Keratoconus International Consortium (KIC)- advancing keratoconus research.

CLINICAL RELEVANCE: The Keratoconus International Consortium (KIC) will allow better understanding of keratoconus. BACKGROUND: Keratoconus is a disorder characterised by corneal elevation and thinning, leading to reduced vision. The current gaps in understanding of this disease will be discussed and the need for a multi-pronged and multi-centre engagement to enhance our understanding of keratoconus will be highlighted. DESIGN: KIC has been established to address the gaps in our understanding of keratoconus with the aim of collecting baseline as well as longitudinal data on several fields. PARTICIPANTS: Keratoconus and control (no corneal condition) subjects from different sites globally will be recruited in the study. METHODS: KIC collects data using an online, secure database, which enables standardised data collection at member sites. Data fields collected include medical history, clinical features, quality of life and economic burden questionnaires and possible genetic sample collection from patients of different ethnicities across different geographical locations. RESULTS: There are currently 40 Australian and international clinics or hospital departments who have joined the KIC. Baseline data has so far been collected on 1130 keratoconus patients and indicates a median age of 29.70 years with 61% being male. A total of 15.3% report a positive family history of keratoconus and 57.7% self-report a history of frequent eye rubbing. CONCLUSION: The strength of this consortium is its international, collaborative design and use of a common data collection tool. Inclusion and analyses of cross-sectional and longitudinal data will help answer many questions that remain in keratoconus, including factors affecting progression and treatment outcomes.

Effects of human platelet lysate on the growth of cultured human corneal endothelial cells.

Human platelet lysate (hPL) as a replacement for foetal bovine serum (FBS) in culturing human corneal endothelium is an emerging area of interest, although there are limited studies evaluating the quality of the hPL being used. Our study aimed to evaluate variations between sources of hPL and to explore the efficacy of hPL (with and without heparin) as a replacement for FBS in culturing human corneal endothelial cells in vitro. Immortalized human corneal endothelial cells (B4G12) and primary human corneal endothelial cells (PHCEnCs, n = 11 donors, age from 36 to 85 years old) were cultured with 5% hPL or FBS. A full characterisation of the effects of hPL and FBS on cell growth was conducted using IncuCyte Zoom (percentage cell confluence and population doubling time, PDT) to analyse cell proliferation. AlamarBlue assays were used to measure cell viability. The concentration of fibrinogen, PDGF, hEGF, VEGF and bFGF in two sources of hPL were analyzed by Enzyme-linked immunosorbent assay. Expression and localization of Na+/K+-ATPase, ZO-1 and CD166 on PHCEnCs and B4G12 cells were assessed with immunofluorescence and immunoblotting. Our results showed that a significant difference in fibrinogen, hEGF and VEGF concentrations was found between two sources of hPL. Heparin impaired the positive effect of hPL on cell growth. PDT and alamarBlue showed that hPL significantly increased proliferation and viability of PHCEnCs in two of three donors, and immunostaining indicated that hPL increased ZO-1 and CD166 expression but not Na+/K+-ATPase on PHCEnCs. In addition, heterogeneities on immunopositivity of Na+/K+-ATPase and ZO-1 and morphology were found on PHCEnCs derived from an individual donor cultured with hPL medium. In conclusion, hPL showed positive effect on primary corneal endothelial cell growth, and maintenance of their cellular characteristics compared to FBS. hPL can be considered as a supplement to replace FBS in PHCEnC culture. However, the variation observed between different hPL sources suggests that a standard quality control monitoring system such as storage time and a minimal concentration of growth factors may need to be established.

Total keratometry in intraocular lens power calculations in eyes with previous laser refractive surgery.

IMPORTANCE: Intraocular lens (IOL) calculations in post-refractive cases remain a concern. Our study identifies improved options for surgeons. BACKGROUND: To evaluate and compare the prediction accuracy of IOL power calculation methods after previous laser refractive surgery using standard keratometry (SK), measured posterior corneal astigmatism (PCA) and total keratometry (TK). DESIGN: Retrospective consecutive cohort. PARTICIPANTS: A total of 50 consecutive patients (72 eyes) at a private institution who underwent cataract surgery with prior laser refractive procedures. METHODS: Methods using SK included ASCRS mean, Barrett True-K no history, Haigis-L and Shammas IOL formulae. Barrett True-K using posterior values (True K TK), Haigis and Holladay 1 Double-K methods using TK were also assessed. Post-surgery refraction was undertaken at minimum 3 weeks following surgery. MAIN OUTCOME MEASURES: Arithmetic and absolute IOL refractive prediction errors, variances in mean arithmetic IOL prediction error, and percentage of eyes within ±0.25D, ±0.50D, ±0.75D and ±1.00D of refractive prediction errors were compared. RESULTS: The Barrett True-K (TK) provided the lowest mean refractive prediction error (RPE) and variance for both prior myopes and hyperopes undergoing cataract surgery. The Barrett True-K (TK) exhibited the highest percentages of eyes within ±0.50D, ±0.75D and ±1.00D of the RPE compared to other formulae for prior myopic patients. CONCLUSIONS AND RELEVANCE: Accuracy of IOL power calculations in post-laser eyes can be improved by the addition of posterior corneal values as measured by the IOLMaster 700. The use of total keratometry may supplement outcomes when no prior refraction history is known.

Donation of discarded ocular tissue in patients undergoing SMILE laser refractive surgery: developing appropriate guidelines.

Tissue Biobanks represent an invaluable resource. Despite the majority of people supporting tissue donation, the actual rate remains low overall. Tissue discarded from surgical procedures represents a further avenue for collection for use in research. We aim to understand the information and consent requirements in a cohort of healthy, post-ophthalmic surgical subjects to optimise future tissue collection in living donors. Patients attending an ophthalmic clinic following refractive surgery for myopia (SMILE) were identified. Patient consent was implied with the completion of the provided survey. The questionnaire included gender, age range and education status. The majority of 31 subjects identified a benefit for future patients as the main motive for potential donation of discarded tissue (71%). Payment for the discarded tissue would not influence their decision in 77.4%. Explanation of the potential benefits of research was the most important information to consider before making a decision to donate. Only 12.9% of patients would have refused to include further information. Almost half of patients felt that the Biobank became the owner of tissue following donation. Current surgical patients may be more inclined to participate in research than the general public because of a sense of duty or an increased understanding of the role of research in evolving treatment. Despite minor uncertainty about the eventual use of the tissue and data, most subjects were positive to donation of discarded ocular tissue and de-identified information. Consent and education processes should be revised within an ophthalmic practice to minimise future patient anxiety.

Comparison of Hill-radial basis function, Barrett Universal and current third generation formulas for the calculation of intraocular lens power during cataract surgery.

IMPORTANCE: This study represents a novel comparison of recently introduced intraocular lens power calculation formulas. BACKGROUND: To compare current new generation formulas for calculating the intraocular lens power for a standard cohort of patients undergoing cataract and lens replacement surgery in a private group practice in Australia. DESIGN: Retrospective case series comparison. PARTICIPANTS: Postoperative results from 400 consecutive patients undergoing implantation of an SN60WF intraocular lens post cataract removal by 12 surgeons were used. METHODS: Refractive outcomes were compared with expected targets to determine the predicted refractive outcomes using the Hill-radial basis function, Barrett Universal II and readily available third or fourth generation intraocular lens power calculation formulas. MAIN OUTCOME MEASURE: Mean absolute predicted error. RESULTS: The mean absolute predicted difference ranged from 0.30 to 0.34 D. There was no overall significant difference in the predicted difference or variance between formulas. All formulas achieved greater than 78.3% of eyes within ±0.5 D of intended refraction. The Hill-radial basis function and Barrett formulas provided the lowest mean numerical error compared with existing formulas in short and long eyes, respectively. The Barrett Universal II formula had the lowest percentage of refractive surprises (>1 D from predicted error) across all axial lengths. CONCLUSIONS AND RELEVANCE: Acceptable outcomes can be achieved with optical biometry, consistent surgical technique and use of current intraocular lens power calculation formulas. The Barrett Universal II formula may provide the lowest risk of refractive surprise compared with other intraocular lens power calculation formulas.

Analysis of the learning curve for pre-cut corneal specimens in preparation for lamellar transplantation: a prospective, single-centre, consecutive case series prepared at the Lions New South Wales Eye Bank.

IMPORTANCE: This study is the first paper to establish a learning curve by a single technician. BACKGROUND: Preparation of pre-cut corneal endothelial grafts commenced at Lions New South Wales Eye Bank in December 2014. The primary objective of this study was to review the safety and reliability of the preparation method during the first year of production. DESIGN: This is a hospital-based, prospective case series. PARTICIPANTS: There were 234 consecutive donor corneal lenticules. METHODS: Donor lenticules were prepared by a single operator using a linear cutting microkeratome. Immediately prior to cutting, central corneal thickness values were recorded. Measurements of the corneal bed were taken immediately following lenticule preparation. Outcomes were separated by blade sizes, and intended thickness was compared to actual thickness for each setting. Early specimens were compared to later ones to assess for a learning curve within the technique. MAIN OUTCOME MEASURE: The main parameter measured is the mean difference from intended lamellar cut thickness. RESULTS: The mean final cut thickness was 122.36 ± 20.35 µm, and the mean difference from intended cut was 30.17 ± 37.45 µm. No significant difference was found between results achieved with early specimens versus those achieved with later specimens (P = 0.425). CONCLUSIONS AND RELEVANCE: Thin, reproducible endothelial grafts can routinely be produced by trained technicians at their respective eye banks without significant concerns for an extended learning curve. This service can reduce perioperative surgical complexity, required surgical paraphernalia and theatre times. The consistent preparation of single-pass, ultrathin pre-cut corneas may have additional advantages for surgeons seeking to introduce lamellar techniques.

The use of donor scleral patch in ophthalmic surgery.

Scleral tissue has been in use in ophthalmology for many years although indications for use have varied. We retrospectively reviewed scleral transplant tissue requests over a 12 month period at a local eye bank and confirmed a small but significant demand for the use of scleral tissue. Iatrogenic surgical complications are the primary indication for use. Our understanding of the indications and outcomes of scleral graft procedures is derived from case reports and small cohort series. We reviewed the current literature on existing indications for its use and discuss the relative outcomes. To our knowledge this represents the first review of scleral transplant indications and further summarises usage rates in the Lions NSW Eye Bank which may provide practical information for those surgeons who use scleral tissue and Eye Banks who supply it.

Assessment of corneal curvature using verion optical imaging system: a comparative study.

BACKGROUND: Keratometry is a critical determinant of the postoperative refractive outcome. This study evaluates the comparability of keratometry measurements obtained using the Verion Optical Imaging System with devices used in current clinical practice. Further, it determines the interobserver reliability of the Verion Optical Imaging System. DESIGN: Retrospective analysis of patient data PARTICIPANTS: Keratometric data was obtained from 100 patients presenting for pre-operative evaluation. Furthermore, repeatability and reproducibility were assessed using 15 healthy volunteers. METHODS: Corneal curvature values acquired by the Verion Optical Imaging System were compared with existing keratometry devices including autokeratometry, partial coherence interferometry (IOLMaster) and Scheimpflug corneal topography (Pentacam). MAIN OUTCOME MEASURES: Direct comparison of corneal power, cylinder, axis of astigmatism and vector analysis were performed using correlation and Bland-Altman analyses. Reproducibility and reliability of the device were assessed using within-subject standard deviation and intraclass correlation coefficients for experienced and inexperienced technicians. RESULTS: There was no statistically significant difference between Verion values and those obtained by other methods in relation to mean keratometry, corneal astigmatism, steep meridian and vector analyses (P > 0.05). Bland-Altman plots showed narrow limits of agreement for keratometry and astigmatism and wider agreement for steep meridian. Intraoperator reliability for both experienced and inexperienced operators and interoperator reproducibility showed no statistically significant differences between values. CONCLUSION: Measurements show no significant difference from those obtained by the other devices. This suggests the Verion system is en par with instruments used in current clinical practice. The Verion Optical Imaging System produces repeatable data with no difference related to operator experience.

Implementation of Organ Culture storage of donor corneas: a 3 year study of its impact on the corneal transplant wait list at the Lions New South Wales Eye Bank.

Organ Culture corneal storage offers an extended storage time and increased donor pool and tissue assessment opportunities. In September 2011, the Lions New South Wales Eye Bank (LNSWEB) moved from hypothermic storage to Organ Culture corneal storage. This study evaluates the impact of implementation of Organ Culture on donor eye retrieval and the corneal transplant waiting list over a 3 year period in NSW, Australia. Retrospective review of the LNSWEB data from September 2011 to August 2014. Tissue collection, waiting list and tissue utilization data were recorded. The data from September 2008 to August 2011 for Optisol-GS storage was used for comparison. The annual donor and cornea collection rate increased 35 % and 44 % respectively with Organ Culture compared to Optisol-GS storage. The utilization rate of corneal tissue increased from 73.4 % with hypothermic storage to 77.2 % with Organ Culture storage. The transplant wait list decreased by 77.3 % from September 2011 to August 2014 and correlated with the increased rate of corneal transplantation (r = -0.9381, p < 0.0001). No other factors impacting the wait list changed over this period. Corneas not used from either storage method were due to unacceptable endothelial cell density/viability. The contamination rate of corneas stored in Organ Culture medium was low at 1.74 %. The Organ Culture storage method increases the corneal donor pool available to Eye banks. The practical benefits of the extended storage time and increased donor assessment opportunities have directly led to an increase in corneal utilization rate and a significant decrease in recipient wait list time.

Lacquer cracks developing after phakic intraocular lens implantation.

PURPOSE: To describe a case of lacquer cracks developing after phakic intraocular lens implantation. METHODS: Case report. RESULTS: A 46-year-old woman diagnosed as having extreme myopia and corrected distance visual acuity of 20/40 presented with decreased vision and a central scotoma less than 24 hours following phakic intraocular lens implantation. Dilated examination revealed the presence of a macular hemorrhage and possible lacquer crack formation. Documented preoperative imaging showed an absence of lacquer cracks in the eye that was operated on. The patient was treated with intravitreal bevacizumab. At 4 weeks postoperatively, imaging confirmed an almost complete resolution of the hemorrhagic pigment epithelial detachment with evidence of lacquer cracks. Uncorrected visual acuity was 20/50 and the patient was asymptomatic. CONCLUSIONS: This is the first reported case of macular crack formation immediately following phakic intraocular lens implantation. Possible contributing factors are discussed.

Femtosecond laser cataract surgery: challenging cases.

PURPOSE OF REVIEW: Emerging data in the peer-reviewed literature indicate that femtosecond laser-assisted cataract surgery (LCS) is a well tolerated and effective alternative to conventional phacoemulsification. Initial reports have largely been based on findings from an optimal patient selection. As confidence with the technology has grown, clinical indications have expanded and the benefit of LCS in high-risk patients with complex cataracts is increasingly being considered. RECENT FINDINGS: We discuss challenging cataract surgery cases, citing the currently available literature alongside experience from over 3000 completed LCS cases at our centre. SUMMARY: Current experience is limited. However, LCS platforms are continuously evolving and improving. The results collected to date would suggest that the precision and safety offered by LCS may improve outcomes in these challenging cases.

Innervation in corneal bioengineering.

Given the crucial role nerves play in maintaining corneal function and integrity, the ability of bioengineered cornea to demonstrate functional nerve regeneration directly influences their longevity and stability. Despite advances in biofabrication techniques and an increasing appreciation of the importance of neural innervation, to this day none have completely replicated the complexity and functionality of the cornea with successful innervation. This review evaluates the materials and fabrication techniques used to produce and enhance innervation in bioengineered cornea. Approaches to facilitating innervation are discussed and methods of assessing innervation compared. Finally, current challenges and future directions for innervated bioengineered cornea are presented, providing guidance for future work. STATEMENT OF SIGNIFICANCE: The functional nerve regeneration in bioengineered corneas directly influences their longevity and stability. Despite advancements in biofabrication techniques and growing recognition of the importance of neural innervation for bioengineered cornea, there remains a lack of comprehensive reviews on this topic. This review addresses the critical gap by evaluating the materials and fabrication techniques employed to promote innervation in bioengineered corneas. Additionally, we discuss various approaches to enhancing innervation, compare assessment methods, and examine both in vitro and in vivo responses. By providing a comprehensive overview of the current state of research and highlighting challenges and future directions, this review aims to provide guidance for inducing innervation of bioengineered cornea.

Tear levels of SFRP1 are significantly reduced in keratoconus patients.

PURPOSE: To measure secreted frizzled-related protein 1 (SFRP1) levels in human tears and to investigate tear SFRP1 as a potential biomarker for keratoconus (KC). METHODS: Tears were collected from control (n = 33) and KC patients (n = 33) using micropipette tubes. Total tear protein was measured using a FluoroProfile Protein Quantification kit. An in-house enzyme-linked immunosorbent assay (ELISA) was developed to measure SFRP1 in control and KC tears. Statistical analyses of age, gender, the association of SFRP1, and total tear protein with KC were conducted. RESULTS: Tear SFRP1 was significantly decreased in KC, compared to age-matched controls (3.41 ng/µl ± 3.12 versus 5.55 ng/µl ± 5.62, respectively; p = 0.039). Conversely, total tear protein was significantly increased in KC, compared to age-matched controls (12.38 µg/µl ± 4.76 versus 9.40 µg/µl ± 3.88, respectively; p = 0.038). The ratio of SFRP1/total tear protein was also found to be significantly decreased in the KC group (p = 0.007). No significant association between tear SFRP1 and total tear protein was detected. CONCLUSIONS: Tear SFRP1 was significantly decreased in age-matched KC versus control patients, and may be further reduced in moderate KC. Tear-SFRP1 levels alone do not provide an obvious biomarker for KC; however, our results provide further evidence that tear-protein profiles are altered in KC, and suggest the involvement of SFRPs in the pathogenesis of KC.

Surgical outcomes and safety of femtosecond laser cataract surgery: a prospective study of 1500 consecutive cases.

OBJECTIVE: To report the surgical outcomes and safety of femtosecond (FS) laser cataract surgery (LCS) with greater surgeon experience, modified techniques, and improved technology. DESIGN: Prospective, interventional case series. PARTICIPANTS: Fifteen hundred consecutive eyes undergoing FS laser cataract and refractive lens exchange surgery in a single group private practice. INTERVENTION: Femtosecond LCS. METHODS: All eyes undergoing LCS between April 2011 and March 2012 were included in the study. Cases underwent anterior capsulotomy, lens fragmentation, and corneal incisions with the Alcon/LenSx FS laser (Alcon/LenSx, Aliso Viejo, CA). The procedure was completed by phacoemulsification and insertion of an intraocular lens. The cases were divided into 2 groups: Group 1, initial experience consisting of the first 200 cases; and group 2, the subsequent 1300 cases performed by the same surgeons. MAIN OUTCOME MEASURES: Intraoperative complication rates and comparison between groups. RESULTS: Both groups were comparable for baseline demographic parameters. Anterior capsule tears occurred in 4% and 0.31% of eyes, posterior capsule tears in 3.5% and 0.31% of eyes, and posterior lens dislocation in 2% and 0% of eyes in groups 1 group 2, respectively (P<0.001 for all comparisons). Number of docking attempts per case (1.5 vs 1.05), incidence of post-laser pupillary constriction (9.5% vs 1.23%), and anterior capsular tags (10.5% vs 1.61%) were significantly lower in group 2 (P<0.001 for all comparisons). CONCLUSIONS: In the authors' experience, the surgical outcomes and safety of LCS improved significantly with greater surgeon experience, development of modified techniques, and improved technology.

Femtosecond cataract surgery: transitioning to laser cataract.

PURPOSE OF REVIEW: The introduction of the femtosecond laser to the field of cataract surgery offers many potential benefits. The femtosecond laser is able to perform three important steps in cataract surgery: capsulotomy, lens fragmentation and corneal incisions. Although evidence in support of its efficacy is accumulating, there is a surgical learning curve that needs to be addressed. This review outlines key issues to consider when contemplating the transition to laser cataract surgery in clinical practice. RECENT FINDINGS: Laser cataract surgery has been shown to be associated with an initial learning curve. Femtosecond lasers produce a more accurate and precise anterior capsulotomy, improve intraocular lens centration and reduce intraocular lens tilt. Visual and refractive outcomes, although in a limited number of studies, have been shown to be at least as good as those of conventional phacoemulsification. The impact of reduced phacoemulsification energy on the corneal endothelium is still being investigated. SUMMARY: The automation of key steps by the use of femtosecond lasers in cataract surgery has several potential advantages. Emerging literature supports the transition from conventional phacoemulsification to the laser cataract surgery.

Femtosecond laser cataract surgery: technology and clinical practice.

The recent introduction of femtosecond lasers to cataract surgery has generated much interest among ophthalmologists around the world. Laser cataract surgery integrates high-resolution anterior segment imaging systems with a femtosecond laser, allowing key steps of the procedure, including the primary and side-port corneal incisions, the anterior capsulotomy and fragmentation of the lens nucleus, to be performed with computer-guided laser precision. There is emerging evidence of reduced phacoemulsification time, better wound architecture and a more stable refractive result with femtosecond cataract surgery, as well as reports documenting an initial learning curve. This article will review the current state of technology and discuss our clinical experience.