indication for corneal transplantation, with Fuchs' endothelial dystrophy (22%) being the most common, followed by corneal edema occurring after cataract surgery (12%) in 2014. Eye banks supplied precut corneal grafts for 68% of LK techniques in 2014. CONCLUSIONS: In the United States, there has been a major shift in preferred keratoplasty techniques over the past decade, with a wide adoption of new LK techniques.

[Research advances of Descemet's membrane endothelial keratoplasty].

In the past ten years, corneal endothelial keratoplasty has been widely and successfully performed in China. As an ideal surgical treatment for corneal endothelial diseases, Descemet's membrane endothelial keratoplastywas only tried out in few hospitals. This article summarized the development of Descemet's membrane endothelial keratoplasty in surgical indications, operation process and postoperative complications in China and abroad for providing references for clinical application.

La estandarización en el trasplante endotelial de membrana de Descemet: resultados de las primeras 450 cirugías / Standardization of the Descemet membrane endothelial keratoplasty technique: Outcomes of the first 450 consecutive cases

OBJETIVOS: Analizar los resultados de 450 casos con diferentes patologías endoteliales intervenidos mediante trasplante endotelial con la técnica de recambio de la membrana de Descemet (DMEK, por sus siglas en inglés: Descemet membrane endothelial keratoplasty) y evaluar las consecuencias de la estandarización de esta técnica. MATERIAL Y MÉTODOS: Se compararon 3 subgrupos consecutivos: el subgrupo I (casos 1-125) representaba la extensión de la curva de aprendizaje; el subgrupo II (casos 126-250) la transición a la estandarización de la técnica y el subgrupo III (casos 251-450) la estandarización propiamente dicha. Se registraron los resultados de agudeza visual mejor corregida pre- y postoperatorios, la densidad de células endoteliales, la paquimetría y las complicaciones. RESULTADOS: A los 6 meses de la cirugía, el 79% de los pacientes alcanzaron una agudeza visual mejor corregida ≥ 0,8 y el 43% ≥ 1. La densidad de células endoteliales media preoperatoria fue 2.530 ± 220 células/mm2, y 1.613 ± 495 células/mm2 al sexto mes poscirugía. La paquimetría era 668 ± 92 μm y 526 ± 46 μm pre- y postoperatoria a los 6 meses, respectivamente. No se encontraron diferencias en cuanto a la agudeza visual mejor corregida, la densidad de células endoteliales o la paquimetría entre los subgrupos (p > 0,05). El desprendimiento del injerto se observó en el 17,3% de los ojos. La tasa de desprendimientos disminuyó del 24 al 12%, y el número de reintervenciones, del 9,6 al 3,5%, del subgrupo I al III respectivamente. CONCLUSIONES: Los resultados visuales y la densidad de células endoteliales tras DMEK son independientes de la estandarización de la técnica quirúrgica. Sin embargo, la estandarización de la técnica podría haber contribuido con un descenso en el número de desprendimientos y con un relativamente bajo número de intervenciones secundarias. A la vista de estos resultados, DMEK podría convertirse en el tratamiento de elección para las enfermedades del endotelio corneal

OBJECTIVES: To evaluate the clinical outcome of the first 450 consecutive cases after Descemet membrane endothelial keratoplasty (DMEK), as well as the effect of standardization of the technique. MATERIAL AND METHODS: Comparison between 3 groups: Group I: (cases 1-125), as the extended learning curve; Group II: (cases 126-250), transition to technique standardization; Group III: (cases 251-450), surgery with standardized technique. Best corrected visual acuity, endothelial cell density, pachymetry and intra- and postoperative complications were evaluated before, and 1, 3 and 6 months after DMEK. RESULTS: At 6 months after surgery, 79% of eyes reached a best corrected visual acuity of≥0.8 and 43%≥1.0. Mean preoperative endothelial cell density was 2,530±220 cells/mm2 and 1,613±495 at 6 months after surgery. Mean pachymetry measured 668±92 μm and 526±46 μm pre- and (6 months) postoperatively, respectively. There were no significant differences in best corrected visual acuity, endothelial cell density and pachymetry between the 3 groups (P > .05). Graft detachment presented in 17.3% of the eyes. The detachment rate declined from 24% to 12%, and the rate of secondary surgeries from 9.6% to 3.5%, from group I to III respectively. CONCLUSIONS: Visual outcomes and endothelial cell density after DMEK are independent of the technique standardization. However, technique standardization may have contributed to a lower graft detachment rate and a relatively low number of secondary interventions required. As such, DMEK may become the first choice of treatment in corneal endothelial disease

Evolution of Endothelial Keratoplasty: Where Are We Headed?

In less than 10 years, the proportion of endothelial keratoplasty (EK) procedures has increased from less than 5% of the corneal grafts in the United States to over half. EK has made corneal grafts safer and provides better and more predictable visual results than standard full-thickness penetrating keratoplasty. Descemet membrane endothelial keratoplasty in particular has dramatically reduced the risk of rejection, allowing reduction in topical corticosteroid use, resulting in a lower incidence of steroid-induced intraocular pressure elevation. By removing the confounding effects of ocular surface disease, which is exacerbated by the sutures and anesthetic corneas associated with full-thickness grafts, EK has revealed that the greatest risk factor for graft failure is filtration surgery, particularly aqueous shunts. As the use of glaucoma filtering tubes continues to increase, they may become a leading cause of corneal decompensation.

Trends in corneal transplantation: indications and techniques.

PURPOSE OF REVIEW: To describe trends in corneal transplantation surgery, including indications for surgery, evolution of lamellar keratoplasty, current surgical techniques, and future directions. RECENT FINDINGS: Over the past decade, anterior and posterior lamellar keratoplasty have begun to supplant penetrating keratoplasty. Surgical techniques continue to change and improve outcomes. In recent years, Descemet membrane endothelial keratoplasty (DMEK) has gained interest as it eliminates the corneal stromal interface, which may limit visual acuity after Descemet stripping automated endothelial keratoplasty. Despite the promising results with improved visual acuity and decreased rejection, the technical challenges associated with DMEK have limited widespread acceptance. With technical refinements and more eye banks providing precut tissue for both Descemet stripping automated endothelial keratoplasty and DMEK, it is likely both procedures will continue to increase over time. SUMMARY: Corneal transplantation has evolved rapidly over the past decade, from full-thickness penetrating keratoplasty towards lamellar keratoplasty to only remove and replace damaged layers of the cornea. Achieving minimal induced astigmatism with excellent visual acuity remains a challenge in corneal transplantation. Further refinements in surgical technique may help improve technical challenges and visual outcomes. In this article, we review changing trends in corneal transplantation and highlight developing medical treatments that may be available in the future.

A comparison of lamellar and penetrating keratoplasty outcomes: a registry study.

OBJECTIVES: To investigate changing patterns of practice of keratoplasty in Australia, graft survival, visual outcomes, the influence of experience, and the surgeon learning curve for endothelial keratoplasty. DESIGN: Observational, prospective cohort study. PARTICIPANTS: From a long-standing national corneal transplantation register, 13 920 penetrating keratoplasties, 858 deep anterior lamellar keratoplasties (DALKs), and 2287 endokeratoplasties performed between January 1996 and February 2013 were identified. METHODS: Kaplan-Meier functions were used to assess graft survival and surgeon experience, the Pearson chi-square test was used to compare visual acuities, and linear regression was used to examine learning curves. MAIN OUTCOME MEASURES: Graft survival. RESULTS: The total number of corneal grafts performed annually is increasing steadily. More DALKs but fewer penetrating grafts are being performed for keratoconus, and more endokeratoplasties but fewer penetrating grafts are being performed for Fuchs' dystrophy and pseudophakic bullous keratopathy. In 2012, 1482 grafts were performed, compared with 955 in 2002, translating to a requirement for 264 extra corneal donors across the country in 2012. Comparing penetrating grafts and DALKs performed for keratoconus over the same era, both graft survival (P <0.001) and visual outcomes (P <0.001) were significantly better for penetrating grafts. Survival of endokeratoplasties performed for Fuchs' dystrophy or pseudophakic bullous keratopathy was poorer than survival of penetrating grafts for the same indications over the same era (P <0.001). Visual outcomes were significantly better for penetrating grafts than for endokeratoplasties performed for Fuchs' dystrophy (P <0.001), but endokeratoplasties achieved better visual outcomes than penetrating grafts for pseudophakic bullous keratopathy (P <0.001). Experienced surgeons (>100 registered keratoplasties) achieved significantly better survival of endokeratoplasties (P <0.001) than surgeons who had performed fewer grafts (<100 registered keratoplasties). In the hands of experienced, high-volume surgeons, endokeratoplasty failures occurred even after 100 grafts had been performed. CONCLUSIONS: More corneal transplants, especially DALKs and endokeratoplasties, are being performed in Australia than ever before. Survival of DALKs and endokeratoplasties is worse than the survival of penetrating grafts performed for the same indications over the same timeframe. Many endokeratoplasties fail early, but the evidence for a surgeon learning curve is unconvincing.

Evolving indications for and trends in keratoplasty in British Columbia, Canada, from 2002 to 2011: a 10-year review.

PURPOSE: The aim of this study was to report the evolving indications for keratoplasty and the shift in the type of keratoplasty performed in British Columbia, Canada, over a 10-year period from 2002 to 2011. METHODS: This was a retrospective database review of all the records of corneal transplant tissues at the Eye Bank of British Columbia, Canada, from January 2002 to December 2011. The patient demographics, indications, and types of transplant performed were analyzed. RESULTS: A total of 4843 corneal transplants were performed in 3742 patients (1968 male and 1774 female) from January 2002 to December 2011. The number of keratoplasties performed ranged from 420 in 2008 to 578 in 2011. The top 4 indications over the 10-year period were Fuchs endothelial dystrophy (FED; 18.9%), aphakic/pseudophakic bullous keratopathy (17.4%), regraft (17.1%), and keratoconus (15.5%). Penetrating keratoplasty (PKP) accounted for 86.5% (4191 transplants) of all keratoplasties performed. Since the introduction of Descemet stripping automated endothelial keratoplasty (DSAEK) in 2007, there was a significant increase in the number of DSAEKs (P < 0.0001) performed and a statistical decline in the number of PKPs (P < 0.0001) performed. Despite only 30 deep anterior lamellar keratoplasties being performed, an increasing trend was observed after 2008 (P = 0.0087). A decreasing trend in PKPs and an increasing trend in DSAEKs were observed for surgeries performed for FED, aphakic/pseudophakic bullous keratopathy, and regraft. CONCLUSIONS: FED has become the top indication for performing a keratoplasty over the 10-year period. There was a shift from PKP to DSAEK performed for endothelial failure. Although the number of deep anterior lamellar keratoplasty surgeries was small, there was a significant increasing trend.

Evolution of endothelial keratoplasty.

Endothelial keratoplasty has evolved into a popular alternative to penetrating keratoplasty (PK) for the treatment of endothelial dysfunction. Although the earliest iterations were challenging and were not widely adopted, the iteration known as Descemet stripping endothelial keratoplasty (DSEK) has gained widespread acceptance. DSEK combines a simplified technique for stripping dysfunctional endothelium from the host cornea and microkeratome dissection of the donor tissue, a step now commonly completed in advance by eye bank technicians. Studies show that a newer endothelial keratoplasty iteration, known as Descemet membrane endothelial keratoplasty (DMEK), provides an even faster and better visual recovery than DSEK does. In addition, DMEK significantly reduces the risk of immunologic graft rejection episodes compared with that in DSEK or in PK. Although the DMEK donor tissue, consisting of the bare endothelium and Descemet membrane without any stroma, is more challenging to prepare and position in the recipient eye, recent improvements in instrumentation and surgical techniques are increasing the ease and the reliability of the procedure. DSEK successfully mitigates 2 of the main liabilities of PK: ocular surface complications and structural problems (including induced astigmatism and perpetually weak wounds), whereas DMEK further mitigates the 2 principal remaining liabilities of PK: immunologic graft reactions and secondary glaucoma from prolonged topical corticosteroid use.

The era of lamellar keratoplasty, evolving surgical techniques in corneal transplantation: the University of Toronto experience.

OBJECTIVE: To analyze the changing trends in corneal transplantation techniques and the way selective lamellar transplantation has influenced our practice. DESIGN: Retrospective survey of all corneal transplants performed by a single practice at Toronto Western Hospital. PARTICIPANTS: All corneal transplants performed by our office since 2002, the year we performed our first lamellar transplant. METHODS: We retrospectively reviewed all keratoplasty procedures performed in our office between January 2002 and December 2010. Procedures were classified as penetrating keratoplasty (PKP); deep lamellar endothelial keratoplasty (DLEK); Descemet's stripping automated endothelial keratoplasty (DSAEK); or deep anterior lamellar keratoplasty (DALK). RESULTS: A total of 1104 procedures were performed in this period (average, 122.6 per year). Of these, 654 were PKPs (59.3%); 107 DLEKs (9.7%); 219 DSAEKs (19.8%); and 124 DALKs (11.2%). The number of PKPs performed decreased by 61.8% over this 9-year survey. For the last 4 years of the study, the proportions of PKP, DSAEK, and DALK procedures performed were 41%, 40%, and 19%, respectively. CONCLUSIONS: This 9-year audit showed that in less than a decade since its introduction at our institution, selective lamellar transplantation has become the procedure of choice for corneal keratoplasty, accounting for 59% of all transplants performed over the past 4 years.

Trends in the indications for corneal graft surgery in the United Kingdom: 1999 through 2009.

OBJECTIVE: To examine trends in the indications for corneal graft surgery in the United Kingdom. METHODS: National Health Service Blood and Transplant data were analyzed for keratoplasty operations performed in the United Kingdom between April 1, 1999, and March 31, 2009, distinguishing the type of graft and the surgical indication. RESULTS: The total number of annual keratoplasty operations increased from 2090 in 1999-2000 to 2511 in 2008-2009. Among these, the annual number of grafts performed for endothelial failure increased from 743 (35.6%) in 1999-2000 to 939 (37.4%) in 2008-2009. The performance of penetrating keratoplasty (PK) for endothelial failure decreased from 98.3% of all grafts in 1999-2000 to 46.6% of all grafts in 2008-2009, while the performance of endothelial keratoplasty increased from 0.3% of all grafts in 1999-2000 to 51.2% of all grafts in 2008-2009. The annual number of grafts performed for keratoconus increased from 514 (24.6%) in 1999 to 564 (22.5%) in 2008-2009. The performance of PK for keratoconus decreased from 88.4% of all grafts in 1999-2000 to 57.1% of all grafts in 2008-2009, while the performance of deep anterior lamellar keratoplasty increased from 8.8% of all grafts in 1999-2000 to 40.1% of all grafts in 2008-2009. The number of annual regraft operations increased from 249 (11.9%) in 1999-2000 to 401 (16.0%) in 2008-2009, most commonly for endothelial failure. In 2008-2009, PK regrafts (78.1%) far outnumbered endothelial keratoplasty regrafts (17.0%). CONCLUSIONS: Endothelial failure is the most common indication for keratoplasty in the United Kingdom, and endothelial keratoplasty is performed more commonly than PK for this indication. The number of grafts performed for pseudophakic bullous keratopathy has remained stable, while the number of grafts performed for Fuchs endothelial dystrophy is likely to continue increasing. Keratoconus is the second most common indication for keratoplasty, and deep anterior lamellar keratoplasty numbers are approaching those for PK. Regraft surgery is the third most common indication for keratoplasty, required in most cases because of endothelial failure.