Healthcare professionals' knowledge and attitudes towards polygenic risk testing for glaucoma.

BACKGROUND: Effective clinical implementation of polygenic risk testing for glaucoma relies on healthcare professionals' attitudes and knowledge of the test. Given the emerging applications of the test, it will likely impact a range of healthcare professionals and will require competency in polygenic risk scores concepts for all those involved in patient care. To our knowledge, this is the first study to assess healthcare professionals' views towards polygenic testing for glaucoma. METHODS: An online cross-sectional questionnaire was distributed to healthcare professionals via relevant professional organisations in Australia. The questionnaire assessed experience and confidence with genetic testing, glaucoma and genetic knowledge, recommendations for the tests, and factors affecting the decision. RESULTS: A total of 94 participants completed the questionnaire. The sample was composed of ophthalmologists (36%), optometrists (21%), orthoptists (17%), general practitioners (16%) and clinical geneticists/genetic counsellors (10%). Although familiarity with polygenic risk scores for glaucoma was low overall (11%), the majority reported a positive attitude towards recommending testing based on known risk factors such as family history (91%) and older age (57%). Over 95% indicated that ophthalmologists would be the most appropriate group to order polygenic risk testing and communicate results. The majority felt they would benefit from more training on polygenic risk scores (93%). CONCLUSIONS: Our findings indicated that multiple groups of healthcare professionals were neither familiar nor confident with the concept of glaucoma polygenic risk testing, and identified training and education needs to support the implementation of testing into clinical practice.

Comparison of penetrating and endothelial keratoplasty in patients with iridocorneal endothelial syndrome: A registry study.

BACKGROUND: To compare graft survival of endothelial keratoplasty (EK) versus penetrating keratoplasty (PK) in patients with iridocorneal endothelial (ICE) syndrome and identify ocular features associated with graft survival. METHODS: Observational, prospective, cohort study. A total of 30 806 first grafts performed between 1985 and 2020 were identified through the Australian Corneal Graft Registry and included in this observational, prospective cohort study. A total of 196 eyes underwent a primary corneal graft for ICE syndrome. Kaplan-Meier graft survival plots and Chi-squared tests were performed to identify graft survival rates for EK and PK. A history of raised intraocular pressure (IOP) was also recorded and analysed. Graft survival of eyes with ICE syndrome were compared to that of other indications. RESULTS: Grafts performed for ICE syndrome increased to 0.8% of all cases during the 2005 to 2020 period compared with 0.5% between 1985 to 2004 (χ2 =9.35, p = 0.002). From 2010, EK surpassed PK as the preferred graft type. Survival of primary grafts in eyes with ICE syndrome was lower than for other indications (log-rank = 56.62, p < 0.001). Graft survival was higher following PK than Descemet stripping (automated) endothelial keratoplasty (DS(A)EK) (log-rank = 10.56, p = 0.001). Graft survival was higher in eyes without a history of raised IOP compared to those with a reported history of raised IOP (log-rank = 13.06, p < 0.001). CONCLUSIONS: ICE syndrome carries a poor prognosis for graft survival. DS(A)EK had a poorer prognosis than PK. A history of raised IOP is associated with higher risk of graft failure.

Attitudes Toward Glaucoma Genetic Risk Assessment in Unaffected Individuals.

Purpose: Integrating polygenic risk scores (PRS) into healthcare has the potential to stratify an individual's risk of glaucoma across a broad population. Glaucoma is the most common cause of irreversible blindness worldwide, therefore effective screening for glaucoma endorsed by the population is highly important. This study assessed the attitude of unaffected individuals toward PRS testing for glaucoma, and sought to identify factors associated with interest in testing. Methods: We surveyed 418 unaffected individuals including 193 with a first-degree relative with glaucoma, 117 who had a recent eye examination, and 108 general members of the community. Results: Overall, 71.3% of the individuals indicated an interest in taking a polygenic risk test for glaucoma. Interest was more likely in those who believed glaucoma to be a severe medical condition (odds ratio [OR] = 14.58, 95% confidence interval [CI] = 1.15-185.50, P = 0.039), those concerned about developing glaucoma (OR = 4.37, 95% CI = 2.32-8.25, P < 0.001), those with an intention to take appropriate measures regarding eye health (OR = 2.39, 95% CI = 1.16-4.95, P = 0.019), and those preferring to know if considered to be at-risk or not (OR = 4.52, 95% CI = 2.32-8.83, P < 0.001). Conclusions: Our results show strong interest in genetic risk assessment for glaucoma among unaffected individuals in Australia. Translational Relevance: These findings represent a valuable assessment of interest in glaucoma polygenic risk testing among potential target populations, which will be integral to the implementation and uptake of novel PRS-based tests into clinical practice.

Outcomes of corneal transplantation in Australia, in an era of lamellar keratoplasty.

Widespread adoption of modern lamellar procedures has altered the pattern of practice of corneal transplantation. Herein, we describe recent findings from the Australian Corneal Graft Registry and place these data into an international context. The total number of grafts reported to the Registry has doubled over the past decade. Deep anterior lamellar keratoplasty is increasingly used for keratoconus, while endokeratoplasty has displaced penetrating keratoplasty for Fuchs endothelial dystrophy. Graft survival and visual outcomes for modern lamellar procedures have shown improvement over time. First deep anterior lamellar and penetrating grafts for keratoconus show comparable survival and long-term best-corrected visual acuity is equivalent. Penetrating grafts for Fuchs endothelial dystrophy exhibit significantly better survival than do endokeratoplasties, largely because the latter undergo more early graft failures. However, visual rehabilitation is swifter in surviving endokeratoplasties. Significantly fewer recipients of a deep anterior lamellar graft or endokeratoplasty require spectacle or contact lens correction, compared with penetrating keratoplasty.

Attitudes Towards Polygenic Risk Testing in Individuals with Glaucoma.

PURPOSE: Glaucoma is the leading cause of irreversible blindness worldwide; however, vision loss resulting from glaucoma generally can be prevented through early identification and timely implementation of treatment. Recently, polygenic risk scores (PRSs) have shown promise in stratifying individual risk and prognostication for primary open-angle glaucoma (POAG) to reduce disease burden. Integrating PRS testing into clinical practice is becoming increasingly realistic; however, little is known about the attitudes of patients toward such testing. DESIGN: Cross-sectional, questionnaire-based study. PARTICIPANTS: Among the participants in the Australian and New Zealand Registry of Advanced Glaucoma, 2369 were invited to participate who fit the inclusion criteria of adults with a diagnosis of POAG who had not received genetic results that explain their condition, were not known to be deceased, resided in Australia, and had agreed to receive correspondence. METHODS: One thousand one hundred sixty-nine individuals (response rate, 49%) with POAG completed the survey evaluating their attitudes towards polygenic risk testing for glaucoma. MAIN OUTCOME MEASURES: Sociodemographic, health, perception, and emotional factors were examined to assess associations with interest in PRS testing. Interest in PRS testing was evaluated through assessing likelihood to take the test to predict personal risk of disease and disease severity, and whether the individual would recommend the test to family members or others. RESULTS: Our results show strong interest in the test, with 69.4% of individuals (798 of 1150) indicating a keenness in testing before diagnosis, had it been available. In particular, interest was seen in those from an urban area (odds ratio [OR], 1.70; 95% confidence interval [CI], 1.15-2.49; P = 0.007), those who perceived their risk of developing glaucoma as higher (OR, 2.05; 95% CI, 1.28-3.29; P = 0.003), and those who were worried about developing glaucoma (OR, 2.07; 95% CI, 1.27-3.37; P = 0.004). People who were interested in testing were more likely to change their eye health-seeking intentions and to recommend testing to family members and others, as well as to undergo testing for prognostication. CONCLUSIONS: These findings will help to facilitate the clinical implementation of PRS testing for glaucoma to reduce irreversible vision loss.

Women's Authorship of Reviews in Ophthalmic Journals Over Time.

PURPOSE: To investigate prevalence and trends in women's authorship of articles in ophthalmic review journals over 2 decades. DESIGN: Literature survey. METHODS: Total number of authors, and number and gender of first and senior (last-named) authors, were identified in all full reviews published in Prog Retin Eye Res, Surv Ophthalmol, and Curr Opin Ophthalmol for the calendar years 1999, 2009, and 2019. The gender of authors was assigned manually by multiple methods. The subspecialty area of each review was captured by keyword and text search. Country of origin was determined from attributions of first and senior authors. RESULTS: The gender of 841 first and senior authors was assigned unequivocally for 471 articles (96%). The frequency of women's authorship rose significantly over time (1999, 2009, 2019) for both first authors (19%, 32%, 44%; P < 0.001) and senior authors (16%, 19%, 29%; P = 0.018). The number of single-author reviews decreased significantly over time (P < 0.001), as did the proportion of reviews with neither a first nor a senior woman author (P < 0.001). Women's first authorship increased over time for reviews on glaucoma (P < 0.001), while women's senior authorship increased for anterior segment/cataract (P = 0.036). The proportion of reviews with a woman first or senior author did not differ by country of origin (P = 0.887 and P = 0.520, respectively). CONCLUSIONS: Women's authorship of articles in ophthalmic review journals increased significantly over the 20-year period, but a gender disparity remained: in 2019, more than 55% of first authors, and more than 70% of senior authors, were men.

DNA methylation at the 9p21 glaucoma susceptibility locus is associated with normal-tension glaucoma.

PURPOSE: Recent genome-wide association studies reported strong association of genetic variation at the CDKN2B/CDKN2B-AS1 locus on 9p21 with normal-tension glaucoma (NTG) in multiple populations. The mechanism by which this locus causes disease remains to be elucidated. We investigated the association of DNA methylation of CpG islands at this locus with NTG. METHODS: We conducted a retrospective case-control study of 178 NTG cases and 202 unaffected controls from Australia. CDKN2B and CDKN2B-AS1 promoter methylation was measured quantitatively using the MassCleave assay, and assessed for association with the disease, and the genotype of the associated risk variants using IBM SPSS statistics 22.0 CpG sites at which methylation status was associated with NTG were validated using pyrosequencing. RESULTS: We identified one CpG site (F1:13-14) in the CDKN2B promoter which showed significant association with NTG (p = 0.001). The association was highly significant in female cases (p = 0.006) but not in male cases (p = 0.054). The association was validated using an independent method confirming the likely association of DNA methylation with NTG in females (p = 0.015), but not in males (p = 0.497). In addition, methylation at CpG sites in CDKN2B was also associated with genotype at rs1063192, which is known to confer risk for NTG. CONCLUSION: This study reveals an association of methylation status in the CDKN2B promoter with NTG, particularly in females. This suggests that the observed genetic association with the disease at this locus could be in part due to epigenetic mechanisms, and is likely to be independent of the association of nonsynonymous coding variation within the gene.

Is there evidence for a surgeon learning curve for endothelial keratoplasty in Australia?

IMPORTANCE: Expected outcomes from endokeratoplasty may vary with surgeon experience. BACKGROUND: It was explored whether a surgeon learning curve exists for Descemet stripping endothelial keratoplasties (manual or automated) performed in Australia. DESIGN: This is a prospective cohort study, with various clinical settings. PARTICIPANTS: There were 2139 recipients of 2615 endothelial grafts, registered by 85 surgeons between January 2006 and December 2013. METHODS: Kaplan-Meier survival analyses and Cox proportional hazards regression were used to examine longitudinal graft survival. Manual and automated Descemet stripping endothelial keratoplasties were analysed together. Pearson chi-squared analyses were performed to examine differences amongst groups. Continuity correction was used for 2 × 2 tests, and statistical significance was set at P < 0.05 (two-sided). MAIN OUTCOME MEASURE: The main parameter measured was endothelial graft survival. RESULTS: Survival of the first 56 registered grafts was significantly poorer than survival of subsequent grafts (χ2  = 8.83, df = 1, P = 0.003), when data were combined for all surgeons. Surgeon workload influenced graft survival significantly (P < 0.001). This variable was retained in multivariate analysis designed to investigate independent factors influencing graft survival. Primary non-functioning grafts were significantly less likely to be reported for endokeratoplasties performed by surgeons with more than 56 registered grafts, compared with those registering 56 or fewer grafts (4.3% vs. 8.5%; χ2  = 18.38, df = 1, P < 0.001). CONCLUSIONS AND RELEVANCE: Our findings suggest that for less experienced or low-volume surgeons, longitudinal graft survival improved once 56 or more endokeratoplasties had been performed, indicative of a learning curve. The learning curve was less apparent for surgeons with 57 or more Descemet stripping endothelial keratoplasties and/or Descemet stripping automated endothelial keratoplasties registered during the 8-year study period. Different learning curves may be anticipated for these two groups of surgeons.

A comparison of endothelial and penetrating keratoplasty outcomes following failed penetrating keratoplasty: a registry study.

PURPOSE: To compare graft survival and visual outcomes for endothelial keratoplasty (EK) after a first penetrating keratoplasty (PK), with outcomes of repeat PK after a first PK. METHODS: 400 eyes with a second graft (65 EKs, 335 PKs) performed after failure of a primary PK were identified through the Australian Corneal Graft Registry, a national prospectively followed cohort. Grafts were performed after January 2008 (follow-up of the second graft extending to 6.75 years maximum). Kaplan-Meier graft survival plots were constructed and Cox proportional hazards regression was used to identify independent risk factors for graft failure. Best-corrected Snellen visual acuity (BCVA) at last follow-up was compared with pregraft acuity. RESULTS: Poor Kaplan-Meier graft survival was observed for PK-EK compared with PK-PK (log-rank=29.66, p<0.001). Variables retained in multivariate analysis as significantly influencing survival of the second graft included graft type (PK-EK or PK-PK, p<0.001), length of survival of the previous PK (global p=0.011), graft era (global p=0.018), occurrence of rejection in the second graft (p=0.005) and a history of raised intraocular pressure at any time (p=0.048), but not indication for the first graft. BCVA improved in the majority of surviving grafts and attainment of 6/12 vision was similar for both PK-EK and PK-PK groups. CONCLUSIONS: Our registry findings suggest that repeat PK may deliver a better outcome in terms of graft survival than EK after a failed PK that was performed initially for keratoconus or pseudophakic bullous keratopathy. For surviving grafts, visual outcomes appeared equivalent across groups.

Adequacy of published screening criteria for retinopathy of prematurity.

BACKGROUND: Criteria for screening preterm infants for retinopathy of prematurity vary around the world. We aimed to analyse the efficacy of alternative screening criteria. DESIGN: We collected retrospective data at a tertiary level neonatal nursery. PARTICIPANTS: Our participants were 1007 babies, born between 1997 and 2011, at <32 weeks gestational age or <1500 g birth weight (as recommended by the National Health and Medical Research Council in 1996), who had completed follow-up to full retinal vascularization, with defined presence or absence of retinopathy of prematurity. METHODS: We determined whether disease would be detected using an alternative Australian screening model (gestational age <30 weeks or birth weight <1250 g) or screening criteria utilized in developed countries with similar standards of neonatal care. MAIN OUTCOME MEASURES: Detection of retinopathy of prematurity is our main outcome. RESULTS: Using several of the alternative criteria, two neonates with clinically significant retinopathy of prematurity, one of whom required laser treatment to preserve sight, would not have been screened, and their disease may have gone undetected. Use of <30 weeks gestational age or <1500 g birth weight as the criteria would still have screened these infants but would have reduced the number of infants screened by 24.9%. CONCLUSIONS: Some commonly utilized international screening criteria for retinopathy of prematurity may risk clinically significant cases being missed and others may screen babies unnecessarily. Alternative criteria should be considered and '<30 weeks gestational age and/or <1500 g birth weight' appears a viable option.

Deep anterior lamellar keratoplasty versus penetrating keratoplasty for treating keratoconus.

BACKGROUND: Keratoconus is an ectatic (weakening) disease of the cornea, which is the clear surface at the front of the eye. Approximately 10% to 15% of patients diagnosed with keratoconus require corneal transplantation. This may be full-thickness (penetrating) or partial-thickness (lamellar). OBJECTIVES: To compare visual outcomes after deep anterior lamellar keratoplasty (DALK) and penetrating keratoplasty for keratoconus, and to compare additional outcomes relating to factors which may contribute to poor visual outcomes (e.g. astigmatism, graft rejection and failure). SEARCH METHODS: We searched a number of electronic databases including CENTRAL, PubMed and EMBASE without using any date or language restrictions. We last searched the electronic databases on 31 October 2013. We also handsearched the proceedings of several international ophthalmic conferences. SELECTION CRITERIA: We included all randomised controlled trials (RCTs) comparing the outcomes of DALK and penetrating keratoplasty in the treatment of keratoconus. DATA COLLECTION AND ANALYSIS: Two authors assessed trial quality and extracted data independently. For dichotomous data (graft failure, rejection, achievement of functional vision) results were expressed as odds ratios (ORs) and 95% confidence intervals (CIs). For continuous data (postoperative best corrected visual acuity (BCVA), uncorrected visual acuity (UCVA), keratometric astigmatism and spherical equivalent) results were expressed as mean differences (MDs) and 95% CIs. MAIN RESULTS: We identified two completed studies, with a total of 111 participants (n = 30 and n = 81), both conducted in Iran, that met our inclusion criteria. Participants had moderate to severe keratoconus pre-operatively and were randomly allocated to receive either DALK or penetrating keratoplasty. Only one eye of each participant was treated as part of the trials. The smaller study had 12 month follow-up data for all participants. For the larger study, four DALK surgeries had to be abandoned due to technical failure and visual and refractive outcomes were not measured in these participants. Follow-up length for the remaining 77 participants ranged from 6.8 to 36.4 months, with all 77 followed for at least three months post-suture removal. Details of the randomisation procedure were unavailable for the smaller study and so sensitivity analyses were conducted to determine if the results from this study had affected the overall results of the review.Neither of the included studies reported a difference between groups on any of the measures of post-graft visual achievement, keratometric astigmatism or spherical equivalent. A single case of graft failure in a penetrating keratoplasty was reported. No postoperative graft failures were reported in the DALK group of either study.Instances of graft rejection were reported in both groups, in both studies. The majority of these cases were successfully treated with steroids. The data, which related to all cases in each study - given that the four cases that did not go ahead as planned had already technically failed without presence of rejection - showed that rejection was less likely to occur in DALK (odds ratio (OR): 0.33, 95% confidence interval (CI) 0.14 to 0.81, GRADE rating: moderate).Results of the sensitivity analysis indicated that inclusion of the Razmju 2011 study did not bias the results with regards to rejection episodes. While sensitivity analysis showed altered results with regards to failure rates, the data available from the Javadi 2010 study alone had a very wide 95% CI, suggesting an imprecise estimate. Therefore, even after removal of the Razmju 2011 data, it is still difficult to draw conclusions regarding superiority of one technique over another with regards to graft failure.DALK was unable to be completed as planned in four cases and in a further three cases, complications during dissection required further intervention. Other adverse events, of varying severity, were reported in both intervention groups with similar frequency. For both types of surgery, these included postoperative astigmatism, steroid induced ocular hypertension and persistent epithelial defects. In recipients of DALK, one participant had interface neovascularisation (a proliferation of blood vessels where the host and donor cornea come together) and one had wrinkling of Descemet's membrane, the basement membrane separating the corneal stroma from the corneal endothelium. In the penetrating keratoplasty groups, one participant required graft resuturing and one had an atonic pupil, a condition in which the pupil dilates and is non-reactive.Overall, the quality of the evidence was rated as very low to moderate, with methodological limitations, incomplete data analysis and imprecision of findings, as well as high risk of bias in several areas for both studies. AUTHORS' CONCLUSIONS: We found no evidence to support a difference in outcomes with regards to BCVA at three months post-graft or at any of the other time points analysed (GRADE rating: very low). We also found no evidence of a difference in outcomes with regards to graft survival, final UCVA or keratometric outcomes. We found some evidence that rejection is more likely to occur following penetrating keratoplasty than DALK (GRADE rating: moderate). The small number of studies included in the review and methodological issues relating to the two, mean that the overall quality of the evidence in this review is low. There is currently insufficient evidence to determine which technique may offer better overall outcomes - final visual acuity and time to attain this, keratometric stabilisation, risk of rejection or failure, or both, and risk of other adverse events - for patients with keratoconus. Large randomised trials comparing the outcomes of penetrating keratoplasty and DALK in the treatment of keratoconus are needed.

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.

Predictive genetic testing experience for myocilin primary open-angle glaucoma using the Australian and New Zealand Registry of Advanced Glaucoma.

PURPOSE: Predictive genetic testing of relatives of known myocilin (MYOC) gene mutation carriers is an appropriate strategy to identify individuals at risk for glaucoma. It is likely to prevent irreversible blindness in this high-risk group because this treatable condition might otherwise be diagnosed late. The Australian and New Zealand Registry of Advanced Glaucoma has established genetic testing protocols for known glaucoma genes, including MYOC. METHODS: Through the Australian and New Zealand Registry of Advanced Glaucoma, we investigated the experience of 40 unaffected individuals who had undergone predictive genetic testing for MYOC mutations through questionnaires. RESULTS: The main motivations for being tested were (i) to make appropriate interventions and (ii) to reduce uncertainty. All our respondents perceived strong benefits, either medical or emotional, in being tested. However, different concerns were raised by the respondents that need to be addressed during counseling. Greater family awareness was reported by the majority of the respondents, and the ability to provide information to children was a strong motivation for being tested. CONCLUSION: This study provides valuable information on the personal and familial impacts of having predictive genetic testing for glaucoma, which will help health professionals to better address the issues faced by patients and provide them adequate support.

Co-expression of a scFv antibody fragment and a reporter protein using lentiviral shuttle plasmid containing a self-processing furin-2A sequence.

It is often desirable to co-express a reporter protein with a potential therapeutic protein, to verify correct targeting of an expression strategy. Vectors containing a viral self-processing 2A sequence have been reported to drive equimolar expression of two or more transgenes from a single promoter. Here, we report on the co-expression of a secreted antibody fragment and an intracellular reporter protein, enhanced yellow fluorescent protein from lentiviral shuttle plasmids by inserting a furin-2A (F2A) sequence between the two cDNAs, in two different orientations, in the expression cassette. We show that the order of these two transgenes relative to the F2A sequence affects expression levels. Reduced expression of each transgene positioned downstream of F2A, compared with upstream of F2A, was observed (p<0.05). Moreover, protein expression from double-cDNA plasmids was significantly lower than from their corresponding single transgene counterparts (p<0.05).

The influence of Australian eye banking practices on corneal graft survival.

OBJECTIVE: To identify eye banking practices that influence corneal graft survival. DESIGN, SETTING AND PARTICIPANTS: Prospective cohort study of records of 19,254 followed corneal grafts in 15160 patients, submitted to the Australian Corneal Graft Registry between May 1985 and July 2012. MAIN OUTCOME MEASURES: Influence of corneal preservation method (organ culture, moist pot, Optisol, other); death-to-enucleation, death-to-preservation and enucleation-to-graft times; transportation by air; graft era; and indication for graft on probability of graft survival at most recent follow-up. RESULTS: In multivariate analysis, 919 penetrating grafts performed using corneas transported interstate by air exhibited worse survival than 14,684 grafts performed using corneas retrieved and used locally (hazard ratio [HR], 1.44; 95% CI, 1.21-1.73; P = 0.001). This was also the case for traditional lamellar grafts (64 corneas transported by air and 813 used locally; HR, 1.69; 95% CI, 1.03-2.78; P = 0.038). Indication for graft influenced survival of penetrating grafts (4611 keratoconus, 727 emergency or high-risk, 10,265 other indication; global P < 0.001) and traditional lamellar grafts (65 keratoconus, 212 emergency or high-risk, 600 other indication; global P < 0.001). The preservation medium in which corneas used for traditional lamellar grafts were stored exerted a marginal influence on graft survival (global P = 0.047). CONCLUSIONS: Donor corneas transported interstate exhibited poorer survival after transplantation than those retrieved and grafted locally. Higher proportions of emergency procedures involving transported corneas did not account for this difference. Where possible, efforts to avoid transportation of corneal tissue by air freight within Australia may be warranted.