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

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 (NO2) and nitrogen oxides (NOx). 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 (PM2.5, per IQR increase) had higher odds of self-reported AMD (OR=1.08, p=0.036), thinner photoreceptor synaptic region (ß=-0.16 µm, p=2.0 × 10-5), thicker photoreceptor inner segment layer (ß=0.04 µm, p=0.001) and thinner RPE (ß=-0.13 µm, p=0.002). Higher levels of PM2.5 absorbance and NO2 were associated with thicker photoreceptor inner and outer segment layers, and a thinner RPE layer. Higher levels of PM10 (PM with an aerodynamic diameter <10 µm) was associated with thicker photoreceptor outer segment and thinner RPE, while higher exposure to NOx was associated with thinner photoreceptor synaptic region. CONCLUSION: Greater exposure to PM2.5 was associated with self-reported AMD, while PM2.5, PM2.5 absorbance, PM10, NO2 and NOx were all associated with differences in retinal layer thickness.

Population screening for glaucoma in UK: current recommendations and future directions.

Effective population screening for glaucoma would enable earlier diagnosis and prevention of irreversible vision loss. The UK National Screening Committee (NSC) recently published a review that examined the viability, effectiveness and appropriateness of a population-based screening programme for primary open-angle glaucoma (POAG). In our article, we summarise the results of the review and discuss some future directions that may enable effective population screening for glaucoma in the future. Two key questions were addressed by the UK NSC review; is there a valid, accurate screening test for POAG, and does evidence exist that screening reduces morbidity from POAG compared with standard care. Six new studies were identified since the previous 2015 review. The review concluded that screening for glaucoma in adults is not recommended because there is no clear evidence for a sufficiently accurate screening test or for better outcomes with screening compared to current care. The next UK NSC review is due to be conducted in 2023. One challenge for POAG screening is that the relatively low disease prevalence results in too many false-positive referrals, even with an accurate test. In the future, targeted screening of a population subset with a higher prevalence of glaucoma may be effective. Recent developments in POAG polygenic risk prediction and deep learning image analysis offer potential avenues to identifying glaucoma-enriched sub-populations. Until such time, opportunistic case finding through General Ophthalmic Services remains the primary route for identification of glaucoma in the UK and greater public awareness of the service would be of benefit.

The Association of Ambient Air Pollution With Cataract Surgery in UK Biobank Participants: Prospective Cohort Study.

Purpose: Air pollution is associated with chronic diseases of later life. Cataract is the most common cause of blindess globally. It is biologically plausible that cataract risk is increased by pollution exposure. Therefore, the relationship between air pollution and incident cataract surgery was examined. Methods: This was a prospective, observational study involving 433,727 UK Biobank participants. Ambient air pollution measures included particulates, nitrogen dioxide (NO2) and nitrogen oxides (NOx). Outdoor air pollution was estimated based on land use regression models. Participants undergoing cataract surgery in either eye were ascertained via data linkage to the National Health Service procedure statistics. Those undergoing cataract surgery within 1 year of baseline assessment and those reporting cataract at baseline were excluded. Cox proportional hazards models were used to examine the associations between air pollutants and incident cataract surgery, adjusting for sociodemographic and lifestyle factors. Results: There were 16,307 incident cases of cataract surgery. Higher exposure to PM2.5 was associated with a 5% increased risk of incident cataract surgery (per interquartile range [IQR] increase). Compared to the lowest quartile, participants with exposures to PM2.5, NO2, and NOx in the highest quartile were 14%, 11%, and 9% more likely to undergo cataract surgery, respectively. A continuous exposure-response relationship was observed, with the likelihood of undergoing cataract surgery being progressively higher with greater levels of PM2.5, NO2, and NOx (P for trend P < 0.001). Conclusions: Although the results of our study showed a 5% increased risk of future cataract surgery following an exposure to PM2.5, NO2, and NOx, the effect estimates were relatively small. Further research is required to determine if the associations identified are causal.

Cohort profile: design and methods in the eye and vision consortium of UK Biobank.

PURPOSE: To describe the rationale, methods and research potential of eye and vision measures available in UK Biobank. PARTICIPANTS: UK Biobank is a large, multisite, prospective cohort study. Extensive lifestyle and health questionnaires, a range of physical measures and collection of biological specimens are collected. The scope of UK Biobank was extended midway through data collection to include assessments of other measures of health, including eyes and vision. The eye assessment at baseline included questionnaires detailing past ophthalmic and family history, measurement of visual acuity, refractive error and keratometry, intraocular pressure (IOP), corneal biomechanics, spectral domain optical coherence tomography (OCT) of the macula and a disc-macula fundus photograph. Since recruitment, UK Biobank has collected accelerometer data and begun multimodal imaging data (including brain, heart and abdominal MRI) in 100 000 participants. Dense genotypic data and a panel of 20 biochemistry measures are available, and linkage to medical health records for the full cohort has begun. FINDINGS TO DATE: A total of 502 665 people aged between 40 and 69 were recruited to participate in UK Biobank. Of these, 117 175 took part in baseline assessment of vision, IOP, refraction and keratometry. A subgroup of 67 321 underwent OCT and retinal photography. The introduction of eye and vision measures in UK Biobank was accompanied by intensive training, support and a data monitoring quality control process. FUTURE PLANS: UK Biobank is one of the largest prospective cohorts worldwide with extensive data on ophthalmic diseases and conditions. Data collection is an ongoing process and a repeat of the baseline assessment including the questionnaires, measurements and sample collection will be performed in subsets of 25 000 participants every 2-3 years. The depth and breadth of this dataset, coupled with its open-access policy, will create a powerful resource for all researchers to investigate the eye diseases in later life.

Multi-centric validation of an in-house-developed beacon-based PCR diagnostic assay kit for Chlamydia and Neisseria and portable fluorescence detector.

OBJECTIVE: The development of an accurate, sensitive, specific, rapid, reproducible, stable-at-room-temperature and cost-effective diagnostic kit, and a low-cost portable fluorescence detector to fulfil the requirements of diagnostic facilities in developing countries. METHODS: We developed the 'Chlamy and Ness CT/NG kit' based on molecular beacons for the detection of Chlamydia trachomatis (CT) and Neisseriagonorrhoeae (NG). Multi-centric evaluation of the CT/NG kit was performed using the commercially available nucleic acid amplification test (NAAT)-based FTD Urethritis basic kit for comparison from December 2014 to November 2016. The stability of the kit reagents at 4 and 37 ˚C and the inter-day reproducibility of results were also analysed. RESULTS: The sensitivity and specificity of the kit were found to be 95.83 and 100.00 % for the detection of C. trachomatis and 93.24 and 99.75 % for N. gonorrhoeae, respectively, when tested against the commercial kit. The positive predictive value (PPV) was 100.00 and 98.57 %, whereas the negative predictive value (NPV) was 99.54 and 98.79 % for C. trachomatis and N. gonorrhoeae, respectively. Analysis of the kappa statistics enhanced the 'inter-rater' κ=0.976 for Chlamydia and κ=0.943 for Neisseria. CONCLUSION: Our kit was found to be as sensitive and specific as commercially available kits. Its low cost and ease of use will make it suitable for the routine diagnosis of C. trachomatis and N. gonorrhoeae in the resource-limited settings of developing countries.

Number of incident cases of the main eye diseases of ageing in the UK Biobank cohort, projected over a 25-year period from time of recruitment.

OBJECTIVES: To estimate the number of new cases of age-related macular degeneration, cataract and glaucoma accruing in the UK Biobank cohort, over a period of 25 years from time of recruitment. Our secondary objective was to assess the statistical power of nested case-control studies of these eye diseases. We aimed to provide quantitative information relevant to UK Biobank's eye disease case ascertainment efforts and to the potential for UK Biobank-based research into the causes of eye disease. METHODS: We constructed a Markov discrete-time state transition model to simulate the population dynamics of the eye disorders within the UK Biobank cohort, using prevalence data from population-based epidemiological studies to derive incidence, and Office for National Statistics data on mortality and migration overseas. RESULTS: By 2023, >900 new cases of each of 'wet' (neovascular) and 'dry' age-related macular degeneration, >1200 cases of primary open angle glaucoma and almost 15 000 cases of cataracts are expected to have accrued in the subcohort of 68 500 participants who had ocular assessment at baseline, with around seven times as many cases of each disease in the whole cohort of 500 000 participants. These predicted incident case numbers generate good or substantial statistical power for a range of nested case-control studies of potential genetic, lifestyle and environmental determinants of disease. CONCLUSIONS: Over the next few years, UK Biobank is expected to generate sufficient numbers of new cases for statistically well-powered studies of the determinants of the major causes of sight loss: age-related macular degeneration, vision-impairing cataract and glaucoma.

Report on the incidence of squamous cell carcinomas affecting the eyelids in England over a 15-year period (2000-2014).

AIMS: The authors report on trends in the incidence of squamous cell carcinoma (SCC) affecting the eyelids in England over a 15-year period and identify associations between demographic factors and SCC risk. METHODS: The National Cancer Registration and Analysis Service identified all cases of eyelid SCC in England between 2000 and 2014. The crude and age-standardised rates of eyelid SCCs in England were calculated. The association of SCC with several known demographic risk factors was then examined to assess their importance in periocular cases. RESULTS: Over the 15 years studied, there were 4022 patients in England diagnosed with a first episode of SCC affecting the eyelids. The age-standardised number of reported cases rose between 2000 and 2014 by a mean of 0.0137 cases per 100 000 population per year (equivalent to a rise in SCC incidence of approximately 2% per year). The mean age-standardised incidence rate of SCC during the study period was 0.63 cases per 100 000 population per year.Age was exponentially correlated with incidence, with an approximate doubling of the risk for every decade over the age of 60. The relative risk of eyelid SCC in men compared with women was 1.9. Social deprivation quintile by income was not found to be associated with risk of SCC. CONCLUSION: The incidence of eyelid SCC in England is rising. In addition, the age-standardised and population-standardised rate of SCC is also rising. A higher risk of SCC is strongly correlated with age and male sex but not with deprivation.

Socioeconomic deprivation and serious ocular trauma in Scotland: a national prospective study.

OBJECTIVE: To identify the population at risk of serious ocular trauma by exploring relationships with socioeconomic factors. DESIGN: National, prospective, population-based, cross-sectional and follow-up study. PARTICIPANTS: Patients with serious ocular trauma requiring hospital admission in Scotland. METHODS: Case definition and ascertainment-cases of serious ocular trauma necessitating admission to hospital under the care of a consultant ophthalmologist were identified using the British Ophthalmological Surveillance Unit reporting scheme. Using the postcode of residence, we assigned a Scottish Index of Multiple Deprivation (SIMD) score, SIMD quintile ( 0%-20% most deprived; 20%-40%, 40%-60%, 60%-80%, 80%-100% least deprived areas), geographical access score as well as the estimated travel time to the nearest general practitioner (GP) practice using either car or public transport for each patient. Population estimates were obtained from the General Register Office for Scotland. MAIN OUTCOME MEASURE: Serious ocular trauma requiring hospital admission. RESULTS: A total of 104 patients (85.6% male) were reported as being admitted with ocular trauma with a median age of 32 years (IQR 24-54). There was a trend for increasing incidence of serious ocular injury with increasing socioeconomic deprivation (p=0.034). Patients from the most deprived areas (SIMD: 0%-20%) were twice as likely to sustain ocular injury compared with those from the least deprived (SIMD: 80%-100%) areas (relative risk: 2.19, 95% CI 1.02 to 4.81). There was no significant difference in the drive/public transport time to GP practices across the SIMD quintiles. CONCLUSIONS: Increasing socioeconomic deprivation was associated with a higher incidence of serious ocular injury. Targeted interventions are needed to address inequality in eye healthcare in deprived areas.

Incidence of eyelid basal cell carcinoma in England: 2000-2010.

INTRODUCTION: Basal cell carcinomas (BCCs) are the most frequently diagnosed type of skin cancer, with eyelid (including canthus) BCCs accounting for a notable proportion of these. Using population-based data from the English Cancer Registries, we report here the incidence of eyelid BCCs in England, for the period 2000-2010. METHODS: ICD-10 and histology codes for eyelid BCCs (including canthus) from the English National Cancer Data Repository were used to identify incident events. Crude incidence rates by age and sex, together with directly standardised incidence rates for eyelid BCCs in England in 3-year cohorts, are presented, in keeping with the reporting practice of the English Cancer Registries. RESULTS: Over the 11-year study period, there were a total of 33 610 recorded eyelid BCCs; 18 146 in females and 15 464 in males. There were regional variations in registrations. Incidence of eyelid BCCs increased with age. No major change in the age-standardised incidence of BCC was observed during the period 2000-2010. Overall, the age-standardised incidence of BCCs during 2008-2010 was similar for males and females (4.51 per 100 000 (95% CI 4.37 to 4.65) and 4.53 per 100 000 (95% CI 4.40 to 4.67), respectively). However, females under 50 years of age had higher incidence rates, and males over 75 years of age had higher rates. CONCLUSIONS: The findings provide the current frequency and distribution of eyelid BCCs in England, highlighting opportunities for health education and improving reporting and registration of events, and for informing service planning.

Bilateral Diffuse Uveal Melanocytic Proliferation (BDUMP) associated with B-cell lymphoma: report of a rare case.

BACKGROUND: Bilateral diffuse uveal melanocytic proliferation (BDUMP) is a paraneoplastic ocular syndrome occurring in patients with systemic, often occult but advanced carcinoma and is the hallmark of poor prognosis. Ocular signs precede manifestation of systemic carcinoma by 3-12 months, highlighting the need for appropriate index of suspicion and prompt evaluation. Treatment options for BDUMP are limited. Investigations are aimed at finding the occult primary malignancy, which can be challenging. Modalities for treatment of the ocular findings include corticosteroids, surgery, external beam radiotherapy, and treatment of the underlying malignant neoplasm. However, it is uncertain whether earlier intervention for the systemic malignancy will impact survival, as this paraneoplastic phenomenon is thought to occur in advanced malignancy. CASE PRESENTATION: We report a unique rare atypical case with BDUMP causing visual loss in a 62-year-old female as the presenting sign of central nervous system (CNS) B-cell lymphoma. Multiple grey or grey brown subretinal lesions with pigment clumps were present in both eyes on fundoscopy and multimodal imaging demonstrated multiple discrete lesions at the level of retinal pigment epithelium. Neuroimaging revealed presence of brainstem and cerebellopontine lesions suggestive of CNS lymphoma, which was further confirmed on biopsy. CONCLUSION: In the current atypical case, prompt diagnosis and immediate referral was key, with detailed systemic evaluation by an internist and oncologist. The reported case is distinct for the reason that BDUMP occurred secondary to primary CNS lymphoma, a hitherto unreported association.

Incidence and treatment of retinopathy of prematurity in England between 1990 and 2011: database study.

AIMS: To study the incidence and treatment of retinopathy of prematurity (ROP) in England, 1990-2011. METHODS: English national Hospital Episode Statistics were analysed, for babies born in hospital and for inpatient admissions, to obtain annual rates of diagnosis of, and treatment for, babies with ROP. National data on low birthweight (LBW) babies, born <1500 g and therefore eligible for ROP screening, were used as denominators in calculating rates of ROP per 1000 babies at risk. RESULTS: The recorded incidence of ROP increased tenfold, from 12.8 per 1000 LBW babies in 1990 to 125.5 per 1000 LBW babies in 2011. Tretment rates for ROP by cryotherapy or laser rose from 1.7 to 14.8 per 1000 LBW babies between 1990 and 2011. In 1990, 13.3% of babies with ROP were treated with cryotherapy, which fell to 0.1% in 2011. Rates for laser treatment rose from 1.8% of babies with ROP in 1999 to 11.7% in 2011. CONCLUSIONS: Increased neonatal survival, improved awareness of ROP and dissemination of guidance on screening and treatment of ROP will all have contributed to the substantial rise in recorded incidence of ROP between 1990 and 2011. Retinal ablation is now almost always performed using laser treatment rather than cryotherapy.

Modelling the prevalence of age-related macular degeneration (2010-2020) in the UK: expected impact of anti-vascular endothelial growth factor (VEGF) therapy.

AIMS: To project the number of cases with age-related macular degeneration (AMD) and the numbers with attributable sight loss in the UK in 2010-2020, taking into account the expected beneficial effect of the new anti-vascular endothelial growth factor (VEGF) therapies. METHODS: A 'system dynamics' approach was used in constructing the model to simulate the dynamics of the disease in large populations. The model computed the pool of affected cases over the simulation period, taking into account the expected demographic changes. Other determinants taken into account included: prevalence; incidence; mortality; and the expected efficacy and coverage of anti-VEGF treatment. RESULTS: In the UK, 608,213 persons in 2010 are estimated to have AMD, and this is expected to increase to 755,867 by the end of the decade. Numbers with sight loss from AMD are expected to rise from 223,224 in 2010 to 291,982 by 2020. Cases with sight loss due to neovascular AMD are expected to increase from 145,697 to 189,890 by the end of the decade. CONCLUSIONS: The model predicts that the beneficial effects of the treatment would be outweighed by the strong anticipated demographic 'ageing' effect. This reaffirms the importance of continuing efforts to develop more effective and more broadly applicable therapies for AMD.