Validated machine learning tools to distinguish immune checkpoint inhibitor, radiotherapy, COVID-19 and other infective pneumonitis.

BACKGROUND: Pneumonitis is a well-described, potentially disabling, or fatal adverse effect associated with both immune checkpoint inhibitors (ICI) and thoracic radiotherapy. Accurate differentiation between checkpoint inhibitor pneumonitis (CIP) radiation pneumonitis (RP), and infective pneumonitis (IP) is crucial for swift, appropriate, and tailored management to achieve optimal patient outcomes. However, correct diagnosis is often challenging, owing to overlapping clinical presentations and radiological patterns. METHODS: In this multi-centre study of 455 patients, we used machine learning with radiomic features extracted from chest CT imaging to develop and validate five models to distinguish CIP and RP from COVID-19, non-COVID-19 infective pneumonitis, and each other. Model performance was compared to that of two radiologists. RESULTS: Models to distinguish RP from COVID-19, CIP from COVID-19 and CIP from non-COVID-19 IP out-performed radiologists (test set AUCs of 0.92 vs 0.8 and 0.8; 0.68 vs 0.43 and 0.4; 0.71 vs 0.55 and 0.63 respectively). Models to distinguish RP from non-COVID-19 IP and CIP from RP were not superior to radiologists but demonstrated modest performance, with test set AUCs of 0.81 and 0.8 respectively. The CIP vs RP model performed less well on patients with prior exposure to both ICI and radiotherapy (AUC 0.54), though the radiologists also had difficulty distinguishing this test cohort (AUC values 0.6 and 0.6). CONCLUSION: Our results demonstrate the potential utility of such tools as a second or concurrent reader to support oncologists, radiologists, and chest physicians in cases of diagnostic uncertainty. Further research is required for patients with exposure to both ICI and thoracic radiotherapy.

A comparison of keratoconus progression following collagen cross-linkage using standard or personalised keratometry thresholds.

OBJECTIVE: To define how estimates of keratoconus progression following collagen cross-linking (CXL) vary according to the parameter selected to measure corneal shape. MATERIALS AND METHODS: 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. RESULTS: 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%). CONCLUSIONS: 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.

Durable responses to ATR inhibition with ceralasertib in tumors with genomic defects and high inflammation.

BACKGROUNDPhase 1 study of ATRinhibition alone or with radiation therapy (PATRIOT) was a first-in-human phase I study of the oral ATR (ataxia telangiectasia and Rad3-related) inhibitor ceralasertib (AZD6738) in advanced solid tumors.METHODSThe primary objective was safety. Secondary objectives included assessment of antitumor responses and pharmacokinetic (PK) and pharmacodynamic (PD) studies. Sixty-seven patients received 20-240 mg ceralasertib BD continuously or intermittently (14 of a 28-day cycle).RESULTSIntermittent dosing was better tolerated than continuous, which was associated with dose-limiting hematological toxicity. The recommended phase 2 dose of ceralasertib was 160 mg twice daily for 2 weeks in a 4-weekly cycle. Modulation of target and increased DNA damage were identified in tumor and surrogate PD. There were 5 (8%) confirmed partial responses (PRs) (40-240 mg BD), 34 (52%) stable disease (SD), including 1 unconfirmed PR, and 27 (41%) progressive disease. Durable responses were seen in tumors with loss of AT-rich interactive domain-containing protein 1A (ARID1A) and DNA damage-response defects. Treatment-modulated tumor and systemic immune markers and responding tumors were more immune inflamed than nonresponding.CONCLUSIONCeralasertib monotherapy was tolerated at 160 mg BD intermittently and associated with antitumor activity.TRIAL REGISTRATIONClinicaltrials.gov: NCT02223923, EudraCT: 2013-003994-84.FUNDINGCancer Research UK, AstraZeneca, UK Department of Health (National Institute for Health Research), Rosetrees Trust, Experimental Cancer Medicine Centre.

Randomised controlled trial of adjunctive triamcinolone acetonide in eyes undergoing vitreoretinal surgery following open globe trauma: The ASCOT study.

BACKGROUND/AIMS: To investigate the clinical effectiveness of adjunctive triamcinolone acetonide (TA) given at the time of vitreoretinal surgery following open globe trauma (OGT). METHODS: A phase 3, multicentre, double-masked randomised controlled trial of patients undergoing vitrectomy following OGT comparing adjunctive TA (intravitreal and subtenons) against standard care (2014-2020). The primary outcome was the proportion of patients with at least 10 Early Treatment Diabetic Retinopathy Study (ETDRS) letter improvement in corrected visual acuity (VA) at 6 months. Secondary outcomes included: change in ETDRS, retinal detachment (RD) secondary to PVR, retinal reattachment, macular reattachment, tractional RD, number of operations, hypotony, elevated intraocular pressure and quality of life. RESULTS: 280 patients were randomised over 75 months, of which 259 completed the study. 46.9% (n=61/130) of patients in the treatment group had a 10-letter improvement in VA compared with 43.4% (n=56/129) of the control group (difference 3.5% (95% CI -8.6% to 15.6%), OR=1.03 (95% CI 0.61 to 1.75), p=0.908)). Secondary outcome measures also failed to show any treatment benefit. For two of the secondary outcome measures, stable complete retinal and macular reattachment, outcomes were worse in the treatment group compared with controls, respectively, 51.6% (n=65/126) vs 64.2% (n=79/123), OR=0.59 (95% CI 0.36 to 0.99), and 54.0% (n=68/126) vs 66.7% (n=82/123), OR=0.59 (95% CI 0.35 to 0.98), for TA vs control. CONCLUSION: The use of combined intraocular and sub-Tenons capsule TA is not recommended as an adjunct to vitrectomy surgery following OGT. TRIAL REGISTRATION NUMBER: NCT02873026.

Face-down positioning or posturing after macular hole surgery.

BACKGROUND: Macular holes cause severe impairment of sight. With the aim of improving the outcome of surgery for macular holes, particularly larger macular holes (those measuring over 400 µm), a variable period of face-down positioning may be advised. This review is an update of a Cochrane Review published in 2011. OBJECTIVES: To evaluate the effect of postoperative face-down positioning on the outcome of surgery for macular hole. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2022, Issue 5), which contains the Cochrane Eyes and Vision Trials Register, Ovid MEDLINE, Ovid Embase, the ISRCTN registry, ClinicalTrials.gov, and the WHO International Clinical Trials Registry Platform. There were no date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 25 May 2022. SELECTION CRITERIA: We included randomised controlled trials (RCTs) in which postoperative face-down positioning was compared to no face-down positioning following surgery for macular holes. The primary outcome of interest was closure of the macular hole. Other outcomes of interest included visual outcomes, quality of life outcomes, and the occurrence of adverse events. Pairs of review authors independently selected studies for inclusion, extracted data, assessed risk of bias, and evaluated the certainty of evidence using GRADE. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. We analysed dichotomous data as risk ratios (RRs), and continuous data as mean differences (MDs), with 95% confidence intervals (CI). The unit of analysis was eyes. MAIN RESULTS: We included eight studies allocating a total of 709 eyes (699 participants). There was heterogeneity in study design, including the control group treatment (from no positioning to strict maintenance of other 'face-forward' postures) and surgical procedures (with or without inner limiting membrane peeling, with or without cataract surgery). There were also different durations of positioning, with two studies using 3 days, two studies using 5 days, and three studies using 10 days of face-down positioning. Whilst the overall risk of bias was low, all included studies were judged to be at high or unclear risk of bias due to absence of assessment of adherence to the 'prescribed' intervention of face-down positioning or posturing. The primary outcome of successful anatomical hole closure at one to six months following surgery was reported in 95 of every 100 eyes of participants advised to position face-down for at least three days after surgery, and in 85 of every 100 eyes of participants not advised to position face-down (RR 1.05, 95% CI 0.99 to 1.12, 709 eyes, 8 studies, I² = 44%). Amongst the 327 eyes of participants with macular holes of at least 400 µm, hole closure was noted in 94 of every 100 eyes of participants advised to position face-down, and in 84 of every 100 eyes of participants not advised to position face-down (RR 1.08, 95% CI 0.93 to 1.26, 5 studies, I² = 62%). Amongst the 129 eyes of participants with macular holes of less than 400 µm, hole closure was noted in 100 of every 100 eyes of participants advised to position face-down, and in 96 of every 100 eyes of participants not advised to position face-down (RR 1.03, CI 0.97 to 1.11, 4 studies, I² = 0%). The certainty of the evidence was low, downgraded for imprecision (CIs including no effect) and study design limitations (with different durations of face-down posturing used in the absence of a dose-response gradient, and limitations in measuring the exposure). Meta-analysis of visual acuity data was challenging given the use of different definitions of postoperative visual outcome across studies. Three studies reported findings by gain in Early Treatment Diabetic Retinopathy Study (ETDRS) letters (MD 2.04, 95% CI -0.01 to 4.09, very low-certainty evidence). Meta-analyses of quality of life data were not possible because of inconsistency in outcome metrics across studies. One study reported no difference between groups in quality of life, as reported on a validated quality of life metric scale (the National Eye Institute Visual Function Questionnaire - 25 (NEI VFQ-25), between face-down positioning for five days and non-face-down positioning (median NEI VFQ-25 score was 89 (interquartile range (IQR) 76 to 94) in the face-down group versus 87 (IQR 73 to 93) in the non-face-down group (adjusted mean difference on a logistic scale 0.02, 95% CI -0.03 to 0.07, P = 0.41)). Two studies reported increased ease of positioning and less pain in non-face-down positioning groups on non-validated 0-to-10-point visual analogue scores. On an ease-of-positioning score running from 0 (very difficult) to 10 (very easy), there were consistent reports of the discomfort associated with face-down positioning: the median participant-reported ease-of-positioning score was 6 (IQR 4 to 8) in those undergoing 5 days of face-down positioning versus 9 (IQR 7 to 10) in the comparator group (P = 0.01). On a pain score with 0 being pain-free and 10 being in severe pain, mean pain score was 6.52 ± 2.48 in the face-down positioning group versus 2.53 ± 2.6 in the non-face-down positioning group. The adverse event of postoperative nerve compression occurred in less than 1 in every 100 (3 per 1000) participants advised to position face-down, and 0 in every 100 participants not advised to position face-down (699 participants, 8 studies, moderate-certainty evidence). AUTHORS' CONCLUSIONS: We identified eight RCTs evaluating face-down positioning following surgery for macular hole. The included studies were not all directly comparable due to differences in the surgical techniques used and the durations of postoperative positioning advised. Low-certainty evidence suggests that face-down positioning may have little or no effect on macular hole closure after surgery. Face-down positioning is a low-risk intervention, with serious adverse events affecting fewer than 1 in 300 people. We suggest that any future trials focus on patients with larger macular holes, with interventions and outcome measures used in previous trials (i.e. with inner limiting membrane peeling, positioning durations of three to five days, and validated quality of life metrics) to allow future meta-analyses to determine any effect with greater precision and confidence.

A randomised controlled trial of adjunctive triamcinolone acetonide in eyes undergoing vitreoretinal surgery for open globe trauma - the ASCOT study.

Background: Eyes sustaining open globe trauma are at high risk of severe visual impairment. Proliferative vitreoretinopathy is the most common cause of retinal detachment and visual loss in eyes with open globe trauma. There is evidence from experimental studies and pilot clinical trials that the use of adjunctive steroid medication triamcinolone acetonide can reduce the incidence of proliferative vitreoretinopathy and improve outcomes of surgery for open globe trauma. Objective: The Adjunctive Steroid Combination in Ocular Trauma or ASCOT study aimed to investigate the clinical effectiveness of adjunctive triamcinolone acetonide given at the time of vitreoretinal surgery for open globe trauma. Design: A phase 3 multicentre double-masked randomised controlled trial randomising patients undergoing vitrectomy following open globe trauma to either adjunctive triamcinolone acetonide or standard care. Setting: Hospital vitreoretinal surgical services dealing with open globe trauma. Participants: Patients undergoing vitrectomy surgery who had sustained open globe trauma. Interventions: Triamcinolone acetonide 4 mg/0.1 ml into the vitreous cavity and 40 mg/1 ml sub-Tenon's or standard vitreoretinal surgery and postoperative care. Main outcome measures: The primary outcome was the proportion of patients with at least 10 letters of improvement in corrected visual acuity at six months. Secondary outcomes included retinal detachment secondary to proliferative vitreoretinopathy, retinal reattachment, macula reattachment, tractional retinal detachment, number of operations, hypotony, elevated intraocular pressure and quality of life. Health-related quality of life was assessed using the EuroQol Five Domain and Visual Function Questionnaire 25 questionnaires. Results: A total of 280 patients were randomised; 129 were analysed from the control group and 130 from the treatment group. The treatment group appeared, by chance, to have more severe pathology on presentation. The primary outcome (improvement in visual acuity) and principal secondary outcome (change in visual acuity) did not demonstrate any treatment benefit for triamcinolone acetonide. The proportion of patients with improvement in visual acuity was 47% for triamcinolone acetonide and 43% for standard care (odds ratio 1.03, 95% confidence interval 0.61 to 1.75, p = 0.908); the baseline adjusted mean difference in the six-month change in visual acuity was -2.65 (95% confidence interval -9.22 to 3.92, p = 0.430) for triamcinolone acetonide relative to control. Similarly, the secondary outcome measures failed to show any treatment benefit. For two of the secondary outcome measures, stable complete retinal reattachment and stable macular retinal reattachment, outcomes for the treatment group were significantly worse for triamcinolone acetonide at the 5% level (respectively, odds ratio 0.59, 95% confidence interval 0.36 to 0.99, p = 0.044 and odds ratio 0.59, 95% confidence interval 0.35 to 0.98, p = 0.041) compared with control in favour of control. The cost of the intervention was £132 per patient. Health economics outcome measures (Early Treatment Diabetic Retinopathy Study, Visual Function Questionnaire 25 and EuroQol Five Dimensions) did not demonstrate any significant difference in quality-adjusted life-years. Conclusions: The use of combined intraocular and sub-Tenon's capsule triamcinolone acetonide is not recommended as an adjunct to vitrectomy surgery for intraocular trauma. Secondary outcome measures are suggestive of a negative effect of the adjunct, although the treatment group appeared to have more severe pathology on presentation. Future work: The use of alternative adjunctive medications in cases undergoing surgery for open globe trauma should be investigated. Refinement of clinical grading and case selection will enable better trail design for future studies. Trial registration: This trial is registered as ISRCTN 30012492, EudraCT number 2014-002193-37, REC 14/LNO/1428, IRAS 156358, Local R&D registration CHAD 1031. Funding: This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (12/35/64) and will be published in full in Health Technology Assessment; Vol. 27, No. 12. See the NIHR Journals Library website for further project information.

Despite advances in surgical techniques, eye trauma remains a leading cause of blindness and visual impairment. The main cause of trauma is a scarring process within the eye ­ proliferative vitreoretinopathy. There is good evidence from laboratory work and small-scale clinical studies that the addition of a steroid medication, triamcinolone acetonide, given in and around the eye at the time of surgery for eye trauma, can reduce the incidence of proliferative vitreoretinopathy scarring and improve the outcomes of surgery. The Adjunctive Steroid Combination in Ocular Trauma or ASCOT study was a multicentre clinical trial designed to test the use of triamcinolone acetonide as an addition to surgery to improve outcomes in eyes with 'open globe' penetrating injuries. A total of 280 patients were recruited and randomised to receive standard surgery or surgery with the additional steroid (triamcinolone acetonide). No benefit was found from the addition of the steroid medication. The addition of steroid medication was not good value for money. Secondary outcome measures suggested that triamcinolone acetonide may have had a negative effect on outcomes, although this may have been due to the presence of more severe cases amongst the patients allocated to receive the additional steroid (triamcinolone acetonide). The use of adjunctive triamcinolone acetonide in eye trauma cases undergoing surgery is therefore not recommended. Future studies with different additional medications and/or more targeted case selection are indicated to improve outcomes for eyes experiencing penetrating trauma.

Incidence and factors for pseudoaccommodation after monofocal lens implantation: the Monofocal Extended Range of Vision study.

PURPOSE: To screen patients with a monofocal intraocular lens (IOL) for incidence of unaided 20/40 and 0.3 LogMAR for distance and near (pseudoaccommodation) and to find factors for pseudoaccommodation. SETTINGS: University Hospitals Sussex NHS Foundation Trust, Brighton, United Kingdom. DESIGN: Prospective study. METHODS: This was a single-eye study ( ClinicalTrials.gov : NCT04011696). At 3 to 9 months, refraction, uncorrected and corrected distance and uncorrected near visual acuity (logMAR), spherical equivalent (SEQ), mesopic pupil size (PS), total eye spherical (Z 40 ), vertical coma (Z 3-1 ) aberrations, reading speed and smallest print size were assessed. Refractive astigmatism (RA) was classified as against-the-rule, with-the-rule, oblique and no astigmatism. Data on preoperative axial length (AL) and anterior chamber depth (ACD) were collected. RESULTS: 29 patients (9.6%, 95% CI, 6.5-13.5) had pseudoaccommodation. In cases vs controls, median SEQ, PS, total Z 40 , Z 3-1 , reading speed, smallest print size, preoperative ACD, preoperative AL were: -0.39 vs 0.0 diopters; 3.62 vs 4.10 mm; 0.01 vs 0.02 µm; 0.018 vs 0.022 µm; 106 vs 133 words per minute; 0.30 vs 0.50 logMAR; 2.94 vs 3.13 mm, 23.4 vs 23.7 mm, respectively. RA was not different between the groups. Univariate analysis revealed preoperative ACD (odds ratio [OR], 0.38, 95% CI, 0.16-0.94, P = .04), SEQ (OR, 0.61, 95% CI, 0.42-0.88, P = .01), total Z 40 (OR, 0.0003, 95% CI, 0.00-0.39, P = .03) and PS (OR, 0.39, 95% CI, 0.22-0.69, P < .041) to be significant. Whereas multivariable logistic regression identified: preoperative AL (OR, 0.62, 95% CI, 0.42-0.91, P = .02), SEQ (OR, 0.49, 95% CI, 0.31-0.78, P = .01), Z 40 (OR, 0.00, 95% CI, 0.0-0.01, P = .01) and PS (OR, 0.41, 95% CI, 0.23-0.75, P = .01) to be significant. CONCLUSIONS: A combination of low myopic SEQ, lower Z 40 , shorter preoperative AL, and smaller PS increases the chances of pseudoaccommodation.

Advance Care Planning and Place of Death During the COVID-19 Pandemic: A Retrospective Analysis of Routinely Collected Data.

Increased advance care planning was endorsed at the start of the Coronavirus disease 2019 (COVID-19) pandemic with the aim of optimizing end-of-life care. This retrospective observational cohort study explores the impact of advanced care planning on place of death. 21,962 records from patients who died during the first year of the pandemic and who had an Electronic Palliative Care Coordination System record were included. 11,913 (54%) had a documented place of death. Of these 5,339 died at home and 2,378 died in hospital. 9,971 (45%) had both a documented place of death and a preferred place of death. Of these, 7,668 (77%) died in their preferred location. Documented elements of advance care planning, such as resuscitation status and ceiling of treatment decisions, were associated with an increased likelihood of dying in the preferred location, as were the number of times the record was viewed. During the COVID-19 pandemic, advanced care planning and the use of digital care coordination systems presented an opportunity for patients and healthcare staff to personalize care and influence end-of-life experiences.

Laser-assisted cataract surgery versus standard ultrasound phacoemulsification cataract surgery.

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.

ANTECEDENTES: La catarata es la principal causa de ceguera en el mundo y, como tal, la cirugía de cataratas es una de las operaciones más realizadas en todo el mundo. Las técnicas quirúrgicas han cambiado radicalmente en el último medio siglo, con las consiguientes mejoras en los desenlaces y la seguridad. Los láseres de femtosegundo se pueden utilizar para realizar los pasos clave de la cirugía de cataratas, como las incisiones corneales, la capsulotomía y la fragmentación del cristalino. La ventaja potencial de la cirugía de cataratas asistida por láser de femtosegundo (FLACS por sus siglas en inglés) es la mayor precisión y reproducibilidad de estos pasos en comparación con las técnicas manuales. Las desventajas son los costes asociados con la tecnología FLACS. OBJETIVOS: Comparar la eficacia y la seguridad de la FLACS con la cirugía de cataratas estándar por facoemulsificación (PCS) con ultrasonido mediante la recopilación de evidencia de ensayos controlados aleatorizados (ECA). MÉTODOS DE BÚSQUEDA: Se realizaron búsquedas en el Registro Cochrane central de ensayos controlados (Cochrane Central Register of Controlled Trials [CENTRAL]; que contiene el Registro de ensayos del Grupo Cochrane de Salud ocular y de la visión [Cochrane Eyes and Vision]; 2022, número 5); en Ovid MEDLINE; Ovid Embase; LILACS; el registro ISRCTN; ClinicalTrials.gov; la ICTRP de la OMS y el sitio web de la Food and Drug Administration (FDA) de los EE. UU. No se aplicaron restricciones de fecha ni de idioma en las búsquedas electrónicas de ensayos. La última búsqueda en las bases de datos electrónicas se realizó el 10 de mayo de 2022. CRITERIOS DE SELECCIÓN: Se incluyeron los ECA en los que la FLACS se comparó con la PCS. OBTENCIÓN Y ANÁLISIS DE LOS DATOS: Tres autores de la revisión examinaron de forma independiente los resultados de la búsqueda, evaluaron el riesgo de sesgo y extrajeron los datos mediante los procedimientos metodológicos estándar previstos por Cochrane. El desenlace principal de esta revisión fueron las complicaciones intraoperatorias en el ojo operado, concretamente, desgarros de la cápsula anterior y posterior. Los desenlaces secundarios incluyeron la agudeza visual corregida a distancia (AVCD), la calidad de la visión (medida por cualquier medida de desenlace notificada por el paciente [PROM] validada), las complicaciones posoperatorias del edema macular cistoide, la pérdida de células endoteliales y la coste­efectividad. La certeza de la evidencia se evaluó mediante el método GRADE. RESULTADOS PRINCIPALES: Se incluyeron 42 ECA realizados en Europa, Norteamérica, Sudamérica y Asia, que reclutaron un total de 7298 ojos de 5831 participantes adultos. En general, los estudios tuvieron riesgo de sesgo incierto o alto. En 16 estudios, los autores informaron vínculos financieros con el fabricante de la plataforma láser evaluada en sus estudios. Trece de los estudios fueron estudios intrapersonales (ojo pareado) con un ojo asignado a un procedimiento y el otro ojo asignado al otro procedimiento. El informe de estos estudios no consideró la naturaleza pareada de los datos. Hubo evidencia de certeza baja de poca o ninguna diferencia en las probabilidades de desarrollar desgarros de la cápsula anterior al comparar FLACS y PCS (odds ratio [OR] de Peto 0,83; intervalo de confianza [IC] del 95%: 0,40 a 1,72; 5835 ojos, 27 estudios). Hubo un desgarro de la cápsula anterior menos por cada 1000 cirugías en el grupo de FLACS en comparación con el grupo de PCS (IC del 95%: 4 menos a 3 más).  Hubo evidencia de certeza baja de menores probabilidades de desarrollar desgarros de la cápsula posterior con FLACS en comparación con PCS (OR de Peto 0,50; IC del 95%: 0,25 a 1,00; 5767 ojos, 26 estudios). Hubo cuatro desgarros de la cápsula posterior menos por cada 1000 cirugías en el grupo de FLACS en comparación con el grupo de PCS (IC del 95%: 6 menos a igual).  Hubo evidencia de certeza moderada de una ventaja muy pequeña en el grupo de FLACS con respecto a la AVCD a los seis meses o más de seguimiento, (diferencia de medias [DM] ­0,01 logMAR; IC del 95%: ­0,02 a 0,00; 1323 ojos, siete estudios). Esta diferencia equivale a 1 letra logMAR entre los grupos y no se considera clínicamente importante. De los tres estudios (1205 participantes) que informaron sobre una variedad de PROM (Cat­PROMS, EQ­5D, EQ­SD­3L, Catquest9­SF y encuesta de pacientes) hasta tres meses después de la cirugía, hubo evidencia de certeza moderada de poca o ninguna diferencia en los diversos parámetros entre los dos grupos de tratamiento. Hubo evidencia de certeza baja de poca o ninguna diferencia en las probabilidades de desarrollar edema macular cistoide al comparar FLACS y PCS (OR de Peto 0,84; IC del 95%: 0,56 a 1,28; 4441 ojos, 18 estudios). Hubo tres casos menos de edema macular cistoide por cada 1000 cirugías en el grupo de FLACS en comparación con el grupo de PCS (IC del 95%: 10 menos a 6 más).  En un estudio, el cociente coste­efectividad incremental (ICER) (diferencia de coste dividida por la diferencia de años de vida ajustados por la calidad [AVAC]) fue de 167 620 GBP al comparar FLACS con SCP. En otro estudio, el ICER fue de 10 703 euros ahorrados por paciente adicional que tuvo un tratamiento exitoso con PCS en comparación con FLACS. La duración varió entre tres minutos a favor de FLACS y ocho minutos a favor de PCS (I 2 = 100%, 11 estudios) (evidencia de certeza baja).  Hubo evidencia de certeza baja de poca o ninguna diferencia importante en la pérdida de células endoteliales al comparar la FLACS con la PCS (DM 12 células por mm 2 a favor de la FLACS; IC del 95%: ­40 a 64; 1512 ojos, 10 estudios).  CONCLUSIONES DE LOS AUTORES: Esta revisión de 42 estudios aporta evidencia de que probablemente haya poca o ninguna diferencia entre la FLACS y la PCS en cuanto a las complicaciones intraoperatorias y posoperatorias, la agudeza visual posoperatoria y la calidad de vida. La evidencia de dos estudios indica que la FLACS podría ser la opción menos coste­efectiva. Muchos de los estudios incluidos solo investigaron medidas de desenlace muy específicas, como el tiempo efectivo de facoemulsificación, el cambio en el recuento de células endoteliales o el brote acuoso, en lugar de las directamente relacionadas con los desenlaces de los pacientes. La notificación estandarizada de las complicaciones y los desenlaces visuales y refractarios de la cirugía de cataratas facilitaría la síntesis futura, y recientemente se han publicado guías al respecto.

Estimating the rate of severe visual loss (wipe-out) following cataract surgery, a British Ophthalmological Surveillance Unit (BOSU) study.

BACKGROUND: A sudden, irreversible reduction in visual acuity ('wipe-out') is a feared complication of cataract surgery. Current literature on wipe-out is limited in quantity and quality, and largely predates modern cataract surgery and imaging techniques. The objectives of our study were to estimate the incidence of wipe-out and to identify potential risk factors. METHODS: We prospectively collated cases of wipe-out occurring in the UK during a 25-month study period using the British Ophthalmic Surveillance Unit reporting system. A total of 21 potential cases of wipe-out were reported, 5 of which met all inclusion and exclusion criteria. RESULTS: The estimated incidence of wipe-out during the study period was 0.00000298, or approximately 3 cases per million cataract operations. All cases of wipe-out occurred exclusively in patients with advanced glaucoma (mean deviation -21.0 decibels or worse in the operated eye), with an over-representation of black people (40%) in our case series. A prior diagnosis of retinal vein occlusion (60%) and elevated post-operative IOP (40%) were more common among individuals suffering from wipe-out compared to the general population, suggesting these factors may contribute to the pathogenesis of wipe-out. CONCLUSIONS: Our study shows that wipe-out is a rare complication, affecting approximately 3 per million undergoing cataract surgery. Patients with advanced glaucoma, black patients, and those with previous retinal vein occlusions may be at greater risk of wipe-out. We hope that the findings of our study will be used to help inform treatment decision-making and the cataract surgery consent process.

Quantitative background parenchymal enhancement and fibro-glandular density at breast MRI: Association with BRCA status.

OBJECTIVES: To investigate whether MRI-based measurements of fibro-glandular tissue volume, breast density (MRBD), and background parenchymal enhancement (BPE) could be used to stratify two cohorts of healthy women: BRCA carriers and women at population risk of breast cancer. METHODS: Pre-menopausal women aged 40-50 years old were scanned at 3 T, employing a standard breast protocol including a DCE-MRI (35 and 30 participants in high- and low-risk groups, respectively). The dynamic range of the DCE protocol was characterised and both breasts were masked and segmented with minimal user input to produce measurements of fibro-glandular tissue volume, MRBD, and voxelwise BPE. Statistical tests were performed to determine inter- and intra-user repeatability, evaluate the symmetry between metrics derived from left and right breasts, and investigate MRBD and BPE differences between the high- and low-risk cohorts. RESULTS: Intra- and inter-user reproducibility in estimates of fibro-glandular tissue volume, MRBD, and median BPE estimations were good, with coefficients of variation < 15%. Coefficients of variation between left and right breasts were also low (< 25%). There were no significant correlations between fibro-glandular tissue volume, MRBD, and BPE for either risk group. However, the high-risk group had higher BPE kurtosis, although linear regression analysis did not reveal significant associations between BPE kurtosis and breast cancer risk. CONCLUSIONS: This study found no significant differences or correlations in fibro-glandular tissue volume, MRBD, or BPE metrics between the two groups of women with different levels of breast cancer risk. However, the results support further investigation into the heterogeneity of parenchymal enhancement. KEY POINTS: • A semi-automated method enabled quantitative measurements of fibro-glandular tissue volume, breast density, and background parenchymal enhancement with minimal user intervention. • Background parenchymal enhancement was quantified over the entire parenchyma, segmented in pre-contrast images, thus avoiding region selection. • No significant differences and correlations in fibro-glandular tissue volume, breast density, and breast background parenchymal enhancement were found between two cohorts of women at high and low levels of breast cancer risk.

Phenotype and genotype of concurrent keratoconus and Fuchs endothelial corneal dystrophy.

PURPOSE: To characterise the phenotype and genotype of concurrent keratoconus and Fuchs endothelial corneal dystrophy (KC + FECD). METHODS: We recruited 20 patients with concurrent KC + FECD for a retrospective observational case series from the United Kingdom and the Czech Republic. We compared eight parameters of corneal shape (Pentacam, Oculus) with two groups of age-matched controls who had either isolated keratoconus (KC) or isolated FECD. We genotyped probands for an intronic triplet TCF4 repeat expansion (CTG18.1) and the ZEB1 variant c.1920G >T p.(Gln640His). RESULTS: The median age at diagnosis of patients with KC + FECD was 54 (interquartile range 46 to 66) years, with no evidence of KC progression (median follow-up 84 months, range 12 to 120 months). The mean (standard deviation (SD)) of the minimum corneal thickness, 493 (62.7) µm, was greater than eyes with KC, 458 (51.1) µm, but less than eyes with FECD, 590 (55.6) µm. Seven other parameters of corneal shape were more like KC than FECD. Seven (35%) probands with KC + FECD had a TCF4 repeat expansion of ≥50 compared to five controls with isolated FECD. The average of the largest TCF4 expansion in cases with KC + FECD (46 repeats, SD 36 repeats) was similar to the age-matched controls with isolated FECD (36 repeats, SD 28 repeats; p = 0.299). No patient with KC + FECD harboured the ZEB1 variant. CONCLUSIONS: The KC + FECD phenotype is consistent with KC but with superimposed stromal swelling from endothelial disease. The proportion of cases with a TCF4 expansion is similar in concurrent KC + FECD and age-matched controls with isolated FECD.

Home-based screening tools for amblyopia: a systematic review.

Amblyopia is an important public health concern. While home-based screening may present an effective solution, this has not been rigorously assessed in a systematic review. A systematic review was performed using Ovid MEDLINE, PubMed, The Cochrane Library, Embase, Web of Science Core Collection, and Clinicaltrials.gov. All studies reporting the diagnostic accuracy of home-based screening tools for amblyopia among children were included. Studies involving orthoptist or ophthalmologist-led screening and adult subjects were excluded. The main outcome measure was the diagnostic accuracy expressed as sensitivity and specificity. Among 3670 studies identified, 28 were eligible for inclusion in our systematic review. The age range of patients were less than 1 month to 16 years old. 7 studies used internet-based tools, 16 used smartphone/tablet applications, 3 used digital cameras, and 3 used home-based questionnaires and visual acuity tools. All studies included a reference standard except one, which was a longitudinal study. 21 studies had full ophthalmological examination whilst 6 studies had validated visual acuity measurement tools as gold standards. Of the 27 studies which compared against a reference test, only 25 studies reported sensitivity and specificity values. Using the QUADAS-2 tool, 50% of studies were deemed to have applicability concern due to patient selection from tertiary centres and unclear methods for recruitment. There is a need to improve the quality of diagnostic accuracy studies, standardise thresholds for detecting amblyopia, and ensure consistent reporting of results. Further research is needed to evaluate the suitability of these tools for amblyopia screening.

Presenting clinical characteristics of open globe injuries in ocular trauma: baseline analysis of cases in the ASCOT national clinical trial.

BACKGROUND/OBJECTIVES: The Adjunctive Steroid Combination in Ocular Trauma (ASCOT) trial is a unique pragmatic, multi-centre, patient and assessor masked, randomised controlled trial. We evaluate the clinical characteristics and pathology of this large trial cohort of patients with open globe injuries undergoing vitreoretinal surgery, including the associations between patient characteristics and their baseline vision. SUBJECTS/METHODS: We (i) summarise demographics, injury history and ocular history of the 280 participants recruited into the ASCOT trial using descriptive statistics; (ii) analyse the national and seasonal variation across England and Scotland in these participant characteristics; and (iii) explore the associations between participant demographic, trauma history, ocular history and presenting baseline visual acuity (measured using the Early Treatment Diabetic Retinopathy Study, ETDRS) using multivariable regression analyses. RESULTS: The majority of participants with open globe penetrating injuries were of white ethnicity (233, 84%), male (246, 88%), with a median age of 43 years (IQR 30-55 years). There was considerable variability in presenting visual acuity with 75% unable to read any letters on the ETDRS chart, whilst the median ETDRS letter score was 58 (IQR 24-80) for those who could read ≥1 letter. The most common causes of injury were workplace related (31%) or interpersonal violence (24%). Previous eye surgery, visual axis corneal scar, lens status, hyphaemia and vitreous haemorrhaging were found to be associated with presenting vision as measured by the ETDRS chart. CONCLUSION: The ASCOT trial provides valuable insights into the spectrum of pathology of patients with open globe eye injuries undergoing vitreoretinal surgery. The identified causes of injury and clinical presentation of the cases will help in training and resource planning to deal with these often challenging surgical cases. TRIAL REGISTRATION: EudraCT No. 014-002193-37. HTA Project 12/35/64.

Laser in Glaucoma and Ocular Hypertension (LiGHT) Trial: Six-Year Results of Primary Selective Laser Trabeculoplasty versus Eye Drops for the Treatment of Glaucoma and Ocular Hypertension.

PURPOSE: The Laser in Glaucoma and Ocular Hypertension (LiGHT) Trial has shown selective laser trabeculoplasty (SLT) to be clinically and cost-effective as a primary treatment of open-angle glaucoma (OAG) and ocular hypertension (OHT) at 3 years. This article reports health-related quality of life (HRQoL) and clinical effectiveness of initial treatment with SLT compared with intraocular pressure (IOP)-lowering eye drops after 6 years of treatment. DESIGN: Prospective, multicenter randomized controlled trial. PARTICIPANTS: Treatment-naive eyes with OAG or OHT initially treated with SLT or IOP-lowering drops. METHODS: Patients were allocated randomly to initial SLT or eye drops. After the initial 3 years of the trial, patients in the SLT arm were permitted a third SLT if necessary; patients in the drops arm were allowed SLT as a treatment switch or escalation. This study is registered at controlled-trials.com (identifier, ISRCTN32038223). MAIN OUTCOME MEASURES: The primary outcome was HRQoL at 6 years; secondary outcomes were clinical effectiveness and adverse events. RESULTS: Of the 692 patients completing 3 years in the LiGHT Trial, 633 patients (91.5%) entered the extension, and 524 patients completed 6 years in the trial (82.8% of those entering the extension phase). At 6 years, no significant differences were found for the EuroQol EQ-5D 5 Levels, Glaucoma Utility Index, and Glaucoma Quality of Life-15 (P > 0.05 for all). The SLT arm showed better Glaucoma Symptom Scale scores than the drops arm (83.6 ± 18.1 vs. 81.3 ± 17.3, respectively). Of eyes in the SLT arm, 69.8% remained at or less than the target IOP without the need for medical or surgical treatment. More eyes in the drops arm exhibited disease progression (26.8% vs. 19.6%, respectively; P = 0.006). Trabeculectomy was required in 32 eyes in the drops arm compared with 13 eyes in the SLT arm (P < 0.001); more cataract surgeries occurred in the drops arm (95 compared with 57 eyes; P = 0.03). No serious laser-related adverse events occurred. CONCLUSIONS: Selective laser trabeculoplasty is a safe treatment for OAG and OHT, providing better long-term disease control than initial drop therapy, with reduced need for incisional glaucoma and cataract surgery over 6 years.

Is preventable sight loss truly preventable? An exploration of a public health indicator for sight loss due to age-related macular degeneration in England.

BACKGROUND: Age-related macular degeneration accounts for the majority of severe sight impairment and sight impairment registration and certifications in adults in the UK [1, 2]. Whilst these treatments are effective in arresting nAMD progression, there is currently no treatment for GA [1, 3, 4]. METHODS: This paper provides an update to the data collected by Bunce et al. [3] and details the number of people certified together with incidence rates for the various types of AMD by: sex, sight impairment status, and for all ages using the 2016/2017 and 2017/2018 CVI due to AMD data for England from the Moorfields Eye Hospital, supplemented with 2017-2018 PHOF indicator 4.12i/E12a data. The study population includes individuals of all ages in England who were newly certified with visual impairment due to AMD. RESULTS: Between 2016 and 2017, CVIs due to AMD totalled to 11,215; between 2017 and 2018, CVIs due to AMD totalled to 10,914. The PHOF indicator 4.12i/E12a assessed showed that overall rates of AMD certifications have steadily declined in England from 131.5 per 100,000 in 2010/2011 to 106.7 per 100,000 in 2017/2018. CONCLUSION: As treatment is available for nAMD, a reduction in nAMD certifications could be expected; however, growth of the elderly population in England combined with there currently being no treatment available for GA means AMD certification rates should be increasing. Therefore, it is postulated that not all cases of AMD are being certified and registered with some likely going undiagnosed.