Indication For Corneal Transplantation Research Articles

Clinical Outcomes in Patients With Traumatic Dehiscence of Penetrating Keratoplasty Grafts.

The purpose of this study was to report clinical characteristics and outcomes of surgical repair for patients with traumatic dehiscence of penetrating keratoplasty (PKP) grafts. Retrospective, consecutive chart review of patients evaluated at Bascom Palmer Eye Institute between 2015 and 2020 with traumatic dehiscence of penetrating keratoplasty grafts. The study cohort consisted of 65 eyes of 65 patients. The mean age at presentation was 72 years (SD 18), with a male predominance (65%). The most common indications for PKP included keratoconus (42%), corneal scar (31%), and Fuchs corneal dystrophy (8%). Dehiscence occurred as a result of blunt trauma in 94% of cases, and the mean wound length was 6.4 clock hours (SD 2.4), with a predominance of inferior dehiscence. The mean presenting visual acuity (VA) was 2.45 logMAR (SD 0.41), and the mean final VA was 2.17 logMAR (SD 0.99). Graft failure occurred in 64% of patients, and 22% underwent repeat PKP. When stratified by indication for corneal transplantation (keratoconus vs. other), there was no significant difference in graft age at the time of rupture, final VA, rate of graft failure, or rate of repeat PKP. Traumatic dehiscence of corneal grafts remains a rare but serious subtype of ocular trauma with generally poor visual prognoses. Presenting VA along with severity of trauma and posterior segment involvement tend to be the worst prognostic factors in final visual outcome.

Overview of Corneal Transplantation for the Nonophthalmologist.

Corneal transplant is a procedure that aims to replace dysfunctional corneal tissue with a transparent graft and is one of the most widely performed transplant surgeries, but its public and professional awareness is low outside of ophthalmology. Corneal tissue consists of 5 major layers that serve to maintain its structural integrity and refractive shape: the epithelium, Bowman's layer, the stroma, Descemet's membrane, and the endothelium. Failure or irreversible damage to any layer of the cornea may be an indication for corneal transplant, and variants of this procedure may be full thickness or selectively lamellar. Complications related to corneal transplantation may occur anywhere from during surgery to years afterward, including rejection, dehiscence, cataract, and glaucoma. Complications should be managed by an ophthalmologist, but other physicians should be aware of prophylactic medications. Topical immunosuppressants and steroids are effective for preventing and treating rejection episodes, whereas there is little evidence to support the use of systemic immunosuppression. Eye protection is recommended for any corneal transplant recipient. Physicians should counsel patients on corneal donation, especially if outside the United States, where donor tissue is in short supply.

Indications and techniques of corneal transplants performed in one center in Southern Poland, in the years 2001–2020

The study aimed to evaluate changes over a period of time in techniques and indications for corneal transplantation in a single center in Poland. Retrospective analysis of corneal transplants performed at the Ophthalmology Department of the District Railway Hospital in Katowice in 2001-2020. Data on indications and surgical technique were collected. A total of 3021 corneal transplantations were performed in the years 2000-2020. The most common technique was penetrating keratoplasty (69,54%), then lamellar grafts-both anterior and posterior (19,63%), and limbal grafts (10,82%). Only in 2007 the number of lamellar keratoplasties exceeded the number of penetrating grafts and accounted for 108 (54,55%), including 85 (42,93%) of Descemet Stripping Automated Endothelial Keratoplasty. The only noticeable trend in changing techniques was a decrease in the number of performed deep anterior lamellar keratoplasties (r 2 = -0.21) over the last seven years. Main indications included bullous keratopathy (23,22%), following keratoconus (18,59%), leukoma (14,67%), keratitis and perforation (14,3%), Fuchs dystrophy (11,4%), and regrafts (7,22%). Leukoma and bullous keratopathy as an indications for corneal transplant have been declining over the years (r2 = 0.60 and r2 = 0.30 respectively). Consecutively, indications such as fuchs dystrophy, regraft and keratitis perforation have increased (r2 = 0.05, r2 = 0.50, r2 = 0.33). The number of keratoplasties gradually increased from 2001 to 2020. It could be possible that the development and spread of new therapeutic alternatives, like corneal cross-linking and scleral lenses, have contributed to the decrease in deep anterior lamellar keratoplasty performed. There was an increasing trend in the percentage of penetrating keratoplasties for failed grafts, Fuchs dystrophy and infectious keratitis.

Indications for keratoplasty in management of corneal ectasia.

The current review aims to describe recent advancements in treatment of corneal ectasias and its effect on indications for corneal transplantation. The majority of patients affected by ectatic corneal disease use contact lenses to correct resulting astigmatism. Patients who are intolerant of contact lenses or cannot achieve acceptable vision through conservative measures could consider keratoplasty. However, continuing advancements in both nonsurgical and surgical treatments are either reducing or delaying the need for keratoplasty in patients affected by ectatic corneal disease. Corneal transplantation has been the mainstay of treatment for patients with advanced ectatic corneal disease. In the past decade, numerous improvements have been occurred to make contact lenses not only more effective for visual correction, but also more comfortable. Although corneal cross-linking is the only proven treatment known to prevent progression of disease, several other therapies show early potential for those in which cross-linking is contraindicated. Patients now have access to a wider range of therapies before considering keratoplasty.

Keratoplasty for keratoconus: advantages and disadvantages

Keratoconus is a progressive bilateral corneal ectasia, accompanied by loss of vision due to high irregular astigmatism, which is the leading indication for corneal transplantation. The review presents a variety of surgical corneal transplantation techniques for keratoconus available today and discussed their advantages and disadvantages.

Indications and Outcomes of Corneal Transplant Surgery in Ghana

Background: Corneal blindness contributes to 25% of all blindness. We review corneal transplant, a common surgical remedy, in Ghana to determine indications and visual outcomes in resource-poor environments.
 Methods: A retrospective cross-sectional study of keratoplasty evaluating indications, pre- and postoperative outcomes complications and their associations, between January 2014 and December 2018 at a teaching hospital in Ghana. Descriptive statistics and McNemar’s test were used for the analyses.
 Results: Seventy-five eyes were studied. The mean ± standard deviation (SD) age of patients was 45.08 ± 17.85 years, the majority being 20–39 years (58.7% were male). Pseudophakia bullous keratopathy (PBK) was the commonest indication for keratoplasty (26.7%) followed by keratoconus (21.3%). Preoperatively 96% of eyes were blind with vision <3/60 with 64% out of the total eyes with vision <1/60. Postoperatively, 60% of all grafts had uncorrected vision of 3/60 or better after the last follow-up. McNemar’s test revealed a statistically significant difference between postsurgical and pre-surgical visual acuity (VA) (p < 0. 001). The median follow-up period was 12 months. The commonest postsurgical complication was raised intraocular pressure (IOP) (22.7%) with a total of 14.7% of grafts failures.
 Conclusion: In this setting, PBK is the leading indication for corneal transplant. Visual outcomes for corneal transplant in this resource poor area are not worse than in other settings. We need to pay attention to corneal transplant services to cater for the expected increase in PBK from the increasing cataract surgical rate.

Trends in surgical procedures and indications for corneal transplantation over 27years in a tertiary hospital in Japan.

To characterize trends in procedures, and indications for corneal transplantation over 27years in a single referral center in Japan. Retrospective study. Data from a consecutive series of corneal transplant surgery cases performed from 1991 to 2017at Ichikawa General Hospital were collected. The surgical procedures, indications, and causes of corneal endothelial dysfunction were evaluated. Among 6,025 transplantations, a total of 3,991 cases underwent penetrating keratoplasty (PKP), 1009 underwent (deep) anterior lamellar keratoplasty, 746 underwent endothelial keratoplasty, and 309 underwent epithelial transplantation. Over that period the frequency of PKP decreased, whereas the frequency of lamellar keratoplasty increased. The four major surgical indications were bullous keratoplasty (BK 30.0%), regraft (24.2%), post-keratitis scars (17.1%), and keratoconus (11.4%). After dividing the study period into four time periods, we found that BK and regraft increased (from 20.3% to 34.5% and 18.2% to 31.1%, respectively), whereas post-keratitis scars and keratoconus decreased (from 26.0% to 9.5% and 14.1% to 7.2%, respectively) between the first and last period. Pseudophakic or aphakic BK were the major causes of corneal endothelial dysfunction until 2010. Cases of laser-iridotomy-induced BK peaked in 35 eyes (34.3% of BK) in 2000 and declined after 2013. Cases of Fuchs endothelial corneal dystrophy increased from 0 in 1991, to 15 eyes (18.5% of BK) in 2017. Lamellar keratoplasty has replaced PKP in our hospital. BK and regraft have increased, whereas post-keratitis scars and keratoconus have decreased. Laser-iridotomy-induced BK has decreased during the past decade, whereas Fuchs endothelial corneal dystrophy has increased.

Deciphering the mechanoresponsive role of \u03b2-catenin in keratoconus epithelium

Keratoconus (KC) is a corneal dystrophy characterized by progressive ectasia that leads to severe visual impairment and remains one of the leading indications for corneal transplantation. The etiology is believed to be multifactorial and alterations have been documented in the biomechanical, biochemical and ultrastructural characteristics of the cornea. While the exact site of disease origin is still debated, changes in the corneal epithelium are believed to occur even before the disease is clinically manifested. In this study we investigate the possible role of β-catenin as mechanotransducer in KC corneal epithelium. The sheets of corneal epithelium removed from keratoconic eyes when they underwent collagen crosslinking as a therapeutic procedure were used for this study. The healthy corneal epithelium of patients undergoing Laser Refractive Surgery for the correction of their refractive error, served as controls. Immunoblotting and tissue immunofluorescence studies were performed on KC epithelium to analyse the expression and localization of β-catenin, E-cadherin, ZO1, α-catenin, Cyclin D1, α-actinin, RhoA, and Rac123. Co-immunoprecipitation of β-catenin followed by mass spectrometry of KC epithelium was performed to identify its interacting partners. This was further validated by using epithelial tissues grown on scaffolds of different stiffness. Histology data reported breaks in the Bowman’s layer in KC patients. We hypothesize that these breaks expose the epithelium to the keratoconic corneal stroma, which, is known to have a decreased elastic modulus and that β-catenin acts as a mechanotransducer that induces structural changes such as loss of polarity (Syntaxin3) and barrier function (ZO1) through membrane delocalization. The results of our study strongly suggest that β-catenin could be a putative mechanotransducer in KC epithelium, thus supporting our hypothesis.

Three novel variants identified within ECM-related genes in Chinese Han keratoconus patients

As the primary indication for corneal transplantation, the pathogenesis of keratoconus remains elusive. Aiming to identify whether any mutation from extracellular-matrix (ECM)-related genes contributes to the patients with sporadic cases of keratoconus (KC) from Chinese Han population, one hundred and fifty-three participants in total were enrolled in our study, including fifty-three KC patients and one hundred healthy controls. Mutational analysis of three ECM-related genes (LOX, COL5A1 and TIMP3) with next-generation sequencing and Sanger sequencing was performed. To further confirm the function of three ECM-related genes in the pathogenesis of keratoconus, we performed Real-time Quantitative PCR in vitro. Results showed that three new sequence variants (c.95 G > A in LOX, c.1372 C > T in COL5A1 and c.476 C > T in TIMP3) were identified in aforementioned ECM-related genes in KC patients without being detected among the healthy controls. According to the results of QPCR, we found that the expression levels of LOX and TIMP3 were decreased in the KC patients, while COL5A1 showed no significant difference of expression. This is the first time to screen so many ECM-related genes in Chinese keratoconus patients using next-generation sequencing. We find numerous underlying causal variants, enlarging lots of mutation spectrums and thus providing new sites for other investigators to replicate and for further research.

Are Corneal Patients Accepting the Transplantation? The Cases of University of Gondar, Tertiary Eye Care and Training Center, Ethiopia.

Background For so long, corneal diseases have been known as one of the leading causes to blindness in the global. This blindness might be due to failure to accept the corneal transplantation. Therefore, this study aimed to determine the prevalence and the root challenges for corneal transplantation acceptance at the University of Gondar tertiary eye care and training center, Ethiopia. Methods An institution-based cross-sectional study was conducted among patients who had an indication for corneal transplantation at the University of Gondar tertiary eye care and training center since January 1, 2017, up to October 30, 2018. A structured questionnaire was used to collect the data and entered into Epi-Info 7 software and analyzed using SPSS version 20. Simple logistic regression was used to identify the associated factors of corneal transplantation acceptance. Associations between outcome and exposure variables were expressed by the adjusted odds ratio with a 95% confidence interval and p value <0.05. Result A total of 116 patients with a mean age of 51 (±21) years participated in the study. The overall acceptance level of corneal transplantation was only 38.8% (95% CI: 29.93, 47.66). Patients with poor knowledge [AOR = 2.41; 95% CI: 1.90, 6.48] and an unfavorable attitude [AOR = 6.33; 95% CI: 2.42, 16.54] were significantly associated with the acceptance of corneal transplantation. Conclusion The study revealed that the corneal transplantation acceptance level was very low. Hence, the government and other concerned stakeholders should give due emphasis to the awareness creation and behavior change communication strategies to increase the acceptance level of corneal transplantation.

Risk of corneal transplantation after phacoemulsification in patients with cornea guttata

AbstractPurposeTo investigate the risk of corneal transplantation after phacoemulsification related to cornea guttata.MethodsIn this retrospective registry‐based cohort study, patient data from the Swedish National Cataract Register for years 2010‐2012 were linked with data from the Swedish Cornea Transplant Register for years 2010‐2017. Altogether, data from 276,354 cataract patients was linked with data from 2,091 patients with primary and secondary endothelial failure as indication for corneal transplantation. Other surgical methods for cataract extraction than phacoemulsification were excluded. If both eyes had surgery, one eye was randomly selected to obtain unrelated samples. A Kaplan‐Meier curve and Cox regression analysis were used to investigate the risk for corneal transplantation due to endothelial failure after phacoemulsification.ResultsOut of the 3,346 phacoemulsification patients with cornea guttata, 153 underwent corneal transplantation within 6.2 years in median. The cumulative transplantation rate, 6 years after the phacoemulsification was 4.8% in the group with cornea guttata and 0.08% in the group without. The annual transplantation rate among the cornea guttata patients during the first year was 1.64% and diminished the following 5 years to 0.55% in average. The annual transplantation rate among the patients without cornea guttata was 0.01% in average after phacoemulsification during the same period of time. The transplantation hazard ratio for cornea guttata present at the phacoemulsification was 67.6 (95% CI: 53.6.0‐85.3, p &lt; 0.001), when adjusting for potential confounders.ConclusionsThe hazard of corneal transplantation after phacoemulsification was 67.6 times higher with cornea guttata than without. Still, the great majority of the patients with cornea guttata did not undergo corneal transplantation during the study period.

Trends in Corneal Transplantation from 2001 to 2016 in Germany: A Report of the DOG–Section Cornea and its Keratoplasty Registry

The purpose of this retrospective panel study was to provide an overview of absolute numbers and of trends in the types of and indications for corneal transplantation in Germany from 2001 to 2016. A questionnaire about absolute numbers, types of transplantation, and indications was sent to 111 ophthalmologic departments in Germany, out of which 94 (85%) provided their data. Since the year 2001, the number of corneal transplantations has increased by 1.5-fold, from 4730 penetrating keratoplasties (PKPs) in 2001 to 7325 penetrating and lamellar keratoplasties in 2016. The shift from penetrating to lamellar procedures began in 2006. In 2014, lamellar procedures (231 [4%] anterior and 2883 [49%] posterior lamellar keratoplasties) surpassed PKPs (2721, 47%) for the first time. Main indications for keratoplasty in Germany (2016) are Fuchs endothelial corneal dystrophy (46%), pseudophakic corneal decompensation (bullous keratopathy, 13%), repeated keratoplasty after graft failure (11%), keratoconus (8%), and corneal scarring (6%; others: 16%). The number of Descemet membrane endothelial keratoplasties (DMEKs) was 12 times higher (3850, 53%) than Descemet stripping automated endothelial keratoplasties (DSAEKs, 319, 4.4%) in 2016. The proportion of deep anterior lamellar keratoplasties (DALKs) never exceeded 6% (269 in 2011). The number of keratoplasties in Germany has increased from 2001 to 2016. Since 2014, posterior lamellar keratoplasties have surpassed PKPs. There was a constant increase of DMEKs, with a 12-fold higher number compared to DSAEKs in 2016. The shorter recovery time after DMEK seems to contribute to the trend toward earlier operative intervention in corneal endothelial diseases.

Changing indications and techniques for corneal transplantations at a tertiary referral center in Turkey, from 1995 to 2014

BackgroundIndications for corneal transplantation in developed and developing nations differ according to the different spectrum of corneal disease in each country.ObjectiveThe purpose of this study is to analyze the changing indications and surgical techniques for corneal transplantation over the past 20 years at a tertiary referral center in Turkey.MethodsWe retrospectively reviewed the records of patients who underwent keratoplasty from January 1995 to December 2014 (between 1995 and 2004, period 1, and between 2005 and 2014, period 2). Patients’ demographic data, indications for corneal transplantation, and the type of surgery were recorded.ResultsThe number of keratoplasties performed ranged from 548 in period 1 to 782 in period 2. Between 1995 and 2004, the leading indications were keratoconus (34.1%), bullous keratopathy (17%), and non-herpetic corneal scar (13.3%), and between 2005 and 2014, they were keratoconus (33.8%), corneal stromal dystrophy (14.2%), and bullous keratopathy (12.7%). All the keratoplasties performed in the 1995–2004 period were penetrating keratoplasty (PKP). During the period 2005–2014, PKP accounted for 93%, automated lamellar keratoplasty 5.8%, and deep anterior lamellar keratoplasty 1.2% of all corneal transplantations.ConclusionKeratoconus was the leading indication for keratoplasty in both periods. In the 2005–2014 period, corneal stromal dystrophy increased significantly. All the keratoplasties performed in period 1 and 93% of all keratoplasties performed in period 2 were PKP.

Outcomes of Wound Dehiscence Post-Penetrating Keratoplasty.

Penetrating keratoplasties (PKs) carry a lifetime risk of developing wound dehiscence, which can lead to severe consequences to vision. To better understand the risk, we analyzed the characteristics and outcomes of a series of patients with wound dehiscence post-PK. Data were collected retrospectively on 31 eyes from 30 patients with a history of wound dehiscence repair post-PK between January 1, 2009, and April 30, 2014, and followed up at the Cornea Service at Wills Eye Hospital. Only patients who had surgical repair of an open wound dehiscence were included, excluding those with wound slippage but no aqueous leak. The mean age at wound dehiscence was 56 years with a mean time from PK to dehiscence of 9.8 years. Among the 31 eyes, 26 (26/31, 84%) had trauma-induced dehiscence, while 5 had unknown causations or no reported trauma. The mean size of dehiscence was 153 ± 66 degrees. Visual outcomes ranged from 20/50 to no light perception, with a majority between 20/100 and hand motion (18/30, 60%). Twenty eyes (20/26, 76%) lost their lens at dehiscence. All 10 phakic eyes lost their lenses. Five patients retained their lens implants and had a better mean visual outcome (average = 20/400) than the 10 patients who lost their implants (average = 20/800) (1 lens status was unknown postdehiscence). Wound dehiscence is a lifelong risk after PK regardless of the age, indication for corneal transplant, and time since transplant. A better visual outcome was associated with retained pseudophakia and clear corneas.

Changes in Technique and Indications for Keratoplasty in Poland, 1989 to 2014: An Analysis of Corneal Transplantations Performed at Saint Barbara Hospital, Trauma Center, Sosnowiec, Poland

BackgroundThe purpose of this work was to study the evolving trends in techniques and indications for corneal transplantation in Poland. MethodsThis retrospective, descriptive analysis of corneal transplantations was performed at the Ophthalmology Department of Saint Barbara Hospital, Trauma Center, Sosnowiec, Poland, between 1988 and 2014. Structure of indications and surgery type rates over 26 years were tabulated by means of 5-year intervals. ResultsBetween 1989 and 2014, 1762 corneal transplantations were performed, including 1375 (78%) cases of penetrating keratoplasty, 137 (8%) lamellar keratoplasty, 112 (6%) patch grafts, and 138 (8%) keratolimbal allografts. The major indications and their respective overall percentage were corneal leucoma (24%), pseudophakic/aphakic bullous keratopathy (22%), Fuchs dystrophy (13%), keratoconus (13%), re-graft (11%), keratitis (9%), and limbal stem cell deficiency (8%), with changes in relative frequency of the leading indications over the following time intervals. The number of corneal transplantations gradually increased during the years reviewed. The rates of lamellar, keratolimbal, and patch grafts have grown dynamically since 2010, reaching 20%, 17%, and 12%, respectively, of procedures performed during 2010 to 2014. ConclusionsOver the past quarter of a century, there has been evolution in corneal transplantation service, from the first penetrating keratoplasty to the wide spectrum of procedures, including femtosecond laser–assisted keratoplasty. Although, since 2010, the rates of lamellar and keratolimbal allografts have grown rapidly, penetrating keratoplasty has remained the leading technique.

Novel Identity and Functional Markers for Human Corneal Endothelial Cells.

PurposeHuman corneal endothelial cell (HCEC) density decreases with age, surgical complications, or disease, leading to vision impairment. Such endothelial dysfunction is an indication for corneal transplantation, although there is a worldwide shortage of transplant-grade tissue. To overcome the current poor donor availability, here we isolate, expand, and characterize HCECs in vitro as a step toward cell therapy.MethodsHuman corneal endothelial cells were isolated from cadaveric corneas and expanded in vitro. Cell identity was evaluated based on morphology and immunocytochemistry, and gene expression analysis and flow cytometry were used to identify novel HCEC-specific markers. The functional ability of HCEC to form barriers was assessed by transendothelial electrical resistance (TEER) assays.ResultsCultured HCECs demonstrated canonical morphology for up to four passages and later underwent endothelial-to-mesenchymal transition (EnMT). Quality of donor tissue influenced cell measures in culture including proliferation rate. Cultured HCECs expressed identity markers, and microarray analysis revealed novel endothelial-specific markers that were validated by flow cytometry. Finally, canonical HCECs expressed higher levels of CD56, which correlated with higher TEER than fibroblastic HCECs.ConclusionsIn vitro expansion of HCECs from cadaveric donor corneas yields functional cells identifiable by morphology and a panel of novel markers. Markers described correlated with function in culture, suggesting a basis for cell therapy for corneal endothelial dysfunction.

Indications for and techniques of keratoplasty at Vietnam National Institute of Ophthalmology.

To report the indications for and techniques of corneal transplantation at Vietnam National Institute of Ophthalmology (VNIO) over a period of 12y (2002-2013). Records of patients who had undergone corneal transplantation at VNIO from January 1, 2002 to January 1, 2014 were reviewed to determine the indication for and type of corneal transplant performed. Patient age, gender, indication for corneal transplantation and surgical technique were recorded and analyzed. Corneal transplantation were underwent in 1390 eyes of 1278 patients with a mean age of 44.9±18.1y during the period under review. The most common indication was infectious corneal ulcer (n=670; 48.2%), followed by corneal scar (n=333, 24.0%), corneal dystrophy (n=138, 9.9%) and failed graft (n=112, 8.1%). Nearly all procedures performed were penetrating keratoplasty (n=1300, 93.5%), with a few lamellar keratoplasty procedures performed: lamellar keratoplasty (n=52, 3.7%), Descemet's stripping automated endothelial keratoplasty (n=27, 1.9%) and deep anterior lamellar keratoplasty (n=11, 0.8%). While the most common indication for keratoplasty was infectious keratitis, nearly all indications for corneal transplantation were managed with penetrating keratoplasty. However, lamellar keratoplasty techniques, including deep anterior lamellar keratoplasty and Descemet's stripping automated endothelial keratoplasty, are being performed with increasing frequency for isolated stromal and endothelial disorders, respectively.

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

To report evolving indications and preferred techniques of corneal transplantation in the United States. Retrospective review. Annual reports from the Eye Bank Association of America on corneal graft distribution in the United States from 2005 through 2014 were reviewed. Number and percentage of corneal grafts distributed for various types of keratoplasty and their surgical indications in the United States. 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. 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.

Endophthalmitis After Penetrating Keratoplasty

To determine the incidence of endophthalmitis after penetrating keratoplasty (PK) and patient and donor risk factors. Retrospective cohort study using national transplant registry data. All corneal transplant recipients (n = 11 320) registered on the United Kingdom Transplant Registry undergoing their first PK between April 1999 and December 2006. Patients who developed endophthalmitis were identified on the transplant registry. In addition, cases where the fellow cornea from the same donor had been transplanted were included. Clinical information regarding donor and recipient characteristics, surgical details, and postoperative outcomes were collected and analyzed. In cases where endophthalmitis was reported, the diagnosis was verified by a follow-up supplementary questionnaire to the surgeon. Logistic regression was used to investigate differences in the factors associated with the development of endophthalmitis. Incidence of endophthalmitis and graft survival. The overall incidence of endophthalmitis occurring after primary PK in the UK was 0.67%. The incidence of endophthalmitis occurring within 6 weeks of surgery was 0.16%. Graft survival after endophthalmitis was 27% (95% confidence interval, 16-38) at 5 years, with a mean best-corrected visual acuity of 1.13 (logarithm of the minimum angle of resolution) for surviving grafts. Factors associated with endophthalmitis were donor cause of death (infection), high-risk cases, and indication for corneal transplantation. Endophthalmitis remains a serious issue, with those affected having reduced graft survival and poor visual outcomes. Management of the identified recipient and donor risk factors are important to reduce endophthalmitis risk. In particular, the increased incidence of endophthalmitis when the donor dies of infection requires further explanation and review of current donor eye retrieval and eye bank practices. The delayed presentation of endophthalmitis cases also raises questions regarding possible sequestration of microbes within the corneal tissue and the effect of antimicrobials in storage media.

Suppression of Neovascularization of Donor Corneas by Transduction with Equine Infectious Anemia Virus-Based Lentiviral Vectors Expressing Endostatin and Angiostatin

Corneal transplantation is the oldest and one of the most successful transplant procedures with a success rate in many studies in excess of 90%. The high success rate is mainly attributable to the relatively immune-privileged status of the eye and the fact that the cornea is largely avascular. However, the success rate in patients with failed grafts is much lower such that regrafting is frequently the top indication for corneal transplantation in many centers. Neovascularization is the most important risk factor for rejection, as it allows access of the immune system to the donor tissue, compromising immune privilege of the graft/eye. We have developed a process to modify donor corneal tissue to prevent rejection by a single exposure to a gene therapy vector before surgery (EncorStat(®)). The vector used is based on clinically relevant equine infectious anemia virus (EIAV)-derived lentiviral platform and contains genes for two potently angiostatic genes, endostatin and angiostatin. We show that incubation of rabbit, primate, and human corneal tissue with the EIAV vector mediates strong, stable expression in the corneal endothelium. We have optimized this process to maximize transduction and, once this is complete, maximize the removal of free vector before transplant. Rabbit corneas treated with two different antiangiogenic expression vectors (EIAV-EndoAngio and to a lesser extent EIAV-Endo:k5) significantly suppressed neovascularization in a rabbit model of corneal rejection. As a result, corneal opacity, edema, and inflammatory infiltrates were reduced in these corneas. This study demonstrates that angiogenesis is a suitable target to prevent corneal rejection, and provides the first proof-of-concept data for the development of EncorStat, an ex vivo gene therapy treatment to prevent corneal rejection.