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26.  Optical coherence tomography angiography of optic nerve head and parafovea in multiple sclerosis 
The British journal of ophthalmology  2014;98(10):1368-1373.
Aims
To investigate swept-source optical coherence tomography (OCT) angiography in the optic nerve head (ONH) and parafoveal regions in patients with multiple sclerosis (MS).
Methods
Fifty-two MS eyes and 21 healthy control (HC) eyes were included. There were two MS subgroups: 38 MS eyes without an optic neuritis (ON) history (MS −ON), and 14 MS eyes with an ON history (MS +ON). The OCT images were captured by high-speed 1050 nm swept-source OCT. The ONH flow index (FI) and parafoveal FI were quantified from OCT angiograms.
Results
The mean ONH FI was 0.160±0.010 for the HC group, 0.156±0.017 for the MS−ON group, and 0.140±0.020 for the MS+ON group. The ONH FI of the MS+ON group was reduced by 12.5% compared to HC eyes (p=0.004). A higher percentage of MS+ON eyes had abnormal ONH FI compared to HC patients (43% vs 5%, p=0.01). Mean parafoveal FIs were 0.126±0.007, 0.127±0.010, and 0.129±0.005 for the HC, MS−ON, and MS +ON groups, respectively, and did not differ significantly among them. The coefficient of variation (CV) of intravisit repeatability and intervisit reproducibility were 1.03% and 4.53% for ONH FI, and 1.65% and 3.55% for parafoveal FI.
Conclusions
Based on OCT angiography, the FI measurement is feasible, highly repeatable and reproducible, and it is suitable for clinical measurement of ONH and parafoveal perfusion. The ONH FI may be useful in detecting damage from ON and quantifying its severity.
doi:10.1136/bjophthalmol-2013-304547
PMCID: PMC4598177  PMID: 24831719
27.  Intraoperative Optical Coherence Tomography Utilizing the RESCAN 700: Preliminary Results from the DISCOVER study 
The British journal of ophthalmology  2014;98(10):1329-1332.
Summary
Significant integrative advances are needed for intraoperative optical coherence tomography (iOCT) to achieve widespread use across ophthalmic surgery. A surgeon feedback system that provides microscope integration, heads-up display, and foot pedal control of the OCT scan location represents a major interval advance in ophthalmic surgery. In this report, we describe the preliminary findings of the DISCOVER study, a multi-surgeon investigational device study examining the role of microscope integrated iOCT systems with surgeon heads-up display feedback (e.g., Carl Zeiss Meditec RESCAN 700, Cole Eye Institute iOCT prototype). During surgical maneuvers in anterior segment and posterior segment surgery, this technology provides rapid visualization of the area of interest and provides the surgeon with information regarding instrument-tissue interactions. This system represents a major advance in iterative technology for iOCT and may provide the first widely available platform for surgeons to seamlessly assimilate this technology into the operating room theater.
doi:10.1136/bjophthalmol-2014-305294
PMCID: PMC4169737  PMID: 24782469
28.  Ophthalmic statistics note 5: diagnostic tests—sensitivity and specificity 
The British Journal of Ophthalmology  2014;99(9):1168-1170.
This is the fifth statistics note produced by the Ophthalmic Statistics Group (OSG) which is designed to be a simple guide to ophthalmic researchers on a statistical issue with an applied ophthalmic example. The OSG is a collaborative group of statisticians who have come together with a desire to raise the statistical standards of ophthalmic researcher by increasing statistical awareness of common issues.
doi:10.1136/bjophthalmol-2014-306055
PMCID: PMC4552896  PMID: 25488948
Diagnostic tests/Investigation; Epidemiology
29.  Hypo-accommodation Responses in Hypermetropic Infants and Children 
Aims
Accommodation to overcome hypermetropia is implicated in emmetropisation. This study recorded accommodation responses in a wide range of emmetropising infants and older children with clinically significant hypermetropia to assess common characteristics and differences.
Methods
A PlusoptiXSO4 photorefractor in a laboratory setting was used to collect binocular accommodation data from participants viewing a detailed picture target moving between 33cm and 2m. 38 typically developing infants were studied between 6-26 weeks of age and were compared with cross-sectional data from children 5-9 years of age with clinically significant hypermetropia (n=15), corrected fully accommodative strabismus (n=14) and 27 age-matched controls.
Results
Hypermetropes of all ages under-accommodated compared to controls at all distances, whether corrected or not (p<0.00001) and lag related to manifest refraction. Emmetropising infants under-accommodated most in the distance, while the hypermetropic patient groups under-accommodated most for near.
Conclusions
Better accommodation for near than distance is demonstrated in those hypermetropic children who go on to emmetropise. This supports the approach of avoiding refractive correction in such children. In contrast, hypermetropic children referred for treatment for reduced distance visual acuity are not likely to habitually accommodate to overcome residual hypermetropia left by an under-correction.
doi:10.1136/bjo.2009.177378
PMCID: PMC4533884  PMID: 20603431
Hyperopia; Accommodation; ocular; Infant; Child; Emmetropisation
30.  Decreased accommodation during decompensation of distance exotropia 
Objective
Disparity cues can be a major drive to accommodation via the CA/C (convergence accommodation to convergence) linkage but, on decompensation of exotropia, disparity cues are extinguished by suppression, so this drive is lost. This study investigated accommodation and vergence responses to disparity, blur and proximal cues in a group of distance exotropes aged between 4-11 years both during decompensation and when exotropic.
Methods
19 participants with distance exotropia were tested using a PlusoptiXSO4 photorefractor set in a remote haploscopic device which assessed simultaneous vergence and accommodation to a range of targets incorporating different combinations of blur, disparity and proximal cues at four fixation distances between 2m and 33cm. Responses on decompensation were compared to those from the same children when their deviation was controlled.
Results
Manifest exotropia was more common in the more impoverished cue conditions. When decompensated for near, mean accommodation gain for the all-cue (naturalistic) target reduced significantly (p<0.0001), with resultant mean under-accommodation of 2.33D at 33cm. The profile of near cues usage changed after decompensation, with blur and proximity driving residual responses, but these remaining cues did not compensate for loss of accommodation caused by the removal of disparity.
Conclusions
Accommodation often reduces on decompensation of distance exotropia as the drive from convergence is extinguished, providing a further reason to try to prevent decompensation for near.
doi:10.1136/bjophthalmol-2011-300138
PMCID: PMC4533888  PMID: 21873311
Distance exotropia; Accommodation; Decompensation; AC/A; CA/C
31.  Ziv-aflibercept in macular disease 
The British Journal of Ophthalmology  2015;99(8):1055-1059.
Background/aims
Aflibercept is an approved therapy for neovascular age-related macular degeneration (AMD) and diabetic macular oedema (DME). In vitro and in vivo studies did not detect toxicity to the retinal pigment epithelium cells using the approved cancer protein, ziv-aflibercept. Our purpose is to determine if ziv-aflibercept can be used in AMD and DME without ocular toxicity, to test the stability of ziv-aflibercept, and to do a cost analysis.
Methods
Prospectively, consecutive patients with AMD or DME and poor vision underwent one intravitreal injection of 0.05 mL of fresh filtered ziv-aflibercept (1.25 mg). Monitoring of best-corrected visual acuity, intraocular inflammation, cataract progression, and retinal structure by spectral domain optical coherence tomography was done at 1 day and 1 week after injection. Ziv-aflibercept activity over 4 weeks was measured by capturing vascular endothelial growth factor by ELISA.
Results
There were no signs of retinal toxicity, intraocular inflammation or change in lens status in four eyes with AMD and two eyes with DME. Visual acuity improved (p=0.05) and central foveal thickness decreased in all patients (p=0.05). Ziv-aflibercept had no loss of anti-VEGF activity when kept at 4°C in polycarbonate syringes over 4 weeks. Similar to bevacizumab, compounded ziv-aflibercept would yield a tremendous saving compared with aflibercept or ranibizumab.
Conclusions
Off-label use of ziv-aflibercept improves visual acuity without ocular toxicity and may offer a cheaper alternative to the same molecule aflibercept.
Trial registration number
NCT02173873.
doi:10.1136/bjophthalmol-2014-306319
PMCID: PMC4518747  PMID: 25677668
Angiogenesis; Macula; Neovascularisation; Drugs
32.  Defining the ideal femtosecond laser capsulotomy 
The British Journal of Ophthalmology  2015;99(8):1137-1142.
Purpose
We define the ideal anterior capsulotomy through consideration of capsular histology and biomechanics. Desirable qualities include preventing posterior capsular opacification (PCO), maintaining effective lens position (ELP) and optimising capsular strength.
Methods
Laboratory study of capsular biomechanics and literature review of histology and published clinical results.
Results
Parameters of ideal capsulotomy construction include complete overlap of the intraocular lens to prevent PCO, centration on the clinical approximation of the optical axis of the lens to ensure concentricity with the capsule equator, and maximal capsular thickness at the capsulotomy edge to maintain integrity.
Conclusions
Constructing the capsulotomy centred on the clinical approximation of the optical axis of the lens with diameter 5.25 mm optimises prevention of PCO, consistency of ELP and capsular strength.
doi:10.1136/bjophthalmol-2014-306065
PMCID: PMC4518749  PMID: 25829488
Treatment Lasers
33.  Prevalence of age-related macular degeneration in the Republic of Ireland 
The British Journal of Ophthalmology  2015;99(8):1037-1044.
Background
Age-related macular degeneration (AMD) remains the most common cause of visual loss among subjects over 50 years of age in the developed world. The Irish Longitudinal study on Ageing (TILDA) is a population-based study of subjects aged 50 years or older, designed to investigate factors that influence ageing, and has enabled this investigation of the prevalence of AMD in the Republic of Ireland (ROI).
Methods
Data collected from a nationally representative sample of community-living older adults aged 50 years and over in ROI over the period November 2009 to July 2011. 5035 participants attended the TILDA health centre for assessment. Retinal photographs were obtained in 4859 of these participants. Retinal grading was performed in a masked fashion using a modified version of the International Classification and Grading System for AMD.
Results
Adjusting for lower response rates among older subjects, the estimated overall prevalence of any AMD was 7.2% (95% CI 6.5% to 7.9%) in the population aged 50 years or older. The estimated prevalence of early AMD was 6.6% (95% CI 5.9% to 7.3%), and the estimated prevalence of late AMD was 0.6% (95% CI 0.4% to 0.8%). Statistically significant associations with AMD included increasing age and family history of the condition.
Conclusions
This is the first study to provide prevalence estimates of AMD in ROI and will inform eye care professionals and policymakers involved in the delivery and planning of care for those afflicted with this condition.
doi:10.1136/bjophthalmol-2014-305768
PMCID: PMC4518752  PMID: 25712825
Epidemiology; Public health; Imaging; Macula; Vision
34.  The mental health of UK ex-servicemen with a combat-related or a non-combat-related visual impairment: does the cause of visual impairment matter? 
The British Journal of Ophthalmology  2015;99(8):1103-1108.
Aims
Since the start of the conflicts in Iraq and Afghanistan, the numbers of young service personnel who have sustained a combat-related visual impairment have increased. This cross-sectional study examined the mental well-being of ex-servicemen (aged 22–55 years) with a visual impairment and determined if the mental health of those with a combat-related visual impairment differed from those whose visual impairment is not combat-related.
Methods
Male ex-service personnel with a visual impairment completed a telephone interview assessing the presence of depressive symptomatology, probable anxiety disorder, post-traumatic stress disorder (PTSD) symptomatology and alcohol misuse. Data were analysed using descriptive statistics.
Results
77 participants were included in the study, reflecting a response rate of 76.2%. Of those with complete data (n=74), 20 ex-servicemen had a combat-related visual impairment. Among ex-service personnel with a combat-related visual impairment, 10.0% (95% CI 0 to 23.2) screened positive for a probable depression, 25.0% (95% CI 6.0 to 44.0) for probable anxiety and 10.0% (95% CI 0 to 23.2) for probable PTSD. The prevalence of probable depression and probable PTSD differed among those with a non-combat-related visual impairment, namely 18.5% (95% CI 8.1 to 28.9) and 16.7% (95% CI 6.8 to 26.7), respectively. Probable anxiety was 18.5% (95% CI 8.1 to 28.9) among non-combat-related visually impaired ex-service personnel. 45.0% (95% CI 23.2 to 66.8) of combat-related visually impaired personnel reported hazardous drinking, compared with 20.4% (95% CI 9.7 to 31.2) of those with a non-combat-related visual impairment.
Conclusions
Mental health problems were prevalent among visually impaired younger ex-servicemen. No statistically significant differences were found in the prevalence of mental health problems among ex-servicemen with a combat-related visual impairment compared with those with a non-combat-related visual impairment.
doi:10.1136/bjophthalmol-2014-305986
PMCID: PMC4518753  PMID: 25908837
Epidemiology; Vision; Trauma; Public health
35.  The scotogenic contact lens: a novel device for treating binocular diplopia 
The British Journal of Ophthalmology  2015;99(8):1022-1024.
Binocular diplopia is a debilitating visual symptom requiring immediate intervention for symptomatic control, whether or not definitive treatment is eventually possible. Where prismatic correction is infeasible, the current standard is occlusion, either by a patch or an opaque contact lens. In eliminating one problem—diplopia—occlusive techniques invariably create another: reduced peripheral vision. Crucially, this is often unnecessary, for the reduced spatial resolution in the periphery limits its contribution to the perception of diplopia. Here, we therefore introduce a novel soft contact lens device that instead creates a monocular central scotoma inversely mirroring the physiological variation in spatial acuity across the monocular visual field, thereby suppressing the diplopia with minimal impact on the periphery. We compared the device against standard eye patching in 12 normal subjects with prism-induced binocular diplopia and 12 patients with binocular diplopia of diverse causes. Indexed by self-reported scores and binocular perimetry, the scotogenic contact lens was comparably effective in eliminating the diplopia while significantly superior in acceptability and its impact on the peripheral visual field. This simple, inexpensive, non-invasive device may thus be an effective new tool in the treatment of a familiar but still troublesome clinical problem.
doi:10.1136/bjophthalmol-2014-305985
PMCID: PMC4518759  PMID: 25680615
Contact lens; Field of vision; Treatment other; Visual perception
36.  Early diagnosis and successful treatment of paraneoplastic melanocytic proliferation 
Background
Paraneoplastic melanocytic proliferation (bilateral diffuse uveal melanocytic proliferation, BDUMP) is a rare but devastating disease that causes progressive visual loss in patients who usually have an occult malignancy. Visual loss occurs as a result of paraneoplastic changes in the uveal tissue.
Methods
In a masked fashion, the serum of two patients with BDUMP was evaluated for the presence of cultured melanocyte elongation and proliferation (CMEP) factor using cultured human melanocytes. We evaluated the efficacy of plasmapheresis as a treatment modality early in the disease in conjunction with radiation and chemotherapy.
Results
The serum of the first case patient was investigated after plasmapheresis and did not demonstrate proliferation of cultured human melanocytes. The serum of the second case was evaluated prior to treatment with plasmapheresis and did induce this proliferation. These findings are in accordance with the diminution of CMEP factor after plasmapheresis. Treatment with plasmapheresis managed to stabilise the ocular disease progression in both patients.
Conclusions
In the past, visual loss due to paraneoplastic melanocytic proliferation was considered progressive and irreversible. We treated two patients successfully with plasmapheresis and demonstrated a relation between CMEP factor in the serum of these patients and proliferation of cultured melanocytes.
doi:10.1136/bjophthalmol-2014-305893
PMCID: PMC4501174  PMID: 25908835
Retina; Imaging; Choroid; Neoplasia
37.  Outcomes of ab interno trabeculectomy with the trabectome by degree of angle opening 
Aim
To analyse ab interno trabeculectomy (AIT) with the trabectome and combined phacoemulsification with AIT (phaco-AIT) by Shaffer angle grade (SG).
Methods
Prospective study of AIT and phaco-AIT with narrow angles of SG≤2 versus open angles ≥3. Outcomes included intraocular pressure (IOP), medications, complications, secondary surgery and success (IOP <21 mm Hg and >20% reduction without further surgery). Exclusion criteria were missing preoperative data and <1 year follow-up.
Results
Of 671 included cases, at 1 year AIT SG≤2 (n=43) had an IOP reduction of 42% from 27.3±7.4 to 15.7±3.0 mm Hg (p<0.01) versus AIT SG≥3 (n=271) with an IOP reduction of 37% from 26.1±7.8 to 16.4±3.9 mm Hg (p<0.01). In phaco-AIT with SG≤2 (n=48), IOP was reduced 24% from 20.7±7.0 to 15.7±3.6 mm Hg (p<0.01) versus phaco-AIT with SG≥3 (n=309) with an IOP reduction of 25% from 22.6±6.4 to 17.0±3.4 mm Hg (p<0.01). There was no difference between SG≤2 and SG≥3 in reduction of IOP or medications, complications, secondary surgery and success rates (p>0.05).
Conclusions
SG≤2 is not associated with worse outcomes in AIT or phaco-AIT.
doi:10.1136/bjophthalmol-2014-305577
PMCID: PMC4501175  PMID: 25336577
Glaucoma; Treatment Surgery; Anterior chamber; Angle
38.  Ciliary neurotrophic factor (CNTF)-mediated ganglion cell survival in a rodent model of non-arteritic anterior ischaemic optic neuropathy (NAION) 
Background
Ciliary neurotrophic factor (CNTF) has been shown to protect retinal ganglion cells (RGCs) in traumatic optic nerve injury. We sought to evaluate this neuroprotective effect of CNTF after an ischaemic event using rodent anterior ischaemic optic neuropathy (rAION), a mouse model of non-arteritic anterior ischaemic optic neuropathy (NAION).
Methods
We induced rAION in Thy1-cyan fluorescent protein (CFP) transgenic mice by exposing the optic nerve to frequency doubled neodymium yttrium aluminium garnet laser pulses following intravenous rose bengal injection. One day after rAION induction, an intravitreal injection of 0.75 μg CNTF or vehicle (sham injection) was given. Animals were euthanised on day 15 after induction, tissues isolated and CFP cells in the RGC layer were counted using stereology in flat-mounted retina. The average number of CFP-positive (CFP+) cells was determined for each study group and the percentages of RGC loss were compared between the different groups.
Results
Two weeks after rAION induction, significantly more (CFP+) cells were preserved in CNTF-treated eyes than in sham-injected controls. Sham-treated animals showed a 58% loss of CFP+ cells. In contrast, CFP+ cell density in CNTF-treated eyes decreased by only 10%, when compared with untreated control eyes. This increased survival was statistically significant (p<0.05).
Conclusions
CNTF exerts a neuroprotective effect in ischaemic optic nerve injury and promotes RGC survival, suggesting that CNTF may be effective in the clinical treatment of human NAION.
doi:10.1136/bjophthalmol-2014-305969
PMCID: PMC4477946  PMID: 25336580
39.  Telemedicine for detecting diabetic retinopathy: a systematic review and meta-analysis 
Objective
To determine the diagnostic accuracy of telemedicine in various clinical levels of diabetic retinopathy (DR) and diabetic macular oedema (DME).
Methods
PubMed, EMBASE and Cochrane databases were searched for telemedicine and DR. The methodological quality of included studies was evaluated using the Quality Assessment for Diagnostic Accuracy Studies (QUADAS-2). Measures of sensitivity, specificity and other variables were pooled using a random effects model. Summary receiver operating characteristic curves were used to estimate overall test performance. Meta-regression and subgroup analyses were used to identify sources of heterogeneity. Publication bias was evaluated using Stata V.12.0.
Results
Twenty articles involving 1960 participants were included. Pooled sensitivity of telemedicine exceeded 80% in detecting the absence of DR, low- or high-risk proliferative diabetic retinopathy (PDR), it exceeded 70% in detecting mild or moderate non-proliferative diabetic retinopathy (NPDR), DME and clinically significant macular oedema (CSME) and was 53% (95% CI 45% to 62%) in detecting severe NPDR. Pooled specificity of telemedicine exceeded 90%, except in the detection of mild NPDR which reached 89% (95% CI 88% to 91%). Diagnostic accuracy was higher with digital images obtained through mydriasis than through non-mydriasis, and was highest when a wide angle (100–200°) was used compared with a narrower angle (45–60°, 30° or 35°) in detecting the absence of DR and the presence of mild NPDR. No potential publication bias was detected.
Conclusions
The diagnostic accuracy of telemedicine using digital imaging in DR is overall high. It can be used widely for DR screening. Telemedicine based on the digital imaging technique that combines mydriasis with a wide angle field (100–200°) is the best choice in detecting the absence of DR and the presence of mild NPDR.
doi:10.1136/bjophthalmol-2014-305631
PMCID: PMC4453504  PMID: 25563767
Diagnostic tests/Investigation; Telemedicine; Retina
40.  A randomised, controlled comparison of latanoprostene bunod and latanoprost 0.005% in the treatment of ocular hypertension and open angle glaucoma: the VOYAGER study 
Aim
To assess the efficacy and safety of latanoprostene bunod (LBN) compared with latanoprost 0.005%, and to determine the optimum drug concentration(s) of LBN in reducing intraocular pressure (IOP) in subjects with open angle glaucoma or ocular hypertension.
Methods
Randomised, investigator-masked, parallel-group, dose-ranging study. Subjects instilled one drop of study medication in the study eye once daily each evening for 28 days and completed five study visits. The primary efficacy endpoint was the reduction in mean diurnal IOP at Day 28.
Results
Of the 413 subjects randomised (LBN 0.006%, n=82; LBN 0.012%, n=85; LBN 0.024%, n=83; LBN 0.040%, n=81; latanoprost, n=82), 396 subjects completed the study. Efficacy for LBN was dose-dependent reaching a plateau at 0.024%–0.040%. LBN 0.024% led to significantly greater reductions in diurnal IOP compared with latanoprost at the primary endpoint, Day 28 (p=0.005), as well as Days 7 (p=0.033) and 14 (p=0.015). The incidence of adverse events, mostly mild and transient, was numerically higher in the LBN treatment groups compared with the latanoprost group. Hyperaemia was similar across treatments.
Conclusions
LBN 0.024% dosed once daily was the lower of the two most effective concentrations evaluated, with significantly greater IOP lowering and comparable side effects relative to latanoprost 0.005%. LBN dosed once daily for 28 days was well tolerated.
Clinical trial number
NCT01223378.
doi:10.1136/bjophthalmol-2014-305908
PMCID: PMC4453588  PMID: 25488946
Clinical Trial; Drugs; Glaucoma; Intraocular pressure; Treatment Medical
41.  Normative data for three tests of visuocognitive function in primary school children: cross-sectional study 
Background/Aims
There is an increasing recognition that visuocognitive difficulties occur in children with neurodevelopmental problems. We obtained normative data for the performance of primary school children using three tests of visuocognitive function that are practicable in a clinical setting.
Methods
We tested 214 children aged between 4 and 11 years without known developmental problems, using tests to assess (1) orientation recognition and adaptive movement (postbox task), (2) object recognition (rectangles task) and (3) spatial integration (contours task).
Results
96% could do the postbox task with ease—only 4% (all aged <9 years) exhibited minor difficulties. Errors in the rectangles task decreased with age: 33% of children aged 4–5 years had major difficulties but >99% of children aged ≥6 years had no, or minor, difficulties. Median scores for the contours task improved with age, and after age 8 years, 99% could see the contour using long-range spatial integration rather than density.
Conclusions
These different aspects of children’s visuocognitive performance were testable in a field setting. The data provide a benchmark by which to judge performance of children with neurodevelopmental problems and may be useful in assessment with a view to providing effective supportive strategies for children whose visuocognitive skills are lower than the expectation for their age.
doi:10.1136/bjophthalmol-2014-305868
PMCID: PMC4453624  PMID: 25712824
Visual perception; Child health (paediatrics); Epidemiology; Rehabilitation; Diagnostic tests/Investigation
42.  A Novel RPGR Mutation Masquerading as Stargardt Disease 
doi:10.1136/bjophthalmol-2013-304822
PMCID: PMC4170590  PMID: 24489377
43.  Arthur Ferguson MacCallan: trachoma pioneer in Egypt 1903–1923 
doi:10.1136/bjophthalmol-2014-306527
PMCID: PMC4413841  PMID: 25813831
Medical Education
44.  EVEREST study report 2: imaging and grading protocol, and baseline characteristics of a randomised controlled trial of polypoidal choroidal vasculopathy 
Purpose
To describe the imaging standards, grading protocol and baseline characteristics of polypoidal choroidal vasculopathy (PCV) from the EVEREST study.
Methods
In a prospective, multicentre study, confocal scanning laser ophthalmoscope indocyanine green angiography (ICGA) was performed using a standardised imaging protocol. All images were graded using standardised, calibrated equipment by fellowship-trained ophthalmologists at the Central Reading Center.
Results
Sixty-one patients with PCV were included in the study. ICGA characteristics included: nodular appearance stereoscopically (56 eyes, 91.8%), hypofluorescent halo (42, 68.9%), abnormal vascular network (54, 88.5%) and pulsation of the polyps (4, 6.6%). Colour fundus photography revealed orange subretinal nodules (34, 55.7%) and massive submacular haemorrhage (8, 13.1%). The mean area of the PCV lesion was 3.11 mm2 (range, 0.2–10.7 mm2). The vascular channels filled within 7.3–32.0 s (mean: 17.9 s) while the mean filling time for polyps was 21.9 s (range, 7.3–40.4 s). Patients with massive submacular haemorrhage were less likely to have abnormal vascular channels seen on ICGA (28.6% vs 83.3% for those without massive haemorrhage, p=0.001).
Conclusions
The imaging and grading protocols and baseline characteristics of a multicentre, randomised controlled trial of PCV are described in detail, and may serve as reference for future randomised, controlled trials on PCV.
Clinical trial number
This work was supported by Novartis Pharma AG, Basel, Switzerland grant number NCT00674323 (clinicaltrials.gov).
doi:10.1136/bjophthalmol-2014-305674
PMCID: PMC4413842  PMID: 25758601
Neovascularisation; Retina; Choroid; Macula
45.  Ophthalmic statistics note 6: effect sizes matter 
doi:10.1136/bjophthalmol-2014-306303
PMCID: PMC4413860  PMID: 25722490
Epidemiology; Medical Education; Public health
46.  Transretinal degeneration in ageing human retina: a multiphoton microscopy analysis 
Aim
Retinal cell remodelling has been reported as a consistent feature of ageing. However, the degree to which this results in transretinal degeneration is unclear. To address this, the authors used multiphoton microscopy to quantify retinal degeneration in postmortem human eyes of two age groups.
Methods
Retinas from six young subjects (18–33 years old) and six older subjects (74–90 years old) were prepared as wholemount preparations. All retinas were stained with 4,6-diamidino-2-phenylindole and imaged by multiphoton confocal microscopy to quantify neuron densities in the retinal ganglion cell layer (RGCL), inner nuclear layer (INL) and outer nuclear layer (ONL). Neurons were counted using automated cell identification algorithms. All retinas were imaged hydrated to minimise tissue artefacts.
Results
In both groups, 56% of the area within the central 4 mm eccentricity and 27% of the area with eccentricity between 4 mm and 7 mm were imaged. Compared with young subjects, the peak RGCL neuron loss in the aged subjects (25.5%) was at 1 mm eccentricity. INL and ONL neuron densities significantly decreased at 1–2 mm eccentricity (8.7%) and 0.5–4 mm eccentricity (15.6%) respectively (P <0.05). The reduction in neuron density in the INL corresponded, spatially, to the region with the greatest neuron loss in the RGCL and ONL.
Conclusions
This is the first study to correlate neurodegeneration in different populations of cells in the ageing retinas. These data confirm that the greatest neuronal loss occurs in the RGCL and ONL in human ageing retinas, whereas the INL is relatively preserved.
doi:10.1136/bjo.2010.180869
PMCID: PMC4406415  PMID: 21183516
47.  Hydroxychloroquine retinopathy screening 
The British journal of ophthalmology  2008;92(12):1653-1655.
Aim
To compare current hydroxychloroquine retinopathy screening practices with the published 2002 American Academy of Ophthalmology (AAO) Preferred Practice Patterns (PPP).
Methods
A multiple-choice survey was distributed to 105 ophthalmologists to assess current screening practices and knowledge of patient risk factors. Results were compared with the PPP guidelines. A cost analysis of the PPP and survey paradigms was conducted.
Results
Sixty-seven (64%) of 105 surveys were completed. The majority (90%) of physicians screen for hydroxychloroquine retinopathy with either central automated threshold perimetry or Amsler grid as recommended by the PPP. Most survey respondents could not correctly identify the evidence-based risk factors. The majority screen more frequently than recommended: 87% screen high-risk patients and 94% screen low-risk patients more frequently than recommended in the PPP. The increased screening frequency of low-risk patients translates into an excess of $44 million in the first five years of therapy. If all patients were screened using exact PPP paradigm, savings could exceed $150 million every 10 years.
Conclusions
Ophthalmologists currently screen for hydroxychloroquine retinopathy correctly, however, their lack of familiarity with evidence-based guidelines may result in excessive follow up. Increasing awareness and implementation of the PPP could potentially reduce hydroxychloroquine retinopathy screening costs significantly.
doi:10.1136/bjo.2008.144402
PMCID: PMC4397565  PMID: 18829634
hydroxychloroquine; plaquenil; toxicity; screening; cost analysis
48.  Simulation contact lenses for AMD health state utility values in NICE appraisals: a different reality 
Background/aims
The National Institute for Health and Care Excellence (NICE) has recommended the use of ranibizumab for neovascular age-related macular degeneration (AMD) and for diabetic macular oedema (DMO) as part of its health technology appraisal process. In the economic evaluations of both interventions, utility values were derived from members of the general public wearing contact lenses with a central opacity that was meant to simulate the blind spot experienced by many patients with advanced retinal disease. This paper tests the validity of the contact lens simulation, and finding it to be invalid, explores the impact on prior economic evaluations.
Methods
Visual acuity, contrast sensitivity and visual fields were assessed with and without simulation lenses in five healthy subjects with normal vision.
Results
We identified important differences between the contact lens simulation and vision loss experienced by patients with AMD. The contact lens simulator did not cause the central scotoma which is characteristic of late-stage AMD and which leads to severe difficulty with everyday activities such as reading or recognising faces and objects. The contact lens instead caused a reduction in retinal illumination experienced by the subjects as a general dimming across the retina.
Conclusions
A contact lens with a central opacity does not simulate a central scotoma. The clinical differences between simulated and actual AMD suggest there has been an underestimation of the severity of AMD health states. This brings into question the validity of the economic evaluations of treatments for AMD and DMO used by NICE.
doi:10.1136/bjophthalmol-2014-305802
PMCID: PMC4392203  PMID: 25351679
Retina; Vision
49.  Advising patients on visual fitness to drive: implications of revised DVLA regulations 
Aim
To examine the relationship between the two UK vision standards for driving: the ability to read a number-plate at 20 m and achieving 6/12 (+0.30 logMAR).
Methods
120 participants were assessed without refractive correction in this cross-sectional study. Vision was assessed with a Snellen chart, Early Treatment of Diabetic Retinopathy Study (ETDRS) style logMAR letter chart and logMAR chart using Landolt rings. Ability to read a post-2001 number-plate was assessed outdoors.
Results
For all charts, there was an ‘overlap zone’ of visions within which it was uncertain whether participants would pass the number-plate test. Within this zone, sensitivity and specificity of the 6/12 cut-off for predicting number-plate performance were reasonable for Snellen and ETDRS style charts, but poor for Landolt. All participants with 6/7.5 Snellen (+0.10 logMAR ETDRS) or better could read a number-plate. Some participants (2–6%) with vision between this level and 6/12 could not read a number-plate, and 14%–15% could read a number-plate but not achieve 6/12.
Conclusions
To best predict drivers’ ability to read a number-plate, vision should be assessed using a logMAR letter chart or a Snellen chart scored by full line. Drivers with 6/7.5 (+0.10 logMAR) or better vision can be advised that they meet the driving standard. Drivers with acuity between 6/9 and 6/12 (+0.12—+0.30 logMAR) should be advised to check their ability to read a number-plate, as some may not be able to. Clinicians will see patients who can read a number-plate, but do not achieve 6/12, who will need improved vision to meet visual requirements for driving.
doi:10.1136/bjophthalmol-2014-306173
PMCID: PMC4392215  PMID: 25381011
Vision
50.  Weight at first detection of retinopathy of prematurity predicts disease severity 
The British journal of ophthalmology  2014;98(11):1565-1569.
Objective
To investigate whether postnatal weight at first detection of retinopathy of prematurity (ROP) can predict preterm infants who will develop severe ROP warranting treatment.
Design
This modern, population-based cohort included 147 infants born at gestational age (GA) <32 weeks in the Gothenburg region during 2011–2012 and screened for ROP at Sahlgrenska University hospital. GA, birth weight (BW), and weekly postnatal weight from birth until postmenstrual age (PMA) 40 weeks data were retrospectively retrieved. Birth weight SD scores (BWSDS) were calculated. ROP data, including first detected ROP stage, maximal ROP stage, ROP treatment, and PMA at first detected sign of ROP were also retrieved. Weight SDS (WSDS) at first ROP detection was calculated.
Results
Stepwise multivariate logistic regression analysis revealed that the best fit-model of risk factors for developing severe ROP warranting treatment included; GA (OR=0.28, CI 95% 0.12 to 0.66, p<0.01) and WSDS at first ROP detection (OR=0.22, CI 95% 0.05 to 0.89, p<0.05).
Conclusions
Low weight and low WSDS at first ROP detection can be useful predictors for ROP warranting treatment.
doi:10.1136/bjophthalmol-2014-304905
PMCID: PMC4389626  PMID: 24963022

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