Iris melanocytic tumours in New Zealand/Aotearoa: presentation, management and outcome in a high UV exposure environment.

BACKGROUND/OBJECTIVES: Iris melanoma, a rare intraocular malignancy, represents the smallest subgroup of uveal melanoma. This first, comprehensive study of iris melanocytic lesions in the high ultraviolet environment in New Zealand/ Aotearoa (NZ) examines diagnosis, management and outcomes. SUBJECTS/METHODS: Retrospective study of iris melanocytic tumours referred to tertiary referral centres in Auckland, NZ, over 20 years (1999-2018). Data analysed include demographics, tumour characteristics, histology, genetic analyses, treatment modalities, recurrence, metastasis, 5-year and overall survival. RESULTS: Cohort (N = 51) was predominantly NZ European (98.0%) with no indigenous Maori, or Pasifika. Median age at presentation was 58 years. Tumours involved a median of two clock hours of iris. The posterior tumour margin extended to the anterior chamber angle in 22 patients (45.8%). Management included initial observation 54.9%, iridectomy/excision biopsy 29.4%, irido-cyclectomy 7.8%, plaque radiotherapy 7.8%, proton beam radiotherapy 7.8%, and ultimately enucleation 17.6%. Histology was performed in 19 cases (37%) with 16 confirmed melanomas (84%). Mean follow-up 4.2 years with median visual acuity of 6/7.5 two years post intervention. Melanoma-related metastasis and mortality occurred in two cases with five-year melanoma-related mortality of 2.0%. CONCLUSION: In a climate with high ultraviolet exposure iris melanocytic tumours occurred almost exclusively in NZ Europeans, however, the majority of cases were category T1, possibly reflecting early diagnosis in the NZ health system. Nonetheless, >50% underwent surgery or radiotherapy, often utilising more than one modality. A high index of suspicion and early referral of iris melanocytic lesions should be considered in regions with high UV exposure.

The Aotearoa Research Into Keratoconus Study: Geographic Distribution, Demographics, and Clinical Characteristics of Keratoconus in New Zealand.

PURPOSE: To investigate the epidemiologic, demographic, and basic clinical characteristics of individuals with keratoconus managed by optometrists in New Zealand (NZ)/Aotearoa. METHODS: A prospective, longitudinal, nationwide, survey protocol was completed for every patient with keratoconus who underwent a consultation with participating optometrists in a 2-year period. Data for each patient included date of birth, sex, self-reported ethnicity, new or previous diagnosis, uncorrected (UCVA) and best-corrected visual acuity (BCVA), type of refractive correction required to obtain BCVA and keratometric readings obtained using keratometry or computerized topography. RESULTS: One thousand eight hundred sixty-nine cases were identified, with a mean age of 41.0 ± 15.7 years, 56.4% being men, and 87.3% with previous diagnosis. The distribution of cases was skewed toward Auckland (41.6%), Waikato (21.3%), Wellington (16.8%), and Bay of Plenty (13.3%). Self-reported ethnicities were predominantly NZ European (54.4%), Maori (24.7%), and Pacific Peoples (15.5%), disproportionate to the general population profile (74.0%, 14.9%, and 7.4% respectively). Most eyes (64.3%) were managed with rigid contact lenses (corneal lens in 34.2%). The mean K-mean was 49.0 ± 5.7 D. The mean UCVA was 6/42 and BCVA was 6/9. Maori and Pacific Peoples had both the highest K-mean and proportions of eyes graded stage IV on the Amsler-Krumeich scale. CONCLUSIONS: The results indicate that keratoconus is relatively common in NZ with at least 1869 patients managed by optometrists in 2 years. Most eyes had mild to moderate disease; however, Maori and Pacific Peoples seem to have greater disease severity. An ethnic predilection is apparent, with Maori and Pacific Peoples overrepresented relative to their population proportions, reinforcing a long-held clinical suspicion.

Prospective one year study of corneal biomechanical changes following high intensity, accelerated cornea cross-linking in patients with keratoconus using a non-contact tonometer.

PURPOSE: To characterize corneal biomechanical properties utilizing a dynamic ultra-high-speed Scheimpflug camera equipped with a non-contact tonometer (CorVis ST, CST) in keratoconic corneas following continuous high intensity, high irradiance corneal cross-linking. DESIGN: Prospective longitudinal single-centre study at a tertiary referral center. METHODS: Corneal biomechanical properties were measured in patients with progressive keratoconus undergoing high intensity (30 mW/cm2), high irradiance (5.4 J/cm2), accelerated corneal cross-linking with continuous exposure to ultraviolet-A for 4 min. CST was used to assess corneal biomechanical properties pre-operatively and at 1, 3, 6 and 12 months post-operatively. CST output videos were further analyzed using several previously reported algorithms. RESULTS: A total of 25 eyes of 25 participants were examined. The mean age of participants was 20.9 ± 5.3 years; 56% were male and 80% were of Maori or Pacific Island origin. Energy absorbed area (mN mm), was the only significantly changed parameter compared to baseline at all time points measuring 3.61 ± 1.19 preoperatively, 2.81 ± 1.15 at 1 month (p = 0.037), 2.79 ± 0.81 (p = 0.033) at 3 months, 2.76 ± 0.95 (p = 0.028) at 6 months and 2.71 ± 1.18 (p = 0.016) at 12 months. CONCLUSIONS: The significant difference between the pre and post-operative energy absorbed area appears to reflect changes in corneal viscous properties that occur following corneal cross-linking.

Five-year results of a prospective, randomised, contralateral eye trial of corneal crosslinking for keratoconus.

BACKGROUND: Few studies have evaluated corneal crosslinking (CXL) in a prospective, randomised fashion. This study aimed to determine the efficacy and safety of CXL to reduce the progression of keratoconus. METHODS: Prospective, unmasked, randomised, contralateral eye controlled trial at a tertiary eye centre. PARTICIPANTS: Individuals with bilateral progressive keratoconus. One eye from each subject was randomised to CXL and the contralateral, untreated eye acted as the control. PRIMARY OUTCOME MEASURE: change in maximum keratometry. SECONDARY OUTCOME MEASURES: uncorrected distance visual acuity, spectacle corrected distance visual acuity, spherical equivalent refraction, simulated keratometry, corneal astigmatism, minimum pachymetry and complications. RESULTS: Thirty-eight individuals (mean age 21.1 ± 6.7 years) were enrolled with one eye treated with CXL. At 5 years, there was a mean decrease in maximum keratometry of treated eyes (-1.45 ± 2.25 D) compared to an increase among the controls (1.71 ± 2.46 D; p < 0.001). There were significant differences between the treated and control groups in the mean change of Steep SimK (-1.07 ± 1.22 vs. 0.96 ± 1.97 D; p < 0.001), Flat SimK (-0.61 ± 1.34 vs. 0.43 ± 1.12 D; p < 0.001), corneal astigmatism (-0.45 ± 1.31 vs. 0.63 ± 1.52 D; p < 0.01) and minimum pachymetry (-32.49 ± 26.32 vs. -13.57 ± 24.11 µm; p < 0.01). Complications included sterile infiltrates (n = 2), microbial keratitis (n = 1), persistent corneal haze/scarring at 5 years (n = 4) and loss of ≥2 lines of corrected distance visual acuity (n = 3). CONCLUSIONS: CXL is an effective and relatively safe intervention to halt or reduce the progression of keratoconus in the majority of eyes for at least 5 years.

Integration and remodelling of a collagen anterior lamellar keratoplasty graft in an animal model - A preliminary report.

There is an international shortage of donor corneas for transplantation to treat the 1.5-2.0 million new cases of blindness secondary to corneal disease. Research has therefore been directed towards the development of artificial corneas using alternative materials such as collagen. The biocompatibility of an acellular collagen-based scaffold for anterior lamellar keratoplasty was investigated in vivo in a rabbit model. This scaffold has previously shown promise as a corneal substitute in vitro. Slit-lamp and Optical Coherence Tomography examinations were carried out at 2 weeks, 1, 2, 3, and 6 months post-operatively. Graft-host integration was investigated using immunohistochemistry of the cornea at 6 months. Results showed that the graft was biocompatible, supported corneal re-epithelialisation, and showed no signs of rejection. Migration of stromal cells into areas of the graft was observed, however this was accompanied by extensive graft digestion. Whilst the scaffold was biocompatible, further modifications to the material or supplementation with matrix metalloproteinase inhibitors are required to bring us closer to a stable and fully integrated corneal substitute.

Measurement of refractive, wavefront, topographic, and keratometric changes attributable to epithelial removal in keratoconus.

OBJECTIVE: The corneal epithelium is able to mask topographic and keratometric abnormalities of the underlying Bowman layer in keratoconus, but its contribution to refractive and wavefront parameters has not yet been studied. This study compared the refractive and aberrometric features of the corneal epithelium and Bowman layer in eyes with keratoconus before and after epithelial debridement. METHODS: Corneal refractive and wavefront variables were measured in patients with keratoconus undergoing corneal crosslinking-immediately before and after epithelial debridement using a third-generation combined corneal topographer, autorefractor, and aberrometer. RESULTS: After epithelial debridement, there were significant changes in spherical equivalent (-1.37 D; p < 0.01) and asphericity (-0.64; p = 0.03). The mean difference in the magnitude of epithelium-induced astigmatism in the 3rd and 5th central millimeter rings was 0.44 ± 3.20 D × 8 and 0.43 ± 2.75 D × 21 (positive cylinder), respectively. Corneal astigmatism axis shifted in the against-the-rule orientation after epithelial debridement. There were no significant changes in any corneal higher-order aberration parameter after epithelial debridement (p > 0.05). CONCLUSIONS: In eyes with keratoconus, epithelial debridement increased the magnitude of anterior corneal prolateness and tended to increase astigmatism and shift its axis toward the against-the-rule orientation. This study supports the notion that the corneal epithelium smooths underlying Bowman layer irregularity in keratoconus.

Microdroplet and spatter contamination during phacoemulsification cataract surgery in the era of COVID-19.

IMPORTANCE: Determine phacoemulsification cataract surgery risk in a Covid-19 era. BACKGROUND: SARS-CoV-2 (Covid-19) transmission via microdroplet and aerosol-generating procedures presents risk to medical professionals. As the most common elective surgical procedure performed globally; determining contamination risk from phacoemulsification cataract surgery may guide personal protection equipment use. DESIGN: Pilot study involving phacoemulsification cataract surgery on enucleated porcine eyes by experienced ophthalmologists in an ophthalmic operating theatre. PARTICIPANTS: Two ophthalmic surgical teams. METHODS: Standardized phacoemulsification of porcine eyes by two ophthalmologists accompanied by an assistant. Fluorescein incorporated into phacoemulsification irrigation fluid identifying microdroplets and spatter. Contamination documented using a single-lens reflex camera with a 532 nm narrow bandpass (fluorescein) filter, in-conjunction with a wide-field blue light and flat horizontal laser beam (wavelength 532 nm). Quantitative image analysis using Image-J software. MAIN OUTCOME MEASURES: Microdroplet and spatter contamination from cataract phacoemulsification. RESULTS: With phacoemulsification instruments fully within the eye, spatter contamination was limited to <10 cm. Insertion and removal of the phacoemulsification needle and bimanual irrigation/aspiration, with irrigation active generated spatter on the surgeons' gloves and gown extending to >16 cm below the neckline in surgeon 1 and > 5.5 cm below the neckline of surgeon 2. A small tear in the phacoemulsification irrigation sleeve, presented a worse-case scenario the greatest spatter. No contamination above the surgeons' neckline nor contamination of assistant occurred. CONCLUSIONS AND RELEVANCE: Cataract phacoemulsification generates microdroplets and spatter. Until further studies on SARS-CoV-2 transmission via microdroplets or aerosolisation of ocular fluid are reported, this pilot study only supports standard personal protective equipment.

Topographic screening reveals keratoconus to be extremely common in Down syndrome.

IMPORTANCE: Keratoconus disproportionately affects people with Down syndrome (DS). This is the first study of its kind in Australasia. BACKGROUND: To investigate the prevalence of keratoconus in DS. DESIGN: Cross-sectional study. PARTICIPANTS: Athletes with DS attending 2017 New Zealand Special Olympics National Summer Games. METHODS: Keratoconus was identified using corneal topography (TMS-4N, Tomey). Topography from both eyes was required to be included. Two independent quantitative criteria were used to indicate keratoconus. The first was keratoconus severity index ≥ 30%. The second, adapted from the literature, required at least four of eight topographic parameters to be abnormal. Data from the worse eye were analysed. Diagnosis in each group was subsequently confirmed qualitatively by three corneal fellowship-trained ophthalmologists. Those with a definitive diagnosis were grouped into Keratoconus Confirmed Group 1 (KCC1) and Keratoconus Confirmed Group 2 (KCC2), respectively. MAIN OUTCOME MEASURES: Keratoconus prevalence, severity, demographics. RESULTS: Of 110 athletes screened, N = 98 were included, mean age 30.0 ± 9.7 years. Using only topographic data, keratoconus was identified in 39 (39.8%) athletes by quantitative topographic criteria 1, and in 63 (64.3%) athletes by criteria 2. Keratoconus was confirmed by qualitative sub-specialist review in 30 (30.6%) (KCC1) and 38 (38.8%) (KCC2) athletes, respectively. Mean keratometry in groups KCC1 and KCC2 were 48.4 ± 3.2D and 48.2 ± 2.9D, respectively. Most were male (KCC1 63.3%, KCC2 76.3%) and of European ethnicity (KCC1 80%, KCC2 78.9%). CONCLUSIONS AND RELEVANCE: We report keratoconus in 30.6% to 38.8% of athletes with DS; therefore, we believe keratoconus screening is indicated in DS for early management.

Characteristics of Platelet Lysate Compared to Autologous and Allogeneic Serum Eye Drops.

Purpose: Platelet lysate produced from platelet apheresis components has been proposed as an alternative to serum eye drops in the treatment of ocular surface disease. This study compared the effects of platelet lysate and serum on growth factor, cytokine and nanoparticle concentrations, and corneal epithelial cell proliferation. Methods: The concentration of growth factors, cytokines, and nanoparticles in platelet lysates manufactured from either fresh or expired platelet apheresis concentrations collected with Trima or Haemonetics technology was characterized and compared with those of allogeneic, autologous, and fetal calf serum. The ability to promote corneal epithelial cell proliferation and wound healing was tested in vitro. Results: Platelet lysate enriched the amount of transforming growth factor ß1, platelet-derived growth factor -AB and -BB, fibroblast growth factor, and epidermal growth factor compared with the two sera groups. The concentrations of insulin-like growth factor 1, hepatocyte growth factor, and fibronectin were significantly lower than in sera. There were no differences in nanoparticle concentrations. There was no significant difference in corneal epithelial cell proliferation. Platelet lysates were comparable to fetal calf serum in accelerating corneal epithelial wound healing in vitro. Conclusions: Fresh and expired platelet lysates from the Trima and Haemonetics systems had higher growth factor concentrations than sera. The ability of platelet lysates to promote corneal epithelial cell proliferation and wound healing was equivalent to sera. Translational Relevance: Platelet lysates may serve as an efficient and reliable source of human growth factors for the treatment of ocular surface diseases.

Measurement of In Vivo Biomechanical Changes Attributable to Epithelial Removal in Keratoconus Using a Noncontact Tonometer.

PURPOSE: To compare the biomechanical properties of the cornea after epithelial removal in eyes with keratoconus undergoing corneal cross-linking. METHODS: Prospective interventional case series at a university hospital tertiary referral center. Corneal biomechanical properties were measured in patients with keratoconus undergoing corneal cross-linking, immediately before and after epithelial debridement by using a dynamic ultrahigh-speed Scheimpflug camera equipped with a noncontact tonometer. RESULTS: The study comprised 45 eyes of 45 patients with a mean age of 19.6 ± 4.9 years (range 14-34). The cornea was found to be 23.7 ± 15.7 µm thinner after epithelial removal (P < 0.01). Corneal stiffness was reduced after epithelial removal as demonstrated by a significant decrease of parameters such as stiffness parameter A1 (12.31, P < 0.01), stiffness parameter-highest concavity (2.25, P < 0.01), A1 length (0.13 mm, P = 0.04), highest concavity radius of curvature (0.26 mm, P = 0.01), highest concavity time (0.22 ms, P = 0.04) and an increase in A1 velocity (-0.01 m/s, P = 0.01), A1 deformation amplitude (-0.03 mm, P ≤ 0.01), A1 deflection length (-0.32 mm, P < 0.01), A2 deformation amplitude (-0.03 mm, P = 0.01), and A2 deflection length (-1.00 mm, P < 0.01). There were no significant differences in biomechanical intraocular pressure (0.15 mm Hg, P = 0.78), deformation amplitude (0.03, P = 0.54), maximum inverse radius (-0.01 mm, P = 0.57), and whole eye movement length (-0.02 mm, P = 0.12). CONCLUSIONS: Dynamic ultrahigh-speed Scheimpflug camera equipped with a noncontact tonometer offers an alternative method for in vivo measurements of the epithelial layer's contribution to corneal biomechanical properties. Our results suggest that corneal epithelium may play a more significant role in corneal biomechanical properties in patients with keratoconus than previously described.

Successful culture of human transition zone cells.

BACKGROUND: Human corneal endothelial cells undergo very little or no proliferation and respond to cell loss by migration and cellular enlargement. Significant cell loss or damage may result in corneal oedema, opacity and loss of vision. In vitro expansion of corneal endothelial cells (CECs) is a promising strategy for corneal regeneration. The transition zone (TZ) may be an alternative source of CECs. The objective of this study was to establish a protocol for TZ cell culture, and to determine their potential to proliferate and differentiate into cells that resemble CECs in vitro. METHODS: An explant culture protocol for the human TZ was established. Cell proliferation was assessed using 5-ethynyl-2'-deoxyuridine (EdU) assay. The expression of stem cell and endothelial markers was assessed using immunohistochemistry and quantitative polymerase chain reaction. RESULTS: TZ cells can be passaged up to 12 times; cells became polygonal 3 to 4 passages before senescence. An average of 41% of cells incorporated EdU over a 5-day period. TZ cells expressed the corneal endothelial proteins ZO-1 and Na+ /K+ ATPase, Col8A2, the periocular mesenchyme marker PITX2, and the neural crest stem cell markers Nestin and Sox10. TZ cells expressed mRNA of a range of neural crest, periocular mesenchyme, and corneal endothelial genes. CONCLUSIONS: TZ cells can proliferate and differentiate into cells that resemble CECs, demonstrating their potential to be an alternative cell source for corneal endothelial cell therapy.

Comparison of corneal biomechanical properties following penetrating keratoplasty and deep anterior lamellar keratoplasty for keratoconus.

IMPORTANCE: Keratoplasty is a surgical procedure to create a more regular optical surface following biomechanical weakening of the cornea in keratoconus. The ideal keratoplasty procedure should also restore corneal biomechanics to that of the healthy cornea. BACKGROUND: This study aimed to evaluate and compare the biomechanical properties of corneas following penetrating keratoplasty (PKP) and predescematic deep anterior lamellar keratoplasty (DALK) to those of healthy eyes. DESIGN: Prospective cross-sectional study. PARTICIPANTS: Two cohorts of post-keratoplasty eyes (42 eyes with PKP and 27 eyes with DALK) with each other, and with a cohort of 152 healthy eyes. METHODS: All eyes were examined by slit-lamp biomicroscopy, tomography, anterior segment-OCT and non-contact tonometry CorVis ST (CST). MAIN OUTCOME MEASURES: CST biomechanical parameters, maximum corneal deformation (MCD) and corneal energy dissipation were compared between keratoplasty techniques, and with healthy eyes. RESULTS: The mean age of participants with PKP and DALK were 35 ± 13.7 and 36.1 ± 12.6 years, respectively. None of the CST parameters were significantly different between PKP and DALK eyes. However, when compared to healthy corneas, numerous parameters were significantly different for both keratoplasty techniques. Of note, MCD was significantly higher in PKP compared to DALK and healthy corneas, after controlling for co-factors. CONCLUSIONS AND RELEVANCE: Neither type of keratoplasty technique utilized in keratoconus completely restored corneal biomechanical properties to that of healthy corneas. However, PKP resulted in a greater number of parameters significantly different to healthy corneas, compared to DALK.

Auckland Cataract Study IV: Practical application of NZCRS cataract risk stratification to reduce phacoemulsification complications.

IMPORTANCE: Reduction of intraoperative complications in phacoemulsification cataract surgery. BACKGROUND: To assess practicability of a risk stratification system, the New Zealand Cataract Risk Stratification (NZCRS) system, in a major teaching hospital service, without investigator oversight, to ascertain whether benefits identified in research studies are maintained in busy clinical practice. DESIGN: Prospective cohort study in a major public teaching hospital. PARTICIPANTS: Five hundred cases of phacoemulsification cataract surgery. METHODS: NZCRS system inserted into 621 consecutive preoperative cataract patient files. Recommendation to allocate higher-risk cases to experienced surgeons. MAIN OUTCOME MEASURES: NZCRS system uptake and adherence, appropriate identification of high risk cases and intraoperative complication rates. RESULTS: NZCRS scores calculated in 500 of 621 (80.5%) cases and 98 (19.6%) scored as "high risk." Cataract surgery (N = 500) performed by: 12 Registrars (20%), 4 Fellows (7.2%), 26 Consultants (72.8%). Risk scores adhered to in 99%. Overall intraoperative complications (3.0%) included iris prolapse 1.6% and posterior capsule tear 0.8%. No statistical difference in complication rates identified between surgeon grades. Mean best-corrected visual acuity was 6/10 (20/32). Postoperatively, cystoid macular oedema occurred in 3.2%. Rescoring by an experienced investigator noted a greater number of "high risk scores" (31.6% vs 19.6%) related to differences in subjective scoring of anterior chamber depth and cataract density. CONCLUSIONS AND RELEVANCE: Practical uptake of cataract risk stratification was promising in this study with NZCRS calculated in 80.5% with 99% adherence to scoring recommendations. Compared to baseline studies, in the day-to-day clinical setting, a continued, decreasing trend in frequency and severity of intraoperative complications was noted. Subjective variability of risk scoring may be further improved by better, objective, standardization.

The Rapid Transformation of Transplantation for Corneal Endothelial Diseases: An Evolution From Penetrating to Lamellar to Cellular Transplants.

The cornea is the major focusing structure of the human eye and the corneal endothelium maintains the relatively dehydrated state of the cornea required for clarity. The endothelial cells respond to disease or injury by migration and cellular enlargement. Our current understanding is that there is a very limited degree of proliferative or regenerative capacity in the human corneal endothelium. Thus, corneal endothelial diseases may result in corneal edema, significantly impact vision and quality of life. Contemporary surgical transplantation options for treating moderate to advanced endothelial dysfunction include penetrating keratoplasty (PK), Descemet stripping endothelial keratoplasty (DSEK), and Descemet membrane endothelial keratoplasty. Advances in surgical techniques aim to bring faster visual recovery and improve visual outcomes; however, there is still a significant donor cornea shortage worldwide and alternative methods for treatment for corneal endothelial disease are rapidly evolving. Indeed, we are at a pivotal point in corneal transplantation for endothelial disease and novel surgical strategies include using 1 donor for multiple recipients, a minimally attached endothelial graft, and Descemet membrane stripping only. Crucially, forthcoming approaches include the use of Rho-Kinase (ROCK) inhibitors, endothelial cell therapy, tissue engineered grafts, and consideration of stem cell techniques. Ultimately, the choice of technique will be dependent on recipient factors such as age, type of endothelial disease, extent of the disease, and associated ocular disorders. The safety and efficacy of these rapidly developing treatments warrant further investigations. In time, some or all of these alternatives for corneal transplantation will alleviate the reliance on limited corneal donor tissue.

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.

In vivo confocal microscopy of the inflamed anterior segment: A review of clinical and research applications.

In vivo confocal microscopy (IVCM) allows non-invasive imaging of the living human cornea, specifically enabling the detection of immune cells in the healthy and diseased ocular anterior segment. Studies using IVCM have provided insight into the effects of contact lens wear on corneal Langerhans cell density and morphology, and the effects of eye drops on conjunctiva-associated lymphoid tissue. IVCM has also been shown to be a useful adjunctive diagnostic tool in distinguishing infective and non-infective uveitis and in diagnosing atypical infective keratitis. In the research setting, this technology has enhanced our understanding of the role of inflammatory cells in corneal neuropathy and angiogenesis. In vivo-ex vivo correlation using animal models has helped overcome some of the difficulties in identifying cell type on IVCM images. As highlighted in this review, currently there are multiple established, and emerging, clinical and research applications for IVCM in the inflamed anterior segment.