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To assess the proportion of patients with raised intraocular pressure (IOP) (≥ 30 mmHg) on the first postoperative day following pars plana vitrectomy (PPV), encirclement and endotamponade and assess the number requiring alteration in management to address elevated IOP. To establish whether review on day one is required. Retrospective case note review of consecutive patients who underwent 23-gauge PPV, 276-encirclement and endotamponade under the care of a single surgeon. All patients as standard received prophylactic anti-glaucoma medication post-surgery (eye drops) to take home but initiate only after day-one review. Statistical analysis was carried out using student t tests and Fisher’s exact tests. Sixty-six patients were examined over a 2-year period. Mean day-one IOP was 22.2 mmHg (SD 7.3, 95% CI 20.4–24.0). Eleven patients (16.7%) had IOP ≥ 30 mmHg. Five patients (7.6%) had management changing decisions made at the day-one postoperative visit. Lens status, endotamponade, preoperative IOP, surgeon grade, cryopexy versus laser retinopexy or preoperative administration of once only 500 mg dose of intravenous acetazolamide did not influence IOP, with no significant difference between these subgroups. No cases of hypotony occurred. A significant minority of patients had elevation of IOP above 30 mmHg, a number of whom required treatment changes to address this. No preoperative risk factors were identified indicating those at risk of high IOP. It is important to identify these potentially harmful IOP elevations, and therefore day-one review is imperative and should be continued.

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

To review the literature up to recent for the use of videos, videogames and dichoptic stimulation as a treatment for amblyopia.There have been three strategies explored. The first is to use videos and videogames monocularly with the normal eye covered. The second is dichoptic stimulation with a common background presented to both eyes and an enriched foreground to the amblyopic eye. The third are games specifically designed to generate stereopsis. Most work has focused on the second of these approaches but both of the first two approaches seem to give a similar improvement of 0.1-0.2 logMAR. One large randomized control trial (RCT) has published showing that dichoptic stimulation is not inferior to patching but no evidence that it was superior. It also showed that video games have their own compliance problems and a second smaller RCT did suggest that videogames, with a game designed by a gaming company, was superior. Most of the work done has had methodological issues and should be considered exploratory rather than definitive.Dichoptic stimulation is a viable treatment option for the treatment of amblyopia. The first trial results have shown results that are not superior to patching but they are not without methodological issues. There is sufficient encouragement to justify further research in this area.

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

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.

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.

A number of professions have a visual standard but there is no standard for surgeons, including surgeons such as ophthalmologists who operate with the aid of a microscope. We review which professions do have a visual standard, the evidence addressing the issue of a visual standard in medicine and surgery, and an international survey of what visual standards other countries apply to ophthalmologists, and performed a survey of the views of the member of the British Royal College of Ophthalmologists. A number of professions, where public safety is an issue, do have a visual standard without compelling supporting evidence. By contrast, all but two countries do not have a visual standard for their ophthalmic surgeons. The survey of members of the British Royal College of Ophthalmologists supported the adoption of such a standard, which would include minimum requirements for both visual acuity and stereoacuity. Good vision is clearly essential for ophthalmologists, as well as for other surgeons and practioners of some other branches of medicine. While there is no evidence to support a specific visual standard, we conclude that one should be adopted until there is definitive evidence to settle the issue on the basis of the precautionary principle as patient safety is involved.

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.

Aims: To determine patients’ preferences for provision of glaucoma follow-up services examining preferences for location, access and personnel for delivery of this care. Methods: 100 patient patients attending the glaucoma outpatient clinic for follow-up review underwent an interview-based assessment during which they completed the visual function questionnaire 25 and ranking of scenario options for provision of follow-up care for their glaucoma. Percentage preferences for aspects of care offered in the conjoint analysis scenario packages and generation of utility values for each of the factor levels included in the scenario design were calculated. Results: Travel time and training of health professional were the most important factors for patients (accounting for over 60%) of their preference. Utility scores were generated for each factor, with shorter travel time and examination by a doctor being the most important features to the patients. Patients who lived furthest from the hospital and had severe visual disability considered the number of visits to complete an episode to be an important feature. Conclusion: Patients ideally would like to travel a short distance and be seen by a doctor when being followed up for their glaucoma.

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.

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 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.

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.

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.

Background: It has been suggested that pregnancy may promote metastases in melanoma and that the contraceptive pill may be an etiologic factor. The purpose of this study is to determine if uveal or conjunctival melanomas express estrogen or progesterone receptors. Methods: Twenty-seven choroidal and five conjunctival melanomas were investigated. Immunohistochemistry was performed using the antibodies ER-D5, which recognizes heat-shock protein 27 (formerly called the estrogen receptor-associated cytoplasmic antigen; ER-1 D5, which recognizes the estrogen receptor; and PgR, which recognizes the progesterone receptor. Results: Most of the conjunctival and uveal melanomas stained strongly for heatshock protein 27 but none of the tumors showed positive nuclear staining for either the estrogen or the progesterone receptor. Conclusions: No evidence was found for either estrogen receptor or progesterone receptor expression in choroidal or conjunctival melanomas. Based on the literature, there is little evidence for these hormones having a role in the development or progression of these tumors.

We read the article of Browning et al 1 about comparative gene expression profiling of human umbilical vein endothelial cells (HUVEC) and ocular vascular endothelial cells with interest. The authors report that primary HUVEC (commercially bought, unpassaged) show enrichment for probe sets involved in embryological development while ocular microvascular endothelial cells (choroidal and retinal) isolated from postmortem human globes 49–52 h after death demonstrated enrichment for probe sets for MHC classes I and II, immune responses and cell signal transduction. Postmortem artefact, including cessation of circulation, needs to be excluded as a possible cause of inflammatory gene …

Age-standardized mortality rates for cancers of the eye among adults in England and Wales are compared with those for cutaneous malignant melanoma. While cutaneous malignant melanoma rates have increased three-fold since 1950-54, rates for cancers of the eye have remained relatively constant over the same period. Collectively, the inconclusive findings of case-control studies for an association between exposure to ultraviolet radiation and uveal melanoma, the lack of supporting dosimetry data, together with the lack of an upward trend in mortality rates for cancers of the eye, suggests that exposure to ultraviolet radiation may not be a major factor in the etiology of uveal melanoma.

PURPOSE To present long-term follow-up data on enucleations and eviscerations carried out with placement of spherical porous polyethylene implants. METHODS A retrospective, interventional, noncomparative case series of all patients undergoing primary evisceration or enucleation surgery from one teaching hospital ophthalmology department. RESULTS In total, 106 cases were identified. Eighty patients (75.5%) underwent enucleation (group A) and 26 (24.5%) underwent evisceration (group B). Patient demographics were similar in both groups. Mean implant size in group A was 20.5 mm and 17.2 mm in group B. Mean follow-up in group A was 40 months (range, 12 to 80 months). Mean follow-up in group B was 63 months (range, 12 to 72 months). Six cases (7.5%) in group A had complications (excluding implant exposure), whereas one case (3.8%) in group B had a complication (excluding implant exposure). Five patients (6.3%) in group A had implant exposure; 14 cases (53.8%) of implant exposure occurred in group B. CONCLUSIONS Our case series revealed a significantly higher incidence of implant exposure after evisceration than after enucleation. Our data suggest that enucleation should be the procedure of choice when removing an eye to minimize the risk of subsequent complications, particularly orbital implant exposure.

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.

Purpose To determine the long-term outcome of periocular sebaceous gland carcinoma and factors predictive of tumor recurrence. Methods A retrospective case note review of all patients with periocular sebaceous gland carcinoma treated at the Queen's Medical Centre, Nottingham, United Kingdom, between 1992 and 1999. Patient age at time of surgery, tumor location, and treatment were recorded. The tumor dimensions and histopathologic description were correlated with tumor recurrence. The general practitioners were contacted to determine whether there had been any further tumor recurrences since the last entry in the hospital notes. Results A total of 11 cases (mean age, 75 years) were reviewed, of which 7 were female. The eyelids were involved in all but 2 cases, and maximum tumor dimension ranged from 6 to 25 mm. Three demonstrated pagetoid spread. Recurrence was seen in all tumors reported as incompletely excised (4 cases), of which only one demonstrated pagetoid spread. Tumour size was not predictive of recurrence. Conclusions In our unit, the best prognostic factor for sebaceous gland carcinoma is a histologic report confirming complete excision of the tumor, whatever the tumor size or pattern of spread identified.

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/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

We describe a case of left upper eyelid necrosis due to Pseudomonas aeruginosa in a patient with Felty syndrome. This is a rare but potentially serious condition. In our patient, medical management and reconstructive surgery achieved a good outcome.

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

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).

Biometry allows determination of the final refractive outcome following cataract extraction with intraocular lens implantation. We compared the accuracy of axial length measurement performed with the slit-lamp supported biometry probe versus a hand-held technique. The two methods of biometry were performed on 32 patients undergoing endocapsular cataract extraction with lens implantation. One of the methods was selected at random in order to predict implant power for a desired refractive outcome using the SRK-T formula. There was no difference in ‘within-subject’ variance of axial length measurement between the two methods (t = 1.74, p = 0.091), and there was no difference in refractive outcome when the power calculations for the two techniques were compared (t = 0.12, p = 0.906). The hand-held technique provides a useful alternative method of biometry in ‘difficult’ patients.

Background: Intraocular smooth muscle tumors have long been a subject of controversy. The advent of immunohistochemistry with antibodies against HMB-45, S-100, smooth muscle actin, desmin, and vimentin has helped greatly in the distinction between smooth muscle tumors and melanocytic lesions. Methods: Twenty-seven archival tissue blocks from patients who had had intraocular leiomyomas or leiomyosarcomas diagnosed were located and fresh sections cut and stained for the above markers. The cases constituted 24 iris lesions and 3 ciliary body lesions. Results: All 24 iris tumors were reclassified as iris melanocytic lesions. Two of the three ciliary body leiomyomas retained their classification, and the third was reclassified as a spindle B-cell melanoma. Conclusion: The authors suggest that intraocular leiomyomas are much rarer than previously suggested and that many of the cases previously reported in the literature are open to question.

The development of retinal detachment is reported in three eyes, of two patients, following implantation of an anterior chamber intraocular lens (AC-IOL) in phakic eyes for the correction of ultra-high myopia. The presence of an AC-IOL may hamper the identification of retinal breaks and removal of the intraocular lens may prove necessary to improve visualisation. Shallowing of the anterior chamber may also occur during, or following, vitreoretinal surgery with risk of endothelial contact. The risks and relative contraindications of AC-IOL implantation into phakic eyes are discussed.

Panretinal photocoagulation (PRP) is tolerated well by most patients using topical anaesthesia alone, though there are a significant number of patients who experience pain. Additional local anaesthesia alternatives for these patients include retrobulbar, peribulbar or subconjunctival injection. Deep introduction of a sharp needle may rarely cause damage to orbital structures, whereas no-needle sub-Tenon irrigation of local anaesthetic solution to the posterior Tenon's space theoretically avoids these risks. A one-quadrant, inferior-nasal, sub-Tenon delivery of 1.5–2 ml plain 2% lignocaine was administered and PRP performed on 12 eyes of 12 patients who were previously intolerant of PRP by topical anaesthesia alone. To assess the efficacy of anaesthesia, patients were asked to score pain, using a visual analogue score chart graded from 0 to 10. If patients were unable to see the chart, or read the accompanying text, a verbal explanation and description of the scoring chart was performed. Where PRP was performed with topical amethocaine 1% alone, pain scores were graded as median 8, mean 8.5 and range 6–10. The administration of sub-Tenon anaesthesia was well tolerated with a median pain score of 1.5, mean 1.9 and range 0–5. PRP after sub-Tenon administration was successfully completed in 11 of the 12 patients with a median pain score of 1.5, mean 1.8 and range of 0–9. The range was wide due to one patient with a high pain score who was intolerant of PRP in spite of the sub-Tenon delivery. Assessment of pain scores demonstrates significantly better anaesthesia with sub-Tenon irrigation than topical treatment alone (p< 0.005, Wilcoxon ranked sign test). If a patient tolerates PRP with simple topical anaesthesia then this is the method of choice. Topical anaesthesia is non-invasive, though if pain is experienced, one-quadrant sub-Tenon anaesthesia can provide effective anaesthesia for PRP with the benefit of seeking to avoid the risks of sharp needle techniques.

Three cases are reported which had features similar to, and evolved in a pattern consistent with central retinal vein occlusions and a fourth case is reported which behaved as a hemispheric vein occlusion. However, they differed from classic retinal vein occlusions by having prominent sheathing of the retinal venous vasculature at presentation, which in all four cases resolved within three weeks. There was no evidence for any of these cases having an inflammatory vasculitis. The significance of this transient sheathing is uncertain.

AIMS/BACKGROUND—Proton beam radiotherapy can effectively treat primary uveal melanomas of any size. Some patients, however, develop adverse late effects following treatment and the purpose of this study was to determine which factors give rise to a poor local outcome. METHODS—The hospital records from a first cohort of 127 patients treated by protons from 1989 to 1992 were reviewed retrospectively. The presence of rubeosis was selected as a measure of significant ocular damage. Split file analysis was performed with 73 cases forming a test group with the remaining 54 cases acting as a validation group. RESULTS—Large tumour size and the presence of retinal detachment were significant, independent risk factors for developing rubeosis for both the test and validation groups. These factors also predicted subsequent enucleation for uncontrolled ocular pain. Patients with tumours too large to plaque and with an associated retinal detachment had a 90% chance of developing rubeosis within 4 years of proton beam radiotherapy. CONCLUSIONS—Patients with a uveal melanoma too large for plaque therapy and an associated retinal detachment run a very high risk of developing rubeosis after proton beam radiotherapy and one third of individuals developing rubeosis required enucleation for pain even if local tumour control was satisfactory.