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1.  Pharmacogenetics of Complement Factor H (Y402H) and treatment of exudative age-related macular degeneration with ranibizumab 
Aims
To determine whether complement factor H (CFH) genotypes have a pharmacogenetic effect on the treatment of exudative age-related macular degeneration (AMD) with ranibizumab.
Methods
A retrospective study of 156 patients with exudative AMD treated with intravitreal ranibizumab monotherapy was conducted. AMD phenotypes were characterized by clinical examination, visual acuity, fundus photography, fluorescein angiography, and injection timing. Patients received intravitreal ranibizumab injections as part of routine ophthalmologic care and were followed for a minimum of nine months. Each patient was genotyped for the single nucleotide polymorphism rs1061170 (Y402H) in the CFH gene.
Results
Baseline lesion size and angiographic type, as well as mean visual acuities at baseline, 6 months, and 9 months were similar among the three CFH genotypes. Over 9 months, patients with both risk alleles received approximately one more injection (p = 0.09). In a recurrent event analysis, patients homozygous for the CFH Y402H risk allele had a 37% significantly higher risk of requiring additional ranibizumab injections (p = 0.04)
Conclusions
In our cohort, response to treatment of AMD with ranibizumab differed according to CFH genotype, suggesting that determining patients' CFH genotype may be helpful in the future in tailoring treatment for exudative AMD with intravitreal ranibizumab.
doi:10.1136/bjo.2008.150995
PMCID: PMC3490485  PMID: 19091853
Complement Factor H; Ranibizumab; Age-Related Macular Degeneration; Pharmacogenetics
2.  Impact of self-reported visual impairment on quality of life in the Ibadan Study of Aging 
Background
Information is lacking on the impact of visual impairment on the quality of life of elderly Africans. This study aims to examine the impact of self reported visual impairment on the quality life of an elderly Nigerian sample.
Methods
A multi-stage stratified sampling of households was implemented to select persons aged 65 years and over (n = 2054) in the south-western and north-central parts of Nigeria. Impairments of distant and near vision were based on subjective self-reports obtained with the use of items derived from the World Health Organization (WHO) multi-country World Health Survey questionnaire. Estimates of quality of life scores were made for normal sighted and visually impaired individuals using the WHO Quality of Life instrument, brief version (WHOQoL-Bref) .
Results
Four hundred and fifty three (22.3%) of the respondents reported impairment for distant vision, 377 (18.4%) for near vision while 312 (15.2) reported impairment for both far and near. Impairment of near vision had a significant impact on all domains of quality of life. Distant vision had less impact, with significant decrement only in the domain of environment. After adjusting for the possible effects of age, sex, and co-occurring chronic physical illness, near vision impairment accounted for 3.92% decrement in the overall quality of life of elderly persons.
Conclusion
Impairment of vision is associated with significant decrement in diverse areas of quality of life in this elderly sample. Problems with near vision were nevertheless more likely than those of distant vision to affect quality of life.
doi:10.1136/bjo.2007.124859
PMCID: PMC2820710  PMID: 18296505
vision impairment; quality of life; elderly population
3.  Expression of heat shock protein 27 and alpha-crystallins in human retinoblastoma after chemoreduction 
Aim
Small heat shock proteins (sHSP) play an important role in the resistance to anticancer drugs. We examined the expression of the sHSP family, HSP27 and α-crystallins, in human retinoblastoma with and without preoperative chemotherapy.
Methods
Eighteen enucleated eyes from patients with retinoblastoma were used. Six patients had undergone chemotherapy before enucleation. Formalin-fixed, paraffin-embedded tissue sections were processed for H&E staining and examined by immunohistochemistry using anti-HSP27 and α-crystallins antibodies.
Results
Eleven of 12 cases with no history of preoperative chemotherapy showed weakly positive or negative staining for HSP27, whereas six and five cases were strongly positive for αA and αB-crystallin, respectively. In the six cases with a history of chemotherapy, several viable retinoblastoma cells remained. Immunoreactivity for HSP27 and αB-crystallin was strongly detected in the cytoplasm of viable retinoblastoma cells, while αA-crystallin immunoreactivity was less marked. Immunoreactivity for HSP27 was significantly higher in retinoblastoma cases with preoperative chemotherapy than in those without chemotherapy (p<0.0001). In contrast, immunoreactivity for αA-crystallin was significantly lower in cases with chemotherapy than in cases without chemotherapy (p<0.01).
Conclusions
HSP27 and αB-crystallin, but not αA-crystallin, were highly expressed in viable tumour cells after chemotherapy, suggesting that HSP27 and αB-crystallin may protect tumour cells from apoptotic signals produced by anticancer drugs in retinoblastoma.
doi:10.1136/bjo.2008.145508
PMCID: PMC3062474  PMID: 18812387
4.  Heidelberg Retina Tomograph 3 machine learning classifiers for glaucoma detection 
Aims
To assess performance of classifiers trained on Heidelberg Retina Tomograph 3 (HRT3) parameters for discriminating between healthy and glaucomatous eyes.
Methods
Classifiers were trained using HRT3 parameters from 60 healthy subjects and 140 glaucomatous subjects. The classifiers were trained on all 95 variables and smaller sets created with backward elimination. Seven types of classifiers, including Support Vector Machines with radial basis (SVM-radial), and Recursive Partitioning and Regression Trees (RPART), were trained on the parameters. The area under the ROC curve (AUC) was calculated for classifiers, individual parameters and HRT3 glaucoma probability scores (GPS). Classifier AUCs and leave-one-out accuracy were compared with the highest individual parameter and GPS AUCs and accuracies.
Results
The highest AUC and accuracy for an individual parameter were 0.848 and 0.79, for vertical cup/disc ratio (vC/D). For GPS, global GPS performed best with AUC 0.829 and accuracy 0.78. SVM-radial with all parameters showed significant improvement over global GPS and vC/ D with AUC 0.916 and accuracy 0.85. RPART with all parameters provided significant improvement over global GPS with AUC 0.899 and significant improvement over global GPS and vC/D with accuracy 0.875.
Conclusions
Machine learning classifiers of HRT3 data provide significant enhancement over current methods for detection of glaucoma.
doi:10.1136/bjo.2007.133074
PMCID: PMC2916743  PMID: 18523087
5.  Imaging of the retinal nerve fibre layer for glaucoma 
Background
Glaucoma is a group of diseases characterised by retinal ganglion cell dysfunction and death. Detection of glaucoma and its progression are based on identification of abnormalities or changes in the optic nerve head (ONH) or the retinal nerve fibre layer (RNFL), either functional or structural. This review will focus on the identification of structural abnormalities in the RNFL associated with glaucoma.
Discussion
A variety of new techniques have been created and developed to move beyond photography, which generally requires subjective interpretation, to quantitative retinal imaging to measure RNFL loss. Scanning laser polarimetry uses polarised light to measure the RNFL birefringence to estimate tissue thickness. Optical coherence tomography (OCT) uses low-coherence light to create high-resolution tomographic images of the retina from backscattered light in order to measure the tissue thickness of the retinal layers and intraretinal structures. Segmentation algorithms are used to measure the thickness of the retinal nerve fibre layer directly from the OCT images. In addition to these clinically available technologies, new techniques are in the research stages. Polarisation-sensitive OCT has been developed that combines the strengths of scanning laser polarimetry with those of OCT. Ultra-fast techniques for OCT have been created for research devices. The continued utilisation of imaging devices into the clinic is refining glaucoma assessment. In the past 20 years glaucoma has gone from a disease diagnosed and followed using highly subjective techniques to one measured quantitatively and increasingly objectively.
doi:10.1136/bjo.2008.145540
PMCID: PMC2907255  PMID: 19028735
6.  Expression of glial cell-derived neurotrophic factor and its receptor in the stem-cell-containing human limbal epithelium 
The British journal of ophthalmology  2008;92(9):1269-1274.
Aim
To evaluate the expression pattern of glial cell line-derived neurotrophic factor (GDNF) with its receptors GDNF family receptor alpha-1 (GFRα-1) and Ret in the human corneal and limbal tissues, as well as in the primary human limbal epithelial cultures (PHLEC).
Methods
Expression of GDNF and its receptors, and the co-localisation with stem cell associated and differentiation markers were evaluated by immunofluorescent staining, western blot analysis and real-time PCR in the fresh human corneoscleral tissues, as well as in the PHLEC. Single cell colony-forming and wound-healing assays were also evaluated in PHLEC.
Results
GDNF and GFRα-1 were found to be expressed by a subset of basal cells and co-localised with ATP-binding cassette, subfamily G (WHITE), member 2 (ABCG2) and p63, but not with cytokeratin 3 in the human limbal basal epithelium. In PHLEC, they were expressed by a small population of cells in the less differentiated stage. The GDNF and GFRα-1-positive subpopulations were enriched for the expression of ABCG2 and p63 (p<0.01). Recombinant human GDNF promoted the proliferation and wound healing of epithelial cells in the PHLEC. In contrast, Ret was abundantly located in the human corneal epithelium except for the basal cells of the limbal epithelium.
Conclusion
These findings indicate that GDNF and GFRα-1 may represent a property for the phenotype of human corneal epithelial precursor cells. GDNF may signal independently of Ret through GFRα-1 in the stem cell-containing limbal epithelium.
doi:10.1136/bjo.2007.132431
PMCID: PMC2906381  PMID: 18723744
7.  Visual and Medical Risk Factors for Motor Vehicle Collision Involvement among Older Drivers 
Aims
To identify visual and medical risk factors for motor vehicle collisions (MVCs).
Methods
Data from four cohorts of older drivers from three states were pooled (n=3,158). Health information was collected at baseline, and MVC data were obtained prospectively. Cox proportional hazards regression was used to estimate rate ratios (RRs) and 95% confidence intervals (CIs) for associations between medical characteristics and MVCs.
Results
A total of 363 MVCs were observed during the study period (1990-1997), of which 145 were at-fault and 62 were injurious. Falls and impaired useful field of view (UFOV1) were positively associated with overall MVCs. At-fault MVCs were also positively associated with falls and UFOV impairment, and inversely with cancer. Injurious MVCs were positively associated with arthritis and neurological disease, and inversely with hypertension.
Conclusions
These findings show similarities and differences across the risk factors for all, at-fault, and injurious MVCs, and point to the need for verification and possible interventions.
doi:10.1136/bjo.2008.144584
PMCID: PMC2747632  PMID: 19019937
automobile driving; data pooling; elderly; vision
8.  HEALTH-RELATED QUALITY OF LIFE AND VISUAL AND COGNTIVE IMPAIRMENT AMONG NURSING HOME RESIDENTS 
Aim
To examine whether the relationship between vision impairment and health-related quality of life (HRQoL) in nursing home residents is impacted by co-existing cognitive impairment.
Methods
This cross-sectional study involved a total of 382 English-speaking older adults (>55 years of age) with ≥13 on the Mini Mental State Exam (MMSE) from seventeen nursing homes in Birmingham, AL. Assessments were taken of visual acuity (Lighthouse Near Visual Acuity Test), cognition (MMSE), and health-related quality of life (Nursing Home Vision-Targeted Health-Related Quality of Life Questionnaire, VF-14, and the SF-36).
Results
A greater portion of participants had both vision and cognitive impairments (38.5%) as compared to those with neither impairment (21.5%), vision impairment alone (13.4%), and cognitive impairment alone (26.7%). Cognitive impairment did not modify the impact of vision impairment on HRQoL. The reduction in HRQoL associated with vision impairment was similar for those with and without cognitive impairment.
Conclusion
The deleterious impact of vision impairment on HRQoL in nursing home residents was not exacerbated by the co-occurrence of cognitive impairment. Aging-related visual impairment in nursing home residents is often reversible through treatment leading to improved HRQoL, and thus it is clinically important to know that cognitive impairment is unlikely to interfere with this benefit.
doi:10.1136/bjo.2008.142356
PMCID: PMC2745735  PMID: 18971236
Nursing Homes; Vision Impairment; Cognitive Impairment; Quality of Life
9.  Progression from macular retinoschisis to retinal detachment in highly myopic eyes is associated with outer lamellar hole formation 
Aims:
To investigate the morphological changes that occur during the development of an early retinal detachment (RD) from a myopic macular retinoschisis (MRS) by optical coherence tomography (OCT).
Methods:
The OCT images of five eyes of five consecutive patients with myopic MRS who developed an RD during the follow-up period were studied.
Results:
The progression from MRS to early RDs went through four stages. In stage 1, OCT images appeared to show a focal irregularity of the thickness of external retina. In stage 2, an outer lamellar hole developed within the thickened area and a small RD developed. In stage 3, the column-like structures overlying the hole seemed to be separated horizontally, and the outer lamellar hole appeared to be larger vertically. In stage 4, the upper edge of the external retina was further elevated and attached to the upper part of the retinoschisis layer accompanied by further enlargement of the RD.
Conclusions:
This longitudinal study showed that the progression from myopic MRS to RD passes through four stages, and the formation of an outer lamellar hole predisposes the retina to a RD. These OCT findings might be useful for considering the surgical indication for eyes with a myopic MRS.
doi:10.1136/bjo.2007.131359
PMCID: PMC2771850  PMID: 18523081
10.  Mutations in the quinolone resistance determining region in Staphylococcus epidermidis recovered from conjunctiva and their association with susceptibility to various fluoroquinolones 
Background:
Staphylococcus epidermidis is one of the prominent pathogens in ocular infection. The prevalence of mutations in the quinolone resistance determining region (QRDR) area in S epidermidis isolated from the ocular surface and its association with fluoroquinolone resistance has not been fully elucidated.
Methods:
Mutations in the QRDR of gyrA, gyrB, parC, and parE genes of 138 isolates of S epidermidis recovered from the human conjunctival flora were analysed. The minimal inhibitory concentrations (MICs) of four fluoroquinolones (levofloxacin, gatifloxacin, moxifloxacin and tosufloxacin) against these isolates were also determined using agar dilution methods.
Results:
The MIC90 values of levofloxacin, gatifloxacin, moxifloxacin and tosufloxacin were 3.13, 1.56, 0.78 and 3.13 μg/ml, respectively. The MIC values of all fluoroquinolones showed a bimodal distribution (susceptible strain and less susceptible strain). Mutations with amino acid substitution in the QRDR were present in 70 (50.7%) isolates. 19 different combinations of mutations were detected: 3 isolates (2.2%) had four mutations, 8 (5.8%) had three mutations, 43 (31.2%) had double mutations and 16 (11.6%) had single mutations. Isolates with mutations in the QRDR of both gyrA and parC (n = 53) were less susceptible to fluoroquinolones.
Conclusions:
The present findings show that approximately half the S epidermidis isolates from the normal human conjunctiva have mutation(s) in the QRDR. The presence of mutations in both gyrA and parC is strongly associated with reduced susceptibility to fluoroquinolones.
doi:10.1136/bjo.2007.129858
PMCID: PMC2771781  PMID: 18460536
11.  Comparison of 4 mg versus 20 mg intravitreal triamcinolone acetonide injections 
Aims
To compare the non-decanted (standard) 4 mg versus the decanted 20 mg intravitreal triamcinolone acetonide (IVTA) injections and to assess their effect on intraocular pressure (IOP).
Methods
We retrospectively reviewed the records of 92 consecutive eyes, which received an intravitreal injection of either dose of triamcinolone acetonide, at a single retina centre. The change in IOP (elevation of at least 5 mm Hg from baseline or above 21 mm Hg) was analysed with a multivariate logistic analysis. The mean follow-up period in both groups was 27 weeks. A subgroup analysis comparing vitrectomised to non-vitrectomised eyes in both groups was also performed.
Results
Of the 92 eyes, 46% (23 of 51) in the 4 mg group versus 30% (12 of 41) in the 20 mg group had an IOP >21 mm of Hg (p = 0.14) after a mean follow-up period of 27 weeks. The vitrectomised eyes (3 of 24) in the 20 mg group had a significantly lower rate of IVTA induced IOP elevation than the non-vitrectomised eyes (9 of 17) (p = 0.013). The IOP elevation occurred significantly earlier in the 4 mg group (vitrectomised eyes 27 (SD 43) days and non-vitrectomised eyes 61 (52) days) than in the 20 mg group (vitrectomised eyes 104 (56) days and non-vitrectomised eyes 119 (82) days), independent of the vitreous status (vitrectomised p = 0.05 and non-vitrectomised p = 0.04). The mean value of initial high IOP in the non-vitrectomised eyes was higher in the 4 mg group than in the corresponding 20 mg group (p = 0.048).
Conclusion
Decanted 20 mg IVTA may not pose a significantly greater risk of IOP elevation than the 4 mg non-decanted IVTA.
doi:10.1136/bjo.2007.126227
PMCID: PMC2776725  PMID: 18420748
12.  The Association between Thyroid Problems and Glaucoma 
The British journal of ophthalmology  2008;92(11):1503-1505.
Aims
To evaluate the association between thyroid problems and glaucoma.
Methods
A population-based cross-sectional sample with 12,376 participants from the 2002 National Health Interview Survey (NHIS). Odds ratios (OR) and 95% confidence intervals (CI) were used to quantify the association between a self-reported diagnosis of glaucoma and a self-reported history of thyroid problems, controlling for demographic characteristics and smoking status.
Results
The overall prevalence of glaucoma was 4.6%; 11.9% reported a history of thyroid problems. The prevalence of glaucoma among those who did and did not report thyroid problems was 6.5% and 4.4%, respectively (p=0.0003). Following adjustment for differences in age, gender, race, and smoking status, the association between glaucoma and thyroid problems remained (OR 1.38, 95% CI 1.08-1.76).
Conclusions
The results of this study lend support to the hypothesis that thyroid disorders may increase the risk of glaucoma. Research should continue evaluating potential mechanisms underlying this relationship and whether the treatment of thyroid problems reduces subsequent glaucoma risk.
doi:10.1136/bjo.2008.147165
PMCID: PMC2708670  PMID: 18927223
13.  Comparison of the Optical Coherence Tomographic Features of Choroidal Neovascular Membranes in Pathologic Myopia versus Age-Related Macular Degeneration, using Quantitative Subanalysis 
The British journal of ophthalmology  2008;92(8):1081-1085.
Aim:
To compare the retinal morphologic characteristics of eyes with choroidal neovascularization (CNV) secondary to pathologic myopia versus eyes with CNV secondary to age-related macular degeneration (AMD), using quantitative optical coherence tomography (OCT) subanalysis.
Methods:
Twenty-one eyes of 21 patients newly diagnosed with CNV secondary to pathologic myopia, and 43 consecutive cases of eyes with newly diagnosed subfoveal CNV secondary to AMD were retrospectively collected. In all patients, StratusOCT images and fluorescein angiograms (FA) were available for analysis. StratusOCT images were analyzed using custom software (termed “OCTOR”), which allowed calculation of the thickness/volume of the neurosensory retina, subretinal fluid (SRF), subretinal tissue (SRT), and pigment epithelial detachments (PEDs). FA images were used to calculate CNV leakage area and CNV lesion size for each eye.
Results:
Total volume of neurosensory retina in the pathologic myopia group was significantly less than in the AMD group (7.10 ± 0.50 mm3 versus 7.76 ± 0.93 mm3, P=0.004). Total volume of SRF in the pathologic myopia group was less than in the AMD group, however the difference was not statistically significant (0.33 ± 1.38 mm3 versus 0.55 ± 0.82 mm3, P=0.434). Total volume of SRT in the pathologic myopia group was less than in the AMD group, however the difference was not statistically significant (0.16 ± 0.15 mm3 versus 0.36 ± 0.60 mm3, P=0.144). Total volume of PED in the pathologic myopia group was markedly less than in the AMD group (0.01 ± 0.03 mm3 versus 1.09 ± 1.89 mm3, P<0.001). On FA, the total leakage of CNV in the AMD group was significantly greater than in the pathologic myopia group (4.17 ± 3.29 DAs versus 0.53 ± 0.58 DAs P<0.001).
Conclusions:
CNV lesions in pathologic myopia were associated with considerably less retinal edema, SRF, and SRT compared with CNV associated with AMD. PEDs were almost negligible in myopic lesions compared with AMD. These findings are consistent with previous clinical and angiographic descriptions of myopic CNV as relatively small lesions with modest exudation.
doi:10.1136/bjo.2008.138891
PMCID: PMC2749310  PMID: 18586903
Pathologic myopia; Choroid neovascularization; Optical coherence tomography; Age-related macular degeneration
14.  Chlamydia pneumoniae infection, complement factor H variants and age-related macular degeneration 
Background/aims
Impaired inhibition of the alternative complement pathway by complement factor H (CFH) is linked to age-related macular degeneration (AMD) based on the strong association between CFH variant and AMD. Chlamydia pneumoniae (C pneumoniae) infection can trigger the alternative pathway, but the evidence for an association between C pneumoniae and AMD is contradictory. This study investigated whether C pneumoniae infection is associated with AMD and whether the presence of C pneumonia modulates AMD risk conferred by CFH variants.
Methods
Genomic DNA extracted from peripheral blood of 148 advanced AMD patients and 162 controls was subjected to Taqman and PCR-RFLP for the CFH polymorphism and PCR for the C pneumoniae gene. Genomic DNA was also examined from microdissected macular cells from 59 AMD and 16 age-matched non-AMD archived slides. χ2 testing was performed for case-control analysis.
Results
C pneumoniae infection was associated with increased risk of AMD (OR = 2.17, p<0.017). A CFH variant was also linked to increased risk of AMD (OR = 1.98, p<0.0001). However, no relationship was found between risk-conferring CFH variant and C pneumoniae (OR = 1.81, p = 0.08).
Conclusion
There is a possible association between AMD and C pneumoniae infection, although CFH may not be directly involved in the pathogenesis of C pneumoniae infection-mediated AMD.
doi:10.1136/bjo.2008.145383
PMCID: PMC2746818  PMID: 18996904
15.  Sources of longitudinal variability in optical coherence tomography nerve-fibre layer measurements 
Aims
The purpose of this study was to compare the day-to-day reproducibility of optical coherence tomography (OCT; StratusOCT, Carl Zeiss Meditec, Dublin, CA) measurements of retinal nerve-fibre layer (RNFL) measurements at time points 1 year apart.
Methods
One eye in each of 11 healthy subjects was examined using the StratusOCT fast RNFL scan protocol. Three fast RNFL scans with signal strength ≥7 were obtained on each of 3 days within a month. This protocol was repeated after 12 months. A linear mixed effects model fitted to the nested data was used to compute the variance components.
Results
The square root of the variance component that was attributed to the differences between subjects was 7.17 μm in 2005 and 7.28 μm in 2006. The square roots of the variance component due to differences between days within a single subject were 1.95 μm and 1.50 μm, respectively, and for within day within a single subject were 2.51 μm and 2.55 μm, respectively. There were no statistically significant differences for any variance component between the two testing occasions.
Conclusions
Measurement error variance remains similar from year to year. Day and scan variance component values obtained in a cohort study may be safely applied for prediction of long-term reproducibility.
doi:10.1136/bjo.2007.129312
PMCID: PMC2743163  PMID: 18523086
16.  Projection OCT fundus imaging for visualising outer retinal pathology in non-exudative age-related macular degeneration 
Aims
To demonstrate ultrahigh-resolution, three-dimensional optical coherence tomography (3D-OCT) and projection OCT fundus imaging for enhanced visualisation of outer retinal pathology in non-exudative age-related macular degeneration (AMD).
Methods
A high-speed, 3.5 μm resolution OCT prototype instrument was developed for the ophthalmic clinic. Eighty-three patients with non-exudative AMD were imaged. Projection OCT fundus images were generated from 3D-OCT data by selectively summing different retinal depth levels. Results were compared with standard ophthalmic examination, including fundus photography and fluorescein angiography, when indicated.
Results
Projection OCT fundus imaging enhanced the visualisation of outer retinal pathology in non-exudative AMD. Different types of drusen exhibited distinct features in projection OCT images. Photoreceptor disruption was indicated by loss of the photoreceptor inner/outer segment (IS/OS) boundary and external limiting membrane (ELM). RPE atrophy can be assessed using choroid-level projection OCT images.
Conclusions
Projection OCT fundus imaging facilities rapid interpretation of large 3D-OCT data sets. Projection OCT enhances contrast and visualises outer retinal pathology not visible with standard fundus imaging or OCT fundus imaging. Projection OCT fundus images enable registration with standard ophthalmic diagnostics and cross-sectional OCT images. Outer retinal alterations can be assessed and drusen morphology, photoreceptor impairment and pigmentary abnormalities identified.
doi:10.1136/bjo.2007.136101
PMCID: PMC2743133  PMID: 18662918
19.  Intravitreal properties of porous silicon photonic crystals 
Aim
To determine the suitability of porous silicon photonic crystals for intraocular drug-delivery.
Methods
A rugate structure was electrochemically etched into a highly doped p-type silicon substrate to create a porous silicon film that was subsequently removed and ultrasonically fractured into particles. To stabilise the particles in aqueous media, the silicon particles were modified by surface alkylation (using thermal hydrosilylation) or by thermal oxidation. Unmodified particles, hydrosilylated particles and oxidised particles were injected into rabbit vitreous. The stability and toxicity of each type of particle were studied by indirect ophthalmoscopy, biomicroscopy, tonometry, electroretinography (ERG) and histology.
Results
No toxicity was observed with any type of the particles during a period of >4 months. Surface alkylation led to dramatically increased intravitreal stability and slow degradation. The estimated vitreous half-life increased from 1 week (fresh particles) to 5 weeks (oxidised particles) and to 16 weeks (hydrosilylated particles).
Conclusion
The porous silicon photonic crystals showed good biocompatibility and may be used as an intraocular drug-delivery system. The intravitreal injectable porous silicon photonic crystals may be engineered to host a variety of therapeutics and achieve controlled drug release over long periods of time to treat chronic vitreoretinal diseases.
doi:10.1136/bjo.2007.133587
PMCID: PMC2666262  PMID: 18441177
21.  Conjunctival hyperaemia with the use of latanoprost versus other prostaglandin analogues in patients with ocular hypertension or glaucoma: a meta-analysis of randomised clinical trials 
Aim:
To conduct a meta-analysis of randomised clinical trials (RCTs) in order to evaluate the development of conjunctival hyperaemia after the use of latanoprost versus travoprost and bimatoprost, in patients with ocular hypertension or glaucoma.
Methods:
In order to identify the potentially relevant RCTs, a systematic literature retrieval was conducted in Medline, Embase and Cochrane Controlled Trials Register (1995–April 2007) databases The outcome measure was the appearance of conjunctival hyperaemia during the study. Statistical analyses included the calculation of odds ratio (OR) and its respective confidence interval, along with intertrial statistical heterogeneity. Publication bias was evaluated through a funnel plot, and a sensitivity analysis was also performed.
Results:
In total, 13 RCTs involving 2222 patients with ocular hypertension or glaucoma were included, five comparing latanoprost versus travoprost, seven comparing latanoprost versus bimatoprost and one comparing latanoprost versus travoprost and bimatoprost. The combined results showed that latanoprost produced lower occurrence of conjunctival hyperaemia than both travoprost (OR = 0.51; 95% CI 0.39 to 0.67, p<0.0001) and bimatoprost (OR = 0.32; 95% CI 0.24 to 0.42, p<0.0001). No significant heterogeneity was found between the included RCTs. There was no evidence of publication bias. In the sensitivity analysis performed, none of the clinical trials included in this meta-analysis has an important impact in the global estimation of OR.
Conclusions:
According to available data, the use of latanoprost is associated with a lower incidence of conjunctival hyperaemia when compared with travoprost and bimatoprost in the treatment of patients with ocular hypertension or glaucoma.
doi:10.1136/bjo.2007.135111
PMCID: PMC2639645  PMID: 19019922
22.  Spectral domain optical coherence tomography for quantitative evaluation of drusen and associated structural changes in non-neovascular age-related macular degeneration 
Background/aims:
To demonstrate how spectral domain optical coherence tomography (SDOCT) can better evaluate drusen and associated anatomical changes in eyes with non-neovascular age-related macular degeneration (AMD) compared with time domain optical coherence tomography (TDOCT).
Methods:
Images were obtained from three eyes of three patients with AMD using an experimental SDOCT system. Both a titanium–sapphire (Ti:sapphire) laser and a superluminescent diode (SLD) were used as a broadband light source to achieve cross-sectional images of the retina. A qualitative and quantitative analysis was performed for structural changes associated with non-neovascular AMD. An automated algorithm was developed to analyse drusen area and volume from SDOCT images. TDOCT was performed using the fast macular scan (StratusOCT, Carl Zeiss Meditec, Dublin, California).
Results:
SDOCT images can demonstrate structural changes associated with non-neovascular AMD. A new SDOCT algorithm can determine drusen area, drusen volume and proportion of drusen.
Conclusions:
With new algorithms to determine drusen area and volume and its unprecedented simultaneous ultra-high speed ultra-high resolution imaging, SDOCT can improve the evaluation of structural abnormalities in non-neovascular AMD.
doi:10.1136/bjo.2008.137356
PMCID: PMC2628537  PMID: 18697811
23.  Effect of latanoprost and timolol on the histopathology of the human conjunctiva 
Aim:
To investigate the effect of timolol and latanoprost on the extracellular matrix organisation, inflammatory infiltration, and expression of matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs) in the human conjunctiva.
Methods:
Conjunctival biopsies were obtained from the inferior fornix during routine cataract surgery from 20 patients with primary open-angle glaucoma, who had received a monotherapy either with timolol or latanoprost, and from 10 non-glaucomatous patients. Specimens were investigated by light microscopy, immunohistochemistry using antibodies against MMP-1,-3, TIMP-2,-3 and CD 68 antibodies and by quantitative transmission electron microscopy.
Results:
The number of collagen fibres was significantly decreased in latanoprost-treated conjunctival specimens compared with timolol-treated eyes (p<0.01) but showed no difference to controls. Amorphous material was increased in both treated groups compared with controls (p<0.001) but was less in latanoprost-treated specimens compared with timolol-treated eyes (p<0.001). Optically clear spaces, probably containing glycosaminoglycans, were significantly reduced in both treated groups—with less of a reduction in latanoprost—compared with timolol-treated eyes (p<0.001). A marked upregulation of MMP-1 and MMP-3 and moderately increased staining for TIMP-2 and TIMP-3 was found in epithelial cells and subepithelial stromal cells of latanoprost-treated eyes. A moderate infiltration with macrophages and inflammatory cells was observed in timolol-treated eyes.
Conclusions:
Latanoprost-treated conjunctival specimens showed a decreased stromal collagen density and a less pronounced inflammatory infiltration. The upregulation of MMP-1 and MMP-3 in latanoprost-treated eyes might explain the reduced extracellular matrix accumulation in the conjunctival stroma. Therefore, latanoprost therapy might have a more favourable effect on the outcome of glaucoma filtering surgery.
doi:10.1136/bjo.2008.140186
PMCID: PMC2628534  PMID: 18971237
24.  Corticosteroids for Bacterial Corneal Ulcers 
Aims
To conduct a preliminary clinical trial assessing whether adjunctive topical corticosteroids improve outcomes in bacterial keratitis and, if no difference is found, to determine the feasibility and sample size necessary for conducting a larger trial to answer this question.
Methods
In this single center, double-masked clinical trial, 42 patients with culture-confirmed bacterial keratitis at Aravind Eye Hospital in India were randomized to receive either topical prednisolone phosphate or placebo. All patients received topical moxifloxacin. The primary outcome was best spectacle-corrected visual acuity (BSCVA) at 3 months, adjusting for enrollment BSCVA and arm. Other pre-specified outcomes included re-epithelialisation time, infiltrate/scar size, and adverse events.
Results
Compared to placebo, the steroid group re-epithelialised more slowly (hazard ratio 0.47, 95% CI 0.23 to 0.94). There was no significant difference in BSCVA or infiltrate/scar size at 3 weeks or 3 months. To have 80% power to detect a 2-line difference in acuity, 360 cases would be required.
Conclusions
Although corticosteroid treatment resulted in a statistically significant delay in re-epithelialisation, this did not translate to a significant difference in visual acuity, infiltrate/scar size, or adverse events. To assess the effect of steroids on acuity, a larger trial is warranted and feasible.
doi:10.1136/bjo.2008.147298
PMCID: PMC2632719  PMID: 18829631
bacterial keratitis; corticosteroids; clinical trial
25.  Atrophy of the lateral geniculate nucleus in human glaucoma detected by magnetic resonance imaging 
Aim:
To determine in vivo whether the lateral geniculate nucleus (LGN) undergoes atrophy in patients with glaucoma and vision loss compared with normal subjects.
Methods:
Following institutional St Michael’s Hospital Research Ethics Board approval, a prospective and masked neuroimaging study was conducted on glaucoma patients with visual-field defects affecting both eyes (n = 10) and age-matched controls (n = 8). Following informed consent, all subjects underwent 1.5-Tesla MRI. Coronal proton density magnetic resonance images of both LGNs were obtained, and LGN height measurements were measured by consensus by three neuroradiologists masked to the diagnosis. Glaucoma and control groups were compared using the t test.
Results:
Both LGNs were identified and visualised by 1.5-Tesla MRI for every subject. Compared with controls, the mean LGN heights in glaucoma were decreased in right (4.09 (0.89) mm vs 4.74 (0.54) mm, p>0.05) and left LGNs (3.98 (0.57) mm vs 4.83 (0.95) mm; p = 0.033). The combined right and left LGN height in glaucoma was significantly decreased compared with controls (8.07 (1.06) mm vs 9.56 (0.86) mm; p = 0.005).
Conclusion:
In vivo MRI evidence of LGN degeneration in human glaucoma is consistent with ex vivo primate and human neuropathological studies. LGN atrophy may be a relevant biomarker of visual system injury and/or progression in some glaucoma patients.
doi:10.1136/bjo.2008.138172
PMCID: PMC2605243  PMID: 18697810

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