Visual outcome following posterior capsule rupture during manual small incision cataract surgery.

BACKGROUND: The quality of cataract surgery can be measured by visual outcome, which is sometimes limited by intraoperative complications, most commonly posterior capsular rupture. AIMS: The aim of the study was to assess visual outcome at the last visit (≥8 weeks) following posterior capsule rupture (PCR) in patients who had manual small incision cataract surgery (MSICS) managed without access to an automated vitrector. METHODS: A review of medical records of all manual small incision cataract surgeries performed between January 2013 and December 2016 at the National Eye Centre, Kaduna, Nigeria was conducted. Descriptive statistics and logistic regression analysis were performed using STATA 14.0 to examine risk factors for the development of a poor visual outcome and to assess the impact of PCR on development of poor visual outcome. RESULTS: In total, 405 patients were operated on with MSICS (50.6% males). Mean age was 62.4 (SD 12.6) years. PCR was the most common complication (n = 19 (4.7%)). The proportion of good outcomes (≥6/18) rose from 12.4% non-PCR and 0.0% for those with PCR at day 1 postoperative review, to 71.5 and 26.3%, respectively, by final follow up (P = 0.001). Patients with PCR were 7.0 (P = 0.0001) times more likely to have borderline/poor visual outcome (<6/18) compared to those without PCR. Age >60 years increased the odds of borderline/poor by 1.4 times (P = 0.002). CONCLUSION: PCR significantly affects the visual outcome of cataract patients in settings with no facilities for automated vitrectomy. Minimizing complications will improve visual outcome of cataract patients and increase uptake of cataract surgical services.

Trends in diabetic retinopathy screening attendance and associations with vision impairment attributable to diabetes in a large nationwide cohort.

AIMS: To investigate diabetic retinopathy screening attendance and trends in certified vision impairment caused by diabetic eye disease. METHODS: This was a retrospective study of attendance in three urban UK diabetic eye screening programmes in England. A survival analysis was performed to investigate time from diagnosis to first screen by age and sex. Logistic regression analysis of factors influencing screening attendance during a 15-month reporting period was conducted, as well as analysis of new vision impairment certifications (Certificate of Vision Impairment) in England and Wales from 2009 to 2019. RESULTS: Of those newly registered in the Routine Digital Screening pathway (n = 97 048), 80% attended screening within the first 12 months and 88% by 36 months. Time from registration to first eye screening was longer for people aged 18-34 years, and 20% were unscreened after 3 years. Delay in first screen was associated with increased risk of referable retinopathy. Although 95% of participants (n = 291 296) attended during the 15-month reporting period, uptake varied considerably. Younger age, social deprivation, ethnicity and duration of diabetes were independent predictors of non-attendance and referable retinopathy. Although the last 10 years has seen an overall reduction in vision impairment certification attributable to diabetic eye disease, the incidence of vision impairment in those aged <35 years was unchanged. CONCLUSIONS: Whilst the majority of participants are screened in a timely manner, there is considerable variation in uptake. Young adults, have sub-optimal attendance, and levels of vision impairment in this population have not changed over the last 10 years. There is an urgent need to explore barriers to/enablers of attendance in this group to inform policy initiatives and tailored interventions to address this issue.

A combined-method approach to trace submarine groundwater discharge from a coastal karst aquifer in Ireland.

Knowledge about the hydraulic connections between submarine groundwater discharge (SGD) and its terrestrial coastal catchment is relevant with regard to the management of marine and coastal waters in karst areas. This study applies different methods and monitoring approaches to trace SGD between the Burren Limestone Plateau and Galway Bay in western Ireland, via an excavated sinkhole shaft and deep conduit. Areas of potential SGD were first delineated based on sea surface temperature anomalies using Landsat satellite images. Two fluorescent dyes and solid wood chips were then used as tracers. Solid wood chips were tested as potential means to circumvent the problem of high dispersion in the sea, impacting on the fluorescent dyes to yield readings below the detection limits. Sampling was conducted at 10 different terrestrial locations and in the sea at Galway Bay. Offshore sampling was conducted in transects over a period of four successive days onboard of a vessel using an automated field fluorometer and a conductivity-temperature-depth sensor. No wood chips were recovered in the sea but both fluorescent dyes were successfully sampled. The estimated travel times are in the order of 100 to 354 m/h, and localised tracer readings correlate well in space and time with low conductivity readings. By confirming hydraulic connections between the two karst features and Galway Bay, the study substantiates the hypothesised importance of Variscan veins with regard to regional groundwater flow in the region.

La connaissance des connexions hydrauliques entre les zones de sorties d'eaux souterraines sous-marines et le bassin terrestre côtier attenant est pertinente pour la gestion des eaux marines et côtières en zones karstiques. Cette étude applique différentes approches méthodologiques et de suivi pour tracer la sortie d'eaux souterraines sous-marines entre le plateau calcaire de Burren et la baie de Galway en Irlande de l'Ouest, via une perte et un conduit profond. Les zones de sorties potentielles d'eaux souterraines sous-marines ont été délimitées dans un premier temps sur la base d'anomalies de température des eaux de mer en utilisant des images satellites Landsat. Deux traceurs fluorescents et des copeaux de bois ont été utilisés comme traceurs. Les copeaux de bois ont été utilisés comme moyen potentiel pour contourner les problèmes de dispersion élevée dans la mer, qui impactent les traceurs fluorescents et engendrent des concentrations sous les limites de détections. L'échantillonnage a été menée sur dix sites différents à terre et en mer dans la baie de Galway. L'échantillonnage en mer e a été mené selon des profils sur une période de quatre jours successifs à bord d'un navire muni d'un fluorimètre de terrain automatique et d'un capteur de conductivité-température-profondeur. Aucun copeau de bois n'a été récupéré en mer, mais les deux traceurs fluorescents ont été échantillonnés avec succès. Les temps de séjour estimés sont de l'ordre de 100 à 354 m/h, et les valeurs de traceurs localisées corrèlent bien en espace et en temps avec les basses valeurs de conductivité électrique. En confirmant les connexions hydrauliques entre les deux phénomènes karstiques et la baie de Galway, l'étude corrobore l'hypothèse de l'importance des veines du cycle varisque sur l'organisation des écoulements régionaux d'eau souterraine dans la région.

El conocimiento de las conexiones hidráulicas entre la descarga submarina de aguas subterráneas (SGD) y su cuenca costera terrestre es relevante para la gestión de las aguas marinas y costeras en las zonas kársticas. Este estudio aplica diferentes métodos y enfoques de monitoreo para el seguimiento de la SGD entre la meseta de caliza de Burren y la bahía de Galway en el oeste de Irlanda, a través de un pozo excavado y un conducto profundo. Las áreas de SGD potenciales fueron delineadas primero basándose en anomalías de la temperatura de la superficie del mar usando imágenes satelitales Landsat. Dos tintes fluorescentes y astillas de madera maciza se utilizaron como trazadores. Las astillas de madera maciza se probaron como medio potencial para eludir el problema de la alta dispersión en el mar, impactando en los colorantes fluorescentes para obtener lecturas por debajo de los límites de detección. El muestreo se llevó a cabo en 10 lugares terrestres diferentes y en el mar en la Bahía de Galway. El muestreo en alta mar se llevó a cabo en transectas durante un período de cuatro días consecutivos a bordo de un buque utilizando un fluorómetro de campo automatizado y un sensor de conductividad-temperatura-profundidad. No se recuperaron astillas de madera en el mar, pero se tomaron muestras exitosas de ambos tintes fluorescentes. Los tiempos de tránsito estimados son del orden de 100 a 354 m/h, y las lecturas del trazador localizadas se correlacionan bien en el espacio y el tiempo con las lecturas de baja conductividad. Al confirmar las conexiones hidráulicas entre las dos características kársticas y la Bahía de Galway, el estudio corrobora la importancia hipotética de las vetas de Variscan con respecto al flujo regional de agua subterránea en la región.

O conhecimento sobre as conexões hidráulicas entre a descarga submarina de águas subterrâneas (DSAS) e sua captação terrestre na costa é relevante no que diz respeito ao gerenciamento de águas marinhas e costeiras em áreas cársticas. Este estudo aplica diferentes métodos e abordagens de monitoramento para rastrear a DSAS entre o platô de calcário de Burren e a baía de Galway, no oeste da Irlanda, por meio de um poço escavado e um conduto profundo. Áreas de potencial DSAS foram primeiramente delineadas com base em anomalias de temperatura da superfície do mar usando imagens do satélite Landsat. Dois corantes fluorescentes e lascas de madeira maciça foram então utilizados como marcadores. Lascas de madeira maciça foram testadas como um meio potencial para contornar o problema de alta dispersão no mar, impactando nos corantes fluorescentes para produzir leituras abaixo dos limites de detecção. A amostragem foi realizada em 10 locais terrestres diferentes e no mar na Baía de Galway. A amostragem fora da costa foi realizada em transectos durante um período de quatro dias sucessivos a bordo de uma embarcação usando um fluorômetro de campo automatizado e um sensor de condutividade-temperatura-profundidade. Nenhuma lasca de madeira foi recuperada no mar, mas os dois corantes fluorescentes foram amostrados com sucesso. Os tempos de viagem estimados são da ordem de 100 a 354 m/h, e as leituras localizadas do traçador se correlacionam bem no espaço e no tempo com as leituras de baixa condutividade. Ao confirmar as conexões hidráulicas entre as duas formações cársticas e a Baía de Galway, o estudo confirma a hipótese da importância das veias variscas em relação ao fluxo regional de águas subterrâneas na região.

Barriers to and enablers of diabetic retinopathy screening attendance: a systematic review of published and grey literature.

AIMS: To identify and synthesize studies reporting modifiable barriers/enablers associated with retinopathy screening attendance in people with Type 1 or Type 2 diabetes, and to identify those most likely to influence attendance. METHODS: We searched MEDLINE, EMBASE, PsycINFO, Cochrane Library and the 'grey literature' for quantitative and qualitative studies to February 2017. Data (i.e. participant quotations, interpretive summaries, survey results) reporting barriers/enablers were extracted and deductively coded into domains from the Theoretical Domains Framework; with domains representing categories of theoretical barriers/enablers proposed to mediate behaviour change. Inductive thematic analysis was conducted within domains to describe the role each domain plays in facilitating or hindering screening attendance. Domains that were more frequently coded and for which more themes were generated were judged more likely to influence attendance. RESULTS: Sixty-nine primary studies were included. We identified six theoretical domains ['environmental context and resources' (75% of included studies), 'social influences' (51%), 'knowledge' (51%), 'memory, attention, decision processes' (50%), 'beliefs about consequences' (38%) and 'emotions' (33%)] as the key mediators of diabetic retinopathy screening attendance. Examples of barriers populating these domains included inaccurate diabetic registers and confusion between routine eye care and retinopathy screening. Recommendations by healthcare professionals and community-level media coverage acted as enablers. CONCLUSIONS: Across a variety of contexts, we found common barriers to and enablers of retinopathy screening that could be targeted in interventions aiming to increase screening attendance.

Ranibizumab pretreatment in diabetic vitrectomy: a pilot randomised controlled trial (the RaDiVit study).

PurposeOur aim was to evaluate the impact of intravitreal ranibizumab pretreatment on the outcome of vitrectomy surgery for advanced proliferative diabetic retinopathy. The objective was to determine the feasibility of a subsequent definitive trial and estimate the effect size and variability of the outcome measure.Patients and methodsWe performed a pilot randomised double-masked single-centre clinical trial in 30 participants with tractional retinal detachment associated with proliferative diabetic retinopathy. Seven days prior to vitrectomy surgery, participants were randomly allocated to receive either intravitreal ranibizumab (Lucentis, Novartis Pharmaceuticals UK Ltd, Frimley, UK) or subconjunctival saline (control). The primary outcome was best-corrected visual acuity 12 weeks following surgery.ResultsAt 12 weeks, the mean (SD) visual acuity was 46.7 (25) ETDRS letters in the control group and 52.6 (21) letters in the ranibizumab group. Mean visual acuity improved by 14 (31) letters in the control group and by 24 (27) letters in the ranibizumab group. We found no difference in the progression of tractional retinal detachment prior to surgery, the duration of surgery, or its technical difficulty. Vitreous cavity haemorrhage persisted at 12 weeks in two of the control group but none of the ranibizumab group.ConclusionRanibizumab pretreatment may improve the outcome of vitrectomy surgery for advanced proliferative diabetic retinopathy by reducing the extent of post-operative vitreous cavity haemorrhage. However, the effect size appears to be modest; we calculate that a definitive study to establish a minimally important difference of 5.9 letters at a significance level of P<0.05 would require 348 subjects in each arm.

Quality of life and functional vision in children treated for cataract-a cross-sectional study.

PurposeChildren with cataract and their families face intensive medical and surgical management, with numerous hospital attendances, topical medications, and surgical procedures, as well as uncertainty about the child's future visual ability, education, and independence. Little is known about the impact on functional visual ability, vision-, and health-related quality of life (VR-, HR-QoL).Patients and methodsSeventy two children aged 2-16 years (mean 8.45, SD 4.1) treated for developmental or secondary cataract and their parents/carers completed three validated instruments measuring functional visual ability, VR-, and HR-QoL: the Cardiff Visual Ability Questionnaire for Children (CVAQC), Impact of Vision Impairment for Children (IVI-C), and PedsQL V 4.0.ResultsAll scores are markedly reduced: median (interquartile range (IQR)) CVAQC score -1.42 (-2.28 to -0.03), mean (SD) IVI-C score 65.67 (16.91), median (IQR) PedsQL family impact score 75 (56.94-88.19), parent report 71.74 (51.98-88.5), self-report 76.09 (61.96-89.13). Psychosocial PedsQL subscores are lower than physical subscores. Parent-completed tools (PedsQL family and parent report) state greater impact on HR-QoL than tools completed by children/young people, particularly in teenagers. Older children/young people have higher functional visual ability scores than younger children.ConclusionsCataract has a marked a long-term impact on functional visual ability and quality of life of children and young people, with HR-QoL affected to degrees reported in children with severe congenital cardiac defects or liver transplants.

The UK Neovascular AMD Database Report 3: inter-centre variation in visual acuity outcomes and establishing real-world measures of care.

PurposeInternational variations in visual acuity (VA) outcomes of eyes treated for neovascular age-related macular degeneration (nAMD) are well-documented, but intra-country inter-centre regional variations are not known. These data are important for national quality outcome indicators. We aimed to determine intra-country and inter-centre regional variations in outcomes for treatment of nAMD.Patients and methodsProspective multicentre national database study of 13 UK centres that treated patients according to a set protocol (three loading doses, followed by Pro-Re-Nata retreatment). A total of 5811 treatment naive eyes of 5205 patients received a total of 36 206 ranibizumab injections over 12 months.ResultsMean starting VA between centres varied from 48.9 to 59.9 ETDRS letters. Mean inter-centre VA change from baseline to 12 months varied from +6.9 letters to -0.6 letters (mean of +2.5 letters). The proportion of eyes achieving VA of 70 letters or more varied between 21.9 and 48.7% at 12 months. Median number of injections (visits) at each centre varied from 5 to 8 (9 to 12), with an overall median of 6 (11). Age, starting VA, number of injections, and visits, but not gender were significantly associated with variation in these VA outcomes (P<0.01). Significant variation between centres persisted even after adjusting for these factors.ConclusionThere are modest differences in VA outcomes between centres in the UK. These differences are influenced, but not completely explained, by factors such as patient age, starting VA, number of injections, and visits. These data provide an indication of the VA outcomes that are achievable in real-world settings.

Leading causes of certifiable visual loss in England and Wales during the year ending 31 March 2013.

PURPOSE: The last article on causes of sight impairment (SI) in England and Wales was for April 2007-March 2008. This report updates these figures for April 2012-March 2013. METHODS: In England and Wales, registration for SI is initiated by completion of a certificate of vision impairment (CVI). The main cause of visual impairment was ascertained for certificates completed April 2012-March 2013. A proportional comparison against April 2007-March 2008 was made. RESULTS: We received 24 009 CVIs of which 10 410 were for severe sight impairment (SSI) and 13 129 were for SI. These numbers were slightly higher than those observed in April 2007-March 2008 (9823 SSI; 12 607 SI). The ratio SI:SSI has remained static with 55% of all certifications being SI. The proportion of certificates without a single main cause has fallen slightly (16.6 to 14%). The proportion of certificates with a main cause of degeneration of the macula and posterior pole (mostly age-related macular degeneration (AMD)) decreased from 58.6 to 50% SSI and from 57.2 to 52.5% SI. Glaucoma remains the second most common cause (11% SSI; 7.6% SI) but hereditary retinal disorders overtook diabetes as third leading cause of SSI. CONCLUSION: AMD is still by far the leading cause of certifications for sight impairment in England and Wales (both SI and SSI). Proportionate changes have been observed since 2008, but it is important to note that a proportionate increase in one condition will impact on others.

Metabolic plasticity in CLL: adaptation to the hypoxic niche.

Metabolic transformation in cancer is increasingly well understood. However, little is known about the metabolic responses of cancer cells that permit their survival in different microenvironments. We have used a nuclear magnetic resonance based approach to monitor metabolism in living primary chronic lymphoid leukemia (CLL) cells and to interrogate their real-time metabolic responses to hypoxia. Our studies demonstrate considerable metabolic plasticity in CLL cells. Despite being in oxygenated blood, circulating CLL cells are primed for hypoxia as measured by constitutively low level hypoxia-inducible factor (HIF-1α) activity and modest lactate production from glycolysis. Upon entry to hypoxia we observed rapid upregulation of metabolic rates. CLL cells that had adapted to hypoxia returned to the 'primed' state when re-oxygenated and again showed the same adaptive response upon secondary exposure to hypoxia. We also observed HIF-1α independent differential utilization of pyruvate in oxygenated and hypoxic conditions. When oxygenated, CLL cells released pyruvate, but in hypoxia imported pyruvate to protect against hypoxia-associated oxidative stress. Finally, we identified a marked association of slower resting glucose and glutamine consumption, and lower alanine and lactate production with Binet A0 stage samples indicating that CLL may be divided into tumors with higher and lower metabolic states that reflect disease stage.

A randomized clinical trial comparing fixed vs pro-re-nata dosing of Ozurdex in refractory diabetic macular oedema (OZDRY study).

OBJECTIVE: To compare the clinical effectiveness and safety of 5-monthly fixed dosing vs pro-re-nata (PRN) Ozurdex treatment in patients with refractory diabetic macular oedema (DMO). DESIGN: Prospective, multicentre, randomized active-controlled non-inferiority clinical trial. PARTICIPANTS: Participants were 100 patients who attended Medical Retina Clinics for management of centre-involving refractory DMO. INTERVENTIONS: Participants were randomized 1 : 1 to either 5-monthly fixed dosing or optical coherence tomography (OCT)-guided PRN regimen of Ozurdex therapy for DMO. Data were collected on best-corrected visual acuity (BCVA), patient-reported outcome measures (PROM), macular thickness and morphology, diabetic retinopathy status, number of injections and adverse events from baseline for a period of 12 months.Main outcome measuresThe primary outcome was the difference between arms in change in BCVA from baseline to 12 months. The prespecified non-inferiority margin was five ETDRS letters. Key secondary outcomes included change in PROM scores, change in macular thickness, change in retinopathy and macular morphology, and safety profile. RESULTS: The mean change in BCVA was +1.48 (SD 14.8) in the fixed arm vs -0.17 (SD 13.1) in the PRN arm, with adjusted effect estimate +0.97, 90% confidence interval (-4.01, +5.95), P=0.02 (per protocol analysis). The conclusions of the ITT analysis were primarily supportive, -0.34 (-5.49, 4.81) P=0.07, but sensitive to an alternative assumption on missing data, +0.28 (-4.72, 5.27) P=0.04. CONCLUSIONS: The mean change in BCVA with 5-monthly fixed dosing of Ozurdex was non-inferior to OCT-guided PRN Ozurdex therapy for refractory DMO based on a per protocol analysis.

Certifications for sight impairment due to age related macular degeneration in England.

OBJECTIVES: To examine variability across England in certification rates for age related macular degeneration (AMD) between 1st April 2011 and 31st March 2012. STUDY DESIGN: Cross-sectional survey. METHODS: An electronic version of the CVI, the ECVI, was used at the Certifications Office, London, to transfer information from paper based certificates into a database. The electronic certifications data set was queried for all certificates completed in England between April 1st 2011 and March 31st 2012 with the main cause of certifiable visual loss being AMD or with the main cause of certifiable visual loss being multiple pathology but a contributory cause being AMD. Data were explored by type of AMD, visual status, age and sex and then directly standardized rates were computed by English region. RESULTS: The Certifications Office received 23,616 CVIs for England between April 2011 and March 2012, of which 10,481 (44%) were people certified severely sight-impaired (blind) (SSI) and 12,689 (54%) were certified as sight-impaired (partial sight) (SI). The remainder did not have visual status classified. AMD contributed to 11546 causes of certification on the CVI forms during this period, 53% of forms being for geographic atrophy (GA)/dry AMD which is currently mostly untreatable. The median (interquartile) age at certification for AMD was 86 (81, 90) years and women were more commonly certified than men (66%). Considerable variability was seen across English regions, although there was consistency in that GA was the more common form in all areas. CONCLUSIONS: There is considerable regional variability in CVI rates in England, which are not attributable to differences in age or sex. Reasons for such variability need examination yet this should not undermine the value of these data in terms of describing those newly registered with sight impairment due to AMD who are predominantly female and over 85 years of age.

Acute corneal hydrops in keratoconus: a national prospective study of incidence and management.

PurposeTo determine incidence and management of acute corneal hydrops in the UK.MethodsWe used the BOSU report card system to survey cases of acute corneal hydrops in patients with keratoconus that occurred in the UK between November 2009 and December 2010. Ophthalmologists who reported a case were sent an initial questionnaire, with a follow-up questionnaire after 6 months. We collected information on the demographics, complications, changes in visual acuity, and management. The 2011 National Census was used as a source for population and ethnicity in the UK.ResultsThere were 73 incident cases of acute corneal hydrops, with a response to the initial questionnaire for 64 (88%) patients and follow-up data at 6 months for 57 (78%) patients. For the 64 confirmed cases the median (interquartile range) age of onset was 31.9 (23.2, 41.3) years and 48 (75%) of the cases occurred in males. A total of 42 (66%) patients were white, 14 (22%) were South Asian, and 7 (11%) were black. The proportion of South Asian and black patients with acute corneal hydrops was significantly higher than in the general population (P<0.001). The minimum estimated annual incidence of acute corneal hydrops in patients with keratoconus was estimated to be 1.43 (1.10, 1.83) per 1000. At 6 months following acute corneal hydrops a decision to proceed with keratoplasty had been made for 12 (20.3%) patients.ConclusionsThis is the first population-based estimate of the incidence of acute corneal hydrops in keratoconus.

Pegylated interferon-α-2b reduces corticosteroid requirement in patients with Behçet's disease with upregulation of circulating regulatory T cells and reduction of Th17.

OBJECTIVE: To determine whether the addition of 26 weeks of subcutaneous peginterferon-α-2b could reduce the requirement for systemic corticosteroids and conventional immunosuppressive medication in patients with Behçet's disease (BD). METHODS: We conducted a multicentre randomised trial in patients with BD requiring systemic therapy. Patients were randomised to 26 weeks of peginterferon-α-2b in addition to their standard care or to standard care only and followed 6-monthly for 3 years with BD activity scores and quality of life questionnaires. Patients at one centre had blood taken to measure regulatory T cells (Tregs) and Th17 cells. RESULTS: 72 patients were included. At months 10-12, while among the entire patient population there was no difference in the corticosteroid dose or immunosuppression use between the treatment groups (adjusted OR 1.04, 95% CI 0.34 to 3.19), post hoc analysis revealed that in patients who were on corticosteroids at baseline the corticosteroid requirement was significantly lower in the peginterferon-α-2b (6.5 (5-15) mg/day) compared with the non-interferon group (10 (8.25-16.5) mg/day, p=0.039). Furthermore, there was a trend towards an improved quality of life that became significant by 36 months (p=0.008). This was associated with a significant rise in Tregs and a decrease in Th17 cells which was still present at 1 year and 6 months after the interferon was stopped. The safety profile was similar with adverse events in 10% in both groups. CONCLUSIONS: The addition of peginterferon-α-2b to the drug regime of BD patients did not significantly reduce their corticosteroid dose required at 1 year. However, in those on corticosteroids at baseline post hoc analysis demonstrated that the addition of peginterferon-α-2b did result in a significant reduction in corticosteroid dose with a significantly improved quality of life and trend to reduce other required immunosuppressive agents. This effect was seen at 1 year and associated with a rise in Tregs suggesting a possible mode for interferon action. TRIAL REGISTRATION NUMBER: ISRCTN 36354474; EudraCT 2004-004301-18.

How many people in England and Wales are registered partially sighted or blind because of age-related macular degeneration?

PURPOSE: The purpose of the study was to determine what proportion of new certifications between 1 April 2007 and 31 March 2008 could be attributed to age-related macular degeneration (AMD) and to describe the AMD-certified population in England and Wales. METHODS: An electronic version of the Certificate of Vision Impairment form (CVI), the ECVI, was used at the certifications office to transfer information from the paper-based certificates into a database. The electronic certifications data set was queried for all certificates completed between 1 April 2007 and 31 March 2008 with the main cause of certifiable visual loss being AMD or with the main cause of certifiable visual loss being multiple pathology but a contributory cause being AMD. The electronic data set was adapted so that a distinction could be made between geographic atrophy (GA) and neovascular AMD (nAMD). RESULTS: The Certifications Office received 23 185 CVIs between April 2007 and March 2008, of whom 9823 (42%) were people registered severely sight impaired (SSI) and 12 607 (52%) were certified as sight impaired (SI). AMD contributed to 13 000 causes of registration on the CVI forms during this period and was the main cause in 11 015 people. In these 11 015 people, GA accounted for 49.3%, nAMD 35.1%, and AMD not specified 15.7%. CONCLUSIONS: The data in this report provide detailed information on CVI registration due to AMD before the widespread adoption of ranibizumab therapy in NHS practice and provide an insight into the burden of vision loss due to AMD at a time of great change in the management of nAMD.

Selective AKR1C3 inhibitors do not recapitulate the anti-leukaemic activities of the pan-AKR1C inhibitor medroxyprogesterone acetate.

BACKGROUND: We and others have identified the aldo-keto reductase AKR1C3 as a potential drug target in prostate cancer, breast cancer and leukaemia. As a consequence, significant effort is being invested in the development of AKR1C3-selective inhibitors. METHODS: We report the screening of an in-house drug library to identify known drugs that selectively inhibit AKR1C3 over the closely related isoforms AKR1C1, 1C2 and 1C4. This screen initially identified tetracycline as a potential AKR1C3-selective inhibitor. However, mass spectrometry and nuclear magnetic resonance studies identified that the active agent was a novel breakdown product (4-methyl(de-dimethylamine)-tetracycline (4-MDDT)). RESULTS: We demonstrate that, although 4-MDDT enters AML cells and inhibits their AKR1C3 activity, it does not recapitulate the anti-leukaemic actions of the pan-AKR1C inhibitor medroxyprogesterone acetate (MPA). Screens of the NCI diversity set and an independently curated small-molecule library identified several additional AKR1C3-selective inhibitors, none of which had the expected anti-leukaemic activity. However, a pan AKR1C, also identified in the NCI diversity set faithfully recapitulated the actions of MPA. CONCLUSIONS: In summary, we have identified a novel tetracycline-derived product that provides an excellent lead structure with proven drug-like qualities for the development of AKR1C3 inhibitors. However, our findings suggest that, at least in leukaemia, selective inhibition of AKR1C3 is insufficient to elicit an anticancer effect and that multiple AKR1C inhibition may be required.