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1.  Case of recurrence of spiradenoma in palpebral conjunctiva 
BMC Ophthalmology  2014;14:85.
To report a rare case of a recurrence of spiradenoma that developed in the upper eyelid.
Case presentation
A 49-year-old woman who had a second recurrence of a tumor in the right palpebral conjunctiva underwent local resection of the lesion with adjunctive cryotherapy to the surgical site. The tumor consisted of smooth, round to oval nodular lesions approximately 1–3 mm in size with enlarged blood vessels. Histopathologically, the solid and well-circumscribed nodule was located beneath the conjunctival epithelium. It was composed of cells with slightly basophilic-to-clear cytoplasm and round-to-oval nuclei arranged in a trabecular pattern. Periodic acid-Schiff stain was positive in the cytoplasm, and the staining disappeared after digesting by diastase. Many cells in mitosis were observed throughout the tumor but no necrotic cells. Immunohistochemistry showed that the Ki-67 labeling index was 12%. From these findings, we diagnosed this tumor as a recurrence of the spiradenoma. There has been no recurrence and no signs of malignancy in the 6 months after the surgical excision.
Our findings indicate that a spiradenoma should be completely excised surgically because of malignant transformation after repeated recurrences.
PMCID: PMC4082681  PMID: 24969313
Spiradenoma; Sweat gland; Eyelids; Repeated recurrences; Immunohistochemistry
2.  Associations of complement factor B and complement component 2 genotypes with subtypes of polypoidal choroidal vasculopathy 
BMC Ophthalmology  2014;14:83.
We previously reported on subtypes of polypoidal choroidal vasculopathy (PCV), and categorized PCV as polypoidal choroidal neovascularization (CNV) and typical PCV. The aim of this study was to clarify whether complement component 2 (C2) and complement factor B (CFB) genotypes are associated with subtypes of polypoidal choroidal vasculopathy, such as polypoidal CNV and typical PCV.
First, we categorized 677 patients into typical age-related macular degeneration (tAMD; 250 patients), PCV (376) and retinal angiomatous proliferation (RAP; 51). Second, we categorized 282 patients with PCV as having polypoidal CNV (84 patients) or typical PCV (198) based on indocyanine green angiographic findings. In total, 274 subjects without AMD, such as PCV and CNV, served as controls. A SNP (rs547154) in the C2 gene and three SNPs (rs541862, rs2072633, rs4151667) in the CFB gene were genotyped, and case–control studies were performed in subjects with these PCV subtypes.
In tAMD, no SNPs were associated with allele distributions. In PCV, rs547154 and rs2072633 were associated with allele distributions. RAP was only associated with rs2072633. After logistic regression analysis with adjustment for confounding factors, tAMD, PCV and RAP were found to be associated with rs2072633.
As to PCV subtypes, there were significant differences in the distributions of rs547154, rs541862 and rs2072633 in the case–control studies for polypoidal CNV, but not between the typical PCV and control groups. Logistic regression analysis with adjustment for confounding factors showed the distributions of rs547154, rs541862 and rs2072633 to differ significantly between the controls and polypoidal CNV cases and that these SNPs were protective. The A/A genotype of rs2072633 was significantly more common in the polypoidal CNV than in the typical PCV group (p = 0.03), even with adjustment for polyp number and greatest linear dimension.
PCV might be genetically divisible into polypoidal CNV and typical PCV. The C2 and CFB gene variants were shown to be associated with polypoidal CNV. Typical PCV was not associated with variants in these genes.
PMCID: PMC4076251  PMID: 24965207
Subtypes of PCV; C2; CFB; Genetic variants
3.  Influence of uncorrected refractive error and unmet refractive error on visual impairment in a Brazilian population 
BMC Ophthalmology  2014;14:84.
The World Health Organization (WHO) definitions of blindness and visual impairment are widely based on best-corrected visual acuity excluding uncorrected refractive errors (URE) as a visual impairment cause. Recently, URE was included as a cause of visual impairment, thus emphasizing the burden of visual impairment due to refractive error (RE) worldwide is substantially higher. The purpose of the present study is to determine the reversal of visual impairment and blindness in the population correcting RE and possible associations between RE and individual characteristics.
A cross-sectional study was conducted in nine counties of the western region of state of São Paulo, using systematic and random sampling of households between March 2004 and July 2005. Individuals aged more than 1 year old were included and were evaluated for demographic data, eye complaints, history, and eye exam, including no corrected visual acuity (NCVA), best corrected vision acuity (BCVA), automatic and manual refractive examination. The definition adopted for URE was applied to individuals with NCVA > 0.15 logMAR and BCVA ≤ 0.15 logMAR after refractive correction and unmet refractive error (UREN), individuals who had visual impairment or blindness (NCVA > 0.5 logMAR) and BCVA ≤ 0.5 logMAR after optical correction.
A total of 70.2% of subjects had normal NCVA. URE was detected in 13.8%. Prevalence of 4.6% of optically reversible low vision and 1.8% of blindness reversible by optical correction were found. UREN was detected in 6.5% of individuals, more frequently observed in women over the age of 50 and in higher RE carriers. Visual impairment related to eye diseases is not reversible with spectacles. Using multivariate analysis, associations between URE and UREN with regard to sex, age and RE was observed.
RE is an important cause of reversible blindness and low vision in the Brazilian population.
PMCID: PMC4076252  PMID: 24965318
Blindness; Visual impairment; Spectacles; Refractive errors; URE; UREN
4.  Management of significant reactivation of old disciform scars in wet Age-Related Macular Degeneration 
BMC Ophthalmology  2014;14:82.
Fibrotic disciform scars represent the end-stage of wet age-related macular degeneration (AMD) and ophthalmologists tend not to treat them. However, reactivation can occur resulting in further worsening of patients. The aim of this study is to describe the clinical outcomes of 10 patients with disciform scars from age-related macular degeneration (AMD) that have subsequently reactivated.
Indocyanine green angiography (ICG) was used to identify the active areas and these “hot spots” (HS) that were subsequently treated with focal laser photocoagulation.
In 10 out of 11 patients with potential reactivation of an AMD scar, a treatable HS was found on the ICG at the border of the disciform scar. The identified HS was treated with focal laser photocoagulation. Post treatment these areas became inactive. However in 2 cases, reactivation occurred requiring retreatment a few months later.
AMD patients who are noted to have disciform scars that are increasing in size and signs of activation such as lipid exudation and subretinal haemorrhage should undergo ICG imaging to look for HS. These patients could benefit from focal laser to stabilize the disease and avoid complications and further peripheral visual loss. It is suspected that these patients may have the polypoidal subtype of AMD.
PMCID: PMC4077557  PMID: 24965122
Age-related macular degeneration; Disciform scar; Indocyanine green angiography; Laser photocoagulation
5.  Evaluating the effectiveness of opportunistic eye screening model for people with Diabetes attending Diabetes clinic at Mnazi Mmoja hospital, Zanzibar 
BMC Ophthalmology  2014;14:81.
Diabetes and its related microvascular complications like Diabetic retinopathy are showing an alarming rise in developing countries like Zanzibar. Objective of the present study is to evaluate the impact of integrating eye screening for all subjects attending the diabetes clinic at Mnazi Mmoja Hospital in Zanzibar and to estimate the prevalence of visual impairment and diabetic retinopathy among the subjects.
This is a cross sectional study involving 356 randomly selected patients who had attended the diabetes clinic between July and August 2012. All subjects underwent comprehensive eye examination including fundus evaluation after dilatation by a cataract surgeon and an ophthalmologist, independently. Data was collected using the designated questionnaire and analysed using the SPSS software. Blindness and visual impairment was defined as presenting VA <3/60 and <6/18 to 6/60 in the better eye respectively and DR was graded using the International classification of Diabetic Retinopathy severity grading scale.
A total of 356/967 subjects were recruited in a duration of 2 months; 176 (49.4%) were male and the mean age was 52.21 (SD 15.3). Targeted eye screening of diabetics showed that 231/356 (65%) of the subjects had eye problems, including potentially blinding conditions that required immediate intervention in contrast to the existing self reported referral where only 10% of an average of 200 diabetics underwent eye checkup in a year. The prevalence of visual impairment was 20.2%; 95% CI: 16.4-24.7 and blindness in 9.3%; 95% CI: 6.7 -12.7. The prevalence of DR was 28.3% and sight-threatening DR was reported in 9%. Among the DR cases, 30% had sight threatening DR including 28% macular edema, 2% severe NPDR and PDR. Multivariate analysis showed a higher risk for any DR in older subjects >50 years (OR: 2.19; 95% CI: 1.14 – 4.25) and in females (OR: 1.92; 95% CI: 1.07 – 3.44).
Opportunistic DR screening model achieved higher yield of identification of visual impairment and DR compared to the yield of 10% of existing self reported Diabetic eye screening model at Zanzibar. Integration of eye screening at diabetes clinics helps in early identification and provision of appropriate treatment for reducing blindness due to diabetes.
PMCID: PMC4078096  PMID: 24957576
Diabetic retinopathy; Screening model; Zanzibar
6.  Congenital cystic eye associated with a low-grade cerebellar lesion that spontaneously regressed 
BMC Ophthalmology  2014;14:80.
Congenital cystic eye is an exceedingly rare ocular malformative disease, originated from the failure in the invagination of the optic vesicle during the fetal period and it can be associated with other ocular and non-ocular abnormalities. Diagnosis is based on clinical, radiological and histological features.
Case presentation
We report a case of a congenital cystic eye associated with a cerebellar lesion accidentally detected at magnetic resonance imaging. Biopsy of the mass has not been performed due to parental rejection. Based on radiologic features and absence of clinical signs, a low-grade glioma diagnosis was hypothesized, but histological characterization was not obtained. Follow-up neuro-imaging 6 months after diagnosis showed that intracranial lesion spontaneously regressed without any treatment.
Our report stresses the importance of early MRI in children with ocular malformations, in order to detect associated intracranial defects, also of non-malformative origin. Additionally, we debate the clinic-radiological features of the intracranial lesions that could allow a wait-and-see policy. We also recommend a strict clinical and neuro-imaging follow-up for these lesions. Finally, biological mechanisms at the base of spontaneous regression of the brain lesions are discussed.
PMCID: PMC4074140  PMID: 24939368
Congenital cystic eye; Anophthalmia; Brain lesion; Spontaneous regression; Magnetic resonance imaging
7.  Prevalence of self-reported early glaucoma eye drop bottle exhaustion and associated risk factors: a patient survey 
BMC Ophthalmology  2014;14:79.
One barrier to patient adherence with chronic topical glaucoma treatment is an inadequate amount of medication available between prescription refills. We examined the self-reported prevalence of early exhaustion of glaucoma eye drops prior to a scheduled refill, and associated risk factors.
This cross-sectional survey was performed at a University-based clinical practice. Glaucoma patients at the University of Washington who were experienced with eye drop application and were on a steady regimen of self-administered glaucoma drops in both eyes took a survey at the time of clinic examination. The main outcome measure was self-reported early eye drop bottle exhaustion.
236 patients were eligible and chose to participate. In general, patients included were relatively healthy (mean 2.3 comorbid medical conditions). Sixty patients (25.4%) reported any problem with early exhaustion of eye drop bottles, and this was associated with visual acuity ≤ 20/70 in the better eye (P = .049). Twelve patients (5.1%) reported that they “often” (5–7 times per year), “usually” (8–11 times per year) or “always” ran out of eye drops prior to a scheduled refill. Patients affected by this higher level (≥5 times yearly) of eye drop bottle exhaustion were more likely to have poor visual acuity in their worse eye ≤ 20/70 (P = .015) and had significantly lower worse-eye logMAR (P = .043).
Self-reported early glaucoma bottle exhaustion regularly affected 5% of patients in our population and 25% reported early exhaustion at least once; the main risk factor was poor vision in at least one eye. These results may not be generalizable to a broad patient population, or to those inexperienced with eye drop self-administration. However, this pilot study compels further evaluation and consideration of early eye drop bottle exhaustion in glaucoma patients.
PMCID: PMC4072615  PMID: 24927769
Glaucoma; Eyedrop; Medication; Treatment; Adherence; Compliance; Visual impairment; Low vision; Blindness
8.  Macular dystrophy associated with the mitochondrial DNA A3243G mutation: pericentral pigment deposits or atrophy? Report of two cases and review of the literature 
BMC Ophthalmology  2014;14:77.
The A3243G point mutation in mitochondrial DNA (mtDNA) is associated with MELAS (mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes) and MIDD syndromes (maternally inherited diabetes and deafness). Both MELAS and MIDD patients can present with visual symptoms due to a retinopathy, sometimes before the genetic diagnosis is made.
Case presentation
Patient 1: 46 year-old woman with diabetes mellitus and hearing loss was referred for an unspecified maculopathy detected during screening evaluation for diabetic retinopathy. Visual acuity was 20/20 in both eyes. Fundus examination showed bilateral macular and peripapillary hyperpigmented/depigmented areas.
Patient 2: 45 year-old woman was referred for recent vision loss in her left eye. History was remarkable for chronic fatigue, migraine and diffuse muscular pain. Visual acuity was 20/20 in her right eye and 20/30 in her left eye. Fundus exhibited several nummular perifoveal islands of retinal pigment epithelium atrophy and adjacent pale deposits in both eyes.
Retinal anatomy was investigated with autofluorescence, retinal angiography and optical coherence tomography. Retinal function was assessed with automated static perimetry, full-field and multifocal electroretinography and electro-oculography. Genetic testing of mtDNA identified a point mutation at the locus 3243.
Observation of RPE abnormalities in the context of suggestive systemic findings should prompt mtDNA testing.
PMCID: PMC4059104  PMID: 24906873
MELAS; MIDD; Macular dystrophy; A3243G
9.  Spectral domain optical coherence tomography in patients after successful management of postoperative endophthalmitis following cataract surgery by pars plana vitrectomy 
BMC Ophthalmology  2014;14:76.
Acute severe postoperative endophthalmitis may lead to severe vision loss. The aim of this study was the analysis of macular microstructure imaged by spectral domain optical coherence tomography in patients after pars plana vitrectomy due to postcataract endophthalmitis.
A cross sectional study was carried out in 17 patients who had cataract surgery in both eyes and underwent unilateral pars plana vitrectomy due to postcataract endophthalmitis. Postoperative best corrected visual acuity was determined in both eyes. Evaluation of macular thickness, macular volume, peripapillary retinal nerve fiber layer thickness and choroidal thickness using enhanced depth imaging technique was performed by spectral domain optical coherence tomography. The measurements obtained in the operated eye were compared to the fellow eye by Wilcoxon matched pair test. Correlation test was performed by Spearman rank order.
A mean postoperative best corrected visual acuity of 63 ± 30 ETDRS letters versus 75 ± 21 letters was achieved in the study and fellow eyes, respectively, after a mean of 5.3 ± 4.5 months (p = 0.1). The mean macular thickness was 320.6 ± 28.8 μm SD in the study eyes compared to 318.4 ± 18.8 μm in the fellow eyes (p = 0.767). No differences were noted in macular volume (p = 0.97) and in peripapillary retinal nerve fiber layer thickness (p = 0.31). Choroidal thickness was significantly lower in the study eyes compared to the fellow eyes (p = 0.018). Epiretinal membrane was found in 7 eyes after endophthalmitis, while in the fellow eyes only in 3 cases (p = 0.13, Fisher’s exact test).
Choroidal thickness decreased significantly after endophthalmitis, but there was no functional correlation with the changes in choroidal microstructure. The development of epiretinal membranes may be associated with either vitrectomy or endophthalmitis in the history. Absence of other significant structural and morphological findings shows that successful treatment may guarantee good clinical results even in long term after this severe postoperative complication.
PMCID: PMC4077685  PMID: 24885759
Spectral domain optical coherence tomography; Postoperative endophthalmitis; Enhanced depth imaging; Choroidal thickness; Vitrectomy
10.  A case of herpes zoster uveitis with severe hyphema 
BMC Ophthalmology  2014;14:74.
Uveitis sometimes causes hyphema, but severe hyphema as a complication following herpes zoster uveitis has rarely been reported. We report a rare case of zoster sine herpete with unusually severe hyphema.
Case presentation
A 41-year-old Japanese female developed hyphema filling almost one-half of the depth of the anterior chamber after a two-week history of unilateral anterior uveitis. Hyphema persisted for four weeks while sectorial iris atrophy became gradually apparent. Systemic prednisolone and valaciclovir resulted in prompt resolution of uveitis and hyphema. Serum anti-varicella zoster virus (VZV) IgG measured by enzyme immunoassay was 116 at presentation and decreased to 20.3 four month later. In addition, the antibody level in aqueous humor was almost 10-fold higher than that in serum examined 9 months after presentation. Because there was no skin lesion, this case was diagnosed as zoster sine herpete. The patient underwent cataract operation due to secondary cataract. The final visual acuity in decimal notation was 1.0, but complications such as severe iris atrophy, wide anterior synechiae, corneal opacity, and decrease in corneal endothelial cell count remained.
Zoster sine herpete is an important differential diagnosis in a case of acute anterior uveitis with severe hyphema, although such cases are quite rare. Measurement of anti-VZV IgG levels by enzyme immunoassay in aqueous humor and serum would be useful in the diagnosis of VZV reactivation. Prompt diagnosis and administration of corticosteroids and anti-herpes virus medication may improve the outcome.
PMCID: PMC4046036  PMID: 24885484
Herpes zoster uveitis; Zoster sine herpete; Hyphema; Anti-varicella zoster virus IgG; Enzyme immunoassay
11.  Increased macular choroidal blood flow velocity and decreased choroidal thickness with regression of punctate inner choroidopathy 
BMC Ophthalmology  2014;14:73.
Changes in choroidal circulation hemodynamics during the course of punctate inner choroidopathy (PIC) remain unknown. The aim of this study was to quantitatively evaluate changes in choroidal blood flow velocity by using laser speckle flowgraphy (LSFG) in patients with PIC.
Case presentation
This PIC patient was initially treated with systemic corticosteroids for 4 months. LSFG measurements were taken 10 consecutive times before treatment and at 1, 3, 12, 20 and 23 months after the initiation of therapy. The mean blur rate (MBR), a quantitative index of relative blood flow velocity, was calculated using LSFG in three regions: Circles 1, 2 and 3 were set at the fovea, a lesion site, and an area of normal-appearing retina, respectively.
The PIC lesions scarred after treatment along with improvements in visual function and outer retinal morphology. When the changing rate of macular flow over the 12-month follow-up period was compared with the MBR before treatment (100%), an increase of 16–37%, 24–49% and 15–18% was detected in Circles 1, 2 and 3, respectively. At the time of PIC recurrence after 20 months, the MBR decreased temporarily but subsequently increased after retreatment with systemic corticosteroids. This trend was accompanied by a decrease in choroidal thickness at the lesion site after retreatment.
Macular choroidal blood flow velocity increased and choroidal thickness decreased concurrently with regression of PIC. The present findings suggest that inflammation-related impairments in choroidal circulation may relate to the pathogenesis of PIC, extending over a wider area in the posterior pole than the PIC lesions per se.
PMCID: PMC4041897  PMID: 24885365
Choroidal blood flow velocity; Choroidal thickness; Enhanced depth imaging optical coherence tomography; Laser speckle flowgraphy; Punctate inner choroidopathy
12.  Analysis of neuroretinal rim distribution and vascular pattern in eyes with presumed large physiological cupping: a comparative study 
BMC Ophthalmology  2014;14:72.
To investigate possible differences in neuroretinal rim distribution, vascular pattern, and peripapillary region appearance between eyes with presumed large physiological optic disc cupping (pLPC) and eyes with minimal optic disc excavation.
We prospectively enrolled consecutive subjects with pLPC and individuals with minimal excavation (optic disc excavation within normal limits; control group). All eyes had normal visual fields and untreated intraocular pressure (IOP) <21 mmHg. Eyes with pLPC required vertical cup-to-disc ratio (VCDR) ≥0.6 and ≥30 months of follow-up with no evidence of glaucomatous neuropathy. For controls, VCDR was limited to ≤0.5. We compared ocular signs and characteristics related to the neuroretinal rim distribution, vascular pattern, peripapillary region appearance and disc size between groups. Whenever both eyes were eligible, one was randomly selected for analysis.
A total of 74 patients (mean age, 45.6 ± 14.9 years) with pLPC and 45 controls (mean age, 44.8 ± 11.6 years) were enrolled (p = 0.76). Median disc size and VCDR was significantly larger in eyes with pLPC compared to controls (p < 0.01). The proportion of eyes with violation of the ISNT rule, laminar dot sign, nasal shifting of the central vessels, nasal excavation and baring of circumlinear vessel was significantly greater in the eyes with pLPC compared to controls (p < 0.01). There were no significant differences regarding the proportions of eyes with peripapillary atrophy between groups (p < 0.09). Finally, disc size was significantly associated with VCDR (r2 = 0.47, p < 0.01), with an increase of 0.21 in VCDR for each 1 mm2 in disc area.
Compared to normal controls, eyes with pLPC may present a higher proportion of optic nerve head findings frequently observed in glaucomatous eyes. This seems to be explained in part by the larger discs found in these eyes. We believe care should be taken while classifying them as glaucomatous or not based solely on these characteristics.
PMCID: PMC4047008  PMID: 24885255
Glaucoma suspect; Intraocular pressure; Optic disc cup; Disc size
13.  The Argus II prosthesis facilitates reaching and grasping tasks: a case series 
BMC Ophthalmology  2014;14:71.
To evaluate the reach-to-grasp performance of patients fitted with an epiretinal artifical retina device.
This was a hospital-based case series consisting of six patients fitted with the Argus II (Second Sight Medical Products Inc, California, USA) retinal prosthesis. Participants were asked to reach out and pick up a high-contrast cuboid object with the prosthesis in the ‘On’, ‘Off’ or ‘Scrambled’ setting presented in a randomised order. The ‘Scrambled’ setting consisted of a random, scattered signal presented to the prosthesis. The session was repeated after a 4–6 week period. Hand movements were measured using motion detection cameras. The number of successful object grasps was calculated.
The number of successful grasps was greater with the prosthesis in the ‘On’ setting (visit 1: median [interquartile range] percentage success: ‘Off’ = 0 [0 to 50]%, ‘On’ = 69 [67 to 95]%, ‘Scrambled’ = 59 [42 to 95]%; Friedman Chi-squared test statistic 6.5, p = 0.04; visit 2 median [IQR] percentage success: ‘Off’ = 0 [0 to 25]%, ‘On’ = 69 [53 to 100]%, ‘Scrambled’ = 28 [13 to 63]%; Friedman Chi-squared test statistic 8.4, p = 0.02).
The use of an electronic retinal prosthesis facilitates reach-and-grasp performance. Further work should explore how performance can be improved with targeted rehabilitation.
PMCID: PMC4039311  PMID: 24885164
Retinal prosthesis; Functional vision; Reach and grasp
14.  Anterior segment dysgenesis associated with Williams-Beuren syndrome: a case report and review of the literature 
BMC Ophthalmology  2014;14:70.
Williams-Beuren syndrome is characterized by mild mental retardation, specific neurocognitive profile, hypercalcemia during infancy, distinctive facial features and cardiovascular diseases. We report on complete ophthalmologic, sonographic and genetic evaluation of a girl with a clinical phenotype of Williams-Beuren syndrome, associated with unilateral anterior segment dysgenesis and bilateral cleft of the soft and hard palate. These phenotypic features have not been linked to the haploinsufficiency of genes involved in the microdeletion.
Case presentation
A term born girl presented at the initial examination with clouding of the right cornea. On ultrasound biomicroscopy the anterior chamber structures were difficult to differentiate, showing severe adhesions from the opacified cornea to the iris with a kerato-irido-lenticular contact to the remnant lens, a finding consistent with Peters' anomaly. Genetic analyses including FISH confirmed a loss of the critical region 7q11.23, usually associated with the typical Williams-Beuren syndrome. Microsatellite analysis showed a loss of about 2.36 Mb.
A diagnosis of Williams-Beuren syndrome was made based on the microdeletion of 7q11.23. The unique features, including unilateral microphthalmia and anterior segment dysgenesis, were unlikely to be caused by the microdeletion. Arguments in favor of the latter are unilateral manifestation, as well as the fact that numerous patients with deletions of comparable or microscopically visible size have not shown similar manifestations.
PMCID: PMC4031488  PMID: 24885071
Williams-Beuren syndrome; Anterior segment dysgenesis; Fluorescence in-situ hybridization; Microdeletion of chromosome 7q11.23; Peters' anomaly; Ultrasound biomicroscopy
15.  Comparison of 1-year therapeutic effect of ranibizumab and bevacizumab for myopic choroidal neovascularization: a retrospective, multicenter, comparative study 
BMC Ophthalmology  2014;14:69.
To compare the long-term efficacy of ranibizumab versus bevacizumab for myopic choroidal neovascularization (CNV).
This was a retrospective, multicenter, comparative, non-randomized study of 64 consecutive patients with myopic CNV treated with ranibizumab (22 patients) or bevacizumab (42 patients). Best-corrected visual acuity (BCVA) and central foveal thickness (CFT) on optical coherence tomography were evaluated before and after treatment. All the patients were followed for at least 12 months.
BCVA (logarithm of the minimal angle of resolution) improved from 0.63 ± 0.30 to 0.43 ± 0.27, 0.41 ± 0.37, 0.40 ± 0.39, 0.39 ± 0.43, and 0.39 ± 0.42 at 1, 2, 3, 6, and 12 months after treatment in the ranibizumab group, and from 0.67 ± 0.28 to 0.52 ± 0.31, 0.49 ± 0.31, 0.47 ± 0.31, 0.42 ± 0.32, and 0.46 ± 0.43 in the bevacizumab group (all P < 0.05 compared with baseline BCVA in each group). CFT decreased by 20.21%, 19.58%, and 22.43% from the baseline 304 ± 76 μm at 3, 6, and 12 months after treatment in the former group, and by 15.20%, 15.67%, and 15.56% from the baseline 297 ± 62 μm in the latter group (all P < 0.05 compared with baseline CFT in each group). BCVA improvement and CFT reduction did not statistically differ when compared at the same periods from treatment between 2 groups. Neither ocular nor systemic safety problems appeared during follow up.
This study showed a similar functional and anatomical improvement after treatment of ranibizumab and bevacizumab for myopic CNV over a 12-month follow-up period.
PMCID: PMC4042135  PMID: 24884970
Anti-VEGF (vascular endothelial growth factor); Bevacizumab; Myopic choroidal neovascularization; Ranibizumab
16.  Enhancement of femtosecond lenticule extraction for visual symptomatic eye after myopia correction 
BMC Ophthalmology  2014;14:68.
The novel Femtosecond lenticule extraction (FLEx) procedure has been considered safe, predictable, and effective in treating myopia and myopic astigmatism, with few complications. However, an enhancement procedure after FLEx may be required in some cases, but has not been reported in detail.
Case presentation
A 24-year-old woman who had undergone bilateral FLEx with the VisuMax femtosecond laser treatment for myopic astigmatism complained of double vision in her left eye after the operation. The manifest refraction was −0.50/-1.25 × 180°. The corneal topography showed a central-inferior steepened zone. The ocular wavefront measurements displayed a high value of total aberrations as well as coma. She was scheduled for an enhancement procedure and it was performed by relifting the primary FLEx flap in the left eye four months later. Ablation was made with the Mel-80 excimer laser. After retreatment, the corresponding aberrations were diminished and the corneal topography turned flattened. Her symptom resolved completely with good visual outcomes.
This first detailed case report demonstrates the feasibility and efficacy of enhancement after FLEx for visual symptomatic eye after myopia correction. An analysis of more cases would be necessary to determine a more definite profile.
PMCID: PMC4032486  PMID: 24884873
Femtosecond lenticule extraction; Enhancement; Myopia; Complication
17.  Role of inflammation in previously untreated macular edema with branch retinal vein occlusion 
BMC Ophthalmology  2014;14:67.
The association of inflammatory factors and the aqueous flare value with macular edema in branch retinal vein occlusion (BRVO) patients remains unclear. The relationship between the aqueous flare value and the vitreous fluid levels of vascular endothelial growth factor (VEGF), interleukin (IL)-6, monocyte chemotactic protein (MCP)-1, soluble intercellular adhesion molecule 1 (sICAM-1), and soluble VEGF receptor-2 (sVEGFR-2) was evaluated to investigate the role of inflammation in BRVO associated with macular edema. Aqueous flare values and the vitreous levels of VEGF, IL-6, MCP-1, sICAM-1, and sVEGFR-2 were compared between previously untreated patients with BRVO and patients with macular hole (MH).
Vitreous samples were obtained from 45 patients during vitreoretinal surgery (28 patients with BRVO and 17 with MH), and the levels of VEGF, IL-6, MCP-1, sICAM-1, and sVEGFR-2 were measured by enzyme-linked immunosorbent assay. Retinal ischemia was evaluated by measuring the area of capillary non-perfusion using fluorescein angiography and the Scion Image program. Aqueous flare values were measured with a laser flare meter and macular edema was examined by optical coherence tomography.
The median aqueous flare value was significantly higher in the BRVO group (12.1 photon counts/ms) than in the MH group (4.5 photon counts/ms, P < 0.001). There were significant correlations between the aqueous flare value and the vitreous levels of VEGF, IL-6, MCP-1, and sICAM-1 in the BRVO group (ρ = 0.54, P = 0.005; ρ = 0.56, P = 0.004; ρ = 0.52, P = 0.006; and ρ = 0.47, P = 0.015, respectively). The aqueous flare value was also significantly correlated with the foveal thickness in the BRVO group (ρ = 0.40, P = 0.037).
Inflammation may induce an increase of vascular permeability and disrupt the blood-aqueous barrier via release of inflammatory factors (VEGF, IL-6, MCP-1, and sICAM-1) in BRVO patients with macular edema.
PMCID: PMC4032564  PMID: 24884703
18.  An easy method to differentiate retinal arteries from veins by spectral domain optical coherence tomography: retrospective, observational case series 
BMC Ophthalmology  2014;14:66.
Recently it was shown that retinal vessel diameters could be measured using spectral domain optical coherence tomography (OCT). It has also been suggested that retinal vessels manifest different features on spectral domain OCT (SD-OCT) depending on whether they are arteries or veins. Our study was aimed to present a reliable SD-OCT assisted method of differentiating retinal arteries from veins.
Patients who underwent circular OCT scans centred at the optic disc using a Spectralis OCT (Heidelberg Engineering, Heidelberg, Germany) were retrospectively reviewed. Individual retinal vessels were identified on infrared reflectance (IR) images and given unique labels for subsequent grading. Vessel types (artery, vein or uncertain) assessed by IR and/or fluorescein angiography (FA) were referenced as ground truth. From OCT, presence/absence of the hyperreflective lower border reflectivity feature was assessed. Presence of this feature was considered indicative for retinal arteries and compared with the ground truth.
A total of 452 vessels from 26 eyes of 18 patients were labelled and 398 with documented vessel type (302 by IR and 96 by FA only) were included in the study. Using SD-OCT, 338 vessels were assigned a final grade, of which, 86.4% (292 vessels) were classified correctly. Forty three vessels (15 arteries and 28 veins) that IR failed to differentiate were correctly classified by SD-OCT. When using only IR based ground truth for vessel type the SD-OCT based classification approach reached a sensitivity of 0.8758/0.9297, and a specificity of 0.9297/0.8758 for arteries/veins, respectively.
Our method was able to classify retinal arteries and veins with a commercially available SD-OCT alone, and achieved high classification performance. Paired with OCT based vessel measurements, our study has expanded the potential clinical implication of SD-OCT in evaluation of a variety of retinal and systemic vascular diseases.
PMCID: PMC4037719  PMID: 24884611
Optical coherence tomography; Spectral domain; Retina vessel
19.  Acquired retinoschisis resolved after 23Gage pars plana vitrectomy in posterior microphthalmos 
BMC Ophthalmology  2014;14:65.
Posterior microphthalmos combined with acquired retinoschisis is a rare entity. This report presents a case of acquired retinoschisis in a patient with posterior microphthalmos and discusses the management for such disease. The patient exhibited acquired peripheral retinal schisis in both eyes.
Case presentation
The patient presented with a fix scotoma and decrease in visual acuity for 2 weeks in his left eye. Ocular examination revealed that his best-corrected visual acuity was 0.6 in right eye and 0.2 in left eye. The patient had amblyopia because of hyperopia with spherical equivalent of +11.75 diopters in the right eye and +12.00 diopters in the left eye. The axial lengths were 18.41 mm in right and 18.43 mm in left eyes respectively. Slip lamp examination found normal anterior segments. Funduscopy showed bilateral retinoschisis in inferotemporal retina. The schisis in right eye was limited to peripheral retina whereas the schisis in left eye was bullous type. The schisis in the left eye extended from the periphery to the posterior macular region in left eye. A pars plana vitrectomy was performed in the left eye and visual acuity was restored to 0.6.
Posterior microphthalmos combined with retinoschisis is rare. When it appears in peripheral retina, the schisis remains stable. In cases where the schisis extends to posterior pole and affects the macula, surgery in the form of pars plana vitrectomy could be an option.
PMCID: PMC4045141  PMID: 24884506
Microphthalmos; Acquired retinoschisis; Pars plana vitrectomy
20.  Hydrocortisone concentration influences time to clinically significant healing of acute inflammation of the ocular surface and adnexa – results from a double-blind randomized controlled trial 
BMC Ophthalmology  2014;14:64.
The efficacy of topical ophthalmic corticosteroids depends upon small modifications in preparations, such as drug concentration.
The aim of this study was to confirm that hydrocortisone acetate (HC-ac) ophthalmic ointments of 2.5% and 1% are more effective than a 0.5% eye ointment.
In this randomized, double-blind, placebo-controlled, parallel-group clinical study, the change of signs and symptoms of acute inflammation of the ocular surface and adnexa was evaluated in 411 subjects.
Median time to clinically relevant response as estimated by 50% reduction in clinical signs and symptoms (CSS) total score over the entire trial was similar for subjects treated with HC-ac 2.5% (73.5 h) and for subjects treated with HC-ac 1.0% (67.7 h) and was considerably and significantly longer for subjects treated with HC-ac 0.5% (111.8 h) [p < 0.001 for both dosages]. All trial medications were safe and well tolerated.
Hydrocortisone acetate 2.5% and Hydrocortisone acetate 1% eye ointments are efficacious and safe treatments for acute inflammations of the ocular surface or adnexa, and showed significantly better efficacy than a control group treated with Hydrocortisone acetate 0.5% therapy.
Trial registration
Current Controlled Trials ISRCTN15464650.
PMCID: PMC4061528  PMID: 24884422
Ophthalmic corticosteroids; Hydrocortisone acetate; Ocular surface; Adnexa; Acute inflammation; Clinical study; Eye ointment; Adaptive design; Treatment outcome
21.  Visual outcome of mega-dose intravenous corticosteroid treatment in non-arteritic anterior ischemic optic neuropathy – retrospective analysis 
BMC Ophthalmology  2014;14:62.
To date, non arteritic anterior ischemic optic neuropathy (NAION) is still incurable. We wish to evaluate the effect of intravenous (IV) corticosteroids on the visual outcome of NAION patients.
Visual parameters were retrospectively compared between NAION patients treated with IV corticosteroids and untreated NAION patients (control). Visual acuity (VA) and Humphrey automated static perimetry visual field (VF) defects of the affected eye were compared between groups at baseline, 1, 3, 6 months, and end of follow-up visits. The VF analysis consisted of number of quadrant involvements and mean deviation (MD).
Each group comprised 23 patients (24 eyes). Mean initial VA was similar in the control and treatment groups (p = 0.8). VA at end of follow-up did not improve in either groups (p = 0.8 treated group, p = 0.1 control group). No improvement and no difference in VF defects were found by either quadrant analysis (p = 0.1 treated group, p = 0.5 control group) or MD analysis (p = 0.2, treated group, p = 0.9 control group). VA and VF parameters tended to be worse in the treated group, although without statistical significance.
Our results suggest that IV corticosteroids may not improve the visual outcome of NAION patients. Since intravenous corticosteroids could potentially cause serious adverse effects, this treatment for NAION is questionable.
PMCID: PMC4017224  PMID: 24886579
Anterior ischemic optic neuropathy; Corticosteroids; Visual acuity; Visual field; Mean deviation
22.  Outcome of surgical management for rhegmatogenous retinal detachment in Behçet’s disease 
BMC Ophthalmology  2014;14:61.
The purpose of the current study is to evaluate the surgical outcome for rhegmatogenous retinal detachment (RD) associated with Behçet’s disease (BD).
The current retrospective study included all patients operated for rhegmatogenous RD associated with BD in our institution from June 2007 to June 2012. Surgical repair was done either by scleral buckling (SB) or pars plana vitrectomy (PPV) according to the topography and clinical criteria of the detachment.
The current study included 7 eyes of 7 patients (6 males and one female). The mean age was 34.3 ± 4.9 years and all patients showed systemic features of BD. In 3 eyes, intravitreal triamcinolone acetonide (IVTA) was injected within 8 weeks prior to the occurrence of rhegmatogenous RD. Five eyes were treated with SB (segmental buckle in 4 cases and encircling buckle in one case) and 2 cases were treated by PPV. One case was initially treated by SB but showed recurrence of RD which was surgically repaired by PPV with successful closure of the retinal break. The retina was successfully reattached in all cases at the end of follow up period (22.0 ± 6.7 months).
Rhegmatogenous RD in BD can be effectively treated by scleral buckling in selected cases and PPV in more complex cases. Intravitreal injections may be a precipitating factor for rhegmatogenous RD.
PMCID: PMC4016621  PMID: 24886487
Rhegmatogenous retinal detachment; Behçet’s disease; Intravitreal injection; Triamcinolone acetonide; Scleral buckling
23.  Low vision due to cerebral visual impairment: differentiating between acquired and genetic causes 
BMC Ophthalmology  2014;14:59.
To gain more insight into genetic causes of cerebral visual impairment (CVI) in children and to compare ophthalmological findings between genetic and acquired forms of CVI.
The clinical data of 309 individuals (mainly children) with CVI, and a visual acuity ≤0.3 were analyzed for etiology and ocular variables. A differentiation was made between acquired and genetic causes. However, in persons with West syndrome or hydrocephalus, it might be impossible to unravel whether CVI is caused by the seizure disorder or increased intracranial pressure or by the underlying disorder (that in itself can be acquired or genetic). In two subgroups, individuals with ‘purely’ acquired CVI and with ‘purely’ genetic CVI, the ocular variables (such as strabismus, pale optic disc and visual field defects) were compared.
It was possible to identify a putative cause for CVI in 60% (184/309) of the cohort. In the remaining 40% the etiology could not be determined. A ‘purely’ acquired cause was identified in 80 of the patients (26%). West syndrome and/or hydrocephalus was identified in 21 patients (7%), and in 17 patients (6%) both an acquired cause and West and/or hydrocephalus was present. In 66 patients (21%) a genetic diagnosis was obtained, of which 38 (12%) had other possible risk factor (acquired, preterm birth, West syndrome or hydrocephalus), making differentiation between acquired and genetic not possible. In the remaining 28 patients (9%) a ‘purely’ genetic cause was identified.
CVI was identified for the first time in several genetic syndromes, such as ATR-X, Mowat-Wilson, and Pitt Hopkins syndrome. In the subgroup with ‘purely’ acquired causes (N = 80) strabismus (88% versus 64%), pale optic discs (65% versus 27%) and visual field defects (72% versus 30%) could be observed more frequent than in the subgroup with ‘purely’ genetic disorders (N = 28).
We conclude that CVI can be part of a genetic syndrome and that abnormal ocular findings are present more frequently in acquired forms of CVI.
PMCID: PMC4021540  PMID: 24886270
Acquired; Cerebral visual impairment; Genetic diseases; Visually impaired children
24.  The Nakuru eye disease cohort study: methodology & rationale 
BMC Ophthalmology  2014;14:60.
No longitudinal data from population-based studies of eye disease in sub-Saharan-Africa are available. A population-based survey was undertaken in 2007/08 to estimate the prevalence and determinants of blindness and low vision in Nakuru district, Kenya. This survey formed the baseline to a six-year prospective cohort study to estimate the incidence and progression of eye disease in this population.
A nationally representative sample of persons aged 50 years and above were selected between January 2007 and November 2008 through probability proportionate to size sampling of clusters, with sampling of individuals within clusters through compact segment sampling. Selected participants underwent detailed ophthalmic examinations which included: visual acuity, autorefraction, visual fields, slit lamp assessment of the anterior and posterior segments, lens grading and fundus photography. In addition, anthropometric measures were taken and risk factors were assessed through structured interviews. Six years later (2013/2014) all subjects were invited for follow-up assessment, repeating the baseline examination methodology.
The methodology will provide estimates of the progression of eye diseases and incidence of blindness, visual impairment, and eye diseases in an adult Kenyan population.
PMCID: PMC4024270  PMID: 24886366
Cohort study; Longitudinal; Eye disease; Africa; Kenya; Cataract; Glaucoma; Age related macular degeneration; Diabetic retinopathy; Refractive error; Incidence; Progression
25.  Evaluation of the vitreous microbial contamination rate in office-based three-port microincision vitrectomy surgery using Retrector technology 
BMC Ophthalmology  2014;14:58.
To perform a microbiological contamination analysis of the vitreous during office-based micro-incision vitrectomy surgery (MIVS) assessing whether the bacteria detected correlated with patient's ocular conjunctival flora.
This is a prospective, interventional, nonrandomized case series of patients undergoing office-based MIVS, anti-VEGF, and dexamethasone intravitreal injections (triple therapy) for the treatment of wet age-related macular degeneration (AMD) and diabetic macular edema (DME).
All patients were operated at a small procedure room in an ambulatory clinic of the Department of Ophthalmology, University of Montreal, Quebec, Canada. Conjunctival samples were done before placing the sclerotomies. The MIVS was done with a 23-gauge retractable vitrector, a 27-gauge infusion line, and a 29-gauge chandelier. Undiluted and diluted vitreous were collected for aerobic, anaerobic and fungal cultures. Outcomes measured were bacterial species identification within samples collected from the conjunctiva and the vitreous.
Thirty-seven patients (37 eyes) were recruited and completed over 17 months of follow-up. Twenty-eight had wet AMD and nine had DME. There were 13 men and 24 women, with a mean age of 78 years. Eighteen patients (46%) had culture positive conjunctival flora. Twenty-six bacterial colonies were tabulated in total from the conjunctival swabs. All bacteria detected were gram-positive bacteria (100%), most commonly: Staphylococcus epidermitis in 11 (42%) and Corynebacterium sp. in 6 (23%). Only 1/18 patients had more than 3 species isolated, 6/18 patients had 2 species and 11/18 patients had 1 species identified on the conjunctival swab. Only 1 of the 37 undiluted midvitreous samples was culture positive, equating to a contamination rate of 2.7%. None of the diluted vitreous samples were culture positive. All cultures were negative for fungus. No serious postoperative complications occurred, including bacterial endophthalmitis, choroidal detachment, and retinal detachment.
This preliminary study of office-based MIVS gives us insights on the ocular surface microbial profile and vitreous contamination rate of performing such procedures outside the OR-controlled environment. Our initial results seem to indicate that there is little risk of bacterial translocation and contamination from the conjunctiva into the vitreous. Therefore, if endophthalmitis occurs post-operatively, the source may likely arise after the procedure. Larger studies are needed to confirm our data.
PMCID: PMC4027993  PMID: 24886149

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