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1.  Combining macula clinical signs and patient characteristics for age-related macular degeneration diagnosis: a machine learning approach 
BMC Ophthalmology  2015;15:10.
To investigate machine learning methods, ranging from simpler interpretable techniques to complex (non-linear) “black-box” approaches, for automated diagnosis of Age-related Macular Degeneration (AMD).
Data from healthy subjects and patients diagnosed with AMD or other retinal diseases were collected during routine visits via an Electronic Health Record (EHR) system. Patients’ attributes included demographics and, for each eye, presence/absence of major AMD-related clinical signs (soft drusen, retinal pigment epitelium, defects/pigment mottling, depigmentation area, subretinal haemorrhage, subretinal fluid, macula thickness, macular scar, subretinal fibrosis). Interpretable techniques known as white box methods including logistic regression and decision trees as well as less interpreitable techniques known as black box methods, such as support vector machines (SVM), random forests and AdaBoost, were used to develop models (trained and validated on unseen data) to diagnose AMD. The gold standard was confirmed diagnosis of AMD by physicians. Sensitivity, specificity and area under the receiver operating characteristic (AUC) were used to assess performance.
Study population included 487 patients (912 eyes). In terms of AUC, random forests, logistic regression and adaboost showed a mean performance of (0.92), followed by SVM and decision trees (0.90). All machine learning models identified soft drusen and age as the most discriminating variables in clinicians’ decision pathways to diagnose AMD.
Both black-box and white box methods performed well in identifying diagnoses of AMD and their decision pathways. Machine learning models developed through the proposed approach, relying on clinical signs identified by retinal specialists, could be embedded into EHR to provide physicians with real time (interpretable) support.
Electronic supplementary material
The online version of this article (doi:10.1186/1471-2415-15-10) contains supplementary material, which is available to authorized users.
PMCID: PMC4417241  PMID: 25623470
Age related macular degeneration; Machine learning; Automated diagnosis; Statistical learning; macula disease
2.  Progression of lower and higher-order aberrations: a longitudinal study 
BMC Ophthalmology  2015;15:11.
The aim of the present study was to investigate the effect of near-work on lower and higher-order aberrations, and its progression over a 9-month period during the school year.
Data from 24 young-adult myopic eyes, and 24 non-myopic eyes were used in this investigation. The lower-order aberrations, coma, spherical aberration (SA), and total root mean square (RMS) of higher order aberrations (total HOA) were measured using an open-field iTrace aberrometer, at both the initial baseline evaluation, and then at the follow-up visits over a 9-month period. Pupil size of 4 mm was used for the aberration measurements.
The group mean (SD) of the subjects (mean age: 23.6 +/- 3.4 years) at the initial and follow-up visit was 0.47D (0.47D) and 0.31D (0.41D), in the non-myopes and -3.58D (2.08D) and -3.86D (2.14D) in the myopes, respectively. Significant increases in myopic refraction were observed. The group mean (SD) total HOA at the initial and final visit was 0.12 (0.08) and 0.11 (0.06) microns, in the non-myopes, and 0.15 (0.08) and 0.15 (0.08) microns, in the myopes, respectively. The group mean RMS of the coma at the initial and final visit was 0.06 (0.04) and 0.07 (0.05), in the non-myopes, and 0.08 (0.06) and 0.09 (0.06) microns, in the myopes, respectively. The group mean SA of the subjects at the initial and last visit was 0.04 (0.04) and 0.03 (0.03), in the non-myopes, and 0.04 (0.04) and 0.04 (0.04) microns, in the myopes, respectively.
There was a significant difference in myopic refraction, over the 9-month assessment period. However, no significant difference in total HOA, SA, and coma between the initial and follow-up visits in both the myopes and the non-myopes was observed.
PMCID: PMC4417337  PMID: 25618162
Spherical aberration; Coma; Higher-order aberrations; Myopia; Longitudinal study; Defocus
3.  Efficacy of selective laser trabeculoplasty for normal tension glaucoma: 1 year results 
BMC Ophthalmology  2015;15:1.
Normal tension glaucoma (NTG) is commonly treated with anti-glaucoma medications. Recently, selective laser trabeculoplasty (SLT) has been demonstrated to lower the intraocular pressure (IOP) and medication use in NTG. The purpose of this study was to investigate the efficacy of a single session of SLT for NTG at 1 year.
This prospective cohort study recruited NTG patients taking anti-glaucoma medication. Potential subjects were excluded if they had had previous glaucoma surgery or laser and also if intraocular surgery or additional SLT procedures were performed after the first treatment. All subjects underwent a 1-month washout. A 30% IOP reduction was set as the target IOP. A single session of SLT was performed to 360 degrees of the trabecular meshwork. At 1-month after SLT, medication was resumed to achieve the target IOP. The IOP was measured every 3 months, and the number of medications was recorded at 3, 6, and 12 months. Only the right eye was used for statistical analysis.
In 41 right eyes, the mean pre-study IOP was 14.3 ± 3.4 mmHg while on 1.5 ± 0.8 eye drops. The post-washout IOP was 16.2 ± 2.2 mmHg. A mean of 191.1 ± 26.3 SLT shots at 1.0 ± 0.07 mJ were applied. There was significant IOP reduction at all time intervals following SLT when compared to the post-washout IOP (P < 0.0001). The number of medications was significantly reduced at all time intervals following SLT when compared to the pre-study level (P < 0.0001). At 12 months, the mean IOP was 12.2 ± 2.2 mmHg while on 1.1 ± 0.9 eye drops.
A single session of SLT for NTG achieved an additional 15% IOP reduction while using 27% less medication at 1 year compared to pre-study levels.
Trial registration
The Clinical Trials Register of the University of Hong Kong HKCTR1847
The European Clinical Trials Database 2014-003305-15 (August 11, 2014) (
PMCID: PMC4417344  PMID: 25571769
Selective laser trabeculoplasty; Normal tension glaucoma; Intraocular pressure; Medication
4.  A prospective, longitudinal, observational cohort study examining how glaucoma affects quality of life and visually-related function over 4 years: design and methodology 
BMC Ophthalmology  2015;15:91.
The aim of this study is to summarize the design and methodology of a prospective, longitudinal, observational cohort study to investigate how glaucoma affects patients’ quality of life and visually-related function over a 4-year period.
One hundred sixty-one (161) subjects were enrolled in this ongoing study. Patients between the ages of 21–85 years with a minimum 2-year diagnosis of primary open-angle glaucoma, chronic primary angle-closure glaucoma or pseudoexfoliation glaucoma were included. Each patient visited Wills Eye Hospital for a baseline visit. Follow-up is planned for a minimum of 4 years, with annual visits. Each visit includes (1) Clinical evaluation: a slit lamp examination, fundoscopy, intraocular pressure measurement, visual field examination, spectral domain optical coherence tomography, Pelli-Robson Contrast Sensitivity test and the Spaeth-Richman Contrast Sensitivity test; (2) a performance based measure: the Compressed Assessment of Ability Related to Vision; and (3) Subjective measures of vision-related quality of life (the National Eye Institute Visual Functioning Questionnaire 25 and the Modified Glaucoma Symptom Scale).
The results of this ongoing, prospective, longitudinal study are expected to shed light on the relationships between clinical measures, performance-based measures and subjective measures of well-being, in order to assess changes in the quality of life and the ability to function of patients with glaucoma over time.
PMCID: PMC4522094  PMID: 26231376
Glaucoma; Vision-related quality of life; Performance-based measures
5.  Effects of myopia on different areas and layers of the macula: a fourier-domain optical coherence tomography study of a chinese cohort 
BMC Ophthalmology  2015;15:90.
To explore the changes in thickness in different areas and layers of the macula under different refractive conditions.
Consecutive participants were enrolled in the study. Optical coherence tomography (OCT) images were obtained using a spectral-domain system. We studied the relationships of the full, inner and outer retinal thicknesses of the fovea, parafovea and perifovea relative to the spherical equivalent (SE) and axial length (AL).
We included 107 eyes; the analysis revealed that the men had thicker foveas (man vs women: 236.70 ± 18.97 μm vs 247.25 ± 16.70 μm P = 0.002) and inner parafoveas (man vs women: 128.35 ± 8.80 μm vs 122.78 ± 6.75 μm P < 0.001) than the women had. Full foveal thickness was not correlated with AL or SE (all P > 0.05), whereas the full para- and perifoveal thicknesses had significant negative correlations with AL (r = –0.243 P = 0.006 and r = –0.446 P < 0.001, for para- and peri- respectively) and positive correlations with SE (r = 0.346 P < 0.001 and r = 0.464 P < 0.001, for para- and peri- respectively). Regarding the layers, the thickness of the inner layer of the fovea increased with the degree of myopia. The average inner and outer layer thicknesses of the para- and perifovea decreased with the degree of myopia (with the SE para, b = 0.307, peri b = 0.457; with the AL para, b = –0.266, peri b = –0.454),with the perifoveal thicknesses decreasing more rapidly.
Macular thickness changes with the degree of myopia; however, the different areas and different layers change in different manners.
Electronic supplementary material
The online version of this article (doi:10.1186/s12886-015-0080-5) contains supplementary material, which is available to authorized users.
PMCID: PMC4522115  PMID: 26231216
Optical coherence tomography; Macular thickness; Inner and outer layer; Myopia
6.  Comparison of corneal endothelial cell measurements by two non-contact specular microscopes 
BMC Ophthalmology  2015;15:87.
Measurement of corneal endothelial cell density is important both for clinical diagnosis as well as clinical studies. Since endothelial cell loss is considered irreversible in humans, even small changes in endothelial cell density are relevant. Therefore it is important to know whether different instruments for endothelial cell density measurements give the same results and can thus be used interchangeably. In this study we compare corneal endothelial cell density and morphometry measurements from two widely used non-contact specular microscopes, the Topcon SP3000P and Konan Noncon Robo SP8000.
Endothelial cell measurements were performed with both the Topcon SP3000P and Konan Noncon Robo SP8000 on 34 eyes of 18 consecutive patients of our cornea clinics with poor image quality being the only exclusion criterion. Images were obtained using the auto-focussing method and manual cell selection. Endothelial cell density (ECD), hexagonal cell ratio (HEX) and coefficient of value (CV) of the endothelial cell layer were calculated by the instruments’ built-in software.
ECD values calculated by the Konan were systematically higher than Topcon values: in 94 % of eyes Konan gave a higher value than Topcon, leading to a mean difference in ECD between the instruments of 187 cells/mm2 (P < 0.001 in paired Wilcoxon test). HEX showed a broad range of values and differed greatly with only weak correlation between the two instruments. CV values for Konan mostly exceeded Topcon values, and only showed a weak correlation between the two instruments as well.
Values for ECD between the Konan and the Topcon do correlate well, but the ECDs calculated by the Konan are systematically higher than Topcon values. Both HEX and CV vary greatly and do not correlate sufficiently. Thus we recommend not to use the Konan and the Topcon instrument interchangeably.
PMCID: PMC4517400  PMID: 26219961
Cornea; Endothelium; Cell density; Specular microscope; Comparison
7.  Small-incision phacotrabeculectomy versus phacoemulsification in refractory acute primary angle closure with cataract 
BMC Ophthalmology  2015;15:88.
Acute primary angle closure (PAC) can be refractory to conventional treatment and intraocular pressure (IOP) is beyond control. Surgical intervention should be considered at the moment. The aim of the study was to compare small-incision phacotrabeculectomy (phacotrab, small-incision trabeculectomy combined with phacoemulsification) with phacoemulsification (phaco) in patients with refractory acute PAC and coexisting cataract.
Analyzed 49 eyes (49 patients) with acute PAC and cataract received small-incision phacotrab (24 eyes) or phaco (25 eyes) randomly. All these cases were refractory to conventional treatment involved the use of preoperative topical IOP-lowering agents, corticosteroids, mannitol, methazolamide and paracentesis to reduce IOP. The effects on best corrected visual acuity (BCVA), IOP, anterior chamber depth (ACD), glaucoma medications, and complications were observed for twelve months.
After operation BCVA of 18 patients (75 %) in phacotrab group and 20 patients (80 %) in phaco group improved compared to preoperative vision. No statistically significant differences in mean BCVA were found between the two groups. The mean postoperative IOP levels at all follow up time points were lower than the mean preoperative IOP in each group (P <0.001). There was statistically significant difference in mean IOP between the two groups only at 12 months postoperatively (P = 0.006). The surgical success rate (without medications, IOP ≤ 21 mmHg) was 83.33 % (20 eyes) and 72 % (18 eyes) in phacotrab group and phaco group respectively at 12 months. No statistically significant differences in the mean ACD were found between the two groups. There were no serious intra- or post-operative complications in the two treatment groups.
Besides phaco, small incision phacotrab may be another effective and safe choice in the treatment of patients with refractory acute PAC and coexisting cataract. Whether phacotrab is more effective in IOP control in the long term needs to be verified in the further.
PMCID: PMC4517567  PMID: 26220093
Acute primary angle closure; Cataract; Phacotrabeculectomy
8.  Changes in central corneal thickness and refractive error after thin-flap laser in situ keratomileusis in Chinese eyes 
BMC Ophthalmology  2015;15:86.
Refractive stability is influenced by alterations in corneal curvature and corneal thickness after laser in situ keratomileusis (LASIK). The aim of this study was to analyze the changes of central corneal thickness (CCT) and refractive error following thin-flap LASIK surgery in Chinese eyes.
One hundred and fifty-eight myopic patients (302 eyes) who underwent thin-flap LASIK surgery were prospectively evaluated. CCT was measured by non-contact specular microscopy before, and 1 day, 1 week, and 1, 3, and 6 months following surgery. Age, refractive error, and optic zone diameter were also recorded.
Preoperatively, the mean CCT was 531.6 ± 24.3 μm. At 1 day, 1 week, and 1, 3, and 6 months after surgery, mean CCTs were 431.4 ± 38.4 μm, 422.6 ± 3 7.8 μm, 427.2 ± 38.0 μm, 434.4 ± 38.2 μm, and 435.6 ± 38.0 μm, respectively. Significant changes were detected in CCT values at each time point after thin-flap LASIK treatment (P < 0.05). The mean preoperative spherical equivalent (SE) was −5.73 ± 2.30 diopters (D). At 1 day, 1 week, and 1, 3, and 6 months after surgery, it was 0.26 ± 0.58 D, 0.54 ± 0.52 D, 0.49 ± 0.53 D, 0.45 ± 0.49 D, and 0.37 ± 0.42 D, respectively. The spherical equivalent refraction at 6 months postsurgery was close to the predicted value (0.34 ± 0.30 D). The changes in CCT within 6 months (4.06 ± 9.99 μm) were negatively correlated with age, preoperative refractive error, and optical zone diameter, respectively (r = −0.180, P < 0.05; r = −0.187, P < 0.001; r = −0.171, P < 0.05, respectively). No significant correlation was found between CCT changes and SE changes at different time points, postoperatively.
CCTs decreased significantly at 1 day after surgery, and continued to decline at 1 week after surgery, then increased over time. From postoperative 1 week, SE over time continually shifted to the myopic side.
PMCID: PMC4517627  PMID: 26220189
Central corneal thickness; Myopia; Non-contact specular microscope; Thin-flap laser in situ keratomileusis; Refractive error
9.  Effects of scleral cross-linking using genipin on the process of form-deprivation myopia in the guinea pig: a randomized controlled experimental study 
BMC Ophthalmology  2015;15:89.
Scleral cross-linking (CXL) is a novel attempt to slow down the axial elongation process in animal eyes. As a natural CXL reagent, genipin would be also effective for the prevention of myopia process. Thus, the present study was designed to evaluate the effects of scleral cross-linking using genipin on the form-deprivation (FD) myopia process of guinea pigs.
Twenty-seven 3-week-old pigmented guinea pigs were randomly divided into three groups. Group A (n = 8) is the untreated control group. Group B (n = 8) is the FD control group, where all eyes were induced with monocular FD for 21 days. In Group C (n = 11), a sub-Tenon injection of 0.10 mL 0.50 % genipin was performed on FD eyes at day 0, 7 and 14 during the 21-day monocular FD. The ocular refraction, axial length, biomechanical test and light and electron microscopy were measured on all eyes to check the efficacy and safety of this scleral CXL technique.
Compared with Group A, significant increases in myopic refractive errors, axial elongation and reductions of scleral fibril diameter and density were observed in the 21-day FD eyes of Group B (P < 0.05). In Group C, the scleral CXL resulted in less myopia and axial elongation as compared with Group B (P < 0.05); a significant thickening of scleral fibrils was found after sub-Tenon injections of genipin; no histological damage on the retina or choroid was observed in Group C at the end of this study.
The FD myopia in guinea pig eyes was effectively blocked by the scleral CXL using sub-Tenon injections of genipin. No histological damage was found on the retina or choroid of these treated eyes. Further studies are needed to examine the long-term efficacy and safety of this CXL technique.
Electronic supplementary material
The online version of this article (doi:10.1186/s12886-015-0086-z) contains supplementary material, which is available to authorized users.
PMCID: PMC4518847  PMID: 26220299
Sclera; Cross-linking; Genipin; Form-deprivation; Myopia; Guinea pig
10.  Whole-exome sequencing reveals a novel CHM gene mutation in a family with choroideremia initially diagnosed as retinitis pigmentosa 
BMC Ophthalmology  2015;15:85.
Genomic mutations in about 200 genes are associated with hereditary retinal diseases. In this study, we screened for the disease-causing gene mutation in a family with X-linked retinal degenerative disease.
Pedigree data were collected and genomic DNA was isolated from peripheral blood of family members, who also underwent comprehensive ophthalmic examination including visual acuity, slit-lamp examination, fundus examination and visual field testing at Qilu Hospital of Shandong University. Whole-exome genomic sequencing was used to screen for gene mutations in the male proband. Sanger sequencing was used to confirm the mutation revealed in this family.
Two affected males underwent ophthalmic examination; retinitis pigmentosa (RP) was diagnosed on the basis of night blindness beginning at an early age, decreasing visual acuity, progressive loss of peripheral vision, attenuation of retinal vessels and pigment disturbance on fundus examination. However, whole-exome sequencing revealed no mutation in RP-associated genes. Instead, we identified a novel hemizygous c.1475_1476insCA mutation in the choroideremia-associated gene (CHM). The mutation was confirmed by Sanger sequencing and further excluded from the possibility as a rare polymorphism. From the genetic data and clinical findings, the diagnosis was corrected to choroideremia (CHM). Further molecular genetic analysis suggested that this novel CHM mutation caused a frame shift (p.Leu492PhefsX7) and encoded a truncated nonfunctional Rab escort protein 1 (REP-1), which caused CHM in this family. Finally, sequencing data for a pregnant female member confirmed that she did not carry the mutation and thus was carrying a healthy infant.
We report a novel CHM mutation, c.1475_1476insCA, identified by whole-exome sequencing in a family with X-linked CHM initially diagnosed as RP. Our findings emphasize the value of a diagnostic approach that associates genetic and ophthalmologic data to facilitate the proper clinical diagnosis of rare hereditary retinal diseases such as CHM.
PMCID: PMC4517409  PMID: 26216097
CHM; Choroideremia; Mutation; Retinitis pigmentosa; Whole-exome sequencing
11.  Is there association between Glutathione S Transferases polymorphisms and cataract risk: a meta-analysis? 
BMC Ophthalmology  2015;15:84.
Glutathione S transferase (GST) polymorphisms have been considered as risk factors for age-related cataracts, but the results remain controversial. In this study, we have performed a meta-analysis to evaluate the association between polymorphisms of GSTM1 and GSTT1 and cataract risk.
Published literature from PubMed and other databases were retrieved. The case–control studies regarding the association between GSTM1 or GSTT1 polymorphism and cataract risk were included. Pooled odds ratio (OR) and 95 % confidence interval (CI) were calculated using random- or fixed-effects model.
Fifteen studies on GSTM1 (3,065 patients and 2,105 controls), and nine studies on GSTT1 (2,374 patients and 1,544 controls) were included. By pooling all the studies, GSTM1 null polymorphism was not associated with cataract risk, and this negative association maintained in subgroup analyses. However, GSTT1 null polymorphism was significantly associated with increased risk of posterior subcapsular (OR, 1.42; 95 % CI, 1.04–1.94) but not other subtypes of cataract. Stratified analyses demonstrated an association of GSTT1 null genotype with increased risk of cataract in Asian (OR, 1.44; 95 % CI, 1.14–1.83) but not Caucasian populations. In addition, seven pooled studies showed no association of cataract risk with the combined GSTM1 and GSTT1 null genotypes.
This meta-analysis suggests that GSTT1 null polymorphism is associated with increased risk of posterior subcapsular cataract. Given the limited sample size, the association between GSTT1 null polymorphism and cataract risk in Asian awaits further investigation.
PMCID: PMC4514966  PMID: 26208492
Glutathione S Transferases; Polymorphisms; Cataract; Meta-analysis
12.  Photodynamic therapy versus anti-vascular endothelial growth factor agents for polypoidal choroidal vasculopathy: A meta-analysis 
BMC Ophthalmology  2015;15:82.
The aim of this study was to evaluate the efficacy and tolerability of photodynamic therapy (PDT) compared to intravitreal vascular endothelial growth factor (VEGF) inhibitors in the treatment of polypoidal choroidal vasculopathy (PCV).
Relevant studies were selected through an extensive search of the PubMed, EMBASE, Web of Science, and Cochrane Library databases. Outcomes of interest included visual outcomes, anatomic variables, and adverse events.
Six studies enrolling a total of 346 patients were included. The weighted mean differences (WMDs) of the mean changes in LogMAR VA when comparing PDT with anti-VEGF were −0.02 (95 % confidence interval [CI]: −0.12–0.08) at 3 months, 0.02 (95 % CI: −0.12–0.16) at 6 months, 0.02 (95 % CI: −0.15–0.18) at 12 months, and −0.17 (95 % CI: −0.90–0.55) at 24 months. There were no significant differences between the two groups at any of the time points. PDT was found to be associated with greater reduction of central retinal thickness (CRT) at six months (WMD: 44.94; 95 % CI: 16.44–73.44; P = 0.002), and it was superior to anti-VEGF therapy in achieving complete polyp regression (odd ratio, OR: 6.85; 95 % CI: 2.15–21.79; P = 0.001).Rates of adverse events did not differ significantly between the two treatments.
PDT appeared to result in greater CRT reduction at six months and higher polyp regression rate. However, the two treatments appear to be comparable in terms of best corrected visual acuity change and adverse events.
PMCID: PMC4513969  PMID: 26209516
polypoidal choroidal vasculopathy; photodynamic therapy; anti- vascular endothelial growth factor
13.  Case report: successful closure of a large macular hole secondary to uveitis using the inverted internal limiting membrane flap technique 
BMC Ophthalmology  2015;15:83.
Macular holes (MHs) are one of the complications of posterior uveitis that can significantly disturb vision. Conventional MH surgery (vitrectomy, internal limiting membrane (ILM) peeling, and gas tamponade) has been reported to show lower closure rates in patients with MHs secondary to uveitis than in patients with idiopathic MHs. Recently, the inverted ILM flap technique has been reported to be effective for treating refractory MHs. Here, we describe the application of this technique in a patient with a large MH secondary to uveitis, and its successful closure.
Case presentation
An 80-year-old woman presented with a chronic, large MH secondary to uveitis. The minimum aperture diameter of the MH was 569 μm and extensive post-inflammatory chorioretinal atrophy was present, which included the juxtafoveal region. Vitrectomy with the inverted ILM flap technique assisted by low molecular weight hyaluronic acid was performed. Three days after surgery, the MH was closed successfully, without excessive gliosis.
The inverted ILM flap technique may be the preferred surgical procedure for the treatment of large MHs secondary to uveitis.
PMCID: PMC4515012  PMID: 26208719
Macular hole; Uveitis; Inverted internal limiting membrane flap technique
14.  23-gauge transconjunctival vitrectomy in eyes with pre-existing functioning filtering blebs 
BMC Ophthalmology  2015;15:81.
We investigated the outcome of 23-gauge transconjunctival pars plana vitrectomy (23G PPV) for the treatment of vitreoretinal disorder in patients with prior trabeculectomy.
We retrospectively reviewed medical records of 23G PPV in 11 eyes that had functioning filtering blebs after trabeculectomy. The main outcome measures were the visual acuity, intraocular pressure (IOP) and subconjunctival fluid height in bleb by anterior segment optical coherence tomography (OCT) before and after the surgery.
Eyes that had 23G PPV showed improvement of visual acuity after the surgery (P =0.003). Mean IOP was 13.82 mmHg before 23G PPV and 15.82 mmHg at 6 months postoperatively, which was statistically insignificant (P = 0.758). The bleb was observed before and after surgery using anterior segment OCT, and the difference in subconjunctival fluid was not statistically significant (P =0.172).
23G PPV did not adversely affect bleb function in eyes with prior trabeculectomy.
PMCID: PMC4513617  PMID: 26204924
Trabeculectomy; Filtering bleb; 23-gauge transconjunctival vitrectomy
15.  Patient experiences in retinal trials: a cross-sectional study 
BMC Ophthalmology  2015;15:80.
Patient-centered care recognizes the obligation to understand and meet patient’s expectations. An individual’s satisfaction has been found to affect health-related decisions and treatment-related behaviours, which in turn affect medical compliance, follow-up, the success of treatment and the appropriate use of services. We studied the expectations, experiences and satisfaction of patients who participated in clinical trials for retinal diseases at the Sydney Eye Hospital.
The study was undertaken at the research clinic of the major public quaternary eye hospital in New South Wales, Australia. A 37-question survey was conducted on patients enrolled in or who had finished a clinical trial for macular disease in the 12 months preceding this study in November 2012. Patient satisfaction was assessed using close-ended, multiple choice questions. First, the decision making process for entering into the clinical trial was evaluated. Then the level of patient understanding and experience during the study was assessed. Finally, there was a series of questions to gauge the participants’ perception of trial outcomes and overall impression gained from the experience.
Eighty patients completed the questionnaire. Overall patient satisfaction was high with the majority of patients stating they would recommend participation in a retinal clinical trial (94 %) and participate in a subsequent trial (78 %). Most patients rated themselves as the most important factor in making the decision to join a trial. Patients felt well informed and expectations were generally felt to be met, however 14 % did not believe that they could withdraw from the study voluntarily. The most common reasons for trial participation were to contribute to medical science and to have improved treatment outcomes.
We found that patients generally found participation in retinal clinical trials to be a positive experience. Factors contributing to dissatisfaction mainly related to inconvenience experienced by transportation and waiting times. We also found that patients felt well informed about the study, but some did not have a complete understanding of their rights, which had been communicated to them when they entered the study. There were both altruistic and self-motivated reasons behind patients’ decisions to join a retinal trial.
Electronic supplementary material
The online version of this article (doi:10.1186/s12886-015-0071-6) contains supplementary material, which is available to authorized users.
PMCID: PMC4511246  PMID: 26202164
Patient satisfaction; Experiences; Clinical trials; Retinal; Macular
16.  Noninvasive vascular imaging of ruptured retinal arterial macroaneurysms by Doppler optical coherence tomography 
BMC Ophthalmology  2015;15:79.
To describe Doppler optical coherence tomography (OCT) imaging of ruptured retinal arterial macroaneurysms (RAMs).
Four eyes of four patients with ruptured RAMs were prospectively studied. Vascular imaging was obtained using swept-source Doppler OCT, and compared with indocyanine green angiography images.
En face projection of Doppler OCT images clearly showed RAMs at the corresponding locations of lesions in the indocyanine green angiography images. In Doppler OCT images, RAMs were located in the inner retina in three eyes and in the medium layer of the retina in one eye. In one eye, detection of RAMs by standard OCT was difficult because of the presence of inner retinal hemorrhage. In one eye, disappearance of blood flow after direct laser photocoagulation could be confirmed by Doppler OCT images.
Doppler OCT imaging may potentially function as a noninvasive complementary procedure with indocyanine green angiography.
PMCID: PMC4510894  PMID: 26198253
Retinal macroaneurysm; Doppler; Optical coherence tomography; Indocyanine green angiography; Three dimensional; Optical coherence tomography angiography
17.  Prospective, randomized, double-blind trial to investigate the efficacy and safety of corneal cross-linking to halt the progression of keratoconus 
BMC Ophthalmology  2015;15:78.
Corneal cross-linking is widely used to treat keratoconus. However, to date, only limited data from randomized trials support its efficacy.
The efficacy and safety of corneal cross-linking for halting progression of keratoconus were investigated in a prospective, randomized, blinded, placebo controlled, multicentre trial. Twenty-nine keratoconus patients were randomized in three trial centres. The mean age at inclusion was 28 years. Longitudinal changes in corneal refraction were assessed by linear regression. The best corrected visual acuity, surface defects and corneal inflammation were also assessed. These data were analysed with a multifactorial linear regression model.
A total of 15 eyes were randomized to the treatment and 14 to the control group. Follow-up averaged 1098 days. Corneal refractive power decreased on average (+/−standard deviation) by 0.35 +/− 0.58 dioptres/year in the treatment group. The controls showed an increase of 0.11 +/− 0.61 dioptres/year. This difference was statistically significant (p = 0.02).
Our data suggest that corneal cross-linking is an effective treatment for some patients to halt the progression of keratoconus. However, some of the treated patients still progressed, whereas some untreated controls improved. Therefore, further investigations are necessary to decide which patients require treatment and which do not.
Trial registration
NCT00626717, Date of registration: February 20, 2008.
PMCID: PMC4508968  PMID: 26194634
18.  Systemic amyloidosis with bilateral conjunctival involvement: a case report 
BMC Ophthalmology  2015;15:77.
Conjunctival amyloidosis is a very rare condition, generally unilateral, and presents mostly as an isolated condition without systemic compromise. Our purpose is to present a new case of systemic amyloidosis with a bilateral conjunctival involvement.
Case Presentation
A 66-years-old caucasian female complaining of conjunctival hemorrhage and chemosis in both eyes for the last five years had been discontinuously treated with topical antibiotics and corticosteroids without any evident improvement. She presented with a pink-yellow infiltration in the inferior conjunctiva of both eyes. Conjunctival biopsy under optical microscopy revealed amyloid deposit, confirmed by Congo red staining. Mucosal biopsy from esophagus and rectus confirmed amyloidosis by Congo red stain. Immunohistochemistry of bone marrow biopsy showed an increased number of plasma cells and an over-expression of light chain kappa subunit. She was treated with corticosteroids and lubrication with an improvement of symptoms. Ocular lesions remained stable after a follow-up of 3 years.
Conjunctival amyloidosis is a rare entity that may be overlooked, and should be differentiated from chronic conjunctivitis and conjunctival malignancies. Although it presents most frequently as a local process, a systemic involvement should always be ruled out.
PMCID: PMC4506761  PMID: 26189153
Ocular amyloidosis; Systemic amyloidosis; Red eye; Conjunctival malignancy
19.  Screening of potential target genes for cataract by analyzing mRNA expression profile of mouse Hsf4-null lens 
BMC Ophthalmology  2015;15:76.
Hsf4 is closely related to the development of cataract. However, the molecular mechanisms remain unknown. This study aimed to explore the molecular mechanisms that how Hsf4 mutations influence development of lens and thus lead to cataract in mouse.
The mRNA expression profile of mouse tissue samples from Hsf4-null and wile-type lenses was downloaded from Gene Expression Omnibus database. Then the LIMMA package was used to screen differentially expressed genes (DEGs) and DAVID was applied to identify the significantly enriched Gene Ontology (GO) categories for DEGs. Furthermore, the protein-protein interaction (PPI) network of DEGs was constructed using Cytoscape and the key modules were selected from the PPI network based on the MCODE analysis.
A total of 216 DEGs were screened, including 51 up- and 165 down-regulated genes. Meanwhile, nine GO terms were obtained, and DEGs such as SGK1, CRY2 and REV1 were enriched in response to DNA damage stimulus. Furthermore, 89 DEGs and 99 gene pairs were mapped into the PPI network and Ubc was the hob node. Two key modules, which contained the genes (e.g. Ubc, Egr1, Ptgs2, Hmox1, Cd44, Btg2, Cyr61 and Fos) were related to response to DNA damage stimulus.
The deletion of Hsf4 affects the expression of many genes, such as Ubc, Ptgs2, Egr1 and Fos. These genes may be involved in the development of cataract and could be used as therapeutic targets for cataract.
PMCID: PMC4506420  PMID: 26187041
Cataract; Differentially expressed gene; Heat shock transcription factor 4; Lens; Module
20.  23 Gauge pars plana vitrectomy for the removal of retained intraocular foreign bodies 
BMC Ophthalmology  2015;15:75.
To evaluate the morpho-functional outcomes and safety of transconjuctival 23-gauge pars plana vitrectomy(PPV) for removal of intraocular foreign bodies (IOFBs).
A retrospective study of 36 consecutive cases (mean age; 34,2 ± 10,9 years (between 15 and 60), 27 M,9 F) of 23-G PPV for the removal of IOFBs during the period of April 2009 and December 2011 and followed 9,4 ± 6,4(2–27) months were conducted. Visual outcomes, slit lamp biomicroscopy, intraocular pressure (IOP), and posterior segment visualization by indirect ophthalmoscopy, A-B mode ultrasonography, and computed orbital tomography were performed for all cases. Main outcomes including anatomic and visual outcomes, and both intraoperative and postoperative complications were recorded.
Of the 36 cases available for the study, the IOFBs (size range, 3 to 12 mm) could be removed in all eyes. Mean preoperative LogMAR BCVA was 1.44 ± 138 (range, 1.00 to 0.00) and mean postoperative LogMAR BCVA at final visit was 0,78 ± 0,98 (range, 1.00 to 0.00). (P = 0,007) Anatomic success was obtained in 97.2 % of eyes. 16 patients needed primary wound repair due to the leakage in insertion sites before the PPV, however remaining 20 cases were not. Fibrin reaction was seen in 8 (22.2 %) patients in early postoperative period, intraocular pressure elevation was detected in 12 (33.3 %) patients in which the silicone oil was used as an intravitreal tamponade, one patient with silicone oil tamponade developed band keratopathy and phthisis bulbi.
23-Gauge PPV is a feasible, effective approach in the surgical management of the patients with posterior segment intraocular foreign bodies.
PMCID: PMC4504162  PMID: 26178019
Pars plana vitrectomy; Intraocular foreign body; Posterior segment surgery; Penetrating ocular trauma
21.  Effect of outdoor activity on myopia onset and progression in school-aged children in northeast china: the sujiatun eye care study 
BMC Ophthalmology  2015;15:73.
Due to its high prevalence and associated sight-threatening pathologies, myopia has emerged as a major health issue in East Asia. The purpose was to test the impact on myopia development of a school-based intervention program aimed at increasing the time student spent outdoors.
A total of 3051 students of two primary (grades 1-5, aged 6-11) and two junior high schools (grades 7-8, aged 12-14) in both urban and rural Northeast China were enrolled. The intervention group (n = 1735) unlike the control group (n = 1316) was allowed two additional 20-min recess programs outside the classroom. A detailed questionnaire was administered to parents and children. Uncorrected visual acuity (UCVA) was measured using an E Standard Logarithm Vision Acuity Chart (GB11533-2011) at baseline, 6-month and 1-year intervals. A random subsample (n = 391) participated in the clinic visits and underwent cycloplegia at the beginning and after 1 year.
The mean UCVA for the entire intervention group was significantly better than the entire control group after 1 year (P < 0.001). In the subgroup study, new onset of myopia and changes in refractive error towards myopia were direction during the study period was significantly lower in the intervention group than in the control group (3.70 % vs. 8.50 %, P = 0.048; -0.10 ± 0.65 D/year vs. -0.27 ± 0.52 D/year, P = 0.005). Changes in axial length and IOP were also significantly lower following the intervention group (0.16 ± 0.30 mm/year vs. 0.21 ± 0.21 mm/year, P = 0.034; -0.05 ± 2.78 mmHg/year vs. 0.67 ± 2.21 mmHg/year, P = 0.006).
Increasing outdoor activities prevented myopia onset and development, as well as axial growth and elevated IOP in children.
Trial registration
Current controlled trials NCT02271373.
Electronic supplementary material
The online version of this article (doi:10.1186/s12886-015-0052-9) contains supplementary material, which is available to authorized users.
PMCID: PMC4495846  PMID: 26152123
Myopia; Refractive error; Outdoor activity; Schoolchildren; Intervention studies
22.  A novel device for assessing dark adaptation in field settings 
BMC Ophthalmology  2015;15:74.
Aberrant dark adaptation is common to many ocular diseases and pathophysiological conditions, including vitamin A deficiency, cardiopulmonary diseases, and hypoxia. Scotopic vision and pupillary responsiveness have typically been measured using subjective, time-consuming methods. Existing techniques are particularly challenging for use in developing country settings, where vitamin A deficiency remains a major public health problem. Our aim was design a compact, low cost, and easily operated device to assess dark adaptation in the field.
The Portable Field Dark Adaptometer (PFDA) incorporates a digital camera, a retinal bleaching flash, and a Ganzfeld light source inside a pair of light-obscuring goggles. After a ~10 min period of dark adaption, the infrared camera digitally records afferent pupillary responses to graded light stimuli (−2.9 to 0.1 log cd/m2). We tested this device in a variety of field settings to assess: a) ease of use and b) whether test data could clearly and accurately depict the well-known dose-response relationship between light intensity and pupil contraction. A total of 822 videos were collected. We used an open source video analysis software to measure pupil size in pixel units. Pupillary responsiveness was expressed as the percent change in pupil size from pre- to post-light exposure. Box plots, t test, and multi-level mixed effects linear regression modeling were used to characterize the relationship between light intensity and pupillary response.
The PFDA was employed with only minor technical challenges in Bangladesh, Kenya, Zambia, and Peru. Our data show a clear linear increase in pupillary constriction with increasing log light intensity. Light intensity was a strong predictor of pupillary response, regardless of baseline pupil size.
The consistent physiological response demonstrated here supports the use of the PFDA as a reliable tool to measure dark adaptation. As a next step, PFDA measurements will be validated against biochemical indicators of vitamin A status and hypoxemia. Ultimately, this new technology may provide a novel approach for nutritional assessment, with potential clinical applications.
Electronic supplementary material
The online version of this article (doi:10.1186/s12886-015-0062-7) contains supplementary material, which is available to authorized users.
PMCID: PMC4496941  PMID: 26156587
Dark adaptometry; Pupil dynamics; Pupillary threshold; Night blindness; Vitamin A
23.  Budget impact assessment of Aprokam® compared with unlicensed cefuroxime for prophylaxis of post-cataract surgery endophthalmitis 
BMC Ophthalmology  2015;15:72.
Intracameral cefuroxime is recommended as prophylaxis against postoperative endophthalmitis (POE) following cataract surgery. Aprokam is the only licensed product for prophylaxis of POE, although unlicensed intracameral cefuroxime may be administered using pre-filled syringes (PFS), either prepared in hospital by reconstituting cefuroxime via serial dilution (prepared PFS), or commercially purchased (purchased PFS). This study aimed to estimate the potential budget impact of using Aprokam over unlicensed cefuroxime for intracameral administration.
A budget impact model (BIM) was developed from UK NHS hospital perspective to estimate the economic impact of adopting Aprokam compared with purchased PFS or prepared PFS for the prophylaxis of POE following cataract surgery over a 5-year time horizon. The BIM incorporated direct costs only, associated with the acquisition, delivery, storage, preparation, and administration of cefuroxime. Resource utilisation costs were also incorporated; resource utilisation was sourced from a panel survey of hospital pharmacists, surgeons, and theatre nurses who are involved in the delivery, storage, preparation, quality assurance, or administration of cefuroxime formulations. Unit costs were sourced from NHS sources; drug acquisition costs were sourced from BNF. The model base case used a hypothetical cohort comprising of 1000 surgeries in the first year and followed a 5.2 % annual increase each year.
The model predicts Aprokam is cost saving compared with purchased PFS, with a modest increase compared prepared PFS over 5 years. There are total savings of £3490 with Aprokam compared with purchased PFS, driven by savings in staff costs that offset greater drug acquisition costs. Compared with prepared PFS, there are greater drug acquisition costs which drive an increased total cost over 5 years of £13,177 with Aprokam, although there are substantial savings in staff costs as well as consumables and equipment costs.
The lower direct costs of using Aprokam compared with purchased PFS presents a strong argument for the adoption of Aprokam where purchased PFS is administered. The additional benefits of Aprokam include increased liability coverage and possible reduction in dilution errors and contaminations; as such, in hospitals where unlicensed prepared PFS is used, modest additional resources should be allocated to adoption of Aprokam.
PMCID: PMC4495806  PMID: 26152124
Aprokam; Cataract surgery; Cefuroxime; Cost analysis; Economic analysis; Post operative endophthalmitis
24.  Comparing the effectiveness and costs of Bevacizumab to Ranibizumab in patients with Diabetic Macular Edema: a randomized clinical trial (the BRDME study) 
BMC Ophthalmology  2015;15:71.
The effectiveness of ranibizumab in the treatment of diabetic macular edema has been proven with large clinical trials. For bevacizumab only two clinical trials have been published and a head-to-head comparison is lacking to date. However, if proved non-inferior to ranibizumab, use of the off-label bevacizumab could reduce costs enormously without a loss in visual acuity. A cost-effectiveness study has been designed to substantiate this hypothesis.
To compare the effectiveness and costs of 1.25 mg of bevacizumab to 0.5 mg ranibizumab given as monthly intravitreal injections during 6 months in patients with diabetic macular edema. It is hypothesized that bevacizumab is non-inferior to ranibizumab regarding its effectiveness.
This is a randomized, controlled, double masked, clinical trial in 246 patients in seven academic trial centres in The Netherlands.
The primary outcome measure is the change in best-corrected visual acuity (BCVA) in the study eye from baseline to month 6. Secondary outcomes are the proportions of patients with a gain or loss of 15 letters or more or a BCVA of 20/40 or more at 6 months, the change in leakage on fluorescein angiography and the change in foveal thickness by optical coherence tomography at 6 months, the number of adverse events in 6 months, and the costs per quality adjusted life-year of the two treatments.
PMCID: PMC4491889  PMID: 26149170
Diabetic retinopathy; Diabetic macular edema; VEGF; Ranibizumab; Lucentis; Bevacizumab; Avastin; Randomized clinical trial
25.  Prevalence of allergic conjunctivitis among basic school children in the Kumasi Metropolis (Ghana): a community-based cross-sectional study 
BMC Ophthalmology  2015;15:69.
There seems a preponderance of hospital-based studies on the prevalence of Allergic Conjunctivitis (AC) compared to community-based ones, particularly among children in Ghana and Africa as a whole. Meanwhile, literature supports the possibility of underdiagnosing AC in the hospital setting; exponentially so when males generally have poor hospital-attending behavior. This may lead to underestimation of the true burden of AC. Consequently, the purpose of the current community-based study was to determine the prevalence of AC among basic school children in the Kumasi Metropolis, while identifying its associated symptoms.
A cross-sectional community-based study involving 1571 students from 11 basic schools (Primary and JHS) participated in the study. Data collection started in November 2011 and was completed in March 2014. After history taking, subjects underwent a battery of tests; visual acuity, objective refraction, anterior and posterior segments examination with a slit-lamp and a direct ophthalmoscope respectively.
The prevalence of AC was 39.9 %. The mean (±SD) age of participants was 8 ± 0.65 years. AC was significantly associated with gender (p < 0.05), but not with age (p > 0.05). A total of 70 % of the students with AC never had any form of treatment.
AC is an endemic ocular disease among basic schools in the Kumasi metropolis and therefore calls for pragmatic and proactive measures to reduce its burden and effects on its victims. Public health measures may be required to help reduce the burden associated with this condition.
PMCID: PMC4488987  PMID: 26134507
Allergic conjunctivitis; Prevalence; Community-based

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