PURPOSE:To compare clinically achieved vaults with the predicted NK-formula V2 (NK-V2) and NK-formula V3 (NK-V3) vaults in a White and Asian population in patients undergoing Implantable Collamer Lens (ICL) surgery. METHODS:Data were collected retrospectively from three surgeons for all patients who had ICL surgery for myopia between September 2020 and August 2022 at Moorfields Eye Hospital. ICL sizing was performed using the optimal NK-V2 sizing formula. The postoperative vault was measured using anterior segment optical coherence tomography. Back calculation was used to evaluate predicted versus achieved vaults for the newer NK-V3 formula. RESULTS:A total of 136 eyes from 72 patients were eligible. Seventy-two eyes of 72 patients were included in the analysis, 50 White (69%) and 22 Asian (31%). The mean residual vault for NK-V2 was -0.08 and -0.11 (P = .76) and NK-V3 was 0.04 and 0.02 (P = .78) for White and Asian, respectively. Mean absolute errors of the White sample were 0.2 and 0.16 for NKV2 and NK-V3, respectively (P = .23). Mean absolute errors of the Asian sample were 0.31 and 0.22 for NK-V2 and NK-V3, respectively (P = .16). There was no statistical significance when comparing mean absolute errors from White and Asian samples for NK-V2 or NK-V3. CONCLUSIONS:NK-V2 formula for ICL sizing, originally derived from an Asian population sample, appeared to perform at least as well in Whites with no adverse outcomes or safety issues. NK-V3 was superior in predicting postoperative vault compared to NK-V2 in Asian eyes and comparable for White eyes. [J Refract Surg. 2025;41(7):e702-e708.].

To define how estimates of keratoconus progression following collagen cross-linking (CXL) vary according to the parameter selected to measure corneal shape. We estimated progression following CXL in 1677 eyes. We compared standard definitions of keratoconus progression based on published thresholds for Kmax, front K2, or back K2, or progression of any two of these three parameters, with the option of an increased threshold for Kmax values ≥ 55D. As corneal thickness reduces unpredictably after CXL, it was excluded from the principal analysis. We then repeated the analysis using novel adaptive estimates of progression for Kmax, front K2, or back K2, developed separately using 6463 paired readings from keratoconus eyes, with a variation of the Bland–Altman method to determine the 95% regression-based limits of agreement (LoA). We created Kaplan-Meier survival plots for both standard and adaptive thresholds. The primary outcome was progression five years after a baseline visit 9–15 months following CXL. Progression rates were 8% with a standard (≥ 1.5D) threshold for K2 or 6% with the static multi-parameter definition. With a ≥ 1D threshold for Kmax, the progression was significantly higher at 29%. With adaptive Kmax or K2, the progression rates were similar (20%) but less than with the adaptive multi-parameter method (22%). Estimates of keratoconus progression following CXL vary widely according to the reference criteria. Using adaptive thresholds (LoA) to define the repeatability of keratometry gives estimates for progression that are markedly higher than with the standard multi-parameter method.

Phototherapeutic keratectomy (PTK) is a treatment for recurrent corneal erosion syndrome (RCES). The aim of this study was to investigate whether deeper ablations yielded greater success rates. Retrospective case notes review with prospective patient-reported outcome measures for all patients who had undergone PTK for RCES at a single tertiary referral unit. Patients received treatment with the Schwind Amaris® 750 s excimer laser. The primary outcome measure was recurrence-free survival of patients with ablation depth ≥ 15 µm compared to < 15 µm. Seventy eyes of 63 patients were included for analysis, of whom 39 (56

distributed under the terms of the Creative Commons Attribution License CC-BY 4.0., which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. DOI: 10.7759/cureus.68643 1. Orthopedics, Tan Tock Seng Hospital, Singapore, Life Sciences and Medicine, King's College London, GBR 5. Ophthalmology, Moorfields Eye Hospital, Corresponding author: Rami Mohamed, rami.mohamed3@nhs.net Abstract Introduction Refractive error is the leading cause of visual exposed to information about refractive surgery guidelines specify how refractive surgery should extent these standards are adhered to in the emerging refractive surgery advertisements on social media Method We retrospectively analyzed the content of refractive "TikTok," shown in the United Kingdom (UK) guidelines set out by The Royal College of Ophthalmologists

BACKGROUND:Although some experts recommend anal cancer screening for disproportionally affected populations including people living with HIV (PWH), condyloma acuminata, human papillomavirus-associated gynecologic dysplasia and cancers, and solid organ transplants, actual screening practices remain understudied. Our objective was to characterize anal cancer screening practices among higher-risk populations in an academic medical system with access to high-resolution anoscopy. METHODS:We extracted outpatient clinical data for the aforementioned populations from January 1, 2015, to August 1, 2022, at 3 sites of an academic medical system. Data included patients' demographics, medical comorbidities, and anal cytology and human papillomavirus testing results. We used χ2 tests and logistic regression to assess for associations between patient characteristics and anal cancer screening. RESULTS:Of 7654 patients, 6.3% received anal cytology screening at least once including 21.7% of PWH, 13.8% of people with condyloma acuminata, 1.1% of people with gynecologic cancers, and 0.5% of people with solid organ transplants. In multivariable analysis, Black patients were 46% less likely to receive screening than White patients (95% confidence interval [CI], 0.40-0.71), and cisgender women were 73% less likely to receive screening than cisgender men (95% confidence interval, 0.20-0.38). Of 485 individuals who received anal cytology screening, 37.5% were only screened once and 70.5% had abnormal cytology on one or more screenings. CONCLUSION:Only one-fifth of PWH received anal cancer screening, and other higher-risk populations had even lower screening rates. Black patients and women were also less likely to be screened. Strategies to improve equitable screening practices for anal cancer are needed.

PURPOSE:To generate a prognostic model to predict keratoconus progression to corneal crosslinking (CXL).DESIGN:Retrospective cohort study.METHODS:We recruited 5025 patients (9341 eyes) with early keratoconus between January 2011 and November 2020. Genetic data from 926 patients were available. We investigated both keratometry or CXL as end points for progression and used the Royston-Parmar method on the proportional hazards scale to generate a prognostic model. We calculated hazard ratios (HRs) for each significant covariate, with explained variation and discrimination, and performed internal-external cross validation by geographic regions.RESULTS:After exclusions, model fitting comprised 8701 eyes, of which 3232 underwent CXL. For early keratoconus, CXL provided a more robust prognostic model than keratometric progression. The final model explained 33% of the variation in time to event: age HR (95% CI) 0.9 (0.90-0.91), maximum anterior keratometry 1.08 (1.07-1.09), and minimum corneal thickness 0.95 (0.93-0.96) as significant covariates. Single-nucleotide polymorphisms (SNPs) associated with keratoconus (n=28) did not significantly contribute to the model. The predicted time-to-event curves closely followed the observed curves during internal-external validation. Differences in discrimination between geographic regions was low, suggesting the model maintained its predictive ability.CONCLUSIONS:A prognostic model to predict keratoconus progression could aid patient empowerment, triage, and service provision. Age at presentation is the most significant predictor of progression risk. Candidate SNPs associated with keratoconus do not contribute to progression risk.

Abstract Background Anal cancer disproportionally affects persons living with HIV (PWH), sexual and gender minorities, and those with gynecologic cancers, condyloma acuminata, and solid organ transplantation. While expert guidance on anal cancer screening exists for PWH, there are no national guidelines for screening any of these populations. We analyzed clinician characteristics associated with anal cancer screening among providers who care for high-risk populations at an academic medical center including infectious disease (ID) specialists, primary care providers (PCPs), and obstetrician/gynecologists (OBGYNs). Methods We retrospectively reviewed medical charts for patients with HIV, gynecologic cancers, condyloma acuminata, solid organ transplantation, and sexual or gender minority status at Beth Israel Deaconess Medical Center and two affiliated clinics from 01/01/2015 - 08/01/2022. We extracted provider specialties, clinic locations, patient panel demographics, and dates of anal cytology and human papillomavirus (HPV) screening tests. We used chi-squared tests to identify provider factors associated with screening. Results Of 1,093 providers, at least one anal cytology test was performed by 93.8% (75/80) of ID providers, 55.2% (376/681) of PCPs, 28.3% (41/145) of OBGYNs, and 24.1% (45/187) of other providers (p < 0.001); among screeners, anal HPV co-testing was performed equally across specialties (54.2%, p = 0.23). Providers were more likely to screen if they cared for PWH (91.8% with 10-49 PWH vs 3.7% for no PWH, p < 0.001), majority cis-men (55.2%, p=0.003), or majority publicly insured patients (51.8%, p < 0.001). Providers were less likely to screen if they cared for majority cis-women (40.9%, p< 0.001) or majority privately insured patients (24.0%, p< 0.001). Screening practices did not differ by the racial composition of providers’ patient panels (p=.21). Conclusion While many ID specialists performed anal cancer screenings, other providers were less likely to screen. Providers caring for many PWH, cis-men, or publicly insured patients were more likely to screen. Additional research is needed to clarify screening guidance and optimize screening practices for all higher-risk populations, especially non-PWH groups. Disclosures Douglas Krakower, MD, Gilead: Grant/Research Support|Merck: Grant/Research Support|U. North Texas Health Sciences Center: Funding for mentoring|UAB: Advisor/Consultant|UpToDate, Inc.: Royalties|Virology Education: Honoraria

BACKGROUND:Cataract is the leading cause of blindness in the world and, as such, cataract surgery is one of the most commonly performed operations globally. Surgical techniques have changed dramatically over the past half century with associated improvements in outcomes and safety. Femtosecond lasers can be used to perform the key steps in cataract surgery, such as corneal incisions, lens capsulotomy and fragmentation. The potential advantage of femtosecond laser-assisted cataract surgery (FLACS) is greater precision and reproducibility of these steps compared to manual techniques. The disadvantages are the costs associated with FLACS technology. OBJECTIVES:To compare the effectiveness and safety of FLACS with standard ultrasound phacoemulsification cataract surgery (PCS) by gathering evidence from randomised controlled trials (RCTs). SEARCH METHODS:We searched the Cochrane Central Register of Controlled Trials (CENTRAL; which contains the Cochrane Eyes and Vision Trials Register; 2022, Issue 5); Ovid MEDLINE; Ovid Embase; LILACS; the ISRCTN registry; ClinicalTrials.gov; the WHO ICTRP and the US Food and Drug Administration (FDA) website. We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 10 May 2022. SELECTION CRITERIA:We included RCTs where FLACS was compared to PCS. DATA COLLECTION AND ANALYSIS:Three review authors independently screened the search results, assessed risk of bias and extracted data using the standard methodological procedures expected by Cochrane. The primary outcome for this review was intraoperative complications in the operated eye, namely anterior capsule, and posterior capsule tears. The secondary outcomes included corrected distance visual acuity (CDVA), quality of vision (as measured by any validated patient-reported outcome measure (PROM)), postoperative cystoid macular oedema complications, endothelial cell loss and cost-effectiveness. We assessed the certainty of the evidence using GRADE. MAIN RESULTS:We included 42 RCTs conducted in Europe, North America, South America and Asia, which enrolled a total of 7298 eyes of 5831 adult participants. Overall, the studies were at unclear or high risk of bias. In 16 studies the authors reported financial links with the manufacturer of the laser platform evaluated in their studies. Thirteen of the studies were within-person (paired-eye) studies with one eye allocated to one procedure and the other eye allocated to the other procedure. These studies were reported ignoring the paired nature of the data. There was low-certainty evidence of little or no difference in the odds of developing anterior capsular tears when comparing FLACS and PCS (Peto odds ratio (OR) 0.83, 95% confidence interval (CI) 0.40 to 1.72; 5835 eyes, 27 studies) There was one fewer anterior capsule tear per 1000 operations in the FLACS group compared with the PCS group (95% CI 4 fewer to 3 more).  There was low-certainty evidence of lower odds of developing posterior capsular tears with FLACS compared to PCS (Peto OR 0.50, 95% CI 0.25 to 1.00; 5767 eyes, 26 studies). There were four fewer posterior capsule tears per 1000 operations in the FLACS group compared with the PCS group (95% CI 6 fewer to same).  There was moderate-certainty evidence of a very small advantage for the FLACS arm with regard to CDVA at six months or more follow-up, (mean difference (MD) -0.01 logMAR, 95% CI -0.02 to 0.00; 1323 eyes, 7 studies). This difference is equivalent to 1 logMAR letter between groups and is not thought to be clinically important. From the three studies (1205 participants) reporting a variety of PROMs (Cat-PROMS, EQ-5D, EQ-SD-3L, Catquest9-SF and patient survey) up to three months following surgery, there was moderate-certainty evidence of little or no difference in the various parameters between the two treatment arms. There was low-certainty evidence of little or no difference in the odds of developing cystoid macular oedema when comparing FLACS and PCS (Peto OR 0.84, 95% CI 0.56 to 1.28; 4441 eyes, 18 studies). There were three fewer cystoid macular oedema cases per 1000 operations in the FLACS group compared with the PCS group (95% CI 10 fewer to 6 more).  In one study the incremental cost-effectiveness ratio (ICER) (cost difference divided by quality-adjusted life year (QALY) difference) was GBP £167,620 when comparing FLACS to PCS. In another study, the ICER was EUR €10,703 saved per additional patient who had treatment success with PCS compared to FLACS. Duration ranged from three minutes in favour of FLACS to eight minutes in favour of PCS (I2 = 100%, 11 studies) (low-certainty evidence).  There was low-certainty evidence of little or no important difference in endothelial cell loss when comparing FLACS with PCS (MD 12 cells per mm2 in favour of FLACS, 95% CI -40 to 64; 1512 eyes, 10 studies).  AUTHORS' CONCLUSIONS: This review of 42 studies provides evidence that there is probably little or no difference between FLACS and PCS in terms of intraoperative and postoperative complications, postoperative visual acuity and quality of life. Evidence from two studies suggests that FLACS may be the less cost-effective option. Many of the included studies only investigated very specific outcome measures such as effective phacoemulsification time, endothelial cell count change or aqueous flare, rather than those directly related to patient outcomes. Standardised reporting of complications and visual and refractive outcomes for cataract surgery would facilitate future synthesis, and guidance on this has been recently published.

Corneal transplantation is the most commonly performed human tissue transplantation procedure worldwide. Because of the large number of transplants, corneal graft failure has become one of the most common indications for corneal transplantation. The relatively recently developed lamellar transplant techniques have brought about specific potential complications leading to graft failure that may require different approaches to repeat transplantation other than penetrating keratoplasty. On the other hand, these new lamellar techniques also provide novel ways of rescuing failed penetrating grafts, with potential advantages over successive penetrating keratoplasties, such as reduced intraoperative risks and faster visual rehabilitation. We summarize the incidence and risk factors of graft failure for penetrating and lamellar (stromal and endothelial) corneal transplants and discuss the various surgical alternatives currently available to rescue such failed grafts, with a focus on the reported outcomes and limitations.

Fuchs endothelial corneal dystrophy (FECD) is characterized by corneal guttae, a reduced endothelial cell density, corneal edema, and loss of vision. Changes in a number of different genes can cause the FECD phenotype. In white populations, approximately 75% of individuals with FECD type 3 have 1 or more expanded copies of a non-coding CTG triplet repeat (termed CTG18.1) situated on Chr18q21.1, within an intron of TCF4.1Wieben ED Aleff RA Tosakulwong N Butz ML Highsmith WE Edwards AO et al.A common trinucleotide repeat expansion within the transcription factor 4 (TCF4, E2-2) gene predicts Fuchs corneal dystrophy.PLoS One. 2012; 7: e49083Crossref PubMed Scopus (171) Google Scholar A small subset of FECD is an early-onset form (FECD type 1; OMIM # 136800) associated with heterozygous missense mutations in the COL8A2 gene.2Biswas S Munier FL Yardley J Hart-Holden N Perveen R Cousin P et al.Missense mutations in COL8A2, the gene encoding the alpha2 chain of type VIII collagen, cause two forms of corneal endothelial dystrophy.Hum Mol Genet. 2001; 10: 2415-2423Crossref PubMed Google Scholar We describe two individuals with the characteristic signs of FECD type 1 who also had striking arcuate clefts in their inferior corneal stroma. To the best of our knowledge this clinical sign has not previously been reported. Patients provided informed consent for participation in this study, which had approval from the regional Research Ethics Committee (17/LO/1671) and adhered to the guidelines of the Declaration of Helsinki. The patient's mother had had a penetrating keratoplasty (PK) at age 39 years. He had astigmatism with a visual acuity of 6/9 right eye (+1.00/−5.00 × 95) and 6/24 left eye (+0.50/−6.00 × 90), improving with a rigid gas permeable contact lens to 6/6 in each eye. There were central corneal guttae and a reduced endothelial cell density (568 cells/mm2 right eye, 524 cells/mm2 left eye) (Fig. 1). The central corneal thickness (CCT) was 627 µm right eye and 620 µm left eye. Corneal tomography confirmed inferior corneal steepening (simulated keratometry 46.6 × 18/39.7 × 108 right eye, and 49.7 × 9/37.9 × 99 left eye). Anterior segment optical coherence tomography (AS-OCT) and confocal microscopy confirmed the presence of a translucent cavity crossed by fibers, but with no evidence of a cellular lining. He had no treatment and the corneal clefts were still present 12 years after presentation, although his rigid gas permeable lens corrected acuity had reduced to 6/36 right eye and 6/12 left eye. There was astigmatism with a corrected visual acuity of 6/60 bilaterally and a refraction of (+1.25/−6.00 × 150) right eye (+1.00/−3.50 × 109) left eye. The vision improved marginally with scleral contact lenses. The peripheral corneal clefts were similar to case 1 (Fig. 2). The corneal guttae were less numerous than case 1, with an endothelial cell density of 636 cells mm2 in the left eye, but the right endothelium could not be visualized. The CCT was 724 µm right eye and 606 µm left eye. Simulated keratometry was 54.7 × 70/47.0 × 160 right eye and 46.7 × 37/45.7 × 127 left eye, with inferior corneal steepening in the region of the clefts. There was no other anterior segment abnormality. The patient's mother, two maternal aunts, a maternal uncle, and a first-degree cousin all had at least one PK or Descemet membrane endothelial keratoplasty (DMEK) for FECD. In none was the presence of a cleft recorded. A decision was made to perform a 9.00 mm right PK decentered slightly to include the cleft. Following surgery, the vision only improved to 6/36 unaided, 6/24 with pinhole viewing, suggestive of amblyopia. Histology demonstrated a reduced endothelial cell density with Descemet membrane of normal thickness without obvious focal protuberances (guttae). This is consistent with a previous description of FECD type 1.3Liskova P Prescott Q Bhattacharya SS Tuft SJ. British family with early-onset Fuchs’ endothelial corneal dystrophy associated with p.L450W mutation in the COL8A2 gene.Br J Ophthalmol. 2007; 91: 1717-1718Crossref PubMed Scopus (32) Google Scholar The stroma appeared normal, but the cleft could not be identified, presumably because it had collapsed. Because the clinical features of both cases were consistent with FECD type 1, we used conventional PCR and Sanger sequencing in patient 2 to screen the COL8A2 genomic region containing the previously reported FECD type 1-associated COL8A2 mutations, c.1349T>G, p.(Leu450Trp), c.1363C > A, p.(Gln455Lys) and c.1370-1371CA>GT.2Biswas S Munier FL Yardley J Hart-Holden N Perveen R Cousin P et al.Missense mutations in COL8A2, the gene encoding the alpha2 chain of type VIII collagen, cause two forms of corneal endothelial dystrophy.Hum Mol Genet. 2001; 10: 2415-2423Crossref PubMed Google Scholar,4Gottsch JD Sundin OH Liu SH Jun AS Broman KW Stark WJ et al.Inheritance of a novel COL8A2 mutation defines a distinct early-onset subtype of Fuchs corneal dystrophy.Invest Ophthalmol Vis Sci. 2005; 46: 1934-1939Crossref PubMed Scopus (166) Google Scholar,5Mok JW Kim HS Joo CK. Q455V mutation in COL8A2 is associated with Fuchs’ corneal dystrophy in Korean patients.Eye. 2009; 23: 895-903Crossref PubMed Scopus (60) Google Scholar We used the forward 5’- GTGACCAGGGGCCTAGTG-3’ and reverse 5’-CCTGCGATGCCAGTCTCAT-3’ primers. This identified a FECD type 1 disease-associated mutation; c.1363C > A, p.(Gln455Lys). To exclude FECD type 3, we performed a combination of a short tandem repeat (STR) assay and triplet repeat primed polymerase chain reaction assay. STR analysis showed the patient had a TCF4 CTG18.1 repeat length of 12 in at least one allele, with a second allele being undetected. Triplet repeat primed polymerase chain reaction assay confirmed the patient was homozygous in allele length and had a CTG18.1 genotype of 12/12. We report 2 unrelated individuals who had corneal endothelial disease consistent with FECD type 1 who also had bilateral peripheral arcuate corneal clefts. In case 2, a missense variant in the COL8A2 gene was identified, which has previously been reported to be causative for FECD type 1.2Biswas S Munier FL Yardley J Hart-Holden N Perveen R Cousin P et al.Missense mutations in COL8A2, the gene encoding the alpha2 chain of type VIII collagen, cause two forms of corneal endothelial dystrophy.Hum Mol Genet. 2001; 10: 2415-2423Crossref PubMed Google Scholar,5Mok JW Kim HS Joo CK. Q455V mutation in COL8A2 is associated with Fuchs’ corneal dystrophy in Korean patients.Eye. 2009; 23: 895-903Crossref PubMed Scopus (60) Google Scholar Segregation analysis for this change could not be performed, and the individual from case 1 was unavailable for investigation. However, arcuate corneal clefts have not been described as a feature of FECD type 1, and it is possible that a second, as yet unidentified, disease process is required for cleft formation. The age of onset of the clefts is unknown, but with no suggestion of a sudden onset. Once established, the clefts are stable, with no documented progression in one individual for an interval of 12 years. In both cases, the peripheral location of the clefts with secondary corneal steepening and astigmatism led to an initial provisional diagnosis of pellucid marginal corneal degeneration.

PURPOSE: To report on 2-year results of accelerated corneal collagen cross-linking (CXL) in progressive ectasia using the Avedro KXL system. DESIGN: Prospective interventional case series. METHODS: A total of 870 patients (1,192 eyes) attending Moorfields Eye Hospital after CXL were included. All patients undergoing CXL had progressive keratoconus. Corneas with a minimum stromal thickness <375 mu m were excluded. Riboflavin 0.1% soak duration was 10 minutes. High-fluence pulsed UVA was delivered at 30 mW/cm(2) for 4 minutes, with a 1.5-second on/off cycle (total energy 7.2 J/cm(2)). Subjective refractive, corneal tomography, and specular microscopy were performed at baseline, 6, 12, and 24 months postoperatively. The primary outcome measure was a change in maximum keratometry (Kmax) at 24 months. RESULTS: Twelve- and 24-month follow-up data were available on 543 and 213 patients, respectively (mean age 25.4 +/- 6.6 years). In mild cones (Kmax < 55 diopter [D]), mean keratometry remained unchanged at 24 months. In more advanced disease, we observed modest corneal flattening compared to baseline (Kmax 63.2 +/- 6.5 D vs 61.9 +/- 8.1 D, P = .02), but no significant changes in central keratometry (K1 or K2). Keratometric stabilization was confirmed in 98.3% of eyes. Mean CDVA, manifest refraction and endothelial cell density did not change. Overall, 2.7% of eyes lost more than 2 lines of CDVA. CONCLUSION: Accelerated pulsed CXL is a safe, effective, and refractively neutral intervention (at 2 years) to halt disease progression in keratoconus. ((C) 2020 Elsevier Inc. All rights reserved.)

Background Keratoconus is a disorder characterized by progressive thinning and distortion of the cornea. If detected at an early stage, corneal collagen cross-linking can prevent disease progression and further visual loss. Although advanced forms are easily detected, reliable identification of subclinical disease can be problematic. Several different machine learning algorithms have been used to improve the detection of subclinical keratoconus based on the analysis of multiple types of clinical measures, such as corneal imaging, aberrometry, or biomechanical measurements. Objective The aim of this study is to survey and critically evaluate the literature on the algorithmic detection of subclinical keratoconus and equivalent definitions. Methods For this systematic review, we performed a structured search of the following databases: MEDLINE, Embase, and Web of Science and Cochrane Library from January 1, 2010, to October 31, 2020. We included all full-text studies that have used algorithms for the detection of subclinical keratoconus and excluded studies that did not perform validation. This systematic review followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) recommendations. Results We compared the measured parameters and the design of the machine learning algorithms reported in 26 papers that met the inclusion criteria. All salient information required for detailed comparison, including diagnostic criteria, demographic data, sample size, acquisition system, validation details, parameter inputs, machine learning algorithm, and key results are reported in this study. Conclusions Machine learning has the potential to improve the detection of subclinical keratoconus or early keratoconus in routine ophthalmic practice. Currently, there is no consensus regarding the corneal parameters that should be included for assessment and the optimal design for the machine learning algorithm. We have identified avenues for further research to improve early detection and stratification of patients for early treatment to prevent disease progression.

PURPOSE:To compare the clinical outcomes in femtosecond laser-assisted deep anterior lamellar keratoplasty (F-DALK) to manual non-laser deep anterior lamellar keratoplasty (M-DALK) for keratoconus in a multi-surgeon public healthcare setting. DESIGN:Single-center, comparative, retrospective interventional case series. METHODS:Population: Consecutive cases of keratoconus treated with big-bubble F-DALK from August 1, 2015, to September 1, 2018 and big-bubble M-DALK from September 1, 2012, to September 30, 2016. SETTING:Moorfields Eye Hospital, London. OBSERVATIONS:Data on preoperative status, operative details, intraoperative and postoperative complications, secondary interventions, and visual outcomes were archived on a customized spreadsheet for analysis. MainOutcomeMeasures: Rate of intraoperative perforation and conversion to penetrating keratoplasty (PK) and the percentage of patients, post removal of sutures (ROS), with corrected distance visual acuity (CDVA) ≥20/40. RESULTS:We analyzed 58 eyes of 55 patients who underwent F-DALK and 326 eyes of 309 patients who underwent M-DALK. Intraoperative perforation of Descemet membrane occurred in 15 of 58 (25.9%) F-DALK cases compared to 148 of 326 (45.4%) M-DALK cases (P = .006). Intraoperative conversion to PK was carried out in 2 of 58 (3.4%) F-DALK cases compared to 80 of 326 (24.5%) M-DALK cases (P = .001). Post ROS, 86.5% of F-DALK eyes had a CDVA of ≥20/40 (15 ± 7.3 months after surgery) compared to 83.7% of M-DALK eyes (24.9 ± 10.6 months) (P = .825). CONCLUSION:Laser automation of some steps in DALK for keratoconus may reduce the rate of intraoperative Descemet perforation and the conversion to PK in a multi-surgeon setting.

Corneal cross-linking (CXL) is typically performed under topical anesthesia, which may be unsuitable in children and individuals with severe anxiety, poor cooperation, or neurodevelopmental issues. We describe a technique of CXL under general anesthesia that uses sevoflurane and propofol with laryngeal airway or nasal oxygen cannulas, and forceps or microsponges to stabilize the eye position intraoperatively. We also developed a simple and time-saving technique of bilateral simultaneous CXL, whereby the second eye can undergo CXL concurrently with the first in a staggered fashion. Using this technique, we have been able to eliminate up to 25% of surgical time required in standard bilateral procedures. Postoperatively, multimodal analgesia was administered to ensure patient comfort and prevent excessive eye rubbing. In total, 21 eyes of 13 subjects ≤18 years of age were treated. During a median follow-up of 14.5 months (range, 4-43), the only complication observed was sterile corneal infiltrate in 1 eye that resolved with a short course of corticosteroids.

ImportanceKeratoconus is an important cause of visual loss in young adults, but little is known about its genetic causes. Understanding the genetic determinants of corneal biomechanical factors may in turn teach us about keratoconus etiology.ObjectivesTo identify genetic associations with corneal biomechanical properties and to examine whether these genetic variants are associated with keratoconus.Design, Setting, and ParticipantsA stage 1 discovery and replication genome-wide association study (GWAS) of corneal biomechanical properties was performed in 2 cross-sectional populations (6645 participants from the European Prospective Investigation into Cancer and Nutrition [EPIC]-Norfolk Eye Study and 2384 participants from the TwinsUK study). In stage 2, the association of genetic determinants identified in stage 1 with keratoconus was examined in a case-control study. A total of 752 patients with keratoconus were compared with 974 TwinsUK participants (undergoing direct sequencing) or 13 828 EPIC-Norfolk participants (undergoing genotyping and imputation) who were not part of the stage 1 analysis. Data were collected from March 1, 1993, through March 13, 2017, and analyzed from November 1, 2015, through February 1, 2018.ExposuresIn stage 1, allele dosage at genome-wide single-nucleotide polymorphisms (SNPs); in stage 2, allele dosage at SNPs with genome-wide significance (P < 5 × 10-8) in stage 1 and not previously reported as associated with corneal disease.Main Outcomes and MeasuresIn stage 1, corneal hysteresis (CH) and corneal resistance factor (CRF), measured with the Ocular Response Analyzer (ORA); in stage 2, association with keratoconus compared with controls.ResultsAmong 6645 participants in the discovery cohort (3635 women (54.7%); mean age, 69 years [range, 48-92 years]), 7 genome-wide significant loci associated with CH or CRF were identified that were independently replicated. Two further suggestive loci were identified after meta-analysis. To date, 5 of the identified loci, at ANAPC1, ADAMTS8, ADAMTS17, ABCA6, and COL6A1, have not previously been reported as associated with corneal disease. The ABCA6 locus (rs77542162) was associated with keratoconus using the TwinsUK (odds ratio [OR], 0.50; 95% CI, 0.27-0.92; P = .03) and EPIC-Norfolk controls (OR, 0.39; 95% CI, 0.22-0.70; P = .002). The other loci were associated with keratoconus using TwinsUK (OR per effect allele for ADAMTS8, 0.51 [95% CI, 0.37-0.71; P = 7.9 × 10-5]; for COL6A1, 1.65 [95% CI, 1.05-2.59; P = .03]) or EPIC-Norfolk (OR per effect allele for ANAPC1, 0.78 [95% CI, 0.68-0.89; P = 3.7 × 10-4]; for ADAMTS17, 0.82 [95% CI, 0.68-0.99; P = .04]) controls.Conclusions and RelevanceFive loci that are associated with corneal biomechanical properties and that have suggestive associations with keratoconus were reported. These findings suggest the role of type VI collagen, extracellular matrix, and connective-tissue development for corneal biomechanics and keratoconus and the role of CH and CRF as biomarkers for keratoconus.

Purpose: We set out to describe the natural history of keratoconus. We included untreated patients, and our key outcome measures were vision, refraction, and corneal curvature. Methods: We included prospective or retrospective studies of pediatric or adult patients who reported 1 or more of visual acuity, refraction, and corneal curvature measures: steep keratometry (K-2), mean keratometry (K-mean), or maximum keratometry (K-max), thinnest pachymetry, corneal transplantation rates, corneal scarring incidence, and patient-reported outcome measures (PROMs). Databases analyzed included Medline, Embase, CENTRAL, and CINAHL. Searches were carried out until October 2018. Bias assessment was carried out using the Joanna Briggs Institute model of evidence-based healthcare. Results: Our search yielded 3950 publication titles, of which 41 were included in our systematic review and 23 were incorporated into the meta-analysis. Younger patients and those with greater K-max demonstrated more steepening of Kmax at 12 months. The meta-analysis for K-max demonstrated a significant increase in K-max of 0.7 diopters (D) at 12 months (95% confidence interval [CI], 0.31-1.14; P = 0.003). Our meta-regression model predicted that patients had 0.8 D less K-max steepening over 12 months for every 10-year increase in age (P = 0.01). Patients were predicted to have 1 D greater K-max steepening for every 5 D of greater baseline K-max (P = 0.003). At 12 months, there was a significant increase in the average K-mean of 0.4 D (95% CI, 0.18-0.65; P = 0.004). Conclusions: We report the first systematic review and meta-analysis of keratoconus natural history data including 11 529 eyes. Younger patients and those with K-max steeper than 55 D at presentation have a significantly greater risk of progression of keratoconus. Closer follow-up and a lower threshold for cross-linking should be adopted in patients younger than 17 years and steeper than 55 D K-max. (C) 2019 by the American Academy of Ophthalmology

To assess a Royston−Parmar flexible parametric survival model to generate a personalised risk profile for keratoconus progression. We re-analysed a historic database of 2723 individuals with keratoconus. A Royston−Parmar survival model was fitted to predict the likelihood of the worse eye progressing to corneal transplantation. We used a backwards selection multivariable fractional polynomial procedure to assist with selection of covariates and identify appropriate transformation(s) to retain in the final model. Time-dependent receiver operating characteristic (ROC) curves from censored survival data using the Kaplan−Meier (KM) method were computed to visually assess how well the model identified eyes likely to progress. In all, 5020 eyes from 2581 patients were available for model development. This included 2378 worst affected eyes, and 313 eyes that progressed to transplantation. The best fitting model [df = 1: Bayes information criterion (BIC) = 1573] included three variables, keratometry [hazard ratio (HR) 0.36: 95% confidence limits (CI) 0.32–0.42], age at baseline [HR 0.97: CI 0.95–0.99] and ethnicity [HR 3.92: CI 2.58–5.95]. Specificity at 1 year was 92.8% (CI 90.4−95.2%) with a corresponding sensitivity of 64.6% (CI 58.9−60.0%). These three prognostic factors account for 41.3% (CI 33.6 – 48.2%) of the variation among the survival curves. Researchers should consider the Royston−Parmar model as an alternative to the Cox model. We illustrate the concepts and our results may lead to better tools that identify individuals at high risk of keratoconus progression.