bluuebunny/crossref_metadata_2025 huggingface dataset:
Familial foveal aplasia
Authors: Murphy R. , Keegan D. , Flitcroft I.
Published: September 2017

Purpose

Foveal aplasia, or hypoplasia, refers to the lack of foveal depression with continuity of all neurosensory layers in the presumed location of the fovea. Whilst it is has been reported in cases of aniridia, albinism, microphthalmia and achromatopsia, foveal hypoplasia as an isolated entity is a rare phenomenon. We describe the presentation of a child and her mother with subsequent discussion on the spectrum of the disease.

Methods

Case report and literary synthesis.

Results

A frustrated 16 year old girl was brought in by her mother for review following several attendances to opticians with best‐corrected visual acuity of 6/9 both eyes. Ophthalmic examination revealed bilateral subtle spoke like cataracts with a featureless macula. There was no nystagmus present. Optical coherence tomography demonstrated lack of a foveal pit without extrusion of the plexiform layers. There was appropriate outer segment lengthening with a widened outer nuclear layer. Although asymptomatic, examination of her mother demonstrated best corrected visual acuity of 6/7.5 both eyes, with foveal tomography confirming foveal aplasia.

Conclusions

Although foveal aplasia typically presents with other ocular pathology, and most often exhibits nystagmus with decreased visual acuity, the entity can exist in isolation and without nystagmus. Familial cases, and those with pre senile cataracts, have been associated with PAX6 gene mutations and subsequent alterations in ocular morphogenesis.
Multimodal imaging of combined harmatoma of the retina and retinal pigment epithelium
Authors: Bobat H. , Kaprinis K. , De Salvo G.
Published: September 2017

Purpose

To describe the use of multimodal imaging in defining the anatomical features of combined harmatoma of the retina and retinal pigment epithelium (CHRRPE) and assess its role in the diagnosis and management of CHRRPE.

Methods

Retrospective case series of three patients with unilateral, juxta‐papillary CHRRPE, who underwent Spectralis Enhanced Depth Imaging Optical Coherence Tomography (EDI‐OCT), MultiColor (MC) and autofluorescence (AF) in addition to a complete ophthalmic examination.

Results

EDI‐OCT demonstrated thickening and disorganisation of retinal architecture, with intraretinal cysts disrupting the retinal layers and a loss of photoreceptors. An overlying epiretinal membrane was shown to be causing ‘mini‐peaks’ of the inner retinal surface in all cases and vitreoretinal traction in two cases. Details of the retinal pigment epithelium (RPE) were revealed, including RPE thickening and sectoral atrophy. MC revealed areas of red‐shifting, demonstrating partial pigmentation. On green reflectance (GR) the degree of inner retinal distortion and extent of macular involvement could be visualised. Near infra‐red (NIRR) reflectance displayed the lesions as areas of hyporeflectance and allowed delineation of the tumour borders. On AF, the lesions were represented by areas of hypo‐autofluorescence that obscured the normal blood vessel hypo‐autofluorescence.

Conclusions

In this case series, multimodal imaging enabled the anatomical characteristics of CHRRPE to be defined in greater detail. NIRR enabled better visualisation of tumour boundaries and the extent of macular involvement, which may be useful in assessing the impact on visual function. GR better defined the degree of inner retinal distortion, which may be useful in surgical management decisions. We believe that multimodal imaging is a valuable adjunct in correctly diagnosing and managing CHRRPE.
Retinal diseases of patients without discomfort associated with retinal abnormalities
Authors: Lee S.
Published: September 2017

Purpose

To identify the retinal diseases in patients who did not complain discomfort of retinal abnormalities.

Methods

A retrospective chart review of 1516 eyes, 765 patients who visited for cataract operation, glaucoma evaluation, refractive surgery was performed. We evaluated fundus abnormalities by fundus examination using slit lamp and systemic risk factors.

Results

The mean age of the 765 patients was 63.2 _ 14.6 years (18‐93 years), and 34.2% were men. Four hundred ninety seven eyes (32.8%) were diagnosed as retinal diseases. Peripheral retinal degeneration that does not need treatment in 119 eyes (include atypical retinitis pigmentosa in 2 eyes), peripheral retinal degeneration that does need barrier laser in 65 eyes, epiretinal membrane in 97 eyes, diabetic retinopathy in 57 eyes, vitreous hemorrhage in 4 eyes, retinal hemorrhage in 23 eyes, retinal vascular occlusion diseases in 16 eyes, degeneration at posterior pole (pp) in 36 eyes (include central serous chorioretinopathy in 1 eye), exudation at pp in 103 eyes, age related macular degeneration (AMD) in 47 eyes were identified. Treatment performed in 104 patients (13.6%), 146 eyes (9.6%) _ medication in 53 eyes, laser photocoagulation in 71 eyes, intravitreal injection in 7 eyes, vitrectomy in 15 eyes. Peripheral retinal degeneration showed significant positive correlations with higher degree myopia (p < 0.001).AMD, vascular occlusion disease, degeneration at pp, exudation at pp showed significant positive correlations with increased age (p < 0.001, = 0.008, < 0.001, < 0.001).

Conclusions

The retinal examination, including the peripheral retina, should be carried out in patients without discomfort of retinal abnormalities.
Functionalized magnetic nanoparticles as a novel strategy for the treatment of diabetic retinopathy
Authors: Amato R. , Dal Monte M. , Lulli M. , Cammalleri M. , Raffa V. , Casini G.
Published: September 2017

Purpose

Neuroprotection‐based strategies may be exploited to treat diabetic retinopathy (DR). Our aim is to establish a method for magnetic nanoparticle (MNP)‐mediated delivery of neuroprotectants to the retina, expecting a prolonged therapeutic action. In the first phase of this project, we assessed the bioavailability and bioactivity of the neuroprotectant octreotide (OCT), a somatostatin analog, delivered as OCT‐MNP.

Methods

The effects of OCT‐MNP and those of free OCT (fOCT) were evaluated in in vitro assays using human retinal endothelial cells (HRECs), in H2O2‐treated ex vivo retinal explants, and in vivo in untreated or in kainate‐injected mouse eyes. In the in vitro assays, vascular endothelial growth factor (VEGF)‐induced HREC proliferation, migration and tube formation were assessed. In the ex vivo and in vivo models, qPCR, histochemical and immunohistochemical techniques were used.

Results

In HRECs, 1 µM OCT‐MNP displayed the same efficacy of 1 µM fOCT in inhibiting VEGF‐induced changes. In H2O2‐treated explants, both 1 µM OCT‐MNP and 1 µM fOCT inhibited apoptosis. In particular, the efficacy of OCT‐MNP was detected at concentrations as low as 0.001 µM. After intraocular injection in mouse eyes, OCT‐MNP were localized to the retinal pigment epithelium and they did not induce any apoptotic sign in the retina. 1 µM OCT‐MNP or fOCT co‐delivered via intraocular injection with 100 µM kainate similarly protected the retina from apoptosis.

Conclusions

OCT‐MNP maintain the functional properties of fOCT, in particular its neuroprotective capabilities. Intraocularly injected OCT‐MNP are not toxic. They penetrate the retina, where they may release OCT in a sustained manner. Although needing confirmatory observations, these preliminary data are encouraging for a possible use of MNP‐mediated drug delivery to treat DR.
The time course of contrast sensitivity recovery after a pigment bleaching is delayed in subjects with abdominal obesity
Authors: Puell M. , Jemni N. , Veselinova‐Nikolova A. , Fernández‐Balbuena A.
Published: September 2017

Purpose

The abdominal obesity is an anthropometric marker associated with inflammation and age‐related macular degeneration (AMD). We examined the association between mesopic contrast recovery dynamics and abdominal obesity in older adults with normal macular health.

Methods

29 eyes of 29 healthy subjects (47–70 years) divided in two groups: a group without abdominal obesity (waist‐to‐height ratio (WHtR) <0.5; n = 15) and a group with abdominal obesity (WtHR ≥ 0.5; n = 14) were examined. The recovery of contrast sensitivity for sine‐wave gratings of low spatial frequency (1 cycles per degree) and low mean luminance (0.1 cd.m−2) was measured within the central retina for 6 minutes in darkness after photo‐pigment bleaching. Sensitivity recovery functions were fitted to an exponential decay function. The time constant for recovery (tau, seconds), elevation and final contrast thresholds (CT) were calculated. The intersession repeatability of the method was determined by the Bland‐Altman coefficient of repeatability (COR). Visual acuity (VA), body mass index (BMI) and WtHR were obtained.

Results

The mean tau was 42 s slower in the group with abdominal obesity (83.84 ± 35.78 s) than in the group without abdominal obesity (41.94 ± 13.70 s) (p < 0.001). The mean elevation and final CTs did not vary significantly between groups. Forward stepwise regression analysis revealed that tau was independently correlated with WtHR (r = 0.74; p < 0.0001), but not with BMI, CT, VA or age. There was no significant relationship between WtHR and CTs. Intersession repeatability of recovery measurements was high (tau, COR = ±16 s).

Conclusions

The time constant for contrast sensitivity recovery after a pigment bleaching increases with abdominal obesity in eyes of older adults with normal macular health. Testing for the combination of these factors would allow for early detection of AMD.
Effects of plasma kallikrein inhibitors in an in vitro RPE oxidative stress model
Authors: Alonso‐Alonso M.L. , Hampton S.L. , Williams J.L. , García‐Gutiérrez M.T. , Fernández‐Bueno I. , Srivastava G.K. , Pastor J.C. , Diebold Y.
Published: September 2017

Purpose

Plasma Kallikrein (PK) Inhibitors (PKI) are a promising treatment for retinal diseases such as diabetic macular edema, where PK activity is implicated. Our aim was to set up an in vitro model of chronic oxidative stress in the retinal pigment epithelium cell line ARPE19 and use it to test the effect of 8 PKI on cell viability and proliferation.

Methods

ARPE19 cells were grown to a sub‐confluence stage, synchronized, and exposed to different dilutions of glucose oxidase (GOx) from Aspergillus niger, culture medium (− control) and benzalkonium chloride (+ control) for 24 hr. Cell viability and apoptosis were analyzed (MTT assay and caspase‐3/7 detection, respectively). The oxidative stressed cells were exposed to 8 different PKI developed by KalVista (Salisbury, UK) at 100 nm and 1 μm. Also, ARPE19 cells were exposed to PKI previously and simultaneously to GOx and cell viability and proliferation were assessed (alamarBlue® assays).

Results

Exposure of ARPE19 to GOx induced dose‐dependent decreased cell viability and increased cell apoptosis. A sub‐lethal GOx dose reducing viability by 30% and increasing apoptosis by 59% was chosen for PKI exposure experiments. Exposure of GOx stressed cells to PKI for 24 hr did not further reduce cell viability after 5 days. No effect on cell proliferation was observed when GOx stressed cells were either pre‐treated or simultaneously exposed to PKI.

Conclusions

GOx oxidative sub‐lethal stress model in ARPE19 cells may be used for screening new drugs with therapeutic potential for retinal diseases. The PKI did not reduce GOx‐induced cytotoxic effects in RPE cells suggesting plasma kallikrein has no role in this stress mechanism. Support: FP7‐PEOPLE‐2013‐IAPP (612218/3D‐NET) and Regional Junta de Castilla y León Scholarship/European Social Fund Program (Va040‐13).
Changes in retinal arteriolar oxygen saturation predict disease activity in patients treated with aflibercept for neovascular age‐related macular degeneration
Authors: Jakobsen D.B. , Torp T.L. , Stefánsson E. , Peto T. , Grauslund J.
Published: September 2017

Purpose

In order to individualize treatment, it is important to identify non‐invasive markers for disease activity in patients with neovascular age‐related macular degeneration (nAMD). In this prospective study we aimed to investigate changes in retinal oxygen saturation in patients with nAMD before and after initial aflibercept therapy.

Methods

Sixty‐six eyes diagnosed with nAMD were included. All patients received three monthly injections with 2.0 mg aflibercept and were then divided into responders and non‐responders according to post‐treatment disease activity. Non‐responders by definition had loss of ≥5 ETDRS letters or residual retinal edema (based on spectral domain‐OCT) or macular hemorrhage. Retinal oximetry (Oxymap T1, Oxymap, Reykjavik, Iceland) was performed at baseline and follow‐up, and images were graded by a trained grader.

Results

At baseline, mean age was 80.0 years and 62.1% were women. Thirty‐six of 66 patients (54.5%) were non‐responders, and these were younger (77.8 vs. 82.8 years, p=0.01) and trended towards a higher increase in retinal arteriolar oxygen saturation from baseline to follow‐up (+1.0% vs. +0.1%, p=0.06). In a multiple logistic regression model, adjusted for sex, age, diabetes and smoking, each 1%‐point increment in retinal arteriolar oxygen saturation from baseline to follow‐up was independently associated with a lower chance of full treatment response (odds ratio 0.78, 95% confidence interval 0.62‐0.98, p=0.036). Retinal venular oxygen saturation did not associate with pre‐ or post‐treatment disease activity.

Conclusions

Retinal oxygen saturation may be a promising marker for disease activity in nAMD. Increasing retinal arteriolar oxygen saturation in response to initial intravitreal aflibercept therapy associates with a 22% lower chance of full treatment response after initial aflibercept therapy.
Intraocular expression of microfibrillar‐associated protein 4 (MFAP4) in patients with neovascular age‐related macular degeneration (nAMD)
Authors: Abrahamsen Ravn L. , Leer Blindbæk S. , Schlosser A. , Koss M. , Dacheva I. , Lind M. , Holmskov U. , Sørensen G.L. , Grauslund J.
Published: September 2017

Purpose

Pharmacological inhibition of the constitutively expressed extracellular matrix integrin ligand MFAP4 is previously shown with efficacy in mouse model of choroidal neovascularization. To evaluate the intraocular expression of MFAP4 in the anterior chamber (CA) and vitreous body (VB) in patients with nAMD (cases) as compared to controls.

Methods

Aqueous humour from 29 patients and vitreous humour of 54 patients were collected during elective cataract surgery and pars plana vitrectomy, respectively. Samples from the CA consisted of three cases and 26 controls and from the VB of 42 cases and 12 controls. The 42 samples from the VB were further divided into four subgroups depending on the subtype of nAMD (CNV with retinal hemorrhage, CNV without retinal hemorrhage, fibrosis, PE‐detachment). Samples were analyzed by the AlphaLISA technique. Wilcoxon rank‐sum test and Kruskall‐Wallis test was used to test for differences between two and multiple groups, respectively.

Results

Median MFAP4 was significantly lower in the anterior chamber as compared to the VB (7.9 Units/ml vs. 17.9 Units/ml, p < 0.0001). There was no difference in the median MFAP4 between cases and controls (CA: 8.1 Units/ml vs. 7.9 Units/ml, p = 0.33) (VB: 17.9 Units/ml vs. 17.8, p = 0.79). Neither were there any differences between nAMD‐subgroups in the VB (18.7 Units/ml vs. 24.4 Unit/ml vs 15.1 Units/ml vs. 17.5 Units/ml, p = 0.57).

Conclusions

These preliminary results demonstrated intraocular expression of MFAP4 in the human eye. Further, a higher expression of MFAP4 was demonstrated in the vitreous body as compared to the anterior chamber. Vitreal MFAP4 does not appear to be regulated with neovascular disease supporting that MFAP4 is constitutively expressed and permissive for integrin activation during neovascularization.
Does femtosecond laser assisted penetrating keratoplasty lead to less astigmatism in keratoconus patients, compared with conventional penetrating keratoplasy?
Authors: Sten L.G.B. , Råen M. , Brevik T.B. , Drolsum L.
Published: September 2017

Purpose

Visual impairing including high irregular astigmatism is a well‐known problem after penetrating keratoplasty (PK). The femtosecond (FS) laser technique allows completely new trephination methods such as the zig‐zag, top hat or the mushroom cutting profiles, which result in a more rapid and stable wound healing. In the present study we compare conventional PK and FS laser PK concerning astigmatism and visual outcome in keratoconus patients 2 years postoperatively

Methods

A total of 67 patients were operated with PK between September 2013 and June 2015 at Oslo University Hospital, Norway. All patients were examined 2 years after surgery. Ten keratoconus patients who were operated with FS laser‐assisted PK (FS group) were included, using Alcon Wavelight FS200 Femtosecond Laser, and compared with a control group who underwent conventional PK (n = 20). Controls were matched for diagnosis, age, gender and time of operation. Postoperative results regarding astigmatism and visual outcome were compared.

Results

At the 2 years follow‐up, the mean logMAR BCVA was 0.17 ± 0.14 in the FS‐group and 0.16 ± 0.19 in the control group (p = 0.89). The mean spherical equivalent was ‐1.91 ± 4.58 in the FS‐group, and ‐3.08 ± 2.81 in the control group (p = 0.39). The mean subjective and corneal cylinder was ‐6.08 ± 2.50 and 7.71 ± 3.78 in the FS‐group, compared to ‐4.89 ± 2.57 (p = 0.24) and 5.73 ± 3.84 in the control group (p = 0.21), respectively. K‐mean was 44.00 D ± 3.99 in the FS‐group and 44.98 D ± 1.63 in the control group (p = 0.50). ECD was 1456 cells/mm²± 325 in the FS‐group, and 1679 cells/mm²± 475 in the control group (p = 0.22).

Conclusions

Even though the study included relatively few eyes, the findings confirm previous studies. No significant difference in astigmatism or visual outcome was found between the two groups 2 years postoperatively.
Corneal confocal microscopy assessment in contact lens discomfort
Authors: Canadas Suarez P. , López‐de la Rosa A. , Arroyo‐del Arroyo C. , López‐Miguel A. , Enríquez‐de‐Salamanca A. , Gonzalez‐Garcia M.J.
Published: September 2017

Purpose

The aim of this study was to analyze whether symptoms of discomfort in CL wearers were associated to changes in the nerve morphology and/or the density of dendritic cells in the corneal sub‐basal nerve plexus.

Methods

Sixty subjects were included: 20 symptomatic CL wearers (SCLW), 20 asymptomatic CL wearers (ACLW), and 20 non wearers (NCLW). Ocular Surface Disease Index (OSDI), visual acuity, tear osmolarity, biomicroscopy findings, tear film break‐up time, corneal and conjunctival staining, Schirmer test, and confocal microscopy were performed. In the confocal images number and density of nerves, density of nerve branches, grade of nerve tortuosity, and density of dendritic cells were analyzed.

Results

OSDI and lid roughness was higher in the SCLW group (p=0.S009 and p=0.04, respectively), limbal hyperaemia was raised in the ACLW group (p=0.S009), and tear osmolarity was increased in both CL wearers groups (p=0.000), in comparison with the NCLW group. Subjects were divided into low and high density of dendritic cells using a 75 cells/mm2 cut‐off. This distribution was significantly different (p=0.04) between the CL wearers (21 and 19 subjects had low and high cell density, respectively) and the NCLW group (16 and 4, respectively). The CL type was significantly different (p=0.011) between CL wearers with low (4 and 17 subjects wear conventional and silicone hydrogel CLs, respectively) and high (11 and 8, respectively) cell density.

Conclusions

Symptoms of discomfort in CL wearers seem not to be related to changes in the nerve morphology or density of dendritic cells in the corneal sub‐basal nerve plexus.
The impact of daily disposable soft contact lens wear on tear film surface quality over a three month period
Authors: Mousavi M. , Garaszczuk I.K. , Jesus D.A. , Szczesna‐Iskander D. , Iskander D.R.
Published: September 2017

Purpose

To study the changes in Tear Film Surface Quality (TFSQ) on a Silicon Hydrogel (SiHy) and a Hydrogel (Hy) daily contact lens (CL), during a follow‐up period of three months.

Methods

Forty‐six subjects aged 25.5 ± 4.3 (mean ± standard deviation) years with a refractive error limited to ±4.50 spherical and ±0.75 cylindrical dioptres were recruited. Based on a pre‐clinical analysis which took into account visual acuity (VA), comfort, and fitting, 31 subjects were fitted with SiHy and 13 with Hy lenses. TFSQ was studied based on measurements of the first and the mean non‐invasive keratography tear break up time (F/M–NIKBUT). All measurements were acquired at baseline, post four hours (4 h) and three months (3 m) of CL lens wear. Ocular Surface Disease Index (OSDI) questionnaire was also completed.

Results

The results of the OSDI questionnaire showed an average improvement of 3.09 and 4.16 units for 3 m visit for SiHy and Hy lens, respectively. Nevertheless, this improvement was not statistically significant (p = 0.144 and p = 0.215). For F‐NIKBUT, there was no significant difference between 4h and 3m measurements (p=0.490 and p = 0.588 for SiHy and Hy lens, respectively). For M‐NIKBUT, there was no significant difference for SiHy and Hy groups between baseline and 4 h (p = 0.052 and p = 0.110, respectively). However, there was a significant difference between baseline and 3 m for SiHy group (p = 0.009) but not for the Hy group (p = 0.376). Lastly, no significant differences were observed between 4 h and 3 m M‐NIKBUT measurements for both lenses (p = 0.746 and p = 0.273 for SiHy and Hy lens, respectively).

Conclusions

The results indicate that estimates of 4 h of lens wear NIKBUT can be used to predict those at a 3 m visit. Also, Hy lens appeared to have less impact on TFSQ than the SiHy lens.
Comparative study of retinal nerve fiber layer and ganglion cell complex thickness between Korean patients with unilateral exfoliation syndrome and normal control
Authors: Lim S.
Published: September 2017

Purpose

To compare retinal nerve fiber layer (RNFL) thickness and ganglion cell complex (GCC) thickness by using spectral domain optical coherence tomography (OCT) in unilateral exfoliation syndrome (XFS) and age matched control.

Methods

This prospective case control study include total of 54 eyes of 27 unilateral XFS patients and 27 age matched control subjects. The retinal nerve fiber layer and ganglion cell complex measurements were performed using spectral domain OCT (RT‐Vue 100, Optovue) after pupillary dilation. Statistical analyses were performed using SPSS for Windows software version 18.0. Independent t test and chi‐square tests were used to compare baseline characteristics of unilateral XFS and Control.

Results

Mean age of XFS was 73.3 years and Age‐matched control was 74.3 years. Both group demonstrated male preponderance; however, there was no statistical difference. Average circumpapilary RNFL and inferior RNFL were significantly thinner in XFS than healthy age matched control. Moreover, average GCC and inferior GCC were thinner in XFS than control.

Conclusions

Patients with XFS without visual field defect showed thinner RNFL thickness and GCC thickness. This findings implicit XFS itself might be an risk factor for development of glaucomatous optic disk and retinal nerve fiber layer damage.
Effects of short oxidative stress exposure on lens epithelial cells
Authors: D'antin J.C. , Barraquer R.I. , Michael R.
Published: September 2017

Purpose

To observe the reactions of lens epithelial cells (LECs) to a short exposure of an elevated oxidative stress. To help find future treatments for the prevention of posterior capsule opacification. Using cultured human lens capsules as an experimental model and hydrogen peroxide (H2O2) as the stress inducer.

Methods

Lens capsule‐ciliary body complexes were extracted from human donor eyes. Samples were exposed to 30 mM H2O2 for 5 min (n = 8) or used as untreated controls (n = 9). H2O2 was applied after lens extraction through intercapsular irrigation using a silicone irrigation ring. Samples were cultured on average for 30 days, during which dark field and lateral illumination photos were taken every 2–3 days. These photos were used to observe and quantify, time until cellular growth and subsequent confluence on the posterior capsule. Three of the controls were not cultured, in order to observe starting conditions.

Results

All control samples showed signs of normal cellular growth on the posterior capsule on average by day 6. LEC proliferation and migration was not observed on H2O2 samples until day 22. Four H2O2 samples showed signs of growth. The overall delay of cell growth compared to control was significant (H2O2 p < 0.001). Until day 29 none of the exposed samples that had shown growth reached confluence. Half of controls were confluent on day 10, 83% on day 20 and all by day 26. The average cellular migration speed of controls and H2O2 samples were very similar, being 3.2 and 3.0 (mm2/day) respectively.

Conclusions

Exposure of lens epithelial cells to an elevated concentration of H2O2 for a short period of time does not seem to lead to immediate cell death as expected, but rather arrests the cell cycle. Surprisingly, after cells have recovered from the oxidative stress, they grow at a normal rate.
Intraocular implant calculation based on the fellow eye measurements
Authors: Kalemaki M.
Published: September 2017

Purpose

To estimate the postoperative refractive error when the use of the IOL‐Master is not possible in Cataract Surgery and the calculation of the Intraocular Lens (IOL) is based on the fellow eye measurements.

Methods

The records of 150 patients who underwent Cataract surgery between September 2015 and September 2016 were reviewed. Performing IOL‐Master measurements was not possible and the calculation of the IOL was based on the IOL‐Master measurements of the fellow eye.

Results

The refractive error was −0.75 sph with a standard deviation from −1.25 to +0.75.

Conclusions

IOL calculation can be based on the IOL‐Master measurements of the fellow eye, when measurements of the eye that is about to be operated cannot be performed.
Nrf‐2 and PGC1‐alpha deletion affects ultrastructural changes in retinal pigmented epithelium associated with the changes of oxidative stress and autophagy markers expression pattern in compound null mice
Authors: Kivinen N. , Viiri J. , Koskela A. , Kettunen M. , Koistinen A. , Winiarczyk M. , Kauppinen A. , Kaarniranta K. , Felszeghy S.
Published: September 2017

Purpose

There is increasing evidence that NF‐E2‐related factor 2 (Nrf‐2) and peroxisome proliferator‐activated receptor‐gamma coactivator 1‐alpha (PGC‐1α) participate in age‐related retinal degeneration process. Our study aimed to provide de novo, in and ex vivo high‐resolution imaging of eyes from different degenerative mouse models mimicking cellular changes observed in aged retinal pigmented epithelium (RPE).

Methods

The gross morphological alterations of eyes were analyzed by in vivo micro MRI. Oxidative stress marker (4‐HNE) and the autophagy regulators (p62/SQSTM1, Beclin‐1, LC3, Ubiquitin) were examined on thin wax sections by highly specific immunohistochemistry using semi‐quantitative computer aided image analysis. Moreover accurate transmission electron microscopy ultrastructural assay was carried out to monitor the organelle changes in the RPE obtained from Nrf‐2/PGC‐1α knockout mice.

Results

Collectively, age‐related autophagy decline and mitochondrial dysfunction was recorded in the RPE joined with upregulation of stress related biomarkers.

Conclusions

Taken together, our experimental data highlight for the first time that common deletion of Nrf‐2 and PGC‐1α might appear to have potential and broad applicability for retinal aging research.
Neuro‐retinal changes evaluation in multiple sclerosis patients: 10 years follow‐up
Authors: Rodrigo M.J. , Garcia‐Martin E. , Orduna E. , Vilades E. , Satue M. , Cipres M. , Obis J.
Published: September 2017

Purpose

To analyze functional and structural changes in the retina and optic nerve (ON) in patients with multiple sclerosis (MS) compared to healthy controls (C) and after 10 years of follow‐up.

Methods

Fifty eyes of patients with mild‐moderate MS were evaluated and compared to 50 eyes of C at a baseline visit and at 10 years of follow‐up. The following functional parameters were evaluated: best‐corrected visual acuity (BCVA), color vision examined with the Ishihara test, and mean deviation of visual field (VF) analyzed using the Humphrey perimetry. The structural parameters of the ON were also studied using the NSITE axonal application of the optical coherence tomograph (OCT) Heidelberg Spectralis.

Results

No differences were found in the functional parameters in MS patients compared to C, neither at 10 years of follow‐up (p > 0.05). However a statistically significant decrease was observed in the structural parameters between C and MS patients at 10 years of follow‐up: mean, nasal‐inferior (NI), temporal‐inferior (TI), temporal (T), temporal‐superior (TS), papillomacular bundle and nasal/temporal (N/T) ratio thickness (p < 0.001), but also in the axonal thickness, specifically in the mean, TI, T, TS, papillomacular bundle and N/T ratio thickness (p < 0.001) measured with OCT in patients with MS after 10 years of disease progression. A higher functional disability using the Expanded Disability Status Scale was also recorded.

Conclusions

Axonal damage can be analyzed and quantified in the retina and ON using the OCT in MS. Patients with MS showed significant decrease in the retina nerve fiber layer at 10 years of follow–up compared to C and a progressive axonal death (without outbreaks) that could be detected and quantified using the OCT, but not with the functional tests (BCVA, color and VF).
Visual function in multiple sclerosis patients treated with Fingolimob during two years of follow‐up
Authors:  Ciprés Alastuey M. , García Martín E. , Bambó Rubio M.P. , Vilades Palomar E. , Satué Palacián M. , Obis Alfaro J. , Rodrigo Sanjuan M.J. , Orduna Hospital E.
Published: September 2017

Purpose

To evaluate visual function changes in multiple sclerosis (MS) patients treated with Fingolimob during two years.

Methods

A total of 31 eyes of 16 MS patients that were going to start Fingolimob treatment were included. All of them underwent an ophtalmic examination including best corrected visual acuity (BCVA) using ETDRS optotype with 100%, 2,5% and 1.25% contrast; contrast sensitivity using CSV 100 E and Pelli‐Robson tests and cromatic vision using Farsworth and Lanthony D15 tests. Quality of life was evaluated by the MSQOL questionnaire. The same protocol was repeated 2 years later.

Results

A significant reduction of visual acuity was observed after two years of follow‐ up in 2.5% (0.33 ± 0.023 vs 0.39 ± 0.16; p < 0.001) and 1.25% (0.43 ± 0.05 vs 0.54 ± 0.22; p < 0.001) contrasts. All CSV frequencies showed a significant decrease except 18 cpd (3 cpd: 1.78 vs 1.73 ± 0.17; 6 cpd: 1.94 ± 0.17 vs 1.85 ± 0.24; 12 cpd: 1.69 vs 1.39 ± 0.37; p < 0.001). A progresive reduction in chromatic vision (Farnsworth and Lanthony test, p < 0.001) was also found. MSQOL‐54 questionnarie result was significatly lower after two years in physical (p = 0.023) and mental (p = 0.032) health sections.

Conclusions

MS patients treated with Fingolimob present progressive changes in visual acuity, contrast sensivity, and chromatic vision. Visual function tests may be an useful tool to evaluate the progression of neurodegenerative diseases and treatment effectiveness.
Ophtara centers of expertise in France: Fostering collaborative research and patient care for rare eye diseases
Authors: Bremond‐Gignac D. , Mincheva Z. , DeVergnes N. , Valleix S. , Robert M.
Published: September 2017

Purpose

The French National Reference Center on Rare Diseases in Ophthalmology OPHTARA was labeled in 2006. This expertise center (re‐labeling in 2017) includes Necker coordinating site, 3 component sites (Paris University Hospitals) and 16 national competence centers. Necker is unique center for rare eye diseases and ocular surgery for children. OPHTARA ensures patient care (children and adults) and covers all rare eye diseases, mostly genetically determined. OPHTARA and ocular genetics laboratory provides optimal genetic diagnosis.

Methods

OPHTARA recent structure gathers together 20 centers of expertise (CEs) localized all over France and 2 overseas territories. The center is attached to the National HealthCare Network SENSGENE and it is unique consortium part of European Reference Network (ERN) EYE, accredited in 2016. Rare eye disorders were divided in 4 goupes: diseases of anterior/posterior segment, of lacrimal/eyelid/orbit/, panocular and syndromic.

Results

OPHTARA is incrementing a database for rare diseases CEMARA including actually 7600 registered patients (2008‐2017). The refferal Center established an optimal overall patient management strategy. OPHTARA develops actions concerning patient diagnosis, monitoring and care, research, clinical trials, education, professional training and information for patients and their families. The reference center defines healthcare protocols and guidelines, being the contact for many patient's associations.

Conclusions

OPHTARA ensures a role of expertise, multidisciplinary care and follow‐up of patients thanks to the specific recognized skills of HCPs experts in rare ocular diseases. The networking could lead to the gathering of the scarce expertise in France to ensure high quality care for rare eye disease patients. European dimension of OPHTARA health care is proved by ERN EYE integration.
Microperimetry by optic nerve atrophy
Authors: Ioyleva E. , Krivosheeva M.
Published: September 2017

Purpose

To develop an algorithm testing of patients with optic nerve atrophy by microperimetry with different types of functional disorders.

Methods

The study included 40 patients with bilateral atrophy of the optic nerve, age 33.0 ± 1.88 years, with confirmed diagnosis of multiple sclerosis. 11 patients had a history of monocular optic neuritis – the first group (11 eyes), 29 without a history of optic neuritis – the second group (29 eyes). Preliminary, a Humphrey HFA‐75i survey was conducted on a 120‐point testing program. Microperimetry was performed on the MR‐1 (Nidek technologies, Vigonza, Italy). We selected a pattern, fixation target, stimulus, test mode. In some cases it is necessary an individual selection of study parameters.

Results

The authors developed an algorithm for testing patients with optic nerve atrophy due to multiple sclerosis. The first group (11 patients) – visus 0.1‐0.4 – pattern macula 12° 10 dB, stimulus Goldmann III, fixation target – single cross 4°. In the first group mean sensivity 8.21 ± 2.3 dB, central visual field defects and unstable fixation 91.81 ± 2.72%.The second group (29 patients) – visus 0.5‐1.0 – pattern retina 40° 20 dB, stimulus Goldmann III, fixation target – four crosses 4°. In the second group mean sensivity 15.32 ± 0.84 dB, central and paracentral visual field defects and stable fixation 91.81 ± 2.72%.The results of microperimetry differed depending on the size of visual field defects and visual acuity. Thus, in the group with low visual acuity, there was a lower central sensitivity and more significant defects of the central field of vision compared to the group with a high visual acuity.

Conclusions

In the “Eye Microsurgery Complex”, Moscow, at the first has been developed an algorithm of microperimetry in patients with MS with different visual acuity and stability of fixation.
Visual status of patient with syndrome of Moebius
Authors: BUSHUYEVA N. , Romanenko D. , Dukhayer S.
Published: September 2017

Purpose

To analyze functional state of visual status in a patient with Moebius syndrome during 16 years of follow‐up.

Methods

Retrospective analysis of clinical course of Moebius syndrome in a patient in the age 0.5 ‐ 16 years.

Results

Parents appealed to the Institute because of unusual state of the child (lack of facial expressions and eye mobility). After the ophthalmologic and neurological examination, a diagnosis was made: Moebius syndrome. Underdevelopment of VII, IX, XII pairs of cranial nerves. Myopic astigmatism. At 10 years old facial asymmetry, exotropy with vertical component, positive traction test on both sides and lagophthalmus 3 mm at downgaze were noted. Best corrected visual acuity of both eyes is 0.2. Perimetry both eyes: concentric narrowing up to 40º from temporal and nasal sides, up to 20º from above and from below. Optic discs are pale, there are pigmentless sections of retinal dystrophy on the periphery and near the optic discs. Pleoptoortoptic treatment was carried out. As a result of regular courses of electrostimulation of extraocular muscles, by the age of 16, a tendency to insignificant motility of the eyes upwards appeared. Convergence was absent. Best corrected visual acuity decreased to 0.1 in both eyes. Significant help in diagnosis was provided by computer pupillography [Bushuyeva NN et al., 2003], which accurately records and measures pupil area. The initial size of the pupil area was: on the right eye 17.9 sq mm, and on the left eye 13.1 sq mm. After the flash, the pupil of the left eye narrowed to 3.7 sq mm and the right eye ‐ to 15.2 sq mm.

Conclusions

Pupillography allows evaluating vegetative nervous system status in Moebius syndrome patients. Electrostimulation of extraocular muscles allows slightly improving ocular motility of these patients. Obtained data needs further investigations on larger number of patients
Timing of changes in the entropy of the electroretinogram with glaucoma
Authors: Sarossy M. , Aliahmad B. , Kumar D.
Published: September 2017

Purpose

The Photopic Negative Response (PhNR) of the electroretinogram (ERG) has been shown to be reduced in glaucoma in clinical studies and animal models. Its slow and noisy nature makes the implicit time of the negative going peak of the response difficult to define, most studies have focussed on the amplitude of the response rather than its timing. In this study, we estimate the timing of changes in signal entropy in a normal and glaucoma cohort from the ERG with the PhNR stimulus.

Methods

The left eyes of 21 glaucoma patients (age 34–86 mean 66.4) and 18 normal aged matched controls (44–84 mean 60.7) were tested. ERGs were measured with the LKC RetEval device with the integrated skin electrodes using a red flash stimulus (4ms) on a blue background (10 cd/m2) after preadaptation using the mini‐Ganzfeld. B‐wave amplitude and implicit time were measured with the device software. Entropy analysis was performed in R on each raw sweep with a sliding window of 150 samples. The window was advanced in increments of one sample. The entropy at each window timepoint was averaged for all the sweeps. The terminal rise in entropy was detected by finding the maximum of the first derivative after filtration with the Komolgorov Zurbenko adaptive (kza) filter.

Results

There was no difference between the glaucomas and controls in the implicit time of the b‐wave (31.1 ms vs 30.6 ms p = 0.66) or its amplitude (19.3 vs 17.0 mv p = 0.18). The timing of the rise in entropy after the b‐wave was significantly different with the glaucoma cohort rising sooner (74.7 ms vs 79.8 ms p = 0.04). The gradient of the entropy rise was not significantly different.

Conclusions

The entropy rise after the flash stimulation corresponds to the end of the electrical activity evoked by the stimulus. The difference in glaucoma may be due to a relative loss of peripheral ganglion cells.
Across‐frequency impairment in seeing a temporal gap
Authors: Hirose N. , Okuda Y. , Mori S.
Published: September 2017

Purpose

To assess the effects of employing separate spatial frequencies for leading and trailing markers on detection of a temporal gap between the two markers.

Methods

Twelve normal observers were tested to measure gap detection thresholds. Gaussian‐windowed sinusoidal gratings were used for markers bounding a gap and thresholds were determined using an adaptive tracking procedure. Spatial frequencies of the leading and the trailing markers were orthogonally manipulated to be either 2 or 4 cpd. The trailing markers were tilted slightly clockwise from the vertical leading markers in order to isolate the effects of frequency change from those of pattern change. In separate blocks of trials, four combinations of the leading and trailing frequencies were tested.

Results

With markers of identical frequency, gap thresholds were higher for 4 cpd than for 2 cpd markers, replicating well‐established findings of impaired temporal resolution with increasing spatial frequency. Gap thresholds for markers of different frequencies were even higher than the 4‐cpd within‐frequency thresholds.

Conclusions

Seeing a temporal gap becomes difficult when spatial frequency change is introduced between gap markers. We propose that temporal processing across different spatial frequency channels leads to impaired gap detection.
Orbital lymphoma presenting as a recurrence of posterior scleritis after treatment with adalimumab
Authors: Deroo L. , Vermeersch H. , Willaert R. , De Keyzer F. , Vanneuville B. , De Schryver I.
Published: September 2017

Purpose

To report a case of recurrent therapy‐resistant posterior scleritis in a patient with seronegative rheumatoid arthritis (RA). Following treatment with a tumor necrosis factor inhibitor (TNFi), an orbital lymphoma masquerading as a recurrence of posterior scleritis occurred.

Methods

Retrospective chart review.

Results

A 62‐year‐old woman was diagnosed with a unilateral posterior scleritis in 2008. Ophthalmological workup, including orbital imaging, confirmed the diagnosis. Complete systemic workup revealed a seronegative RA. Due to limited responsiveness to corticosteroids and conventional immunosuppressive therapy, adalimumab, a TNFi, was successfully initiated. Despite a recurrence‐free period of 27 months, a relapse of posterior scleritis occurred. Systemic evaluation and orbital imaging showed a small orbital mass. Orbital biopsy confirmed the diagnosis of an extranodal marginal zone lymphoma or MALT.

Conclusions

Adalimumab is effective as a second‐line anti‐inflammatory drug in posterior scleritis. Studying the link between lymphoma and RA, several reports confirm an increased risk of lymphomas in RA with high disease activity. Although TNFi increases the risk of melanoma, there appears to be no increased risk of lymphoma. Whether it may be related to the underlying disease rather than to the treatment, ophthalmologists should be aware of the risk of a lymphoma.
Immunosuppression for uveal effusion syndrome – a report of two cases
Authors: Staniszewski B. , Forrester J.V. , Kuffova L.
Published: September 2017

Purpose

Uveal effusion syndrome (UES) is a rare inflammatory disease characterised by massive choroidal detachment due to accumulation of fluid in the suprachoroidal space. There may also be an associated exudative retinal detachment (ERD). The cause of UES is not known but can be primary due to connective tissue disease (1) or secondary to inflammatory disease. We report two cases of secondary UES cases which were refractory to treatment and discuss further management.

Methods

A case series of two patients presenting to a hospital in United Kingdom with ocular symptoms secondary to UES.

Results

Case 1 presented with reduced vision and photopsia in one eye without obvious signs of inflammation while case 2 presented with a painful red eye associated with epiphora and increased intraocular pressure. Large uveal effusions and ERD were clinically apparent on fundoscopy in both patients and an inflammatory etiology was presumed. Both patients suffered a severe relapsing course requiring repeated adjustments to their immunosuppressive therapies ‐ several pulses of intravenous methylprednisolone for exacerbations of the disease plus mycophenolate mofetil (MMF) (case 1) and azathioprine (case 2). Failure to respond required a cycle of cyclophosphamide (pulse 15 mg/kg/infusion) which settled the disease in case 2. However, case 1 failed to respond and is treated with 8‐weekly course of Remsima infusions (anti‐TNFa, 5 mg/kg/infusion) which led to essentially complete resolution of the effusion while maintaining patient's vision.

Conclusions

UES is a rare condition which is difficult to manage. In cases of secondary inflammatory UES a range of immunosuppressants may be required to achieve resolution of the disease.

1. Forrester et.al (1990) The uveal effusion syndrome and trans‐scleral flow. Eye 4: 354‐65.
Probability distribution function of complex systems
Authors: Chen Jincan , Liu Tie , Huang Zhifu , Su Guozhen
Published: September 2017

Based on the probability distribution observed in some complex systems and an assumption that the entropies of complex systems satisfy a pseudo additivity, it is expounded that a new probability distribution function is suitable for not only a single complex system but also a coupling complex system, and consequently, a statistical theory of complex systems can be established in the extensive-like framework.
Magnetic Mesoporous Silica/Chitosan/Polyproline: A Novel Nanocomposite Toward Sensing of Some Clinically Relevant Biomolecules
Authors: Hasanzadeh Mohammad , Hassanpour Soodabeh , Saadati Arezoo , Shadjou Nasrin , Mokhtarzadeh Ahad
Published: September 2017

In this paper, free-radical polymerization inside magnetic mesoporous silica has been investigated in order to open a route to functional polymer–silica composite nanomaterials with well-defined mesoporosity. Proline monomers integrated with chitosan (CS) were electropolymerized into amino-functionalized magnetic mesoporous silica. The fabrication of polyproline-amino-functionalized magnetic mesoporous silica–CS nanohybrid on glassy carbon electrode (GCE) was performed using one step electrodeposition regime. Field emission scanning electron microscopy (FE-SEM) was confirmed as produced nanohybrid material containing polyproline (PPR) into the pores of magnetic (Fe3O[Formula: see text] mobile crystalline material-41 grafted with 3-aminopropyl groups (MMS) which leads to increase of surface coverage of PPR. The results indicate that PPR was successfully generated inside the pores of the amino-functionalized Mobil Composition of Matter No. 41 (nPrNH2-MCM-41) and that the amine group was capable of protonating the polymer, producing polyproline, the most conductive one, without the addition of another acid source during the polymerization step. Therefore, it was evaluated some electrochemical aspects of the prepared nanohybrid using cyclic voltammetry, differential pulse voltammetry and linear sweep voltammetry. Finally, the electroactivity of polyproline -Fe3O4-nPrNH2-MCM-41-chitosan nanohybrid (PPR-MMS-CS) modified GCE toward detection and determination of some clinically relevant small biomolecules was studied.
Workshop on Internet Economics (WIE2016) Final Report
Authors: claffy kc , Clark David
Published: September 2017

On December 8-9 2016, CAIDA hosted the 7th interdisciplinary Workshop on Internet Economics (WIE) at the UC San Diego's Supercomputer Center. This workshop series provides a forum for researchers, Internet facilities and service providers, technologists, economists, theorists, policy makers, and other stakeholders to inform current and emerging regulatory and policy debates. This year we first returned to the list of aspirations we surveyed at the 2014 workshop, and described the challenges of mapping them to actions and measurable progress. We then reviewed evolutionary shifts in traffic, topology, business, and regulatory models, and (our best understanding of) the economics of the ecosystem. These discussions inspired an extended thought experiment for the second day of the workshop: outlining a new telecommunications legislative framework, including proposing a set of goals and scope of such regulation, and minimal list of sections required to pursue and measure progress toward those goals. The format was a series of focused sessions, where presenters prepared 10-minute talks on relevant issues, followed by in-depth discussions. This report highlights the discussions and presents relevant open research questions identified by participants. Slides presented and this report are available at http://www.caida.org/workshops/wie/1612/.