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26.  The effect of incorrect scanning distance on boundary detection errors and macular thickness measurements by spectral domain optical coherence tomography: a cross sectional study 
BMC Ophthalmology  2014;14(1):148.
To investigate the influence of scan distance on retinal boundary detection errors (RBDEs) and retinal thickness measurements by spectral domain optical coherence tomography (SD-OCT).
10 eyes of healthy subjects, 10 eyes with diabetic macular edema (DME) and 10 eyes with neovascular age-related macular degeneration (AMD) were examined with RTVue SD-OCT. The MM5 protocol was used in two consecutive sessions to scan the macula. For the first session, the device was set 3.5 cm from the eye in order to obtain detectable signal with low fundus image quality (suboptimal setting) while in the second session a distance of 2.5 cm was set with a good quality fundus image. The signal strength (SSI) value was recorded. The score for retinal boundary detection errors (RBDE) was calculated for ten scans of each examination. RBDE scores were recorded for the whole scan and also for the peripheral 1.0 mm region. RBDE scores, regional retinal thickness values and SSI values between the two sessions were compared. The correlation between SSI and the number of RBDEs was also examined.
The SSI was significantly lower with suboptimal settings compared to optimal settings (63.9±12.0 vs. 68.3±12.2, respectively, p = 0.001) and the number of RBDEs was significantly higher with suboptimal settings in the “all-eyes” group along with the group of healthy subjects and eyes with DME (9.1±6.5 vs. 6.8±6.3, p = 0.007; 4.4±2.6 vs. 2.5±1.6, p = 0.035 and 9.7±3.3 vs. 5.1±3.7, p = 0.008, respectively). For these groups, significant negative correlation was found between the SSI and the number of RBDEs. In the AMD group, the number of RBDEs was markedly higher compared to the other groups and there was no difference in RBDEs between optimal and suboptimal settings with the errors being independent of the SSI. There were significantly less peripheral RBDEs with optimal settings in the “all-eyes” group and the DME subgroup (2.7±2.6 vs. 4.2±2.8, p = 0.001 and 1.4±1.7 vs. 4.1±2.2, p = 0.007, respectively). Retinal thickness in the two settings was significantly different only in the outer-superior region in DME.
Optimal distance settings improve SD-OCT SSI with a decrease in RBDEs while retinal thickness measurements are independent of scanning distance.
PMCID: PMC4280767  PMID: 25428608
Optical coherence tomography; Image segmentation; Imaging pitfalls; Diabetic retinopathy; Macular degeneration
27.  Overexpression p21WAF1/CIP1 in suppressing retinal pigment epithelial cells and progression of proliferative vitreoretinopathy via inhibition CDK2 and cyclin E 
BMC Ophthalmology  2014;14(1):144.
P21 is one kind of cyclin-dependent kinase inhibitor that can prevent cells from going through the G1/S phase checkpoint and inhibit cell proliferation. Proliferative vitreoretinopathy (PVR) is a proliferative response in the eye. The aim of this study was to determine whether p21Waf1/Cip1 (p21) suppresses the proliferation and migration of retinal pigment epithelial (RPE) cells in vitro and controls PVR development in vivo.
Cell cycle analyses and transwell assays were conducted to assess cell proliferation characteristics and the migration ability of RPE cells after transfection with p21. Western blot and reverse-transcription polymerase chain reaction technologies were used to detect the expression of p21, CDK2 and cyclinE in RPE cells and rabbit retinal tissues. The impact of increasing p21 expression on PVR development was conducted by implantation of an adenovirus vector containing rabbit p21 (rAd-p21) in a PVR rabbit model. The prevalence of PVR and retinal detachment was determined by indirect ophthalmoscopy on days 3, 7, 14, and 21 after the injection of rAd-p21 into the vitreous. B scans and hematoxylin-eosin staining were employed to check rabbit retinas on day 21.
Cell cycle analyses and transwell assays showed that p21 inhibited the proliferation and migration of RPE cells. Increased expression of p21 was detected in cultured RPE cells and rabbit retinas after transfection with the p21 gene, whereas levels of CDK2 and cyclinE were decreased. The increase in p21 expression effectively suppressed the development of PVR in a rabbit model.
The increase in p21 expression in RPE cells not only inhibits the proliferation and migration of RPE cells in vitro, but also suppresses the development of PVR in vivo, which indicates its therapeutic potential in treating PVR.
PMCID: PMC4255444  PMID: 25421815
P21Waf1/Cip1; Cell cycle arrest; Retinal pigment epithelial cells; Proliferative vitreoretinopathy
28.  Choroidal thickness measurement by enhanced depth imaging and swept-source optical coherence tomography in central serous chorioretinopathy 
BMC Ophthalmology  2014;14(1):145.
We evaluated subfoveal choroidal thickness measured with two different forms of optical coherence tomography (OCT), enhanced-depth imaging (EDI) and swept-source (SS) OCT, in central serous chorioretinopathy (CSC).
Fifty-six eyes of 48 patients diagnosed with acute or chronic CSC, were studied prospectively. Subfoveal choroidal thickness was measured as the distance between the outer border of the retinal pigment epithelium-Bruch’s membrane complex, and the chorioscleral border under the fovea. Subfoveal choroidal thickness was measured using EDI-OCT and SS-OCT. We also measured serous retinal detachment (SRD) only with SS-OCT. The Pearson correlation coefficient was used to assess the correlation between subfoveal choroidal thickness values determined by the two different OCT modalities.
The mean patient age was 52 ± 13 years (range, 32–82 years). Among the 56 eyes, 21 had acute CSC and 35 had chronic CSC. Subfoveal choroidal thickness measured with EDI-OCT was 336.6 ± 91.6 μm in acute and 388.0 ± 103.4 μm in chronic CSC. With SS-OCT, the thickness in acute CSC was 332.0 ± 96.7 μm and that in chronic CSC was 392.6 ± 101.3 μm. Acute CSC (p <0.001, correlation coefficient; r = 0.99) and chronic CSC (p <0.001, correlation coefficient; r = 0.97) values obtained with the two different OCT modalities correlated significantly. Among the 56 eyes, 43 (19 eyes with acute and 24 with chronic CSC) were evaluable for SRD height by SS-OCT. The mean SRD height was 128.9 ± 83.6 μm in acute cases and 96.3 ± 62.0 μm in chronic cases.
Subfoveal choroidal thickness obtained with two different OCT modalities correlated significantly.
PMCID: PMC4255445  PMID: 25421855
29.  Retinal microvascular abnormalities overlying choroidal nodules in neurofibromatosis type 1 
BMC Ophthalmology  2014;14(1):146.
Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder involving aberrant proliferation of multiple tissues of neural crest origin. Retinal vascular alterations in NF1 have rarely been reported in the literature and their nature is not clear. This study describes distinctive retinal microvascular alterations and their relationship to choroidal nodules in patients with neurofibromatosis type 1.
This was a retrospective study where records of seventeen consecutive patients with diagnosis of NF1, presenting Lisch nodules and choroidal alterations, and 17 age and gender-matched healthy control patients were evaluated. Fundus photographs, near infrared reflectance and enhanced depth imaging - optical coherence tomography images were reviewed. Retinal microvascular abnormalities and choroidal and retinal alterations in proximity of the retinal microvacular alterations were carefully noted.
6 patients (35%) presented distinctive microvascular abnormalities. These consisted of small, tortuous vessels with a “spiral” or “corckscrew” aspect. They were second or third order, small tributaries of the superior or inferior temporal vein. These vessels were all located overlying choroidal alterations as observed with near infrared reflectance. Enhanced depth imaging - optical coherence tomography showed alteration of choroidal vasculature due to the presence of choroidal nodules but otherwise retinal and choroidal cross-sections were unremarkable for morphology.
Retinal microvascular alterations overlying choroidal nodules in patients with NF1 can be considered another distinctive characteristic of the disease. Although the nature of these alterations is not clear, the authors speculate that functional disorders of vasomotor nerve cells, which originate in the embryonal neural crest can lead to their formation.
PMCID: PMC4258815  PMID: 25424184
Neurofibromatosis type 1; Retinal microvascular alterations; Near infrared reflectance; Optical coherence tomography-enhanced depth imaging; Phakomatoses
30.  Rare ocular features in a case of Kabuki syndrome (Niikawa-Kuroki syndrome) 
BMC Ophthalmology  2014;14(1):143.
Kabuki syndrome is a multi-system disorder with peculiar facial features, and ophthalmic abnormalities are frequently involved. This case report of a child with Kabuki syndrome describes two new previously unreported ophthalmic conditions.
Case presentation
A 3-year-old Taiwanese boy with Kabuki syndrome had a short stature, spinal dysraphism, intellectual disability and typical facial features. Ophthalmic findings which have been previously reported in the literature and in this patient, included ptosis, esotropia, coloboma of the iris, retina, choroid and optic disc, and microcornea. The newly identified ophthalmic features in this patient included colobomatous microphthalmos and a dysplastic and elevated disc without central cupping. The genetic analysis identified an MLL2 gene mutation.
The presentations of a dysplastic disc and colobomatous microphthalmia are rarely reported in patients with Kabuki syndrome, but these ophthalmic abnormalities may affect vision. Detailed ophthalmic evaluations in children with Kabuki syndrome are advised.
PMCID: PMC4251844  PMID: 25421742
Kabuki syndrome; Colobomatous microphthalmia; Optic disc dysplasia; MLL2 gene mutation
31.  Achromobacter buckle infection diagnosed by a 16S rDNA clone library analysis: a case report 
BMC Ophthalmology  2014;14(1):142.
In clinical settings, bacterial infections are usually diagnosed by isolation of colonies after laboratory cultivation followed by species identification with biochemical tests. However, biochemical tests result in misidentification due to similar phenotypes of closely related species. In such cases, 16S rDNA sequence analysis is useful. Herein, we report the first case of an Achromobacter-associated buckle infection that was diagnosed by 16S rDNA sequence analysis. This report highlights the significance of Achromobacter spp. in device-related ophthalmic infections.
Case presentation
A 56-year-old woman, who had received buckling surgery using a silicone solid tire for retinal detachment eighteen years prior to this study, presented purulent eye discharge and conjunctival hyperemia in her right eye. Buckle infection was suspected and the buckle material was removed. Isolates from cultures of preoperative discharge and from deposits on the operatively removed buckle material were initially identified as Alcaligenes and Corynebacterium species. However, sequence analysis of a 16S rDNA clone library using the DNA extracted from the deposits on the buckle material demonstrated that all of the 16S rDNA sequences most closely matched those of Achromobacter spp. We concluded that the initial misdiagnosis of this case as an Alcaligenes buckle infection was due to the unreliability of the biochemical test in discriminating Achromobacter and Alcaligenes species due to their close taxonomic positions and similar phenotypes. Corynebacterium species were found to be contaminants from the ocular surface.
Achromobacter spp. should be recognized as causative agents for device-related ophthalmic infections. Molecular species identification by 16S rDNA sequence analysis should be combined with conventional cultivation techniques to investigate the significance of Achromobacter spp. in ophthalmic infections.
PMCID: PMC4255664  PMID: 25421607
32.  The control effect of orthokeratology on axial length elongation in Chinese children with myopia 
BMC Ophthalmology  2014;14(1):141.
To retrospectively compare axial elongation in children with different degrees of myopia wearing spectacles and undergoing ortho-k treatment.
The medical records of 128 patients who were fitted with spectacles or orthokeratology (ortho-k) lenses in our clinic between 2008 and 2009 were reviewed. Ortho-k group comprised 65 subjects and 63 subjects wearing spectacles were included in the control group. Subjects were also divided into low-myopia, moderate-myopia and high-myopia groups, based on the basic spherical equivalent refractive error. Axial length periodically measured over 2-year of lens wear and changes in axial length were compared between treatment groups and between subgroups with different degrees of myopia.
The control group exhibited more changes in axial length than the ortho-k group at both 12 months (0.39 ± 0.21 mm vs 0.16 ± 0.17 mm, p <0.001) and 24 months (0.70 ± 0.35 mm vs 0.34 ± 0.29 mm, p <0.001). Axial length elongation was estimated to be slower by about 51% in the ortho-k group. Similar results were found for the subgroups (49%, 59% and 46% reductions, respectively). In the group with low and moderate myopia, the annual increases in axial length were significantly different between the ortho-k and control groups during both the first ( Low myopia: 0.19 ± 0.17 mm vs 0.40 ± 0.18 mm, p = 0.001; Moderate myopia: 0.14 ± 0.18 mm vs 0.45 ± 0.22 mm, p <0.001) and second ( Low myopia: 0.18 ± 0.14 mm vs 0.32 ± 0.19 mm, p = 0.012; Moderate myopia: 0.18 ± 0.16 mm vs 0.34 ± 0.30 mm, p = 0.030) years. In the high myopia groups, significant differences were only found between the ortho-k and control groups during the first year (0.16 ± 0.18 mm vs 0.34 ± 0.22 mm, p = 0.004). The 2-year axial elongation was significantly associated with initial age (p <0.001) and treatment (p <0.001), but not with gender, initial refractive error, initial axial length, initial corneal curvature.
This 2-year study indicates that ortho-k contact lens wear is effective for reducing myopia progression in children with low, moderate and high myopia.
PMCID: PMC4280707  PMID: 25417926
Myopia; Orthokeratology; Axial length; Retrospective analysis
33.  Funduscopic results after 4-year follow-up treatment with ranibizumab for age-related macular degeneration in a region of Spain 
BMC Ophthalmology  2014;14(1):138.
The study aims to survey longstanding funduscopic and functional outcomes of age-related macular degeneration (AMD) after ranibizumab treatment and verify the accuracy of a new method to compare the retinal thickness measured with different optical coherence tomography (OCT) tools.
Case series included 314 eyes with 2–4 years of follow-up. Main Outcome Measures were visual acuity (VA), number of injections, retinal thickness, OCT morphology, and final macular funduscopic status.
One hundred twenty-two men and 177 women (mean age, 78.3 years) were included. The mean time to the first injection was 17.3 ± 14.6 days. Initial VA was O.8(20/125) ± 0.5; 0.7(20/100) ± 0.5 at 3 months; 0.8(20/125) ± 0.5 at a year; 1(20/200) ± 0.6 at year 2; 1(20/200) ± 0.6 at year 3 and 1.1(20/250) ± 0.6 at year 4. Number of visits at 3 months was 2.7 ± 0.8; 7.3 ± 2.1 at a year; 5.2 ± 2.7 along the 2nd year; 3.9 ± 2.3 at year 3 and 3.6 ± 2.2 at year 4. Number of injections at 3 months was 2.6 ± 0.5; 3.9 ± 1.5 at a year; 1.1 ± 1.5 along the 2nd year; 1.5 ± 2.4 at year 3 and 1.8 ± 3.1 at year 4. Patients with worse VA outcomes received more injections and were older. The formula to calculate changes in retinal thickness showed a 30% reduction in thickness, which correlated well with the OCT morphology. Patients with polypoidal choroidal vasculopathy (PCV) had a worse final outcome. The final disciform macular status (37%) was related to fewer injections and a greater decrease in thickness. Final well-preserved maculas (12.%) needed more injections and treatment changes; those that were atrophic at the final visit (30.8%) had a worse initial VA and greater decrease in thickness at the 3-month visit.
Younger patients had better final outcomes. Our method to compare retinal thickness using different OCT tools worked well. The final visual outcome after a long follow-up was poor, which may be related to advanced age, poor initial VA, and the high incidence of final fibrosis or atrophy.
PMCID: PMC4251670  PMID: 25416399
Age-related macular degeneration (AMD); Ranibizumab; Optical coherence tomography (OCT); Atrophy; Disciform scar; Outcome
34.  Association of rs6982567 near GDF6 with neovascular age-related macular degeneration and polypoidal choroidal vasculopathy in a Han Chinese cohort 
BMC Ophthalmology  2014;14(1):140.
Growth differentiation factor 6 (GDF6) has been reported to be a novel disease gene for age-related macular degeneration (AMD) in Caucasians. This study aimed to investigate whether rs6982567 was associated with neovascular AMD (nAMD) or polypoidal choroidal vasculopathy (PCV) in a Han Chinese cohort.
A total of 612 participants (251 PCV patients, 157 nAMD patients and 204 controls) were included in this study. The SNaPshot system was used to genotype the rs6982567. PLINK software was used to evaluate the genotypes and allele frequencies of patients and controls.
The allele frequencies of rs6982567 were not significantly associated with nAMD, PCV or PCV and nAMD combined. Subjects with the TT genotype had a 2.42-fold greater risk of PCV (95% confidence interval, 1.07-5.43, p = 0.0290) than subjects with CC genotype. A recessive model of rs6982567 was statistically significantly associated with PCV (odds ratio, 2.29; 95% confidence interval, 1.04-5.05; p = 0.0351). However, the association did not withstand stringent Bonferroni correction. There were no significant differences in genotype distributions or models in nAMD.
There was a possible weak association between the rs6982567 near GDF6 and PCV in this replication study with an independent Han Chinese cohort. A complete survey of the GDF6 locus with a larger sample size is needed in future studies.
PMCID: PMC4251681  PMID: 25416513
Han Chinese population; Neovascular age-related macular degeneration; Polypoidal choroidal vasculopathy; Polymorphisms; Growth differentiation factor 6
35.  Comparison of the Adult Strabismus Quality of Life Questionnaire (AS-20) with the Amblyopia and Strabismus Questionnaire (ASQE) among adults with strabismus who seek medical care in China 
BMC Ophthalmology  2014;14(1):139.
The impact of strabismus on visual function, self-image, self-esteem, and social interactions might decrease health-related quality of life (HRQoL). This study aimed to evaluate the psychometric properties and clinical applications of two strabismus-specific HRQoL questionnaires in the cultural context of China.
The Chinese versions of the Adult Strabismus Quality of Life Questionnaire (AS-20) and the Amblyopia and Strabismus Questionnaire (ASQE) were self-administered to 304 adults with strabismus. The Cronbach’s α coefficient was calculated to assess the internal consistency reliability. The criterion-related validity was identified by exploring Spearman’s correlation with the most widely used vision-specific quality of life questionnaire NEI-VFQ-25. One-way ANOVA was employed to examine the differences in the quality of life of strabismus patients with visually normal adults and with other eye diseases patients.
Significantly positive correlations with NEI-VFQ-25 were shown in both scales (r = 0.21 - 0.44, p <0.05, p <0.01). Both scales could distinguish individuals with strabismus from visually normal adults (p <0.001) and adults with other eye diseases (p <0.001). The overall Cronbach’s α value were 0.91 for the AS-20 and 0.89 for the ASQE; and for the subscales, the α value ranged from 0.68 to 0.90.
This was the first cross-sectional study to compare the psychometric properties of two strabismus-targeted questionnaires, AS-20 and ASQE in the context of Chinese culture. Both AS-20 and ASQE showed satisfactory and comparable properties for measuring HRQoL in strabismus patients.
PMCID: PMC4258794  PMID: 25416453
Quality of life; Adult strabismus; Questionnaire; Chinese
36.  Lying-down nystagmus and head-bending nystagmus in horizontal semicircular canal benign paroxysmal positional vertigo: are they useful for lateralization? 
BMC Ophthalmology  2014;14(1):136.
Lateralization of horizontal semicircular canal benign paroxysmal positional vertigo (HSC-BPPV) is very important for successful repositioning. The directions of lying-down nystagmus (LDN) and head-bending nystagmus (HBN) have been used as ancillary findings to identify the affected sites. This retrospective study was performed to evaluate the lateralizing values of LDN and HBN using clinical and laboratory findings for lateralizing probabilities in patients with HSC-BPPV.
For 50 HSC-BPPV patients with asymmetric direction-changing horizontal nystagmus (DCHN) during the head-rolling test (HRT) using Frenzel goggles, the directions of LDN and HBN were evaluated and compared to those determined by video-oculography. Directional LDN was defined as the contralesional direction of nystagmus in geotropic types and the ipsilesional direction in apogeotropic types. Directional HBN was defined as the opposite direction relative to directional LDN. We also analyzed LDN and HBN in 14 patients with a history of ipsilesional peripheral vestibulopathy, caloric abnormality or conversion from other types of BPPV (such as probable localized HSC-BPPV, pro-BPPV).
LDN and HBN were seen in 68% (34/50) and 76% (38/50) of patients, respectively. Of these, 19 (55.9%), and 28 (73.7%) patients showed directional LDN and HBN, respectively. The proportion of patients with directional LDN and HBN was much smaller among the pro-BPPV patients (4/12 for LDN, 3/10 for HBN).
LDN and HBN did not seem to predict lateralization in patients with HSC-BPPV. To improve the prediction of lateralization of HSC-BPPV, it is necessary to modify the maneuvers used to elicit LDN or HBN, especially in cases of symmetric DCHN during HRT.
PMCID: PMC4246445  PMID: 25413310
Benign paroxysmal positional vertigo; Nystagmus; Semicircular canals
37.  Acquired focal choroidal excavation associated with multiple evanescent white dot syndrome: observations at onset and a pathogenic hypothesis 
BMC Ophthalmology  2014;14(1):135.
The mechanism underlying focal choroidal excavation (FCE) remains largely unknown. We evaluated the sequential progression of FCE generation using enhanced depth imaging optical coherence tomography (EDI-OCT) in a patient with multiple evanescent white dot syndrome (MEWDS).
Case presentation
A 37-year-old woman suffered MEWDS in the right eye. EDI-OCT showed the loss of photoreceptor inner segment/outer segment junction line, detachment between the retinal pigment epithelium (RPE) and Bruch’s membrane, and dome-shaped, moderately reflective, focal photoreceptor-layer lesions corresponding to perifoveal white dots. The region with pigment epithelium detachment involved RPE/Bruch’s membrane ruptures. After 1 month, almost all white dots spontaneously resolved together with improvements of the perifoveal OCT findings. Interestingly, perifoveal region developed a conforming-type FCE. An abnormal hyper-reflective lesion on OCT, regarded as fibrosis formation, simultaneously appeared within the choroid below the FCE and subsequently increased in size.
These results suggest that the RPE/Bruch’s membrane disruption due to chorioretinal abnormalities and subsequent intrachoroidal scar formation play a role in the pathogenesis on an acquired FCE.
PMCID: PMC4246602  PMID: 25410093
Choroidal thickness; Enhanced depth imaging optical coherence tomography; Focal choroidal excavation; Multiple evanescent white dot syndrome
38.  Effects of extraocular muscle surgery in children with monocular blindness and bilateral nystagmus 
BMC Ophthalmology  2014;14(1):137.
Monocular infantile blindness may be associated with bilateral horizontal nystagmus, a subtype of fusion maldevelopment nystagmus syndrome (FMNS). Patients often adopt a significant anomalous head posture (AHP) towards the fixing eye in order to dampen the nystagmus. This clinical entity has also been reported as unilateral Ciancia syndrome. The aim of the study was to ascertain the clinical features and surgical outcome of patients with FMNS with infantile unilateral visual loss.
In this retrospective case series, nine consecutive patients with FMNS with infantile unilateral visual loss underwent strabismus surgery to correct an AHP and/or improve ocular alignment. Outcome measures included amount of AHP and deviation at last follow-up.
Eye muscle surgery according to the principles of Kestenbaum resulted in a marked reduction or elimination of the AHP. On average, a reduction of AHP of 1.3°/mm was achieved by predominantly performing combined horizontal recess-resect surgery in the intact eye. In cases of existing esotropia (ET) this procedure also markedly reduced the angle of deviation. A dosage calculation of 3 prism diopters/mm was established.
We advocate a tailored surgical approach in FMNS with infantile unilateral visual loss. In typical patients who adopt a significant AHP accompanied by a large ET, we suggest an initial combined recess-resect surgery in the intact eye. This procedure regularly led to a marked reduction of the head turn and ET. In patients without significant strabismus, a full Kestenbaum procedure was successful, while ET in a patient with a minor AHP was corrected by performing a bimedial recession.
PMCID: PMC4255448  PMID: 25413480
Monocular blindness; Manifest latent nystagmus
39.  Preliminary study of the association between corneal histocytological changes and surgically induced astigmatism after phacoemulsification 
BMC Ophthalmology  2014;14(1):134.
Surgically induced astigmatism (SIA) was one of the factors that influences the desirable refractive outcome, and it was related to the length, type, location, structure of the incision and to the suture closure technique, etc. The aim was to evaluate the association of corneal histocytological changes with SIA after phacoemulsification.
The study enrolled 68 cases of cataract patient (68 eyes). Corneal histocytological parameters at corneal incision, central cornea and contralateral incision obtained by confocal microscope through focusing (CMTF) were compared preoperatively and 1 week, 2 weeks, 1 month, 3 months and 6 months postoperatively. These biometric parameters included the endothelial cell density, keratocyte density of posterior stromal layer, and the morphological changes. SIA was calculated by Jaffe’s vector analysis.
1 From preoperatively to 1 week, 2 weeks, 1 month, 3 months and 6 months postoperatively, the endothelail cell density was decreased significantly (p < 0.05). Keratocyte density of posterior stroma layer was increased significantly only at 1 week, 2 weeks, 1 month, 3 months postoperatively (p <0.05), but not statistically significant (p = 0.173) at 6 months postoperatively compared to preoperative values. 2 The histocytological observations indicated that the morphology changed significantly postoperatively at the corneal incision, including the cell absent area, wave-like area, dot-like and mass-like hyperreflection, stripe-like absent area, in the endothelial layer, and the keratocyte activation, microfolds, irregular hyporeflective or hyperreflective belt, and a little dot-like hyperreflection in the posterior stroma layer. 3 The reduction of the endothelial cell density at the corneal incision at 1 week, 2 weeks, 1 month postoperatively, were positively correlated with SIA (P1 week = 0.003, P2 weeks = 0.003, P1 month = 0.032), while others were not associated with SIA statistically.
The reduction of endothelail cell density and the histocytological changes at the corneal incision were associated with SIA. The underlining mechanism needs further study.
Electronic supplementary material
The online version of this article (doi:10.1186/1471-2415-14-134) contains supplementary material, which is available to authorized users.
PMCID: PMC4256752  PMID: 25409954
Cataract; Phacoemulsification; Corneal endothelium; Corneal keratocytes; Confocal microscopy; SIA
40.  Retinal ganglion cell analysis in multiple evanescent white dot syndrome 
BMC Ophthalmology  2014;14(1):132.
Multiple evanescent white dot syndrome (MEWDS) is an acute and usually unilateral retinopathy that occurs predominantly in young adults. This report presents the outcomes of ganglion cell analysis (GCA) in MEWDS.
Case presentation
A 41-year-old woman was diagnosed as MEWDS in right eye. At her initial visit, the deviation map of the ganglion cell analysis showed there was a decrease of the ganglion cell layer (GCL) + inner plexiform layer (IPL) thickness in both eyes, even though her left eye was not affected. A 29-year-old woman was also diagnosed as MEWDS in right eye. Although the deviation map of ganglion cell analysis showed there was a decrease of the GCL + IPL thickness in both eyes at her initial visit, her right eye was not affected.
GCA indicated there was a decrease (<1% of the distribution of normals) of the ganglion cell layer + inner plexiform layer thickness in both the affected and fellow eyes in 7 of 9 patients diagnosed as MEWDS in our hospital. Although the lesions responsible for MEWDS are thought to disrupt the photoreceptor outer segments, we observed changes in the inner retina in both the affected and fellow eye of MEWDS patients.
PMCID: PMC4251852  PMID: 25407162
Optical coherence tomography; Ganglion cell analysis; MEWDS
41.  A case of phacolytic glaucoma with anterior lens capsule disruption identified by scanning electron microscopy 
BMC Ophthalmology  2014;14(1):133.
Phacolytic glaucoma is induced by lens protein or macrophages that have leaked through a macroscopically intact anterior lens capsule. Here, we report a case of phacolytic glaucoma with anterior lens capsule disruptions visualized by scanning electron microscopy (SEM).
Case presentation
A 71-year-old man was referred to our institute for increased intraocular pressure (IOP) in the right eye. Slit-lamp biomicroscopic examination revealed corneal edema, the presence of inflammatory cells and iridescent crystalline in the anterior chamber, and a hypermature cataract in the right eye. Despite treatment with topical glaucoma medication (0.15% brimonidine, 1% brinzolamide/0.5% timolol, and 0.03% bimatoprost) and systemic mannitol, his IOP remained uncontrolled. Light microscopy was used to examine the aqueous humor obtained via anterior chamber paracentesis and the anterior lens capsule obtained via intracapsular cataract extraction (ICCE), which revealed that the anterior lens capsule was intact. However, SEM revealed full-thickness disruptions in the anterior lens.
This is the first reported case of phacolytic glaucoma with disruptions of the anterior lens capsule confirmed by SEM.
PMCID: PMC4251857  PMID: 25407294
Phacolytic glaucoma; Lens capsule; Scanning electron microscopy (SEM)
42.  Optical coherence tomography for an in-vivo study of posterior-capsule-opacification types and their influence on the total-pulse energy required for Nd:YAG capsulotomy: a case series 
BMC Ophthalmology  2014;14(1):131.
Posterior capsule opacification (PCO) is the most common post-operative complication associated with cataract surgery and is mostly treated with Nd:YAG laser capsulotomy. Here, we demonstrate the use of high-resolution spectral-domain optical coherence tomography (OCT) as a technique for PCO analysis. Additionally, we evaluate the influence of PCO types and the distance between the intraocular lens (IOL) and the posterior capsule (PC), i.e., the IOL/PC distance, on the total-pulse energy required for the Nd:YAG laser posterior capsulotomy.
47 eyes with PCO scheduled for the Nd:YAG procedure were examined and divided into four categories: fibrosis, pearl, mixed type and late-postoperative capsular bag distension syndrome. Using custom-made computer software for OCT image analysis, the IOL/PC distances in two dimensions were measured. The IOL/PC distances were compared with those of a control group of 15 eyes without PCO. The influence of the different PCO types and the IOL/PC distance on the total-pulse energy required for the Nd:YAG procedure was analyzed.
The total-pulse energy required for a laser capsulotomy differs significantly between PCO types (p = 0.005, Kruskal-Wallis test). The highest energy was required for the fibrosis PCO type, followed by mixed, pearl and late-postoperative capsular bag distension syndrome. The IOL/PC distance also significantly influenced the total-pulse energy required for laser capsulotomy (p = 0.028, linear regression). Lower total-pulse energy was expected for a larger IOL/PC distance.
Our study indicates that the PCO types and the IOL/PC distance influence the total-pulse energy required for Nd:YAG capsulotomy. The presented OCT method has the potential to become an additional tool for PCO characterization. Our results are important for a better understanding of the photodisruptive mechanisms in Nd:YAG capsulotomy.
PMCID: PMC4273457  PMID: 25403826
Capsular bag distension syndrome; Capsulotomy; High-resolution spectral-domain optical coherence tomography; Nd:YAG; Posterior capsule opacification
43.  ‘’The association of normal tension glaucoma with Buerger’s disease: a case report‘’ 
BMC Ophthalmology  2014;14(1):130.
To report a case of a 48-year-old man with Buerger’s disease who presented with bilateral normal-tension glaucoma (NTG).
Case presentation
A 48-year-old man who had been diagnosed with Buerger’s disease 12 years ago, and received bilateral below-the-knee amputations for ischemic ulcers of the lower limbs, presented at our clinic due to a sudden loss of visual acuity in the left eye. A fundus exam revealed a cup-to-disc ratio of 0.5 for the right eye and 0.8 for the left eye, arteriolar constriction in both eyes, retinal edema in the inferopapillary area, and splinter hemorrhages and soft exudate in the left eye. We diagnosed the patient as having acute nasal branch retinal artery occlusion in the left eye and bilateral NTG, as a result of the ophthalmologic examination and the other findings.
Although the pathomechanism of NTG is still unknown, previous studies have suggested that patients with NTG show a higher prevalence of vasospastic disorders. We present the second report of NTG associated with Buerger’s disease to be described in the literature.
PMCID: PMC4246490  PMID: 25394691
Buerger’s disease; Normal tension glaucoma; Branch retinal artery occlusion
44.  Evaluation of a new method of irrigation and aspiration for removal of ophthalmic viscoelastic device during cataract surgery in a porcine model 
BMC Ophthalmology  2014;14(1):129.
To determine if a method for irrigation and aspiration (I/A) during cataract surgery provides effective removal of ophthalmic viscoelastic device (OVD).
Japanese porcine eyes were used to evaluate I/A performance with Technique 1 (the I/A tip placed on the center of the anterior surface of the IOL), Technique 2 (the I/A tip alternately pressed near the edge of the IOL optic anterior surface on one side and then the other to tilt the IOL back and forth), and Technique 3 (the I/A tip inserted behind the IOL optic, between it and the posterior capsule). Techniques 1 and 2 were compared using the Miyake-Apple posterior view video technique to visualize the flow of irrigation fluid containing triamcinolone acetonide particles behind the IOL. To check the efficacy of OVD removal from behind the IOL for of all three I/A techniques, OVD with fluorescein beads were inserted inside the lens capsule before implantation of the IOL. After each I/A technique, eyes were prepared for Miyake–Apple viewing and pictures of the lens capsule were taken using fluorescent microscopy. Residual fluorescein beads in the capsular bag were analyzed.
Technique 1 resulted in a straight flow of fluid behind the IOL, while Technique 2 resulted in a vortex flow. The average amount of OVD retained inside the capsule after using Technique 2 or 3 was significantly lower than after using Technique 1 (p <0.0001).
Technique 2 proved to remove more effectively fluorescein bead-labelled OVD under the IOL than Technique 1.
Electronic supplementary material
The online version of this article (doi:10.1186/1471-2415-14-129) contains supplementary material, which is available to authorized users.
PMCID: PMC4232668  PMID: 25376934
Intraocular lens; Ophthalmic viscoelastic device; Irrigation; Aspiration
45.  Time trend of prevalence of self-reported cataract and its association with prolonged sitting in Taiwan from 2001 and 2013 
BMC Ophthalmology  2014;14(1):128.
Prolong sitting has been found associated with metabolic disorders. Little is known about the self-reported cataract status in general population of Taiwan, not to mention its relation to prolong sitting. We aimed to examine the prevalence of cataract between 2001 and 2013 in Taiwan and to the association between prolonged sitting and cataract.
We used three data sets with those aged 40 years and older from the National Health Interview Survey (NHIS) from 2001 (n = 8334), 2009 (n = 11207), and 2013 (n = 10940). Subsequent statistical analyses involved chi-square test, t test, and logistic regression modeling. SUDAAN was used to account for sampling scheme.
The prevalence of cataract ranged from 10.7% in 2001, 13.13% in 2009, to 11.84% in 2013. Participants who sat for more than 7 hours per day had a significantly higher risk of cataract (OR = 1.20, CI = (1.04-1.39)) compared with those who sat for fewer than 3 hours per day after controlling for age and other risk factors like being older or female, lower education level, not being currently employed, living in a highly urbanized area, having hypertension, diabetes, myopia, and being an former smoker (compared to a never smoker).
Increased daily sitting time was associated with cataract, especially for people who sat more than 7 hours per day.
PMCID: PMC4232657  PMID: 25370503
Prevalence of cataract; Prolonged sitting; National Health Interview Survey; Taiwan
46.  Instability of 24-hour intraocular pressure fluctuation in healthy young subjects: a prospective, cross-sectional study 
BMC Ophthalmology  2014;14(1):127.
Elevated intraocular pressure (IOP) is a major risk factor for the development and/or progression of glaucoma, and a large diurnal IOP fluctuation has been identified as an independent risk factor of glaucoma progression. However, most previous studies have not considered the repeatability of 24-hour IOP measurements. The aim of this study was to evaluate the instability of 24-hour IOP fluctuations in healthy young subjects.
Ten healthy young volunteers participated in this prospective, cross-sectional study. Each subject underwent 24-hour IOP and systolic/diastolic blood pressure (SBP/DBP) assessments both in sitting and supine positions every 3 hours, once a week for 5 consecutive weeks. Mean ocular perfusion pressure (MOPP) was then calculated for both positions. The intraclass correlation coefficients (ICCs) of maximum, minimum, and fluctuation parameters were computed for IOP, SBP/DBP, and MOPP. Fluctuation was defined as the difference between maximum and minimum values during a day.
Among the serial measurements taken over a 24-hour rhythm, the maximum/minimum values of IOP, as well as BP, showed excellent agreement: regardless of position, all ICC values were over 0.800. Most of the BP fluctuation values also showed excellent agreement. IOP fluctuation, however, did not show excellent agreement; the ICC of sitting IOP fluctuation was just 0.212. MOPP fluctuation also showed poor agreement, especially in the sitting position (ICC, 0.003).
On a day to day basis, 24-hour IOP fluctuations were not highly reproducible in healthy young volunteers. Our results imply that a single 24-hour IOP assessment may not be a sufficient or suitable way to characterize circadian IOP fluctuations for individual subjects.
PMCID: PMC4232688  PMID: 25370361
Blood pressure; Fluctuation; Glaucoma; Intraocular pressure
47.  Computer aided quantification for retinal lesions in patients with moderate and severe non-proliferative diabetic retinopathy: a retrospective cohort study 
BMC Ophthalmology  2014;14(1):126.
Detection of retinal lesions like micro-aneurysms and exudates are important for the clinical diagnosis of diabetes retinopathy. The traditional subjective judgments by clinicians are dependent on their experience and can be subject to lack of consistency and therefore a quantification method is worthwhile.
In this study, 10 moderate non-proliferative diabetes retinopathy (NPDR) patients and 10 severe NPDR ones were retrospectively selected as a cohort. Mathematical morphological methods were used for automatic segmentation of lesions. For exudates detection, images were pre-processed with adaptive histogram equalization to enhance contrast, then binary images for area calculation were obtained by threshold classification. For micro-aneurysms detection, the images were pre-processed by top-hat and bottom-hat transformation, then Otsu method and Hough transform were used to classify micro-aneurysms. Post-processing morphological methods were used to preclude the false positive noise.
After segmentation, the area of exuduates divided by optic disk area (exudates/disk ratio) and counts of microaneurysms were quantified and compared between the moderate and severe non-proliferative diabetic retinopathy groups, which had significant difference(P < 0.05).
In conclusion, morphological features of lesion might be an image marker for NPDR grading and computer aided quantification of retinal lesion could be a practical way for clinicians to better investigates diabetic retinopathy.
PMCID: PMC4232650  PMID: 25359611
Diabetic retinopathy; Fundus lesions; Exudation; Microaneurysms
48.  Factors associated with childhood ocular morbidity and blindness in three ecological regions of Nepal: Nepal pediatric ocular disease study 
BMC Ophthalmology  2014;14(1):125.
Nepal Pediatric Ocular Diseases Study is a three year longitudinal population based study. Here we present the baseline survey report which aims to investigate various risk factors associated with childhood ocular morbidity and blindness in three ecological regions of Nepal.
This baseline survey is a population based cross sectional study. The investigation was conducted in a district from each of the following regions: Terai, Hill and Mountain. The Village Development Committees (VDCs) from each district were selected by random sampling. Three Community health workers were given training on vision screening and identification of abnormal ocular signs in children. They conducted a house to house survey in their respected districts examining the children and gathering a standardized set of data variables. Children with abnormal vision or ocular signs were then further examined by pediatric ophthalmologists.
A total of 10950 children aged 0–10 years (5403 from Terai, 3204 from the hills, 2343 from the mountains) were enrolled in the study. However 681 (6.2%) were non responders. The male to female ratio was 1.03. The overall prevalence of ocular morbidity was 3.7% (95% CI of 3.4%-4%) and blindness was 0.07% (95% CI of 0.02%-0.12%). Ocular morbidity was more prevalent in the mountain region whereas blindness was more prevalent in the Terai region.
Children from the Terai region were more likely to suffer from congenital ocular anomalies compared to the other regions. Children whose mother smoked, drank alcohol, or was illiterate were significantly afflicted with ocular diseases (p < 0.05). In addition,a higher prevalence of ocular disease was related to children with past medical history of systemic illnesses, abnormal postnatal period or missing childhood vaccinations. Blindness was more prevalent in children who suffered from a systemic illness. Females and under-nourished children were more likely to have ocular morbidity and blindness.
It was found that childhood blindness was more prevalent in the Terai region, the undernourished, females and in those with co-morbid systemic illnesses. This study strongly suggests that prevention of childhood blindness requires additional resources to address these disparity.
PMCID: PMC4210562  PMID: 25338763
Nepal; Blindness; Pediatric; Ocular
49.  Chronic unilateral chemosis following the use of amlodipine besylate 
BMC Ophthalmology  2014;14(1):124.
This case report describes a patient with chronic unilateral chemosis, likely due to treatment with amlodipine besylate.
Case presentation
A 52-year-old man visited the clinic with symptoms of foreign body sensation and puffiness in his right eye, which had persisted for 4 months. There were no other symptoms, such as itching and pain, in his right eye and no specific symptoms in his left eye. He had been treated for hypertension and hyperlipidemia for the previous 5 months with once daily amlodipine besylate/atorvastatin (Caduet) and candesartan cilexetil (Atacand). Examination revealed marked swelling of the inferior bulbar conjunctiva in the right eye. Evaluation revealed no specific causes for the longstanding chemosis. A change of medication to telmisartan/hydrochlorothiazide (Micardis Plus) without amlodipine besylate resulted in significant improvements in his symptoms after 1 month and complete remission after 8 months.
Prior to invasive evaluation including biopsy, specific drugs should be considered as possible causes of idiopathic longstanding conjunctival chemosis.
PMCID: PMC4216336  PMID: 25335530
Amlodipine; Calcium channel blocker; Chemosis; Conjunctiva; Edema
50.  Intraocular pressure rise is predictive of vision improvement after intravitreal triamcinolone acetonide for diabetic macular oedema: a retrospective analysis of data from a randomised controlled trial 
BMC Ophthalmology  2014;14(1):123.
Intravitreal triamcinolone acetonide (IVTA) is an effective treatment for recalcitrant diabetic macular oedema (DMO). It has been shown to improve vision with benefits persisting up to five years. The most common initial side effect of IVTA treatment is rise in intraocular pressure, occurring in approximately 50% of patients within the first 6 months of treatment. We evaluated whether there is a correlation between the development of intraocular pressure rise and improvement in vision.
Analysis of individual data from 33 eyes of 33 participants treated with IVTA for DMO from a prospective, randomised, double-masked, placebo controlled trial. The degree of intraocular pressure (IOP) rise was correlated with improvement in best-corrected visual acuity (BCVA) at 1 and 6 months.
The proportion of eyes gaining 5 or more logMAR letters was higher in eyes with greater IOP rise (p = 0.044). Better absolute improvement in BCVA at 6 months (p = 0.045) was also found in eyes with greater IOP rise. Regression analyses revealed a correlation between IOP rise of 10 or more mmHg and absolute BCVA improvement at 6 months (odds ratio 1.22, 95% confidence interval 1.01-1.48, p = 0.039), but not at 1 month.
IOP rise and vision improvement appear to be correlated following IVTA for DMO, suggesting that the mechanisms that cause both may be linked.
Trial Registration
Clinical NCT00167518, September 5, 2005.
PMCID: PMC4223852  PMID: 25335434
Intravitreal triamcinolone; Diabetic macular oedema; Vision improvement; Intraocular pressure rise; Adverse events; Efficacy

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