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1.  Association of systemic and ocular risk factors with neurosensory retinal detachment in diabetic macular edema: a case–control study 
BMC Ophthalmology  2014;14:47.
Background
Diabetic macular edema (DME) with neurosensory retinal detachment (NSD) remains an important cause of visual loss in patients with diabetes. The aim of the study was to elucidate the association of systemic and ocular risk factors with NSD in DME.
Methods
In a retrospective case–control study, we reviewed clinical records of all the subjects with DME seen between January 2010 and December 2010. Cases and controls were selected based on optical coherence tomography and stereoscopic biomicroscopy review. NSD was defined as subfoveal fluid accumulation under detached retina with or without overlying foveal thickening. The association between the presence of NSD, blood pressure, lipid status and various other biochemical parameters was evaluated.
Results
Group I (cases) included 37 eyes of 33 patients having DME with NSD and Group II (controls) included 30 eyes of 21 patients having DME without NSD. Patients ranged in age (mean ± SD) from 50 to 62 years (56.6 +/-6.78) for cases and from 51 to 65 years (58.4+/-7.84) for controls. The duration of diabetes ranged from 4 to 15 year (mean 9.45+/-6.08) among cases and 4 to 14 years (9.7+/-5.12) among controls. Significant risk factors for NSD were high values of systolic and diastolic blood pressure (p = 0.039 and 0.043 respectively).
Conclusion
High systolic and diastolic blood pressures are independent and significant risk factors for NSD in DME.
doi:10.1186/1471-2415-14-47
PMCID: PMC3984633  PMID: 24716846
Diabetic macular edema; Neurosensory retinal detachment; Risk factors; Blood Pressure
2.  Long-term outcomes of unilateral lateral rectus recession versus recess-resect for intermittent exotropia of 20-25 prism diopters 
BMC Ophthalmology  2014;14:46.
Background
The purpose of this study was to compare surgical outcomes of unilateral lateral rectus recession (ULR) and unilateral recess-resect (RR) for intermittent exotropia of 20-25 prism diopters (PD).
Methods
In this retrospective study, ULR was performed on 82 patients and RR on 98 patients for the treatment of intermittent exotropia of 20-25 PD with a follow-up period of 24 months or more. The main outcome measures were postoperative exodeviation angles and final success rates. A surgical success was considered to be an alignment within 10 PD.
Results
The mean follow-up duration after the surgery was 53.8 ± 26.4 months in the ULR group and 52.5 ± 27.4 months in the RR group (p = 0.482). The mean deviation angles at postoperative 1 day were -0.49 PD (esodeviation) in the ULR group and -1.98 PD in the RR group. Subsequently, at postoperative 1 week, 1 and 3 months, the deviations became more exotropic in the ULR group than in the RR group (p < 0.05). However, the mean deviation angles at 6 months, 1 and 2 years and at the final follow-up did not significantly differ between the two groups. Surgical success at the final follow-up was achieved for 50 patients (60.9%) in the ULR group and 55 patients (56.1%) in the RR group (p = 0.511).
Conclusions
ULR is an effective surgical method for treatment of moderate-angle intermittent exotropia of 20-25 PD, showing results similar to those of RR.
doi:10.1186/1471-2415-14-46
PMCID: PMC3983853  PMID: 24708678
Intermittent exotropia; Unilateral lateral rectus recession; Recess-resect; Moderate-angle exotropia
3.  Prevalence of infectious keratitis in Central China 
BMC Ophthalmology  2014;14:43.
Background
The baseline data pertaining to the national epidemiological survey of infectious keratitis remain scarce in China, and currently there is no corneal blindness control strategy developed by the nation.
Methods
Geographically defined cluster sampling was used to randomly select a cross-section of residents from representative urban and rural populations in Hubei Province. Participants were selected from village registers, followed by door-to-door household visits. The assessment items included a structured interview, visual acuity testing, external eye examination, and anterior segment examination using slit lamp. Causes and sequelae of corneal disease were identified according to uniform customized protocol.
Results
The prevalence of presenting corneal diseases was 0.8% (211/26 305), while the prevalence of infectious keratitis was 0.148% (39/26 305). The prevalences of viral, bacterial, and fungal keratitis were 0.065, 0.068, and 0.015%, respectively. There were no significant differences found between the prevalences of viral (accounting for 43.6%) and bacterial (accounting for 46.2%) corneal ulcers. cases of Acanthamoeba keratitis were not found. Infectious keratitis was the leading cause of corneal blindness (85.7%), and the prevalence of blindness in at least one eye resulting from infected corneas was 0.091% (95% CI: 0.067-0.127%).
Conclusions
Viral and bacterial mechanisms constitute the most important risk factors for infectious corneal ulcers in Central China. To reduce the rate and severity of infectious keratitis, he public health care policy should be focused on designing cost-effective strategies and operational programs for the prevention and prompt treatment of infectious corneal ulcers.
doi:10.1186/1471-2415-14-43
PMCID: PMC3976152  PMID: 24690368
Infectious keratitis; Corneal diseases; Corneal blindness; Visual ability
4.  Trabeculectomy with versus without releasable sutures for glaucoma: a meta-analysis of randomized controlled trials 
BMC Ophthalmology  2014;14:41.
Background
The aim of this study was to compare the efficacy and tolerability of trabeculectomies performed with and without releasable sutures in the treatment of patients with uncontrolled glaucoma.
Methods
A comprehensive literature meta-analysis was performed, comparing trabeculectomies performed with and without releasable sutures. The primary efficacy measure was the weighted mean difference (WMD) in percentage intraocular pressure reduction (IOPR%) at the follow-up end point. The secondary efficacy measure was the risk ratio (RR) for complete and qualified success rates of trabeculectomy at the follow-up end point. Trabeculectomy tolerability estimates were measured by the RR for adverse events. All the outcomes were reported with a 95% confidence interval (CI).
Results
The WMD of the IOPR% from baseline was −4.56 (range −9.24–0.12) when trabeculectomies without releasable sutures were compared with trabeculectomies with releasable sutures. Trabeculectomies with releasable sutures were associated with numerically greater, but nonsignificant, efficacy in terms of lowered IOP compared with trabeculectomies without releasable sutures. The complete and qualified success rate of the two surgical procedures were comparable, with RRs of 0.92 (range 0.80–1.04) and 0.99 (range 0.89–1.11), respectively, at the follow-up endpoints. Trabeculectomies without releasable sutures were associated with a significantly higher frequency of hypotony and flat anterior chambers than trabeculectomies with releasable sutures, with pooled RRs of 4.04 (range 1.88–8.68) and 2.57 (range 1.25–5.30), respectively.
Conclusion
Although the two surgical procedures resulted in equivalent efficacy in IOP control, the trabeculectomies performed with releasable sutures were better tolerated than those without releasable sutures.
doi:10.1186/1471-2415-14-41
PMCID: PMC3976541  PMID: 24685235
Releasable sutures; Trabeculectomy; Meta-analysis
5.  Clinical utility of spectral analysis of intraocular pressure pulse wave 
BMC Ophthalmology  2014;14:30.
Background
To evaluate the clinical utility of spectral analysis of intraocular pressure pulse wave in healthy eyes of a control group (CG), patients having glaucomatous optic disc appearance or ocular hypertension, and patients with primary open angle glaucoma or primary angle closure glaucoma.
Methods
This is a prospective study that enrolled 296 patients from a single glaucoma clinic. Age matched CG consisted of 62 individuals. Subjects underwent comprehensive clinical diagnostic procedures including intraocular pressure (IOP) measurement with dynamic contour tonometry (DCT) and Goldmann applanation tonometry (GAT). DCT time series were analyzed with custom written software that included signal preprocessing, filtering and spectral analysis. An amplitude and energy content analysis, which takes into account non-stationarity of signals but also provides methodology that is independent of IOP and ocular pulse amplitude (OPA) levels, was applied. Spectral content up to the 6th harmonic of the pressure pulse wave was considered. Statistical analyses included descriptive statistics, normality test, and a multicomparison of medians for independent groups using Kruskal-Wallis test.
Results
GAT IOP showed statistical significance (Kruskal-Willis test p < 0.05) for three out of 10 considered multiple comparisons, DCT IOP and OPA showed statistically significant results in five and seven cases, respectively. Changes in heart rate and central corneal thickness between the groups were statistically significant in two cases. None of the above parameters showed statistically significant differences between CG and the suspects with glaucomatous optic disc appearance (GODA). On the other hand, spectral analysis showed statistically significant differences for that case.
Conclusions
Spectral analysis of the DCT signals was the only method showing statistically significant differences between healthy eyes and those of GODA suspects.
doi:10.1186/1471-2415-14-30
PMCID: PMC3975190  PMID: 24620786
Glaucoma; Intraocular pressure; Dynamic contour tonometry; Ocular pulse wave
6.  Diode laser transscleral cyclophotocoagulation followed by phacotrabeculectomy on medically unresponsive acute primary angle closure eyes: the long-term result 
BMC Ophthalmology  2014;14:26.
Background
To explore the intraocular pressure-lowering effect and complications of diode laser transscleral cyclophotocoagulation (DLTSC) followed by phacotrabeculectomy on medically unresponsive acute primary angle closure eyes.
Methods
Nine eyes of nine medically unresponsive acute primary angle closure patients were enrolled. All the patients underwent cyclophotocoagulation followed by phacotrabeculectomy to control the prolonged acute attack. Data were recorded prospectively and then analyzed retrospectively. The reduction in intraocular pressure, improvement of vision and the complications were evaluated.
Results
After DLTSC, the IOP of all the patients were reduced, but all were above 21 mmHg under topical anti-glaucoma medications. After phacotrabeculectomy, the IOP of all the patients was decreased. At the final visit, the vision of all the patients was improved and the IOP of all the patients was below 21 mmHg without anti-glaucoma medications. There were no complications during the DLTSC and phacotrabeculectomy. Uveitis was the common complications after the both procedures, which were resolved by medication treatment.
Conclusion
Diode laser transscleral cyclophotocoagulation followed by phacotrabeculectomy is an alternative procedure to control the intraocular pressure of medically unresponsive acute primary angle closure eyes with few complications.
doi:10.1186/1471-2415-14-26
PMCID: PMC3975279  PMID: 24606842
Diode laser transscleral cyclophotocoagulation; Acute primary angle closure; Phacotrabeculectomy
7.  Normal-tension glaucoma and obstructive sleep apnea syndrome: a prospective study 
BMC Ophthalmology  2014;14:27.
Background
Today, identified risk factors for normal-tension glaucoma (NTG) include abnormal ocular blood flow, abnormal blood coagulation, systemic hypotension, ischemic vascular disorders, and autoimmune diseases. However, pathogenesis of the condition remains unclear. On the other hand, there are also a few studies suggesting that the obstructive sleep apnea syndrome (OSAS) may compromise optic nerve head perfusion and cause glaucomatous optic neuropathy by creating transient hypoxemia and increasing vascular resistance. In this study, we evaluated the possible association between OSAS and NTG.
Methods
We recruited 24 patients with NTG and 24 age and sex matched controls who were also similar for systemic risk factors such as diabetes mellitus (DM), hypertension (HT) and hypercholesterolemia. All patients and controls underwent over-night polysomnography (PSG) for the diagnosis of OSAS and calculation of Apnea-Hypopnea Index (AHI).
Results
Patients and controls were statistically similar in terms of age, sex, gender, smoking, systemic risk factors, neck circumference and body mass index. The subjects with AHI ≥ 20 were accepted as OSAS. Ten (41.7%) of 24 patients with NTG and 3 (12.5%) of 24 controls had OSAS (p < 0.05).
Conclusions
The prevalence of OSAS was higher in patients with NTG and the difference between patient and control groups was statistically significant (p < 0.05).
doi:10.1186/1471-2415-14-27
PMCID: PMC3975309  PMID: 24612638
Normal-tension glaucoma; Obstructive sleep apnea
8.  Blood expression levels of chemokine receptor CCR3 and chemokine CCL11 in age-related macular degeneration: a case–control study 
BMC Ophthalmology  2014;14:22.
Background
Dysregulation of the CCR3/CCL11 pathway has been implicated in the pathogenesis of choroidal neovascularisation, a common feature of late age-related macular degeneration (AMD). The aim of this study was to investigate the expression of CCR3 and its ligand CCL11 in peripheral blood in patients with neovascular AMD.
Methods
Patients with neovascular AMD and healthy controls were included. Blood samples were obtained and prepared for flow cytometry to investigate the expression of CCR3. Levels of CCL11 were measured in plasma using Cytometric Bead Array. Differences between the groups were tested using Kruskal-Wallis test and Mann–Whitney U test.
Results
Patients (n = 83) with neovascular AMD and healthy control persons (n = 114) were included in the study. No significant difference in the expression of CCR3 was found on CD9+ granulocytes when comparing patients suffering from neovascular AMD with any of the control groups. We did not find any alteration in CCL11 levels in patients among the age matched groups. There was no correlation between expression of CCR3/CCL11 and clinical response to treatment with anti-vascular endothelial growth factor (VEGF).
Conclusion
Our results do not suggest a systemic alteration of the CCR3/CCL11 receptor/ligand complex in patients with neovascular AMD.
doi:10.1186/1471-2415-14-22
PMCID: PMC3942269  PMID: 24575855
Age-related macular degeneration; chemokine; CCR3; CCL11
9.  Agreement between Orbscan II, VuMAX UBM and Artemis-2 very-high frequency ultrasound scanner for measurement of anterior chamber depth 
BMC Ophthalmology  2014;14:20.
Background
The aim was to compare the anterior chamber depth (ACD) measurements taken with Orbscan II, ultrasound biomicroscopy (UBM) and the Artemis-2 VHF (very-high-frequency) ultrasound scanner in normal subjects.
Methods
In this prospective study, one eye from each of 60 normal subjects was randomly selected. Three subjects dropped out of the study because they were apprehensive about the UBM examination; their data were excluded entirely. Measurements of ACD were taken with the Orbscan II, UBM and Artemis-2 VHFUS. Results were obtained for coefficient of variance (CV) and intra-class correlation coefficient (ICC), and statistical analysis was by repeated-measures analysis of variance (ANOVA) for intra-observer repeatability. ANOVA and Bland–Altman analyses were used to determine limits of agreement (LOA) between the three instruments.
Results
The average ACD (± standard deviation) was 3.13 ± 0.34 mm, 2.96 ± 0.27 mm and 2.87 ± 0.31 mm for the Orbscan II, UBM and Artemis-2 VHFUS, respectively. The repeatability scores were 0.015 ± 0.014%, 0.08 ± 0.09% and 0.07 ± 0.06% for the Orbscan II, UBM and Artemis-2 VHFUS, respectively. The ICC for repeatability of Orbscan II, UBM and Artemis-2 VHFUS measurements was high and equal to 0.99%. The intra-observer repeatability scores of the ACD measurement p-values using Orbscan II, UBM and Artemis-2 VHFUS were 0.12, 0.70 and 0.10, respectively. The mean difference and standard deviations for ACD measurements using Orbscan II vs UBM, Orbscan II vs Artemis-2 VHFUS and UBM vs Artemis-2 VHFUS were 0.17 ± 0.31 mm, 0.27 ± 0.34 mm and 0.10 ± 0.18 mm, respectively. LOAs were 0.78 to -0.44 mm, 0.93 to -0.39 mm and 0.45 to -0.26 mm. ANOVA revealed a statistically significant difference between the Orbscan II, UBM and Artemis-2 VHFUS (p < 0.0001).
Conclusions
Measurements by the three instruments show high repeatability. UBM and the Artemis-2 VHFUS can be used interchangeably, but the Orbscan II cannot be used interchangeably with UBM or the Artemis-2 VHFUS.
doi:10.1186/1471-2415-14-20
PMCID: PMC3936803  PMID: 24564379
Anterior chamber depth; Artemis-2 VHF; Normal eyes; Orbscan II; Ultrasound biomicroscopy; Ultrasound scanner
10.  Intraocular pressure-lowering efficacy and safety of bimatoprost 0.03% therapy for primary open-angle glaucoma and ocular hypertension patients in China 
BMC Ophthalmology  2014;14:21.
Background
To report the clinical outcomes in Chinese patients with primary open-angle glaucoma and ocular hypertension treated with bimatoprost 0.03% therapy.
Methods
Two hundred sixty-three Chinese patients with primary open-angle glaucoma and ocular hypertension who needed initial or additional intraocular pressure (IOP) lowering were recruited in this prospective, open-label, multicenter clinical study and were treated with bimatoprost 0.03%. Patients received bimatoprost 0.03% as initial, replacement or adjunctive IOP-lowering therapy, and follow-up visits were performed at week 1, and month 1 and 3 of the bimatoprost treatment. The efficacy outcome measure was the post-treatment IOP level. The safety outcome measures included the rate of medication-related symptoms, physical signs, reported adverse events, and the level of conjunctival hyperemia.
Results
Among 240 patients who could be categorized by pre-existing therapies and the bimatoprost therapy regimen in the study, IOP values observed in all medication conditions showed significant IOP reduction at all study visits compared with baseline. At 3 months, 8.0 ± 3.7 mmHg (32.0%) reduction in IOP was observed in treatment-naive patients after bimatoprost monotherapy; in the patients previously on various therapy regimens, 1.9 ± 2.8 mmHg (9.5%) to 6.4 ± 6.1 mmHg (24.8%) additional IOP lowering was achieved after switching to bimatoprost monotherapy or bimatoprost combination therapy. The most common adverse event was conjunctival hyperemia, mainly of trace and mild intensity.
Conclusions
Our results show that bimatoprost 0.03% was effective in lowering IOP with favorable safety in Chinese primary open-angle glaucoma and ocular hypertension patients.
doi:10.1186/1471-2415-14-21
PMCID: PMC3943806  PMID: 24568617
Bimatoprost; Glaucoma; Ocular hypertension; Intraocular pressure; Conjunctival hyperemia
11.  Epidemiology and treatment outcomes of diabetic retinopathy in a diabetic population from Cameroon 
BMC Ophthalmology  2014;14:19.
Background
Diabetic retinopathy (DR) is the most common microvascular complication of diabetes. It can lead to significant visual loss. The aim of this study was to determine the frequency and clinical profile of diabetic retinopathy, and assess the outcomes of laser photocoagulation therapy in a diabetic population in Cameroon.
Methods
We carried out a prospective cohort study during 24 months in the Department of Ophthalmology of the Douala General Hospital, Cameroon. We included all diabetic patients who were referred from diabetes clinics for ophthalmologic evaluation. Data included type and duration of diabetes, visual acuity, intra-ocular pressure, results of fundoscopy and fluorescein angiography, and outcomes two months after treatment with laser photocoagulation.
Results
We included 407 patients; 88% had type 2 diabetes. Their mean duration of diabetes was 6.4 years (SD=6.6). Forty point three percent (164/407) of patients were found to have DR on fundoscopy. Of the 164 patients with DR, 63.4% (104/164) had non-proliferative and 36.6% (60/164) had proliferative DR. Diabetic maculopathy was found in 14.5% (59/407) of all participants, and 36% (59/164) of patients with DR. There was a strong correlation between the duration of diabetes and retinopathy status (p < 0.001, r = 0.9541). Overall, 17.4% (71/407) of patients were eligible for laser photocoagulation. Of these, 66.2% (47/71) were treated, and 78.7% (37/47) of treated patients came back for control two months later. Among these treated patients an improvement of the retinopathy was noted in 73% (27/37), no change in 16.2% (6/37) and a worsening in 10.8% (4/37). Severe proliferative DR was significantly associated with treatment failure (p < 0.001).
Conclusions
The frequency of DR may be high among diabetic patients in Cameroon. There was a good uptake of laser photocoagulation therapy among patients affected by DR in our setting, with good treatment outcomes. Interventions to prevent diabetes and increase the precocity of diagnosis and treatment of DR should be scaled up.
doi:10.1186/1471-2415-14-19
PMCID: PMC3941950  PMID: 24564334
Diabetes; Diabetic retinopathy; Photocoagulation; Cameroon
12.  Spectral-domain optical coherence tomography evaluation of postoperative cystoid macular oedema following phacoemulsification with intraoperative complication 
BMC Ophthalmology  2014;14:16.
Background
To report the rate of cystoid macular oedema (CMO) as detected by spectral-domain optical coherence tomography (SD-OCT) after intraoperative complication during phacoemulsification. The secondary objectives include comparing mean macular thickness and best-corrected visual acuity (BCVA) between those who developed postoperative CMO against those who did not.
Methods
This is a prospective cohort study conducted in a tertiary hospital between July 2009 and June 2010. Serial SD-OCT and BCVA were performed at baseline, 1 week, 6 weeks and 16 weeks postoperatively.
Results
Single eyes from 47 subjects were analyzed; of these 16 (34%) eyes developed CMO. In the CMO group, mean macular thickness (±SD) increased sharply by 56 μm from 273 ± 24 μm at baseline to 329 ± 31 μm at 16 weeks; whereas in the non-CMO group, macular thickness showed a slight increase of 14 μm from 259 ± 21 μm to 272 ± 20 μm. In the CMO group, mean BCVA (in logarithm of minimum angle of resolution) improved modestly from 0.92 ± 0.66 to 0.66 ± 0.41 at week 16; while in the non-CMO group, mean BCVA improved markedly from 0.98 ± 0.59 to 0.21 ± 0.13. The two groups differed significantly in mean macular thickness (p < 0.001) and mean BCVA (p < 0.001) at 16 weeks.
Conclusion
As detection rate of CMO is high, postoperative OCT monitoring for patients with intraoperative complications allows earlier diagnosis and treatment.
doi:10.1186/1471-2415-14-16
PMCID: PMC3932987  PMID: 24533465
Cystoid macular oedema; Spectral-domain optical coherence tomography; Phacoemulsification; Intraoperative complication
13.  Reviewer acknowledgement 2013 
BMC Ophthalmology  2014;14:14.
Contributing reviewers
The editors of BMC Ophthalmology would like to thank all of our reviewers who have contributed to the journal in Volume 13 (2013).
doi:10.1186/1471-2415-14-14
PMCID: PMC3922300
14.  Association of TLR7 and TSHR copy number variation with Graves’ disease and Graves’ ophthalmopathy in Chinese population in Taiwan 
BMC Ophthalmology  2014;14:15.
Background
Graves’ disease (GD) and Graves’ ophthalmopathy (GO) are autoimmune disorders, which might be influenced by genetic factors. Copy number variation (CNV) is an important source of genomic diversity in humans, and influences disease susceptibility. This study investigated the association between CNV in the TSHR and TLR7 genes and the development of GD and GO in a Chinese population in Taiwan.
Methods
For this case-control study, sample from 196 healthy controls and 484 GD patients, including 203 patients with GO were studied. CNV was detected by real-time polymerase chain reaction (PCR) using TaqMan™ probes and the relative copy number (CN) was estimated by using the comparative Ct method.
Results
The differences in the distribution of TSHR CNV in healthy controls and GD patients were statistically significant (p value = 0.01). However, the difference in the distribution of TSHR CNV in the control group and the GO group was not statistically significant (p value = 0.06). For TLR7 CNV, the results were not significantly different when we compared the distribution in healthy controls and GD patients and in healthy controls and GO patients (p values for Fisher’s exact test were 0.13 and 0.09, respectively). However, a lower than normal CNV for TLR7 (CNV < 2 for female and CNV < 1 for male) was found to have a protective effect against the development of GD (odds ratio (OR) = 0.24; 95% confidence interval (CI), 0.07-0.75) after adjusting for age and gender.
Conclusions
These results suggested that TSHR and TLR7 CNV might be associated with susceptibility to GD.
doi:10.1186/1471-2415-14-15
PMCID: PMC3929160  PMID: 24517461
Graves’ disease; Graves’ ophthalmopathy; Copy number variation; TSHR; TLR7; Taiwan
15.  On the ocular findings in ochronosis: a systematic review of literature 
BMC Ophthalmology  2014;14:12.
Background
Ochronosis/Alkaptonuria is a tyrosine metabolism disorder where accumulation of homogentisic acid, in eye, skin, cartilage and several other connective tissues leads to a black pigmentation of the affected tissues. It is autosomal-recessive inherited in men with a frequency of 1-9/1,000,000. While it is clear that pigment deposits lead to joint destruction, renal stone formation and cardiac valvulopathy respectively, the significance of ocular findings is still unclear. We therefore aim to evaluate the frequency and clinical significance of ocular findings in ochronosis and discuss possible therapeutic options.
Methods
Systematic review of literature via Medline and Web of Science. Only case reports in English, German, French, Spanish or Italian documenting detailed ophthalmologic examination were included.
Results
Our search revealed 36 case reports including 40 patients. Average age at the onset of ocular signs was 40.6 years. The most frequent sign was symmetric brown sclera pigmentation present in 82.5 percent of the patients. “Oil-drops”, brown pigment spots in the limbus are generally considered pathognomonic but were a little less frequent (75 percent). Vermiform pigment deposits at the level of the conjunctiva or increased conjunctival vessel diameter is also frequent. We found an increased incidence of central vein occlusion and elevated intraocular pressure going along with chamber angle hyperpigmentation. Another condition observed twice is rapid progressive astigmatism attributable to corneoscleral pigment accumulation.
Conclusion
Our observations suggest that ocular findings are of double relevance. First, characteristic ocular findings can anticipate the time of diagnosis and second, ocular findings may complicate to various conditions putting sight at risk. Opthalmologists and general physicians should be aware of both. Therapeutic options include protein restriction, administration of high dose vitamin C or nitisonone. Evidence for all of them is limited.
doi:10.1186/1471-2415-14-12
PMCID: PMC3915032  PMID: 24479547
Hereditary ochronosis; Endogenous ochronosis; Alkaptonuria; Oil-drops; Eye; Opththalmology; Homogentisic acid; Ocular; Homogentisic acid oxidase deficiency
16.  Biomechanical parameters of the cornea measured with the Ocular Response Analyzer in normal eyes 
BMC Ophthalmology  2014;14:11.
Background
To evaluate the relationships between Reichert Ocular Response Analyzer (ORA) parameters corneal hysteresis (CH) and corneal response factor (CRF) and ocular dimensions, age and intraocular pressure.
Methods
Two hundred and twelve eyes of 212 participants with no ocular pathology had CH and CRF measured with the ORA. Intraocular pressure (IOP) was measured with the Dynamic Contour tonometer and central corneal thickness (CCT) was also evaluated. Partial least squares linear regression (PLSLR) analyses were performed to examine the relationships between each response variable, CH and CRF, and the predictor variables age, corneal curvature (CC), axial length (AL), CCT and IOP.
Results
CH was positively associated with CCT and negatively associated with age (scaled coefficients: CCT 0.62, p < 0.0001; age -0.55, p <0.0001; r2 = 0.25). CRF was positively associated with CCT and DCT IOP and negatively associated with age and AL (scaled coefficients: CCT 0.89, p < 0.0001; DCT IOP 0.46, p < 0.01; age – 0.60, p < 0.0001; AL -0.37, p < 0.01; r2 = 0.43). There was no significant association between CC and CH or CRF.
Conclusions
The study suggests that age and CCT are strongly associated with CH and CRF, and that the latter is also influenced by AL and IOP. However, the variables studied could explain only 25% and 43% of the measured variation in CH and CRF, respectively, suggesting other factors also affect the values of these measurements.
doi:10.1186/1471-2415-14-11
PMCID: PMC3922776  PMID: 24479520
17.  Fear of falling in age-related macular degeneration 
BMC Ophthalmology  2014;14:10.
Background
Prior studies have shown age-related macular degeneration (AMD) to be associated with falls. The purpose of this study is to determine if (AMD) and AMD-related vision loss are associated with fear of falling, an important and distinct outcome.
Methods
Sixty-five persons with AMD with evidence of vision loss in one or both eyes and 60 glaucoma suspects with normal vision completed the University of Illinois at Chicago Fear of Falling questionnaire. Responses were Rasch analyzed. Scores were expressed in logit units, with lower scores demonstrating lesser ability and greater fear of falling.
Results
Compared to glaucoma suspect controls, AMD subjects had worse visual acuity (VA) (median better-eye VA = 20/48 vs. 20/24, p < 0.001) and worse contrast sensitivity (CS) (binocular CS = 1.9 vs. 1.5 log units, p < 0.001). AMD subjects were also older, more likely to be Caucasian, and less likely to be employed (p < 0.05 for all), but were similar with regards to other demographic and health measures. In multivariable models controlling for age, gender, body habitus, strength, and comorbid illnesses, AMD subjects reported greater fear of falling as compared to controls (β = -0.77 logits, 95% CI = -1.5 to -0.002, p = 0.045). In separate multivariable models, fear of falling increased with worse VA (β = -0.15 logits/1 line decrement, 95% CI = -0.28 to -0.03, p = 0.02) and CS (β = -0.20 logits/0.1 log unit decrement, 95% CI = -0.31 to -0.09, p = 0.001). Greater fear of falling was also associated with higher BMI, weaker grip, and more comorbid illnesses (p < 0.05 for all).
Conclusions
AMD and AMD-related vision loss are associated with greater fear of falling in the elderly. Development, validation, and implementation of methods to address falls and fear of falling for individuals with vision loss from AMD are important goals for future work.
doi:10.1186/1471-2415-14-10
PMCID: PMC3922687  PMID: 24472499
Fear of falling; Falls; Age-related macular degeneration; Disability; Older adults; Visual acuity; vision loss; Physical function; Safety
18.  Presbyopia: a pilot investigation of the barriers and benefits of near visual acuity correction among a rural Filipino population 
BMC Ophthalmology  2014;14:9.
Background
Presbyopia is the age-related decline in accommodation that diminishes the ability of the eye to focus on near objects. Presbyopia is common and easy to correct; however, many communities lack access to basic eye care. The purpose of this project was to assess the burden of uncorrected presbyopia in a rural Filipino population and to pilot an intervention aimed at increasing access to reading glasses in the community.
Methods
Individuals above the age of 40 who presented to a health outreach in the Philippines were invited to undergo a near vision exam to detect the presence of functional presbyopia and be fitted with ready-made, single-vision glasses. The change in stereoacuity was used as a surrogate measure of functional improvement after near vision correction. A questionnaire was administered to assess this population’s perceived barriers and benefits to correcting near vision.
Results
The average age of the participants was 57 ± 11 years, with 87.6% of participants having an uncorrected near visual acuity of <20/50. Reading glasses improved near vision to 20/40 or better in 77.7% of participants having near-vision impairment (uncorrected near visual acuity of <20/40). Over 75% of participants also showed improvement in stereoacuity. Cost, rather than availability, was perceived to be the greater barrier to the procurement of glasses, and 84% of participants reported that the glasses dispensed would greatly improve their ability to earn a living.
Conclusions
Dispensing ready-made, single-vision glasses is a simple and cost-effective intervention to improve near vision and enhance depth perception. A greater understanding of the barriers and benefits to correcting near vision will inform the design and execution of a sustainable program to correct presbyopia in developing countries.
doi:10.1186/1471-2415-14-9
PMCID: PMC3908502  PMID: 24467667
Presbyopia; Quality of life; Survey; Near vision; Stereoacuity; Reading glasses
19.  Efficacy and safety of widely used treatments for macular oedema secondary to retinal vein occlusion: a systematic review 
BMC Ophthalmology  2014;14:7.
Background
Macular oedema secondary to retinal vein occlusion (RVO) can cause vision loss due to blockage of the central retinal vein (CRVO) or a branch retinal vein (BRVO). This systematic review assessed the efficacies of widely used treatments for macular oedema secondary to RVO and the feasibility of conducting indirect comparisons between these therapies.
Methods
A systematic review was undertaken in November 2010, including a literature search for trials in medical databases and relevant websites. Abstracts, conference presentations and unpublished studies were considered. Studies were data-extracted and quality assessed by two independent researchers. Outcome measures included the mean change in best corrected visual acuity (BCVA) from baseline in the study eye and/or number of patients gaining at least 10 letters from baseline to 6 months or the nearest equivalent time point.
Results
Fourteen unique randomized controlled trials (RCTs) were identified. Ranibizumab 0.5 mg produced greater improvements in BCVA at 6 months than sham in BRVO (mean difference 11.0 letters, 95% confidence interval [CI] 7.83, 14.17) and CRVO (mean difference 14.10 letters, 95% CI 10.51, 17.69) in two double-blind sham-controlled RCTs. Pooled data from two double-blind, sham-controlled RCTs showed that improvements in BCVA were also significantly better for dexamethasone intravitreal (IVT) implant 0.7 mg compared with sham in patients with BRVO or CRVO (mean difference 2.5 letters, 95% CI 0.7, 4.3); the difference was significant for BRVO alone, but not CRVO alone. A significantly greater proportion of patients with BRVO gained ≥15 letters with laser therapy vs. no treatment at 36 months in a large prospective RCT (odds ratio 3.16, 95% CI 1.25, 8.00), whereas no difference was observed at 9 months in a smaller study. Three studies reported no benefit for laser therapy in CRVO. No indirect comparisons with ranibizumab were feasible due to differences in study design and baseline characteristics.
Conclusions
Data from RCTs for ranibizumab and dexamethasone IVT demonstrate that both new agents constitute significant improvements over the previously widely accepted standard of care (laser therapy) for the treatment of BRVO and CRVO. However, head-to-head studies are needed to assess the relative efficacies of licensed therapies for RVO.
doi:10.1186/1471-2415-14-7
PMCID: PMC3904417  PMID: 24447389
Retinal vein occlusion; Ranibizumab; Dexamethasone intravitreal; Laser; Branch retinal vein occlusion; Central retinal vein occlusion
20.  Refractive change in the adult rabbit eye after corneal relaxation with the femtosecond laser 
BMC Ophthalmology  2014;14:8.
Background
A new procedure to correct myopia that does not disturb the cornea in the optical zone and avoids injuring the corneal epithelium could be a key advance in corneal refractive surgery. The aim of this study is to observe the refractive change in the adult rabbits undergoing femtosecond laser-assisted multilayer intrastromal ablation in the mid-periphery of the cornea without injury of epithelium.
Method
The right eyes of 8 New Zealand White adult rabbits were used for the experiments. A 60-kHz femtosecond laser delivery system was used, and three lamellar layers of laser pulses were focused starting at a corneal depth of 180 μm and ending at 90 μm from the surface, with each successive layer placed 45 μm anterior to the previous layer. In the interface of the applanation contact lens cone, a 6-mm diameter aluminum circle was placed at the center to block the laser, limiting ablation to the mid-periphery of the cornea. The laser settings were as follows: spot/line separation, 10 μm; diameter, 8.0 mm; energy for ablating the stroma, 1.3 μJ. An authorefractor was used to assess the manifest refraction.
Results
Mean spherical equivalent (SE) (mean ± SD, SD: standard deviation) was significantly increased at postoperative week 1 (1.67 ± 0.26 D, p < 0.0001), month 1 (1.65 ± 0.23 D, p < 0.0001), and month 3 (1.60 ± 0.22 D, p < 0.0001) compared to baseline (0.68 ± 0.27 D). Mean spherical equivalent showed no significant change between postoperative week 1 and month 3 (p = 0.1168).
Conclusion
Femtosecond laser-assisted multilayer corneal intrastromal ablation in the mid-periphery may cause a consequent hyperopic shift with no refractive regression.
doi:10.1186/1471-2415-14-8
PMCID: PMC3917590  PMID: 24447397
21.  Four-year analysis of cataract surgery rates in Shanghai, China: a retrospective cross-sectional study 
BMC Ophthalmology  2014;14:3.
Background
The cataract surgery rate (CSR) is a critical index used to show that cataract blindness is being eliminated. It is considered to be tightly connected to social economic development; however, it is still extremely low in developing countries such as China. Although Shanghai is the most economically developed city in China, its CSR and the obstacles for increasing its CSR have not been previously evaluated.
Methods
A retrospective cross-sectional study was conducted. By analyzing the data in the “Shanghai Cataract Operations Database” from 2006 to 2009, the CSR in Shanghai was calculated. The numbers of cataract surgeries between urban and suburban districts as well as among various medical institutions were compared.
Results
The CSR in Shanghai increased from 1741 in 2006 to 2210 in 2009, reflecting a 26.94% improvement. Phacoemulsification was the most frequent surgical choice for cataract removal, accounting for 94.93% of total cataract surgeries by 2009. In addition, by 2009, the CSR in urban districts had reached 5468, but only 532 in the suburbs. During 2009, cataract surgery records in 68 district hospitals, 23 medical centers, and 6 private hospitals comprised 32.05%, 52.33%, and 15.62%, respectively, of the total. There was a nearly 3.3-fold increase in the number of surgeries performed in private hospitals in the past four years. Furthermore, the average number of cataract surgeries per doctor that took place in private hospitals per year reached 207, which exceeded the average of 145 that took place in medical centers.
Conclusions
Until 2009, the CSR in Shanghai remained below the rates of social development and fell short of targets suggested by the World Health Organization (WHO). Furthermore, increasing the CSR in the suburbs as well as in district hospitals is an important issue that needs to be addressed.
doi:10.1186/1471-2415-14-3
PMCID: PMC3893501  PMID: 24410915
Cataract surgery rate; Districts; Medical institutions; Restricting factors; Shanghai
22.  Cataract subtype risk factors identified from the Korea National Health and Nutrition Examination survey 2008–2010 
BMC Ophthalmology  2014;14:4.
Background
To assess the socio-demographic and health-related risk factors associated with cataract subtypes in Korea.
Methods
A total of 11,591 participants (aged ≥40 years) were selected from the Korean National Health and Nutrition Examination Survey between 2008 and 2010. The Korean Ophthalmologic Society conducted detailed ophthalmologic examinations on these participants based on the Lens Opacity Classification System III. Risk factors for developing any type of cataract, and its subtypes (nuclear, cortical, posterior subcapsular and mixed), were identified from univariate and multivariate logistic regression analysis.
Results
The prevalence of cataracts was 40.1% (95% CI, 37.8 − 42.3%) in participants over 40 years old. Older age, lower monthly household income, lower education, hypercholesterolemia, hypertension, and diabetes mellitus (DM) were independent risk factors for development of any cataract. Older age, lower monthly household income, lower education, hypercholesterolemia, and DM were independent risk factors for development of pure cortical cataracts. Older age, lower education, metabolic syndrome, and DM were independent risk factors for development of pure nuclear cataracts. Older age and DM were independent risk factors for development of pure posterior subcapsular cataracts. Older age, lower monthly household income, lower education, and DM were independent risk factors for development of mixed cataracts.
Conclusion
Although socioeconomic disparities are related to cataract development, this study identified several “modifiable” risk factors that may help to lower the incidence of cataracts and associated vision loss. Improved control of blood pressure, blood, glucose, and cholesterol may help to reduce the incidence of cataracts in the general Korean population.
doi:10.1186/1471-2415-14-4
PMCID: PMC3928645  PMID: 24410920
Cataract; Cataract subtype; Cataract risk factors; KNHANES
23.  Health literacy of common ocular diseases in Nepal 
BMC Ophthalmology  2014;14:2.
Background
Poor health literacy is often a key cause of lack of or delayed uptake of health care services. The aim of this study was to assess the health literacy of common ocular diseases, namely cataract, glaucoma, night blindness, trachoma and diabetic retinopathy in Nepal.
Methods
A cross sectional study of 1741 participants randomly selected from non-triaged attendants in the outpatient queue at Tilganga Institute of Ophthalmology, a semi urban general population of Bhaktapur district of Kathmandu Valley and patients attending rural outreach clinics. Participants responded to trained enumerators using verbally administered, semi structured questionnaires on their awareness and knowledge of cataract, glaucoma, diabetic retinopathy, night blindness, and trachoma.
Results
The awareness of cataract across the entire sample was 49.6%, night blindness was 48.3%, diabetic retinopathy was 29%, glaucoma was 21.3% and trachoma was 6.1%. Patients presenting to rural outreach clinics had poorer awareness of cataract, glaucoma, diabetic retinopathy, night blindness and trachoma compared to those from a semi-urban community and an urban eye hospital (p<0.05), Old age was directly associated with poorer awareness of cataract, glaucoma, night blindness, trachoma and diabetic retinopathy (p<0.05). Female gender was associated with lower awareness of cataract, glaucoma, night blindness and trachoma (p<0.05). Literacy was associated with greater awareness of cataract, glaucoma, diabetic retinopathy, night blindness and trachoma (p<0.05). Higher education was significantly associated with greater awareness of cataract, night blindness and trachoma (p<0.05). Multivariate analysis found that the awareness of common ocular diseases was significantly associated with level of education (p<0.05). Similarly, awareness of cataract, glaucoma, trachoma and night blindness was associated with female gender (p<0.05) whereas awareness of cataract, night blindness, trachoma and diabetic retinopathy was associated with age (p<0.05) but the awareness glaucoma and diabetic retinopathy was associated with camps.
Conclusions
Low awareness of common ocular conditions is associated with factors such as female gender, old age, lower levels of education and rural habitation. A would be successful health promotion programs should specifically target health determinants to promote health literacy and to ensure timely utilization of eye care services.
doi:10.1186/1471-2415-14-2
PMCID: PMC3898060  PMID: 24400641
Cataract; Diabetic retinopathy; Glaucoma; Health literacy; Nepal; Night blindness; Trachoma
24.  Laser in situ keratomileusis for astigmatism ≤ 0.75 Diopter combined with low myopia: a retrospective data analysis 
BMC Ophthalmology  2014;14:1.
Background
This study examined the refractive and visual outcome of wavefront-optimized laser in situ keratomileusis (LASIK) in eyes with low myopia and compound myopic astigmatism ≤ 0.75 diopter (D).
Methods
153 eyes from 153 consecutive myopic patients (74 male, 79 female; mean age at surgery 40.4 ± 10.4 years) who had a preoperative refractive cylinder ≤ 0.75 D and a manifest sphere between -0.25 D and -2.75 D, and who had completed 4-month follow-up. Three subgroups defined by the magnitude of preoperative manifest refractive cylinder (0.25, 0.50, and 0.75 D) were formed. Manifest refraction, uncorrected and corrected visual acuity were assessed pre- and postoperatively. The astigmatic changes achieved were determined using the Alpins vector analysis.
Results
After 4 months (120.0 ± 27.6 days) of follow-up, a mean uncorrected distant visual acuity of 0.07 ± 0.11 logMAR and a mean manifest refraction spherical equivalent of -0.06 ± 0.56 D were found. There was no statistically significant difference in efficacy and safety between the preoperative cylinder groups. Astigmatic overcorrection for preoperative cylinder of ≤ 0.50 D was suggested by the correction index, the magnitude of error, the index of success, and the flattening index.
Conclusions
Low myopic eyes with a preoperative cylinder of ≤ 0.50 D were significantly overcorrected with regard to cylinder correction when combined with low myopic LASIK. Accordingly, we are cautious in recommending full astigmatic correction for eyes with low myopia and manifest cylinder of ≤ 0.50 D.
doi:10.1186/1471-2415-14-1
PMCID: PMC3890523  PMID: 24393469
Alpins vector method; Cylinder axis; Induced astigmatism; Laser in situ keratomileusis; Low astigmatism; Low myopia
25.  Risk factors of a reduced response to ranibizumab treatment for neovascular age-related macular degeneration – evaluation in a clinical setting 
BMC Ophthalmology  2013;13:84.
Background
To identify risk factors for being a “reduced responder” to ranibizumab treatment in a clinical setting in patients with neovascular age-related macular degeneration.
Methods
This retrospective study included 165 eyes of 165 consecutive patients with choroidal neovascularisation secondary to neovascular, age-related macular degeneration. Eyes were treated with three intravitreal injections of ranibizumab, followed by PRN (pro re nata) dosing thereafter. All patients were reevaluated every four weeks and then followed for six months. Reduced responders were defined as patients with a loss in visual acuity of at least 1 visual acuity line at the last follow-up and/or persistent intraretinal or subretinal fluid or detectable choroidal neovascularisation at the last follow-up, compared to baseline.
Results
Overall, 58 out of 165 eyes (35.2%) were considered to be reduced responders to treatment at the end of follow-up. The initial CNV size at baseline was correlated with the risk of being a reduced responder at the end of follow-up (p = 0.017).
Conclusion
We identified the initial lesion size as a predictor for a reduced response to treatment in this study. Patients with a large initial lesion size should be thoroughly informed about the possible poorer response to the intravitreal treatment.
doi:10.1186/1471-2415-13-84
PMCID: PMC3878195  PMID: 24359591
Ranibizumab; Lucentis; Age-related macular degeneration; Response to treatment

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