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26.  1-year results of combined half-dose photodynamic therapy and ranibizumab for polypoidal choroidal vasculopathy 
BMC Ophthalmology  2015;15:66.
Background
To evaluate the efficacy and safety of half-dose photodynamic therapy (PDT combined with ranibizumab for polypoidal choroidal vasculopathy (PCV). PCV is commonly treated with a combination of anti-vascular endothelial growth factor and standard-dose photodynamic therapy (PDT). Choroidal ischemia and visual loss can be resulted from the standard-dose PDT. Half-dose PDT has proved to produce similar results and safety profile in treating central serous chorioretinopathy. Half-dose PDT may offer an alternative for PCV cases where the damage to choroidal vasculature maybe less. Here, we report the efficacy of treating PCV cases with combination of ranibizumab and half-dose PDT.
Methods
In this prospective, non-comparative, interventional case series, 19 treatment-naive eyes were treated with combined half-dose PDT and ranibizumab. All subjects were followed up for 12 months with measurement of best-corrected visual acuity (BCVA), central foveal thickness (CFT) by optical coherence tomography. Indocyanine green angiogram (ICG) was performed every 3-monthly, and subjects assessed in terms of polyp regression rates, changes in vision and central foveal thickness, need to repeat half-dose PDT. Subgroup analysis was performed based on ICG features.
Results
The mean logMAR BCVA improved from 0.64 at baseline to 0.41 at 12 months. The mean CFT improved from 459.6mum at baseline to 384.2mum at 12 months. The difference between baseline BCVA and CFT and that at 12 months were statistically significant (both P = 0.03). Polyp regression rate after one half-dose PDT was 42.1 %. This was 61.5 % in the polyp-only group, while that in the branching-vascular-network (BVN) group was 0 % (P = <0.01).
Conclusion
Half-dose PDT combined with intravitreal ranibizumab was able to induce high polyp regression rate in PCV cases that had one single polyp.
doi:10.1186/s12886-015-0061-8
PMCID: PMC4485362  PMID: 26122636
Age related macular degeneration; Half-dose; Half-fluence; Photodynamic therapy; Polypoidal choroidal vasculopathy; Ranibizumab; Verteporfin
27.  Visual signs and symptoms in patients with the visual variant of Alzheimer disease 
BMC Ophthalmology  2015;15:65.
Background
Prominent visual symptoms can present in the visual variant of Alzheimer’s disease (VVAD). Ophthalmologists have a significant role to play in the early diagnosis of VVAD.
Methods
We retrospectively reviewed the files of ten consecutive patients diagnosed with VVAD. All patients had a full neuro-ophthalmologic examination, a formal neurological and neuro-psychological testing, and cerebral MRI to confirm diagnosis. In addition, functional neuroimaging was obtained in seven patients.
Results
The common primary symptom at presentation with all patients was difficulty with near vision (reading difficulty n = 8, “visual blur” in near vision n = 2), and difficulty writing (n = 3). Following assessment, impaired reading and writing skills were evident in 9/10 and 8/10 patients respectively. Median distance visual acuity was 20/25 and at near the median visual acuity was J6. Partial homonymous visual field defect was detected in 80 % (8/10) of the patients. Color vision was impaired in all patients when tested with Ishihara pseudoisochromatic plates, but simple color naming was normal in 8/9 tested patients. Simultanagnosia was present in 8/10 patients. Vision dysfunction corresponded with cerebral MRI findings where parieto-occipital cortical atrophy was observed in all patients. PET scan (5 patients) or SPECT (2 patients) revealed parieto-occipital dysfunction (hypometabolism or hypoperfusion) in all 7 tested patients
Conclusions
Visual difficulties are prominent in VVAD. Dyslexia, incomplete homonymous hemianopia, preserved color identification with abnormal color vision on Ishihara, and simultanagnosia were all symptoms observed frequently in this patient series. Ophthalmologists should be aware of the possibility of neurodegenerative disorders such as VVAD in patients with unexplained visual complaints, in particular reading difficulties.
doi:10.1186/s12886-015-0060-9
PMCID: PMC4485862  PMID: 26122482
Alzheimer; Reading difficulty; Homonymous hemianopsia; Simultanagnosia
28.  Factors affecting cataract surgical coverage and outcomes: a retrospective cross-sectional study of eye health systems in sub-Saharan Africa 
BMC Ophthalmology  2015;15:67.
Background
Recently there has been a great deal of new population based evidence on visual impairment generated in sub-Saharan Africa (SSA), thanks to the Rapid Assessment of Avoidable Blindness (RAAB) survey methodology. The survey provides information on the magnitude and causes of visual impairment for planning services and measuring their impact on eye health in administrative “districts” of 0.5–5 million people. The survey results describing the quantity and quality of cataract surgeries vary widely between study sites, often with no obvious explanation. The purpose of this study was to examine health system characteristics that may be associated with cataract surgical coverage and outcomes in SSA in order to better understand the determinants of reducing the burden of avoidable blindness due to cataract.
Methods
This was a descriptive study using secondary and primary data. The outcome variables were collected from existing surveys. Data on potential district level predictor variables were collected through a semi-structured tool using routine data and key informants where appropriate. Once collected the data were coded and analysed using statistical methods including t-tests, ANOVA and the Kruskal-Wallis analysis of variance test.
Results
Higher cataract surgical coverage was positively associated with having at least one fixed surgical facility in the area; availability of a dedicated operating theatre; the number of surgeons per million population; and having an eye department manager in the facility. Variables that were associated with better outcomes included having biometry and having an eye department manager in the facility.
Conclusions
There are a number of health system factors at the district level that seem to be associated with both cataract surgical coverage and post-operative visual acuity outcomes. This study highlights the needs for better indicators and tools by which to measure and monitor the performance of eye health systems at the district level. It is unlikely that epidemiological data alone is sufficient for planning eye health services within a district and health managers and study coordinators need to consider collecting supplementary information in order to ensure appropriate planning can take place.
doi:10.1186/s12886-015-0063-6
PMCID: PMC4485868  PMID: 26122748
Blindness; Cataract; Health systems
29.  Protective effect of 14-3-3 antibodies on stressed neuroretinal cells via the mitochondrial apoptosis pathway 
BMC Ophthalmology  2015;15:64.
Background
Previous studies demonstrate changes of autoantibody concentrations against retinal and optic nerve head antigens in the serum of glaucoma patients in comparison to healthy persons. These antibodies belong to the natural autoimmunity. Previous studies showed up regulated, but also significantly down-regulated autoantibody levels. These antibodies have the ability to influence protein profiles of neuroretinal cells and possibly hold neuroprotective potential, as we have been able to demonstrate before. Aim of this study was to analyse the serum and antibody effect of glaucoma patients on neuroretinal cells in more detail and also determine the impact of antibodies found down-regulated in glaucoma patients on the pathogenesis of the neurodegenerative disease glaucoma.
Methods
Neuroretinal cells (RGC-5) were incubated with serum either from glaucoma patients or healthy controls for 24 h. Mass spectrometric analysis was performed after cell lysis. Furthermore the neuroretinal cells were preincubated with different and concentrations of 14-3-3 antibodies (0.005, 0.1, 0.5, 1, 5 and 10 μg/ml) and then stressed with H2O2, staurosporine or glutamate. Viability tests were performed with crystal violet and ROS tests with DCFH-DA. Antibody location in the cell after antibody incubation was performed with immunoccytochemical methods. Additionally mass spectrometric analysis was performed with the cells after antibody incubation.
Results
Protein expression analysis with Maldi-Orbitrap MS showed changes in the expression level of regulatory proteins in cells incubated with glaucoma serum, e.g. an up-regulation of 14-3-3 and a down-regulation of Calmodulin. After preincubation of the cells with anti-14-3-3 antibody and stressing the cells, we detected an increase in viability of up to 22 % and a decrease in reactive oxygen species (ROS) of up to 31 %. Proteomic 1 analysis involvement of the mitochondrial apoptosis pathway in this protective effect and immunohistochemical analysis showed an antibody uptake in the cells.
Conclusion
We found significant effects of serum antibodies on proteins of neuroretinal cells especially of the mitochondrial apoptosis pathway. Furthermore we detected a protective potential of antibodies down-regulated in glaucoma patients. The changed autoantibodies belong to the natural autoimmunity. We conclude that changes in the natural autoimmunity of patients with glaucoma can negatively impact regulatory functions.
Electronic supplementary material
The online version of this article (doi:10.1186/s12886-015-0044-9) contains supplementary material, which is available to authorized users.
doi:10.1186/s12886-015-0044-9
PMCID: PMC4482181  PMID: 26115916
Autoantibodies; Glaucoma; Neurodegeneration; Natural autoimmunity; Neuroprotection
30.  Intraocular lens dislocation and tube shunt in the posterior chamber: a case report 
BMC Ophthalmology  2015;15:63.
Background
To describe management of a case of intraocular lens (IOL) and capsular bag (CB) dislocation in an eye with an Ahmed glaucoma valve in the posterior chamber.
Case presentation
A 75-year-old pseudophakic man with open-angle glaucoma and diabetic retinopathy developed neovascular glaucoma. After two intravitreous injections of bevacizumab and panretinal photocoagulation were administered, the new vessels regressed. However, goniosynechiae were observed over 360° of the angle. An Ahmed glaucoma valve model FP7 was implanted with the tube in the posterior chamber with adequate intraocular pressure control. Nineteen years after cataract surgery, when the IOL-CB complex became dislocated, they were sutured transclerally to the sulcus without Ahmed glaucoma valve modification. After a coughing episode, the vitreous pushed the IOL-CB complex forward and the tube was behind the IOL-CB complex. A 25-gauge posterior vitrectomy was performed, and the tube was returned to in front of the optic of the IOL using a forceps tip through a sclerotomy.
Conclusion
This case suggested that management of IOL-CB dislocation can modify glaucoma shunt function. A complete pars plana vitrectomy may be required in order to reposition the dislocated IOL-CB complex in the presence of a posterior chamber drainage tube implant.
doi:10.1186/s12886-015-0046-7
PMCID: PMC4475289  PMID: 26094031
Neovascular glaucoma; Ahmed glaucoma valve; Intraocular lens dislocation; Posterior vitrectomy
31.  Vitrectomy with internal limiting membrane peeling vs no peeling for Macular Hole-induced Retinal Detachment (MHRD): a meta-analysis 
BMC Ophthalmology  2015;15:62.
Background
we conducted our meta-analysis of published studies to assess existing evidence about the efficacy and safety of vitrectomy with ILM peeling vs. that of vitrectomy with no ILM peeling for Macular hole-induced retinal detachment.
Methods
Databases, including Pubmed, Cochrane Library, Ovid, Web of Science, Wanfang and CNKI, were searched to identify studies comparing outcomes following vitrectomy with ILM peeling and that with no ILM peeling for macular hole-induced retinal detachment. The meta-analysis was performed by RevMan 5.1.
Results
Six comparative studies comprising 180 eyes were identified. It was indicated that the rate of retinal reattachment (Odds ratio (OR) = 3.03, 95 % Confidence interval (CI):1.35 to 6.78; P = 0.007) and macular hole closure (OR = 6.74, 95 % CI:3.26 to 13.93; P < 0.001) after initial surgery was higher and the rate of recurrent retinal detachment (OR = 0.08, 95 % CI:0.02 to 0.30; P = 0.0002) was lower in the group of vitrectomy with ILM peeling than that in the group of vitrectomy with no ILM peeling. However, the improved BCVA (Weighted mean difference (WMD) = 0.14, 95 % CI: −0.20 to 0.47; P = 0.42) and the rate of postoperative complications were similar between the two groups.
Conclusion
Vitrectomy with internal limiting membrane peeling is an efficient and safe procedure for macular hole-induced retinal detachment.
doi:10.1186/s12886-015-0048-5
PMCID: PMC4475314  PMID: 26091910
Macular hole-induced retinal detachment; Vitrectomy; Internal limiting membrane peeling; Meta-analysis
32.  Association of TCF4 polymorphisms and fuchs’ endothelial dystrophy: a meta-analysis 
BMC Ophthalmology  2015;15:61.
Background
Studies investigating the associations between transcription factor 4 (TCF4) genetic polymorphisms and Fuchs’ endothelial dystrophy (FED) have reported controversial results. Therefore, this meta-analysis aims to clarify the effects of TCF4 polymorphisms on FED risk.
Methods
A meta-analysis was conducted to assess the association between four single nucleotide polymorphisms (SNPs) inTCF4 and the risk of FED. Relevant studies were selected through an extensive search of PubMed, EMBASE, and the Web of Science databases. Pooled odds ratio (OR) and 95 % confidence interval (CI) were calculated using the random-effects model.
Results
Thirteen studies were included in this systematic review and meta-analysis. The pooled results showed that there was a strong positive association between the TCF4 rs613872 polymorphism and FED risk in all the genetic models tested (G allele vs. T allele: OR = 4.19, 95 % CI = 3.53–4.97; GG vs. GT/TT: OR = 4.27, 95 % CI = 2.54–7.19; GG/GT vs. TT: OR = 6.29, 95 % CI = 4.23–8.93; GG VS. TT: OR = 10.64, 95 % CI = 5.28–21.41; GT VS. TT: OR = 6.08, 95 % CI = 4.28–8.64). Statistic evidence was also detected for a significant association between three other SNPs and the risk of FED.
Conclusions
This meta-analysis suggested a genetic association between four TCF4 polymorphisms (rs613872, rs2286812, rs17595731, and rs9954153) and the risk of FED.
doi:10.1186/s12886-015-0055-6
PMCID: PMC4474332  PMID: 26087656
33.  Spontaneous hyphaema secondary to bleeding from an iris vascular tuft in a patient with a supratherapeutic International normalised ratio: case report 
BMC Ophthalmology  2015;15:60.
Background
Iris vascular tufts are rare iris stromal vascular hamartomas. Patients with iris vascular tufts generally remain asymptomatic until presenting with a spontaneous hyphaema or with mild intraoperative pupil margin haemorrhage during anterior segment surgery. This is the first reported case of spontaneous hyphaema from iris vascular tuft related to a documented supratherapeutic International Normalised Ratio as a predisposing factor. At 86 years of age, this patient also represents the oldest documented first occurrence of bleeding from an iris vascular tuft.
Case presentation
An 86 year old Caucasian lady presented with sudden and persisting loss of vision in her right eye, ocular pain and vomiting. She had a supratherapeutic International Normalised Ratio of 3.9 related to Warfarin use. Her intraocular pressure in the right eye was raised at 55 mmHg, with a 1.6 mm hyphaema and multiple iris vascular tufts visible around the entire pupil.
Conclusion
The present case highlights the risk of anticoagulation therapy as a predisposing factor for spontaneous hyphaema and adds to the management considerations for this condition. It also demonstrates the need for Ophthalmologists to be aware of iris vascular tufts as a cause for spontaneous hyphaema, independent of age and systemic associations.
doi:10.1186/s12886-015-0050-y
PMCID: PMC4465471  PMID: 26071139
Iris vascular tuft; hyphaema; supratherapeutic INR; anticoagulation
34.  One-year outcomes of small-incision lenticule extraction (SMILE): mild to moderate myopia vs. high myopia 
BMC Ophthalmology  2015;15:59.
Background
The purpose of this study was to compare the refractive outcomes of small incision lenticule extraction (SMILE) in high-myopic patients with those of mild- to moderate-myopic patients.
Methods
This study included 183 eyes of 92 myopic patients treated with SMILE using a VisuMax 500-kHz femtosecond laser. Treated eyes were divided into two groups, according to the preoperative spherical equivalent (SE): mild to moderate myopia (A group, <−6.0 D) and high myopia (B group, ≥ − 6.0 D). Follow-up visits were at 1 day, 1 week, and 1, 3, 6, and 12 months. The outcome measures included uncorrected distance visual acuity (UDVA), best-corrected distance visual acuity (BDVA), postoperative SE, efficacy index, safety index, and predictability.
Results
Preoperative SE was −5.05 ± 0.71 D in the A group and −7.67 ± 1.01 D in the B group. No differences were observed between −0.13 ± 0.38 D in the A group and −0.24 ± 0.35 D in the B group 12 months postoperatively (p = 0.18). At 12 months postoperatively, 93.1 % and 76.8 % had an UDVA of 20/20 or better in the A and B groups, respectively. In the A group, 87.9 % and 96.6 % were within ±0.5 D and ±1.0 D, respectively, of the intended correction; in the B group, 88.0 % and 97.6 % were within ±0.5 D and ±1.0 D, respectively. The efficacy index was 1.04 ± 0.19 in the A group and 0.99 ± 0.19 in the B group. The safety index was 1.27 ± 0.17 for the A group and 1.24 ± 0.17 for the B group. The efficacy and safety index were not significantly different between the two groups 12 months postoperatively (p = 0.141 and p = 0.307, respectively).
Conclusions
This study showed that SMILE is effective and safe for correcting high myopia, as well as mild to moderate myopia.
doi:10.1186/s12886-015-0051-x
PMCID: PMC4462177  PMID: 26059895
Small incision lenticule extraction; One year; long term
35.  Systemic adalimumab induces peripheral corneal infiltrates: a case report 
BMC Ophthalmology  2015;15:57.
Background
Tumor necrosis factor-alpha inhibitors are widely used agents in the treatment of immune disorders such as rheumatoid arthritis and inflammatory bowel disease. Despite their anti-inflammatory action, paradoxical drug-induced inflammatory events have been occasionally associated with the use of infliximab, etanercept, and in a lesser extent adalimumab. However, eye involvement is uncommon and anterior uveitis is the only reported ocular adverse manifestation. It can be induced by etanercept, but has also been described during adalimumab therapy. We present here the first report of recurrent peripheral corneal infiltrates following subcutaneous injections of adalimumab.
Case presentation
A 34 year-old Caucasian woman with Crohn’s disease presented to the emergency department with bilateral red eyes and discomfort 36 hours after she received her bimonthly dose of subcutaneous adalimumab. Examination revealed bilateral peripheral corneal infiltrates with characteristic features of immune infiltrates. Symptoms and infiltrates regressed after topical corticosteroid therapy, but recurred after each adalimumab injection over the following weeks.
Conclusion
Paradoxical immune reactions associated with tumor necrosis factor-alpha inhibitors may result either from hypersensitivity mechanisms, or from immune-complex deposition via anti-adalimumab antibodies. Both mechanisms could explain this newly described manifestation. Care should be taken to search for corneal infiltrates in the event of red eye symptoms during adalimumab therapy since they respond to topical corticosteroids and do not necessarily prompt the discontinuation of the immunosuppressive therapy.
Electronic supplementary material
The online version of this article (doi:10.1186/s12886-015-0047-6) contains supplementary material, which is available to authorized users.
doi:10.1186/s12886-015-0047-6
PMCID: PMC4456692  PMID: 26044064
Cornea; Adalimumab; Tumor necrosis factor-alpha inhibitor; Adverse effects; Peripheral infiltrate; Crohn's disease
36.  Effectiveness and relevant factors of 2 % rebamipide ophthalmic suspension treatment in dry eye 
BMC Ophthalmology  2015;15:58.
Background
Rebamipide with mucin secretagogue activity was recently approved for the treatment of dry eye. The efficacy and safety in the treatment of rebamipide were shown in two pivotal clinical trials. It was the aim of this study to evaluate the effect of 2 % rebamipide ophthalmic suspension in patients with dry eye and analyze relevant factors for favorable effects of rebamipide in clinical practice.
Methods
This was a retrospective cohort study of 48 eyes from 24 patients with dry eye treated with 2 % rebamipide ophthalmic suspension. Dry eye-related symptom score, tear film break-up time (TBUT), fluorescein ocular surface staining score (FOS) and the Schirmer test were used to collect the data from patients at baseline, and at 2, 4, 8, and 12 week visits. To determine the relevant factors, multiple regression analyses were then performed.
Results
Mean dry eye-related symptom score showed a significant improvement from the baseline (14.5 points) at 2, 4, 8 and 12 weeks (9.80, 7.04, 7.04 and 7.83 points, corrected P value <0.001, respectively). Median FOS showed a significant improvement from the baseline (3.0 points) at 2, 4, 8 and 12 weeks (2.0, 2.0, 1.0 and 1.0 points, corrected P value <0.001, respectively). TBUT and Schirmer test values were not significantly improved after the treatment. For ocular symptoms, three parameters (foreign body sensation, dry eye sensation and ocular discomfort) showed significant improvements at all visits. The multiple regression analyses showed that the fluorescein conjunctiva staining score was significantly correlated with the changes of dry eye-related symptom score at 12 weeks (P value = 0.017) and dry eye-related symptom score was significantly correlated with independent variables for the changes of FOS at 12 weeks (P value = 0.0097).
Conclusions
Two percent rebamipide ophthalmic suspension was an effective therapy for dry eye patients. Moreover the fluorescein conjunctiva staining score and dry eye-related symptom score might be good relevant factors for favorable effects of rebamipide.
Electronic supplementary material
The online version of this article (doi:10.1186/s12886-015-0040-0) contains supplementary material, which is available to authorized users.
doi:10.1186/s12886-015-0040-0
PMCID: PMC4456696  PMID: 26048396
Dry eye; Rebamipide; Relevant factor; Dry eye-related symptom; Fluorescein ocular surface staining score
37.  The role of Syk signaling in antifungal innate immunity of human corneal epithelial cells 
BMC Ophthalmology  2015;15:55.
Background
Fungal keratitis is a kind of intractable and sight-threatening diseases. Spleen-tyrosine kinase (Syk) is a non-receptor tyrosine kinase, which plays an important role in the signaling pathway of the receptors. In the current study, we investigate the expression and function of Syk in human corneal epithelial cells with Aspergillus fumigatus (A. fumigatus) infection.
Methods
Cultured telomerase-immortalized human corneal epithelial cells (THCEs) were treated with A. fumigatus hyphae with or without treatment of Syk inhibitors. Activation of Syk and the role of Syk in regulating inflammatory cytokines and chemokines expression were evaluated. The mRNA expression was determined by real time PCR, and protein activation was measured by western blotting.
Results
Syk protein was detected in THCEs, and its activation was enhanced after treatment of A. fumigatus hyphae. Expression of inflammatory cytokines (IL-1β and IL-6) and chemokines (IL-8 and CXCL1) mRNA were significantly increased after stimulation of A. fumigatus hyphae in THCEs. Activation of Syk and expression of IL-1β, IL-6, IL-8 and CXCL1 by A. fumigatus hyphae were blocked by Syk inhibitors.
Conclusion
These findings demonstrate that normal human corneal epithelial cells produce Syk, and Syk activation plays an important role in regulating A. fumigatus hyphae-induced inflammatory responses in THCEs.
doi:10.1186/s12886-015-0041-z
PMCID: PMC4451931  PMID: 26036769
Syk signaling; Fungal infection; Innate immunity; Human corneal epithelial cells
38.  Mydriasert pupillary dilation for cataract surgery: an economic and clinical study 
BMC Ophthalmology  2015;15:56.
Background
Mydriasert is an insoluble ophthalmic insert indicated for mydriasis prior to cataract surgery, which gradually releases the active ingredients: tropicamide (0.25 mg) and phenylephrine (5.38 mg). This study aimed to evaluate the cost of Mydriasert compared with conventional mydriatic eye drops to induce pupil dilation prior to cataract surgery using a budget impact model.
Methods
A cohort-based, decision tree, budget impact model was developed to estimate the drug, consumable and staff costs for achieving mydriasis with Mydriasert compared to mydriatic eye drops (tropicamide [1 %] plus phenylephrine [10 %]). Insights from structured interviews with clinicians (n = 5) experienced in using both Mydriasert and mydriatic eye drops and results from the current clinical study of patients undergoing cataract surgery (n = 144) at a Greater London district general hospital were used to obtain key input parameters for the model, and to validate the model approach.
Results
The base case analysis in a cohort of 1763 patients undergoing cataract surgery showed that when Mydriasert substituted mydriatic eye drops, annual total costs decreased by 18 % and annual total nurse time decreased from 235.1 hours to 44.1 hours over one year (2012–2013).
Conclusions
This study demonstrated that despite its higher unit cost than mydriatic eye drops, Mydriasert resulted in overall savings in health-care costs, mainly associated with reduced nursing time. The economic model developed could assist National Health Service managers and local payers to estimate the budget impact of the introduction of Mydriasert into different clinical settings.
doi:10.1186/s12886-015-0042-y
PMCID: PMC4454272  PMID: 26036871
Mydriasert; Mydriasis; Mydriatics; Mydriatic eye drops; Cataract surgery; Economic model
39.  Brimonidine reduces TGF-beta-induced extracellular matrix synthesis in human Tenon’s fibroblasts 
BMC Ophthalmology  2015;15:54.
Background
Brimonidine is a highly selective α2 adrenergic agonist that has been widely used in anti-glaucoma eyedrops. The aim of this study was to investigate its putative anti-fibrotic role in the fibrosis caused by activated Tenon’s fibroblasts.
Methods
Primary cultured human Tenon’s fibroblasts were exposed to 2.0 ng/mL of transforming growth factor-β1 (TGF-β1) for up to 48 h. In the presence of various concentrations of brimonidine (from 0.0 to 10.0 μM), the expression levels of fibronectin, collagen types I and III, and β-actin were determined by Western immunoblots. The expression of phosphorylated SMAD2/3 (p-SMAD2/3) was then evaluated using immunofluorescence.
Results
TGF-β1 significantly increased the synthesis of fibronectin and collagens in human Tenon’s fibroblasts; however brimonidine treatment distinctly attenuated the TGF-β1-induced production of extracellular matrix (ECM) proteins. TGF-β1 also changed the cellular morphology to be plump, while brimonidine treatment returned the cells to a spindle shape, similar to control fibroblasts. Regarding p-SMAD2/3, brimonidine treatment did not show any apparent changes in its expression.
Conclusions
Our data revealed that brimonidine reduces TGF-β-induced ECM synthesis in human Tenon’s fibroblasts in vitro. This finding implies that topical administration of brimonidine may be helpful in reducing the fibrosis caused by the long-term use of topical anti-glaucoma medications.
Electronic supplementary material
The online version of this article (doi:10.1186/s12886-015-0045-8) contains supplementary material, which is available to authorized users.
doi:10.1186/s12886-015-0045-8
PMCID: PMC4454273  PMID: 26017119
Fibroblast; Fibrosis; Brimonidine; Transforming growth factor-β; Glaucoma
40.  Lymphoma of the orbit masquerading as Tolosa-Hunt syndrome 
BMC Ophthalmology  2015;15:51.
Background
Tolosa-Hunt syndrome is a rare clinical syndrome characterized by painful ophthalmoplegia and ipsilateral cranial neuropathies. It is caused by an inflammatory process of unknown etiology.
Case presentation
We present a case of a 77-year-old white man with history of Waldenstrom’s macroglobulinemia transforming to large B-cell lymphoma who presented to a community physician complaining of 4 months of isolated right retro-orbital pain and later with diplopia, ptosis, 6th nerve and pupil-sparing partial 3rd nerve palsies as well as progressive neurological findings. His clinical course was complicated by debilitating neurological symptoms and multiple hospitalizations leading to a delay in diagnosis caused by incomplete initial workup.
Conclusion
This case is a reminder that lymphoproliferative disorders often mimic other neurologic disorders and that Tolosa-Hunt is a rare diagnosis that must be considered a diagnosis of exclusion.
doi:10.1186/s12886-015-0037-8
PMCID: PMC4450859  PMID: 25971316
Lymphoma; Tolosa-Hunt; Neuro-imaging; Cavernous sinus; MRI
41.  Intra-observer and inter-observer repeatability of ocular surface interferometer in measuring lipid layer thickness 
BMC Ophthalmology  2015;15:53.
Background
Tear lipid morphology is important for normal tear function. Recently, there have been clinical studies using interferometry to assess lipid layer thickness (LLT). The aim of the study is to examine the repeatability of a commercially available interferometer.
Methods
Two observers measured LLT in twenty Asian subjects (20 eyes) using an interferometer (LipiView® ocular surface interferometer, TearScience Inc, Morrisville, NC). Dry eye symptoms, tear break up time (TBUT) and corneal fluorescein staining were also prospectively evaluated.
Results
Data for 20 participants are presented for either right or left eye (randomly selected). The mean LLT ± standard deviation of these participants was 53.53 ± 14.59 nm. When a single observer repeated the imaging on the same day, the coefficient of repeatability was 16 nm and the 95 % limits of agreement were between −11 nm and 18 nm. When a different observer repeated the scan, the coefficient of repeatability was 13 nm and limits of agreement were −9 nm and 16 nm. LLT was not significantly associated with TBUT, presence of any corneal staining in any corneal zones, or symptomatic status.
Conclusion
With the repeatability of measurements being known, the significance of LLT changes measured by this interferometer may be better interpreted. In this small Asian study, the LLT was lower than previously reported studies.
doi:10.1186/s12886-015-0036-9
PMCID: PMC4462010  PMID: 25975974
Imaging; Human; Clinical study; Cornea; Lipid; Tear
42.  Systematic review and mixed treatment comparison of intravitreal aflibercept with other therapies for diabetic macular edema (DME) 
BMC Ophthalmology  2015;15:52.
Background
This was an indirect comparison of the effectiveness of intravitreal aflibercept (IVT-AFL) 2 mg every 8 weeks after 5 initial monthly doses (or if different periods, after an initial monthly dosing period) (2q8) and other diabetic macular edema (DME) therapies at doses licensed outside the USA.
Methods
A comprehensive search was undertaken to source relevant studies. Feasibility networks were prepared to identify viable comparisons of 12-month outcomes between IVT-AFL 2q8 and therapies licensed outside the USA, which were assessed for clinical and statistical homogeneity. Pooled effect sizes (mean difference [MD] and relative risk/risk ratio [RR]) were calculated using fixed- and random-effects models. Indirect comparisons were performed using Bucher analysis. If at least one ‘head-to-head’ study was found then a mixed treatment comparison (MTC) was performed using Bayesian methods. Two 12-month comparisons could be undertaken based on indirect analyses: IVT-AFL 2q8 versus intravitreal ranibizumab (IVR) 0.5 mg as needed (PRN) (10 studies) and IVT-AFL 2q8 versus dexamethasone 0.7 mg implants (three studies).
Results
There was an increase in mean best-corrected visual acuity (BCVA) with IVT-AFL 2q8 over IVR 0.5 mg PRN by 4.67 letters [95% credible interval (CrI): 2.45–6.87] in the fixed-effect MTC model (10 studies) and by 4.82 letters [95% confidence interval (CI): 2.52–7.11] in the Bucher indirect analysis (four studies). IVT-AFL 2q8 doubled the proportion of patients gaining ≥ 10 Early Treatment Diabetic Retinopathy Study letters at 12 months compared with dexamethasone 0.7 mg implants (RR = 2.10 [95% CI: 1.29–3.40]) in the fixed-effect model. There were no significant differences in safety outcomes between IVT-AFL 2q8 and IVR 0.5 mg PRN or dexamethasone 0.7 mg implants.
Conclusions
Studies of IVT-AFL 2q8 showed improved 12-month visual acuity measures compared with studies of IVR 0.5 mg PRN and dexamethasone 0.7 mg implants based on indirect comparisons. These analyses are subject to a number of limitations which are inherent in indirect data comparisons.
Electronic supplementary material
The online version of this article (doi:10.1186/s12886-015-0035-x) contains supplementary material, which is available to authorized users.
doi:10.1186/s12886-015-0035-x
PMCID: PMC4467379  PMID: 25975823
Intravitreal aflibercept; Diabetic macular edema (DME); Intravitreal ranibizumab; Meta-analysis; Systematic review
43.  Protective effect of high concentration of BN52021 on retinal contusion in cat eyes 
BMC Ophthalmology  2015;15:50.
Background
Blunt injuries/contusion on eyes might cause retina blunt trauma. This study is to evaluate the protective function of BN52021 against retinal trauma.
Methods
A total of 70 cats, 6 months old, were divided into six groups: Group A to E (n = 12) and normal control (N) group (n = 10). The right eyes in Group A to E were contused. All experiments were performed under general anesthetization. Retrobulbar injections of medication in right eyes were performed. Cats were administrated with 0.5 mL of normal saline (NS), dimethyl sulphoxide, 0.2 g/L BN52021, 1 g/L BN52021 and 5 g/L BN52021, respectively. Cats in Group N were administrated with 0.5 mL of NS. Intraocular pressure (IOP), flash electroretinogram (ERG), and retinal nerve fiber layer (RNFL) thickness were measured. Hematoxylin and eosin (HE) staining and transmission electron microscope (TEM) were detected.
Results
No significant difference was observed in IOP levels among groups. Comparing with cats in Group N, those in Group A to E showed significant lower amplitudes of rod a- and b-waves (P < 0.05). Amplitudes of rod a- and b-waves were increased by administration of high concentration of BN52021 (≥1 g/L). Moreover, high concentration of BN52021 decreased the RNFL thickness increased by contusion. Axons in RNFL in Group E arranged neatly at 7 days after modeling.
Conclusions
The degenerated axons caused by contusion were repaired by BN52021. The administration of high concentration of (≥1 g/L) BN52021 could partially repair retinal function in contused cat eyes.
doi:10.1186/s12886-015-0030-2
PMCID: PMC4440277  PMID: 25956877
Retina trauma; BN52021; Electroretinogram; Intraocular pressure; Retinal nerve fiber layer
44.  Corneal thickness, epithelial thickness and axial length differences in normal and high myopia 
BMC Ophthalmology  2015;15:49.
Background
Corneal biometric parameters can possibly be influenced by high myopia (HM). The influence of HM on corneal thickness (CT), epithelial thickness (ET) has not yet been clearly established. The aim of this study is to observe ET, CT and axial length (AL) differences between in normal and subjects with HMs and to investigate factors influencing the corneal biometric parameters and AL, such as age and gender.
Methods
A total of 97 normal subjects (97 eyes) and 48 HM subjects (48 eyes) were included. The ET and CT of the central 6-mm diameter (17 regions) and the AL data were captured. The 17 corneal and epithelial regions were the center (1 mm radius, area a), the inner ring (2.5 mm radius, area b), the outer ring (3 mm radius, area c) and the 8 radial scan lines in eight directions (Superior (1) , SN (2), Nasal (3), IN (4), Inferior (5), IT (6), Temporal (7), ST (8)) with an angle of 45° between each consecutive scan line (a, b 1–8, c 1–8).
Results
The ALs were increased about 4 mm in the HMs (P < 0.001). No differences in ET were observed; in contrast, significantly thicker CTs were observed in the HMs in 16 regions except the b5 subregion. In normal group, age was negatively correlated with AL but not CCT and CET and gender was correlated with CET. In HM group, age was not correlated with CCT , AL or CET and gender was correlated with AL and CCT but not CET.
Conclusions
CT was thicker in the HMs but not ET. Age and gender should be considered for AL, CT and ET in both normal and HM group.
doi:10.1186/s12886-015-0039-6
PMCID: PMC4433086  PMID: 25947156
Axial length; Corneal thickness; Epithelial thickness; High myopia; Optical coherence tomography
45.  Intraorbital haematoma during a commercial flight: a case report 
BMC Ophthalmology  2015;15:47.
Background
Intraorbital haematoma is a rare clinical entity which can be caused by orbital traumas, neoplasms, surgeries nearby sinuses and orbit, vascular malformations, acute sinusitis, systemic abnormalities, barotrauma and valsalva maneuver.
Case Presentation
A 74-year-old male presented with sudden onset of ocular pain, upper eye lid swelling, proptosis and diplopia after a commercial flight. After complete ophthalmic ocular examination including pupillary light reflexes and laboratory examinations; computed tomography and magnetic resonance imaging of orbit revealed a subperiostal mass-like lesion in the right retrobulbar-extraconal region which was compatible with intraorbital haematoma. Visual acuity was not compromised so we planned a conservative approach with close observation. We administered systemic corticosteroid and topical dorzolamide/timolol combination therapy. At the first month follow-up, intraorbital haematoma resolved without significant sequelae.
Conclusion
Intraorbital haematoma can be managed by conservative approach without any intervention if it does not threat visual acuity or optic nerve. We experienced a case of intraorbital haematoma during a commercial flight. We discussed the rarity of this condition and its management.
doi:10.1186/s12886-015-0034-y
PMCID: PMC4438462  PMID: 25946992
Intraorbital haematoma; Commercial flight; Subperiostal haematoma
46.  Primary extranodal marginal zone B-cell lymphoma with diffuse uveal involvement and focal infiltration of the trabecular meshwork: a case report and review of literature 
BMC Ophthalmology  2015;15:48.
Background
Primary extranodal marginal zone lymphoma (EMZL) of the uvea is a rare condition and diagnosis may be challenging. We aim to report the clinical, histopathologic and immunohistochemical findings in a case of primary EMZL with diffuse uveal involvement and focal infiltration of the trabecular meshwork.
Case presentation
A 38-year-old male presented with 2-year progressive vision loss in the right eye. Fundus examination showed choroidal thickening with diffuse retinal pigment epithelium (RPE) changes and inferior exudative retinal detachment. Ultrasonography revealed low-reflective masses with diffuse thickening of the choroid involving the optic nerve and orbit. Despite treatment with steroids, his symptoms progressed over time. One year later, visual acuity of the right eye markedly decreased to no light perception and enucleation was performed. Histopathological findings revealed infiltrates of malignant cells in the choroid, iris, ciliary body and trabecular meshwork. Immunohistochemistry confirmed the diagnosis of primary uveal EMZL.
Conclusions
This is the first case reporting primary EMZL diffusely involving the uvea with focal infiltration of the trabecular meshwork.
doi:10.1186/s12886-015-0038-7
PMCID: PMC4494801  PMID: 25947067
47.  Association between retinal vein occlusion, axial length and vitreous chamber depth measured by optical low coherence reflectometry 
BMC Ophthalmology  2015;15:45.
Background
Results of ocular biometric measurements in retinal vein occlusion (RVO) eyes are still inconclusive and controversial. The aim of this study was to evaluate the association between ocular axial length (AL), vitreous chamber depth (VCD) and both central (CRVO) and branch retinal vein occlusions (BRVO) using optical low coherence reflectometry (OLCR).
Methods
Both eyes of 37 patients with unilateral CRVO (mean age: 66 ± 14 years, male:female - 21:16) and 46 patients with unilateral BRVO (mean age: 63 ± 12 years, male:female - 24:22) were enrolled in this study. The control group consisted of randomly selected single eyes of 67 age and gender matched volunteers without the presence or history of RVO (mean age: 64 ± 14 years, male:female - 34:33). Optical biometry was performed by OLCR biometer (LenStar LS 900). Average keratometry readings, central corneal thickness (CCT), anterior chamber depth (ACD), lens thickness (LT), AL and VCD of eyes with RVO were compared with those of fellow eyes using paired t-tests and with those of control eyes using independent t-tests.
Results
Mean CCT, ACD and LT, average keratometry readings of affected RVO eyes, unaffected fellow eyes and control eyes was not statistically different in either groups. In eyes with CRVO mean AL and VCD of affected eyes were significantly shorter than those of control eyes (p < 0.001, p < 0.05), mean difference in AL and VCD between the affected and control eyes was 0.56 ± 0.15 mm and 0.45 ± 0.19 mm, respectively. In eyes with BRVO, mean AL of the affected eyes was significantly shorter with a mean difference of 0.57 ± 0.15 mm (p < 0.001) and the VCD was significantly shorter with a mean difference of 0.61 ± 0.15 mm (p < 0.001) comparing with the control eyes.
Conclusion
Shorter AL and VCD might be a potential anatomical predisposing factor for development either of CRVO or BRVO.
doi:10.1186/s12886-015-0031-1
PMCID: PMC4423091  PMID: 25925557
Retinal vein occlusion; Central retinal vein occlusion; Branch retinal vein occlusion; Axial length; Vitreous chamber depth; Optical low coherence reflectometry
48.  The prevalence of and major risk factors associated with diabetic retinopathy in Gegharkunik province of Armenia: cross-sectional study 
BMC Ophthalmology  2015;15:46.
Background
Diabetic retinopathy (DR) is one of the leading causes of blindness in adults in industrialized countries and the emerging cause of blindness in developing countries. The objective of this study was to describe the prevalence of DR and risk factors associated with it among diabetic patients.
Methods
The analytical cross-sectional survey and eye screenings were carried out among 625 diabetic patients from urban and rural areas of Gegharkunik region. DR was assessed by dilated ophthalmoscopy and defined based on the WHO International Classification of Diseases. The survey instrument, included questions about demographics, disease history, health status, medication use and healthy lifestyle. Descriptive statistics and logistic regression were used to analyze the data.
Results
The prevalence of DR in the sample was 36.2%. A total of 90.2% of patients with DR had non-proliferative, while 9.8% had proliferative DR. In bivariate analysis, age, diabetes duration, being under insulin treatment, blood glucose level, having non-communicable diseases were significantly associated with DR. In the adjusted analysis being under insulin treatment (OR = 3.24; 95% CI: 1.56–6.75), diabetes duration (OR = 1.23; 95% CI: 1.16–1.31) and age (OR = 1.05; 95% CI: 1.02–1.08) were independently associated with DR.
Conclusion
Earlier diagnosis of diabetes and DR can help to control some of these factors and prevent further complications and vision loss. Population-based educational programs on diabetes and diabetic retinopathy and continuous medical education on diabetes management can improve diabetes care and self-management and prevent eye complications.
doi:10.1186/s12886-015-0032-0
PMCID: PMC4440508  PMID: 25925666
Diabetes; Diabetic retinopathy; Risk factors; Diabetes duration and Insulin treatment
49.  Intravitreal aflibercept (Eylea) injection for cystoid macular edema secondary to retinitis pigmentosa - a first case report and short review of the literature 
BMC Ophthalmology  2015;15:44.
Background
Cystoid macular edema (CME) in retinitis pigmentosa (RP) has been managed in several ways as documented in the literature, with little success, though. The aim of our study was to report for the first time in literature the use of aflibercept in a patient with RP and CME.
Case presentation
A 52-year-old man presented for blurred vision in his right eye. Best-corrected visual acuity (BCVA) was 3/10 in his right eye and 7/10 in his left eye. Physical examination and appropriate laboratory tests lead to the diagnosis of bilateral RP with CME in the right eye. Retinal thickness in the foveal area of the right eye was 631 μm. The patient was treated with a single intravitreal injection of 0.05 ml/0.5 mg aflibercept. One month later, BCVA of the right eye increased to 4/10, while BCVA of the left eye was unchanged. RT in the right eye decreased to 129 μm. Multifocal electroretinogram response did not improve, yet peaks were better-shaped and no areas of eccentral vision were present. Three and six months after injection, these improvements were maintained.
Conclusion
This first-reported case indicates that intravitreal aflibercept injection for addressing CME in RP seems to be an effective treatment.
doi:10.1186/s12886-015-0033-z
PMCID: PMC4482192  PMID: 25925748
Retinitis pigmentosa; Cystoid macular edema; Aflibercept; Eylea
50.  Disappearance of soft drusen and subsequent development of choroidal neovascularization following macular hole surgery: a case report 
BMC Ophthalmology  2015;15:43.
Background
Drusen are important risk factor for neovascular age-related macular degeneration (AMD) and have a dynamic nature as they can enlarge, newly form, or disappear over time. There have been few reports on drusen regression or choroidal neovascularization (CNV) development after macular hole surgery. We report, to our knowledge, the first case of both drusen regression and subsequent CNV development within 7 months of successful macular hole surgery.
Case presentation
A 73-year-old woman presented with a stage 3 full-thickness macular hole and large, confluent soft macular drusen in the right eye and a neovascular age-related macular degeneration (AMD) in the fellow eye. Four months after the successful macular hole surgery, significant regression of drusen was seen, especially in the temporal area to the fovea. Three months later, the patient developed CNV and her best-corrected visual acuity decreased to 20/100, despite further regression of macular drusen.
Conclusions
Macular hole patients with macular soft drusen need to be carefully followed up after surgery for possible drusen regression and CNV development.
doi:10.1186/s12886-015-0029-8
PMCID: PMC4424516  PMID: 25928705
Drusen; Choroidal neovascularization; Macular hole; Surgery

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