To develop a sensitive point-of-care testing (POCT) aqueous vascular endothelial growth factor (VEGF) detection system, and assess its role for predicting the response to anti-VEGF treatment in ...macular edema secondary to retinal vein occlusion (RVO-ME) patients.
An automatic point-of-care aqueous humor Magnetic Particle Chemiluminescence Enzyme Immuno-Assay (MPCLEIA) VEGF detection system was developed. The predictive values of aqueous cytokine levels, in combination with imaging parameters, on anatomical treatment response (ATR, the relative central macular thickness change ΔCMT/bl-CMT) were analyzed.
The automatic MPCLEIA system was able to provide results in 45 min with only 20 μL sample. Among the 57 eyes with available pre- and post-treatment evaluation, ATR significantly correlated with levels of interleukin (IL)-6, IL-8, monocyte chemoattractant protein-1 (MCP-1) and VEGF measured by Luminex xMAP platform, and VEGF measured by MPCLEIA. Optimal cut-off values for these biomarkers were 13.26 ng/L, 23.57 ng/L, 1,110.12 ng/L, 105.52 ng/L, and 85.39 ng/L, respectively. Univariate analysis showed significant associations between ATR category (good response if ATR≤-25 % or poor response otherwise) and IL-6, IL-8, MCP-1, VEGF-xMAP, and VEGF-MPCLEIA (p<0.05). Multivariate logistic regression revealed that ATR category was significantly associated with aqueous VEGF-MPCLEIA (p=0.006) and baseline(bl)-CMT (p=0.008). Receiver operating characteristics analysis yielded an AUC of 0.959 for the regression model combining VEGF-MPCLEIA and bl-CMT, for predicting ATR category.
Our novel MPCLEIA-based automatic VEGF detection system enables accurate POCT of aqueous VEGF, which shows promise in predicting the treatment response of RVO-ME to anti-VEGF agents when combined with bl-CMT.
To describe the prevalence of and risk factors for epiretinal membrane (ERM) in a multi-ethnic population and to evaluate possible racial or ethnic differences.
Cross-sectional study.
Participants of ...the Multi-Ethnic Study of Atherosclerosis (MESA), examined at the second visit of the MESA when retinal photography was performed.
Data on 5960 participants aged 45 to 84 years from MESA, including white, black, Hispanic, and Chinese persons from 6 United States communities, were analyzed. Epiretinal membrane was assessed from digital nonstereoscopic fundus photographs and was defined as cellophane macular reflex (CMR) without retinal folds or preretinal macular fibrosis (PMF) with retinal folds. Risk factors were assessed from standardized interviews, clinical examinations, and laboratory investigations.
Epiretinal membrane prevalence by ethnic or racial group and risk factors associated with ERM.
The prevalence of any ERM was 28.9%, of which 25.1% were CMR cases and 3.8% were PMF cases. The prevalence of ERM was significantly higher in Chinese persons (39.0%), compared with Hispanic (29.3%), white (27.5%), or black (26.2%; P<0.001) persons. In multivariate models, increasing age (odds ratio OR, 1.19; 95% confidence interval CI, 1.06-1.34, per year increase in age), diabetes (OR, 1.92; 95% CI, 1.39-2.65), and hypercholesterolemia (OR, 1.33; 95% CI, 1.04-1.69) were significantly associated with CMR.
This study showed that ERM was significantly more common in Chinese persons compared with whites, blacks, and Hispanics. Risk factors for ERM were increasing age, presence of diabetes, and hypercholesterolemia.
To determine the prevalence of and factors associated with amblyopia in a sample of Australian preschool children.
Population-based, cross-sectional study.
The Sydney Paediatric Eye Disease Study ...examined 2461 (73.8% participation) children aged between 6 and 72 months from 2007 to 2009.
Visual acuity (VA) was assessed in children aged ≥ 30 months using the Electronic Visual Acuity system, and a subset using the logarithm of the minimum angle of resolution chart. Amblyopia was categorized into unilateral and bilateral subtypes: Unilateral amblyopia was defined as a 2-line difference in reduced VA between the 2 eyes, in addition to strabismus, anisometropia, and/or visual axis obstruction; bilateral amblyopia was defined as bilateral reduced VA with either bilateral visual axis obstruction or significant bilateral ametropia. Information on ethnicity, birth parameters, and measures of socioeconomic status were collected in questionnaires completed by parents.
Amblyopia.
We included 1422 children aged 30 to 72 months, of whom 27 (1.9%) were found to have amblyopia or suspected amblyopia. Mean spherical equivalent for the amblyopic eyes was +3.57 diopters, with a mean VA of 20/50. Only 3 of the 27 amblyopic children had previous diagnoses or treatments for amblyopia. In regression analysis controlling for age, gender, and ethnicity, amblyopia was significantly associated with hyperopia (odds ratio OR, 15.3; 95% confidence interval CI, 6.5-36.4), astigmatism (OR, 5.7; 95% CI, 2.5-12.7), anisometropia (OR, 27.8; 95% CI, 11.2-69.3), and strabismus (OR, 13.1; 95% CI, 4.3-40.4). There were no significant associations of amblyopia with low birthweight (<2500 g), preterm birth (<37 weeks), maternal smoking, age, gender, ethnicity, or measures of socioeconomic status (all P>0.05).
Amblyopia was found in 1.9% of this Australian preschool sample, which is comparable with prevalence rates reported by other recent studies in preschool children. Refractive errors, particularly significant hyperopia and astigmatism, in addition to anisometropia and strabismus, were the major amblyogenic factors. There was a low amblyopia detection rate in this preschool population, which suggests that different strategies are required to improve current vision screening strategies in preschoolers.
The authors have no proprietary or commercial interest in any of the materials discussed in this article.
Retinal arterioles, venules and capillaries are differentially affected in diabetes, and studying vascular alterations may provide information on pathogenesis of diabetic retinopathy (DR). We ...conducted a cross-sectional study on 49 diabetic patients, who underwent fundus photography and optical coherence tomographic angiography (OCT-A). Fundus photographs were analysed using semi-automated software for arteriolar and venular parameters, including central retinal arteriolar equivalent (CRAE), central retinal venular equivalent (CRVE) and fractal dimension (FD). Capillary parameters were measured using OCT-A, including capillary density index (CDI) and capillary FD of superficial (SVP) and deep (DVP) vascular plexuses. Severe DR was defined as severe non-proliferative DR and proliferative DR. We found that eyes with severe DR had narrower CRAE and sparser SVP CDI than eyes without. In logistic regression analysis, capillary parameters were more associated with severe DR than arteriolar or venular parameters. However, combining arteriolar, venular and capillary parameters provided the strongest association with severe DR. In linear regression analysis, eyes with poorer visual acuity had lower CRAE and FD of arterioles, venules, and DVP capillaries. We concluded that the retinal microvasculature is globally affected in severe DR, reflecting widespread microvascular impairment in perfusion. Arteriolar, venular and capillary parameters provide complementary information in assessment of DR.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Diabetic retinopathy (DR) is a retinal microvascular disease characterized by inflammatory and angiogenic pathways. In this study, we evaluated NLRP3 inflammasome in a double transgenic mouse model, ...Akimba (Ins2
xVEGF
), which demonstrates hyperglycemia, vascular hyperpermeability and neovascularization seen in the proliferative DR. Retinal structural integrity, vascular leakage and function were examined by fundus photography, fluorescein angiography, optical coherence tomography, retinal flat mounts, laser speckle flowgraphy (LSFG), and electroretinography in Akimba and its parental strains, Akita (Ins2
) and Kimba (trVEGF029) mice. Inflammatory mechanisms involving NLRP3 inflammasome were investigated using real time-PCR, immunohistochemistry, ELISA and western blots. We observed an increased vascular leakage, reduced retinal thickness, and function in Akimba retina. Also, Akimba retina depicts decreased relative flow volume measured by LSFG. Most importantly, high levels of IL-1β along with increased NLRP3, ASC, and Caspase-1 at mRNA and protein levels were observed in Akimba retina. However, the in vivo functional role remains undefined. In conclusion, increased activation of macroglia (GFAP), microglia (Iba-1 and OX-42) and perivascular macrophages (F4/80 and CD14) together with pro-inflammatory (IL-1β and IL-6) and pro-angiogenic markers (PECAM-1, ICAM-1, VEGF, Flt-1, and Flk-1), suggested a critical role for NLRP3 inflammasome in the Akimba mouse model depicting advanced stages of DR pathogenesis.
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CONTEXT Fungal keratitis is a potentially blinding condition that is rarely seen with contact lens wear. OBJECTIVE To describe a nationwide outbreak of fungal keratitis caused by Fusarium species ...among contact lens wearers in Singapore. DESIGN, SETTING, AND PATIENTS Nationwide, hospital-based case series. All cases of fungal keratitis among contact lens wearers in all ophthalmology departments in Singapore were reviewed along with the charts of all contact lens wearers with culture-proven fungal keratitis from March 2005 through May 2006. A standardized telephone interview was conducted to obtain additional clinical information. MAIN OUTCOME MEASURE Diagnosis of Fusarium keratitis associated with contact lens wear. RESULTS During the study period, 66 patients (68 affected eyes) were diagnosed with Fusarium keratitis associated with contact lens wear; the estimated annual national incidence is 2.35 cases per 10 000 contact lens wearers (95% confidence interval, 0.62-7.22). Patients ranged in age from 13 to 44 years (mean SD, 27.1 8.4 years), of which 32 (48.5%) were men. The vast majority (65 patients; 98.5%) wore soft, disposable contact lenses; 62 patients (93.9%) reported using 1 brand of contact lens cleaning solution (ReNu, Bausch & Lomb, Rochester, NY), including 42 patients (63.6%) who recalled using ReNu with MoistureLoc. Most patients (81.8%) reported poor contact lens hygiene practices, including overnight use of daily wear contact lenses (19.7%), and use of contact lenses past the replacement date (43.9%). The final best-corrected visual acuity ranged from 20/20 to 20/80. Five patients (5 eyes; 7.4%) required emergency therapeutic or tectonic corneal transplantation. CONCLUSIONS A new and evolving epidemic of Fusarium keratitis associated with contact lens wear was found in Singapore. Physicians and eye care practitioners worldwide need to be aware of the likelihood of similar outbreaks emerging among contact lens wearers.
To describe and compare ocular component growth curves among different refractive error groups in Singaporean children.
Data collected yearly in 1775 Asian children aged 6 to 10 years with at least ...three visits were analyzed. Cycloplegic refractive error and biometry variables were measured by autorefractor and A-scan ultrasound machine. Growth curves were compared between five groups: persistent hyperopia of spherical equivalent (SE) > +1.00 D, emmetropizing hyperopia of SE > +1.00 D on the first visit and between -0.50 D and +1.00 D subsequently, persistent emmetropia of SE between -0.50 D and +1.00 D, incident myopia of SE <or= -0.50 D at subsequent visits, and persistent myopia of SE <or= -0.50 D.
The axial length and vitreous chamber elongated faster in the children younger than 10 years, but elongation slowed with age. Growth patterns of axial length and vitreous chamber in the children with newly developed or persistent myopia (P < 0.01) showed faster elongation than in the emmetropic children. The anterior chamber deepened until approximately 9 or 10 years of age but became shallower as the myopic and emmetropic children grew older. Conversely, the lens thinned at younger ages and thickened at older ages for all except the persistently hyperopic children.
In young Asian children, the axial length and vitreous chamber depth increased, but the elongation slowed with age. There was a U-shaped growth curve for lens thickness and an inverted U-shaped curve for anterior chamber depth. The findings of early lens thinning followed by thickening suggest a two-phase growth of the lens.
The natural history and clinical significance of pachydrusen is unclear. This study aims to compare the longitudinal changes of eyes with pachydrusen and soft drusen and progression to exudative ...macular neovascularisation (MNV). Patients with a diagnosis of MNV in one eye only and the fellow eye was selected as the study eye. Study eyes were required to have pachydrusen or soft drusen on fundus photographs and follow up of at least 2 years or until exudative MNV occurred. Systematic grading was performed at baseline and change in drusen area and onset of exudative MNV recorded over the period of follow up. A total of 75 eyes from 75 patients (29 with pachydrusen and 46 with soft drusen) were included. There was no difference in the rate of progression to exudative MNV in the soft and pachydrusen groups (13.3% versus 24.1%, p = 0.38). Pachydrusen, as compared to soft drusen, was associated with polypoidal choroidal vasculopathy subtype (85.7% versus 16.7%, p < 0.01) and the location of exudation was co-localised with soft drusen but not with pachydrusen. There was a higher rate of increase in soft drusen area compared to pachydrusen area (27.7 ± 31.9%/year versus 8.7 ± 12.4%/year respectively, p < 0.01). We found no difference in the proportion of eyes that developed exudative MNV in this study however characterisation of drusen evolution patterns revealed a strong association with exudative MNV subtype.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
To examine the 6-year incidence, progression, associated risk factors, and impact of myopic macular degeneration (MMD) in a myopic population in Singapore.
We examined myopic (spherical equivalent ...≤-0.5 diopters) adults (N = 2157 persons and 3661 eyes) who were phakic at baseline and participated in both baseline and 6-year follow-up visits of the Singapore Epidemiology of Eye Diseases study. Eye examinations, including visual acuity, subjective refraction and axial length (AL) measurements, were performed. MMD was graded from fundus photographs following the META-PM classification. Vision-related quality of life was assessed with Rasch-transformed scores from reading, mobility, and emotional domains of the Impact of Vision Impairment questionnaire.
The 6-year eye-specific incidence of MMD among myopic eyes was 1.2% (95% CI, 0.9%-1.6%). Older age, worse spherical equivalent, and longer AL at baseline were associated with MMD incidence (all P < 0.001). The 6-year eye-specific progression of MMD in 288 eyes with baseline MMD was 17.0% (95% CI, 12.6%-21.4%). More severe MMD at baseline, worse spherical equivalent, and longer AL (all P < 0.05) were associated with MMD progression. Patients with Meta-PM categories 3 and 4 had worse best-corrected visual acuity and poorer vision-related quality of life outcomes than those without MMD (all P < 0.05).
Over a 6-year period, one in 80 myopic eyes developed MMD and one in six with existing MMD had MMD progression. Myopia severity and AL were strong predictors of MMD development and progression. Eyes with severe MMD were at higher risk of MMD progression than those with less severe MMD, and were associated with poorer visual acuity and vision-related quality of life.
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