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  1. Article ; Online: Relationship between Intraocular Pressure Fluctuation and Visual Field Progression Rates in the United Kingdom Glaucoma Treatment Study.

    Rabiolo, Alessandro / Montesano, Giovanni / Crabb, David P / Garway-Heath, David F

    Ophthalmology

    2024  

    Abstract: Purpose: To investigate whether intraocular pressure (IOP) fluctuation is associated independently with the rate of visual field (VF) progression in the United Kingdom Glaucoma Treatment Study.: Design: Randomized, double-masked, placebo-controlled ... ...

    Abstract Purpose: To investigate whether intraocular pressure (IOP) fluctuation is associated independently with the rate of visual field (VF) progression in the United Kingdom Glaucoma Treatment Study.
    Design: Randomized, double-masked, placebo-controlled multicenter trial.
    Participants: Participants with ≥5 VFs (213 placebo, 217 treatment).
    Methods: Associations between IOP metrics and VF progression rates (mean deviation [MD] and five fastest locations) were assessed with linear mixed models. Fluctuation variables were mean Pascal ocular pulse amplitude (OPA), standard deviation (SD) of diurnal Goldmann IOP (diurnal fluctuation), and SD of Goldmann IOP at all visits (long-term fluctuation). Fluctuation values were normalized for mean IOP to make them independent from the mean IOP. Correlated nonfluctuation IOP metrics (baseline, peak, mean, supine, and peak phasing IOP) were combined with principal component analysis, and principal component 1 (PC1) was included as a covariate. Interactions between covariates and time from baseline modeled the effect of the variables on VF rates. Analyses were conducted separately in the two treatment arms.
    Main outcome measures: Associations between IOP fluctuation metrics and rates of MD and the five fastest test locations.
    Results: In the placebo arm, only PC1 was associated significantly with the MD rate (estimate, -0.19 dB/year [standard error (SE), 0.04 dB/year]; P < 0.001), whereas normalized IOP fluctuation metrics were not. No variable was associated significantly with MD rates in the treatment arm. For the fastest five locations in the placebo group, PC1 (estimate, -0.58 dB/year [SE, 0.16 dB/year]; P < 0.001), central corneal thickness (estimate, 0.26 dB/year [SE, 0.10 dB/year] for 10 μm thicker; P = 0.01) and normalized OPA (estimate, -3.50 dB/year [SE, 1.04 dB/year]; P = 0.001) were associated with rates of progression; normalized diurnal and long-term IOP fluctuations were not. In the treatment group, only PC1 (estimate, -0.27 dB/year [SE, 0.12 dB/year]; P = 0.028) was associated with the rates of progression.
    Conclusions: No evidence supports that either diurnal or long-term IOP fluctuation, as measured in clinical practice, are independent factors for glaucoma progression; other aspects of IOP, including mean IOP and peak IOP, may be more informative. Ocular pulse amplitude may be an independent factor for faster glaucoma progression.
    Financial disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
    Language English
    Publishing date 2024-02-13
    Publishing country United States
    Document type Journal Article
    ZDB-ID 392083-5
    ISSN 1549-4713 ; 0161-6420
    ISSN (online) 1549-4713
    ISSN 0161-6420
    DOI 10.1016/j.ophtha.2024.02.008
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Patient acceptability of intravitreal complement inhibitors in geographic atrophy (GA): protocol for a UK-based cross-sectional study.

    Dinah, Christiana / Enoch, Jamie / Ghulakhszian, Arevik / Sekhon, Mandeep / Crabb, David P / Taylor, Deanna J

    BMJ open

    2024  Volume 14, Issue 1, Page(s) e075713

    Abstract: Introduction: Geographic atrophy (GA) is the advanced form of the non-neovascular ('dry') type of age-related macular degeneration (AMD). Previously untreatable, complement inhibitors delivered by regular intravitreal injections have recently been ... ...

    Abstract Introduction: Geographic atrophy (GA) is the advanced form of the non-neovascular ('dry') type of age-related macular degeneration (AMD). Previously untreatable, complement inhibitors delivered by regular intravitreal injections have recently been demonstrated to slow down the progression of GA lesions in phase 3 trials. One such treatment, Syfovre (pegcetacoplan), was approved by the US Food and Drug Administration in February 2023. These therapies slow down, but do not stop or reverse, the progression of GA; they may also increase the risk of developing the neovascular ('wet') type of AMD. In light of these developments, this study aims to quantify the acceptability of these new intravitreal injection treatments to patients with GA in the UK and explore factors that may influence the acceptability of these treatments.
    Methods and analysis: In this cross-sectional, non-interventional study, the primary objective is to determine the proportion of patients with GA that find regular intravitreal therapy acceptable for slowing the progression of GA. We will use a validated acceptability questionnaire in order to quantify the acceptability of new treatments among patients with GA. The correlation between acceptability and functional and structural biomarkers of GA will be established. We will also explore demographic, general health and ocular factors that may influence acceptability. 180 individuals with a diagnosis of GA will be recruited from 7 to 8 participating National Health Service trusts across the UK. Multiple regression analysis will be conducted to determine the simultaneous effects of multiple factors on patient acceptability.
    Ethics and dissemination: The study received ethical approval from the Health Research Authority on 14 March 2023 (IRAS Project ID: 324854). Findings will be disseminated through peer-reviewed publications and conference presentations to the medical retina community, as well as through dialogue with patients and macular disease charities.
    MeSH term(s) Humans ; Geographic Atrophy/drug therapy ; Cross-Sectional Studies ; Complement Inactivating Agents/therapeutic use ; State Medicine ; Macular Degeneration/drug therapy ; United Kingdom ; Intravitreal Injections ; Angiogenesis Inhibitors/therapeutic use ; Wet Macular Degeneration/drug therapy
    Chemical Substances Complement Inactivating Agents ; Angiogenesis Inhibitors
    Language English
    Publishing date 2024-01-18
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2599832-8
    ISSN 2044-6055 ; 2044-6055
    ISSN (online) 2044-6055
    ISSN 2044-6055
    DOI 10.1136/bmjopen-2023-075713
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Measures of multiple deprivation and visual field loss in glaucoma clinics in England: lessons from big data.

    Rathore, Mehal / Shweikh, Yusrah / Kelly, Stephen R / Crabb, David P

    Eye (London, England)

    2023  Volume 37, Issue 17, Page(s) 3615–3620

    Abstract: Background/objectives: To examine the association between multiple deprivation with late diagnosis and rapid worsening of glaucoma in patients in English hospital eye services (HES).: Methods: 602,439 visual fields (VFs) were extracted from five ... ...

    Abstract Background/objectives: To examine the association between multiple deprivation with late diagnosis and rapid worsening of glaucoma in patients in English hospital eye services (HES).
    Methods: 602,439 visual fields (VFs) were extracted from five regionally different glaucoma clinics in England. Mean Deviation (MD) worse than -12 dB was used as a surrogate definition for advanced VF loss at diagnosis in patients with ≥2 reliable VF records. MD loss worse than -1 dB per year was used to define rapid VF progression in patients with ≥6 VFs. Patient data were stratified into deciles of the Index of Multiple Deprivation (IMD) from residential postcodes.
    Results: There was an association between IMD and advanced VF loss at diagnosis in 44,956 patients with 18% (293/1608) and 11% (771/6929) in the most and least deprived IMD decile, respectively. Age-corrected odds ratio (OR) for having advanced VF loss at entry into HES was 1.42 (95% confidence interval [CI] 1.21-1.67) and 0.75 (95% CI: 0.66-0.85) in the most and least deprived IMD decile respectively (reference = fifth decile). In 15,094 patients with follow up data (median [interquartile range] of 6.9 [4.5, 10.0] years), the proportion having rapid VF progression did not differ across the IMD spectrum.
    Conclusion: Large-scale VF data from clinics indicates that glaucoma severity at presentation to English HES is associated with levels of multiple deprivation. We found no evidence to suggest likelihood of having rapid VF progression during follow-up is associated with IMD; this hints at equity of glaucoma care and outcomes once patients are in English HES.
    MeSH term(s) Humans ; Visual Fields ; Big Data ; Retrospective Studies ; Disease Progression ; Glaucoma/diagnosis ; Glaucoma/complications ; Visual Field Tests ; England/epidemiology ; Vision Disorders/diagnosis ; Vision Disorders/epidemiology ; Intraocular Pressure
    Language English
    Publishing date 2023-05-10
    Publishing country England
    Document type Journal Article
    ZDB-ID 91001-6
    ISSN 1476-5454 ; 0950-222X
    ISSN (online) 1476-5454
    ISSN 0950-222X
    DOI 10.1038/s41433-023-02567-z
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Letter to the Editor: Expected Improvement in Structure-Function Agreement With Macular Displacement Models.

    Montesano, Giovanni / Garway-Heath, David F / Crabb, David P

    Translational vision science & technology

    2022  Volume 11, Issue 10, Page(s) 14

    MeSH term(s) Humans ; Macular Edema ; Retinal Diseases
    Language English
    Publishing date 2022-10-11
    Publishing country United States
    Document type Letter ; Comment
    ZDB-ID 2674602-5
    ISSN 2164-2591 ; 2164-2591
    ISSN (online) 2164-2591
    ISSN 2164-2591
    DOI 10.1167/tvst.11.10.14
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Estimating the Distribution of True Rates of Visual Field Progression in Glaucoma.

    Montesano, Giovanni / Crabb, David P / Wright, David M / Rabiolo, Alessandro / Ometto, Giovanni / Garway-Heath, David F

    Translational vision science & technology

    2024  Volume 13, Issue 4, Page(s) 15

    Abstract: Purpose: The purpose of this study was to estimate the distribution of the true rates of progression (RoP) of visual field (VF) loss.: Methods: We analyzed the progression of mean deviation over time in series of ≥ 10 tests from 3352 eyes (one per ... ...

    Abstract Purpose: The purpose of this study was to estimate the distribution of the true rates of progression (RoP) of visual field (VF) loss.
    Methods: We analyzed the progression of mean deviation over time in series of ≥ 10 tests from 3352 eyes (one per patient) from 5 glaucoma clinics, using a novel Bayesian hierarchical Linear Mixed Model (LMM); this modeled the random-effect distribution of RoPs as the sum of 2 independent processes following, respectively, a negative exponential distribution (the "true" distribution of RoPs) and a Gaussian distribution (the "noise"), resulting in a skewed exGaussian distribution. The exGaussian-LMM was compared to a standard Gaussian-LMM using the Watanabe-Akaike Information Criterion (WAIC). The random-effect distributions were compared to the empirical cumulative distribution function (eCDF) of linear regression RoPs using a Kolmogorov-Smirnov test.
    Results: The WAIC indicated a better fit with the exGaussian-LMM (estimate [standard error]: 192174.4 [721.2]) than with the Gaussian-LMM (192595 [697.4], with a difference of 157.2 [22.6]). There was a significant difference between the eCDF and the Gaussian-LMM distribution (P < 0.0001), but not with the exGaussian-LMM distribution (P = 0.108). The estimated mean (95% credible intervals, CIs) "true" RoP (-0.377, 95% CI = -0.396 to -0.359 dB/year) was more negative than the observed mean RoP (-0.283, 95% CI = -0.299 to -0.268 dB/year), indicating a bias likely due to learning in standard LMMs.
    Conclusions: The distribution of "true" RoPs can be estimated with an exGaussian-LMM, improving model accuracy.
    Translational relevance: We used these results to develop a fast and accurate analytical approximation for sample-size calculations in clinical trials using standard LMMs, which was integrated in a freely available web application.
    MeSH term(s) Humans ; Visual Fields ; Bayes Theorem ; Glaucoma/diagnosis ; Eye ; Software
    Language English
    Publishing date 2024-04-09
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2674602-5
    ISSN 2164-2591 ; 2164-2591
    ISSN (online) 2164-2591
    ISSN 2164-2591
    DOI 10.1167/tvst.13.4.15
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Improving the Power of Glaucoma Neuroprotection Trials Using Existing Visual Field Data.

    Montesano, Giovanni / Quigley, Harry A / Crabb, David P

    American journal of ophthalmology

    2021  Volume 229, Page(s) 127–136

    Abstract: Purpose: Selecting reliable visual field (VF) test takers could improve the power of randomized clinical trials in glaucoma. We test this hypothesis via simulations using a large real world data set.: Design: Methodology analysis: assessment of how ... ...

    Abstract Purpose: Selecting reliable visual field (VF) test takers could improve the power of randomized clinical trials in glaucoma. We test this hypothesis via simulations using a large real world data set.
    Design: Methodology analysis: assessment of how improving reliability affects sample size estimates.
    Methods: A variability index (VI) estimating intertest variability was calculated for each subject using the residuals of the regression of the mean deviation over time for the first 6 tests in a series of at least 10 examinations for 2,804 patients. Using data from the rest of the series, we simulate VFs at regular intervals for 2 years. To simulate the neuroprotective effect (NE), we reduced the observed progression rate by 20%, 30%, or 50%. The main outcome measure was the sample size to detect a significant difference (P < .05) at 80% power.
    Results: In the first experiment, we simulated a trial including one eye per subject, either selecting randomly from the database or prioritizing patients with low VI. We could not reach 80% power for the low NE with the available patients, but the sample size was reduced by 38% and 49% for the 30% and 50% NE, respectively. In the second experiment, we simulated 2 eyes per subject, one of which was the control eye. The sample size (smaller overall) was reduced by 26% and 38% for the 30% and 50% NE by prioritizing patients with low VI.
    Conclusions: Selecting patients with low intertest variability can significantly improve the power and reduce the sample size needed in a trial.
    MeSH term(s) Disease Progression ; Glaucoma/drug therapy ; Humans ; Intraocular Pressure ; Neuroprotection ; Randomized Controlled Trials as Topic ; Reproducibility of Results ; Vision Disorders/prevention & control ; Visual Field Tests ; Visual Fields
    Language English
    Publishing date 2021-04-24
    Publishing country United States
    Document type Journal Article
    ZDB-ID 80030-2
    ISSN 1879-1891 ; 0002-9394
    ISSN (online) 1879-1891
    ISSN 0002-9394
    DOI 10.1016/j.ajo.2021.04.008
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Reply.

    Higgins, Bethany E / Montesano, Giovanni / Wright, David M / Hogg, Ruth E / Crabb, David P

    Ophthalmology science

    2023  Volume 3, Issue 3, Page(s) 100377

    Language English
    Publishing date 2023-08-03
    Publishing country Netherlands
    Document type Journal Article
    ISSN 2666-9145
    ISSN (online) 2666-9145
    DOI 10.1016/j.xops.2023.100377
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Piloting a forced-choice task to elicit treatment preferences in geographic atrophy.

    Enoch, Jamie / Ghulakhszian, Arevik / Sekhon, Mandeep / Crabb, David P / Taylor, Deanna J / Dinah, Christiana

    BMC research notes

    2023  Volume 16, Issue 1, Page(s) 244

    Abstract: Objective: Geographic Atrophy (GA) is the advanced form of the non-neovascular ('dry') type of age-related macular degeneration (AMD) and responsible for one-quarter of legal blindness in the UK. New therapies delivered by intravitreal injection are in ... ...

    Abstract Objective: Geographic Atrophy (GA) is the advanced form of the non-neovascular ('dry') type of age-related macular degeneration (AMD) and responsible for one-quarter of legal blindness in the UK. New therapies delivered by intravitreal injection are in late-stage development, and two such therapies (pegcetacoplan (Syfovre) and avacincaptad pegol (Izervay)) have now been approved for clinical use by the US Food and Drug Administration. These therapies slow down, but do not stop or reverse, progression of GA and they may also increase the risk of developing the neovascular ('wet') type of AMD. Within a larger study exploring the acceptability of these new treatments to people living with GA, we developed a forced-choice exercise to evaluate how participants weigh up benefits and drawbacks of different treatment regimens. This research note reports quantitative and qualitative findings from this exercise.
    Results: Twenty-eight participants took part in this exercise. The exercise demonstrated that participants were generally, although not unanimously, in favour of less frequent treatment for GA that was slightly less efficacious in terms of preserving visual function but presented a lower risk of developing wet AMD. Even among a small sample, the exercise demonstrated the highly personal and idiosyncratic decision-making processes influencing participants' choices of preferred hypothetical GA treatment.
    MeSH term(s) Humans ; Geographic Atrophy/drug therapy ; Macular Degeneration/drug therapy
    Language English
    Publishing date 2023-09-30
    Publishing country England
    Document type Journal Article
    ZDB-ID 2413336-X
    ISSN 1756-0500 ; 1756-0500
    ISSN (online) 1756-0500
    ISSN 1756-0500
    DOI 10.1186/s13104-023-06531-8
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Improving the Accuracy and Speed of Visual Field Testing in Glaucoma With Structural Information and Deep Learning.

    Montesano, Giovanni / Lazaridis, Georgios / Ometto, Giovanni / Crabb, David P / Garway-Heath, David F

    Translational vision science & technology

    2023  Volume 12, Issue 10, Page(s) 10

    Abstract: Purpose: To assess the performance of a perimetric strategy using structure-function predictions from a deep learning (DL) model.: Methods: Visual field test-retest data from 146 eyes (75 patients) with glaucoma with (median [5th-95th percentile]) 10 ...

    Abstract Purpose: To assess the performance of a perimetric strategy using structure-function predictions from a deep learning (DL) model.
    Methods: Visual field test-retest data from 146 eyes (75 patients) with glaucoma with (median [5th-95th percentile]) 10 [7, 10] tests per eye were used. Structure-function predictions were generated with a previously described DL model using cicumpapillary optical coherence tomography (OCT) scans. Structurally informed prior distributions were built grouping the observed measured sensitivities for each predicted value and recalculated for each subject with a leave-one-out approach. A zippy estimation by sequential testing (ZEST) strategy was used for the simulations (1000 per eye). Ground-truth sensitivities for each eye were the medians of the test-retest values. Two variations of ZEST were compared in terms of speed (average total number of presentations [NP] per eye) and accuracy (average mean absolute error [MAE] per eye), using either a combination of normal and abnormal thresholds (ZEST) or the calculated structural distributions (S-ZEST) as prior information. Two additional versions of these strategies employing spatial correlations were tested.
    Results: S-ZEST was significantly faster, with a mean average NP of 213.87 (SD = 28.18), than ZEST, with a mean average NP of 255.65 (SD = 50.27) (P < 0.001). The average MAE was smaller for S-ZEST (1.98; SD = 2.37) than ZEST (2.43; SD = 2.69) (P < 0.001). Spatial correlations further improved both strategies (P < 0.001), but the differences between ZEST and S-ZEST remained significant (P < 0.001).
    Conclusions: DL structure-function predictions can significantly improve perimetric tests.
    Translational relevance: DL structure-function predictions from clinically available OCT scans can improve perimetry in glaucoma patients.
    MeSH term(s) Humans ; Visual Field Tests/methods ; Visual Fields ; Deep Learning ; Algorithms ; Glaucoma/diagnosis ; Retinal Ganglion Cells
    Language English
    Publishing date 2023-10-13
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2674602-5
    ISSN 2164-2591 ; 2164-2591
    ISSN (online) 2164-2591
    ISSN 2164-2591
    DOI 10.1167/tvst.12.10.10
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  10. Article: Towards a Therapy for Geographic Atrophy: A Patient's Experience.

    Enoch, Jamie / Ghulakhszian, Arevik / Sekhon, Mandeep / Crabb, David P / Taylor, Deanna J / Dinah, Christiana

    Patient preference and adherence

    2023  Volume 17, Page(s) 299–310

    Abstract: Purpose: Geographic atrophy (GA) is the advanced form of the non-neovascular (dry) type of age-related macular degeneration. Presently, GA cannot be treated. However, new therapies administered by intravitreal injection are in late-stage development. ... ...

    Abstract Purpose: Geographic atrophy (GA) is the advanced form of the non-neovascular (dry) type of age-related macular degeneration. Presently, GA cannot be treated. However, new therapies administered by intravitreal injection are in late-stage development. These can slow down, but do not stop or reverse, GA progression. The acceptability of these emerging therapies to people with GA is currently unknown. The present case study explores the perspectives of a person living with GA who took part in the terminated Phase 3 clinical trial of Lampalizumab, a candidate intravitreal treatment for GA. We explored this patient's perspective on the retrospective acceptability of regular Lampalizumab injections, and the prospective acceptability of future intravitreal therapies for GA.
    Patients and methods: A 78-year-old woman living in the UK was recruited as part of a mixed-methods pilot study and interviewed by telephone, regarding: her experience of the Lampalizumab trial injections; and her thoughts regarding emerging intravitreal therapies for GA. The Framework Method was used for initial inductive analysis of the interview transcript. Subsequently, deductive analysis was undertaken, informed by the Theoretical Framework of Acceptability (TFA).
    Results: For this participant, intravitreal injections in the Lampalizumab trial were acceptable, although streamlining processes within the clinic would have improved the patient experience. Regarding prospective acceptability of new intravitreal therapies, the participant considered a delay in progression of GA a valuable goal. Potential discomfort, anxiety and inconvenience associated with regular intravitreal injections would be acceptable in the context of preserving her vision for as long as possible.
    Conclusion: Analysis of one participant's experience demonstrates the value of exploring GA patients' unique views on the acceptability of new intravitreal treatments. Larger prospective studies will provide more insight that help to optimise treatment design and delivery, thereby maximising likelihood of adherence and persistence when these therapies eventually arrive in clinic.
    Language English
    Publishing date 2023-02-01
    Publishing country New Zealand
    Document type Case Reports
    ZDB-ID 2455848-5
    ISSN 1177-889X
    ISSN 1177-889X
    DOI 10.2147/PPA.S386662
    Database MEDical Literature Analysis and Retrieval System OnLINE

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