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1.  Intraobserver variability of Confocal Scanning Laser Ophthalmoscopy with and without Stereo photographs 
The British journal of ophthalmology  2009;93(11):1552-1553.
doi:10.1136/bjo.2008.144618
PMCID: PMC3747839  PMID: 19854740
Glaucoma; confocal scanning laser ophthalmoscopy; screening; stereo photographs; intraobserver variability
2.  On the origin of ‘guttae’ 
The British journal of ophthalmology  2014;98(9):1308-1310.
doi:10.1136/bjophthalmol-2014-305069
PMCID: PMC4324629  PMID: 25012533
5.  Normative optical coherence tomography measurements in children 
doi:10.1136/bjophthalmol-2012-301658
PMCID: PMC3417148  PMID: 22426801
7.  Cancer-associated retinopathy caused by benign thymoma 
doi:10.1136/bjo.2008.151563
PMCID: PMC3487380  PMID: 20424218
9.  Correlation between visual acuity and cognitive functions 
A possible association between visual acuity (VA) and dementia was investigated in 2716 subjects who were aged between 53 and 102 at first visit and had varying degrees of dementia. Better VA was found to be significantly correlated with a lower dementia level (person coefficient range 0.146–0.261 over 10 years of follow-up, all correlations are significant, p<0.0001) as well as with a higher global cognitive score (person coefficient range −0.254 to −0.318 over 10 years of follow-up, all correlations are significant, p<0.0001), a grade encompassing 19 different cognitive tests. This correlation remained significant after adjustment for age, years of education, gender, use of ophthalmic drugs and years of follow-up.
doi:10.1136/bjophthalmol-2013-304149
PMCID: PMC4060517  PMID: 24169658
10.  Quality of Life and Cancer-Related Needs in Patients with Choroidal Melanoma 
The British journal of ophthalmology  2013;97(11):10.1136/bjophthalmol-2013-303635.
Aims
To assess quality of life (QoL) indices and their associations with treatment modality, sociodemographics, and cancer-related needs in choroidal melanoma patients.
Methods
Patients (N=99) treated at the University of California, Los Angeles for choroidal melanoma within the prior 5 years (M = 2.05) completed questionnaires assessing demographics, cancer-related needs, vision-specific QoL, depressive symptoms, and concern about recurrence. Visual acuity, comorbidities, treatment modality (radiotherapy, enucleation), and years since diagnosis were gathered from medical records. Primary analyses were multiple regressions.
Results
Although concern about cancer recurrence was elevated, QoL was better than in other oncology samples and comparable to healthy samples on some outcomes. Enucleation was associated with worse vision-specific QoL, and presence of comorbid diseases was associated with worse vision-specific QoL, depressive symptoms, and concern about cancer recurring (all ps<.05). Patients who experienced at least one stressful life event in the past year (versus no events) reported more depressive symptoms (p<.01). Report of more unmet cancer needs was associated with worse vision-specific QoL, depressive symptoms and more concern about recurrence (all ps<.05), uniquely explaining 5%–12% of the variance.
Conclusions
For choroidal melanoma patients an average of two years after treatment, number of physical comorbidities and unmet cancer needs were the strongest correlates of poorer QoL.
doi:10.1136/bjophthalmol-2013-303635
PMCID: PMC3838665  PMID: 24037609
quality of life; choroid neoplasms; cancer
11.  Optic Nerve Head Morphology in Glaucoma Patients of African Descent is Strongly Correlated to Retinal Blood Flow 
The British journal of ophthalmology  2014;98(11):1551-1554.
BACKGROUND/AIMS
To examine the relationship between change in optic nerve head (ONH) morphology and retinal blood flow in patients with open-angle glaucoma (OAG) of African (AD) and European descent (ED) over three years.
METHODS
112 patients with OAG (29 AD; 83 ED) underwent assessment of ONH morphology using Heidelberg retinal tomography (HRT-III) and retinal blood flow using confocal scanning laser Doppler. Repeated measures analysis of covariance was used to compare baseline and 3-year measurements and Pearson correlations were calculated to evaluate the relationships.
RESULTS
In OAG patients of AD, change in superior mean retinal blood flow was strongly, negatively correlated with change in cup/disc (C/D) area ratio (r=−0.78, p=0.020) and cup area (r=−0.75, p=0.0283) and strongly, positively correlated with change in rim area (r=0.74, p=0.0328) over three years. In OAG patients of AD, change in inferior mean retinal blood flow was strongly, negatively correlated with changes in C/D area ratio (r=−0.88, p=0.0156) and linear C/D ratio (r=−0.86, p=0.0265) over three years. In OAG patients of ED, these correlations were weak and did not reach statistical significance.
DISCUSSION
OAG patients of AD may have a stronger vascular component to their glaucoma pathophysiology than patients of ED.
doi:10.1136/bjophthalmol-2013-304393
PMCID: PMC4206567  PMID: 24964797
glaucoma; retina; optic nerve
12.  A new method using xenogeneicacellular dermal matrix in the reconstruction of lacrimal drainage 
The British Journal of Ophthalmology  2014;98(11):1583-1587.
Aims
To prospectively evaluate the reliability and efficacy of a new treatment for the reconstruction of the lacrimal duct using a new histo-engineered material, xenogeneic (bovine) acellular dermal matrix.
Method
Five patients (five eyes) with partial or total absence of the lacrimal duct were included in the study. Four patients (four eyes) suffered from traumatic injuries to the lacrimal duct and one patient (one eye) had congenital absence of the lacrimal drainage system. A pedal graft of conjunctiva was taken from the fornix area and rolled into a tube structure after being attached to the acellular dermal matrix.
Results
The average duration of follow-up for the patients was 7.2 months (ranging from 6 to 12 months). After surgery, the new duct in the nasal cavity could be observed above the middle turbinate by nasal endoscopy. Patency was confirmed by pressing in the area of the lacrimal sac and visualising air bubbles in the nasal cavity. Additionally, the meatus above the middle turbinate of the nasal cavity was stained and visualised after patients underwent Jones dye test 1 (JDT1). Five tear ducts proved to be effective through irrigation testing and epiphora symptoms were alleviated in all cases.
Conclusions
The newly reconstructed lacrimal duct, formed by the shift of autogenous conjunctival petal and the attachment of acellular dermal matrix, was successful in all five cases and suggests a new solution for the complex lacrimal duct lesion and congenital anomalies of the lacrimal duct.
doi:10.1136/bjophthalmol-2014-304932
PMCID: PMC4215284  PMID: 25271909
Lacrimal duct; Graft
13.  Concordance between common dry eye diagnostic tests 
Purpose
Large variations in results of diagnostic tests for mild to moderate dry eye are widely recognised. The purpose of this study was to assess if there was concordance between common dry eye diagnostic tests.
Methods
A total of 91 subjects were recruited to the study. The tear film and ocular surface were evaluated using the phenol red thread test, tear break up time (TBUT), biomicroscopic examination and impression cytological (IC) assessment of conjunctival goblet cells. Dry eye symptoms were assessed using McMonnies questionnaire and statistical correlations between all tests were assessed.
Results
This study cohort did not include severe aqueous deficient dry eye patients as determined by the phenol red thread test (PRT). A statistically significant difference was noted between PRT results and all other tests (***P ≤ 0.001). Only meibomian gland pathology, McMonnies questionnaire, reduced goblet cell density and TBUT (≤7 seconds) demonstrated correlation determined by McNemar’s test.
Conclusion
A correlation was only found between tests assessing lipid/mucous deficiency (meibomian gland evaluation, goblet cells density, TBUT, and McMonnies questionnaire).
doi:10.1136/bjo.2007.131722
PMCID: PMC4211111  PMID: 18782801
correlation dry eye diagnostic tests
14.  Recent advances in OCT imaging of the lamina cribrosa 
The British Journal of Ophthalmology  2014;98(Suppl 2):ii34-ii39.
The lamina cribrosa (LC) is believed to be the site of injury to retinal ganglion cell axons in glaucoma. The ability to visualise this structure has the potential to help increase our understanding of the disease and be useful in the early detection of glaucoma. While for many years the research on the LC was essentially dependent on histology and modelling, a number of recent advances in optical coherence tomography (OCT) have dramatically improved the ability to visualise the LC, such that it is now possible to image the LC in vivo in humans and animals. In this review, we highlight recent advances in OCT imaging of the LC, in the technology, processing and analysis, and discuss the impact that these will have on the ability to diagnose and monitor glaucoma, as well as to expand our understanding of its pathophysiology. With this manuscript, we aspire to share our excitement on the achievements and potential of recent developments as well as advise caution regarding the challenges that remain before imaging of the LC and optic nerve can be used routinely in clinical practice.
doi:10.1136/bjophthalmol-2013-304751
PMCID: PMC4208343  PMID: 24934221
Glaucoma; Imaging; Intraocular Pressure; Optic Nerve; Anatomy
15.  On improving the use of OCT imaging for detecting glaucomatous damage 
The British Journal of Ophthalmology  2014;98(Suppl 2):ii1-ii9.
Aims
To describe two approaches for improving the detection of glaucomatous damage seen with optical coherence tomography (OCT).
Methods
The two approaches described were: one, a visual analysis of the high-quality OCT circle scans and two, a comparison of local visual field sensitivity loss to local OCT retinal ganglion cell plus inner plexiform (RGC+) and retinal nerve fibre layer (RNFL) thinning. OCT images were obtained from glaucoma patients and suspects using a spectral domain OCT machine and commercially available scanning protocols. A high-quality peripapillary circle scan (average of 50), a three-dimensional (3D) scan of the optic disc, and a 3D scan of the macula were obtained. RGC+ and RNFL thickness and probability plots were generated from the 3D scans.
Results
A close visual analysis of a high-quality circle scan can help avoid both false positive and false negative errors. Similarly, to avoid these errors, the location of abnormal visual field points should be compared to regions of abnormal RGC+ and RNFL thickness.
Conclusions
To improve the sensitivity and specificity of OCT imaging, high-quality images should be visually scrutinised and topographical information from visual fields and OCT scans combined.
doi:10.1136/bjophthalmol-2014-305156
PMCID: PMC4208344  PMID: 24934219
Glaucoma; Imaging; Optic Nerve; Psychophysics
16.  Characterisation of Schlemm's canal cross-sectional area 
The British Journal of Ophthalmology  2014;98(Suppl 2):ii10-ii14.
Purpose
To compare three methods of Schlemm's canal (SC) cross-sectional area (CSA) measurement.
Methods
Ten eyes (10 healthy volunteers) were imaged three times using spectral-domain optical coherence tomography (Cirrus HD-OCT, Zeiss, Dublin, California, USA). Aqueous outflow vascular structures and SC collector channel ostia were used as landmarks to identify a reference location within the limbus. SC CSA was assessed within a 1 mm segment (±15 frames of the reference, 31 frames in all) by three techniques. (1) Using a random number table, SC CSA in five random frames from the set of 31 surrounding the reference were measured and averaged. (2) The most easily visualised SC location (subjective) was measured, and (3) SC CSA was measured in all 31 consecutive B-scans, and averaged. (comprehensive average, gold standard). Subjective and random CSAs were compared with the comprehensive by general estimating equation modelling, and structural equation modelling quantified agreement.
Results
The average from five random locations (4175±1045 µm2) was not significantly different than that obtained from the gold standard comprehensive assessment (4064±1308 µm2, p=0.6537). Subjectively located SC CSA (7614±2162 µm2) was significantly larger than the comprehensive gold standard SC CSA (p<0.0001). The average of five random frames produced significantly less bias than did subjective location, yielding a calibration line crossing the ‘no-bias’ line.
Discussion
Subjectively located SC CSA measurements produce high estimates of SC CSA. SC assessed by measuring five random locations estimate CSA was similar to the gold standard estimate.
doi:10.1136/bjophthalmol-2013-304629
PMCID: PMC4208345  PMID: 24590558
Aqueous humour; Imaging
17.  Optical coherence tomography imaging of macular oedema 
The British Journal of Ophthalmology  2014;98(Suppl 2):ii24-ii29.
Macular oedema (ME) occurs in a wide variety of pathological conditions and accounts for different degrees of vision loss. Early detection of ME is therefore critical for diagnosis and therapeutic management. Optical coherence tomography (OCT) is a non-contact, diagnostic method that uses infrared light, which allows the analysis of the retinal structure by means of high-resolution tomographic cross sections. The identification, localisation, quantification and long-term follow-up of fluid collections are the most important capabilities of OCT. Since the introduction of OCT in clinical practice, it has become an invaluable diagnostic tool and different patterns of ME have been reported. The purpose of this manuscript is to review OCT profiles of ME according to the aetiology and describe what has been reported regarding intraretinal features in vivo.
doi:10.1136/bjophthalmol-2014-305305
PMCID: PMC4208347  PMID: 24934220
Macula; Imaging; Retina; Vitreous
18.  Examining the Association Between Age-Related Macular Degeneration and Motor Vehicle Collision Involvement: A Retrospective Cohort Study 
The British journal of ophthalmology  2013;97(9):10.1136/bjophthalmol-2013-303601.
Background
Little is known about motor vehicle collision (MVC) risk in older drivers with age-related macular degeneration (AMD). The purpose of this study is to examine associations between MVC involvement and AMD presence and severity.
Methods
In a retrospective cohort study pooling the samples from four previous studies, we examined associations between MVC rate and older drivers with early, intermediate, or advanced AMD as compared to those in normal eye health. MVC data were based on accident reports obtained from the state agency that compiles this information.
Results
MVC rate was highest among those in normal eye health and progressively declined among those with early and intermediate disease, and then increased for those with advanced AMD. However, only for drivers with intermediate AMD was the MVC rate significantly different (lower) as compared to those in normal eye health, regardless of whether the rate was defined in terms of person-years (RR 0.34, 95% CI 0.13–0.89) or person-miles (RR 0.35, 95% CI 0.13–0.91) of driving.
Conclusion
These results suggest that older drivers with intermediate AMD have a reduced risk of collision involvement. Further research should investigate whether self-regulatory driving practices by these drivers (avoiding challenging driving situations) underlies this reduced risk.
doi:10.1136/bjophthalmol-2013-303601
PMCID: PMC3837568  PMID: 23832967
driving; age-related macular degeneration; vision impairment
19.  Survey of childhood blindness and visual impairment in Botswana 
The British journal of ophthalmology  2011;95(10):1365-1370.
Background/aims
In terms of blind-person years, the worldwide burden of childhood blindness is second only to cataracts. In many developing countries, 30–72% of childhood blindness is avoidable. The authors conducted this study to determine the causes of childhood blindness and visual impairment (VI) in Botswana, a middle-income country with limited access to ophthalmic care.
Methods
This study was conducted over 4 weeks in eight cities and villages in Botswana. Children were recruited through a radio advertisement and local outreach programmes. Those ≤15 years of age with visual acuity <6/18 in either eye were enrolled. The WHO/Prevention of Blindness Eye Examination Record for Children with Blindness and Low Vision was used to record data.
Results
The authors enrolled 241 children, 79 with unilateral and 162 with bilateral VI. Of unilateral cases, 89% were avoidable: 23% preventable (83% trauma-related) and 66% treatable (40% refractive error and 31% amblyopia). Of bilateral cases, 63% were avoidable: 5% preventable and 58% treatable (33% refractive error and 31% congenital cataracts).
Conclusion
Refractive error, which is easily correctable with glasses, is the most common cause of bilateral VI, with cataracts a close second. A nationwide intervention is currently being planned to reduce the burden of avoidable childhood VI in Botswana.
doi:10.1136/bjo.2010.189068
PMCID: PMC4127423  PMID: 21242581
20.  Cataract and Cognitive Impairment: A Review of the Literature 
Acquired cataract and cognitive impairment are both common age related problems, and ophthalmologists are increasingly likely to encounter patients who have both. Dementia types which display early visuo-perceptual impairment may present first to ophthalmology services. When these patients have coexisting cataract it may be difficult to distinguish visual complaints due to cataract from those due to dementia.
The interaction between visual impairment due to cataract, and neurodegenerative disorders affecting the central visual pathways, is not fully understood. Visual impairment due to cataract may stress impaired attentional mechanisms, and cataract extraction may improve cognitive performance in some patients with early cognitive impairment; however the benefits of cataract surgery in established dementia are less clear. Here we review the literature on this subject and consider the implications for practice.
doi:10.1136/bjo.2009.165902
PMCID: PMC4119932  PMID: 20807709
Cataract; Dementia; Cognitive impairment; Visuo-perceptual impairment
21.  Photobiomodulation in the treatment of patients with non-center-involving diabetic macular oedema 
The British journal of ophthalmology  2014;98(8):1013-1015.
Purpose
Far-red/near-infrared phototherapy or photobiomodulation (PBM) has recently been reported to be an effective and non-invasive treatment method to inhibit lesions of diabetic retinopathy (DR) in animals. This study investigated the safety and efficacy of PBM in diabetic patients to treat non-center-involving diabetic macular oedema (NCDME).
Methods
This was a non-randomised, consecutive, case series, where 4 patients with type 2 diabetes with NCDME were treated for 160 s per day with PBM for 2–9 months. Demographic data including age, sex, HbA1c%, electronic ETDRS visual acuity, and retinal and macular thickness were measured using spectral domain ocular coherence tomography (SD-OCT) before and after treatment.
Results
Four eyes of 4 patients were treated, with fellow eyes serving as untreated controls. Daily PBM treatment for only 80 s per treatment twice daily caused a significant reduction in focal retinal thickening in all 4 treated eyes. No adverse effects attributable to therapy were noted by the patients or study investigators during the study period.
Conclusions
PBM potentially offers a non-invasive and cost-effective therapeutic option for patients with NCDME. Further studies of this therapeutic option in DR are warranted
doi:10.1136/bjophthalmol-2013-304477
PMCID: PMC4106479  PMID: 24682183
22.  Investigation of the peptidoglycan sensing molecule, PGLYRP-2, in murine inflammatory uveitis 
Background/aim
Peptidoglycan (PGN) recognition proteins (PGLYRPs) are innate immune molecules that recognise bacterial cell wall PGN, and participate in several inflammatory diseases such as arthritis. We sought to elucidate the contribution of PGLYRPs in murine uveitis (intraocular inflammatory disease) elicited by PGN, and the extent to which systemically administered PGN alters uveitis compared with arthritis versus locally triggered ocular responses.
Methods
Mice deficient for PGLYRP-2, PGLYRP-3 or PGLYRP-4 were administered PGN by an intraperitoneal or intraocular injection. Arthritis was assessed by near-infrared imaging and histopathology, while uveitis was measured by intravital videomicroscopy and histopathology.
Results
Systemic PGN exposure predisposed to arthritis through a PGLYRP-2 dependent mechanism. By contrast, systemic PGN exposure did not predispose to uveitis, and PGLYRP-2 deficiency had no impact on the development the uveitis. When PGN was administered locally, a robust uveitis ensued, which occurred independently of PGLYRP-2. Regardless of whether PGN was administered systemically or locally, neither PGLYRP-3 nor PGLYRP-4 deficiency significantly altered ocular inflammation compared with wild-type control animals.
Conclusions
Our findings highlight the complexity of PGLYRPs and how PGLYRP-2 may use different molecular pathways in the joints versus eyes. Collectively, our results support a non-essential or redundant role for PGLYRPs-2, -3, -4 in uveitis.
doi:10.1136/bjophthalmol-2012-302650
PMCID: PMC4084548  PMID: 23361435
23.  In Vivo High-Frequency Contrast-Enhanced Ultrasonography of Choroidal Melanoma in Rabbits: Imaging Features and Histopathologic Correlations 
The British journal of ophthalmology  2013;97(7):10.1136/bjophthalmol-2013-303343.
Purpose
To evaluate the utility of in vivo imaging of rabbit model of choroidal melanoma utilizing high-frequency contrast-enhanced ultrasound (HF-CE-US) with 2-or 3-dimensional modes, and to correlate the sonographic findings with histopathologic characteristics.
Methods
Five New Zealand white rabbits which were immunosuppressed with daily cyclosporin A were inoculated into their right eyes with aliquots of 1.5×106 / 50 µL of 92.1 human uveal melanoma cells cultured in RPMI. At week 4, the tumor-bearing eyes were imaged using high-frequency ultrasound with microbubble contrast agent to determine the 2-dimensional tumor size and relative blood volume and by 3-dimensional mode to determine tumor volume. Histologic tumor burden was quantified in enucleated eyes by ImageJ software, and microvascular density (MVD) was determined by counting vascular channels in PAS without hematoxylin sections.
Results
Utilizing HF-CE-US, melanomas were visualized as relatively hyperechoic regions in the images. The correlation coefficients of sonographic size or volume compared with histologic area were 0.72 and 0.70, respectively. The sonographic tumor relative blood volume correlated with the histologic tumor vascularity (R2=0.92, P=0.04)
Conclusions
There is a positive correlation between in vivo sonographic tumor volume/size and histologic tumor size in our rabbit choroidal melanoma model. HF-CE-US corresponds to microvascular density and blood volume.
doi:10.1136/bjophthalmol-2013-303343
PMCID: PMC3863377  PMID: 23645822
24.  EFFECT OF ISOMETRIC EXERCISE ON CHOROIDAL BLOOD FLOW IN PATIENTS WITH AGE-RELATED MACULAR DEGENERATION (AMD) 
The British journal of ophthalmology  2010;94(12):1629-1631.
Aim
To investigate the choroidal vascular regulation in age related macular degeneration (AMD) we compared the regulatory responses induced by isometric exercise in control subjects and patients with AMD.
Methods
Seventeen eyes of 17 patients with dry AMD in the study eye and 19 eyes of 19 controls were included in this study. Both groups were well matched in regards to age, race and gender. Brachial artery blood pressure determinations and laser Doppler flowmetry (Oculix) measurements of relative foveolar choroidal blood velocity, volume, and flow were obtained in the study eye of each subject during 30 seconds of baseline, and then, during 3 minutes of isometric exercise consisting of squeezing a hand grip in each hand. Similar measurements were then also obtained during the two minutes following the cessation of exercise. Using non-paired, two-tailed t-test, changes in circulatory parameters during exercise and following the end of exercise were compared between AMD patients and control subjects. The slope for the relationship between circulatory changes and perfusion pressure changes was calculated and compared between AMD patients and controls using linear regression analysis. Analysis of data was performed in a masked fashion. Circulatory measurements are shown in arbitrary units (AU).
Results
There were no statistically significant differences between the changes in ChBVel, ChBVol and ChBFlow observed in control subjects and AMD patients during the isometric exercise phase and after exercise.
Conclusions
Our results suggest that the response of the choroidal circulation to this type of isometric exercise resulting in a moderate increase in blood pressure does not seem to be affected by AMD.
doi:10.1136/bjo.2009.176859
PMCID: PMC4077432  PMID: 20837789
Isometric exercises; choroidal blood flow; Age-Related Macular Degeneration (AMD)
25.  Family history, near work, outdoor activity, and myopia in Singapore Chinese preschool children 
The British journal of ophthalmology  2010;94(8):1012-1016.
Aims
To investigate the risk factors for myopia, including near work and outdoor activity, in Singapore Chinese preschool children.
Methods
A cross-sectional study, with disproportionate random sampling by 6-month age groups, of 3009 Singapore Chinese children aged 6–72 months was performed. Information on family history, near work and outdoor activity was obtained. Spherical equivalent refraction (SEA) was assessed.
Results
Children with two myopic parents were more likely to be myopic (adjusted OR=1.91; 95% CI 1.38 to 2.63) and to have a more myopic SER (regression coefficient=−0.35; 95% CI −0.47 to −0.22) than children without myopic parents. For each 1 cm taller height, the SER was more myopic by 0.01 dioptres. Neither near work nor outdoor activity was associated with preschool myopia.
Conclusions
A family history of myopia was the strongest factor associated with preschool myopia. In contrast, neither near work nor outdoor activity was found to be associated with early myopia. These data suggest that genetic factors may play a more substantial role in the development of early-onset myopia than key environmental factors.
doi:10.1136/bjo.2009.173187
PMCID: PMC4041336  PMID: 20472747

Results 1-25 (414)