Changing Trends in Corneal Transplantation in Aotearoa/New Zealand, 1991 to 2020: Effects of Population Growth, Cataract Surgery, Endothelial Keratoplasty, and Corneal Cross-Linking for Keratoconus.

PURPOSE: The purpose of this study was to identify trends in the primary indication for keratoplasty in New Zealand/Aotearoa (NZ) after significant population growth, increase in the number of cataract surgeries per population, widespread adoption of endothelial keratoplasty, and introduction of corneal cross-linking for keratoconus. METHODS: Statistical analysis of the New Zealand National Eye Bank's prospective database of all keratoplasties was performed between January 1991 and January 2020. Indications for keratoplasty were isolated for the primary diagnosis. RESULTS: In total, 6840 corneas were transplanted with mean 236 ± 57.5 transplants/year, increasing from 2.55 to 6.06 per 100,000 NZ population/year. Over the past decade, the number of transplant recipients aged 60 years or older has increased and recipients aged 20 to 39 years have plateaued. In 2019, for the first time, regraft became the most common indication (30.9%), followed by keratoconus (27.9%) and corneal dystrophy (18.8%), with a steady decline in bullous keratopathy. Proportions of the keratoplasty technique changed dramatically: penetrating keratoplasty fell from 91.4% in 2006 to 55.0% in 2019, Descemet's stripping endothelial keratoplasty increased from 0% to 29.5%, anterior lamellar keratoplasty increased from 2.5% to 5.7%, and Descemet membrane endothelial keratoplasty increased from 0% to 9.1%. CONCLUSIONS: Keratoplasty trends in Aotearoa/NZ have changed considerably because of the evolution of phacoemulsification and keratoplasty techniques. Unlike proportions observed overseas, NZ still performs penetrating keratoplasties in over half of all transplants. Corneal cross-linking may be having an early effect of reducing keratoplasty rates for keratoconus.

Repeat corneal transplantation in Auckland, New Zealand: Indications, visual outcomes and risk factors for repeat keratoplasty failure.

IMPORTANCE: In New Zealand, repeat keratoplasty has become the second leading indication for corneal transplantation. BACKGROUND: To report the indications, outcomes and survival of repeat keratoplasty and evaluate the risk factors for graft failure. DESIGN: Retrospective study in a public corneal service. PARTICIPANTS: Two hundred nineteen patients undergoing 279 repeat keratoplasty procedures during 1991-2017. METHODS: The New Zealand National Eye Bank prospectively collects data on all corneal transplants. This was utilized to identify patients undergoing repeat keratoplasty in Auckland. Clinical records were retrospectively reviewed. MAIN OUTCOME MEASURES: Graft survival and visual outcome. RESULTS: The repeat keratoplasty technique was penetrating keratoplasty (PK) in 242 cases (86.7%) and endothelial keratoplasty in 37 (13.3%). The most common primary indication was keratoconus (46.6%). The most common indication for repeat keratoplasty was endothelial decompensation (37.6%). For PK performed as a repeat keratoplasty, the median survival in years was 12.0 for first, 3.5 for second and 2.3 for third repeat keratoplasty. Keratoconus had the longest graft survival (median 13.0 years). In surviving grafts, median visual acuity was 6/15 at 1 year and 6/12 at 2 years. On multivariate analysis, regraft number (P = .022), non-European ethnicity (P = .007), concurrent surgical procedure (P < .0005), lower donor endothelial density (P = .028), previous glaucoma surgery (P < .0005), postoperative raised intraocular pressure (P = .001) and graft rejection (P = .032) were associated with keratoplasty failure. CONCLUSIONS AND RELEVANCE: Repeat keratoplasty survival is affected by multiple interacting factors and prognosis worsens with each subsequent regraft. These results will help guide clinicians in addressing patients' individual risk factors when embarking on repeat corneal transplant surgery.

Riding the cell jamming boundary: Geometry, topology, and phase of human corneal endothelium.

It is important to assess the viability of eye-banked corneas prior to transplantation due to inherent senescence and known loss of endothelial cells during surgical manipulation. Corneal endothelial cells have a complex basal and paracellular shape making them challenging to accurately measure, particularly in oedematous ex vivo tissue. This study used calibrated centroidal Voronoi Diagrams to segment cells in images of these human corneas, in order to characterize endothelial geometry, topology, and phase. Hexagonal cells dominated the endothelia, with most comprised of five different pleomorphs exhibiting self-similar topological coarsening through most of the endothelial cell density range. There was a linear relationship between cell size and shape, though cells with greater than six sides were present in larger proportions than cells with less. Hexagonal cell regularity was stable and largely independent of density. Cell and tissue phase was also examined, using the cell shape index relative to the recently discovered 'cell jamming' phase transition boundary. Images showed fluid endothelia with a range of shape indices spanning the boundary, independent of density but dependent on hexagonal regularity. The cells showed a bimodal distribution centred at the boundary, with the largest proportion of cells on the fluid side. A shoulder at the boundary suggested phase switching via shape transformation across the energy barrier, with cells either side having distinctly different size and shape characteristics. Regular hexagonal cells were closest to the boundary. This study showed the corneal endothelium acts as a glassy viscous foam characterized by well-established physical laws. Endothelial cell death transiently and locally increases cell fluidity, which is subsequently arrested by jamming of the pleomorphically diverse cell collective, via rearrangement and shape change of a small proportion of cells, which become locked in place by their neighbours thereby maintaining structural equilibrium with little energy expenditure.

Morphometry of organ cultured corneal endothelium using Voronoi segmentation.

The endothelial viability of eye-banked corneas must be assessed before transplantation, yet phase-contrast images of the endothelium of corneas stored in an Organ Culture system have a huge variety of endothelial appearance at different focal planes, due to stromal swelling and an evaluation technique that swells the cells and their intercellular spaces to make them visible. This makes them difficult to assess using common edge-based segmentation methodologies that have mostly been developed in vivo using specular microscopy. Additionally, as the endothelial cell architecture has radically different form at apical and basal poles, segmentation of only the apical view cannot describe the cell as a whole. Using custom software, this study instead defines the cell borders using a calibrated Voronoi diagram, a region-based image segmentation technique that uses a point cloud of cell centroids as the only input required to measure the size (polymegathism) and shape (pleomorphism) of the endothelial cells. Measurements included the range and variation in the cell area and density, the number of cell sides, and several novel shape descriptors. A dataset of endothelial cell measurements was compiled from 2000 images of 678 corneas comprising 354,998 cells, and validated by comparison to previous studies from a variety of tissue sources, imaging modalities, and analysis techniques. While there were some differences in cell size variation and pleomorphic composition than seen in some other studies, much of the data was directly comparable, demonstrating fast and accurate endothelial cell morphometry at a large scale for a wide range of routine organ cultured corneas.

New Zealand trends in corneal transplantation over the 25†years 1991-2015.

AIMS: To report the 25-year longitudinal trends in indications and corneal transplantation techniques in New Zealand. METHODS: Statistical analysis of prospectively acquired New Zealand National Eye Bank (NZNEB) electronic database from 1991 to 2015 inclusive. Subjects were recipients of corneal transplants in 62 centres supplied by the NZNEB. Main outcome measures were indications, recipient age and transplantation techniques. RESULTS: From January 1991 to December 2015, NZNEB supplied tissue for 5574 corneal transplants, increasing annually from 89 (1991) to 290 (2015). Penetrating keratoplasty remained the most commonly performed technique throughout the 25-year period, although it decreased from 98.9% of all transplants in 1991 to 60.3% in 2015. There was a corresponding increase in deep anterior lamellar and endothelial keratoplasty over the most recent decade from 2.5% to 7.2% and 4.9% to 31.4%, respectively. Keratoconus remained the leading indication for keratoplasty through to 2015 (34.5%). Regrafts (23.1%) and Fuchs endothelial corneal dystrophy (17.0%) have become more common indications, while bullous keratopathy has become less common (10.8%). There was a bimodal distribution in age with peaks at 20-29 and 60-79 years. There was a reduction in recipients under age 40 and corresponding increase in the percentage of recipients aged 40-69. CONCLUSION: Changing indications and increasing uptake of lamellar keratoplasty have been significant international trends over the last 25 years. However, New Zealand's corneal disease and population characteristics create unique longitudinal trends, with keratoconus remaining the leading indication and penetrating keratoplasty the leading technique from 1991 to 2015.

The New Zealand National Eye Bank study: trends in the acquisition and storage of corneal tissue over the decade 2000 to 2009.

PURPOSE: To evaluate trends in the acquisition, storage, and utilization of donated corneal tissue in New Zealand, 2000 to 2009. METHODS: The New Zealand National Eye Bank records were analyzed for the decade January 2000 to December 2009. Variables analyzed included donor demographics (age, sex, and ethnicity), donor source, donor cause of death, death-to-preservation interval (DPI), corneal storage time, tissue contamination, endothelial assessment, cornea suitability for transplantation, and corneal tissue utilization. RESULTS: A total of 1268 eye donors were identified during the 10-year period. Overall, 36% (n = 457) were female and 64% male (n = 813). Median donor age was 67 years, and 23% of donors were younger than 50 years (range, 5-90 years). There was a decrease in donor age over the decade (P = 0.006). The median DPI was 18.5 hours. No relationship was identified between cornea suitability for transplantation and DPI (P = 0.28) or donor gender (P = 0.54). There was a low microbial contamination rate (1%). Human immunodeficiency virus, hepatitis B, or hepatitis C serology was positive in 48 donors (4%). Overall, 90% of corneas were suitable for transplantation with a high utilization rate (88%). A novel association was identified between male sex and lower corneal endothelial cell density (P = 0.03). CONCLUSIONS: This New Zealand National Eye Bank analysis identified trends in the acquisition, storage, and utilization of donated corneal tissue throughout New Zealand over the past decade and provides valuable additional information to the international eye bank data.

Trends in the distribution of donor corneal tissue and indications for corneal transplantation: the New Zealand National Eye Bank Study 2000-2009.

BACKGROUND: To investigate the indications for corneal transplantation and the distribution of donor corneal tissue in New Zealand. DESIGN: Analysis of the prospective database of the New Zealand National Eye Bank. PARTICIPANTS: A total of 2205 corneal transplants were assessed. METHODS: New Zealand National Eye Bank records were analysed for the decade 2000-2009. MAIN OUTCOME MEASURES: Variables analysed included donor corneal tissue distribution (including public and private sectors), indications for transplantation, donor corneal tissue recipient demographics (age and gender) and corneal transplantation type. RESULTS: An average of 220 corneal transplants were performed each year over the 10-year period (n=2205). The median recipient age was 45years (range 3 to 102years) and 54.0% of recipients were male. In total 71.8% of transplants were performed in the public health sector. Surgeons in the Auckland metropolitan area performed 47.2% of all corneal transplants. The most common indications for corneal transplantation were: keratoconus (41.1%), repeat transplant (17.0%), aphakic/pseudophakic bullous keratopathy (13.9%), corneal dystrophy (10.7%), keratitis (7.9%) and trauma (3.7%). Overall, penetrating keratoplasty accounted for 90.7% of all corneal transplants, however, during the latter half of the study there was a progressive shift in transplantation type, with deep anterior lamellar keratoplasty and Descemet's stripping endothelial keratoplasty combined accounting for 32.3% of all transplants in the final year of the study period. CONCLUSIONS: This New Zealand National Eye Bank study provides valuable data regarding the indications for corneal transplantation, transplant recipient demographics and changes in transplantation type in New Zealand over the past decade.

The New Zealand National Eye Bank: survival and visual outcome 1 year after penetrating keratoplasty.

PURPOSE: To identify potential donor, recipient, surgical, and postoperative factors that may influence survival and visual outcome of penetrating keratoplasty (PKP). METHODS: As part of a prospective longitudinal study, the electronic records of the New Zealand National Eye Bank were analyzed for the 10-year period from 1994-2003. Both univariate and multivariate analysis was performed. RESULTS: During the study period, the New Zealand National Eye Bank supplied 1820 corneas for PKP and 1629 (90%) had 1-year follow-up data. Overall, the 1-year survival rate was 87% (n = 1429). Donor factors including age, donor source, cause of death, death-to-preservation interval, endothelial cell density, donor lens status, and storage duration, were not significantly associated with decreased survival. The leading cause of PKP failure was irreversible rejection (7%, n = 114). Independent risk factors identified for decreased PKP survival were: 1 or more episodes of reversible rejection, active inflammation at PKP, preexisting corneal vascularization, intraoperative complications, small graft size (≤ 7.25 mm), large graft size (≥ 8.5 mm), preoperative glaucoma, and a preoperative diagnosis of regraft or trauma. A best-corrected Snellen visual acuity of 6/12 or better was achieved in 60% of eyes [mean: 6/15 (logarithm of the minimum angle of resolution 0.40)]. Keratoconus and Fuchs endothelial dystrophy were the diagnoses with best survival and visual outcome, whereas, bullous keratopathy, trauma or noninfective keratitis were associated with poorer visual outcome. CONCLUSIONS: Several independent risk factors were identified that significantly influenced PKP first year survival outcome. This information is valuable to patients and surgeons with respect to determining prognosis and clinical decision making.

Recurrence of keratoconic pathology in penetrating keratoplasty buttons originally transplanted for keratoconus.

PURPOSE: Study aimed to examine buttons removed from patients originally grafted for KC (group 1) for signs of recurrence at a cellular level and compare them with buttons removed from patients originally grafted for other conditions (group 2). The study further aimed to compare buttons from group 1 exhibiting high astigmatism (group 3) with the other buttons in the study (group 4). METHODS: Together with clinical data, corneal buttons were collected at repeat penetrating keratoplasty and labeled immunohistochemically with a panel of antibodies to structural proteins to assist microanatomical interpretation. Image analysis of montaged images of many individual sections was performed using custom software. The resulting data were analyzed statistically for significant differences between groups 1/2 and 3/4. RESULTS: Little evidence of KC recurrence could be found despite statistically significant differences between groups 1/2 in corneal thinning at both graft-host junction (GHJ) (P = 0.035) and within the graft (P = 0.001), epithelial thickening at the GHJ only (P < 0.001), high astigmatism (P = 0.028), and history of high intraocular pressure (P = 0.032) or rejection (P = 0.002) and between groups 3/4 in corneal thinning at both GHJ (P = 0.002) and within the graft (P = 0.003), epithelial thickening at the GHJ only (P = 0.003), and high astigmatism (P < 0.001). CONCLUSION: This study has highlighted the rarity of recurrence of KC in transplanted donor corneas and the corresponding difficulty in detecting early signs of the disease.

Clinicopathological features of severe corneal blood staining associated with proliferative diabetic retinopathy.

A 54-year-old man with a history of severe proliferative diabetic retinopathy in both eyes and profound visual impairment presented with severe corneal blood staining in the left eye secondary to a "spontaneous" total hyphaema and raised intraocular pressure in an eye with iris neovascularization. Despite anterior chamber washout, the cornea remained virtually opaque and thickened. The subject subsequently underwent pars plana vitrectomy with endolaser using a temporary keratoprosthesis, insertion of a Morcher iris-surround intraocular lens and penetrating keratoplasty. Histopathology of the excised corneal button revealed fine eosinophilic granules composed of aggregations of haemoglobin and its breakdown products dispersed throughout the stroma, with occasional foci of weakly positive Perl staining for intracellular haemosiderin. Fluorescence confocal microscopy revealed a marked increase in fluorescence throughout the corneal stroma and the basal epithelial layer. This case highlights the microstructural features and aspects of the surgical management of severe corneal blood staining.

The New Zealand National Eye Bank study 1991-2003: a review of the source and management of corneal tissue.

PURPOSE: To evaluate donor demographics and source, donor tissue processing and storage, biologic contamination, and the utilization and distribution of corneal tissue procured by the New Zealand National Eye Bank. METHODS: As part of a prospective longitudinal study, the electronic records of the NZNEB for the 13-year period 1991-2003 were analyzed for each year with respect to donor demographics, donor source and cause of death, death-to-preservation interval, storage methods, endothelial assessment, biologic contamination, corneal tissue utilization, and distribution. RESULTS: During the study period, 3221 corneas were retrieved from 1628 donors (69.8% male, 30.2% female), with the mean age of donors 59.4 years (SD 18.3 years) and range 4 to 95 years. No significant correlation was identified between donor age group (using 10-year intervals) and the proportion of corneas suitable for transplantation. Donors were procured from the Coroner's service (67.6%), public hospitals, (23.5%) and multiorgan donors (7.1%). The most common causes of donor death were cardiovascular disease, trauma, and cerebrovascular disease. Average storage duration increased from 3.5 to 11.8 days when organ culture replaced hypothermic storage in 1992. Biologic contamination occurred in 5% of all donor corneas. The most common bacterial and fungal isolates were coagulase-negative staphylococci and Candida spp, respectively. A significant decrease in contamination rate over the years of the study was identified. Overall, 79.4% of corneal tissue procured was used for corneal transplantation (75.8% for penetrating keratoplasty, 2.1% for lamellar keratoplasty, and 1.5% for unspecified transplants), and 21.6% was discarded. Most common reasons for discarding tissue were biologic contamination, abnormal serology, and failed endothelial assessment. CONCLUSION: Analysis of the NZNEB database provides valuable information in relation to eye banking and corneal transplantation in New Zealand. Significant trends were identified in donor demographics, donor procurement source, improved donor tissue processing and storage, decreased biologic contamination, and increased utilization of corneal tissue.

Morphological changes in keratoconus: pathology or pathogenesis.

Keratoconus was first discriminated from other corneal ectatic diseases in 1854. Since that time the morphological characteristics of keratoconic progression have been invaluable in the diagnosis of the condition. The key clinical features used to identify keratoconus have remained essentially the same since the introduction of the slit-lamp biomicroscope. Only relatively recently has the development of computerized corneal topography revolutionized the diagnosis of early keratoconus. Analysis of peer-reviewed literature databases revealed a steady chronological increase in pathological research into the progress of keratoconus. This overview describes the recent advances in our understanding of keratoconic pathology and highlights the interactions within the cornea that may be important in the pathogenesis of this condition.

Confocal imaging of the human keratocyte network using the vital dye 5-chloromethylfluorescein diacetate.

BACKGROUND: The human corneal stroma consists of intercalated layers of collagen and keratocytes. These cells are known to maintain the stroma and aid in repair but it is likely they have other crucial roles throughout the cornea. The complexity of their anatomy is revealed in this study by ex vivo in situ images of the human keratocyte covering a range of ages. METHODS: Human donor corneas of different ages were stained with 5-chloromethylfluorescein diacetate (CMFDA), a dye that is anchored and retained within the cell cytoplasm. The tissue was fixed, sectioned, mounted, and then imaged using a confocal laser scanning microscope at various magnifications and tissue planes. The digital image sets were transferred to multifunction image processing software for analysis and production of 3-D stereo images of keratocyte networks throughout the stroma. RESULTS: High quality images of CMFDA-stained cells revealed differences in the structure and orientation of keratocytes in the anterior, central and posterior stroma, which did not differ throughout the age-range studied. This method reveals very fine cell process ramifications not previously visualized, orientated in lateral and antero-posterior directions, and it confirms the potential for multidirectional communication between keratocyte networks. CONCLUSIONS: This qualitative study found consistency of keratocyte morphology in the normal human cornea throughout life. It confirmed differences in keratocyte anatomy, and the potential for rapid cellular communication by multiple interconnecting processes supporting cohesive keratocyte activity. This high-resolution 3-D microscopic study should assist in identifying gross deviant cellular behaviour in post-surgical and disease states.