To quantify the levels of tissue inhibitor of metalloproteinase 4 (TIMP4) and its ratios with free metalloproteinases (MMP) in the aqueous humor of patients with primary open angle glaucoma (POAG), pseudoexfoliation syndrome (PXS) and pseudoexfoliative glaucoma (PXG) and to evaluate a possible imbalance between MMPs and TIMPs in these samples.
Free MMP2, MMP3, MMP9, TIMP1, TIMP2, TIMP4 concentrations and active levels of MMP2 and MMP3 were determined with immunoassay ELISA and activity assay kits in 168 aqueous samples.
TIMP4 was elevated in glaucoma patients(POAG: 0.95 ± 0.49 PXG: 1.28 ± 1.38 pg/ml. p < 0.001). POAG, PXS and PXG samples demonstrated higher MMP2, TIMP1 and TIMP2 concentrations (p < 0.001). Samples from the PXS and PXG groups had a lower total/active MMP2 ratio (p < 0.004 and p < 0.008 respectively). Stoichiometric analysis showed an overbalance of TIMPsover MMPs in both POAG & PXG groups,especially of TIMP4.
TIMP4 elevation is a novel finding in glaucomatous eyes. A disregulation of extracellular matrix homeostasis is suggested in POAG, PXS and PXG.
Glaucoma; Pseudoexfoliation; Metalloproteinases; TIMP4; TIMP/MMP ratios
The purpose of this study was to evaluate the relationship between patterns of localized retinal nerve fiber layer (RNFL) defects and the degree of myopia in patients with normal-tension glaucoma (NTG).
We retrospectively reviewed medical records of patients with high myopia (42 eyes; spherical equivalent [SE] < −6.0 diopters [D]), low to moderate myopia (93 eyes; SE −6.0D ~ and −0.5D), and emmetropia (65 eyes; SE −0.5D ~ +0.5D), all of which were diagnosed as having NTG with localized RNFL defects. On RNFL photographs, the proximity of the RNFL defect to the center of the fovea (angle I) and the sum of the angular width of the defects (angle II) were determined. The patterns of localized RNFL defects were then compared with respect to differences in angles I and II.
Angle I was significantly smaller in the high myopia group than in the low to moderate myopia group (p = 0.028) and the emmetropia group (p = 0.044), while angle II was significantly larger in the high myopia group compared with the low to moderate myopia group and the emmetropia group (p < 0.001, p = 0.007).
Among subjects with NTG, localized RNFL defects are wider and closer to the fovea in eyes with high myopia than those with low to moderate myopia or emmetropia.
Myopia; RNFL defect; Normal-tension glaucoma; Refractive error
To report a patient with penetrating keratoplasty (PKP) graft endothelial failure implanted with toric intraocular lens (IOL) who was treated with Descemet stripping endothelial keratoplasty (DSAEK).
A 40 year old male patient implanted with toric intraocular lens for the treatment of post PKP astigmatism, presented for the treatment of graft endothelial failure’. The patient had uncorrected distance visual acuity (UDVA) 20/200 not correcting with manifest refraction. The patient reported excellent visual acuity after cataract surgery and toric IOL implantation. DSAEK was performed in order to minimally affect keratometry and retain correspondence of the anterior cornea astigmatism with the toric IOL astigmatic power. Three months postoperatively the cornea was clear with no edema. UDVA was 20/40 and corrected distance visual acuity was 20/25 with +1.50-1.00 × 20.
This report describes a unique case of DSAEK for treatment of a failed PKP in a patient previously implanted with a toric IOL. DSAEK was an effective alternative of PKP in this patient for the preservation of the toric IOL’s effect.
Descemet stripping automated endothelial keratoplasty; Post penetrating keratoplasty astigmatism; Toric intraocular lens
To report the effect of subtenon injections of natural leukocyte interferon α-2a (IFNα) on best corrected visual acuity (BCVA) and central macular thickness (CMT) in a patient with diabetic macular edema (DME).
A 66-year-old man affected by DME, with glycated hemoglobin (HbA1c) at 6.9%, refractory to laser grid treatment and intravitreal injections of triamcinolone, was selected to receive a cycle of three subtenon injections/week of IFNα (1×106 IU/ml). BCVA and CMT, using spectral domain ocular coherence tomography (SD-OCT), were evaluated preoperatively and at 1 week, 1 month, 4 months, and 1 year postoperatively. BCVA and CMT were significantly improved at 1 week after the three injections (20/200 vs. 20/40 and 498 μm vs. 237 μm, respectively). BCVA remained stable during the 1-year follow-up. CMT was slightly increased, but was still lower than the baseline value (215 μm, 255 μm, and 299 μm during the follow-up visits). No adverse events were recorded, with the exception of mild subconjunctival hemorrhage at the injection site.
IFNα, with its immunomodulatory, anti-proliferative and anti-angiogenic actions, was effective in improving BCVA and reducing CMT in refractory DME. Further randomized controlled studies are required to assess the effect of IFNα alone or in combination with other therapies for DME treatment.
Diabetic macular edema; Interferon; Subtenon injections; Central macular thickness; Spectral domain optical coherence tomography
We present two cases of transient vacuolar changes in the anterior subcapsular space of the crystalline lens in patients after posterior chamber phakic intraocular lens implantation.
Implantable collamer lenses (ICL) were implanted in healthy myopic patients. Vacuolar changes developed just after the irrigating procedure through the narrow space between the ICL and the crystalline lens. Slit-lamp examinations and spectral domain optical coherence tomography showed bleb-like lesions in the anterior subcapsular space of one eye in each case, though the lesions gradually improved without visual deterioration. Consequently, the lesions turned into a few anterior subcapsular small faint opacities.
Direct irrigation of the narrow space confined by the ICL and the crystalline lens is at risk for the development of vacuolar changes in the crystalline lens. The observed spontaneous reversal indicates that surgeons should not rush to surgical intervention but rather opt for close follow over several weeks.
Implantable collamer lens; Phakic intraocular lens; Vacuolar change; Crystalline lens; Subcapsular opacities
To report engorged vessel occlusion after repeated intravitreal injections of bevacizumab to treat the macular oedema in a case of arteriovenous malformation.
A 37-year-old woman presented with a sudden, painless loss of vision in her left eye. Her visual acuity was 20/200 in the left eye, and 20/20 in the right eye. Ophthalmoscopic examination revealed an abnormal tangle of vessels and enlarged draining veins. A fluorescence angiogram revealed fluorescence leakage at a turn near the fovea. Horizontally oriented optical coherence tomography revealed an increased macular thickness and an accumulation of intraretinal fluid, indicating macular oedema. After three intravitreal injections of 1.25 mg bevacizumab, her vision improved to 20/20. Ophthalmoscopic examination revealed a decreased calibre of the previously engorged draining veins and ghost vessels. Repeated horizontally oriented optical coherence tomography revealed a decreased macular thickness and the absence of an intraretinal cyst. At the 2-year follow-up visit, the vision of the patient was stable.
This finding implies that certain middle-size vessels can become occluded during anti- vascular endothelium growth factor (anti-VEGF) therapy, which could induce fatal complications if it occurred in the heart or brain. Clinicians should be cautious of the potential thrombotic effects on systemic blood vessels when administering anti-VEGF treatment.
Quantitative evaluation of mosaics of photoreceptors and neurons is essential in studies on development, aging and degeneration of the retina. Manual counting of samples is a time consuming procedure while attempts to automatization are subject to various restrictions from biological and preparation variability leading to both over- and underestimation of cell numbers. Here we present an adaptive algorithm to overcome many of these problems.
Digital micrographs were obtained from cone photoreceptor mosaics visualized by anti-opsin immuno-cytochemistry in retinal wholemounts from a variety of mammalian species including primates. Segmentation of photoreceptors (from background, debris, blood vessels, other cell types) was performed by a procedure based on Rudin-Osher-Fatemi total variation (TV) denoising. Once 3 parameters are manually adjusted based on a sample, similarly structured images can be batch processed. The module is implemented in MATLAB and fully documented online.
The object recognition procedure was tested on samples with a typical range of signal and background variations. We obtained results with error ratios of less than 10% in 16 of 18 samples and a mean error of less than 6% compared to manual counts.
The presented method provides a traceable module for automated acquisition of retinal cell density data. Remaining errors, including addition of background items, splitting or merging of objects might be further reduced by introduction of additional parameters. The module may be integrated into extended environments with features such as 3D-acquisition and recognition.
Mammalian photoreceptor cells; Automatical counting; Adaptive algorithm; Continuous optimization; Total variation denoising
The contaminated contact lens provides Pseudomonas aeruginosa an ideal site for attachment and biofilm production. Continuous contact of the eye to the biofilm-infested lens can lead to serious ocular diseases, such as keratitis (corneal ulcers). The biofilms also prevent effective penetration of the antibiotics, which increase the chances of antibiotic resistance.
For this study, 22 Pseudomonas aeruginosa isolates were obtained from 36 contact lenses and 14 contact lens protective fluid samples. These isolates were tested against eight commonly used antibiotics using Kirby-Bauer disk diffusion method. The biofilm forming potential of these isolates was also evaluated using various qualitative and quantitative techniques. Finally, a relationship between biofilm formation and antibiotic resistance was also examined.
The isolates of Pseudomonas aeruginosa tested were found resistant to most of the antibiotics tested. Qualitative and quantitative biofilm analysis revealed that most of the isolates exhibited strong biofilm production. The biofilm production was significantly higher in isolates that were multi-drug resistant (p < 0.0001).
Our study indicates that multi-drug resistant, biofilm forming Pseudomonas aeruginosa isolates are mainly involved in contact lens associated infections. This appears to be the first report from Pakistan, which analyzes both antibiotic resistance profile and biofilm forming potential of Pseudomonas aeruginosa isolates from contact lens of the patients with contact lens associated infections.
Antibiogram; Biofilm; Pseudomonas aeruginosa; Contact lens
The vascular endothelial growth factor (VEGFA) gene has been suggested to play an important role in the pathogenesis of diabetic retinopathy (DR). However, the results have been inconsistent. In this study, we performed a meta-analysis to clarify the associations between VEGFA polymorphisms and DR risk.
Published literature from PubMed, EMBASE, Web of Science and Google Scholar were retrieved. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using fixed- or random-effects model.
A total of eight studies (1204 cases and 1198 controls) for rs699947 polymorphism and ten studies (1666 cases and 1782 controls) for rs2010963 polymorphism were included in the meta-analysis. The results suggested that rs699947 polymorphism was marginally associated with DR under a homogeneous co-dominant model (AA vs. CC: OR = 1.69, 95% CI = 1.03-2.77, p = 0.040) and a dominant model (AA + AC vs. CC: OR = 1.38, 95% CI = 1.01-1.90, p = 0.040), whereas the association between rs2010963 polymorphism and DR was not significant under all genetic models (all p > 0.05). In the subgroup analysis, the effect size for rs699947 polymorphism was only marginally significant among European populations under a dominant model (OR = 1.47, 95% CI = 1.07–2.02, p = 0.018), but not among East Asians. After exclusion of outliers which were the source of between-study heterogeneity, there was significant association between rs699947 polymorphism and DR under a homogeneous co-dominant model (OR = 1.64, 95% CI = 1.18-2.28, p = 0.003), even after multiple comparison correction.
Our meta-analysis confirmed the significant association between rs699947 polymorphism and DR after exclusion of outliers, and rs2010963 polymorphism might be not associated with DR.
The vascular endothelial growth factor gene; Polymorphism; Diabetic retinopathy; Meta-analysis
Goldenhar Syndrome is characterized by malformations of multiple anatomical districts. Between these, bulbar dermoids are common and represent a significant clinical problem as they can affect both ocular function and aesthetic comfort.
Histologic characterization of dermoids has been extensively performed; however, no reports exist describing in vivo confocal microscopy (IVCM) of these lesions. We aimed to (i) describe the in vivo confocal morphology of limbal dermoids in Goldenhar syndrome and (ii) compare these findings with standard light microscopy.
A 15-year-old Caucasian female affected by Goldenhar Syndrome showed a left, infero-temporal, limbal neoformation, with extension to the left orbital region. Prior to surgical removal, IVCM was performed with the Heidelberg Retina Tomograph II, Cornea Module, using the “section” modality. The IVCM sections showed structures resembling corneal epithelium and vascular structures. Surgical removal of the lesion was decided as it caused poor eyelid closure. After surgical removal, sectioning and standard optical microscopy were performed. The comparison between IVCM imaging and standard microscopy sections were highly correlated in the detection of the pilar and vascular structures.
This study showed that IVCM may be a useful technique to study limbal dermoids, given its ability to detect typical microscopic features and its comparability to optical microscopy, which is the current standard.
In vivo confocal microscopy; Goldenhar syndrome; Dermoid
Cataract is among the major causes of vision impairment and blindness worldwide. Epidemiological studies support the role of antioxidants in the etiology of cataract, but the evidence for one specific antioxidant over another is inconsistent. Few studies have examined the association of cataract with fruit and vegetable intake with inconclusive results. In the present study, the relationship between cataract and fruit and vegetable intake and dietary and blood levels of carotenoids, vitamins C and E were examined in a Spanish Mediterranean population.
The present work is an analysis of data from 599 elderly ( ≥ 65 years) participants from the Spanish segment of the EUREYE study. This is a European multi-center cross-sectional population-based study. Cataract was diagnosed using a slit-lamp examination and defined as any lens opacity in either eye or evidence of its removal (cataract extraction). Energy-adjusted intake of fruit and vegetables and antioxidant vitamins was estimated using a semi-quantitative food frequency questionnaire. Plasma concentrations of vitamin C were analyzed by a colorimetric method and carotenoids and α-tocopherol by a HPLC method. The associations between cataract and quartiles of fruit and vegetable intake and plasma antioxidants were investigated using logistic regression models.
Of the 599 elderly recruited, 433 (73%) had cataract or cataract extraction, 54% were women and 46% were men. After adjustments, increasing quartiles of combined fruit and vegetable intake were associated with decreasing reduction of odds of cataract or cataract extraction, (P for trend = 0.008). Increasing quartiles of dietary intakes from 107 mg/d of vitamin C showed a significant decreasing association with prevalence of cataract or cataract extraction (P for trend = 0.047). For vitamin E, a protective association was found from intakes from 8 mg/d, but no linear trend was observed across quartiles of intake (P for trend = 0.944).
High daily intakes of fruit and vegetables and vitamins C and E were associated with a significantly decreased of the prevalence of cataract or cataract surgery. This study reinforces the WHO recommendations on the benefits of diets rich in fruit and vegetables.
Cataract; Fruit intake; Vegetables intake; Antioxidant vitamins; WHO recommendations
Dry eye (DE) is a common eye disease, and appropriate animal models are essential to explore the pathogenesis and therapy of DE. In this study, we aimed to establish rabbit models by three methods.
In group A, the lacrimal gland, Harderian gland, and nictitating membrane of the left eyes were surgically removed. In group B, the bulbar conjunctiva of the left eyes was burned with 50% trichloroacetic acid. In group C, both methods above were used. The right eyes served as normal controls. The Schirmer I test (SIt), fluorescein staining, and impression cytology were evaluated at baseline and on days 28, 42, and 56.
Both the SIt and goblet cell density were significantly lower in operated eyes compared to the control eyes, while the corneal fluorescein staining scores in the operated eyes were significantly higher than in the control eyes on days 28, 42, and 56 (p < 0.05, p < 0.01 or p < 0.001). The SIt and goblet cell densities in groups B and C were significantly lower than group A on days 28, 42, and 56 (p < 0.05, p < 0.01 or p < 0.001). In addition, the corneal fluorescein staining scores in group C were significantly higher than either group A or group B on days 28, 42, and 56, while fluorescein staining scores were higher in group B than group A on days 42 and 56 days (p < 0.05, p < 0.01 or p < 0.001), with mean score 3.8 ± 1.30 (group A), 7.4 ± 1.14 (group B) and 10.8 ± 1.30 (group C) on day 56.
Results suggest that three separate DE models, with mild, moderate, and severe manifestations of DE, could be stably established, in which conjunctival goblet cells took an important role.
Dry eye; Rabbit model; Conjunctival impression cytology; Corneal fluorescein staining; Schirmer I test
To investigate the biomechanical properties of the cornea measured with the Ocular Response Analyzer (ORA) and their association with the anterior segment parameters representing the geometric dimensions including the corneal volume and anterior chamber volume.
A retrospective review of 1020 patients who visited the BGN Eye Clinic was done. The mean radius of the corneal curvature, corneal astigmatism, corneal volume, anterior chamber depth, and anterior chamber volume were measured with an anterior segment tomographer. The central corneal thickness (CCT) was measured with an ultrasonic pachymeter. The corneal diameter was measured with an Orbscan as White to White. Cornea hysteresis (CH), corneal resistance factor (CRF), Goldmann correlated intraocular pressure (IOPg), and cornea-compensated IOP (IOPcc) were measured with an ORA. Multiple linear regression models were constructed with CH and CRF as the dependent variables and age, gender, and the anterior segment parameters as the covariates.
958 eyes from 958 patients (mean age 26.7 years; male 43.4%) were included in this study after excluding some eyes according to the exclusion criteria. The mean CH and CRF were 10.1 and 9.9 mmHg, respectively. The mean IOPg and IOPcc were 14.8 and 15.8 mmHg. The multivariate analysis showed that CH was negatively associated with the mean radius of the cornea curvature (regression coefficient = - 0.481, p = 0.023) and positively associated with CCT (regression coefficient =0.015, p < 0.001) and corneal volume (regression coefficient =0.059, p = 0.014). The association between CH and the corneal diameter, anterior chamber depth, and anterior chamber volume were not statistically significant. The evaluation of CRF showed that CRF was negatively associated with the mean radius of the cornea curvature (regression coefficient = - 0.540, p = 0.013), and positively associated with CCT (β = 0.026, p < 0.001). The association between CRF and the corneal diameter, corneal volume, anterior chamber depth, and anterior chamber volume were not statistically significant.
The CH was shown to be positively associated with the corneal volume and the association between CH and the anterior chamber volume were not significant. The associations of CRF with the corneal volume or anterior chamber volume were not significant.
Autoimmune retinopathy (AR) and Cancer-Associated Retinopathy (CAR) are associated with a diverse repertoire of anti-retinal autoantibodies (AAbs) but not all antigenic targets have been characterized. Identification of new AAbs may help with clinical diagnosis and prognosis of retinal dysfunction in AR. The goal was to identify frequently targeted retinal autoantigens within the 60-70-kDa molecular weight range.
Human retinal proteins were separated by SDS-PAGE and 2D gel electrophoresis (2-DE) and sera from AR patients with and without cancer were used to identify immunoreactive proteins by Western blotting. Proteins were identified following separation by electrophoresis, Coomassie staining using in-gel trypsin digestion and mass spectrometric analysis. Circulating serum hsp60 and anti-hsp60 antibody levels were determined by quantitative ELISA.
Retrospective evaluation of 819 patients with anti-retinal AAbs showed that 29% patients had AAbs targeted proteins between 60-70-kDa. Shotgun mass spectrometry of human retinal proteins present in 1D-gel found 66 species within this range. To identify the immunoreactive proteins, we performed Western blots of 2-DE gels and showed a group of heat shock proteins (hsps), including hsp60 and CRMP proteins that were frequently recognized by AR patient AAbs, irrespective of cancer status. These results were validated by immunostaining of purified hsp60 and CRMP2 proteins. ELISA results revealed that patients with AR and CAR had significantly increased levels of serum anti-hsp60 antibodies compared to control healthy subjects (p < 0.0001). However, circulating hsp60 protein was not significantly elevated in sera of either patient group.
Different anti-retinal antibodies frequently co-exist in a single patient, creating antibody-arrays related to the syndrome. Hsps and CRMP-2 are newly identified autoantigens in AR. A frequent co-association of anti-hsp antibodies with other anti-retinal AAbs may augment pathogenic processes, leading to retinal degeneration.
Autoantibody; Autoimmune retinopathy; CAR; Retina; Autoantigen; Heat shock proteins; CRMP-2
To develop a side-view imaging technique for observing the dynamic behavior of posterior chamber structures (PCSs) in porcine eyes which mimics closed-eye cataract surgery in humans.
Enucleated porcine eyes were placed into liquid nitrogen for 5 seconds and immediately bisected at about a 45-degree angle to the equatorial plane. The anterior portion was attached firmly to a glass slide with superglue and sprinkled with wheat flour. Phacoemulsification and aspiration (PEA) was performed as in humans on 10 consecutive porcine eyes. The movements of the PCSs were monitored through the glass slide with a high-resolution video camera set below the cut surface of the eye. The intraocular pressure (IOP) was monitored during the surgery. The highest IOP, operation time, and volume of irrigation fluid of 10 whole eyes were compared to that obtained from the bisected eyes glued to a glass slide. In a second set of experiments, the strength of the seal between the bisected eye and the glass slide was tested in three sets of eyes: 1) frozen eye fixed with superglue with wheat flour for 3 min; 2) frozen eye fixed with superglue for 3 min; and 3) non-frozen eye fixed with superglue for 30 min. The highest IOP that led to a disruption of the seal was compared among the three groups.
PEA was successfully performed on 9 of 10 (90%) eyes with the movements of the PCSs clearly observed. The average maximum intraocular pressure of the 9 bisected eyes was 55.8 ± 4.7 mmHg and that for the 10 unbisected eyes was 55.3 ± 5.0 mmHg (P = 0.650). The frozen eye fixed with superglue in combination with wheat flour (Group 1) had the strongest sealing strength with an average IOP at the breaking point of 117.3 ± 36.2 mmHg.
Our side-view imaging technique can be used to evaluate the changes of the PCSs during intraocular surgery and for surgical training of new residents.
Side-view imaging; Posterior chamber structures; Cataract surgery; Porcine eyes
The antioxidant melatonin effectively scavenges highly toxic hydroxyl radicals. Decreases in circulating melatonin levels have been reported in patients with diseases that become more serious with advancing age. The purpose of the present study was to explore the relationship between circulatory melatonin level and the extent of senile cataracts. To this end, we assessed the urinary excretion levels of 6-sulphatoxymelatonin (aMTS6), a major metabolite of melatonin.
A total of 22 patients (aged 64 ± 7 years; 12 males and 10 females) with senile cataracts and 22 healthy controls (aged 61 ± 8 years, 12 males and 10 females) were studied. aMTS6 urine levels were measured using commercial ELISA kits. Each aMTS6 level was expressed as [aMTS6] (in ng)/[mg] creatinine. As the data were not normally distributed, the Mann–Whitney U-test was employed to assess the statistical validity of the difference observed.
The aMT6 level in nocturnal urine was 17.87 ± 14.43 ng aMTS6/mg creatinine (mean ± SD) in senile cataract patients; this was 76% of the level measured in age- and gender-matched controls (23.28 ± 16.27 ng aMTS6/mg creatinine). This difference in nocturnal urine aMTS6 level between senile cataract patients and controls was not statistically significant (p = 0.358).
The urinary aMTS6 level did not differ between subjects with and without senile cataracts.
Senile cataract; 6-sulphatoxymelatonin; Antioxidant
Cataract is an extremely common visual condition of ageing. Evidence suggests that visual impairment influences driving patterns and self-regulatory behavior among older drivers. However, little is known about the psychological effects of driver self-regulation among older drivers. Therefore, this study aimed to describe driver self-regulation practices among older bilateral cataract patients and to determine the association between self-regulation and depressive symptoms.
Ninety-nine older drivers with bilateral cataract were assessed the week before first eye cataract surgery. Driver self-regulation was measured via the Driving Habits Questionnaire. Depressive symptoms were assessed using the 20-item Center for Epidemiological Studies Depression Scale. Visual, demographic and cognitive data were also collected. Differences between self-regulators and non self-regulators were described and linear regression modeling used to determine the association between driver self-regulation and depressive symptoms score.
Among cataract patients, 48% reported self-regulating their driving to avoid at least one challenging situation. The situations most commonly avoided were driving at night (40%), on the freeway (12%), in the rain (9%) and parallel parking (8%). Self-regulators had significantly poorer contrast sensitivity in their worse eye than non self-regulators (p = 0.027). Driver self-regulation was significantly associated with increased depressive symptoms after controlling for potential confounding factors (p = 0.002).
Driver self-regulation was associated with increased depressive symptoms among cataract patients. Further research should investigate this association among the general older population. Self-regulation programs aimed at older drivers may need to incorporate mental health elements to counteract unintended psychological effects.
Older drivers; Cataract; Self-regulation; Depression
Icare PRO (ICP) is a new Rebound tonometer that is able to measure intraocular pressure (IOP) in both sitting and reclining positions. In this study, the gold standard Goldmann tonometer (GAT) was compared to ICP and Tono-Pen AVIA (TPA). Hypothesis was that repeatability of GAT is superior to ICP and TPA.
36 eyes of 36 healthy caucasian individuals, 13 male and 26 females, 17 right and 19 left eyes have been included in this prospective, randomized, cross-sectional study. The study was conducted at a single site (Dept. of Ophthalmology, UniversityHospital Zurich, Switzerland). Primary outcome measures were Intraclass correlation coefficients (ICC) and coefficients of variation (COV) and test-retest repeatability as visualized by Bland-Altman analysis. Secondary outcome measures were IOP in sitting (GAT, ICP and TPA) and in reclining (ICP and TPA) position.
Mean IOP measured by GAT was 14.9±3.5 mmHg. Mean IOP measured by ICP was 15.6±3.1 mmHg (with TPA 14.8±2.7 mmHg) in sitting and 16.5±3.5 mmHg (with TPA 17.0±3.0 mmHg) in reclining positions. COVs ranged from 2.9% (GAT) to 6.9% (ICP reclining) and ICCs from 0.819 (ICP reclining) to 0.972 (GAT).
Repeatability is good with all three devices. GAT has higher repeatability compared to the two tested hand-held devices with lowest COVs and highest ICCs. IOP was higher in the reclining compared to the sitting position.
The study was registered to the Clinical Trials Register of the US National Institute of Health, NCT01325324.
To determine the role played by vascular endothelial growth factor (VEGF) in polypoidal choroidal vasculopathy (PCV) based on an interventional immunology theory.
Eyes with PCV were divided in a masked fashion into those with choroidal hyperpermeability (HP group) and those with normal choroidal permeability (NP group) based on the indocyanine green angiograms. The inter-rater agreement rate was evaluated using Fleiss’ kappa. Patients were treated by intravitreal ranibizumab (IVB). The central choroidal thickness and central foveal thickness (CFT) at the baseline and 7 days after the treatment were measured by optical coherence tomography.
Among the 57 consecutive eyes diagnosed with PCV, 42 eyes of 42 patients met the inclusion criteria (21 eyes/HP group vs 21 eyes /NP group). Central choroidal thickness in HP group was significantly thicker than that in the NP group (P < .001, Mann–Whitney U test). The inter-rater agreement was high with a Fleiss’ kappa = 0.95, P < .0001. The percentage reduction in the CFT in HP group (14.0%) was significantly less than that in NP group (20.4%; P = .013, Mann–Whitney U test).
Eyes with PCV that are associated with choroidal hyper-permeability may not be strongly associated with VEGF-related pathology, and may not respond favorably to anti-VEGF monotherapy.
AMD; Drug; Enhanced depth imaging optical coherence tomography interventional immunology; Ranibizumab
Investigations used to aid diagnosis and prognosticate outcomes in ocular inflammatory disorders are based on techniques that have evolved over the last two centuries have dramatically evolved with the advances in molecular biological and imaging technology. Our improved understanding of basic biological processes of infective drives of innate immunity bridging the engagement of adaptive immunity have formed techniques to tailor and develop assays, and deliver targeted treatment options. Diagnostic techniques are paramount to distinguish infective from non-infective intraocular inflammatory disease, particularly in atypical cases. The advances have enabled our ability to multiplex assay small amount of specimen quantities of intraocular samples including aqueous, vitreous or small tissue samples. Nevertheless to achieve diagnosis, techniques often require a range of assays from traditional hypersensitivity reactions and microbe specific immunoglobulin analysis to modern molecular techniques and cytokine analysis. Such approaches capitalise on the advantages of each technique, thereby improving the sensitivity and specificity of diagnoses. This review article highlights the development of laboratory diagnostic techniques for intraocular inflammatory disorders now readily available to assist in accurate identification of infective agents and appropriation of appropriate therapies as well as formulating patient stratification alongside clinical diagnoses into disease groups for clinical trials.
Diagnosis; Uveitis; Ocular inflammation; Hypersensitivity; Polymerase chain reaction; Immunoglobulin; Cytokines; Autoimmunity; Autoregulation
To report a case of bilateral optic disc oedema and associated optic neuropathy in the setting of FOLFOX chemotherapy.
A case of a 57-year-old male being treated with FOLFOX chemotherapy for stage 3B colorectal cancer, who developed bilateral optic disc oedema and associated left sided optic neuropathy is described. The patient presented following cycles 7, 8 and 9 of chemotherapy with a history of bilateral simultaneous intermittent inferior altitudinal field defects. These episodes progressed to bilateral optic nerve oedema and a subsequent left sided optic neuropathy. The patient’s symptoms and oedema regressed with discontinuation of chemotherapy.
This is the first report suggesting a vasospastic role of 5-fluoruracil in 5-FU associated optic neuropathy. It highlights that 5-FU may have the potential to cause arterial vasospasm outside the cardiac vasculature, resulting in end-organ optic nerve ischaemia.
Optic neuropathy; Ischaemic optic neuropathy; FOLFOX; Fluorouracil
The aim of the project was to develop a novel method for diabetic retinopathy screening based on the examination of tear fluid biomarker changes. In order to evaluate the usability of protein biomarkers for pre-screening purposes several different approaches were used, including machine learning algorithms.
All persons involved in the study had diabetes. Diabetic retinopathy (DR) was diagnosed by capturing 7-field fundus images, evaluated by two independent ophthalmologists. 165 eyes were examined (from 119 patients), 55 were diagnosed healthy and 110 images showed signs of DR. Tear samples were taken from all eyes and state-of-the-art nano-HPLC coupled ESI-MS/MS mass spectrometry protein identification was performed on all samples. Applicability of protein biomarkers was evaluated by six different optimally parameterized machine learning algorithms: Support Vector Machine, Recursive Partitioning, Random Forest, Naive Bayes, Logistic Regression, K-Nearest Neighbor.
Out of the six investigated machine learning algorithms the result of Recursive Partitioning proved to be the most accurate. The performance of the system realizing the above algorithm reached 74% sensitivity and 48% specificity.
Protein biomarkers selected and classified with machine learning algorithms alone are at present not recommended for screening purposes because of low specificity and sensitivity values. This tool can be potentially used to improve the results of image processing methods as a complementary tool in automatic or semiautomatic systems.
Diabetic retinopathy screening; Tear fluid biomarkers; Quantitative mass spectrometry; Pattern recognition
Despite their side-effects and the advent of systemic immunosuppressives and biologics, the use of corticosteroids remains in the management of patients with uveitis, particularly when inflammation is associated with systemic disease or when bilateral ocular disease is present. The use of topical corticosteroids as local therapy for anterior uveitis is well-established, but periocular injections of corticosteroid can also be used to control mild or moderate intraocular inflammation. More recently, intraocular corticosteroids such as triamcinolone and steroid-loaded vitreal inserts and implants have been found to be effective, including in refractory cases. Additional benefits are noted when ocular inflammation is unilateral or asymmetric, when local therapy may preclude the need to increase the systemic medication.
Implants in particular have gained prominence with evidence of efficacy including both dexamethasone and fluocinolone loaded devices. However, an appealing avenue of research lies in the development of non-corticosteroid drugs in order to avoid the side-effects that limit the appeal of injected corticosteroids. Several existing drugs are being assessed, including anti-VEGF compounds such as ranibizumab and bevacizumab, anti-tumour necrosis factor alpha antibodies such as infliximab, as well as older cytotoxic medications such as methotrexate and cyclosporine, with varying degrees of success. Intravitreal sirolimus is currently undergoing phase 3 trials in uveitis and other inflammatory pathways have also been proposed as suitable therapeutic targets. Furthermore, the advent of biotechnology is seeing advances in generation of new therapeutic molecules such as high affinity binding peptides or modified high affinity or bivalent single chain Fab fragments, offering higher specificity and possibility of topical delivery.
Angiolymphoid hyperplasia with eosinophilia (ALHE) is an uncommon benign lesion, primarily occurring in the head and neck. ALHE arising from the ocular adnexa is rare, and the bilateral presentation is especially rare in the eyelids.
A 64-year-old Japanese man presented with tearing. Multiple nodules, approximately 5 mm in size, were observed in bilateral upper and lower eyelids. Surgical excisions of the both eyelids masses were performed. Histopathological examination of the excised masses demonstrated proliferated blood vessels lined by plump endothelial cells together with a lymphoid and eosinopilic infiltrate, compatible with a diagnosis of ALHE. Flow cytometry studies showed that the mass consisted of mostly CD3-positive cells. During two-year follow-up, no recurrence of the mass was observed and the patient had no subjective symptom of tearing
ALHE may occur in the bilateral eyelids. The cause of ALHE remains uncertain, but our results of flow cytemetry suggest that T cells are related to the pathogenesis of this disease.
Angiolymphoid hyperplasia with eosinophilia; Kimura’s disease; Flow cytometry
Mycotic keratitis in human cornea has been rarely reported to be associated with a co-infection of filamentous fungi and yeast. This paper aims to report a case of mycotic keratitis concurrently infected by Exserohilum mcginnisii and Candida parapsilosis.
A Chinese female presented two superposed corneal infiltrates with different size and texture on her left eye. In vivo confocal microscopy showed hyper-reflective multiple linear with highly branching structures distributing in the anterior corneal stroma. Inoculations of the corneal lesion scrape concurrently grew two similar superposed colonies on Sabouraud dextrose and chocolate agar plate. The larger colony exhibited mould, cottony and floccose at the edge, while the smaller one showed creamy and shiny surface. Modified slide culture for mould revealed hyphae were septate, and conidia were brown, smooth-walled, cylindrical to slight clavate with 6 to 13 pseudosepta. Based on the morphology of microscopic and macroscopic characteristics, the mould was identified as Exserohilum mcginnisii. Smear of the non-mould colony showed ellipse or ovoid budding yeast-like cells with abundant pseudomycelium. Vitek Yeast Biochemical Card test identified the yeast as Candida parapsilosis. With treatment of combined oral itraconazole with topical amphotericin B, a complete resolution of the corneal infiltrate was achieved within 1.5 months.
This is the first documented case of human corneal infection by Exserohilum mcginnisii, and also the first report providing evidence of mycotic keratitis in human cornea concurrently infected by filamentous fungi and yeast.
Mycotic keratitis; Exserohilum mcginnisii; Candida parapsilosis