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1.  A new quality assessment parameter for optical coherence tomography 
Aim
To create a new, automated method of evaluating the quality of optical coherence tomography (OCT) images and to compare its image quality discriminating ability with the quality assessment parameters signal to noise ratio (SNR) and signal strength (SS).
Methods
A new OCT image quality assessment parameter, quality index (QI), was created. OCT images (linear macular scan, peripapillary circular scan, and optic nerve head scan) were analysed using the latest StratusOCT system. SNR and SS were collected for each image. QI was calculated based on image histogram information using a software program of our own design. To evaluate the performance of these parameters, the results were compared with subjective three level grading (excellent, acceptable, and poor) performed by three OCT experts.
Results
63 images of 21 subjects (seven each for normal, early/moderate, and advanced glaucoma) were enrolled in this study. Subjects were selected in a consecutive and retrospective fashion from our OCT imaging database. There were significant differences in SNR, SS, and QI between excellent and poor images (p = 0.04, p = 0.002, and p<0.001, respectively, Wilcoxon test) and between acceptable and poor images (p = 0.02, p<0.001, and p<0.001, respectively). Only QI showed significant difference between excellent and acceptable images (p = 0.001). Areas under the receiver operating characteristics (ROC) curve for discrimination of poor from excellent/acceptable images were 0.68 (SNR), 0.89 (IQP), and 0.99 (QI).
Conclusion
A quality index such as QI may permit automated objective and quantitative assessment of OCT image quality that performs similarly to an expert human observer.
doi:10.1136/bjo.2004.059824
PMCID: PMC1860175  PMID: 16424531
2.  Ultrahigh resolution optical coherence tomography in non-exudative age related macular degeneration 
Aim
To describe the appearance of the non-exudative forms of age related macular degeneration (AMD) as imaged by ultrahigh resolution optical coherence tomography (UHR-OCT).
Methods
A UHR-OCT ophthalmic imaging system, which utilises a femtosecond laser light source capable of ~3 μm axial resolution, was employed to obtain retinal cross sectional images of patients with non-exudative AMD. Observational studies of the resulting retinal images were performed.
Results
52 eyes of 42 patients with the clinical diagnosis of non-exudative AMD were imaged using the UHR-OCT system. 47 of the 52 (90%) eyes had the clinical diagnosis of drusen and/or retinal pigment epithelial (RPE) changes. In these patients, three patterns of drusen were apparent on UHR-OCT: (1) distinct RPE excrescences, (2) a saw toothed pattern of the RPE, and (3) nodular drusen. On UHR-OCT, three eyes (6%) with a clinical diagnosis of non-exudative AMD had evidence of fluid under the retina or RPE. Two of these three patients had findings suspicious for subclinical choroidal neovascularisation on UHR-OCT.
Conclusion
With the increased resolution of UHR-OCT compared to standard OCT, the involvement of the outer retinal layers are more clearly defined. UHR-OCT may allow for the detection of early exudative changes not visible clinically or by angiography.
doi:10.1136/bjo.2005.076612
PMCID: PMC1860181  PMID: 16424532
4.  A “throttle” mechanism in the central retinal vein in the region of the lamina cribrosa 
The British Journal of Ophthalmology  2006;91(9):1190-1193.
Aims
To demonstrate a constriction in the central retinal vein in the region of the lamina cribrosa.
Methods
A prospective comparative interventional study of 13 controls and 19 patients with central retinal vein occlusion (CRVO) using colour Doppler imaging of the central retinal artery and vein in the region of the lamina cribrosa and optic nerve posterior to the globe.
Results
In controls peak velocities in the vein were higher in the region of the lamina cribrosa than the optic nerve, mean 175 mm/second (mm/s) and 49 mm/s respectively, p<0.0001. The velocities in the artery were also higher in the region of the lamina cribrosa, mean 122 mm/s and 92 mm/s, p = 0.007. The variability of the velocities in the region of the lamina cribrosa was 7.4% in the artery and 15.2% in the vein. The mean ratio of the velocities in the vein (4.2 (SD 2.1)) was significantly higher than the mean ratio in the artery (1.4 (SD 0.4), p<0.0001). In CRVO, the mean ratio in the vein was lower in the affected eyes (2.2 (SD 1.9), p<0.01) and fellow unaffected eyes (2.2 (SD 1.0), p = 0.003) than controls. The values were stable in eight after radial optic neurotomy.
Conclusion
The presence of a constriction of the vein in the region of the lamina cribrosa can be inferred from the presence of higher blood velocities at this site than further back in the optic nerve. In CRVO there may be a more uniform narrowing of the vein along its course in the nerve. Neurotomy did not affect the measurements.
doi:10.1136/bjo.2006.102798
PMCID: PMC1954902  PMID: 17005545
5.  Identification of ganglion cell neurites in human subretinal and epiretinal membranes 
The British Journal of Ophthalmology  2006;91(9):1234-1238.
Aim
To determine whether neural elements are present in subretinal and epiretinal proliferative vitreoretinopathy (PVR) membranes as well as in diabetic, fibrovascular membranes removed from patients during vitrectomy surgery.
Methods
Human subretinal and epiretinal membranes of varying durations were immunolabelled with different combinations of antibodies to glial fibrillary acidic protein, vimentin, neurofilament protein and laminin.
Results
Anti‐neurofilament‐labelled neurites from presumptive ganglion cells were frequently found in epiretinal membranes and occasionally found in subretinal membranes. In addition, the neurites were only observed in regions that also contained glial processes.
Conclusions
These data demonstrate that neuronal processes are commonly found in human peri‐retinal cellular membranes similar to that demonstrated in animal models. These data also suggest that glial cells growing out of the neural retina form a permissive substrate for neurite growth and thus may hold clues to factors that support this growth.
doi:10.1136/bjo.2006.104612
PMCID: PMC1954915  PMID: 17108012
6.  Evaluation of a new soft tipped injector for the implantation of foldable intraocular lenses 
The British Journal of Ophthalmology  2006;91(8):1070-1102.
Aim
To evaluate the R‐INJ‐04 soft‐tipped injector, a new injector with an integral round nozzle manufactured by Rayner Intraocular Lenses, England.
Methods
16 Rayner C‐flex intraocular lenses (IOLs; Rayner Intraocular lenses, England) ranging between +10 and +30 D (2 for each power) were tested. An ophthalmic viscoelastic device (Healon, AMO, Santa Ana, California, USA) was applied to the injectors. The IOLs were loaded according to the company injector's instructions for use and were injected into a Petri dish. After the injection, all the IOLs and nozzles were evaluated by gross (macroscopic) and microscopic analyses and photographed under a light microscope. One lens of each power and the cartridge used for the implantation were then sent for further analysis by scanning electron microscopy (SEM). The rest of the IOLs were tested for power and modulation transfer function (MTF).
Results
All the injections were successful. No damage to the IOLs or to the injectors was found by gross examination, light microscopy and SEM. No deposits were found on the IOL optical surfaces or haptics. Power and MTF analysis showed a close match with the original measurements.
Conclusion
Our results suggest that the R‐INJ‐04 soft‐tipped injector is safe for the implantation of the C‐flex IOL with power range from 10 to 30 D. No structural damage to the IOLs or to the injectors was found, and the lens power and light transmission properties were not damaged in any way by the injection process.
doi:10.1136/bjo.2006.103192
PMCID: PMC1954791  PMID: 17135340
7.  Iris atrophy in patients with newly diagnosed multibacillary leprosy: at diagnosis, during and after completion of multidrug treatment 
The British Journal of Ophthalmology  2006;91(8):1019-1022.
Aim
To describe the prevalence and incidence of iris atrophy in patients with multibacillary (MB) leprosy.
Methods and patients
Prospective longitudinal cohort study. 301 newly diagnosed patients with MB leprosy were followed up during the 2 years of treatment with multidrug therapy (MDT) and for a further 5 years with biannual ocular examinations. Incidence of iris atrophy was calculated as the number of patients with iris atrophy per person‐year (PY) of follow‐up among those who did not have iris atrophy at baseline. Stepwise multiple regression confirmed the presence of specific associations of demographic and clinical characteristics (p<0.05) with iris atrophy, detected by univariate analysis.
Results
Iris atrophy was present in 6 (2%) patients at enrolment. During MDT, with 445 PYs of follow‐up, 9 patients developed iris atrophy (IR 0.02, 95% CI 0.01 to 0.04) that was associated with cataract (HR 15.13, 95% CI 3.71 to 61.79, p<0.001) and corneal opacities (HR 6.83, 95% CI 1.62 to 28.8, p = 0.009). After MDT, with 2005 PYs of follow‐up, 60 patients developed iris atrophy (IR 0.03, 95% CI 0.023 to 0.039) that was associated with age (per decade; HR 1.40, 95% CI 1.10 to 1.78, p = 0.006), skin smear positivity (HR 3.50, 95% CI 1.33 to 9.24, p = 0.011), cataract (HR 3.66, 95% CI 1.85 to 7.25, p<0.001), keratic precipitates (HR 2.76, 95% CI 1.02 to 7.47, p = 0.046) and corneal opacity (HR 3.95, 95% CI 1.86 to 8.38, p<0.001).
Conclusions
Iris atrophy continues to develop in 3% of patients with MB leprosy every year after they complete a 2‐year course of MDT, and is associated with age, increasing loads of mycobacteria, subclinical inflammation, cataract and corneal opacity.
doi:10.1136/bjo.2006.107177
PMCID: PMC1954795  PMID: 17108015
8.  Human papillomavirus in normal conjunctival tissue and in conjunctival papilloma: types and frequencies in a large series 
The British Journal of Ophthalmology  2006;91(8):1014-1015.
Aim
To examine conjunctival papilloma and normal conjunctival tissue for the presence of human papillomavirus (HPV).
Methods
Archival paraffin wax‐embedded tissue from 165 conjunctival papillomas and from 20 histological normal conjunctival biopsy specimens was analysed for the presence of HPV by PCR. Specimens considered HPV positive using consensus primers, but with a negative or uncertain PCR result using type‐specific HPV probes, were analysed with DNA sequencing.
Results
HPV was present in 86 of 106 (81%) β‐globin‐positive papillomas. HPV type 6 was positive in 80 cases, HPV type 11 was identified in 5 cases and HPV type 45 was present in a single papilloma. All the 20 normal conjunctival biopsy specimens were β‐globin positive and HPV negative.
Conclusion
There is a strong association between HPV and conjunctival papilloma. The study presents the largest material of conjunctival papilloma investigated for HPV and the first investigation of HPV in normal conjunctival tissue. HPV types 6 and 11 are the most common HPV types in conjunctival papilloma. This also is the first report of HPV type 45 in conjunctival papilloma.
doi:10.1136/bjo.2006.108811
PMCID: PMC1954828  PMID: 17166894
9.  Human papillomavirus and pterygium. Is the virus a risk factor? 
The British Journal of Ophthalmology  2006;91(8):1016-1018.
Background
Pterygium is a disease of unknown origin and pathogenesis that might be vision threatening. It is characterised by a wing‐like conjunctival overgrowth of the cornea. Several studies have investigated human papillomavirus (HPV) as a risk factor for the development of pterygia, but the results are inconclusive.
Aim
To investigate a large sample of pterygia for the presence of HPV in order to clarify the putative association between pterygia and HPV.
Methods
100 specimens of pterygium from Danish patients and 20 normal conjunctival biopsy specimens were investigated for the presence of HPV with PCR technique using β‐globin primers to access the quality of the extracted DNA and the HPV primers MY09/11 and GP5+/6+. HPV‐positive specimens underwent subsequent HPV typing with type‐specific HPV primers and further investigation with DNA in situ hybridisation (ISH).
Results
90 of 100 investigated pterygia proved suitable for HPV analysis by PCR. As β‐globin could not be amplified, 10 specimens were excluded from the study. 4 of 90 pterygia harboured HPV. HPV type 6 was identified in all four HPV‐positive pterygia. The 20 normal conjunctival biopsy specimens were β‐globin positive and HPV negative. All four pterygia that were HPV type 6 positive were DNA ISH negative.
Conclusions
The low presence of HPV DNA in pterygia does not support the hypothesis that HPV is involved in the development of pterygia in Denmark.
doi:10.1136/bjo.2006.108829
PMCID: PMC1954836  PMID: 17179167
10.  Expression of p27(KIP1) and cyclin D1, and cell proliferation in human pterygium 
Background
The pterygium is a growth onto the cornea of fibrovascular tissue that is continuous with the conjunctiva, whereas the mechanisms of cell proliferation in pterygium epithelium are unknown.
Aim
To analyse the histopathology and the expression of cell cycle‐related molecules in pterygium tissues.
Methods
Seven pterygia were surgically removed using the bare‐sclera procedure, and three normal bulbar conjunctivas were also obtained. Formalin‐fixed, paraffin‐wax‐embedded tissues were analysed by immunohistochemistry with anti‐p27(KIP1), cyclin D1 and Ki‐67 antibodies.
Results
Conjunctival epithelium consisted of several layers of round cells with a few goblet cells. Nuclear immunoreactivity for p27(KIP1) was noted in many normal epithelial cells, where cyclin D1 and Ki‐67‐positive nuclei were intermingled. A variety of goblet cells were located in the superficial layer of the pterygium head as well as those of the body epithelia. Several pterygium epithelial cells were p27(KIP1) positive, whereas nuclear immunoreactivity for cyclin D1 and Ki‐67 was detected in many epithelial cells. By contrast, immunoreactivity for p27(KIP1), cyclin D1 and Ki‐67 was hardly detected in the pterygium stroma.
Conclusion
It is suggested that pterygium growth and development are associated with the proliferation of epithelium, which is possibly involved in the expression of cell cycle‐related molecules.
doi:10.1136/bjo.2006.110387
PMCID: PMC1955677  PMID: 17179165
11.  Inhibition of experimental corneal neovascularisation by bevacizumab (Avastin) 
Aim
To evaluate the effect of topically administered bevacizumab (Avastin) on experimental corneal neovascularisation in rats.
Methods
Silver nitrate sticks (75% silver nitrate, 25% potassium nitrate) were used to perform chemical cauterisation on the corneas of 16 eyes from 16 male Long Evans rats. For the following 7 days, the 10 eyes in the treatment group were instilled with bevacizumab 4 mg/ml drops twice daily, whereas the 6 eyes in the control group received placebo (normal saline drops twice daily). Digital photographs of the cornea were analysed to determine the area of cornea covered by neovascularisation as a percentage of the total corneal area.
Results
In the bevacizumab‐treated eyes, neovascularisation covered, on average, 38.2% (15.5%) (mean (SD)) of the corneal surface compared with 63.5% (5.0%) in the control group (p<0.02, Mann–Whitney U test).
Conclusion
Topically administered bevacizumab (Avastin) at a concentration of 4 mg/ml limits corneal neovascularisation following chemical injury in the male Long Evans rat model.
doi:10.1136/bjo.2006.107912
PMCID: PMC1955569  PMID: 17179168
12.  Clinical assessment of two new contrast sensitivity charts 
Background
Contrast sensitivity measurement in UK clinical practice is most commonly performed with the Pelli–Robson chart.
Aims
To compare the repeatability of two new contrast sensitivity charts and to measure their agreement with the Pelli–Robson charts.
Method
Contrast sensitivity was measured monocularly using two versions of the Mars letter contrast sensitivity chart, two presentations on the Test Chart 2000 and two versions of the Pelli–Robson chart. Bland–Altman techniques were used to assess repeatability and agreement.
Results
53 subjects were recruited with visual acuity from 6/4 to 6/72. The coefficient of repeatability was 0.182 for the Pelli–Robson chart, 0.121 for the Mars chart and 0.238 for Test Chart 2000. Limits of agreement with the Pelli–Robson chart were −0.29 to +0.15 log units for the Mars letter contrast sensitivity chart and −0.32 to +0.78 log units for the Test Chart 2000. For patients with poor contrast sensitivity, the limits of agreement between the Test Chart 2000 and the Pelli–Robson chart improved from −0.33 to +0.15 log units.
Conclusion
In a population of hospital ophthalmology patients, the coefficient of repeatability is better for the Mars chart and worse for the Test Chart 2000 when compared with the Pelli–Robson chart. The electronic test chart does not agree well with the Pelli–Robson chart, although this might simply be due to the performance of liquid crystal display screens at low contrast levels. The Mars letter contrast sensitivity chart shows good validity and reasonable agreement with the Pelli–Robson chart.
doi:10.1136/bjo.2006.109280
PMCID: PMC1955579  PMID: 17166891
13.  Positive correlation between pigment epithelium‐derived factor and monocyte chemoattractant protein‐1 levels in the aqueous humour of patients with uveitis 
Aim
To evaluate whether aqueous humour levels of pigment epithelium‐derived factor (PEDF) are associated with monocyte chemoattractant protein‐1 (MCP‐1) in patients with uveitis.
Methods
Aqueous humour levels of MCP‐1 and PEDF were determined by ELISA in 34 uveitis samples and 9 cataract control samples.
Results
Aqueous humour MCP‐1 and PEDF levels were significantly higher in patients with infectious or non‐infectious uveitis than in controls (mean (SD) 32.3 (10.7) ng/ml vs 4.48 (1.10) ng/ml vs 0.47 (0.10) ng/ml, and 8.40 (1.30) μg/ml vs 5.01 (0.92) μg/ml vs 1.32 (0.22) μg/ml, respectively, p<0.001). A positive correlation between PEDF and MCP‐1 was found in patients with uveitis (r = 0.39, p<0.01).
Conclusion
The results demonstrated that aqueous humour levels of PEDF were positively associated with MCP‐1 in patients with uveitis. The present observations suggest that aqueous humour levels of PEDF may be a marker of inflammation in uveitis.
doi:10.1136/bjo.2006.109843
PMCID: PMC1955592  PMID: 17166895
14.  Antipermeability and antiproliferative effects of standard and frozen bevacizumab on choroidal endothelial cells 
Background
Bevacizumab is an antiangiogenic compound developed to target tumour vessels. Its off‐label use in ophthalmology requires in vitro testing on ocular cells.
Aim
To quantify the antipermeability and antiproliferative effects of bevacizumab on cultured choroidal endothelial cells (CECs). It was examined whether deep‐freezing of bevacizumab attenuates its antiangiogenic activity.
Methods
Porcine CECs were cultured in permeable insert systems. Permeability of the cell monolayers was quantified by a fluorescent isothiocyanate‐dextran assay after treatment with vascular endothelial growth factor (VEGF; 20–100 ng/ml) alone and in combination with bevacizumab (0.1–1 mg/ml). Proliferation of the CECs was tested using a “wound scratch” assay. The experiments were repeated with bevacizumab after freezing at −20°C for 5 days.
Results
Bevacizumab significantly reduced VEGF‐induced permeability in a dose‐dependant manner. A molar ratio of 2.6:1 of bevacizumab to VEGF was required for complete blocking of VEGF‐induced rise in permeability. CEC proliferation was significantly blocked by bevacizumab (0.5 mg/ml). Thawed bevacizumab after deep freezing showed a moderate, but not statistically significant loss in activity.
Conclusion
Bevacizumab significantly reduces VEGF‐induced permeability and proliferation of CECs. Freezing and thawing of bevacizumab will affect its biological activity.
doi:10.1136/bjo.2006.109702
PMCID: PMC1955593  PMID: 17179166
15.  The relationship between accommodative amplitude and the ratio of central lens thickness to its equatorial diameter in vertebrate eyes 
Aim
To determine the relationship between accommodative amplitude and central lens thickness/equatorial lens diameter (CLT/ELD) ratio in vertebrates.
Methods
Midsagittal sections of lenses from fixed, post mortem eyes from 125 different vertebrate species were photographed. Their CLT/ELD ratios were correlated with independently published measurements of their accommodative amplitudes. Using the non‐linear finite element method (FEM), the efficiency of zonular traction (the absolute change in central radius of curvature per unit force [|ΔCR|/F]) for model lenses with CLT/ELD ratios from 0.45 to 0.9 was determined.
Results
Vertebrates with CLT/ELD ratios ⩽0.6 have high accommodative amplitudes. Zonular traction was found to be most efficient for those model lenses having CLT/ELD ratios ⩽0.6.
Conclusions
Vertebrates with lenses that have CLT/ELD ratios ⩽0.6 – i.e. “long oval” shapes – have the greatest accommodative amplitudes; e.g. primates, diving birds and diurnal birds of prey. Vertebrates that have oval or spherical shaped lenses, like owls and most mammals, have low accommodative amplitudes. Zonular traction was found to be most efficient when applied to model lenses with CLT/ELD ratios ⩽0.6. The implications of these findings on the mechanism of accommodation are discussed.
doi:10.1136/bjo.2006.107524
PMCID: PMC1955594  PMID: 17050574
crystalline lens; accommodative amplitude; central lens thickness/equatorial lens diameter ratio; vertebrate
16.  Vitreoretinal morphology in active ocular toxoplasmosis: a prospective study by optical coherence tomography 
Aim
To investigate the third generation optical coherence tomography (OCT3) findings in patients with active ocular toxoplasmosis.
Methods
A prospective observational case series, including 15 patients with active ocular toxoplasmosis in at least one eye evaluated at a single centre. Vitreoretinal morphological features at baseline and changes within a 24‐week follow‐up interval on OCT3 were evaluated.
Results
The active ocular toxoplasmosis lesion was classified clinically as punctate (n = 6), focal (n = 6) or satellite (n = 3). Retinal layers were hyper‐reflective at the active lesion site, and some degree of retinal pigment epithelium‐choriocapillaris/choroidal optical shadowing was seen in all patients. In general, the retina was thinned at the active lesion site in eyes with punctate lesions and thickened in eyes with focal and satellite lesions. When detected by OCT3, the posterior hyaloid appeared thickened. While focally detached over punctate lesions, the posterior hyaloid was partially detached, but still attached to the lesion in focal and satellite lesions. Additional findings (not detected on clinical examination) include diffuse macular oedema (n = 6), vitreomacular traction (n = 3) and maculoschisis (n = 1). During follow‐up, a decrease in retinal thickness and focal choriocapillaris/choroidal relative hyper‐reflectivity were observed at the former lesion site, and posterior vitreous detachment progressed/occurred in all patients.
Conclusion
OCT3 enabled identification of morphological features underestimated on clinical examination in patients with ocular toxoplasmosis, which may expand the clinical spectrum of the disease. Further studies are needed to verify the relevance of OCT3 in assisting with the diagnosis and management of ocular toxoplasmosis.
doi:10.1136/bjo.2006.108068
PMCID: PMC1955597  PMID: 17135336
17.  Correlations in refractive errors between siblings in the Singapore Cohort Study of Risk factors for Myopia 
Background
The prevalence of myopia in parts of South East Asia has risen dramatically over the past 1–2 generations, suggesting that environmental factors may be particularly important determinants of refractive development in these populations.
Aim
To assess the contribution of familial factors (shared genes and/or shared family environment) to refractive error and ocular component dimensions of school‐aged children in Singapore.
Methods
Data were available for 315 children who had one or more siblings also participating in the Singapore Cohort Study of the Risk factors for Myopia (SCORM). Refractive error and ocular biometric parameters were measured under cycloplegia at baseline when children were 7–9 years, and at yearly follow‐up sessions for the next 3 years, using consistent clinical procedures. The time children spent performing a variety of nearwork‐related tasks was obtained from questionnaires. Familial influences were assessed by calculating between‐sibling correlations.
Results
After adjusting for age and sex, the between‐sibling correlation in refractive error was 0.447 (95% CI 0.314 to 0.564), suggesting that familial factors account for 63–100% of the variation in the cohort. The between‐sibling correlation for 1‐year change in refractive error was similarly high, at 0.420 (95% CI 0.282 to 0.543). All ocular component dimensions were correlated significantly between siblings, especially for corneal curvature and vitreous chamber depth—the major structural determinants of refraction. The amount of time siblings spent engaged in nearwork tasks (reading, watching TV, playing video games, computing) and in outdoor activities was also highly correlated between siblings (p<0.001).
Conclusion
Shared genes and/or shared environment are important factors in the refractive development of children in Singapore. Because the time spent in nearwork tasks is highly correlated between siblings, epidemiological studies will benefit from precise, quantitative measures of refractive error in parents and more distant relatives in order to begin to dissociate genetic and environmental sources of variation.
doi:10.1136/bjo.2006.107441
PMCID: PMC1955602  PMID: 17135339
18.  Diurnal IOP control with bimatoprost versus latanoprost in exfoliative glaucoma: a crossover, observer‐masked, three‐centre study 
Aim
To evaluate the diurnal intraocular pressure (IOP) control and safety of bimatoprost versus latanoprost in exfoliative glaucoma (XFG).
Methods
One eye of 129 consecutive patients with XFG (mean (SD) age 66.5 (8.3) years) was included in this prospective, observer‐masked, three‐centre, crossover comparison. After a 4–6 week medicine‐free period patients were randomised to bimatoprost or latanoprost monotherapy for 3 months. Patients were then switched to the opposite treatment for another 3 months. At the end of the washout and the treatment periods diurnal IOP was measured at 0800, 1300, and 1800.
Results
At baseline the IOP (mean (SD)) was 28.0 (4.0), 26.9 (3.6), and 25.9 (3.6) mm Hg, at the three time points, respectively. Both treatments significantly reduced mean diurnal IOP at month 3. Mean diurnal IOP was 26.9 (3.5) mm Hg at baseline, 17.6 (3.3) mm Hg with bimatoprost, and 18.6 (3.6) mm Hg with latanoprost (p<0.0001). Furthermore, lower IOP values were obtained with bimatoprost at all time points (17.9 (3.4), 17.3 (3.3), and 17.6 (3.5) mm Hg, respectively) compared with latanoprost (18.7 (3.6), 18.5 (3.6), and 18.6 (4.1) mm Hg, respectively). The corresponding mean differences (0.8, 1.1, and 1.0 mm Hg, respectively) were all significant (p<0.001 for each comparison). Significantly more patients with XFG obtained a target diurnal IOP <17 mm Hg with bimatoprost than with latanoprost, 55/123 (45%) v 34/123 (28%); (p = 0.001), and significantly fewer patients were non‐responders with bimatoprost than with latanoprost (5 v 13, p = 0.021). More patients reported at least one adverse event with bimatoprost than with latanoprost (58 v 41 at 3 months; p = 0.0003).
Conclusion
This crossover study suggests that better diurnal IOP control is obtained with bimatoprost than with latanoprost in patients with XFG.
doi:10.1136/bjo.2006.106690
PMCID: PMC1955604  PMID: 17124241
intraocular pressure; bimatoprost; latanoprost; glaucoma
19.  Predictive factors for short‐term visual outcome after intravitreal triamcinolone acetonide injection for diabetic macular oedema: an optical coherence tomography study 
Aim
To evaluate the predictive factors for visual outcome after intravitreal triamcinolone acetonide injection to treat refractory diabetic macular oedema (DME).
Methods
A retrospective chart review of patients with DME who met the following inclusion criteria was performed: clinically significant diabetic macular oedema, receipt of a 4 mg/0.1 ml intravitreal triamcinolone acetonide injection and an optical coherence tomography (OCT) of the macula performed up to 10 days before injection. All patients received a full ophthalmic examination including best‐corrected Snellen visual acuity (VA). The main outcome measure was the mean change in vision 3 months after injection.
Results
Data from 73 eyes of 59 patients were analysed. After a mean follow‐up of 324 days, the mean change in vision was −0.075 logarithm of minimum angle of resolution (logMAR) units, with 27.3% improving ⩾3 lines, 6.8% declining ⩾3 lines and 60.2% remaining stable within 1 line of baseline vision. Statistical analysis was performed using multivariate generalised estimating equations on the basis of data from 52 eyes of 42 patients. Factors associated with an improvement in vision 3 months after injection were worse baseline VA (−0.27 logMAR units/unit increase in baseline VA, p = 0.002) and presence of subretinal fluid (−0.17 logMAR units, p = 0.06). The presence of cystoid macular oedema negatively affected the visual outcome (0.15 logMAR units, p = 0.03). In addition, the presence of an epiretinal membrane (ERM) was associated with less visual improvement. ERM modified the effect of baseline VA as demonstrated by a significant interaction between these two variables (0.34 logMAR units/unit increase in baseline VA, p = 0.04).
Conclusions
OCT factors and baseline VA can be useful in predicting the outcomes of VA 3 months after intravitreal triamcinolone acetonide injection in patients with refractory DME.
doi:10.1136/bjo.2006.105783
PMCID: PMC1955611  PMID: 17108013
20.  The effect of changing intraocular pressure on the corneal and scleral curvatures in the fresh porcine eye 
Aim
To measure corneal and scleral radii of curvature in response to intraocular pressure (IOP).
Methods
Using digital photographic profile images of 16 fresh porcine eyes, the curvatures of the cornea and sclera were determined in response to five consecutive incremental 100 μl saline intravitreal injections. IOP was measured and ocular rigidity calculated. Elastic moduli of the cornea and sclera were estimated.
Results
Intraocular pressure and the radius of curvature of the sclera increased linearly with increasing volume. There was no statistical change in corneal curvature. The elasticity of the cornea and sclera was constant during the 15–50 mm Hg increase in IOP. The estimated range of the elastic moduli of the cornea and sclera were, respectively 0.07–0.29 MPa and 0.2 MPa to 0.5 MPa. The scleral rigidity ranged from 0.0017 to 0.0022.
Conclusions
The elastic moduli of the cornea and sclera are independent of IOP. The modulus of elasticity of the sclera is higher than that of the cornea. Elevation of IOP changes the curvature of the sclera but not that of the cornea. Porcine scleral rigidity is similar to human scleral rigidity. Scleral curvature could be a novel method for measuring IOP.
doi:10.1136/bjo.2006.110221
PMCID: PMC1955613  PMID: 17151057
21.  Mechanical energy from intraocular instruments cause emulsification of silicone oil 
Aim
The complications of intraocular silicone oil include emulsification, which may lead to vision‐threatening disorders such as keratopathy, secondary glaucoma and retinopathy. The authors study the effect of mechanical energy from surgical instruments on the emulsification of silicone oil.
Methods
Three different handpieces (phacofragmentation, phacoemulsification, high‐speed vitrectomy) were placed at the interface of balanced salt solution and silicone oil (1000 and 5000 cst, 200 fluid; Dow Corning). The phacofragmentation handpiece was evaluated over different ultrasound powers and duration. Emulsification was quantified with phase‐contrast microscopy and manual counting of digital photographs by a masked examiner. In addition, phacoemulsification was performed in the anterior chamber of a human ex vivo eye with full‐fill silicone oil.
Results
Emulsification increases with higher phacofragmentation power and duration and is greater for 1000 cst silicone oil. Emulsification of silicone oil occurs with phacoemulsification and high‐speed vitrectomy handpieces.
Conclusions
The energy from surgical handpieces is sufficient to result in silicone oil emulsification.
doi:10.1136/bjo.2006.103994
PMCID: PMC1955622  PMID: 17035273
silicone oils; phacoemulsification; phacofragmentation; vitrectomy
22.  Raising the benchmark for the 21st century—the 1000 cataract operations audit and survey: outcomes, Consultant‐supervised training and sourcing NHS choice 
Purpose
Clinical outcomes for phacoemulsification surgery are still compared with the almost 10‐year‐old benchmark of the 1997–98 National Cataract Surgery Survey (NCSS) published in this journal. Extraneous to the peer‐reviewed research literature, more recent databases suggest much better results may be being obtained. This offered the rare opportunity to perform an audit as research investigating if this was indeed the case and a new benchmark is needed, with the additional standard of rigorous study peer review by independent senior ophthalmologists. At this pilot centre for Patient Choice provision, all cataract surgery was performed on Consultant‐supervised training lists, a novel extension in‐sourcing care using public resources rather than to an independent sector that may not be supervised by NHS Consultants. Patient satisfaction was also surveyed. We asked whether the NCSS is out‐of‐date, and whether good outcomes on Choice schemes are compatible with Consultant‐led training within the National Health Service?
Methods
An audit of 1000 consecutive patients undergoing cataract surgery on Patient Choice at the Western Eye Hospital between October 2002 and September 2004. All subjects were scheduled for phacoemulsification. A novel policy was extending “choice” onto training list slots for this period. A validated questionnaire assessed patient satisfaction.
Results
A best corrected visual acuity of 6/12 or better was obtained in 93% of cases. Over 80% of cases were ±1 D of target refraction (65.7% within 0.5 D). The total incidence of complications was 8.7%. Overall incidence of major complications was 2.4%. Incidence of vitreous loss was 1.1% and that of endophthalmitis 0.1%. Complications rates were lowest for consultants (less than 1%). User satisfaction with having cataract surgery on “patient choice” was high.
Conclusions
Cataract surgery under patient choice on supervised training lists is associated with a visual outcome and an incidence of complications at least as good as the published national average. User satisfaction is high. Cataract surgery under patient choice is compatible with training activity in receiving hospitals. The improvement in outcomes since the 1997–98 NCSS suggest that the accepted standards for complication rates should be updated to reflect the fact that phacoemulsification has become an established procedure.
doi:10.1136/bjo.2006.104216
PMCID: PMC1955623  PMID: 17050577
cataract surgery; outcomes; training; patient choice; independent treatment centres
23.  Effect of systemic bevacizumab therapy on retinal pigment epithelial detachment 
Background
To evaluate the effect of systemic bevacizumab (Avastin®) therapy on pigment epithelial detachment (PED) secondary to age‐related macular degeneration (AMD) and to identify prognostic factors for PED regression and improvement in best corrected visual acuity (BCVA).
Study design
Prospective uncontrolled pilot study.
Methods
Nine patients (nine eyes) received three systemic bevacizumab treatments at 2 week intervals and were examined at baseline, weeks 1, 2, 4, 6 and month 3 by using optical coherence tomography (Stratus OCT™, Carl Zeiss© Meditec, Dublin, California, USA). Changes in maximum PED height and greatest linear diameter (GLD) were planimetrically analysed by using Adobe Photoshop CS and correlated with retinal morphological changes and changes in BCVA.
Results
Systemic bevacizumab therapy was well tolerated. Mean maximum PED height decreased significantly by 21% as early as 1 week (−96 µm (SD 48.8), p<0.01). At 3 months follow‐up, two PEDs resolved completely, mean maximum PED height decreased significantly by 39% (−179 µm (SD 178), p = 0.02) and mean PED GLD by 24% (−714 µm (SD 1010), p = 0.07). Mean BCVA improved significantly by week 2 (+8.7 letters (SD 5.7), p<0.01) and at 3 months with 12.7 letters (SD 6.4) (p<0.01).
Conclusion
In the examined nine patients, systemic bevacizumab therapy showed evidence for an effect on PED secondary to neovascular AMD in terms of a decrease in lesion height and diameter. A high PED at baseline was found to be a negative predictive factor for visual outcome.
doi:10.1136/bjo.2006.102467
PMCID: PMC2266832  PMID: 17050580
AMD; PED; VEGF; bevacizumab; OCT
24.  Some dissociating factors in the analysis of structural and functional progressive damage in open‐angle glaucoma 
Aim
To identify the presence, and origin, of any “dissociating factors” inherent to the techniques for evaluating progression that mask the relationship between structural and functional progression in open‐angle glaucoma (OAG).
Methods
23 patients (14 with OAG and 9 with ocular hypertension (OHT)) who had received serial Heidelberg Retina Tomograph (HRT II) and Humphrey Field Analyser (HFA) examinations for ⩾5 years (mean 78.4 months (SD 9.5), range 60–101 months) were identified. Evidence of progressive disease was retrospectively evaluated in one eye of each patient using the Topographic Change Analysis (TCA) and Glaucoma Progression Analysis (GPA) for the HRT II and HFA, respectively.
Results
Six patients were stable by both techniques; four exhibited both structural and functional progression; seven exhibited structural progression, only, and six showed functional progression, only. Three types of dissociating factors were identified. TCA failed to identify progressive structural damage in the presence of advanced optic nerve head damage. GPA failed to identify progressive functional damage at stimulus locations, with sensitivities exhibiting test‐retest variability beyond the maximum stimulus luminance of the perimeter, and where a perimetric learning effect was apparent.
Conclusion
The three dissociating factors accounted for nine of the 13 patients who exhibited a lack of concordance between structural and functional progressive damage.
doi:10.1136/bjo.2005.087213
PMCID: PMC1954725  PMID: 17050585
25.  Diagnosis from fundus photographs 
Aim
To investigate the way in which ophthalmologists observe fundi and make diagnoses from their observations.
Methods
A set of 12 test photographs was presented to 9 ophthalmologists. The subjects were asked to identify the features in the photographs that are important for forming a diagnosis and were also asked to form differential diagnoses. The scanpaths of the subjects were recorded during their inspection of the photographs. Subsequently, they were asked to trace over the important features of four of the photographs.
Results
The correctness of the diagnoses was described by weighted numerical scores. Differential diagnoses made after 30 s of inspection were significantly better than those made after 5 s. Irrespective of correctness, the reported diagnoses were dominated by the most obvious features of the photograph. Incorrect diagnoses were made either because the subjects failed to identify the significant features of the photograph or because they failed to comprehend the significance of the identified features.
Conclusion
Accurate funduscopy involves both perception of diagnostic features and cognitive interpretation of these features. Verbal reports, eye movement recordings and tracings reveal the features and interpretations used to make a diagnosis. These techniques will be used in a subsequent study to evaluate the relative contributions of formal training and experience to the development of diagnostic skills.
doi:10.1136/bjo.2006.105726
PMCID: PMC1954734  PMID: 17166892

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