Publications by authors named "Praveen J Patel"

99 Publications

Clinical update on metamorphopsia: epidemiology, diagnosis and imaging.

Curr Eye Res 2021 Apr 7. Epub 2021 Apr 7.

NIHR Biomedical Research Centre at Moorfields Eye Hospital and UCL Institute of Ophthalmology, London, United Kingdom.

Purpose: To discuss the pathophysiology of metamorphopsia, its characterisation using retinal imaging and methods of assessment of patient symptoms and visual function.

Methods: A literature search of electronic databases was performedResults: Metamorphopsia has commonly been associated with vitreomacular interface disorders (such as epiretinal membrane) and has also regularly been noted in diseases of the retina and choroid, particularly age-related macular degeneration and central serous chorioretinopathy. Developments in optical coherence tomography retinal imaging have enabled improved imaging of the foveal microstructure and have led to the localisation of the pathophysiology of metamorphopsia within the retinal layers of the macula. Alteration of alignment of inner and outer retinal layers at various retinal loci has been identified using multimodal imaging in patients with metamorphopsia in a range of conditions. Although the Amsler Grid assessment of metamorphopsia is a useful clinical indicator, new emerging methods of metamorphopsia assessment with psychophysical tests such as M-CHARTS and preferential hyperacuity perimetry, have been developed.

Conclusions: It appears that there is a complex relationship between visual acuity and metamorphopsia symptoms that vary between retinal conditions. Although metamorphopsia has traditionally been challenging to measure in the clinic, advances in technology promise more robust, easy-to-use tests. It is possible that home assessment of metamorphopsia, particularly in conditions such as age-related macular degeneration, may help to guide the need for further clinic evaluation and consideration of treatment.
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http://dx.doi.org/10.1080/02713683.2021.1912779DOI Listing
April 2021

Alcohol Consumption and Incident Cataract Surgery in Two Large UK Cohorts.

Ophthalmology 2021 Feb 8. Epub 2021 Feb 8.

NIHR Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust & UCL Institute of Ophthalmology, London, United Kingdom; Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom.

Purpose: To examine the association of alcohol consumption and type of alcoholic beverage with incident cataract surgery in 2 large cohorts.

Design: Longitudinal, observational study.

Participants: We included 469 387 participants of UK Biobank with a mean age of 56 years and 23 162 participants of European Prospective Investigation of Cancer (EPIC)-Norfolk with a mean age of 59 years.

Methods: Self-reported alcohol consumption at baseline was ascertained by a touchscreen questionnaire in UK Biobank and a food-frequency questionnaire in EPIC-Norfolk. Cases were defined as participants undergoing cataract surgery in either eye as ascertained via data linkage to National Health Service procedure statistics. We excluded participants with cataract surgery up to 1 year after the baseline assessment visit or those with self-reported cataract at baseline. Cox proportional hazards models were used to examine the associations of alcohol consumption with incident cataract surgery, adjusted for age, sex, ethnicity, Townsend deprivation index, body mass index (BMI), smoking, and diabetes status.

Main Outcome Measures: Incident cataract surgery.

Results: There were 19 011 (mean cohort follow-up of 95 months) and 4573 (mean cohort follow-up of 193 months) incident cases of cataract surgery in UK Biobank and EPIC-Norfolk, respectively. Compared with nondrinkers, drinkers were less likely to undergo cataract surgery in UK Biobank (hazard ratio [HR], 0.89; 95% confidence interval [CI], 0.85-0.93) and EPIC-Norfolk (HR, 0.90; 95% CI, 0.84-0.97) after adjusting for covariables. Among alcohol consumers, greater alcohol consumption was associated with a reduced risk of undergoing cataract surgery in EPIC-Norfolk (P < 0.001), whereas a U-shaped association was observed in the UK Biobank. Compared with nondrinkers, subgroup analysis by type of alcohol beverage showed the strongest protective association with wine consumption; the risk of incident cataract surgery was 23% and 14% lower among those in the highest category of wine consumption in EPIC-Norfolk and UK Biobank, respectively.

Conclusions: Our findings suggest a lower risk of undergoing cataract surgery with low to moderate alcohol consumption. The association was particularly apparent with wine consumption. We cannot exclude the possibility of residual confounding, and further studies are required to determine whether this association is causal in nature.
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http://dx.doi.org/10.1016/j.ophtha.2021.02.007DOI Listing
February 2021

Predicting Incremental and Future Visual Change in Neovascular Age-Related Macular Degeneration Using Deep Learning.

Ophthalmol Retina 2021 Jan 28. Epub 2021 Jan 28.

NIHR Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust, UCL Institute of Ophthalmology, London, United Kingdom. Electronic address:

Purpose: To evaluate the predictive usefulness of quantitative imaging biomarkers, acquired automatically from OCT scans, of cross-sectional and future visual outcomes of patients with neovascular age-related macular degeneration (AMD) starting anti-vascular endothelial growth factor (VEGF) therapy.

Design: Retrospective cohort study.

Participants: Treatment-naive, first-treated eyes of patients with neovascular AMD between 2007 and 2017 at Moorfields Eye Hospital (a large, United Kingdom single center) undergoing anti-VEGF therapy.

Methods: Automatic segmentation was carried out by applying a deep learning segmentation algorithm to 137 379 OCT scans from 6467 eyes of 3261 patients with neovascular AMD. After applying selection criteria, 926 eyes of 926 patients were analyzed.

Main Outcome Measures: Correlation coefficients (R values) and mean absolute error (MAE) between quantitative OCT (qOCT) parameters and cross-sectional visual function, as well as the predictive value of these parameters for short-term visual change, that is, incremental visual acuity (VA) resulting from an individual injection, as well as VA at distant time points (up to 12 months after baseline).

Results: Visual acuity at distant time points could be predicted: R = 0.80 (MAE, 5.0 Early Treatment Diabetic Retinopathy Study [ETDRS] letters) and R = 0.7 (MAE, 7.2 ETDRS letters) after injection at 3 and at 12 months after baseline (P < 0.001 for both), respectively. Best performing models included both baseline qOCT parameters and treatment response. Furthermore, we present proof-of-principle evidence that the incremental change in VA from an injection can be predicted: R = 0.14 (MAE, 5.6 ETDRS letters) for injection 2 and R = 0.11 (MAE, 5.0 ETDRS letters) for injection 3 (P < 0.001 for both).

Conclusions: Automatic segmentation enables rapid acquisition of quantitative and reproducible OCT biomarkers with potential to inform treatment decisions in the care of neovascular AMD. This furthers development of point-of-care decision-aid systems for personalized medicine.
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http://dx.doi.org/10.1016/j.oret.2021.01.009DOI Listing
January 2021

Association of ambient air pollution with age-related macular degeneration and retinal thickness in UK Biobank.

Br J Ophthalmol 2021 Jan 25. Epub 2021 Jan 25.

UCL Institute of Ophthalmology, National Institute for Health Research Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London, Greater London, UK.

Aim: To examine the associations of air pollution with both self-reported age-related macular degeneration (AMD), and in vivo measures of retinal sublayer thicknesses.

Methods: We included 115 954 UK Biobank participants aged 40-69 years old in this cross-sectional study. Ambient air pollution measures included particulate matter, nitrogen dioxide (NO) and nitrogen oxides (NO). Participants with self-reported ocular conditions, high refractive error (< -6 or > +6 diopters) and poor spectral-domain optical coherence tomography (SD-OCT) image were excluded. Self-reported AMD was used to identify overt disease. SD-OCT imaging derived photoreceptor sublayer thickness and retinal pigment epithelium (RPE) layer thickness were used as structural biomarkers of AMD for 52 602 participants. We examined the associations of ambient air pollution with self-reported AMD and both photoreceptor sublayers and RPE layer thicknesses.

Results: After adjusting for covariates, people who were exposed to higher fine ambient particulate matter with an aerodynamic diameter <2.5 µm (PM, per IQR increase) had higher odds of self-reported AMD (OR=1.08, p=0.036), thinner photoreceptor synaptic region (β=-0.16 µm, p=2.0 × 10), thicker photoreceptor inner segment layer (β=0.04 µm, p=0.001) and thinner RPE (β=-0.13 µm, p=0.002). Higher levels of PM absorbance and NO were associated with thicker photoreceptor inner and outer segment layers, and a thinner RPE layer. Higher levels of PM (PM with an aerodynamic diameter <10 µm) was associated with thicker photoreceptor outer segment and thinner RPE, while higher exposure to NO was associated with thinner photoreceptor synaptic region.

Conclusion: Greater exposure to PM was associated with self-reported AMD, while PM, PM absorbance, PM, NO and NO were all associated with differences in retinal layer thickness.
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http://dx.doi.org/10.1136/bjophthalmol-2020-316218DOI Listing
January 2021

Choroidal macrovessels: multimodal imaging findings and review of the literature.

Br J Ophthalmol 2021 Jan 4. Epub 2021 Jan 4.

Ocular Oncology Service, Moorfields Eye Hospital NHS Foundation Trust, London, UK.

Background/aims: To describe clinical and multimodal imaging features in a cohort of choroidal macrovessels.

Methods: Demographics and multimodal imaging features of 16 eyes of 13 patients with choroidal macrovessels were reviewed. The multimodal imaging included colour fundus photography, fundus autofluorescence (FAF), spectral domain enhanced depth imaging optical coherence tomography (OCT), en face OCT, OCT-angiography (OCT-A), B-scan ultrasonography (US), fluorescein angiography (FFA) and indocyanine green angiography (ICGA).

Results: Three patients had bilateral involvement. On colour fundus photography, three patterns were evident (a clearly visible orange-red vessel; a track of pigmentary changes; spots of mild pigmentary changes). Vessel orientation was horizontal (11 eyes), oblique (4 eyes) or vertical (1 eye). In 2 eyes, the vessel was extra-macular. OCT in all cases showed a hyporeflective choroidal area with posterior shadowing and elevation of the overlying retina. Subretinal fluid was present in 4 eyes. FAF (12 eyes) was normal (7 eyes) or showed a hypofluorescent/hyperfluorescent track (4 eyes) or linear hyperautofluorescence (1 eye). En-face OCT (2 eyes) revealed the course of the macrovessel at the level of choroid and choriocapillaris. On OCT-A (2 eyes) the vessel had a reflectivity similar to surrounding vessels but larger diameter. B-scan US (8 eyes) showed a nodular hypoechogenic lesion. FFA (5 eyes) showed early focal hyperfluorescence (4 eyes) not increasing in later phases, or was normal (1 eye). ICGA (6 eyes) showed early hyperfluorescence of the vessel.

Conclusions: Choroidal macrovessels can mimic other entities, leading to underdiagnosis. Appreciating relevant features on different imaging modalities will aid a correct diagnosis.
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http://dx.doi.org/10.1136/bjophthalmol-2020-318095DOI Listing
January 2021

Relationships between retinal layer thickness and brain volumes in the UK Biobank cohort.

Eur J Neurol 2021 May 20;28(5):1490-1498. Epub 2021 Jan 20.

NIHR Biomedical Research Centre, Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London, UK.

Background And Purpose: Current methods to diagnose neurodegenerative diseases are costly and invasive. Retinal neuroanatomy may be a biomarker for more neurodegenerative processes and can be quantified in vivo using optical coherence tomography (OCT), which is inexpensive and noninvasive. We examined the association of neuroretinal morphology with brain MRI image-derived phenotypes (IDPs) in a large cohort of healthy older people.

Methods: UK Biobank participants aged 40 to 69 years old underwent comprehensive examinations including ophthalmic and brain imaging assessments. Macular retinal nerve fibre layer (mRNFL), macular ganglion cell-inner plexiform layer (mGCIPL), macular ganglion cell complex (mGCC) and total macular thicknesses were obtained from OCT. Magnetic resonance imaging (MRI) IDPs assessed included total brain, grey matter, white matter and hippocampal volume. Multivariable linear regression models were used to evaluate associations between retinal layers thickness and brain MRI IDPs, adjusting for demographic factors and vascular risk factors.

Results: A total of 2131 participants (mean age 55 years; 51% women) with both gradable OCT images and brain imaging assessments were included. In multivariable regression analysis, thinner mGCIPL, mGCC and total macular thickness were all significantly associated with smaller total brain (p < 0.001), grey matter and white matter volume (p < 0.01), and grey matter volume in the occipital pole (p < 0.05). Thinner mGCC and total macular thicknesses were associated with smaller hippocampal volume (p < 0.02). No association was found between mRNFL and the MRI IDPs.

Conclusions: Markers of retinal neurodegeneration are associated with smaller brain volumes. Our findings suggest that retinal structure may be a biomarker providing information about important brain structure in healthy older adults.
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http://dx.doi.org/10.1111/ene.14706DOI Listing
May 2021

Phenotyping of retinal neovascularization in ischemic retinal vein occlusion using wide field OCT angiography.

Eye (Lond) 2020 Nov 30. Epub 2020 Nov 30.

NIHR Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London, UK.

Background/objectives: Abnormal retinal neovascularization caused by ischemic retinal vein occlusion (RVO) is a frequent cause of visually significant vitreous hemorrhage. The early detection of new vessels may be challenging and often requires the use of invasive tests such as fundus fluorescein angiography (FA). We demonstrate the use of wide-field optical coherence tomography angiography (WF-OCTA) in the detection and characterization of neovascularization secondary to ischemic RVO.

Subjects/methods: We conducted a retrospective observational case series of patients diagnosed with ischemic RVO between August 2018 and March 2019, who underwent WF-SS-OCTA imaging (PLEX Elite 9000, Carl Zeiss Meditec). We performed real-life montage imaging, covering the involved area and compared the findings of WF-SS-OCTA to standard clinical examination and when available, ultrawide-field fluorescein angiography (UWF-FA, Optos 200TX).

Results: In the included 39 eyes with ischemic RVO, neovascularization elsewhere (NVE) was encountered in 16 of 39 eyes (41%) on WF-OCTA and were characterized as sea-fan type vessels and nodular type vessels, based on their appearance and localization. NVE was identified in 4/39 eyes on standard clinical examination, equating to a detection rate of 10.3%. All were of a sea-fan morphology. In one case, NVE found on WF-OCTA was not observed on UWF-FA, which was a nodular type. Neovascularization of the disc (NVD) was detected in one eye.

Conclusions: WF-OCTA may become a useful noninvasive tool in the detection of neovascularization in patients with ischemic RVO. Furthermore, the characterization of different morphologies of neovascularization detected by WF-OCTA could be of clinical relevance.
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http://dx.doi.org/10.1038/s41433-020-01317-9DOI Listing
November 2020

Retinal asymmetry in multiple sclerosis.

Brain 2021 02;144(1):224-235

NIHR Biomedical Research Centre, Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London, UK.

The diagnosis of multiple sclerosis is based on a combination of clinical and paraclinical tests. The potential contribution of retinal optical coherence tomography (OCT) has been recognized. We tested the feasibility of OCT measures of retinal asymmetry as a diagnostic test for multiple sclerosis at the community level. In this community-based study of 72 120 subjects, we examined the diagnostic potential of the inter-eye difference of inner retinal OCT data for multiple sclerosis using the UK Biobank data collected at 22 sites between 2007 and 2010. OCT reporting and quality control guidelines were followed. The inter-eye percentage difference (IEPD) and inter-eye absolute difference (IEAD) were calculated for the macular retinal nerve fibre layer (RNFL), ganglion cell inner plexiform layer (GCIPL) complex and ganglion cell complex. Area under the receiver operating characteristic curve (AUROC) comparisons were followed by univariate and multivariable comparisons accounting for a large range of diseases and co-morbidities. Cut-off levels were optimized by ROC and the Youden index. The prevalence of multiple sclerosis was 0.0023 [95% confidence interval (CI) 0.00229-0.00231]. Overall the discriminatory power of diagnosing multiple sclerosis with the IEPD AUROC curve (0.71, 95% CI 0.67-0.76) and IEAD (0.71, 95% CI 0.67-0.75) for the macular GCIPL complex were significantly higher if compared to the macular ganglion cell complex IEPD AUROC curve (0.64, 95% CI 0.59-0.69, P = 0.0017); IEAD AUROC curve (0.63, 95% CI 0.58-0.68, P < 0.0001) and macular RNFL IEPD AUROC curve (0.59, 95% CI 0.54-0.63, P < 0.0001); IEAD AUROC curve (0.55, 95% CI 0.50-0.59, P < 0.0001). Screening sensitivity levels for the macular GCIPL complex IEPD (4% cut-off) were 51.7% and for the IEAD (4 μm cut-off) 43.5%. Specificity levels were 82.8% and 86.8%, respectively. The number of co-morbidities was important. There was a stepwise decrease of the AUROC curve from 0.72 in control subjects to 0.66 in more than nine co-morbidities or presence of neuromyelitis optica spectrum disease. In the multivariable analyses greater age, diabetes mellitus, other eye disease and a non-white ethnic background were relevant confounders. For most interactions, the effect sizes were large (partial ω2 > 0.14) with narrow confidence intervals. In conclusion, the OCT macular GCIPL complex IEPD and IEAD may be considered as supportive measurements for multiple sclerosis diagnostic criteria in a young patient without relevant co-morbidity. The metric does not allow separation of multiple sclerosis from neuromyelitis optica. Retinal OCT imaging is accurate, rapid, non-invasive, widely available and may therefore help to reduce need for invasive and more costly procedures. To be viable, higher sensitivity and specificity levels are needed.
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http://dx.doi.org/10.1093/brain/awaa361DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7880665PMC
February 2021

Insights From Survival Analyses During 12 Years of Anti-Vascular Endothelial Growth Factor Therapy for Neovascular Age-Related Macular Degeneration.

JAMA Ophthalmol 2021 01;139(1):57-67

Moorfields Eye Hospital National Health Service (NHS) Foundation Trust, London, United Kingdom.

Importance: Although multiple imputation models for missing data and the use of mixed-effects models generally provide better outcome estimates than using only observed data or last observation carried forward in clinical trials, such approaches usually cannot be applied to visual outcomes from retrospective analyses of clinical practice settings, also called real-world outcomes.

Objective: To explore the potential usefulness of survival analysis techniques for retrospective clinical practice visual outcomes.

Design, Setting, And Participants: This retrospective cohort study covered a 12-year observation period at a tertiary eye center. Of 10 744 eyes with neovascular age-related macular degeneration receiving anti-vascular endothelial growth factor (VEGF) therapy between October 28, 2008, and February 1, 2020, 7802 eyes met study criteria (treatment-naive, first-treated eyes starting anti-VEGF therapy). Eyes were excluded from the analysis if they received photodynamic therapy or macular laser, any previous anti-VEGF therapy, treatment with anti-VEGF agents other than ranibizumab or aflibercept, or had an unknown date or visual acuity (VA) value at first injection.

Main Outcomes And Measures: Kaplan-Meier estimates and Cox proportional hazards modeling were used to consider VA reaching an Early Treatment Diabetic Retinopathy Study (ETDRS) letter score of 70 (Snellen equivalent, 20/40) or better, duration of VA sustained at or better than 70 (20/40), and VA declining to 35 (20/200) or worse.

Results: A total of 7802 patients (mean [SD] age, 78.7 [8.8] years; 4776 women [61.2%]; and 4785 White [61.3%]) were included in the study. The median time to attaining a VA letter score greater than or equal to 70 (20/40) was 2.0 years (95% CI, 1.87-2.32) after the first anti-VEGF injection. Predictive features were baseline VA (hazard ratio [HR], 1.43 per 5 ETDRS letter score or 1 line; 95% CI, 1.40-1.46), baseline age (HR, 0.88 per 5 years; 95% CI, 0.86-0.90), and injection number (HR, 1.12; 95% CI, 1.10-1.15). Of the 4439 of 7802 patients (57%) attaining this outcome, median time sustained at an ETDRS letter score of 70 (20/40) or better was 1.1 years (95% CI, 1.1-1.2).

Conclusions And Relevance: In this cohort study, patients with neovascular age-related macular degeneration beginning anti-VEGF therapy were more likely to experience positive visual outcomes within the first 2.0 years after treatment, typically maintaining this outcome for 1.1 years but then deteriorating to poor vision within 8.7 years. These findings demonstrate the potential usefulness of the proposed analyses. This data set, combined with the statistical approach for retrospective analyses, may provide long-term prognostic information for patients newly diagnosed with this condition.
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http://dx.doi.org/10.1001/jamaophthalmol.2020.5044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7677877PMC
January 2021

Investigation of the efficacy of an online tool for improving the diagnosis of macular lesions imaged by optical coherence tomography.

J Optom 2021 Apr-Jun;14(2):206-214. Epub 2020 Oct 31.

Optometrist, Brooks and Wardman, Nottingham, UK.

Purpose: Optical coherence tomography (OCT) is a non-invasive method for diagnosis and monitoring of retinal (typically, macular) conditions. The unfamiliar nature of OCT images can present considerable challenges for some community optometrists. The purpose of this research is to develop and assess the efficacy of a novel internet resource designed to assist optometrists in using OCT for diagnosis of macular disease and patient management.

Methods: An online tool (OCTAID) has been designed to assist practitioners in the diagnosis of macular lesions detected by OCT. The effectiveness of OCTAID was evaluated in a randomised controlled trial comparing two groups of practitioners who underwent an online assessment (using clinical vignettes) based on OCT images, before (exam 1) and after (exam 2) an educational intervention. Participants' answers were validated against experts' classifications (the reference standard). OCTAID was randomly allocated as the educational intervention for one group with the control group receiving an intervention of standard OCT educational material. The participants were community optometrists.

Results: Random allocation resulted in 53 optometrists receiving OCTAID and 65 receiving the control intervention. Both groups performed similarly at baseline with no significant difference in mean exam 1 scores (p = 0.21). The primary outcome measure was mean improvement in exam score between the two exam modules. Participants who received OCTAID improved their exam score significantly more than those who received conventional educational materials (p = 0.005).

Conclusion: Use of OCTAID is associated with an improvement in the combined skill of OCT scan recognition and patient management decisions.
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http://dx.doi.org/10.1016/j.optom.2020.07.006DOI Listing
October 2020

Quantitative Analysis of OCT for Neovascular Age-Related Macular Degeneration Using Deep Learning.

Ophthalmology 2021 May 24;128(5):693-705. Epub 2020 Sep 24.

NIHR Biomedical Research Centre for Ophthalmology, Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London, United Kingdom; Google Health, London, United Kingdom.

Purpose: To apply a deep learning algorithm for automated, objective, and comprehensive quantification of OCT scans to a large real-world dataset of eyes with neovascular age-related macular degeneration (AMD) and make the raw segmentation output data openly available for further research.

Design: Retrospective analysis of OCT images from the Moorfields Eye Hospital AMD Database.

Participants: A total of 2473 first-treated eyes and 493 second-treated eyes that commenced therapy for neovascular AMD between June 2012 and June 2017.

Methods: A deep learning algorithm was used to segment all baseline OCT scans. Volumes were calculated for segmented features such as neurosensory retina (NSR), drusen, intraretinal fluid (IRF), subretinal fluid (SRF), subretinal hyperreflective material (SHRM), retinal pigment epithelium (RPE), hyperreflective foci (HRF), fibrovascular pigment epithelium detachment (fvPED), and serous PED (sPED). Analyses included comparisons between first- and second-treated eyes by visual acuity (VA) and race/ethnicity and correlations between volumes.

Main Outcome Measures: Volumes of segmented features (mm) and central subfield thickness (CST) (μm).

Results: In first-treated eyes, the majority had both IRF and SRF (54.7%). First-treated eyes had greater volumes for all segmented tissues, with the exception of drusen, which was greater in second-treated eyes. In first-treated eyes, older age was associated with lower volumes for RPE, SRF, NSR, and sPED; in second-treated eyes, older age was associated with lower volumes of NSR, RPE, sPED, fvPED, and SRF. Eyes from Black individuals had higher SRF, RPE, and serous PED volumes compared with other ethnic groups. Greater volumes of the majority of features were associated with worse VA.

Conclusions: We report the results of large-scale automated quantification of a novel range of baseline features in neovascular AMD. Major differences between first- and second-treated eyes, with increasing age, and between ethnicities are highlighted. In the coming years, enhanced, automated OCT segmentation may assist personalization of real-world care and the detection of novel structure-function correlations. These data will be made publicly available for replication and future investigation by the AMD research community.
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http://dx.doi.org/10.1016/j.ophtha.2020.09.025DOI Listing
May 2021

An open-source data set of anti-VEGF therapy in diabetic macular oedema patients over 4 years and their visual acuity outcomes.

Eye (Lond) 2021 May 26;35(5):1354-1364. Epub 2020 Jun 26.

Moorfields Eye Hospital, London, UK.

Objectives: The objective of this paper is to evaluate visual acuity (VA) outcomes of intravitreal anti-vascular endothelial growth factor (VEGF) in diabetic macular oedema (DMO).

Methods: In this retrospective cohort study, electronic medical records for all patients undergoing intravitreal injections in a tertiary referral centre between March 2013 and October 2018 were analysed. Treatment response in terms of VA outcomes was reported for all eyes over a 4-year observation period.

Results: Our cohort includes 2614 DMO eyes of 1964 patients over 48 months. Cox proportional-hazards modelling identified injection number (hazard ratio (HR) = 1.18), male gender (HR = 1.13) and baseline VA (HR = 1.09) as independent predictors to reach a favourable visual outcome of more than 70 Early Treatment Diabetic Retinopathy Study letters. Half of our cohort reached 70 letters 1.9 months after starting anti-VEGF therapy. Of those that reached 70 letters, 50% fell below 70 letters by 14.7 months.

Conclusion: To date, this is the largest single centre cohort study and over the longest observation period reporting on real-life outcomes of anti-VEGF in DMO. We have made an anonymised version of our data set available on an open-source data repository as a resource for clinical researchers globally.
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http://dx.doi.org/10.1038/s41433-020-1048-0DOI Listing
May 2021

Four-year outcomes of aflibercept treatment for neovascular age-related macular degeneration: Results from real-life setting.

Eur J Ophthalmol 2020 Jun 25:1120672120938565. Epub 2020 Jun 25.

NIHR Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London, UK.

Background: To assess long-term structural and functional outcomes of intravitreal aflibercept (Eylea) treatment for neovascular macular degeneration (nAMD) in a real-word setting.

Design And Methods: This was a retrospective, single-centre, non-randomized interventional cohort analysis. Data from treatment-naive patients with nAMD funded for treatment with intravitreal aflibercept in the period between 1 September 2013 and 28 February 2014 and who finished 4-year follow-up entered the analysis. Epidemiological data, visual acuity (VA) measured on ETDRS charts and injection numbers were recorded. Spectral domain optical coherence tomography (SD-OCT) data including presence or absence of macular fluid and automated central subfield macular thickness (CSMT) at year 1, 2, 3 and 4 were also recorded.

Results: Ninety-four eyes of 89 patients finished 4-year follow-up. The mean number of aflibercept injections received over 4 years was 19.3. At baseline, the mean VA (SD) (Snellen) was 54.1 ± 15.5 (20/100) ETDRS letters whilst the mean CSM (SD) was 296 ± 81 µm. At 4 years, the mean VA (SD) (Snellen) was 60.4 ± 20.0 (20/63) ETDRS letters ( < 0.0001). Mean CSMT (SD) was 218 ± 79 μm ( < 0.0001). Thirty-three percent of eyes gained ⩾15 ETDRS letters at end of 4 years, and 66 (70%) eyes had no macular fluid at the end of the follow-up.

Conclusion And Relevance: The results suggest that good long-term morphological and functional treatment outcomes can be achieved using intravitreal aflibercept for nAMD in a real-life clinical setting.
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http://dx.doi.org/10.1177/1120672120938565DOI Listing
June 2020

Individualizing Therapy for Neovascular Age-Related Macular Degeneration with Aflibercept (VITAL): A Two-Year Prospective, Interventional Single-Centre Trial.

Ophthalmol Ther 2020 Sep 18;9(3):563-576. Epub 2020 Jun 18.

NIHR Biomedical Research Centre At Moorfields Eye Hospital NHS Foundation Trust, UCL Institute of Ophthalmology, London, UK.

Aims: To report the mean change in Early Treatment Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity (BCVA) and reading performance (reading acuity and maximum reading speed (MRS) using the MNREAD test) between baseline and 24 months in treatment-naïve patients with neovascular age-related macular degeneration (nAMD) treated with intravitreal aflibercept injections.

Methods: A prospective, open-label, interventional non-randomised case series with 24 months' duration. Patients were recruited to the study from medical retina clinics at Moorfields Eye Hospital. Intravitreal injections of 2.0 mg aflibercept in the study eye were administered using a fixed dosing regimen during the first year and a treat-and-extend treatment regimen during the second year of treatment.

Results: Fifty patients were enrolled with a mean age (SD) of 78.7 (7.6) years; a mean BCVA of 62.8 ETDRS letters; mean reading acuity of 0.52 logMAR; mean maximum reading speed (MRS) of 141.3 words per minute and a central macular thickness of 322.6 µm at baseline. The mean improvement in BCVA was 6.4 letters for the 44 patients (88%) for whom data was available at 2 years. The mean improvement in reading acuity was 0.13 logMAR with an improvement in MRS of 2.9 words per minute. The mean reduction in CRT from baseline was 104.8 µm.

Conclusions: Aflibercept treatment of nAMD using fixed dosing in year 1 and treat and extend in year 2 leads to improvements in reading ability, visual acuity and retinal morphology which were maintained to 2 years of treatment.

Trial Registration: ClinicalTrials.gov Identifier NCT02441816, the VITAL study.
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http://dx.doi.org/10.1007/s40123-020-00267-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7406599PMC
September 2020

One-year real-life results on effect of intravitreal aflibercept in patients with diabetic macular oedema switched from ranibizumab.

Eur J Ophthalmol 2020 May 26:1120672120927275. Epub 2020 May 26.

NIHR Biomedical Research Centre, Moorfields Eye Hospital NHS Foundation Trust, UCL Institute of Ophthalmology, London, UK.

Purpose: To assess visual and optical coherence tomography-derived anatomical outcomes of treatment with intravitreal aflibercept (Eylea®) for diabetic macular oedema in patients switched from intravitreal ranibizumab (Lucentis®).

Design: Retrospective, cohort study.

Participants: Ninety eyes (of 67 patients) receiving intravitreal anti-vascular endothelial growth factor therapy were included.

Methods: This is a retrospective, real-life, cohort study. Each patient had visual acuity measurements and optical coherence tomography scans performed at baseline and 12 months after the first injection of aflibercept was given.

Main Outcome Measures: We measured visual acuities in Early Treatment Diabetic Retinopathy Study letters, central foveal thickness and macular volume at baseline and at 12 months after the first aflibercept injection was given.

Results: Ninety switched eyes were included in this study. The mean (standard deviation) visual acuity was 63 (15.78) Early Treatment Diabetic Retinopathy Study letters. At baseline, the mean (standard deviation) central foveal thickness was 417.7 (158.4) μm and the mean macular volume was 9.96 (2.44) mm. Mean change in visual acuity was +4 Early Treatment Diabetic Retinopathy Study letters (p = 0.0053). The mean change in macular volume was -1.53 mm in SW group (p = 0.21), while the change in central foveal thickness was -136.8 μm (p = 0.69).

Conclusion: There was a significant improvement in visual acuity and in anatomical outcomes in the switched group at 12 months after commencing treatment with aflibercept for diabetic macular oedema.
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http://dx.doi.org/10.1177/1120672120927275DOI Listing
May 2020

Intravitreal aflibercept for diabetic macular oedema in real-world: 36-month visual acuity and anatomical outcomes.

Eur J Ophthalmol 2020 May 19:1120672120925034. Epub 2020 May 19.

NIHR Biomedical Research Centre, Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London, UK.

Background/aims: To assess structural and functional outcomes of treatment with intravitreal aflibercept (®Eylea) for diabetic macular oedema in treatment-naïve patients.

Methods: Sixty-four eyes receiving intravitreal anti-vascular endothelial growth factor therapy were included in the data analysis of this retrospective, real-life study which follow-up was 3 years. Each patient had corrected visual acuity in Early Treatment Diabetic Retinopathy Study letters and optical coherence tomography central foveal thickness and macular volume performed at baseline, 12, 24 and 36 months. Patients were initiated on a loading phase of five 1-monthly intravitreal aflibercept injections, followed by injections if needed as per clinicians' discretion.

Results: The mean number of aflibercept injections received over 3 years was 12.59. At baseline, the mean visual acuity (standard deviation) (Snellen) was 61.45 (16.30) (20/63) Early Treatment Diabetic Retinopathy Study letters, the mean central foveal thickness (standard deviation) was 422 (138) µm, while the mean macular volume (standard deviation) was 9.51 (2.01) mm. At 36 months, the mean visual acuity (standard deviation) (Snellen) was 68.34 (13.66) (20/50) Early Treatment Diabetic Retinopathy Study letters (p = .0003). Mean central foveal thickness (standard deviation) was 303 (106) µm (p < .0001) and mean macular volume (standard deviation) was 8.35 (1.62) mm (p = .0022) at 36 months. Sixteen (25%) eyes gained ≥15 ETDRS letters at month 36, and 33 (52%) eyes had a decrease in central foveal thickness of ≥ 100 µm at the same time.

Conclusion: There was a significant improvement in visual acuity and in anatomical outcomes in aflibercept-treated eyes at 36 months after commencing treatment for diabetic macular oedema in real-life settings. The good vision and anatomical outcomes were maintained over second and third year of treatment with mean 2.93 and 2.57 intravitreal injections, respectively.
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http://dx.doi.org/10.1177/1120672120925034DOI Listing
May 2020

Ambient Air Pollution Associations with Retinal Morphology in the UK Biobank.

Invest Ophthalmol Vis Sci 2020 05;61(5):32

,.

Purpose: Because air pollution has been linked to glaucoma and AMD, we characterized the relationship between pollution and retinal structure.

Methods: We examined data from 51,710 UK Biobank participants aged 40 to 69 years old. Ambient air pollution measures included particulates and nitrogen oxides. SD-OCT imaging measured seven retinal layers: retinal nerve fiber layer, ganglion cell-inner plexiform layer, inner nuclear layer, outer plexiform layer + outer nuclear layer, photoreceptor inner segments, photoreceptor outer segments, and RPE. Multivariable regression was used to evaluate associations between pollutants (per interquartile range increase) and retinal thickness, adjusting for age, sex, race, Townsend deprivation index, body mass index, smoking status, and refractive error.

Results: Participants exposed to greater particulate matter with an aerodynamic diameter of <2.5 µm (PM2.5) and higher nitrogen oxides were more likely to have thicker retinal nerve fiber layer (β = 0.28 µm; 95% CI, 0.22-0.34; P = 3.3 × 10-20 and β = 0.09 µm; 95% CI, 0.04-0.14; P = 2.4 × 10-4, respectively), and thinner ganglion cell-inner plexiform layer, inner nuclear layer, and outer plexiform layer + outer nuclear layer thicknesses (P < 0.001). Participants resident in areas of higher levels of PM2.5 absorbance were more likely to have thinner retinal nerve fiber layer, inner nuclear layer, and outer plexiform layer + outer nuclear layers (β = -0.16 [95% CI, -0.22 to -0.10; P = 5.7 × 10-8]; β = -0.09 [95% CI, -0.12 to -0.06; P = 2.2 × 10-12]; and β = -0.12 [95% CI, -0.19 to -0.05; P = 8.3 × 10-4], respectively).

Conclusions: Greater exposure to PM2.5, PM2.5 absorbance, and nitrogen oxides were all associated with apparently adverse retinal structural features.
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http://dx.doi.org/10.1167/iovs.61.5.32DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7405693PMC
May 2020

Impact of injection frequency on 5-year real-world visual acuity outcomes of aflibercept therapy for neovascular age-related macular degeneration.

Eye (Lond) 2021 Feb 7;35(2):409-417. Epub 2020 Apr 7.

National Institute of Health Research Moorfields Biomedical Research Centre, Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London, UK.

Background: To evaluate the impact of injection frequency on yearly visual outcomes of patients treated with intravitreal aflibercept for neovascular age-related macular degeneration (nAMD) over a period of 5 years in a tertiary ophthalmic centre.

Design: Single centre, retrospective cohort study.

Participants: Consecutive treatment-naive nAMD patients initiated on aflibercept injections 5 years ago.

Methods: The Moorfields OpenEyes database was searched for consecutive patients who were initiated on intravitreal aflibercept for nAMD in 2013-14 and the visual acuity (VA) in Early Diabetic Retinopathy Study (ETDRS) letters and injection records per year were recorded for a period of 5 years. Analyses of the whole cohort and a sub-sample of 5-year completers were done. The cohort was further grouped into Group A (on continuous treatment), Group B (early cessation of treatment) and Group C (interrupted treatment) to evaluate the relation between treatment frequency and visual outcomes.

Main Outcome Measures: The primary end point was change in VA at 5 years; secondary outcomes included proportion of eyes that gained or maintained VA, number of injections received and the effect of treatment frequency.

Results: Data were collected on 468 patients (512 eyes). Sixty-six percent of the patients completed 5-year follow-up. The mean age of the whole cohort was 79.5 ± 8.5 years and the mean baseline VA was 58.3 ± 15.4 letters. Amongst the completers, final VA change was -2.9 (SD 23.4) ETDRS letters and the cumulative number of injections over 5 years was 24.2 (10.6). Group A had three letter gain and received significantly higher cumulative number of injections over 5 years than Group B and C (31.8, 14.6 and 18.4 respectively, p = 0.001). After adjusting for age and baseline VA, on average, final VA was +8.0 letters higher in the ≥20 injections group than the <20 group (p = 0.001).

Conclusions: Aflibercept therapy results in sustained good visual outcome over 5 years in neovascular AMD eyes when early and persistent treatment is given.
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http://dx.doi.org/10.1038/s41433-020-0851-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8026582PMC
February 2021

Widefield optical coherence tomography angiography for early detection and objective evaluation of proliferative diabetic retinopathy.

Br J Ophthalmol 2021 01 19;105(1):118-123. Epub 2020 Mar 19.

NIHR Biomedical Research Centre for Ophthalmology, Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London, UK.

Purpose: To evaluate the utility of widefield optical coherence tomography angiography (WF-OCTA) compared with clinical examination in grading diabetic retinopathy in patients diagnosed clinically with proliferative diabetic retinopathy (PDR) or severe non-proliferative diabetic retinopathy (NPDR).

Design: This retrospective observational case series included patients diagnosed clinically with PDR or severe NPDR. Patients underwent standard clinical examination and WF-OCTA imaging (PLEX Elite 9000, Carl Zeiss Meditec AG) using 12×12 montage scans between August 2018 and January 2019. Two trained graders identified neovascularisation at the disc (NVD) and neovascularisation elsewhere (NVE) on WF-OCTA which were compared with the clinical examination, and to ultra-widefield fluorescein angiography (UWFA) when available.

Results: Seventy-nine eyes of 46 patients were evaluated. Of those, 57 eyes were diagnosed clinically with PDR, and 22 with severe NPDR. NVD was detected on OCTA-B scan as preretinal hyperreflective material (PRHM) in 39 eyes (100%) with evident flow signals in 79.5% compared with 51.3% detected clinically. We further classified NVD on OCTA into four subtypes and found that subtypes 1 and 2 could not be seen on clinical examination alone. WF-OCTA detected NVE in 81% of the cases compared with 55.7% detected clinically. Using WF-OCTA resulted in a higher percentage of PDR grading (88.6%) than on clinical examination (72.2%). When available, UWFA confirmed the WF-OCTA diagnosis in the majority of cases.

Conclusion: This study demonstrates that WF-OCTA has a higher detection rate of PDR than clinical examination. This suggests that this modality could be used non-invasively for the purpose of early detection and characterisation of neovascularisation.
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http://dx.doi.org/10.1136/bjophthalmol-2019-315365DOI Listing
January 2021

Burden of Illness in Geographic Atrophy: A Study of Vision-Related Quality of Life and Health Care Resource Use.

Clin Ophthalmol 2020 8;14:15-28. Epub 2020 Jan 8.

Genentech, Inc., A Member of the Roche Group, South San Francisco, CA, USA.

Purpose: To gain comprehensive information on the burden of illness due to geographic atrophy (GA).

Methods: This cross-sectional study with a retrospective chart review involved patients aged ≥70 years with physician-confirmed bilateral symptomatic GA due to age-related macular degeneration (GA group), as well as patients of similar age with no ophthalmic condition that in the opinion of the investigator affected visual function (non-GA group). Data relating to patients' current disease status and sociodemographics were self-reported on patient questionnaires at study entry and extracted from patient charts. Historical data on health care resource utilization (HCRU) were also collected via patient questionnaires and retrospective chart review (GA group only). Overall vision-related functioning and quality of life (QoL) were compared between the GA and non-GA groups using the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) composite and subscales, and change in vision over the past year was assessed using the Global Rating of Change Scale.

Results: Vision-related functioning and QoL were poorer in patients with vs without GA (n=137 vs 52), as demonstrated by significantly lower NEI-VFQ-25 composite score (mean, 53.1 vs 84.5 points, respectively; <0.001), as well as lower subscale scores for near activities, distance activities, dependency, driving, social functioning, mental health, role difficulties, color vision, and peripheral vision. Substantially more patients with GA than without GA reported worsening in vision over the past year (82% vs 25%, respectively; odds ratio, 13.55; <0.001). In the GA group, associated mean annual costs for direct ophthalmological resource use per patient amounted to €1772 (mostly for tests/procedures), and for indirect ophthalmological resource use, €410 (mostly for general practitioner visits).

Conclusion: Patients with GA experience a poorer level of vision-related function and QoL than their peers, especially in relation to driving. GA is also associated with notable HCRU/associated costs, mostly direct costs attributed to diagnostic tests/procedures.
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http://dx.doi.org/10.2147/OPTH.S226425DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6955611PMC
January 2020

Recommendations by a UK expert panel on an aflibercept treat-and-extend pathway for the treatment of neovascular age-related macular degeneration.

Eye (Lond) 2020 10 3;34(10):1825-1834. Epub 2020 Jan 3.

Bayer plc, Reading, UK.

Objectives: This report aims to provide clear recommendations and practical guidance from a panel of UK retinal experts on an aflibercept treat-and-extend (T&E) pathway that can be implemented in clinical practice. These recommendations may help service providers across the NHS intending to implement a T&E approach, with the aim of effectively addressing the capacity and resource issues putting strain on UK neovascular age-related macular degeneration (nAMD) services while promoting patients' best interests throughout.

Methods: Two structured roundtable meetings of retinal specialists were held in London, UK on 7 December 2018 and 1 March 2019. These meetings were organised and funded by Bayer.

Results: The panel provided recommendations for an aflibercept T&E pathway and developed specific criteria based on visual acuity, retinal morphology and optical coherence tomography imaging to guide reduction, maintenance and extension of injection intervals. They also discussed the extension of treatment intervals by 2- or 4-week adjustments to a maximum treatment interval of 16 weeks, the management of retinal fluid and the stopping of treatment.

Conclusions: The long-term benefits of implementing a T&E pathway may include superior visual outcomes compared with a pro re nata (PRN; as needed) protocol, and a lower treatment burden compared with a fixed protocol, which is likely to improve service capacity. Furthermore, the predictable nature of a T&E approach compared with a PRN service may aid capacity planning for the future nAMD treatment demand.
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http://dx.doi.org/10.1038/s41433-019-0747-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7608090PMC
October 2020

Associations with photoreceptor thickness measures in the UK Biobank.

Sci Rep 2019 12 19;9(1):19440. Epub 2019 Dec 19.

NIHR Biomedical Research Centre, Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London, United Kingdom.

Spectral-domain OCT (SD-OCT) provides high resolution images enabling identification of individual retinal layers. We included 32,923 participants aged 40-69 years old from UK Biobank. Questionnaires, physical examination, and eye examination including SD-OCT imaging were performed. SD OCT measured photoreceptor layer thickness includes photoreceptor layer thickness: inner nuclear layer-retinal pigment epithelium (INL-RPE) and the specific sublayers of the photoreceptor: inner nuclear layer-external limiting membrane (INL-ELM); external limiting membrane-inner segment outer segment (ELM-ISOS); and inner segment outer segment-retinal pigment epithelium (ISOS-RPE). In multivariate regression models, the total average INL-RPE was observed to be thinner in older aged, females, Black ethnicity, smokers, participants with higher systolic blood pressure, more negative refractive error, lower IOPcc and lower corneal hysteresis. The overall INL-ELM, ELM-ISOS and ISOS-RPE thickness was significantly associated with sex and race. Total average of INL-ELM thickness was additionally associated with age and refractive error, while ELM-ISOS was additionally associated with age, smoking status, SBP and refractive error; and ISOS-RPE was additionally associated with smoking status, IOPcc and corneal hysteresis. Hence, we found novel associations of ethnicity, smoking, systolic blood pressure, refraction, IOP and corneal hysteresis with photoreceptor thickness.
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http://dx.doi.org/10.1038/s41598-019-55484-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6923366PMC
December 2019

The Relationship Between Ambient Atmospheric Fine Particulate Matter (PM2.5) and Glaucoma in a Large Community Cohort.

Invest Ophthalmol Vis Sci 2019 11;60(14):4915-4923

National Institute for Health Research (NIHR) Biomedical Research Centre at Moorfields Eye Hospital National Health Service Foundation Trust & UCL Institute of Ophthalmology, London, United Kingdom.

Purpose: Glaucoma is more common in urban populations than in others. Ninety percent of the world's population are exposed to air pollution above World Health Organization (WHO) recommended limits. Few studies have examined the association between air pollution and glaucoma.

Methods: Questionnaire data, ophthalmic measures, and ambient residential area air quality data for 111,370 UK Biobank participants were analyzed. Particulate matter with an aerodynamic diameter < 2.5 μm (PM2.5) was selected as the air quality exposure of interest. Eye measures included self-reported glaucoma, intraocular pressure (IOP), and average thickness of macular ganglion cell-inner plexiform layer (GCIPL) across nine Early Treatment Diabetic Retinopathy Study (ETDRS) retinal subfields as obtained from spectral-domain optical coherence tomography. We examined the associations of PM2.5 concentration with self-reported glaucoma, IOP, and GCIPL.

Results: Participants resident in areas with higher PM2.5 concentration were more likely to report a diagnosis of glaucoma (odds ratio = 1.06, 95% confidence interval [CI] = 1.01-1.12, per interquartile range [IQR] increase P = 0.02). Higher PM2.5 concentration was also associated with thinner GCIPL (β = -0.56 μm, 95% CI = -0.63 to -0.49, per IQR increase, P = 1.2 × 10-53). A dose-response relationship was observed between higher levels of PM2.5 and thinner GCIPL (P < 0.001). There was no clinically relevant relationship between PM2.5 concentration and IOP.

Conclusions: Greater exposure to PM2.5 is associated with both self-reported glaucoma and adverse structural characteristics of the disease. The absence of an association between PM2.5 and IOP suggests the relationship may occur through a non-pressure-dependent mechanism, possibly neurotoxic and/or vascular effects.
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http://dx.doi.org/10.1167/iovs.19-28346DOI Listing
November 2019

Objective Evaluation of Proliferative Diabetic Retinopathy Using OCT.

Ophthalmol Retina 2020 02 11;4(2):164-174. Epub 2019 Sep 11.

NIHR Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London, United Kingdom. Electronic address:

Purpose: To present the routine use of OCT and OCT angiography (OCTA) for the objective diagnosis and monitoring of proliferative diabetic retinopathy (PDR).

Design: Retrospective, observational case series.

Participants: Patients with diabetic retinopathy imaged using a standardized PDR protocol.

Methods: Patients routinely imaged with a standardized PDR protocol between March 2017 and January 2019 were included. This included a 12×9-mm structural OCT volume centered on the macula and a 6×6-mm OCTA scan centered on the optic nerve head obtained using a Topcon swept-source system (DRI OCT-1 Triton, Topcon, Tokyo, Japan). Ultra-widefield fluorescein angiography (FA) was also performed when clinically indicated. The ground truth for each case was determined by merging the findings from biomicroscopy and imaging modalities to generate the maximum level of detection for each finding.

Main Outcome Measures: Detection rates of new-onset, regression, and reactivation of neovascularization of the disc (NVD) and neovascularization elsewhere (NVE) using different modalities (biomicroscopy/color photography, structural OCT, B-scan OCTA, en face OCTA). Detection of progression of tractional retinal detachment (TRD).

Results: A total of 383 eyes of 204 patients were evaluated. After excluding patients without PDR or with insufficient image quality, 47 eyes of 35 patients were included. For the detection of new-onset NVD and NVE, structural OCT had the highest detection rate (100%) of all modalities. However, for the detection of regression or reactivation of neovascularization (NV), B-scan OCTA had the highest detection rate (100%). Structural OCT detected regression only in 45.5% of cases, resulting in a low detection rate of reactivation (12.5%). Among 10 eyes with TRD, OCT detected fovea-threatening TRD during follow-up in 7 eyes, resulting in vitrectomy.

Conclusions: This study demonstrates the utility of novel multimodal imaging in the daily management of patients with PDR. Posterior pole structural OCT had the best detection rate for NV, and B-scan OCTA showed the most potential for objective monitoring of disease after treatment.
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http://dx.doi.org/10.1016/j.oret.2019.09.004DOI Listing
February 2020

Moorfields AMD database report 2: fellow eye involvement with neovascular age-related macular degeneration.

Br J Ophthalmol 2020 05 14;104(5):684-690. Epub 2019 Oct 14.

NIHR Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, Moorfields Eye Hospital NHS Foundation Trust, London, UK

Background/aims: Neovascular age-related macular degeneration (nAMD) is frequently bilateral, and previous reports on 'fellow eyes' have assumed sequential treatment after a period of treatment of the first eye only. The aim of our study was to analyse baseline characteristics and visual acuity (VA) outcomes of fellow eye involvement with nAMD, specifically differentiating between sequential and non-sequential (due to macular scarring in the first eye) antivascular endothelial growth factor treatment and timelines for fellow eye involvement.

Methods: Retrospective, electronic medical record database study of the Moorfields AMD database of 6265 patients/120 286 single entries with data extracted between 21 October 2008 and 9 August 2018. The data set for analysis consisted of 1180 sequential, 807 non-sequential and 3410 unilateral eyes.

Results: Mean VA (ETDRS letters±SD) of sequentially treated fellow eyes at baseline was significantly higher (63±13), VA gain over 2 years lower (0.37±14) and proportion of eyes with good VA (≥70 letters) higher (46%) than the respective first eyes (baseline VA 54±16, VA gain at 2 years 5.6±15, percentage of eyes with good VA 39%). Non-sequential fellow eyes showed baseline characteristics and VA outcomes similar to first eyes. Fellow eye involvement rate was 32% at 2 years, and median time interval to fellow eye involvement was 71 (IQR: 27-147) weeks.

Conclusion: This report shows that sequentially treated nAMD fellow eyes have better baseline and final VA than non-sequentially treated eyes after 2 years of treatment. Sequentially treated eyes also had a greater proportion with good VA after 2 years.
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http://dx.doi.org/10.1136/bjophthalmol-2019-314446DOI Listing
May 2020

Comparison of Associations with Different Macular Inner Retinal Thickness Parameters in a Large Cohort: The UK Biobank.

Ophthalmology 2020 01 21;127(1):62-71. Epub 2019 Aug 21.

NIHR Biomedical Research Centre, Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London, United Kingdom; Discipline of Clinical Ophthalmology and Eye Health, University of Sydney Medical School, Sydney, Australia.

Purpose: To describe and compare associations with macular retinal nerve fiber layer (mRNFL), ganglion cell complex (GCC), and ganglion cell-inner plexiform layer (GCIPL) thicknesses in a large cohort.

Design: Cross-sectional study.

Participants: We included 42 044 participants in the UK Biobank. The mean age was 56 years.

Methods: Spectral-domain OCT macular images were segmented and analyzed. Corneal-compensated intraocular pressure (IOPcc) was measured with the Ocular Response Analyzer (Reichert, Corp., Buffalo, NY). Multivariable linear regression was used to examine associations with mean mRNFL, GCC, and GCIPL thicknesses. Factors examined were age, sex, ethnicity, height, body mass index (BMI), smoking status, alcohol intake, Townsend deprivation index, education level, diabetes status, spherical equivalent, and IOPcc.

Main Outcome Measures: Thicknesses of mRNFL, GCC, and GCIPL.

Results: We identified several novel independent associations with thinner inner retinal thickness. Thinner inner retina was associated with alcohol intake (most significant for GCIPL: -0.46 μm for daily or almost daily intake compared with special occasion only or never [95% confidence interval (CI), 0.61-0.30]; P = 1.1×10), greater social deprivation (most significant for GCIPL: -0.28 μm for most deprived quartile compared with least deprived quartile [95% CI, -0.42 to -0.14]; P = 6.6×10), lower educational attainment (most significant for mRNFL: -0.36 μm for less than O level compared with degree level [95% CI, -0.45 to 0.26]; P = 2.3×10), and nonwhite ethnicity (most significant for mRNFL comparing blacks with whites: -1.65 μm [95% CI, -1.86 to -1.43]; P = 2.4×10). Corneal-compensated intraocular pressure was associated most significantly with GCIPL (-0.04 μm/mmHg [95% CI, -0.05 to -0.03]; P = 4.0×10) and was not associated significantly with mRNFL (0.00 μm/mmHg [95% CI, -0.01 to 0.01]; P = 0.77). The variables examined explained a greater proportion of the variance of GCIPL (11%) than GCC (6%) or mRNFL (7%).

Conclusions: The novel associations we identified may be important to consider when using inner retinal parameters as a diagnostic tool. Associations generally were strongest with GCIPL, particularly for IOP. This suggests that GCIPL may be the superior inner retinal biomarker for macular pathophysiologic processes and especially for glaucoma.
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http://dx.doi.org/10.1016/j.ophtha.2019.08.015DOI Listing
January 2020

Effect of total anti-VEGF treatment exposure on patterns of choroidal neovascularisation assessed by optical coherence tomography angiography in age-related macular degeneration: a retrospective case series.

BMJ Open Ophthalmol 2019 9;4(1):e000244. Epub 2019 Apr 9.

Medical retina Department, Moorfields Eye Hospital NHS Foundation Trust, London, UK.

Objective: To compare clinical characteristics of patients suffering from neovascular age-related macular degeneration (nAMD) with mature and immature choroidal neovascularisation (CNV) as assessed by optical coherence tomography angiography (OCTA). To explore the effect of total anti-vascular endothelial growth factor exposure on the occurrence of mature CNV when correcting for potential confounders.

Methods And Analysis: In this retrospective case series, we included 40 eyes of 36 patients with nAMD with CNV assessed by OCTA at the Manchester Eye Hospital between June 2016 and June 2017. A retinal specialist masked to patient information graded CNV depicted on OCTA scans. For statistical comparisons, we used t-tests, Fisher's exact tests and a mixed-effects logistic regression model.

Results: 18 patients (20 eyes) were treatment naïve, and the mean number of intravitreal injections (IVI) in the remaining eyes was 18.4 (range 2-71). The mean duration of nAMD was 19.3 months (range 0-87.4). 25 eyes (62.5%) exhibited mature CNV. Eyes with mature CNV did not differ from those with immature CNV regarding age (+2.8 years; p=0.288) or duration of disease (+9.4 months; p=0.061). However, they had a higher number of IVIs (+3.1; p=0.035). Among eyes with best corrected visual acuity over 25 letters, there was a strong association between the number of IVIs (0 vs 1-20: OR 68.01 [95% CI 1.30 to 3546.99; p=0.036], 0 vs >20 IVI: OR 380.01 [95% CI 2.60 to 55 464.89; p=0.019]) and maturity status when correcting for potential confounders.

Conclusion: Maturity status of CNV as assessed by OCTA may indicate treatment exposure of CNV in nAMD.
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http://dx.doi.org/10.1136/bmjophth-2018-000244DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6528762PMC
April 2019

Swept-Source OCT and Near-Infrared Reflectance Patterns in Choroidal Nevi.

Ophthalmol Retina 2019 05 7;3(5):429-435. Epub 2019 Jan 7.

National Institute for Health and Research (NIHR) Biomedical Centre at Moorfields Eye Hospital and University College London Institute of Ophthalmology, London, United Kingdom; Ocular Oncology Service, St. Bartholomew's Hospital and Moorfields Eye Hospital, London, United Kingdom; University College London Institute of Ophthalmology, London, United Kingdom.

Purpose: To describe the 3 distinct patterns of choroidal nevi in swept-source (SS) OCT and apply that classification to a cohort of consecutive choroidal nevi. Also, we aim to describe the findings of these lesions in near-infrared reflectance (NIR) at different wavelengths (820 and 1050 nm).

Design: Single-center, retrospective, observational study.

Participants: One hundred four consecutive patients with choroidal nevi.

Methods: Retrospective analysis of choroidal nevi imaged with SS OCT and NIR.

Main Outcome Measures: Lesions were classified according to OCT patterns as type A (high reflectivity with optical shadowing), type B (medium reflectivity with partial visualization of the scleral boundary), and type C (hyporeflective with complete visualization of the scleral boundary).

Results: Of 104 choroidal nevi, 97 lesions (93.3%) could be classified into 1 of the SS OCT patterns. Forty-nine percent corresponded to type A, 26% corresponded to type C, and 18.3% corresponded to type B. In NIR (n = 820), 76% of lesions were hyperreflective, whereas in NIR (n = 1050), most of the lesions were hyporeflective (59.6%; inverse reflectance).

Conclusions: Choroidal nevi present distinct patterns according to SS OCT features. Clinical implications are yet to be determined. In NIR, inverse reflectance may be a consequence of the confocality of the device, rather than a property of the lesions.
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http://dx.doi.org/10.1016/j.oret.2019.01.001DOI Listing
May 2019

Action on neovascular age-related macular degeneration (nAMD): recommendations for management and service provision in the UK hospital eye service.

Eye (Lond) 2019 03;33(Suppl 1):1-21

The Action on nAMD Group, Birmingham, UK.

This report by a group of UK retina specialists and health professionals considers best practice recommendations for the management of sight-threatening neovascular age-related macular degeneration (nAMD), based on collective experience and expertise in routine clinical practice. The authors provide an update for ophthalmologists, allied healthcare professionals and commissioners on practice principles for optimal patient care and service provision standards. Refinement of care pathways for nAMD has improved access to intravitreal anti-vascular endothelial growth factor therapy but there are still variations in care and reported outcomes between clinic centres. Innovative organisational models of service provision allow providers to better match capacity with increasing demand. The authors review the recent NICE guideline for diagnosis and management of AMD, considerations for switching therapies and stopping treatment and need for regular monitoring of non-affected fellow eyes in patients with unilateral nAMD. Actions for delivery of high-quality care and to improve long-term patient outcomes are discussed. Local pathways need to detail nAMD target time to treat, maintenance of review intervals to ensure proactive treatment regimens are delivered on time and appropriate discharge for patients deemed low risk or no longer benefiting from treatment. Actual visual acuity outcomes achieved and maintenance of the level of vision when disease stability is achieved are considered good measures for judging the quality of care in the treatment of patients with nAMD. Robust community referral pathways must be in place for suspected reactivation of choroidal neovascularisation and rapid referral for second eye involvement. Practical considerations for intravitreal injection therapy are outlined.
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http://dx.doi.org/10.1038/s41433-018-0300-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6474281PMC
March 2019

Intravitreal aflibercept for diabetic macular oedema: Moorfields' real-world 12-month visual acuity and anatomical outcomes.

Eur J Ophthalmol 2020 May 26;30(3):557-562. Epub 2019 Feb 26.

NIHR Biomedical Research Centre, Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London, UK.

Objectives: To assess structural and functional outcomes of treatment with intravitreal aflibercept (Eylea) for diabetic macular oedema in treatment-naive patients.

Design: This is a retrospective, real-life, cohort study.

Participants And Methods: In all, 92 diabetic patients (102 eyes) receiving intravitreal anti-vascular endothelial growth factor therapy were included. A total of 99 aflibercept-treated eyes were included in the statistical analysis. Each patient had corrected visual acuity in Early Treatment Diabetic Retinopathy Study letters and optical coherence tomography central foveal thickness and macular volume performed at baseline and 12 months. Patients were initiated on a loading phase of five monthly intravitreal aflibercept injections, followed by injections if needed as per clinicians' discretion.

Results: The mean number of aflibercept injections received was 6.92. At baseline, the mean visual acuity (standard deviation; Snellen) was 59.7 (16.1) (20/63) Early Treatment Diabetic Retinopathy Study letters, the mean central foveal thickness (standard deviation) was 431 (129) µm, while the mean macular volume (standard deviation) was 9.53 (1.79) mm. At 12 months, the mean visual acuity (standard deviation; Snellen) was 69.6 (15.2; 20/40) Early Treatment Diabetic Retinopathy Study letters (p < .0001). Mean central foveal thickness (standard deviation) was 306 (122) μm (p < .0001) and mean macular volume (standard deviation) was 8.43 (1.58) mm (p < .0001) at 12 months; 33 (33.67%) eyes gained ⩾15 Early Treatment Diabetic Retinopathy Study letters at month 12, and 50 (55.55%) eyes had a decrease in central foveal thickness of ⩾100 µm.

Conclusion: There was a significant improvement in visual acuity and in anatomical outcomes in aflibercept-treated eyes at 12 months after commencing treatment for diabetic macular oedema in real-life settings.
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http://dx.doi.org/10.1177/1120672119833270DOI Listing
May 2020