Personalising screening of sight-threatening diabetic retinopathy - qualitative evidence to inform effective implementation.

BACKGROUND: Internationally, systematic screening for sight-threatening diabetic retinopathy (STDR) usually includes annual recall. Researchers and policy-makers support extending screening intervals, citing evidence from observational studies with low incidence rates. However, there is little research around the acceptability to people with diabetes (PWD) and health care professionals (HCP) about changing eye screening intervals. METHODS: We conducted a qualitative study to explore issues surrounding acceptability and the barriers and enablers for changing from annual screening, using in-depth, semistructured interviews analysed using the constant comparative method. PWD were recruited from general practices and HCP from eye screening networks and related specialties in North West England using purposive sampling. Interviews were conducted prior to the commencement of and during a randomised controlled trial (RCT) comparing fixed annual with variable (6, 12 or 24 month) interval risk-based screening. RESULTS: Thirty PWD and 21 HCP participants were interviewed prior to and 30 PWD during the parallel RCT. The data suggests that a move to variable screening intervals was generally acceptable in principle, though highlighted significant concerns and challenges to successful implementation. The current annual interval was recognised as unsustainable against a backdrop of increasing diabetes prevalence. There were important caveats attached to acceptability and a need for clear safeguards around: the safety and reliability of calculating screening intervals, capturing all PWD, referral into screening of PWD with diabetic changes regardless of planned interval. For PWD the 6-month interval was perceived positively as medical reassurance, and the 12-month seen as usual treatment. Concerns were expressed by many HCP and PWD that a 2-year interval was too lengthy and was risky for detecting STDR. There were also concerns about a negative effect upon PWD care and increasing non-attendance rates. Amongst PWD, there was considerable conflation and misunderstanding about different eye-related appointments within the health care system. CONCLUSIONS: Implementing variable-interval screening into clinical practice is generally acceptable to PWD and HCP with important caveats, and misconceptions must be addressed. Clear safeguards against increasing non-attendance, loss of diabetes control and alternative referral pathways are required. For risk calculation systems to be safe, reliable monitoring and clear communication is required.

Safety and acceptability of an organic light-emitting diode sleep mask as a potential therapy for retinal disease.

PurposeThe purpose of the study was to study the effect of an organic light-emitting diode sleep mask on daytime alertness, wellbeing, and retinal structure/function in healthy volunteers and in diabetic macular oedema (DMO).Patients and methodsHealthy volunteers in two groups, 18-30 yrs (A), 50-70 yrs (B) and people with DMO (C) wore masks (504 nm wavelength; 80 cd/m2 luminance; ≤8 h) nightly for 3 months followed by a 1-month recovery period. Changes from baseline were measured for (means): psychomotor vigilance task (PVT) (number of lapses (NL), response time (RT)), sleep, depression, psychological wellbeing (PW), visual acuity, contrast sensitivity, colour, electrophysiology, microperimetry, and retinal thickness on OCT.ResultsOf 60 participants, 16 (27%) withdrew, 8 (13%) before month 1, due to sleep disturbances and mask intolerance. About 36/55 (65%) who continued beyond month 1 reported ≥1 adverse event. At month 3 mean PVT worsened in Group A (RT (7.65%, P<0.001), NL (43.3%, P=0.005)) and mean PW worsened in all groups (A 28.0%, P=0.01, B 21.2%, P=0.03, C 12.8%, P<0.05). No other clinically significant safety signal was detected. Cysts reduced/resolved in the OCT subfield of maximal pathology in 67% Group C eyes. Thinning was greater at 3 and 4 months for greater baseline thickness (central subfield P<0.001, maximal P<0.05).ConclusionSleep masks showed no major safety signal apart from a small impairment of daytime alertness and a moderate effect on wellbeing. Masks were acceptable apart from in some healthy participants. Preliminary data suggest a beneficial effect on retinal thickness in DMO. This novel therapeutic approach is ready for large clinical trials.

Cost-effectiveness of community versus hospital eye service follow-up for patients with quiescent treated age-related macular degeneration alongside the ECHoES randomised trial.

OBJECTIVES: To assess the cost-effectiveness of optometrist-led follow-up monitoring reviews for patients with quiescent neovascular age-related macular degeneration (nAMD) in community settings (including high street opticians) compared with ophthalmologist-led reviews in hospitals. DESIGN: A model-based cost-effectiveness analysis with a 4-week time horizon, based on a 'virtual' non-inferiority randomised trial designed to emulate a parallel group design. SETTING: A virtual internet-based clinical assessment, conducted at community optometry practices, and hospital ophthalmology clinics. PARTICIPANTS: Ophthalmologists with experience in the age-related macular degeneration service; fully qualified optometrists not participating in nAMD shared care schemes. INTERVENTIONS: The participating optometrists and ophthalmologists classified lesions from vignettes and were asked to judge whether any retreatment was required. Vignettes comprised clinical information, colour fundus photographs and optical coherence tomography images. Participants' classifications were validated against experts' classifications (reference standard). Resource use and cost information were attributed to these retreatment decisions. MAIN OUTCOME MEASURES: Correct classification of whether further treatment is needed, compared with a reference standard. RESULTS: The mean cost per assessment, including the subsequent care pathway, was £411 for optometrists and £397 for ophthalmologists: a cost difference of £13 (95% CI -£18 to £45). Optometrists were non-inferior to ophthalmologists with respect to the overall percentage of lesions correctly assessed (difference -1.0%; 95% CI -4.5% to 2.5%). CONCLUSIONS: In the base case analysis, the slightly larger number of incorrect retreatment decisions by optometrists led to marginally and non-significantly higher costs. Sensitivity analyses that reflected different practices across eye hospitals indicate that shared care pathways between optometrists and ophthalmologists can be identified which may reduce demands on scant hospital resources, although in light of the uncertainty around differences in outcome and cost it remains unclear whether the differences between the 2 care pathways are significant in economic terms. TRIAL REGISTRATION NUMBER: ISRCTN07479761; Pre-results.

The design and implementation of a study to investigate the effectiveness of community vs hospital eye service follow-up for patients with neovascular age-related macular degeneration with quiescent disease.

IntroductionStandard treatment for neovascular age-related macular degeneration (nAMD) is intravitreal injections of anti-VEGF drugs. Following multiple injections, nAMD lesions often become quiescent but there is a high risk of reactivation, and regular review by hospital ophthalmologists is the norm. The present trial examines the feasibility of community optometrists making lesion reactivation decisions.MethodsThe Effectiveness of Community vs Hospital Eye Service (ECHoES) trial is a virtual trial; lesion reactivation decisions were made about vignettes that comprised clinical data, colour fundus photographs, and optical coherence tomograms displayed on a web-based platform. Participants were either hospital ophthalmologists or community optometrists. All participants were provided with webinar training on the disease, its management, and assessment of the retinal imaging outputs. In a balanced design, 96 participants each assessed 42 vignettes; a total of 288 vignettes were assessed seven times by each professional group.The primary outcome is a participant's judgement of lesion reactivation compared with a reference standard. Secondary outcomes are the frequency of sight threatening errors; judgements about specific lesion components; participant-rated confidence in their decisions about the primary outcome; cost effectiveness of follow-up by optometrists rather than ophthalmologists.DiscussionThis trial addresses an important question for the NHS, namely whether, with appropriate training, community optometrists can make retreatment decisions for patients with nAMD to the same standard as hospital ophthalmologists. The trial employed a novel approach as participation was entirely through a web-based application; the trial required very few resources compared with those that would have been needed for a conventional randomised controlled clinical trial.

High prevalence in Malawi of sight-threatening retinopathy and visual impairment caused by diabetes: identification of population-specific targets for intervention.

AIMS: To report the prevalence of all grades of diabetic retinopathy and associations with demographic, clinical and biochemical variables in people with diabetes in Southern Malawi. METHODS: We report baseline data from a 24-month prospective cohort study. Subjects were systematically sampled from two hospital-based, primary care diabetes clinics. Visual acuity, glycaemic control, systolic blood pressure, HIV status, urine albumin-creatinine ratio, and haemoglobin and serum lipid levels were assessed. Retinopathy was graded at an accredited reading centre using modified Wisconsin grading of four-field mydriatic photographs. RESULTS: A total of 357 subjects were studied. Of these, 13.4% subjects were HIV-positive and 15.1% had anaemia. The overall prevalence rates of any retinopathy, sight-threatening diabetic retinopathy and proliferative retinopathy were 50.1% (95% CI 44.9-55.3), 29.4% (95% CI 24.7-34.1) and 7.3% (95% CI 4.6-10.0), respectively. In multivariate logistic analysis the presence of sight-threatening retinopathy was associated with duration of diabetes (odds ratio 1.11, 95% CI 1.05-1.17), HbA1c (odds ratio 1.31, 95% CI 1.13-1.50), systolic blood pressure (odds ratio 1.03, 95% CI 1.01-1.04), haemoglobin (odds ratio 0.98, 95% CI 0.96-0.99) and LDL cholesterol (odds ratio 1.63, 95% CI 1.18-2.25). No significant association with HIV status was observed. In all, 3.6 and 1.4% of people in our study cohort had visual acuity worse than 6/18 and 6/60 in the better eye, respectively. CONCLUSIONS: The present study found a prevalence of sight-threatening retinopathy in diabetes clinics in one Sub-Saharan African country of approximately four times that reported in recent European studies and a prevalence of proliferative retinopathy approximately 10 times higher. The association of sight-threatening retinopathy with lower haemoglobin level is a new finding. Our results highlight the urgent need for provision of services for retinopathy detection and management to avoid a large burden of vision loss.

Epidemiology of diabetic retinopathy and maculopathy in Africa: a systematic review.

AIM: To summarize findings from studies reporting the prevalence and incidence of diabetic retinopathy and diabetic maculopathy in African countries in light of the rising prevalence of diabetes mellitus. METHODS: Using a predefined search strategy, we systematically searched MEDLINE, EMBASE, Science Citation index and Conference Proceedings Citation index, African Index Medicus and the grey literature database 'OpenSIGLE' for studies published between January 1990 and February 2011. Included studies reported prevalence or incidence of diabetic retinopathy or diabetic maculopathy of subjects with diabetes resident in African countries. RESULTS: Sixty-two studies from 21 countries were included: three population-based surveys; two cohort studies; five case-control studies; 32 diabetes clinic-based, nine eye clinic-based and 11 other hospital-based surveys. Included studies varied considerably in terms of patient selection, method of assessing the eye and retinopathy classification. In population-based studies, the reported prevalence range in patients with diabetes for diabetic retinopathy was 30.2 to 31.6%, proliferative diabetic retinopathy 0.9 to 1.3%, and any maculopathy 1.2 to 4.5%. In diabetes clinic-based surveys, the reported prevalence range for diabetic retinopathy was 7.0 to 62.4%, proliferative diabetic retinopathy 0 to 6.9%, and any maculopathy 1.2 to 31.1%. No obvious association between prevalence and income level of the country was detected. CONCLUSIONS: Large, community-based cross-sectional and cohort studies are needed to investigate rates and determinants of prevalence of diabetic retinopathy, incidence and progression in Africa. Consensus is needed on the most appropriate methods of identification and classification of retinopathy for research and clinical practice. Estimates of prevalence of diabetic retinopathy, proliferative diabetic retinopathy and maculopathy are comparable with recent European and American studies.

Verteporfin photodynamic therapy for neovascular age-related macular degeneration: cohort study for the UK.

OBJECTIVES: The verteporfin photodynamic therapy (VPDT) cohort study aimed to answer five questions: (a) is VPDT in the NHS provided as in randomised trials?; (b) is 'outcome' the same in the nhs as in randomised trials?; (c) is 'outcome' the same for patients ineligible for randomised trials?; (d) is VPDT safe when provided in the NHS?; and (e) how effective and cost-effective is VPDT? DESIGN: Treatment register. SETTING: All hospitals providing VPDT in the NHS. PARTICIPANTS: All patients attending VPDT clinics. INTERVENTIONS: Infusion of verteporfin followed by infrared laser exposure is called VPDT, and is used to treat neovascular age-related macular degeneration (nAMD). The VPDT cohort study advised clinicians to follow patients every 3 months during treatment or active observation, retreating based on criteria used in the previous commercial 'TAP' (Treatment of Age-related macular degeneration with Photodynamic therapy) trials of VPDT. MAIN OUTCOME MEASURES: The primary outcome was logarithm of the minimum angle of resolution monocular best-corrected distance visual acuity (BCVA). Secondary outcomes were adverse reactions and events; morphological changes in treated nAMD (wet) lesions; and for a subset of patients, 6-monthly contrast sensitivity, generic and visual health-related quality of life (HRQoL) and resource use. Treated eyes were classified as eligible for the TAP trials (EFT), ineligible (IFT) or unclassifiable (UNC). RESULTS: Forty-seven hospitals submitted data for 8323 treated eyes in 7748 patients; 4919 eyes in 4566 patients were treated more than 1 year before the last data submission or had completed treatment. Of 4043 eyes with nAMD in 4043 patients, 1227 were classified as EFT, 1187 as IFT and 1629 as UNC. HRQoL and resource use data were available for about 2000 patients. The mean number of treatments in years 1 and 2 was 2.3 and 0.4 respectively. About 50% of eyes completed treatment within 1 year. BCVA deterioration in year 1 did not differ between eligibility groups. EFT eyes lost 11.6 letters (95% confidence interval 10.1 to 13.0 letters) compared with 9.9 letters in VPDT-treated eyes in the TAP trials. EFT eyes had poorer BCVA at baseline than IFT and UNC eyes. Adverse reactions and events were reported for 1.4% of first visits - less frequently than those reported in the TAP trials. Associations between BCVA in the best-seeing eye with HRQoL and community health and social care resource use showed that the 11-letter difference in BCVA between VPDT and sham treatment in the TAP trials corresponded to differences in utility of 0.012 and health and social service costs of £60 and £92 in years 1 and 2, respectively. VPDT provided an incremental cost per quality-adjusted life-year (QALY) of £170,000 over 2 years. CONCLUSIONS: VPDT was administered less frequently than in the TAP trials, with less than half of those treated followed up for > 1 year in routine clinical practice. Deterioration in BCVA over time in EFT eyes was similar to that in the TAP trials. The similar falls in BCVA after VPDT across the pre-defined TAP eligibility groups do not mean that the treatment is equally effective in these groups because deterioration in BCVA can be influenced by the parameters that determined group membership. Safety was no worse than in the TAP trials. The estimated cost per QALY was similar to the highest previous estimate. Although VPDT is no longer in use as monotherapy for neovascular AMD, its role as adjunctive treatment has not been fully explored. VPDT also has potential as monotherapy in the management of vascular malformations of the retina and choroid and with trials underway in neovascularisation due to myopia and polypoidal choroidopathy. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Anti-VEGF compounds in the treatment of neovascular age related macular degeneration.

Age-related macular degeneration (AMD) is the leading cause of blindness among elderly patients in developed countries. Although the pathogenesis of AMD is still largely unknown, it is now well known that vascular endothelial growth factor (VEGF) plays a pivotal role in the growth of the abnormal blood vessels (i.e. choroidal neovascularization, CNV) which characterizes the "wet form" of this ocular disease. Therefore, inhibiting VEGF has turned out to be a good way of more effectively controlling neovascular AMD. VEGF is a heparin-binding glycoprotein with potent angiogenic, mitogenic and vascular permeability-enhancing activities specific for endothelial cells. Currently two anti-VEGF compounds have been approved by the US Food and Drug Administration (FDA) for the treatment of neovascular AMD: pegaptanib and ranibizumab. Off-label usage of bevacizumab, an anti-VEGF agent similar to ranibizumab, has also become fairly common. The substantial improvement of visual acuity noticed in patients treated with ranibizumab has made this drug the gold standard for AMD therapy. However, as with many new therapies, there are unresolved issues, including safety, cost, and dosing frequency. This review describes in details the properties and efficacy of the three anti-VEGF agents in use in clinical practice. Promising emerging anti-VEGF strategies (VEGF-trap, small interfering RNA, tyrosine kinase inhibitors) which aim to improve outcomes, safety and treatment burden through novel mechanisms of action are also discussed.

Effectiveness of ranibizumab for neovascular age-related macular degeneration using clinician-determined retreatment strategy.

AIMS: To report the effectiveness of intravitreal ranibizumab treatment for neovascular age-related macular degeneration in a tertiary centre. METHODS: 1 year prospective cohort study of patients with a diagnosis of neovascular age-related macular degeneration on fundus fluorescein angiography treated with ranibizumab. Patients received three consecutive monthly treatments, followed by a clinician-determined re-treatment strategy. Data collected included demographic details, baseline and subsequent follow-up visit measurements, refraction protocol best corrected visual acuity (BCVA), contrast sensitivity (CS) and central foveal thickness (CFT) on optical coherence tomography. RESULTS: 81 patients were included in the study. The mean age was 79.5 years with a male:female ratio 32:49. The mean number of treatments was 5.6 ± 2.3. Visual outcomes at 12 months showed 17.1% gained ≥ 15 letters BCVA, 97.4% lost <15 letters and 2.5% lost ≥ 15 letters. Mean changes at 12 months were: BCVA +3.7 ± 11.1 (p<0.01); CS +2.3 ± 5.1 letters (p<0.001); CFT -100.1 ± 111.9 µm (p<0.001). CONCLUSIONS: Clinician-determined re-treatment after a three-dose initiation phase appears to be less effective in improving BCVA than in randomised controlled trials.

Incidence of neovascularization in the fellow eye of patients with unilateral retinal angiomatous proliferation.

AIMS: The aim of this study is to describe the incidence and characteristics of neovascularization in the fellow eye of patients with retinal angiomatous proliferation (RAP). METHODS: This is a retrospective study conducted on all patients with a diagnosis of unilateral RAP commencing treatment in a single centre between November 2002 and January 2010. Clinical biomicroscopic examination, fluorescein angiography, and if required, indocyanine green angiography, and optical coherence tomography were used to evaluate all patients. RESULTS: In all, 37 patients had a follow-up of ≥1 year, 28 ≥2 years, and 11 ≥3. Patients who developed RAP in the fellow eye were: 2 of 37 (5.4%) within 1 year of follow-up, 4 of 28 (14.2%) within 2 years, and 4 of 11 (36.3%) within 3 years. CONCLUSION: In our case series, the risk of neovascularization in the fellow eye of patients with unilateral RAP increased with time. Approximately one-third of patients with a 3-year follow-up developed a bilateral disease. Our findings warrant further large-scale investigation.

Baseline clinical measures and early response predict success in verteporfin photodynamic therapy for neovascular age-related macular degeneration.

PURPOSE: To analyse the influence of baseline clinical characteristics on the outcome of verteporfin photodynamic therapy (VPDT) for neovascular age-related macular degeneration (nAMD). METHODS: A total of 1008 patients commencing VPDT for nAMD in a single UK centre entered a prospective observational study between 1999 and 2006 and were followed for 2 years. Longitudinal linear mixed-effects modelling was applied to assess the influence of baseline covariates, such as best corrected visual acuity (BCVA), contrast sensitivity (CS), age, lesion size, and lesion type, on changes of BCVA over time in patients after VPDT. A logistic regression analysis was used to analyse clinical features significantly associated with treatment failure. RESULTS: Study eye BCVA was significantly better on average throughout the course of treatment in patients with better baseline BCVA and CS in the study eye (P<0.001 and P<0.01, respectively) and lower age (P=0.01). Mean BCVA showed a significant reduction over time with a significant quadratic relationship between 0 and 6 months and with stabilisation between 6 and 9 months. Patients with better BCVA and worse CS at baseline, and those in whom BCVA dropped during the first 3 months of follow-up, were more likely to lose >/=15 letters after 12 months. CONCLUSIONS: Findings from our large longitudinal data set provide estimates of likely outcome based on baseline features and response at 3 months in patients commencing a course of VPDT for nAMD. Statistical modelling built up for this large data set can be applicable to other studies in ophthalmology research.

Neovascular age-related macular degeneration: decision making and optimal management.

AIM: To review the decision-making processes and dilemmas in the delivery of services for neovascular age-related macular degeneration (nAMD) and describe its optimal management. METHODS: Review of literature and presentation of illustrative cases. RESULTS: Guidelines are available to aid commissioners and providers of services but with important gaps in advice. Increasing awareness of variants and diseases that mimic nAMD means that clinicians need to carefully assess lesions at presentation, using stereo imaging, fluorescein and indocyanine green angiography, and new generation optical coherence tomography. Current evidence supports the use of ranibizumab as first-line therapy. Evidence is unclear on the most appropriate treatment regime, especially in protocols relying on clinician-determined re-treatment. Current consensus recommends initiation with monthly injections for 3 months followed by maintenance comprising regular monthly visits with clinician-determined re-treatment. Further evidence on treatment protocols and the comparison with bevacizumab is awaited. CONCLUSIONS: Owing to incomplete evidence base health professionals face a large number of controversies and dilemmas in care pathways for patients with nAMD. Treatment should be delivered against protocols developed locally in a systematic manner with consensus and a cautious approach to change.

Early response of retinal angiomatous proliferation treated with intravitreal pegaptanib: a retrospective review.

AIMS: To evaluate the early functional and anatomical responses to intravitreal pegaptanib in patients with retinal angiomatous proliferation (RAP). METHODS: Retrospective review of consecutive patients newly diagnosed with RAP treated with intravitreal pegaptanib (0.3 mg). Examination at baseline and 12 weekly intervals included refraction protocol best corrected visual acuity (BCVA), fluorescein angiography (FA), and optical coherence tomography (OCT). At intervening 6 weekly visits a reduced protocol assessment included BCVA and OCT. RESULTS: A total of 16 eyes of 16 patients (12 female, mean age 76.0 years) with RAP at baseline (15 stage 3, one stage 2) were treated. One patient had poor response, losing 20 ETDRS letters after one injection and was switched to photodynamic therapy combined with intravitreal triamcinolone. Mean BCVA (n=15) was baseline 45+/-11 (mean+/-SD) letters, 12 weeks 43+/-14 letters, 24 weeks 40+/-14 letters; the reduction from baseline to 24 weeks was statistically significant (P=0.04). Vision remained stable defined as +/-15 letters of baseline BCVA in 13 (87%) of patients 2 (13%) lost >15 letters. Mean OCT central foveal thickness (CFT) (n=13) was: baseline 325+/-123 microm, 12 weeks 343+/-130 microm, 24 weeks 321+/-115 microm; difference at 24 weeks was not statistically significant (P=0.9). A pigment epithelial detachment was present in 12 cases; height was reduced in 10 cases at 24 weeks. Persistent leakage on FA was seen in 13 out of 15 cases at 24 weeks. CONCLUSION: Early results of treatment of RAP with intravitreal pegaptanib suggest some stabilizing effect on this normally progressive disease.

Verteporfin therapy in occult with no classic CNV due to AMD: results of the Photodynamic Therapy in Occult-Only Lesions study.

PURPOSE: To provide further information on verteporfin photodynamic therapy in occult with no classic choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD). METHODS: Verteporfin therapy was administered at baseline and then at months 3, 6, and 9, if fluorescein leakage from CNV was evident on angiography. RESULTS: Of 202 patients enrolled, 184 completed 12 months. Each patient was treated in one eye only. All study eyes received verteporfin therapy at baseline, with a progressive decrease in the number treated at subsequent visits (mean 2.5 treatments during 12 months). The mean change in visual acuity letter score from baseline to month 12 was -11.9. At month 12, 164 eyes (82.4%) had lost <30 letters of visual acuity, 123 eyes (61.8%) had lost <15 letters, 78 eyes (39.2%) had lost <5 letters, 31 (15.6%) had >5-letter increase, and 7 (3.5%) had >15-letter improvement. The percentage of eyes with fluorescein leakage from CNV decreased from 75.5% at month 3 to 25.1% at month 12. Adverse events were documented for 54% patients. Few patients had treatment-associated adverse events (7%). Acute severe visual acuity decrease occurred in two eyes (1%), one of which had visual acuity that returned to baseline by the next follow-up visit. CONCLUSIONS: This study provides additional evidence that over 12 months, verteporfin is generally well tolerated and maintains or improves visual acuity in over one-third of eyes containing occult-only CNV. Verteporfin also improved anatomical outcomes by reducing leakage from CNV in at least two-thirds of eyes.

Observational prospective study of the effectiveness in routine clinical practice of verteporfin photodynamic therapy in patients with neovascular age-related macular degeneration.

AIMS: To investigate effectiveness in routine clinical practice of verteporfin photodynamic therapy (PDT) for neovascular age-related macular degeneration (nAMD). PATIENTS AND METHODS: Patients commencing PDT for nAMD in a single UK centre entered a prospective observational 7-year study and were followed for 2 years. Best-corrected visual acuity (BCVA) and contrast sensitivity (CS) were measured at each visit by accredited technicians after full protocol refraction on standardised charts. Reasons for failure to complete the course of therapy were documented. RESULTS: 1008 patients entered the study between 1999 and 2006. 81% and 52% completed 12 and 24 months' follow-up respectively (excluding administrative censoring). Results at 12 and 24 months respectively were: maintenance of BCVA 62%, 63%; drop in mean BCVA (letters) 10.1, 9.4; numbers of treatments 2.9, 3.5. The mean CS remained stable. No correlation of change in BCVA outcome between first and second treated eyes in 82 bilateral cases was detected. Loss to follow-up was significantly associated with age, CS and distance from the treating centre. CONCLUSIONS: PDT delivered in clinical practice is at least as effective as that reported in randomised clinical trials and uses fewer treatments.

The introduction of verteporfin photodynamic therapy in the UK: PDT users group (PDTUG) surveillance programme report 1.

AIMS: To report overall patient recruitment characteristics and visual acuity (VA) outcome related to baseline lesion characteristics for patients with choroidal neovascularisation (CNV) treated with verteporfin photodynamic therapy (PDT) during its introduction into routine National Health Service practice. METHODS: Thirteen treatment centres prospectively submitted data on patients undergoing verteporfin PDT for CNV of mixed aetiology between November 1999 and May 2004 into the PDT Users Group (PDTUG) surveillance database. The primary outcome was the proportion of eyes losing <15 letters of VA at 12 and 24 months, follow-up compared with the baseline examination. RESULTS: One thousand eight hundred and ninety-four eyes of 1755 patients were analysed. Lesion characteristics at baseline were: classic no occult 1152 (67.4%), predominantly classic with occult 531 (31.1%). Recruitment rate rose steadily from 13 in the first to 188 in the final quarter. Data were available at 12 months on 1010 (53.3%) and at 24 months on 310 (16.4%) eyes. The proportion of eyes losing <15 letters was 71% (716/1010) at 12 months and 70% (217/310) at 24 months. At 12 months 91% (917/1010) of patients lost <30 letters. The mean number of PDT treatments for the cohort was 2.4 in the first 12 months. An adverse reaction or event was reported in 8.1% (364/4515) of treatments. Non-visual adverse events were infrequent. CONCLUSIONS: Efficacy and safety of verteporfin PDT in reducing vision loss in macular degeneration can be reproduced in routine clinical practice. Compared to the TAP study, the fewer treatments needed in the PDTUG cohort indicate the potential for better cost-effectiveness.

Changes in optic nerve head blood flow in children with cerebral malaria and acute papilloedema.

OBJECTIVE: To investigate capillary blood flow in the optic nerve head (ONH) of children with cerebral malaria. METHODS: Malawian children with cerebral malaria admitted to a paediatric research ward were examined by direct and indirect ophthalmoscopy. ONH blood flow was measured using laser Doppler flowmetry (LDF) in suitable patients. Mean blood volume and velocity were obtained from 30 to 60 s recordings from the temporal ONH and used to calculate blood flow. These were compared with admission variables, funduscopic findings and disease outcomes. RESULTS: 45 children with cerebral malaria had LDF recordings; 6 subsequently died and 5 survivors had neurological sequelae. 12 (27%) had papilloedema. The mean microvascular blood volume was higher in patients with papilloedema (3.28 v 2.54 arbitrary units, p = 0.002). The blood velocity correlated directly with haematocrit (r = 0.46, p = 0.001) and inversely with blood glucose (r = -0.49, p = 0.001). CONCLUSION: The increase in ONH microvascular blood volume in papilloedema measured by LDF is consistent with current theories of pathogenesis of papilloedema. LDF has potential as a tool to distinguish papilloedema from pseudopapilloedematous disc swellings. The relationship between blood velocity and haematocrit may relate to levels of sequestration in cerebral malaria.