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Purpose: We develop a mathematical model that predicts aqueous humor (AH) production rate by the ciliary processes and aqueous composition in the posterior chamber (PC), with the aim of estimating how the aqueous production rate depends on the controlling parameters and how it can be manipulated. Methods: We propose a compartmental mathematical model that considers the stromal region, ciliary epithelium, and PC. All domains contain an aqueous solution with different chemical species. We impose the concentration of all species on the stromal side and exploit the various ion channels present on the cell membrane to compute the water flux produced by osmosis, the solute concentrations in the AH and the transepithelial potential difference. Results: With a feasible set of parameters, the model predictions of water flux from the stroma to the PC and of the solute concentrations in the AH are in good agreement with measurements. Key parameters which impact the aqueous production rate are identified. A relevant role is predicted to be played by cell membrane permeability to K+ and Cl−, by the level of transport due to the Na+-H+ exchanger and to the co-transporter of Na+/K+/2Cl−; and by carbonic anhydrase. Conclusions: The mathematical model predicts the formation and composition of AH, based on the structure of the ciliary epithelium. The model provides insight into the physical processes underlying the functioning of drugs that are adopted to regulate the aqueous production. It also suggests ion channels and cell membrane properties that may be targeted to manipulate the aqueous production rate.

We consider a theoretical model for the flow of Newtonian fluid through a long flexible-walled channel which is formed from four compliant and rigid compartments arranged alternately in series. We drive the flow using a fixed upstream flux and derive a spatially one-dimensional model using a flow profile assumption. The compliant compartments of the channel are assumed subject to a large external pressure, so the system admits a highly collapsed steady state. Using both a global (linear) stability eigensolver and fully nonlinear simulations, we show that these highly collapsed steady states admit a primary global oscillatory instability similar to observations in a single channel. We also show that in some regions of the parameter space the system admits a secondary mode of instability which can interact with the primary mode and lead to significant changes in the structure of the neutral stability curves. Finally, we apply the predictions of this model to the flow of blood through the central retinal vein and examine the conditions required for the onset of self-excited oscillation. We show that the neutral stability curve of the primary mode of instability discussed above agrees well with canine experimental measurements of the onset of retinal venous pulsation, although there is a large discrepancy in the oscillation frequency.

Age-related macular degeneration (AMD) is a leading cause of blindness. Late AMD can be classified into exudative (commonly known as wet AMD [wAMD]) or dry AMD, both of which may progress to macular atrophy (MA). MA causes irreversible vision loss and currently has no approved pharmacological treatment. The standard of care for wAMD is treatment with anti-vascular endothelial growth factors (VEGFs). However, recent evidence suggests that anti-VEGF treatment may play a role in the development of MA. Therefore, it is important to identify risk factors for the development of MA in patients with wAMD. For example, excessive blockade of VEGF through intense use of anti-VEGF agents may accelerate the development of MA. Patients with type III macular neovascularization (retinal angiomatous proliferation) have a particularly high risk of MA. These patients are characterized as having a pre-existing thin choroid (age-related choroidopathy), suggesting that the choroidal circulation is unable to respond to increased VEGF expression. Evidence suggests that subretinal fluid (possibly indicative of residual VEGF activity) may play a protective role. Patients receiving anti-VEGF agents must be assessed for overall risk of MA, and there is an unmet medical need to prevent the development of MA without undertreating wAMD.

ObjectiveNeovascular age-related macular degeneration (nAMD) causes damage to the macula and severe vision loss. Bevacizumab is the most cost-effective nAMD treatment. The TANDEM trial was designed to determine whether, in patients with nAMD, low-dose bevacizumab is non-inferior to the standard dose in terms of visual deterioration and whether a bimonthly regimen is non-inferior to monthly, treatment as required, regimens.MethodsThis was a multicentre, 2×2 factorial, double-masked, non-inferiority randomised trial with patients considered eligible if they met the National Institute for Health and Care Excellence criteria for nAMD treatment with ranibizumab. Participants were randomly assigned to standard (1.25 mg) or low (0.625 mg) dose bevacizumab and either monthly or bimonthly review regimen. The primary outcome was time to vision deterioration, defined as reduction of ≥15 letters (three lines) during the loading phase (visual acuity scores at visits B and C compared with the initial visit A), or ≥6 letters (one line) during the maintenance phase (visual acuity scores at subsequent visits compared with mean vision at visits A–C).ResultsIn total 812 participants (918 eyes) were randomised into the trial. The low dose showed some evidence of being non-inferior to standard dose (HR 1.07; 95% CI 0.80 to 1.42), however, there was no strong evidence of bimonthly review being non-inferior to monthly review (HR 1.45; 95% CI 1.09 to 1.94). There was no difference in visual acuity when assessed at 9 months and no major differences in the frequency of serious adverse events or reactions between the groups.ConclusionThe standard dose of bevacizumab can be halved without compromising efficacy. Bimonthly review cannot be considered to be no worse than monthly review.

BACKGROUND/AIMS: Health-related quality of life (HRQoL) in age-related macular degeneration (AMD) is difficult to estimate as most generic tools underestimate vision. Our aim was to measure the effect of AMD on generic and visual quality of life and how it relates to handicap. We also aimed to validate the NG82 NICE AMD classification. Finally, we studied if a bolt-on visual domain increased the EQ-5D sensitivity to AMD. PATIENTS AND METHODS: Ninety-six patients with AMD participated in this observational cross-sectional study. Visual (VF-14) and generic questionnaires (EQ-5D) with VIS, and the London handicap scale (LHS) was used to quantify HRQoL and handicap. ANOVA and regression analysis were used to identify significant associations. RESULTS: Visual dysfunction in AMD has a significant effect in VF-14 (P

The retina is composed of two main layers—the neuroretina and the retinal pigment epithelium (RPE)—that are separated by a potential gap termed the sub-retinal space (SRS). Accumulation of fluid in the SRS may result in a retinal detachment. A key function of the RPE is to prevent fluid accumulation in the SRS by actively pumping fluid from this space to the choroid. We have developed a mathematical model of this process that incorporates the transport of seven chemical species: Na + , K + , Cl − , HCO 3 − , H + , CO 2 and H 2 CO 3 . This allows us to estimate solute and water fluxes and to understand the role of the different membrane ion channels. We have performed a global sensitivity analysis using the extended Fourier amplitude sensitivity test to investigate the relative importance of parameters in generating the model outputs. The model predicts that flow across the RPE is driven by an osmotic gradient in the cleft gap between adjacent cells. Moreover, the model estimates how water flux is modified in response to inhibition of membrane ion channels and carbonic anhydrase (CA). It provides a possible explanation for how CA inhibitors, which are used clinically to prevent fluid accumulation in the SRS, may be acting.

We consider a theoretical model for the flow of Newtonian fluid through a long flexible-walled channel which is formed from four compliant and rigid compartments arranged alternately in series. We drive the flow using a fixed upstream flux and derive a spatially one-dimensional model using a flow profile assumption. The compliant compartments of the channel are assumed subject to a large external pressure, so the system admits a highly collapsed steady state. Using both a global (linear) stability eigensolver and fully nonlinear simulations, we show that these highly collapsed steady states admit a primary global oscillatory instability similar to observations in a single channel. We also show that in some regions of the parameter space the system admits a secondary mode of instability which can interact with the primary mode and lead to significant changes in the structure of the neutral stability curves. Finally, we apply the predictions of this model to the flow of blood through the central retinal vein and examine the conditions required for the onset of self-excited oscillation. We show that the neutral stability curve of the primary mode of instability discussed above agrees well with canine experimental measurements of the onset of retinal venous pulsation, although there is a large discrepancy in the oscillation frequency. doi:10.1017/S1446181119000117

Purpose Investigating patients’ perceptions of their illness can provide important insights into the experience and management of the illness and associated treatment, and enhance understanding of variations in adherence to prescribed medication. The Common-Sense Model of Self-Regulation (CSM) provides a theoretical framework for the study of illness cognitions, health behavior, and adherence to health recommendations. The aim of this study was to use the CSM to investigate the experience of glaucoma and its treatment from the patients’ perspective, and to apply these insights to classify and clarify issues related to nonadherence with treatment. Patients and methods A qualitative investigation using semi-structured interviews took place in two outpatient glaucoma clinics. Thirty-three patients with primary open-angle glaucoma using hypotensive eye drops participated in the study. Deductive content analysis was used to analyze the interview data. Results Issues relating to nonadherence with hypotensive eye drops and patients’ experience with their glaucoma and treatment were identified. Treatment schedule and patient factors were classified as common barriers to adherence. Further themes include experienced symptoms of glaucoma, illness coherence, and the emotional and practical consequences of the illness. Conclusion Findings provide important insights into the emotional and practical outcomes of glaucoma for patients, perceived symptoms of the illness, and insights into patient memory and cognition. These findings provide supporting evidence for the importance of conducting theoretically driven qualitative investigations of patients’ experience with glaucoma and their treatment, and provide suggestions on key issues that need to be addressed in future multidimensional interventions aimed at improving adherence and patient quality of life.

Purpose In recent years there has been an increase in evidence for the functional and psychosocial benefits of correcting strabismus/heterotropia in adults. This study aimed to establish whether there has been an associated change in the frequency of strabismus surgery performed on adults in England since 2000. Methods Data on strabismus surgery performed in England between 2000 and 2014 were obtained from Hospital Episode Statistics, Health and Social Care Information Centre, England. The frequency of strabismus surgery was analysed for different age groups. Data were considered in the context of total population data for England, obtained from the Office for National Statistics Results There was little change in the total number of strabismus operations performed in 2000 to 2014 (1% reduction). In the same period the number of operations performed on children aged 0-¬‐15 years decreased by 17%. In contrast, there was a 24% increase in the number of strabismus operations performed on patients aged 15 years or older. Conclusions Although strabismus surgery is still most commonly performed on children, the data show there has been a significant increase in the number of strabismus operations performed on adults. We speculate that this increase is connected to the growing weight of evidence detailing the functional and psychosocial consequences of strabismus. These results have potential implications for the delivery of future care

The retinal pigment epithelium (RPE) is the outermost cell layer of the retina. It has several important physiological functions, among which is removal of excess fluid from the sub-retinal space by pumping it isotonically towards the choroid. Failure of this pumping leads to fluid accumulation, which is closely associated with several pathological conditions, such as age-related macular degeneration, macular oedema and retinal detachment. In the present work we study mechanisms responsible for fluid transport across the RPE with the aim of understanding how fluid accumulation can be prevented. We focus on two possible mechanisms, osmosis and electroosmosis, and develop a spatially resolved mathematical model that couples fluid and ion transport across the epithelium, accounting for the presence of Na+, K+ and Cl- ions. Our model predicts spatial variability of ion concentrations and the electrical potential along the cleft gap between two adjacent cells, which osmotically drives the flow across the lateral membranes. This flow is directed from the sub-retinal space to the choroid and has a magnitude close to measured values. Electroosmosis is subdominant by three orders of magnitude to osmosis and has an opposite direction, suggesting that local osmosis is the main driving mechanism for water transport across the RPE.

Background Amblyopia (lazy eye) affects the vision of approximately 2% of all children. Traditional treatment consists of wearing a patch over their ‘good’ eye for a number of hours daily, over several months. This treatment is unpopular and compliance is often low. Therefore, results can be poor. I-BiT is a system, based on stereo technology using shutter glasses, designed to treat amblyopia using dichoptic stimulation. This trial uses a redesigned system for home use and includes eye-tracking capability. Methods/design This is a randomised controlled trial involving three groups of 40 patients each, aged between 3.5 and 12 years, with a diagnosis of (1) anisometropic amblyopia, (2) mixed or strabismic amblyopia prior to strabismic surgery and (3) mixed or strabismic amblyopia who have just undergone strabismus surgery. They will be randomised in a 1:1 ratio between I-BiT and control and will receive treatment, at home over a 6-week period. Their visual acuity will be assessed independently at baseline, mid-treatment (week 3), at the end of treatment (week 6) and, for those receiving the active I-BiT treatment, 4 weeks after completing treatment (week 10). The primary endpoint will be the change in visual acuity from baseline to the end of treatment. Secondary endpoints will be additional visual acuity measures, patient acceptability, compliance and the incidence of adverse events. Discussion This is a randomised controlled trial using the redesigned I-BiT™ system to determine if this is a feasible treatment strategy for the management of anisometropic, strabismic and mixed amblyopia. Trial registration ISRCTN Number/Clinical trials.gov, ID: NCT02810847. Registered on 23 June 2016. Electronic supplementary material The online version of this article (10.1186/s13063-019-3523-0) contains supplementary material, which is available to authorized users.

To determine whether the oxygen toxicity hypothesis can explain the distinctive spatio-temporal patterns of retinal degeneration associated with human retinitis pigmentosa (RP) and to predict the effects of antioxidant and trophic factor treatments under this hypothesis.Three mathematical models were derived to describe the evolution of the retinal oxygen concentration and photoreceptor density over time. The first model considers only hyperoxia-induced degeneration, while the second and third models include mutation-induced rod and cone loss respectively. The models were formulated as systems of partial differential equations, defined on a two-dimensional domain spanning the region between the foveal center and the ora serrata, and were solved numerically using the finite element method.The mathematical models recapitulate patterns of retinal degeneration which involve preferential loss of photoreceptors in the parafoveal/perifoveal and far-peripheral retina, while those which involve a preferential loss of midperipheral photoreceptors cannot be reproduced. Treatment with antioxidants or trophic factors is predicted to delay, halt, or partially reverse retinal degeneration, depending upon the strength and timing of treatment and disease severity.The model simulations indicate that while the oxygen toxicity hypothesis is sufficient to explain some of the patterns of retinal degeneration observed in human RP, additional mechanisms are necessary to explain the full range of behaviors. The models further suggest that antioxidant and trophic factor treatments have the potential to reduce hyperoxia-induced disease severity and that, where possible, these treatments should be targeted at retinal regions with low photoreceptor density to maximize their efficacy.

The retina is the tissue layer at the back of the eye that is responsible for light detection. Whilst equipped with a rich supply of oxygen, it has one of the highest oxygen demands of any tissue in the body and, as such, supply and demand are finely balanced. It has been suggested that the protein neuroglobin (Ngb), which is found in high concentrations within the retina, may help to maintain an adequate supply of oxygen via the processes of transport and storage. We construct mathematical models, formulated as systems of reaction-diffusion equations in one-dimension, to test this hypothesis. Numerical simulations show that Ngb may play an important role in oxygen transport, but not in storage. Our models predict that the retina is most susceptible to hypoxia in the regions of the photoreceptor inner segment and inner plexiform layers, where Ngb has the potential to prevent hypoxia and increase oxygen uptake by 30-40 %. Analysis of a simplified model confirms the utility of Ngb in transport and shows that its oxygen affinity ([Formula: see text] value) is near optimal for this process. Lastly, asymptotic analysis enables us to identify conditions under which the piecewise linear and quadratic approximations to the retinal oxygen profile, used in the literature, are valid.

The group of genetically mediated diseases, known collectively as retinitis pigmentosa (RP), cause retinal degeneration and, hence, loss of vision. The most common inherited retinal degeneration, RP is currently untreatable. The retina detects light using cells known as photoreceptors, of which there are two types: rods and cones. In RP, genetic mutations cause patches of photoreceptors to degenerate and typically directly affect either rods or cones, but not both. During disease progression, degenerate patches spread and the unaffected photoreceptor type also begins to degenerate. The cause underlying these phenomena is currently unknown. The oxygen toxicity hypothesis proposes that secondary photoreceptor loss is due to hyperoxia (toxically high oxygen levels), which results from the decrease in oxygen uptake following the initial loss of photoreceptors. In this paper, we construct mathematical models, formulated as 1D systems of partial differential equations, to investigate this hypothesis. Using a combination of numerical simulations, asymptotic analysis and travelling wave analysis, we find that degeneration may spread due to hyperoxia, and generate spatio-temporal patterns of degeneration similar to those seen in vivo. We determine the conditions under which a degenerate patch will spread and show that the wave speed of degeneration is a monotone decreasing function of the local photoreceptor density. Lastly, the effects of treatment with antioxidants and trophic factors, and of capillary loss, upon the dynamics of photoreceptor loss and recovery are considered.

A computer-based interactive binocular treatment system (I-BiT) for amblyopia has been developed, which utilises commercially available 3D ‘shutter glasses’. The purpose of this pilot study was to report the effect of treatment on visual acuity (VA) in children with amblyopia. Thirty minutes of I-BiT treatment was given once weekly for 6 weeks. Treatment sessions consisted of playing a computer game and watching a DVD through the I-BiT system. VA was assessed at baseline, mid-treatment, at the end of treatment, and at 4 weeks post treatment. Standard summary statistics and an exploratory one-way analysis of variance (ANOVA) were performed. Ten patients were enrolled with strabismic, anisometropic, or mixed amblyopia. The mean age was 5.4 years. Nine patients (90%) completed the full course of I-BiT treatment with a mean improvement of 0.18 (SD=0.143). Six out of nine patients (67%) who completed the treatment showed a clinically significant improvement of 0.125 LogMAR units or more at follow-up. The exploratory one-way ANOVA showed an overall effect over time (F=7.95, P=0.01). No adverse effects were reported. This small, uncontrolled study has shown VA gains with 3 hours of I-BiT treatment. Although it is recognised that this pilot study had significant limitations—it was unblinded, uncontrolled, and too small to permit formal statistical analysis—these results suggest that further investigation of I-BiT treatment is worthwhile.

PURPOSE: To describe changes in intraocular pressure (IOP) in the 'alternative treatments to Inhibit VEGF in Age-related choroidal Neovascularisation (IVAN)' trial (registered as ISRCTN92166560).DESIGN: Randomised controlled clinical trial with factorial design.PARTICIPANTS: Patients (n=610) with treatment naïve neovascular age-related macular degeneration were enrolled and randomly assigned to receive either ranibizumab or bevacizumab and to two regimens, namely monthly (continuous) or as needed (discontinuous) treatment.METHODS: At monthly visits, IOP was measured preinjection in both eyes, and postinjection in the study eye.OUTCOME MEASURES: The effects of 10 prespecified covariates on preinjection IOP, change in IOP (postinjection minus preinjection) and the difference in preinjection IOP between the two eyes were examined.RESULTS: For every month in trial, there was a statistically significant rise in both the preinjection IOP and the change in IOP postinjection during the time in the trial (estimate 0.02 mm Hg, 95% CI 0.01 to 0.03, pCONCLUSIONS: Anti-vascular endothelial growth factor agents induce increases in IOP of small and uncertain clinical significance.TRIAL REGISTRATION NUMBER: ISRCTN92166560.

PURPOSE. In glaucoma, elevated intraocular pressure causes a progressive loss of retinal ganglion cells and results in optic neuropathy. The authors propose a potential mechanism for cell death, whereby elevated intraocular pressure causes fluid to permeate axonal membranes, creating a passive intracellular fluid flow within the axons. It is hypothesized that this intracellular flow locally depletes the adenosine triphosphate (ATP) concentration, disrupting axonal transport and leading to cell death. METHODS. A mathematical model was developed that takes into account the biomechanical principles underpinning the proposed hypothesis, and was solved to determine the implications of the mechanism. RESULTS. The model suggests that the raised intraocular pressures present in glaucoma are adequate to produce significant intracellular fluid flow. In the periphery of the optic nerve head, this flow may be sufficient to disrupt the diffusion of ATP and hence interrupt active axonal transport. CONCLUSIONS. The mathematical model demonstrates that it is physically plausible that a passive intracellular fluid flow could significantly contribute to the pathophysiology of the retinal ganglion cell axon in glaucoma. (Invest Ophthalmol Vis Sci. 2009; 50: 3750-3758) DOI: 10.1167/iovs.08-2396

The retina confers upon us the gift of vision, enabling us to perceive the world in a manner unparalleled by any other tissue. Experimental and clinical studies have provided great insight into the physiology and biochemistry of the retina; however, there are questions which cannot be answered using these methods alone. Mathematical and computational techniques can provide complementary insight into this inherently complex and nonlinear system. They allow us to characterise and predict the behaviour of the retina, as well as to test hypotheses which are experimentally intractable. In this review, we survey some of the key theoretical models of the retina in the healthy, developmental and diseased states. The main insights derived from each of these modelling studies are highlighted, as are model predictions which have yet to be tested, and data which need to be gathered to inform future modelling work. Possible directions for future research are also discussed. Whilst the present modelling studies have achieved great success in unravelling the workings of the retina, they have yet to achieve their full potential. For this to happen, greater involvement with the modelling community is required, and stronger collaborations forged between experimentalists, clinicians and theoreticians. It is hoped that, in addition to bringing the fruits of current modelling studies to the attention of the ophthalmological community, this review will encourage many such future collaborations.

PurposeTo determine the opinions from a patient perspective on relevant variables in the delivery of treatment for neovascular age-related macular degeneration (nAMD).MethodsPilot interviews with patients and doctors were conducted to identify what variables in the provision of a nAMD service were important. This led to the generation of two sets of scenario options. Subsequently 100 patients undergoing active treatment for nAMD in the National Health Service University Hospital, United Kingdom underwent interview assessment. They were asked to rank their preferences for provision of their care with reference to these two sets of scenario options. Using conjoint analysis, percentage preferences, and utility scores for each variable in each scenario design were calculated.ResultsNinety-five patients completed the preference ranking for both scenarios. Eight patients ranked worse vision as preferable to better vision and were excluded on the basis that they had not understood the task. The results of the remaining 87 patients are presented. The most important factor to patients was having good vision, followed by a one-stop service and less frequent follow up. The least important factors were label status of the drug, cost to the health service, and grade of the injector.ConclusionPatients regard good vision and minimal visits to the hospital above the status of injector, label status of drug, or cost to the NHS.

Objectives The ultrastructural appearance of retinal capillaries can yield important information about disease mechanisms, but is not well characterised in human post mortem samples. We therefore aimed to create a baseline for the appearance of capillaries and establish how this is influenced by post mortem fixation delays and donor age. Methods Electron microscopy was used to characterise retinal capillaries in 20 anonymous donors (with no known eye diseases) of various ages and with various post mortem fixation delays. In addition, samples from six patients with conditions that are known to affect the retinal vasculature (four cases of type 2 diabetes without diabetic retinopathy, one case of diabetic retinopathy and one case of macular telangiectasia type 2) were analysed. Results Vacuoles were found in capillary basement membranes at the vessel–glia interface in all samples, from both the normal and disease cases. Vacuole frequency increased with donor age but was not influenced by post mortem fixation delays. Conclusion Vacuoles in the basement membrane are a normal feature of adult human retinal capillaries and do not indicate disease. Their incidence increases with age and might be a contributing factor to late-onset pathologies of the retinal vasculature.

The aim of this study was to evaluate the cost-effectiveness of second-eye cataract surgery for older women with minimal visual dysfunction in the eye to be operated on from a Health and Personal Social Services perspective, compared to waiting list controls who had already undergone first-eye cataract surgery.A cost-utility analysis was undertaken alongside a randomized controlled trial of second-eye cataract surgery in secondary care ophthalmology clinics. A total of 239 women over 70 years old with one unoperated cataract were randomized to cataract surgery (expedited, approximately 4 weeks) or control (routine surgery, 12 months wait). Outcomes were measured in terms of quality-adjusted life years (QALYs), with health-related quality of life estimated using the EuroQol EQ-5D.The operated group had costs which were, on average, pound646 more than the control group (95% confidence interval, pound16-1276, P0.04) and had a mean QALY gain of 0.015 (95% confidence interval, -0.039 to 0.068, P=0.59) per patient over 1 year. Therefore, the incremental cost-utility ratio was pound44,263 over the 1-year trial period. In an analysis modelling costs and benefits over patients' expected lifetime, the incremental cost per QALY was pound17,299, under conservative assumptions.Second-eye cataract surgery is not likely to be cost-effective in the short term for those with mild visual dysfunction pre-operation. In the long term, second-eye cataract surgery appears to be cost-effective unless carer costs are included.

Severe cases of blepharospasm resistant to botulinum toxin represent a challenging clinical problem. Over the last 10 years, we have adopted a staged surgical management of these cases with an initial upper lid orbicularis myectomy (combined with myectomy of procerus and corrugator supercilius as appropriate) and then 4-6 months later a brow suspension with autologous fascia lata. The aim of this study was to assess the outcome of this staged surgical approach.A questionnaire was sent to all patients who had undergone the procedure and the clinical records reviewed.Fourteen patients had undergone the procedure of which 13 were alive. They were sent a questionnaire and 10 of them responded. All had both procedures. Eight of the 10 reported great benefit from the surgery, one some benefit, and one was worse off. All patients still required botulinum toxin injections after the surgery.Majority, but not all, of the patients in our series greatly benefitted from this staged surgical approach.

Central retinal vein occlusions (CRVOs) are rarely treatable; most therapy is directed towards prevention or treatment of complications. Bilateral CRVO can be due to serum hyperviscosity, which affects 15% of all patients with Waldenstrom's macroglobulinaemia (WM). Although previously reported in a handful of cases, bilateral CRVO is a rare presenting feature.Illustrated case reports of three patients presenting with bilateral CRVO due to undiagnosed WM.Plasma exchange, which successfully restored vision in two patients, was followed by long-term cytotoxic therapy.Plasma electrophoresis should be performed in all patients with retinal vein occlusions to exclude a paraproteinaemia. In patients with bilateral venous changes, there should be a very high level of suspicion of hyperviscosity, with the possibility of effective early therapy.

Objective first eye cataract surgery reduces the risk of falling. Most cataracts in elderly people are bilateral. Some binocular functions (e.g. stereopsis) are associated with falls. We aimed to determine if second eye cataract surgery reduces the risk of falling and to measure associated health gain. Study design and setting we randomised 239 women over 70, who had been referred to a hospital ophthalmology department, with one unoperated cataract, to expedited (approximately 4 weeks) or routine (12 months wait) surgery. Falls were ascertained by diary, with follow-up every 3 months for 12 months. We measured health status after 6 months. Results visual function (especially stereopsis) improved in the operated group. Over 12 months follow-up, 48 (40%) operated participants fell at least once, 22 (18%) fell more than once. Forty-one (34%) unoperated participants fell at least once, 22 (18%) fell more than once. Rate of falling was reduced by 32% in the operated group, but this was not statistically significant (rate ratio 0.68, 95% CI 0.39, 1.19, P = 0.18). Confidence, visual disability and handicap all improved in the operated compared with the control group. Conclusion second eye cataract surgery improves visual disability and general health status. The effect on rate of falling remains uncertain.

Background/aim: A third of elderly people fall each year. Poor vision is associated with increased risk of falls. The authors aimed to determine if first eye cataract surgery reduces the risk of falling, and to measure associated health gain. Methods: 306 women aged over 70, with cataract, were randomised to expedited (approximately 4 weeks) or routine (12 months wait) surgery. Falls were ascertained by diary, with follow up every 3 months. Health status was measured after 6 months. Results: Visual function improved in the operated group (corrected binocular acuity improved by 0.25 logMAR units; 8% had acuity worse than 6/12 compared with 37% of controls). Over 12 months of follow up, 76 (49%) operated participants fell at least once, and 28 (18%) fell more than once. 69 (45%) unoperated participants fell at least once, 38 (25%) fell more than once. Rate of falling was reduced by 34% in the operated group (rate ratio 0.66, 95% confidence interval 0.45 to 0.96, p = 0.03). Activity, anxiety, depression, confidence, visual disability, and handicap all improved in the operated group compared with the control group. Four participants in the operated group had fractures (3%), compared with 12 (8%) in the control group (p = 0.04). Conclusion: First eye cataract surgery reduces the rate of falling, and risk of fractures and improves visual function and general health status.

BACKGROUND: Bevacizumab (Avastin®) is as effective as ranibizumab (Lucentis®) in the treatment of neovascular age-related macular degeneration (nAMD). However it has two important structural differences. First, it has two active sites instead of one; second, it retains the Fc portion of the antibody which would be expected to confer a significantly longer half-life. These agents have been associated with systemic complications including strokes, so it is desirable to use the smallest effective dose. Furthermore, the standard dosing regimen requires monthly hospital visits, which present a significant challenge both to the hospital services and to the patients (who are elderly).METHODS/DESIGN: Patients ≥50 years who are eligible for anti-vascular endothelial growth factor (VEGF) treatment of nAMD in the NHS, who are either newly referred for treatment or have reactivation of nAMD and who have not received treatment to either eye for the previous six months. We have designed a factorial multi-centre masked randomised controlled trial using bevacizumab as the intervention, with patients randomised to one of four arms: to standard or low dose and to monthly or two-monthly patient review. The aim is to recruit sufficient patients (around 1,000) to obtain 304 patients meeting the endpoint over a four-year period. The primary endpoint is time to treatment failure to be analysed using Cox regression.DISCUSSION: This randomised control trial will show if half dose and two monthly as required is as effective as full dose and monthly regimes. A two monthly as required regimen of Bevacizumab would significantly reduce both the cost and the service delivery burden for the treatment of nAMD while a reduced dose would be expected to enhance the safety profile of this treatment regime.TRIAL REGISTRATION: International Standard Randomised Controlled Trial Number: ISRCTN95654194 , registered on 22 September 2009.

Purpose: There is no easy way to estimate the intracranial pressure (ICP) non-invasively. The retinal vein can exhibit large amplitude oscillations at the level of the lamina cribrosa under certain circumstances. The aim of this study was to develop a theoretical understanding of the conditions required to establish this vigorous oscillatory behaviour and whether observations of it could lead to a non-invasive estimate of the ICP. Methods: A mathematical model was constructed in which the central retinal vein was modelled as two Starling resistors in series, one located in the eye and the other in the cerebrospinal fluid (CSF) space, separated by a region where it was not collapsible corresponding to its course within the optic nerve itself. The intraocular pressure (IOP) and ICP were modelled as sinusoidal wave forms. Results: The model predicts an approximately linear relationship between the IOP and the ICP at the point of onset of oscillatory behaviour. The predicted onset IOP also depends weakly on the retinal blood flow rate and the vein diameter and is only mildly sensitive to the phase difference between the two pressure waveforms. The predicted onset curve shows encouraging agreement with measurements in canines. Conclusions: The model suggests that it may be possible to estimate of the ICP from observations of the retinal venous pulse using a modified form of ophthalmodynamometry.

BACKGROUND Patients with uveal melanoma can be treated by a number of modalities. As none of the different treatments offer a survival advantage, a key factor in choosing among treatments is their differential impact on patients9 quality of life. A short, patient based questionnaire was developed and validated for evaluating outcomes following treatment for uveal melanoma. METHODS The 21 item measure of outcome in ocular disease (MOOD) assesses the patient9s view of outcome in terms of visual function and the impact of treatment. The reliability and validity of the three MOOD scores (total, vision, impact) were evaluated in 176 patients who had been treated for uveal melanoma (75 brachytherapy, 78 proton beam radiotherapy, 23 enucleation). Of these, 165 patients also completed the SF-36. RESULTS All three MOOD scales met standard criteria for acceptability, reliability, and validity. The proportion of missing data was low, and responses to all items were well distributed across response categories. Internal consistency, assessed by Cronbach9s alpha coefficients, exceeded the standard criterion of 0.70 for all three summary scores. Item total correlations ranged from 0.22 to 0.77 (mean item total correlation 0.58), indicating good homogeneity. Test-retest correlations for all three summary scores exceeded 0.85. Scaling assumptions, assessed by item convergent and discriminant validity correlations, were met for the vision and impact scores. The MOOD showed good content validity, as assessed by review by ophthalmologists and patients. Construct validity was demonstrated by high intercorrelations between the vision and impact scores and the total scale; higher scores for patients who reported being very satisfied compared with those who were not very satisfied and for those who reported persistent red eye compared with those who did not have this complication (known group differences/hypothesis testing); moderate correlations between the MOOD and the SF-36 and visual acuity (convergent validity); and low correlations between the MOOD and age and sex (discriminant validity). CONCLUSIONS The MOOD is a practical and scientifically sound patient based measure which can be used in research and audit to evaluate outcomes following treatment for uveal melanoma. It takes 5 minutes to complete and meets standard psychometric criteria for reliability and validity.

Treatment of choroidal melanoma by chemotherapy is usually unsuccessful, with response rates of less than 1% reported for dacarbazine (DTIC)-containing regimens which show 20% or more response rates in skin melanoma. Recently, we reported the activity of several cytotoxic agents against primary choroidal melanoma in an ATP-based tumour chemosensitivity assay (ATP-TCA). In this study, we have used the same method to examine the sensitivity of choroidal melanoma to combinations suggested by our earlier study. Tumour material from 36 enucleated eyes was tested against a battery of single agents and combinations which showed some activity in the previous study. The combination of treosulfan with gemcitabine or cytosine arabinoside showed consistent activity in 70% and 86% of cases, respectively. Paclitaxel was also active, particularly in combination with treosulfan (47%) or mitoxantrone (33%). Addition of paclitaxel to the combination of treosulfan + cytosine analogue added little increased sensitivity. For treosulfan + cytosine arabinoside, further sequence and timing experiments showed that simultaneous administration gave the greatest suppression, with minor loss of inhibition if the cytosine analogue was given 24 h after the treosulfan. Administration of cytosine analogue 24 h before treosulfan produced considerably less inhibition at any concentration. While we have so far been unable to study metastatic tumour from choroidal melanoma patients, the combination of treosulfan with gemcitabine or cytosine arabinoside shows activity ex vivo against primary tumour tissue. Clinical trials are in progress. © 1999 Cancer Research Campaign

Purpose Uveal melanoma undergoes haematogenous dissemination, particularly to the liver. It is routine practice to screen for metastatic disease. The purpose of this study was to evaluate such screening tests and to determine their value in detecting metastatic disease at presentation. Methods In this study of a series of 245 patients with uveal melanoma of whom 55 (22%) died, the sensitivity, specificity, positive and negative predictive powers and likelihood ratio of the blood tests, chest radiographs and liver ultrasound investigations performed at diagnosis were determined. Results All the screening investigations were found to have a low yield, but the most sensitive were those for gamma-glutamyl transpeptidase (γGT;sensitivity 21%) and alkaline phosphatase (sensitivity 25%), with 7GT being more specific (specificity 92%). No blood test had a positive predictive power greater than 50%. The chest radiograph and liver ultrasonography were both 100% specific but had sensitivities of 2% and 14% respectively. Conclusions Only the chest radiograph and liver ultrasonography had positive predictive powers greater than 50% and these tests had very poor sensitivity. We conclude that there is no good test available for screening for metastatic uveal melanoma.

AIM—To investigate the effects of single, short term (5 or 30 minutes) exposures to thiotepa or 5-fluorouracil (5-FU) on collagen lattice contraction and retinal pigment epithelial (RPE) cell proliferation. METHODS—For collagen contraction studies, RPE cells seeded into free floating type I collagen lattices were exposed to single 5 or 30 minute treatments with thiotepa (0.06-4 mg/ml), or 5-FU (0.25-25 mg/ml), or phosphate buffered saline alone as a control. For proliferation studies, RPE cell monolayers were similarly exposed to these agents. The degree of contraction, effects on cell number, and viability were determined up to 14 days after treatment. RESULTS—Contraction of collagen lattices containing RPE cells and proliferation of RPE cells were significantly inhibited (p

Sir, We thank Dr Yeo1 for the kind comments and would like to answer the specific points raised: The lists were training lists and trainees started on the straight forward cases and avoided, for example, white cataracts, pseudo-exfoliation, and vitrectomized eyes initially and we believe that this is the standard practice. The trainers were not blinded and there was no clear tendency to take over early, please note that completed number of cases in the 6-month block ranged from 151 to 194. In fact, the program was designed with reverse module training to ensure that this was minimized as repeatedly taking over cases both reduces confidence and interferes with learning, which we were keen to avoid. There is a tension between the six sigma approach, adopted here, to try and reduce the risk of an adverse event to more than six standard deviations from the mean (or one in a million) with evidence-based medicine (which is two standard deviations from the mean (or one in twenty) and requires a control arm). The advantage of the six sigma approach is that it is potentially much more responsive to change, easier to implement, and has the added advantage of setting a higher standard to aim for. We think that the role of a randomized control trial is best indicated when there is equipoise between the competing options, which we do not think is the situation here. So, while the authors are supporters of evidence-based medicine and actively undertake clinical trials, here the improvements were achieved by implementing what we thought would be a much better system, in keeping with the six sigma approach, followed by evaluation. It should be noted that the trainee surgeons were not selected but were simply the next three in-line on the basis of their appointment dates to the program. Although the numbers are small, what we have shown is proof of principle that it is possible to train a cataract surgeon without an initial high-risk phase for the patient and we would now consider it inappropriate to revert, even for a control arm in a trial. We see the challenge now is to make these results the norm and not the exception.

Background: Amblyopia (lazy eye) affects the vision of approximately 2% of all children. Traditional treatment consists of wearing a patch over their ‘good’ eye for a number of hours daily, over several months. This treatment is unpopular and compliance is often low. Therefore results can be poor. A novel binocular treatment which uses 3D technology to present specially developed computer games and video footage (I-BiT™) has been studied in a small group of patients and has shown positive results over a short period of time. The system is therefore now being examined in a randomised clinical trial. Methods/design: Seventy-five patients aged between 4 and 8 years with a diagnosis of amblyopia will be randomised to one of three treatments with a ratio of 1:1:1 - I-BiT™ game, non-I-BiT™ game, and I-BiT™ DVD. They will be treated for 30 minutes once weekly for 6 weeks. Their visual acuity will be assessed independently at baseline, mid-treatment (week 3), at the end of treatment (week 6) and 4 weeks after completing treatment (week 10). The primary endpoint will be the change in visual acuity from baseline to the end of treatment. Secondary endpoints will be additional visual acuity measures, patient acceptability, compliance and the incidence of adverse events. Discussion: This is the first randomised controlled trial using the I-BiT™ system. The results will determine if the I-BiT™ system is effective in the treatment of amblyopia and will also determine the optimal treatment for future development. Trial registration: ClinicalTrials.gov identifier: NCT01702727 Keywords: Amblyopia, I-BiT™, Randomised clinical trial, Lazy eye, Child, Visual acuity, Binocular

To evaluate the safety of an intensive cataract surgery training programme. An intensive cataract surgery training programme was implemented in August 2010 for year 3 ophthalmology trainees in the East Midlands Deanery North Rotation (United Kingdom). Trainees participated in extra-ocular surgery and 50 h of virtual reality cataract surgery simulator training over a 2-year period. Their third year comprised 6 months of intensive phacoemulsification training in a tertiary centre followed by a 6-month period of consolidation in a district general hospital. The complication rates and case numbers were evaluated after the first 2 years of implementation. At 2 years, three trainees had completed a full year of intensive training. In the first 6 months of training, Trainee 1 completed 156 cases, Trainee 2 completed 194 cases, and Trainee 3 completed 151 full cases as primary surgeons with an average rate of posterior capsule rupture (PCR) of 1%. At 12 months, Trainee 1 completed 291, Trainee 2 completed 318, and Trainee 3 completed 294 cases, with an average PCR rate of 0.66%. The trainees required 84 lists on average to complete 150 full cataract procedures. The combination of simulation and the new intensive training programme is safer than the traditional programme for cataract surgery training.

Both cutaneous and uveal melanoma undergo haematogenous dissemination. Detection of tyrosinase mRNA by reverse transcription-polymerase chain reaction (RT-PCR) has been described as an extremely sensitive way of detecting circulating viable melanoma cells in the peripheral venous blood, and this technique may be of value in the early detection of dissemination. Also, it has been suggested that surgical manipulation of the eye, such as occurs during enucleation, can provoke uveal melanoma dissemination. The purpose of this study was to evaluate whether tyrosinase mRNA is detectable in the peripheral blood of patients with uveal and cutaneous melanoma and in patients with uveal melanoma undergoing surgical procedures on the eye harbouring the tumour. Venous blood samples from 36 patients diagnosed as having active uveal melanoma and from six patients with advanced metastatic cutaneous melanoma were analysed. In addition, blood samples were spiked with known numbers of cells from three cell lines and four primary uveal melanoma cultures. The reported sensitivity of the technique was confirmed, with an ability to detect down to one cell per ml of blood. All 51 blood samples from the 36 patients with uveal melanoma were negative, and this included 20 perioperative blood samples. The test was also negative for the six patients with advanced cutaneous melanoma. There were two positives among 31 control samples analysed. This study demonstrates that there are far fewer circulating viable melanocytes than has been previously supposed in patients with melanoma and that the RT-PCR is of no clinical value in detecting metastatic melanoma disease. There was no evidence for surgery causing a bolus of melanoma cells to enter the peripheral circulation. Images Figure 1 Figure 2

The outer blood–retinal barrier is composed of a monolayer of retinal pigment epithelium, Bruch’s membrane and the choriocapillaris which is fenestrated. Endothelial proliferation and breaching of Bruch’s membrane leads to the neovascular form of age-related macula degeneration (ARMD). The aim of this study was to generate an in vitro model that mimics more faithfully the phenotype of the choriocapillaris and the trilayer architecture in vitro . A trilayer culture model was generated with retinal pigment epithelium (ARPE-19) cell cultures on the epithelial surface of amniotic membrane and with human umbilical vein-derived endothelial cells on the other surface. A control model for the effect of retinal pigment epithelium on endothelial changes was generated with corneal epithelial cells replacing the ARPE-19. Both human umbilical vein-derived endothelial and ARPE-19 cells formed confluent monolayers on respective surfaces of the amnion. The human umbilical vein-derived endothelial cells in the trilayer became fenestrated when co-cultured with the ARPE-19 cells, but not with corneal epithelial cells, or when grown as monolayers on the amnion, showing a loss of fidelity of origin in the presence of ARPE-19 cells. These cells also revealed VE-cadherin and ZO-1 at cell–cell contacts from 24 h in the trilayer. The tight junctional molecules, occludin and ZO-1, were localized to cell–cell contact regions in the retinal pigment epithelium, both in the monolayer and in the trilayer system. Permeability of the trilayer was tested by using fluorescein and fluorescein-conjugated tracers under flow. At 72 h the trilayer severely restricted transfer of sodium fluorescein (NaF) (ten-fold reduction) whilst transfer of a 4 kDa FITC-conjugated dextran was virtually occluded, confirming a restrictive barrier. Ultrastructural studies showed the retinal pigment epithelium monolayer was polarized with microvilli present on the apical surface. Paracellular clefts showed numerous tight junctional-like appositions, similar to that seen on amnion alone. This study demonstrates that ARPE-19 and human umbilical vein-derived endothelial cells can be co-cultured on the amniotic membrane and that the resultant cross-talk leads to formation of a fenestrated endothelium, whilst maintaining a polarized restrictive epithelial layer. The fenestrated endothelial phenotype achieved in this human in vitro trilayer model is a first and offers an outer-retinal barrier which approaches the in vivo state and has potential for studies into induced junctional disruption, endothelial proliferation and migration: features of ARMD.

To evaluate the cost-effectiveness of first eye cataract surgery compared with no surgery from a health service and personal social services perspective.An economic evaluation undertaken alongside a randomised controlled trial of first eye cataract surgery in secondary care ophthalmology clinics. A sample of 306 women over 70 years old with bilateral cataracts was randomised to cataract surgery (expedited, approximately four weeks) or control (routine, 12 months wait); 75% of participants had baseline acuity of 6/12 or better. Outcomes included falls and the EuroQol EQ-5D.The operated group cost a mean pounds sterling 2004 (bootstrapped) more than the control group over one year (95% confidence interval (CI), pounds sterling 1363 to pounds sterling 2833) (p0.001), but experienced on average 0.456 fewer falls, an incremental cost per fall prevented of pounds sterling 4390. The bootstrapped mean gain in quality adjusted life years (QALYs) per patient was 0.056 (95% CI, 0.006 to 0.108) (p0.001). The incremental cost-utility ratio was pounds sterling 35 704, above the currently accepted UK threshold level of willingness to pay per QALY of pounds sterling 30 000. However, in an analysis modelling costs and benefits over patients' expected lifetime, the incremental cost per QALY was pounds sterling 13 172, under conservative assumptions.First eye cataract surgery, while cost-ineffective over the trial period, was probably cost-effective over the participants' remaining lifetime.

Trends in eye cancer mortality are presented for the USA and England and Wales during the period 1955-89. Mortality rates have fallen by 58% in the USA during this period. The fall in mortality is paralleled by an equal fall in incidence rates in the USA. In England and Wales, mortality rates and incidence rates have remained relatively constant during the last three decades. The explanation for these differences between the USA and England and Wales is unknown.

BACKGROUND--In current ophthalmic practice day-case surgery cataract patients are conventionally discharged and then reviewed the following morning thus limiting the advantages of what 'true' day-case surgery strives to achieve. The aim of this study was to see if there was a difference in outcome between 'true' day-case cataract surgery and non-day-care surgery. METHODS--A total of 387 consecutive cataract operations were followed, comprising 122 local anaesthetic day-cases, 149 local anaesthetic non-day-cases, 63 general anaesthetic non-day-cases, and 53 general anaesthetic day-cases. RESULTS--Although not randomised the groups were comparable with respect to age, operator grade, sex, presence of diabetes, anaesthetic type, pre and postoperative visual acuities, and time to first planned outpatient visit. There were 10 early postoperative complications in the day-case group (5.71% of total) and 14 in the non-day-case group (6.6% of total), the commonest complications in both groups were raised intraocular pressure, corneal oedema, and wound leaks. One patient in each group had an early complication that necessitated attending the casualty department. The visual outcomes in both groups were comparable. CONCLUSIONS--These findings suggest that there were no preventable complications within the constraints of the number of operations studied and that no additional risk is attached to 'true' day-case surgery relative to non-day-case surgery.

Background: Key issues in the quality of care for people with cataracts in the UK include hospital waiting lists, complication rates from surgery, and the use of junior surgeons. The main objective of this study was to investigate the relative importance that older people attach to these factors when given theoretical choices over options for cataract surgery. Method: A systematic sample of 194 individuals aged 60–84 years on a general practice register in Nottingham were invited to take part in an interview based survey. Respondents ranked 11 "cataract surgery packages" containing different waiting list lengths, complication risks, and surgeon grades. Conjoint analysis was performed to determine the relative importance of these factors for individuals and for the group as a whole. Results: Of the 194 subjects invited to participate, 146 (72%) completed the interview. For the group as a whole the "averaged importance" of the factors was: complication risk 45.8%; waiting time 41.1%, surgeon grade 13.1%. Analysis of importance scores for individuals showed that some were particularly concerned about complication risk while others were more concerned about waiting times. There was a strong negative correlation between importance scores for these factors (Spearman's rho –0.78, p

BACKGROUND/AIM—There has been no consistent pattern reported on how mortality for uveal melanoma varies with age. This information can be useful to model the complexity of the disease. The authors have examined ocular cancer trends, as an indirect measure for uveal melanoma mortality, to see how rates vary with age and to compare the results with their other studies on predicting metastatic disease. METHODS—Age specific mortality was examined for England and Wales, the USA, and Canada. A log-log model was fitted to the data. The slopes of the log-log plots were used as measure of disease complexity and compared with the results of previous work on predicting metastatic disease. RESULTS—The log-log model provided a good fit for the US and Canadian data, but the observed rates deviated for England and Wales among people over the age of 65 years. The log-log model for mortality data suggests that the underlying process depends upon four rate limiting steps, while a similar model for the incidence data suggests between three and four rate limiting steps. Further analysis of previous data on predicting metastatic disease on the basis of tumour size and blood vessel density would indicate a single rate limiting step between developing the primary tumour and developing metastatic disease. CONCLUSIONS—There is significant underreporting or underdiagnosis of ocular melanoma for England and Wales in those over the age of 65 years. In those under the age of 65, a model is presented for ocular melanoma oncogenesis requiring three rate limiting steps to develop the primary tumour and a fourth rate limiting step to develop metastatic disease. The three steps in the generation of the primary tumour involve two key processes—namely, growth and angiogenesis within the primary tumour. The step from development of the primary to development of metastatic disease is likely to involve a single rate limiting process.

AIMS—Overexpression of c-myc protein has independent prognostic significance in a variety of primary and metastatic cutaneous melanomas which suggests a possible role for this gene in melanomagenesis. We have therefore examined the importance of this oncogene in uveal melanoma and studied the coexpression of two other gene products, Bcl-2 and p53, which might contribute to its effect. METHODS—The percentage of cells positive for nuclear c-myc expression was estimated by flow cytometric analysis of nuclei extracted from paraffin blocks. The expression of Bcl-2 and p53 protein was assessed by immunohistochemistry. A total of 71 tumours were studied and the results compared with survival with a mean follow up period of 6 years. RESULTS—c-myc was expressed in >50% of the cells by 70% of the tumours, and was independently associated with improved survival in a Cox multiple regression model. Although Bcl-2 was expressed by the majority of the cells in 67% tumours, it was without effect on prognosis. None of the cases studied showed convincing positivity for p53. Analysis of coexpression showed that the best survival was seen in c-myc+/Bcl-2+ tumours and the worst in c-myc−/Bcl-2− tumours. CONCLUSION—The finding of improved rather than reduced survival in c-myc positive tumours is at variance with skin melanoma. There was no evidence to suggest that c-myc was modulated by upregulation of Bcl-2 or p53 inactivation/mutation. Although Bcl-2 is unlikely to have any effect on tumour growth or metastasis, it could contribute to the general lack of susceptibility to apoptosis in these tumours. Keywords: uveal melanoma; c-myc; p53; Bcl-2

AIM—To determine whether fetal and infant growth, as assessed by weight at birth and weight at 1 year, are related to intraocular pressure. METHODS—717 men and women born in Hertfordshire between 1920 and 1930, for whom records of birth weight and weight at 1 year were available, were examined. Visual fields were assessed using the Takagi central 25 degree 75 point static threshold screening program. Tonometry was performed using the Perkin's tonometer. The disc was assessed by direct ophthalmoscopy through dilated pupils. RESULTS—A significant inverse relation was found between systolic blood pressure and birth weight. However, no association was found between birth weight or weight at 1 year and intraocular pressure, cup/disc ratio, or visual field defects. CONCLUSIONS—There was no evidence to support fetal or infant growth as being important factors for the subsequent development of raised intraocular pressure. Keywords: birth weight; intraocular pressure; cup/disc ratio; visual field defects

AIMS—To examine the course taken by individual retinal ganglion cell axons through the human lamina cribrosa. METHODS—Retinal ganglion cell axons were labelled using the retrograde tracer horseradish peroxidase applied directly to the optic nerve in two normal human eyes removed during the course of treatment for extraocular disease. RESULTS—A majority of axons took a direct course through the lamina cribrosa but a significant minority, in the range 8-12%, deviated to pass between the cribrosal plates in both central and peripheral parts of the optic disc. CONCLUSIONS—It is postulated that these axons would be selectively vulnerable to compression of the lamina cribrosa in diseases such as glaucoma in which the intraocular pressure is increased. Keywords: retina; optic nerve; glaucoma; lamina cribrosa

Editor—Increasing concern over the poor quality of medical research, and particularly over the conduct of clinical trials, has been voiced by the editors of the major medical journals. This unease has taken expression in the form of the CONSORT statement,1 2 which states the criteria by which a trial should be judged. Unfortunately, most trials are not vigorously assessed until their results are submitted to a journal for publication–a time when it is too late for any errors in trial design to be remedied. There is also the second major problem of negative …

We have analysed 64,417 patient-attendances by 56,409 patients to a dedicated ophthalmic new patient service to assess the demographic and epidemiological parameters of this population. Forty-three point five per cent were male and 56.5% female. Nine per cent of patients were under 16 years of age while 27.5% were over 70 years. Comparison of patients attending an outreach new patient clinic with that at the main hospital showed that a higher proportion of patients under 16 years were seen at the outreach clinic (p < 0.001), whereas the main clinic saw a higher proportion of patients in the 16-69 year age group (p < 0.001).