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IntroductionThere is a need to find alternatives to the use of human donor corneas in transplants because of the limited availability of donor organs, the incidence of graft complications, as well as the inability to successfully perform corneal transplant in patients presenting limbal deficiency, neo-vascularized or thin corneas, etc. We have designed a clinical trial to test a nanostructured fibrin-agarose corneal substitute combining allogeneic cells that mimics the anterior human native cornea in terms of optical, mechanical and biological behaviour.Methods and analysisThis is a phase I-II, randomised, controlled, open-label clinical trial, currently ongoing in ten Spanish hospitals, to evaluate the safety and feasibility, as well as clinical efficacy evidence, of this bioengineered human corneal substitute in adults with severe trophic corneal ulcers refractory to conventional treatment, or with sequelae of previous ulcers. In the initial phase of the trial (n=5), patients were sequentially recruited, with a safety period of 45 days, receiving the bioengineered corneal graft. In the second phase of the trial (currently ongoing), subjects are block randomised (2:1) to receive either the corneal graft (n=10), or amniotic membrane (n=5), as the control treatment. Adverse events, implant status, infection signs and induced neovascularization are evaluated as determinants of safety and feasibility of the bioengineered graft (main outcomes). Study endpoints are measured along a follow-up period of 24 months, including 27 post-implant assessment visits according to a decreasing frequency. Intention to treat, and per protocol, and safety analysis will be performed.Ethics and disseminationThe trial protocol received written approval by the corresponding Ethics Committee and the Spanish Regulatory Authority and is currently recruiting subjects. On completion of the trial, manuscripts with the results of phases I and II of the study will be published in a peer-reviewed journal.Trial registrationCT.gov identifier: NCT01765244 (Jan2013). EudraCT number: 2010-024290-40 (Dec2012).

Background/aimsThis retrospective multicentric panel study provides absolute numbers, types of and indications for corneal transplantation in Germany from 2011 to 2021 and sets them into the international context.MethodsA questionnaire was sent to the 104 German ophthalmologic surgery departments and 93 (89%) provided their data.ResultsThe number of reported keratoplasties more than doubled from 2011 (n=4474) to 2021 (n=8998). Lamellar keratoplasties (49% posterior (n=2883), 4% anterior (n=231)) surpassed penetrating keratoplasty (PKP, 47%, n=2721) for the first time in 2014. Since 2016, Descemet’s membrane endothelial keratoplasty (DMEK) has become the predominant keratoplasty procedure in Germany. Its number increased by 1.5-fold from 3850 (2016) to 5812 (2021). Main indications in 2021 were Fuchs’ endothelial corneal dystrophy (FECD, 43%), pseudophakic corneal decompensation (12%), repeated keratoplasty (11%), infections (7%), keratoconus (6%) and corneal scarring (4%, others: 9%). The PKP percentage decreased from 70.2% in 2011 (n=3141) to 31.7% in 2021 (n=2853). Descemet’s stripping (automated) endothelial keratoplasties (DSAEKs) decreased to 1% in 2021 (n=74). 98.6% of all posterior lamellar keratoplasties were DMEKs in Germany in 2021. The number of deep anterior lamellar keratoplasties (DALKs) remained comparable from 2011 (n=269) to 2021 (n=251, 2.8%).ConclusionMain indications for corneal transplantation in Germany (2021) were FECD and pseudophakic corneal decompensation. DMEK is by far the predominant corneal transplantation procedure since 2016 followed by PKP, whose absolute number decreased only slightly during the decade from 2011 to 2021. DALK proportions remain low, but stable, whereas DSAEK decreased annually and plays a minor role in Germany.Trial registration number NCT03381794.

Purpose To investigate the effect of posterior corneal surface abnormalities following deep anterior lamellar keratoplasty (DALK) on visual outcomes and high order aberrations (HOA). Methods A retrospective cohort study was conducted on DALK cases. Patients were divided into two groups: Group A with posterior corneal surface abnormalities (interface haze, pre-Descemet’s scarring, central Descemet’s membrane (DM) perforation, and central DM folds) and Group B (control group) with regular posterior surface. Visual acuity, refractive outcomes, contrast sensitivity, and HOA were assessed in both groups. Results This study included 84 eyes of 78 patients. Group A included 42 eyes of 38 patients and an equal number of control eyes were randomly included in group B. Group A exhibited significantly lower corrected distance visual acuity (CDVA) compared to Group B (Mean LogMAR 0.45 ± 0.25 in group A vs 0.31 ± 0.21 in group B, P  = 0.012). Subgroup analysis revealed the lowest visual acuity in eyes with multiple posterior surface abnormalities, although the difference was not statistically significant. The mean topographic astigmatism was significantly higher in group A than in group B (4.47 ± 2.36 diopters vs 3.11 ± 2.16 diopters, respectively, P  = 0.001). No significant differences were found between the 2 groups regarding total eye or corneal HOA. Contrast sensitivity was significantly lower in Group A at lower spatial frequencies ( P  = 0.013 and P  = 0.004 at 3 and 6 cycles per degree, respectively), particularly in eyes with large DM perforations. Conclusion Posterior corneal surface abnormalities after DALK can negatively impact visual outcomes, especially contrast sensitivity.

Corneal blindness is one of the major causes of reversible blindness, which can be managed with transplantation of a healthy donor cornea. It is the most successful organ transplantation in the human body as cornea is devoid of vasculature, minimizing the risk of graft rejection. The first successful transplant was performed by Zirm, and since then, corneal transplantation has seen significant evolution. It has been possible because of the relentless efforts by researchers and the increase in knowledge about corneal anatomy, improvement in instruments and advancements in technology. Keratoplasty has come a long way since the initial surgeries wherein the whole cornea was replaced to the present day where only the selective diseased layer can be replaced. These newer procedures maintain structural integrity and avoid catastrophic complications associated with open globe surgery. Corneal transplantation procedures are broadly classified as full-thickness penetrating keratoplasty and partial lamellar corneal surgeries which include anterior lamellar keratoplasty [sperficial anterior lamellar keratoplasty (SALK), automated lamellar therapeutic keratoplasty (ALTK) and deep anterior lamellar keratoplasty (DALK)] and posterior lamellar keratoplasty [Descemet stripping automated endothelial keratoplasty (DSAEK) and Descemet membrane endothelial keratoplasty (DMEK)] broadly.

Endothelial transplantation has recently been accepted worldwide, in the long history of corneal transplantation. The introduction of endothelial keratoplasty (Descemet stripping automated endothelial keratoplasty and Descemet membrane endothelial keratoplasty) has enabled us to expand the surgical indications owing to the low incidence of rejection and quick recovery of visual function. New technologies have been developed to ensure stable postoperative outcomes with a shorter learning curve, such as transplantation using cultured human endothelial cells and induced pluripotent stem cells (iPS) or new devices such as artificial endothelium. This review discusses the history and characteristics of corneal transplantation alongside new treatment options that may offer hope for patients with endothelial disease in the future.

We aimed to investigate the functionality of human decellularized stromal laminas seeded with cultured human corneal endothelial cells as a tissue engineered endothelial graft (TEEK) construct to perform endothelial keratoplasty in an animal model of corneal endothelial damage. Engineered corneal endothelial grafts were constructed by seeding cultured human corneal endothelial cell (hCEC) suspensions onto decellularized human corneal stromal laminas with various coatings. The functionality and survival of these grafts with cultured hCECs was examined in a rabbit model of corneal endothelial damage after central descemetorhexis. Rabbits received laminas with and without hCECs (TEEK and control group, respectively). hCEC seeding over fibronectin-coated laminas provided an optimal and consistent endothelial cell count density and polygonal shape on the decellularized laminas, showing active pump fuction. Surgery was performed uneventfully as standard Descemet stripping automated endothelial keratoplasty (DSAEK). Corneal transparency gradually recovered in the TEEK group, whereas haze and edema persisted for up to 4 weeks in the controls. Histologic examination showed endothelial cells of human origin covering the posterior surface of the graft in the TEEK group. Grafting of decellularized stroma carriers re-surfaced with human corneal endothelial cells ex vivo can be a readily translatable method to improve visual quality in corneal endothelial diseases.

To evaluate the efficacy and safety of a cultured human corneal endothelial cell (cHCEC) product in eyes with bullous keratopathy (BK). Combined analysis of multicenter phase II and III clinical trials. This analysis involved 15 BK eyes in the phase II trial and 12 BK eyes in the phase III trial that underwent cHCEC transplant therapy. Safety was assessed in all the cases. Efficacy was assessed in 17 cases with exclusion of the low- and medium-dose groups in the phase II trial. The primary endpoint was a corneal endothelial cell density of 1000 cells/mm 2 or more at 24 weeks post-transplant, which was attained in 94.1% of the eyes (16 of 17), with a 95% CI of 71.3–99.9%. Additionally, 82.4% of the eyes (14 of 17) met the secondary endpoint of reduction in corneal thickness to less than 630 µm without corneal epithelial edema within the same time frame, with a 95% CI of 56.6–96.2%. The mean decrease in corneal thickness from baseline to 24 weeks post-transplant was −187.4 µm (95% CI, −240.2 µm to −134.5 µm). Furthermore, all the eyes exhibited improvement in best-corrected visual acuity from baseline to 24 weeks post-transplant (95% CI, 80.5–100.0%). By 24 weeks post-transplant, 88.9% of the patients (24 of 27) had experienced adverse events, which were mostly local, mild, and transient. The cHCEC product of this study reconstitutes the corneal endothelial layer with high cellular density and restores corneal thickness and improves visual acuity.

Due to its instantaneous and visible results for patients both anatomically and visually, anterior lamellar keratoplasty is a field of great interest to corneal surgeons. Newer techniques of DALK, femtosecond assisted DALK, TILK, and more have inherent advantages that make them supersede older techniques of keratoplasty by far. Mastering DALK: A Video Textbook on Deep Anterior Lamellar Keratoplasty by Dr. Soosan Jacob combines the practical explanation of written text with the dynamic demonstration of surgical videos. From pre-operative to post-operative patient management and every surgical technique in between, this unique book and its included video website is a complete education on DALK. This includes the history and basics of lamellar keratoplasty, as well as tutorials on various surgical techniques currently in use, advice for complex situations, and management of possible complications. Each chapter includes high-quality photographs and illustrations and is paired with videos on the accompanying website to demonstrate techniques and provide step-by-step instructions. The surgeries in these videos are performed and narrated by the same team of leading international experts who have also written all of the clinical tips, tricks, and pearls of wisdom throughout the book. Some videos include: Retrieving the Lost Bubble DALK Surgery with Type 1 Big Bubble Groove Peel DALK Femtosecond Laser Assisted DALK SMILE Away a Dermoid Any surgeon looking to add anterior lamellar keratoplasty to their practice will appreciate the digestible nature of Mastering DALK: A Video Textbook on Deep Anterior Lamellar Keratoplasty, which provides both the crucial detail of a book and the irreplaceable value of visual demonstration.

Corneal transplantation is the only treatment available to restore vision for individuals with blindness due to corneal endothelial dysfunction. However, severe shortage of available donor corneas remains a global challenge. Functional regulatory compliant tissue-engineered corneal endothelial graft substitute can alleviate this reliance on cadaveric corneal graft material. Here, isolated primary human corneal endothelial cells (CEnCs) propagated using a dual media approach refined towards regulatory compliance showed expression of markers indicative of the human corneal endothelium, and can be tissue-engineered onto thin corneal stromal carriers. Both cellular function and clinical adaptability was demonstrated in a pre-clinical rabbit model of bullous keratopathy using a tissue-engineered endothelial keratoplasty (TE-EK) approach, adapted from routine endothelial keratoplasty procedure for corneal transplantation in human patients. Cornea thickness of rabbits receiving TE-EK graft gradually reduced over the first two weeks, and completely recovered to a thickness of approximately 400 µm by the third week of transplantation, whereas corneas of control rabbits remained significantly thicker over 1,000 µm ( p  < 0.05) throughout the course of the study. This study showed convincing evidence of the adaptability of the propagated CEnCs and their functionality via a TE-EK approach, which holds great promises in translating the use of cultured CEnCs into the clinic.

Corneal disease ranks as the fifth leading cause of global blindness, affecting more than 10 million individuals. Donor corneal transplantation, keratoplasty, remains the mainstay of addressing loss of corneal clarity. Historically, full-thickness penetrating keratoplasty (PK) has been one of the most successful and widely performed transplant procedures, although predominantly available in developed countries. The landscape for corneal transplantation has changed dramatically over the last two decades with the emergence of partial-thickness transplantation techniques and corneal cross-linking, which provide less invasive means of treating diseases like Fuchs’ dystrophy and keratoconus, respectively. Currently, PK is often performed in eyes with complex problems and at high risk of graft failure. In fact, repeat grafting has become the second most common indication for PK. Furthermore, a significant shortage of donor corneas persists, with half of the global population lacking access to tissues. This shortage is particularly pronounced in developing countries, which lack the necessary infrastructure to support corneal transplantation despite bearing the highest burden of corneal blindness. Artificial corneal devices, known as keratoprostheses, have been posited as a remedy for various constraints of conventional keratoplasty and have demonstrated promising outcomes, particularly in high-risk cases. Synthetic devices are not subject to the risk of allograft rejection or endothelial failure. In resource-limited areas, keratoprostheses could potentially replace donor keratoplasty by eliminating the costly eye banking system to access, preserve and distribute the short-lived fresh donor tissues. Herein, we report the design, surgical technique, indications and early outcomes of clinical-stage fully synthetic keratoprostheses currently undergoing trials globally.