Estimating excess visual loss from neovascular age-related macular degeneration in the UK during the COVID-19 pandemic: a retrospective clinical audit and simulation model.

OBJECTIVES: To report the reduction in new neovascular age-related macular degeneration (nAMD) referrals during the COVID-19 pandemic and estimate the impact of delayed treatment on visual outcomes at 1 year. DESIGN: Retrospective clinical audit and simulation model. SETTING: Multiple UK National Health Service (NHS) ophthalmology centres. PARTICIPANTS: Data on the reduction in new nAMD referrals were obtained from four NHS Trusts comparing April 2020 with April 2019. To estimate the potential impact on 1-year visual outcomes, a stratified bootstrap simulation model was developed drawing on an electronic medical records dataset of 20 825 nAMD eyes from 27 NHS Trusts. MAIN OUTCOME MEASURES: Simulated mean visual acuity and proportions of eyes with vision ≤6/60, ≤6/24 and ≥6/12 at 1 year under four hypothetical scenarios: 0-month, 3-month, 6-month and 9-month treatment delays. Estimated additional number of eyes with vision ≤6/60 at 1 year nationally. RESULTS: The number of nAMD referrals dropped on average by 72% (range 65%-87%). Simulated 1-year visual outcomes for 1000 nAMD eyes with a 3-month treatment delay suggested an increase in the proportion of eyes with vision ≤6/60 from 15.5% (13.2%-17.9%) to 23.3% (20.7%-25.9%), and a decrease in the proportion of eyes with vision ≥6/12 (driving vision) from 35.1% (32.1%-38.1%) to 26.4% (23.8%-29.2%). Outcomes worsened incrementally with longer modelled delays. Assuming nAMD referrals are reduced to this level for 1 month nationally, these simulated results suggest an additional 186-365 eyes with vision ≤6/60 at 1 year. CONCLUSIONS: We report a large decrease in nAMD referrals during the COVID-19 lockdown and provide an important public health message regarding the risk of delayed treatment. As a conservative estimate, a treatment delay of 3 months could lead to a >50% relative increase in the number of eyes with vision ≤6/60 and 25% relative decrease in the number of eyes with driving vision at 1 year.

The long-term efficacy and safety of fluocinolone acetonide intravitreal implant 190 µg (ILUVIEN®) in diabetic macular oedema in a multi-ethnic inner-city population.

PURPOSE: The purpose of this study is to report the long-term efficacy and safety of 0.19 mg fluocinolone acetonide intravitreal implant (ILUVIEN®) in pseudophakic eyes with diabetic macular oedema in a multi-ethnic patient cohort. METHODS: This is a single-centre retrospective analysis of patients with persistent diabetic macular oedema, despite previous anti-vascular endothelial growth factor and/or steroid treatment, treated with the ILUVIEN implant according to national guidelines. Patients with follow-up of less than 24 months were excluded. Best corrected visual acuity, central retinal thickness and intraocular pressure were evaluated at baseline and month 3, 12, 24 and 36 post-treatment. A sub-group analysis was performed on eyes with 36-month follow-up data. RESULTS: In total, 24 eyes (24 patients) completed at least 24 months of follow-up, of which 9 completed 36 months of follow-up. Three-fourths of the patients were black or South Asian (blacks, Asians and minority ethnic). Improvement in mean best corrected visual acuity was seen at year 1 and year 3 improving from 0.62 LogMAR at baseline to 0.55 LogMAR at year 1 and 0.47 LogMAR at year 3 (all p > 0.05). Mean central retinal thickness also showed a progressive reduction from 471 µm at baseline to 397 µm at year 1 and 339 µm at year 3 (all p < 0.05). Four eyes required intraocular pressure-lowering drops post-implant. Supplementary treatment for persistent or recurrent diabetic macular oedema was necessary in 13 eyes over the total study period of 3 years. Blacks, Asians and minority ethnic patients had a worse response compared with white patients. CONCLUSION: The ILUVIEN implant was effective and safe in the treatment of multi-ethnic patients with diabetic macular oedema refractory to conventional therapies, improving the vision and macular anatomy, without significant adverse events up to 36 months post-treatment.

Graphene oxide-based rechargeable respiratory masks.

Respiratory masks having similar standards of 'N95', defined by the US National Institute for Occupational Safety and Health, will be highly sought after, post the current COVID-19 pandemic. Here, such a low-cost (∼$1/mask) mask design having electrostatic rechargeability and filtration efficiency of >95% with a quality factor of ∼20 kPa-1 is demonstrated. This filtration efficacy is for particles of size 300 nm. The tri-layer mask, named PPDFGO tri, contains nylon, modified polypropylene (PPY), and cotton nonwoven fabrics as three layers. The melt-spun PPY, available in a conventional N95 mask, modified with graphene oxide and polyvinylidene fluoride mixture containing paste using a simple solution casting method acts as active filtration layer. The efficacy of this tri-layer system toward triboelectric rechargeability using small mechanical agitations is demonstrated here. These triboelectric nanogenerator (TENG)-assisted membranes have high electrostatic charge retention capacity (∼1 nC/cm2 after 5 days in ambient condition) and high rechargeability even in very humid conditions (>80% RH). A simple but robust permeability measurement set up is also constructed to test these TENG-based membranes, where a flow rate of 30-35 L/min is maintained during the testing. Such a simple modification to the existing mask designs enabling their rechargeability via external mechanical disturbances, with enhanced usability for single use as well as for reuse with decontantamination, will be highly beneficial in the realm of indispensable personal protective equipment.

Lithium, sodium and magnesium ion conduction in solid state mixed polymer electrolytes.

Alkali and alkaline earth metal-ion batteries are currently among the most efficient electrochemical energy storage devices. However, their stability and safety performance are greatly limited when used with volatile organic liquid electrolytes. A solid state polymer electrolyte is a prospective solution even though poor ionic conductivity at room temperature remains a bottleneck. Here we propose the mixing of two similar polymer matrices, poly(dimethyl siloxane) and poly(ethylene oxide), to address this challenge. The resulting electrolyte matrix is denser and significantly improves room-temperature ionic conductivity. Ab initio analyses of the reaction between the cations and the polymers show that oxygen sites act as entrapment sites for the cations and that ionic conduction likely occurs through hopping between adjacent oxygen sites. Molecular dynamics simulations of the dynamics of both polymers and the dynamics of the polymer mix show that the more frequent and more pronounced molecular vibrations of the polymer mix are likely responsible for reducing the time between two consecutive oxygen entrapments, thereby speeding up the conduction process. This hypothesis is experimentally validated by the practically useful ionic conductivity (σ≈ 10-4 S cm-1 at 25 °C) and the improved safety parameters exhibited by a transparent flexible multi-cation (Li+, Na+ and Mg2+) conducting solid channel made up of the above mixed polymer system.

The Risk of Posterior Capsule Rupture during Phacoemulsification Cataract Surgery in Eyes with Previous Intravitreal Anti Vascular Endothelial Growth Factor Injections.

PURPOSE: To investigate if previous intravitreal anti vascular endothelial growth factor (VEGF) injections are a predictor for posterior capsule rupture (PCR) during phacoemulsification cataract surgery. SETTING: National Health Service: Whipps Cross University Hospital Eye Treatment Centre. District General, London, United Kingdom DESIGN:: Single centre, retrospective, electronic medical record (EMR) database study with univariate analysis. METHODS: EMR (Medisoft) was used to extract data for eyes undergoing phacoemulsification surgery between 01.08.16 to 01.01.18. Patient demographics, indication for intravitreal therapy, treatment type, number of previous intravitreal injections (IVI), diabetic status, surgeon grade and operative complications were included as variables for analysis. RESULTS: Data was available for 4047 cataract operations. Of these, 108 had undergone previous anti-VEGF IVI treatment. Three eyes were noted to have pre-operative PC trauma and were excluded from the final analysis. The logistic regression analysis after exclusion of the eyes with pre-existing damage to the PC confirmed that prior anti-VEGF IVI treatment was associated with an increased risk of PCR when compared to the non IVI group (9.26% vs 1.88%, p<0.0001). There is a dose dependent relationship between the number of anti-VEGF injections and the likelihood of PCR. CONCLUSIONS: Previous intravitreal anti-VEGF injections are significantly correlated with an increased risk of surgical PCR despite the absence of visible structural damage to the PC pre-operatively.

Risk of posterior capsular rupture during phacoemulsification cataract surgery in eyes with previous intravitreal antivascular endothelial growth factor injections.

PURPOSE: To investigate whether previous intravitreal antivascular endothelial growth factor (VEGF) injections are a predictor for posterior capsular rupture (PCR) during phacoemulsification cataract surgery. SETTING: Whipps Cross University Hospital Eye Treatment Centre, London, United Kingdom. DESIGN: Single-center, retrospective, electronic medical record (EMR) database study with univariate analysis. METHODS: Data were extracted from an EMR system on eyes undergoing phacoemulsification surgery between August 1, 2016, and January 1, 2018. Patient demographics, indication for intravitreal therapy, treatment type, the number of previous intravitreal injections (IVIs), diabetic status, surgeon grade, and operative complications were included as variables for analysis. RESULTS: Data were available for 4047 cataract operations. Of these, 108 (2.7%) had undergone previous anti-VEGF IVI treatment. Three eyes were noted to have preoperative PC trauma and were excluded from the final analysis. The logistic regression analysis after exclusion of the eyes with pre-existing damage to the PC confirmed that previous anti-VEGF IVI treatment was associated with an increased risk of PCR when compared with the non-IVI group (6.67% vs 1.88%, P < .0001). There is a dose-dependent relationship between the number of anti-VEGF injections and the likelihood of PCR. CONCLUSIONS: Previous intravitreal anti-VEGF injections are significantly correlated with an increased risk of surgical PCR, despite the absence of visible structural damage to the posterior capsule preoperatively.

Macular edema associated with non-infectious uveitis: pathophysiology, etiology, prevalence, impact and management challenges.

Macular edema (ME) is the most common sight-threatening complication in uveitis. The diagnostic and therapeutic management of the uveitic macular edema (UME) might be challenging due to the complex diagnostic workup and the difficulties physicians face to find the underlying cause, and due to its usually recurrent nature and the fact that it can be refractory to conventional treatment. Some of the mild cases can be treated with topical steroids, which can be combined with non-steroid anti-inflammatory drugs. However, immunomodulators such as methotrexate, tacrolimus, azathioprine, cyclosporine and mycophenolate mofetil together with anti-tumor necrosis factor-α (anti-TNF alpha) monoclonal antibodies such as adalimumab and infliximab, may be required to control the inflammation and the associated ME in refractory cases, or when an underlying disease is present. This review of the literature will focus mostly on the non-infectious UME.

Patient-reported outcomes in the RELIGHT clinical trial of ranibizumab in diabetic macular oedema.

BACKGROUND/AIMS: The RELIGHT clinical trial used an individualised treatment regimen of ranibizumab to treat diabetic macular oedema (DMO). We report findings from two patient-reported outcome instruments. METHODS: The National Eye Institute Visual Function Questionnaire (NEI-VFQ) was administered before starting treatment (M0) and at M6, 12 and 18. The Macular Disease Society Treatment Satisfaction Questionnaire (MacTSQ) was administered 1 month after treatment start (M1) and at M6, 12 and 18. Relationships between best-corrected visual acuity (BCVA) in the study eye (SE) and the status of the eye at baseline (as better or worse eye by BCVA) and the two instrument measures were investigated. RESULTS: BCVA in the SE correlated strongly with the NEI-VFQ composite scores and the majority of the subscales but not with the MacTSQ subscales. Statistically significant improvements were observed in the majority of the subscales of the NEI-VFQ at M6, 12 and 18. For the MacTSQ, improvements between baseline M6, 12 and 18 were seen for subscale 1 but only reached statistical significance at M12. In subscale 2, the changes in mean scores were statistically significant at all timepoints. CONCLUSIONS: Although ranibizumab treatment in DMO over an 18-month period resulted in improvements in visual functioning and patient satisfaction, no correlation was found between the instruments used to measure these outcomes. Our finding of a lack of correlation between BCVA and the MacTSQ suggests the presence of psychophysical factors not measured by traditional means.

Mechanistic insight into the improved Li ion conductivity of solid polymer electrolytes.

Polymer based solid electrolytes (SEs) are envisaged as futuristic components of safer solid state energy devices. But the semi-crystalline nature and slow dynamics of the host polymer matrix are found to hamper the ion transport through the solid polymer network and hence solid state devices are still far beyond the scope of practical application. In this study, we unravel the synergistic roles of Li salt (LiClO4) and two different polymers - polyethylene oxide (PEO) and polydimethyl siloxane (PDMS), in the Li ion transport through their solid blend based electrolyte. A detailed study using dielectric spectroscopy and thermo-mechanical analysis is conducted to understand the tunability of the PEO chain dynamics with LiClO4 and the mechanism of hopping of Li ions by forming ion pairs with oxygen dipoles on the PEO backbone is established. Despite the lack of PDMS's capability to solvate ions and promote ion transport directly, its proper mixing within the PEO host matrix is demonstrated to enhance ion transport due to the influence of PDMS on the segmental dynamics of PEO. A detailed molecular dynamics study supported by experimental validation suggests that even inert polymers can affect the dynamics of the active host matrix and increase ion transport, leading to next generation high ionic conductivity solid matrices, and opens new avenues in designing polymer based transparent electrolytes.

United Kingdom Diabetic Retinopathy Electronic Medical Record (UK DR EMR) Users Group: report 4, real-world data on the impact of deprivation on the presentation of diabetic eye disease at hospital services.

AIM: To assess the impact of deprivation on diabetic retinopathy presentation and related treatment interventions, as observed within the UK hospital eye service. METHODS: This is a multicentre, national diabetic retinopathy database study with anonymised data extraction across 22 centres from an electronic medical record system. The following were the inclusion criteria: all patients with diabetes and a recorded, structured diabetic retinopathy grade. The minimum data set included, for baseline, age and Index of Multiple Deprivation, based on residential postcode; and for all time points, visual acuity, ETDRS grading of retinopathy and maculopathy, and interventions (laser, intravitreal therapies and surgery). The main  outcome measures were (1) visual acuity and binocular visual state, and (2) presence of sight-threatening complications and need for early treatment. RESULTS: 79 775 patients met the inclusion criteria. Deprivation was associated with later presentation in patients with diabetic eye disease: the OR of being sight-impaired at entry into the hospital eye service (defined as 6/18 to better than 3/60 in the better seeing eye) was 1.29 (95% CI 1.20 to 1.39) for the most deprived decile vs 0.77 (95% CI 0.70 to 0.86) for the least deprived decile; the OR for being severely sight-impaired (3/60 or worse in the better seeing eye) was 1.17 (95% CI 0.90 to 1.55) for the most deprived decile vs 0.88 (95% CI 0.61 to 1.27) for the least deprived decile (reference=fifth decile in all cases). There is also variation in sight-threatening complications at presentation and treatment undertaken: the least deprived deciles had lower chance of having a tractional retinal detachment (OR=0.48 and 0.58 for deciles 9 and 10, 95% CI 0.24 to 0.90 and 0.29 to 1.09, respectively); in terms of accessing treatment, the rate of having a vitrectomy was lowest in the most deprived cohort (OR=0.34, 95% CI 0.19 to 0.58). CONCLUSIONS: This large real-world study suggests that first presentation at a hospital eye clinic with visual loss or sight-threatening diabetic eye disease is associated with deprivation. These initial hospital visits represent the first opportunities to receive treatment and to formally engage with support services. Such patients are more likely to be sight-impaired or severely sight-impaired at presentation, and may need additional resources to engage with the hospital eye services over complex treatment schedules.

Intravitreal fluocinolone acetonide implant (ILUVIEN®) for diabetic macular oedema: a literature review.

Diabetic macular oedema (DMO) is a common complication of diabetic retinopathy and may lead to severe visual loss. In this review, we describe the pathophysiology of DMO and review current therapeutic options such as macular laser photocoagulation, anti-vascular endothelial growth factor agents, and steroid implants with a focus on the new fluocinolone acetonide implant, ILUVIEN®. The results of the Fluocinolone Acetonide in Diabetic Macular Edema (FAME) studies are also presented together with the results of real-world studies to support the clinical use of ILUVIEN® in achieving efficient resolution of DMO and improving vision and macular anatomy in this challenging group of patients.

Treatment of refractory diabetic macular edema with a fluocinolone acetonide implant in vitrectomized and non-vitrectomized eyes.

AIM: To report real-life data on the use of an intravitreal fluocinolone acetonide implant in the treatment of refractory diabetic macular edema (DME) in pars plana vitrectomized (PPV) and non-PPV eyes. METHODS: This was a comparative retrospective observational study of 23 eyes with chronic DME. Best-corrected visual acuity (BCVA) and central macular thickness (CMT) were recorded at baseline, 1, 4 and 12mo. Descriptive statistics and non-parametric tests were performed to analyze and compare PPV and non-PPV eyes. RESULTS: Seven PPV and 16 non-PPV eyes were included in the study. Median BCVA in the non-PPV group varied from 0.65 logMAR [Interquartile range (IQR): 0.40] at baseline to 0.42 logMAR (IQR: 0.40) at 12mo. Median CMT varied from 430 µm (IQR: 131.3) at baseline to 317 µm (IQR: 107.5) at 12mo. Median BCVA in the PPV group varied from 0.60 logMAR (IQR: 0.62) at baseline to 0.74 logMAR (IQR: 0.34) at 12mo. Median CMT varied from 483 µm (IQR: 146) at baseline to 397 µm (IQR: 132) at 12mo. Of 0/7 eyes and 1/16 eyes in the PPV and non-PPV eyes respectively had a baseline visual acuity of 6/12 or better (0.3 logMAR). At last follow up, 1/7 and 5/16 eyes in the PPV and non-PPV group respectively achieved a visual acuity of 6/12 or better. CONCLUSION: Visual outcomes are modest following the use of the fluocinolone acetonide implant for chronic DME. The steroid implant is a useful treatment option in the management of refractory DME in vitrectomized and non-vitrectmized eyes.

On the development of multifunctional luminescent supramolecular hydrogel of gold and egg white.

Highly stable, luminescent, and printable/paintable supramolecular egg white hydrogel-based surface enhanced Raman scattering (SERS) matrix is created by an in situ synthesis of gold clusters inside a luminescent egg white hydrogel (Au-Gel). The synthesis of stable luminescent egg-white-based hydrogel, where the hydrogel can act as a three dimensional (3D) matrix, using a simple cross-linking chemistry, has promising application in the biomedical field including in 3D cell culturing. Furthermore, this functional hydrogel is demonstrated for micromolar-level detection of Rhodamine 6G using the SERS technique, where Au-Gel is painted over a flexible cellulose pad.

Combination therapy with focal laser photocoagulation and intravitreal ranibizumab for polypoidal choroidal vasculopathy: a case series.

PURPOSE: The study aim is to describe the clinical outcomes of patients with polypoidal choroidal vasculopathy (PCV) treated with focal argon laser photocoagulation and ranibizumab combination therapy. METHODS: This study is a retrospective case series of 6 patients (6 eyes) diagnosed with PCV who received combination therapy with argon laser photocoagulation and ranibizumab and have at least 12 months follow-up. Argon laser photocoagulation was applied directly to the polypoidal lesions as identified on indocyanine green angiography and followed by a course of intravitreal ranibizumab injections. The primary outcome measures were the mean change in logMAR visual acuity and the mean change in central macular thickness (CMT) at final follow-up. RESULTS: The mean (SD) duration of follow-up was 1.09 (0.22) years. At the final follow-up the difference (95% confidence interval [CI]) in logMAR acuity was 0.48 (0.10-0.74) (p=0.01) and the difference (95% CI) in CMT was 207 µm (35-490) (p=0.02) on optical coherence tomography. The mean (SD) number of ranibizumab injections per eye was 4.83 (3.6). The mean (SD) number of laser treatments per eye was 1.16 (0.4). CONCLUSIONS: In this study, combination therapy with focal argon laser photocoagulation and intravitreal ranibizumab resulted in improved visual acuity and clinical outcomes for patients with PCV for up to 1 year.