bluuebunny/crossref_metadata_2025 huggingface dataset:
A novel method for measuring outcome of orbital decompression in Graves’ orbitopathy
Authors: Baldeschi L.
Published: September 2015

To evaluate the outcome of a graded bone removal rehabilitative infero‐medial orbital decompression in Graves’ orbitopathy (GO) by means of a novel stratified appraisal (NSA) versus the traditional group analysis (TGA). This retrospective follow‐up study included all the orbits decompressed (06/1999–12/2005), at the Department of Ophthalmology University of Amsterdam by one surgeon (L.B.), using the technique under evaluation. NSA assessed or quantified: (i) the invasiveness of surgery, allowing to calculate a mean index of invasiveness per orbit (MIIO) and per patient (MIIP) (25% ≤ values ≤ 100%); (ii) at ≥ 6 months postoperatively surgical targets (desired exophthalmos reduction, improvement of retroocular tension, reduction of peri‐orbital puffiness, resolution of lagophthalmos) were scored as achieved or not allowing to calculate a mean index of targets achieved per orbit (MITAO) and per patient (MITAP) (0 ≤ values ≤ 1); (iii) an index of diplopia (ID) (decompression‐induced / decompressio‐cured diplopia); (iv) demographics and preoperative characteristics were compared after stratification of the included orbits for surgical target; surgical outcomes were assessed after stratification for amount of desired exophthalmos reduction and invasiveness of surgery. TGA examined the entire series as a single homogeneous cohort independently of the different targets and invasiveness of surgery. NSA and TGA were compared and complications noted. 151 orbits of 84 patients (78% female, mean age 45.5 ± 9.7 years) were included. The NSA detected differences among groups within the studied cohort, the overall achievement of surgical targets was high, indices precisely quantified the extent of applied surgery and surgical results, at variance with results obtained with TGA. A negligible complication rate was recorded. The NSA may represent a step forward towards a more comprehensive and accurate evaluation of decompression surgery outcomes.
Orbital implantation of biocompatible magnets for the treatment of intractable nystagmus
Authors: Verity D.H. , Kennard C. , Pankhurst Q. , Geoffrey E.R.
Published: September 2015

Intractable acquired nystagmus causes debilitating symptoms and medical and surgical treatment is typically unsatisfactory. We describe a pilot study in which pairs of custom‐designed titanium‐encased magnets were sequentially implanted in an adult male patient with recalcitrant vertical nystagmus to achieve a reversible dampening of the nystagmus in the primary position. Under general anaesthesia, one magnet was sutured within the inferior retractor sheath, and, with the globe in the primary position, the fellow magnet was secured to the orbital floor with histoacryl glue, thereby dampening the nystagmus. The procedure was repeated on the fellow orbit several weeks later. This pilot study on a single patient was completed without complication, and has achieved a dramatic improvement in objective and subjective visual functions, including the spatial distribution of eye position during fixation in the primary position, together with a marked subjective improvement in quality of life. NIHR funding has been secured to extend this study to a larger cohort of patients to determine the extent and duration of this dampening effect in a larger cohort of patients.
Consecutive esotropia in contralateral recess‐resect for recurrent intermittent exotropia after unilateral recess‐resect
Authors: Cho S.Y. , Lee S.Y.
Published: September 2015

Purpose

To report consecutive esotropia in contralateral recess‐resect for recurrent intermittent exotropia after unilateral recess‐resect. To evaluate the surgical outcome of ‘modified contralateral recess‐resect’ for intermittent exotropia after unilateral recess‐resect.

Methods

36 subjects were included in this retrospective study. All underwent, as a primary surgery for intermittent exotropia, unilateral recess‐resect on the non‐dominant eye. They were assigned to the subsequent contralateral recess‐resect(CRR, n = 19, surgical dosages based on Wright's surgical table) or modified contralateral recess‐resect (MRR, n = 17, surgical dosages 5Δ reduced on Wright's surgical table) for recurrent exotropia. Surgical success rate was evaluated. Re‐operation rate or prism glasses prescription rate due to consecutive esotropia was evaluated.

Results

The mean follow‐up duration after the reoperation was 25.8 months in CRR group and 24.0 months in MRR group. Surgical success rate was 47.4% in CRR group and 76.5% in MRR group (p = 0.078). Recurrence rate was 0% in CRR group and 17.6% in MRR group (p = 0.059). Re‐operation rate or prism glasses prescription rate due to consecutive esotropia was 52.6% in CRR group and 5.9% in MRR group (p = 0.003).

Conclusions

Final outcomes were better in MRR group than in CRR group. Consecutive esotropia was significantly more frequent in CRR group than in MRR group. To reduce consecutive esotropia in surgery for recurrent exotropia, MRR is recommended.
MicroRNA‐124 regulates transforming growth factor β1‐induced epithelial‐mesenchymal transition in the retinal pigment epithelium by Down‐regulating expression of the RhoG
Authors: Jun J.H. , Joo C.K.
Published: September 2015

Purpose

MicroRNA‐124 (miR‐124) is thought to be involved in the epithelial‐mesenchymal transition (EMT) of retinal pigment epithelium (RPE). In the present study, we investigated the regulation of miR‐124 on EMT induced by transforming growth factor β1 (TGF‐β1) in human RPE cells (APRE‐19).Methods

The expression of miR‐124 was evaluated after treatment of TGF‐β1 by quantitative RT‐PCR. Phenotypic alterations were analyzed by western blot analysis and immunocytochemical staining. Target validation was performed to identify the putative target of miR‐124 by luciferase reporter assay.

Results

The expression level of microRNA‐124 (miR‐124) was down‐regulated during the progression of EMT. Overexpression of miR‐124 upregulated the levels of zonular occludens 1 and RPE65, and down‐regulated fibronectin, α‐smooth muscle actin, and vimentin. Furthermore, inhibition of endogenous miR‐124 increased and decreased the levels of mesenchymal and epithelial factors, respectively. TargetScan predicted two well‐conserved and two vertebrate‐only conserved miR‐124 target sequences in the 3′ untranslated region (UTR) of the RHOG mRNA. Direct targeting of this 3′ UTR by miR‐124 was demonstrated using a luciferase assay. Silencing of RHOG using a specific siRNA had identical effects on EMT regulation. Overexpression of miR‐124 repressed TGF‐β1‐induced RPE cell‐collagen gel lattice contraction by altering cell spreading/cell‐to‐cell adhesion.

Conclusions

This study describes the regulation of EMT in RPE cells by TGF‐β1/miR‐124/RHOG signaling and suggests that the supplement of miR‐124 expression would be a crucial therapeutic target for the prevention or treatment of proliferative vitreoretinopathy.
Myofibroblasts in proliferative diabetic retinopathy can originate from infiltrating fibrocytes and through endothelial‐to‐mesenchymal transition (EndoMT)
Authors: Abu El Asrar A. , De Hertogh G. , van den Eynde K. , Alam K. , Van Raemdonck K. , Opdenakker G. , Van Damme J. , Geboes K. , Struyf S.
Published: September 2015

Purpose

The fibrovascular epiretinal membranes from patients with proliferative diabetic retinopathy (PDR) are characterized by the accumulation of a large number of myofibroblasts. We explored the hypothesis that proliferating endothelial cells via endothelial‐to‐mesenchymal transition (EndoMT) and/or bone marrow‐derived circulating fibrocytes contribute to the myofibroblast population present in PDR membranes.

Methods

Epiretinal membranes from 14 patients with PDR were studied by immunohistochemistry. In addition, we investigated the phenotypic changes that take place in human retinal microvascular endothelial cells following exposure to transforming growth factor‐β1 (TGF‐ β1), connective tissue growth factor (CTGF) and the proinflammatory cytokines interleukin‐1β (IL‐1β) and tumor necrosis factor‐a (TNF‐a).

Results

All membranes contained neovessels expressing the endothelial cell marker CD31. CD31+ endothelial cells co‐expressed the fibroblast/myofibroblast markers fibroblast‐specific protein‐1 (FSP‐1) and a‐SMA, indicative for the occurrence of endoMT. In the stroma, cells expressing FSP‐1, a‐SMA, the leukocyte common antigen CD45, and the myelomonocytic marker CD11b were detected. Double labeling showed co‐localization of CD45 with FSP‐1 and a‐SMA and co‐localization of CD11b with a‐SMA and matrix metalloproteinase‐9, demonstrating the presence of infiltrating fibrocytes. Retinal microvascular endothelial cells changed morphology upon cytokine exposure, lost the expression of endothelial cell markers (endothelial nitric oxide synthase and vascular endothelial‐cadherin) and started to express mesenchymal markers (calponin, snail, transgelin and FSP‐1).

Conclusions

These results suggest that endothelial cells as well as circulating fibrocytes may differentiate into myofibroblasts in the diabetic eye and contribute to pathologic fibrosis in PDR.
Target region sequencing in sporadic congenital cataracts reveals a new genotype‐phenotype relation for the GALK1 gene
Authors: Li D. , Yang J. , Ye H. , Tang Y. , Luo Y. , Lu Y.
Published: September 2015

Purpose

The purpose of this study was to investigate the genetic effects underlying sporadic congenital cataracts (SCC).

Methods

We collected DNA samples from 74 SCC patients and 20 traumatic cataract (TC) patients in the same age group as normal controls and performed genomic sequencing of 61 cataract‐related genes (including introns, exons and 10 bases from the 3′ and 5′ ends) by target region capture and next generation sequencing. We chose previously reported cataract‐related genes and also included other lens disease‐related genes, including microphthalmia (SOX2, PAX6, OTX2, RAX, FOXE3 and CRYBA4); aniridia (FOXC1, PITX2 and PITX3); Marfan syndrome (FBN1); ectopia lentis (ADAMTSL4 and ADAMTS17) and Alport syndrome (COL4A5).

Results

By filtering the SNPs that were previously deposited in the NCBI SNP database (dbSNP) or were associated with TC cases, we identified 72 novel variants in 40 genes from 49 patients. The mutation frequency of the GALK1 gene was much higher than the other tested genes, with mutations detected 10 times in 7 patients; followed by CRYBB3 and FBN1 the mutation of which were detected 4 times. Moreover, we observed a posterior polar‐cataract phenotype in 86% (6 out of 7) of SCC patients with mutations in GALK1.

Conclusions

We conclude that genetic mutations could be important contributing factors to non‐hereditary congenital cataract; for example, GALK1, the most frequently mutated gene in this group of patients, was related to the posterior polar subtype of cataract.
Comparison of Optical Coherence Tomography Measurement Reproducibility between Children and Adults
Authors: Kim S.H. , Chung H.K. , Han Y.G. , Oh S.
Published: September 2015

Purpose

To compare the reproducibility of SD‐OCT (spectral‐domain optical coherence tomography) measurements of RNFL (retinal nerve fiber layer) and macular thickness between children and adults.

Methods

Seventy‐one eyes of 71 healthy myopic children and 71 eyes of 71 normal adults were enrolled. RNFL and macular thicknesses were measured by one operator, with a brief rest between measurements. The two measurements were obtained using the eye tracking and retest function of Spectralis SD‐OCT. Reproducibility was evaluated with reference to COVs (coefficients of variation) and ICCs (intraclass correlation coefficients). The ICC values of the RNFL and macular thicknesses were compared, respectively between the two groups, by Fisher's z‐test.

Results

The RNFL and macular thicknesses did not differ between the two groups. The COVs of the RNFL measurements ranged from 0.945 to 4.531% in the children group and from 0.496 to 1.391% in the adults group. In most of the RNFL sectors, the ICCs of the children group (range: 0.784–0.987) were significantly lower than those of the adults group (range: 0.986–0.993). The COVs of the macular measurements ranged from 0.496 to 1.157% in the children group and from 0.275 to 0.656% in the adults group. The ICCs (range: 0.859–0.973) in the children group, significantly lower than for the adults (range: 0.989–0.995), in all of the macular sectors.

Conclusions

The reproducibility of SD‐OCT RNFL and macular measurements for healthy myopic children was excellent, albeit statistically lower than that for adults.
Impact of disease modifying anti‐rheumatic drugs (DMARDs) on the uveitis risk in juvenile idiopathic arthritis
Authors: Tappeiner C. , Klotsche J. , Schenck S. , Niewerth M. , Minden K. , Heiligenhaus A.
Published: September 2015

Purpose

To analyze the influence of methotrexate (MTX), Tumour necrosis factor (TNF) inhibitors, and their combination on uveitis occurrence in juvenile idiopathic arthritis.

Methods

Data of a nation‐wide prospective rheumatological and ophthalmological database in Germany were evaluated for the years 2002 to 2013. Patient with JIA disease duration of less than 12 months at initial documentation and with a follow‐up of ≥ 2 years were included in this analysis. Discrete‐time survival analysis was performed to evaluate the impact of disease modifying anti‐rheumatic drugs (DMARDs) on the occurrence of uveitis.

Results

A total of 3,512 JIA patients fulfilled the inclusion criteria (mean age 8.3 ± 4.8 years, female 65.7%, ANA‐positive 53.2%, mean age at arthritis onset 7.8 ± 4.8 years, mean follow‐up time 3.6 ± 2.4 years). Uveitis manifested in 180 patients (5.1%) within one year after JIA onset, and in further 251 patients (7.1%) after the first year. MTX (HR 0.63, p = 0.022), TNF inhibitors (HR 0.56, p < 0.001) and a combination of the two (HR 0.10, p < 0.001) in the year before uveitis onset significantly reduced the risk for uveitis. MTX treatment within the first year after JIA diagnosis revealed the lowest uveitis risk (HR 0.29, p < 0.001).

Conclusions

DMARDs in JIA patients significantly reduce the risk for uveitis onset. A relevant protective effect was found especially for early MTX use within the first year of arthritis onset and for the combination of MTX with a TNF inhibitor.
Intraocular Pharmacokinetics of Povidone‐iodine and the Effect of Repeat Injection with low concentration on the Experimental S. epidermidis Endophthalmitis
Authors: Byon I. , Kim K. , Yu J. , Yoon I. , Lee J.
Published: September 2015

Purpose

To investigate the safety and a half‐life of intravitreal povidone‐iodine (PVI) and the efficacy of single and repeat PVI injection in experimental S. epidermidis endophthalmitis.

Methods

In Phase I study, the pharmacokinetics and the safety of PVI were investigated. Forty New Zealand White rabbits receiving intravitreal 0.1% and 0.3% PVI were divided into Group I and II. The pharmacokinetics of PVI was analyzed using high performance liquid chromatography (HPLC). To confirm the safety of intravitreal PVI, electroretinography (ERG) and histologic examination were conducted at baseline, 6 and 12 hours. In Phase II study, the efficacy of PVI for the treatment of S. epidermidis endophthalmitis was evaluated in 4 groups (n = 10 in each group). After the induction of S. epidermidis endophthalmitis, 0.1% and 0.3% PVI were injected once in Group A and B, and three times every second day in Group C and D respectively. The fellow eyes receiving sham injection were the control. ERG, histologic examination and vitreous culture for S. epidermidis were conducted at day 14.

Results

In Phase I, 0.1% and 0.3% PVI groups did not show notable retinal damage in ERG and histologic findings and half‐life in vitro was 3.27 and 3.58 hours, respectively. In Phase II, all Groups showed a significant improvement of endophthalmitis, compared to the controls. However, four eyes in Group A and 3 eyes in Group B demonstrated a bacterial growth in vitreous at day 14, but none in Group C and D. In the histologic findings, retinal damage was detected as lymphocyte infiltration in the inner retinal layers of eyes with bacterial growth.

Conclusions

0.1% and 0.3% PVI can be tolerated in rabbit eyes. Half‐life of the PVI was about 3 hours in vitreous. Repeat PVI injection with low concentration is likely to be effective and safe for the treatment of S. epidermidis endophthalmitis.
αB‐Crystallin Phosphorylation as a Precursor to Cataractogenesis
Authors: Thornell E. , Ecroyd H. , Aquilina A.
Published: September 2015

Purpose

The molecular mechanism behind age‐related cataract formation is yet to be elucidated, although phosphorylation induced hyperactivity of αB‐crystallin (αB) and its subsequent association with fibre cell membranes has been implicated. This study evaluates the effect phosphorylation of αB at three well characterised sites (S19, S45 and S59) has on its chaperone activity and aims to characterise αB's membrane association with a focus on its role in cataractogenesis.

Methods

The chaperone activity of αB phosphomimics (S→D) were measured via aggregation assays using creatine phosphokinase (CPK) as a substrate. In vivo association of αB phosphoisotypes with two abundant membrane proteins, connexin 46 (cx46) and aquaporin 0 (AQP0) in aged human lenses was visualised using Duolink proximity assays and confocal microscopy.

Results

The chaperone activity of αB increased with an increase in modification sites. Modification at the S19 and S59 residues activated αB to a greater extent than at S45. In the lens, phosphorylated αB was found to interact with Cx46 and AQP0 at cell membranes.

Conclusions

This study confirms that multiple phosphorylation events of αB cause a cumulative increase in activity, and that membrane association, at least in part, is mediated by interactions with membrane pore proteins. The proposed mechanism of cataractogenesis is that phosphorylation induced increases in substrate affinity of αB may lead to increased association with membrane pore proteins, leading to the obstruction of the diffusion of small molecules into inner regions of the lens, contributing to cataract formation.
Expression of histamine receptors in the gerbil retinal neurons
Authors: Miyachi E. , Imada H. , Ohkuma M. , Sakai K.
Published: September 2015

Purpose

The presence of histamine receptors (HRs) in mammalian retinae has been reported by several laboratories. In order to confirm the presence of histaminergic pathway in the retina, we made experiments using physiological and immunohistochemical analyses.

Methods

All experiments were performed using the gerbil (Meriones unguiculatus). The activity of the HR was measured by fura‐2 based calcium‐imaging technique and by whole‐cell patch‐clamp technique from slice preparation of the retina. Localizations of the subtypes of HRs, H1 receptor (H1R), H2 receptor (H2R) and H3 receptor (H3R), were examined by avidin‐biotin‐peroxidase complex immunocytochemical staining or immunofluorescence in retinae from 1 to 350 postnatal days. All animal experiments are approved by the ethics committee of Fujita Health University.

Results

Physiology: A bath application of 100 µM histamine increased the intracellular calcium concentration in some retinal ganglion cells (RGCs). Under voltage‐clamp condition, histamine increased the amplitude of the outward or inward current in some RGCs.

Immunohistochemistry: We found that H1R, H2R and H3R expressed on RGCs. H1R expresses through the retinal maturation. On the other hand, the expressions of H2R and H3R became maximum from 14 to 21 postnatal days. Since the gerbil opens the eyes at 3 weeks old, it is considered that the H2R and H3R play some specific roles at the formation of the early visual system. Histidine decarboxylase, which produces histamine from histidine, also expressed in RGCs, and moreover, each of HRs and histidine decarboxylase were co‐localized at the same RGCs.

Conclusions

Our findings suggest that RGCs interact with each other via histamine, and that histamine is one of the important neurotransmitters and/or neuromodulators in the visual information processings of the mammalian retina.
Association between drusen and blood test results in a colony of 1,174 monkeys
Authors: Nishiguchi K. , Yokoyama Y. , Fujii Y. , Furukawa T. , Ono F. , Shimozawa N. , Togo M. , Suzuki M. , Nakazawa T.
Published: September 2015

Purpose

To ascertain the association between fundus drusens and biological parameters in a colony of 1174 monkeys.

Methods

Presence or absence of drusens was determined through the assessment of fundus photos taken during 2011 – 2013 from 1,174 Macaca fascicularis at Tsukuba Primate Research Center. Biological data from these monkeys including blood test result, age, sex, and body weight were tested for an association between the presence of drusens by applying t‐test and logistic regression analysis.

Results

We identified 387 and 787 monkeys with and without drusens, respectively. Among them, 317 and 628 monkeys with and without drusens that had a complete biological data set were further studied. After comparing each parameter in monkeys with and without drusens, 13 factors with a significance of P < 0.1 (t‐test) were selected for logistic regression analysis. Regression analysis showed association of age (odds ratio: 1.092, 95% confidence interval: 1.061–1.125) and platelet count (odds ratio: 1.022, 95% confidence interval: 1.005–1.038) with drusens. In addition, an association was implicated between drusens and white blood cell count (odds ratio: 1.005, 95% confidence interval: 1.000–1.011).

Conclusions

Age, platelet count, and white blood cell count may be associated with the development of drusens in Macaca fascicularis.
Spontaneous and mechanically induced Ca2+ activity changes in hESC‐RPE cells during maturation
Authors: Abu Khamidakh A. , Juuti‐Uusitalo K. , Caetano dos Santos F. , Skottman H. , Hyttinen J.
Published: September 2015

Purpose

The aim of this study was to investigate changes in spontaneous Ca2+ activity and mechanically induced intercellular Ca2+ communication in human embryonic stem cells‐derived retinal pigment epithelium (hESC‐RPE) during maturation.

Methods

In this study, we assessed Ca2+ activity in hESC‐RPE cells cultured for 9 or 28 days. Ca2+ imaging was done using a Ca2+‐sensitive fluorescence dye fluo‐4‐AM. Spontaneous Ca2+ activity and mechanically induced intercellular Ca2+ communication were recorded in control conditions, in the absence of extracellular Ca2+, after depletion of intracellular Ca2+ stores with thapsigargin, in presence of a gap junction blocker α‐glycyrrhetinic acid and a P2‐receptor blocker suramin.

Results

9 days cells exhibited twice lower spontaneous Ca2+ activity and 4‐fold higher mechanically induced intercellular Ca2+ communication compared to 28 days cells. Absence of extracellular Ca2+ reduced spontaneous Ca2+ activity in 9 days cells and almost completely inhibited it in 28 days cells, while having no effect on mechanically induced intercellular Ca2+ communication. Depletion of intracellular Ca2+ stores abolished spontaneous Ca2+ activity in 9 days and 28 days cells, as well as mechanically induced intercellular Ca2+ communication in 28 days cells, while not affecting the latter in 9 days cells. Blockade of gap junctions and P2‐receptors had no effect on spontaneous Ca2+ activity or mechanically induced intercellular Ca2+ communication in cells from both time points.

Conclusions

Our results show that hESC‐RPE cells undergo significant Ca2+ signaling re‐arrangements during maturation: the cells increase spontaneous Ca2+ activity, while decreasing their intercellular Ca2+ communication.
Case report of ring ciliary body and choroidal lymphoma
Authors: Bogdali A. , Markiewicz A. , Jakubowska B. , Romanowska Dixon B.
Published: September 2015

Purpose

The aim of the study was to analyze case of ring ciliary body and choroidal lymphoma.

Methods

Retrospective analysis.

Results

54 years old man was sent in October 2014 to Department of Ophthalmology of the Jagiellonian University Medical College in Cracow with diagnosis of choroidal melanoma in left eye. Tumor was detected accidently. BCVA in both eyes was 1.0. Intraocular pressure in both eye was correct. In patients history stomach lymphoma treated in 1996 with radiotherapy and chemiotherapy. In fundus examination we found mass located temporally in choroid and cilary body. Ultrasound examination (USG and UBM) showed ciliary body and choroidal mass located between 2 and 7 clock hour (almost 180 degrees), thickness 8.2 mm, base 14.30 mm. The patient was qualified to biopsy of ciliary body and choroidal mass and I‐125 brachytherapy. During 2 weeks tumor enlarged, was located in 270–300 degrees and looks like ciliary body ring melanoma (thickness 9.0 mm, base 23.3 mm) with iris elevation and conjunctival edema. Enucleation of left eyeball was performed. Histopathological examination reveled neoplasma malignum probabiliter non epitheliale. Lypmoma malignum – marginal zone lymphoma. Immunohistochemical profile of tumor showed experesion CD20+, CD5‐, CD23‐, CD3‐, lack of expression lambda gains.

Conclusions

Lypmoma malignum – marginal zone lymphoma may occur like ciliary body and choroidal ring which should be considered in the differential diagnosis of intraocular tumors.
Multicenter clinical trial of high‐intensity focused ultrasound treatment in glaucoma patients without previous filtering surgery
Authors: Aptel F. , Denis P. , Rouland J.F. , Renard J.P. , Bron A.M.
Published: September 2015

Purpose

To evaluate the efficacy and safety of the ultrasonic circular cyclocoagulation procedure in patients with open‐angle glaucoma naïve of previous filtering surgery.

Methods

Prospective non‐comparative interventional clinical study conducted in five French University Hospitals. Thirty eyes of 30 patients with open‐angle glaucoma, intraocular pressure (IOP) > 21 mmHg and with no previous filtering glaucoma surgeries were sonicated with a probe comprising six piezoelectric transducers. The six transducers were activated with a 6‐s exposure time. Complete ophthalmic examinations were performed before the procedure and at 1 day, 1 week, 1, 2, 3, 6 and 12 months after the procedure. Primary outcomes were surgical success (defined as IOP reduction from baseline ≥ 20% and IOP > 5 mmHg with possible retreatment and without hypotensive medication adjunction) at the last follow‐up visit and vision‐threatening complications. Secondary outcomes were mean IOP at each follow‐up visit compared to baseline, medication use, complications and retreatments.

Results

IOP was significantly reduced (p < 0.05) from a mean preoperative value of 28.2 ± 7.2 mmHg (n = 3.6 hypotensive medications) to 19.6 ± 7.9 mmHg at 12 months (n = 3.1 hypotensive medications and n = 1.1 procedures) (mean IOP reduction of 30%). Success was achieved in 63% of eyes (19/30) at 12 months (mean IOP reduction of 37% in these eyes). No major intra‐ or postoperative complications occurred.

Conclusions

The ultrasonic circular cyclocoagulation procedure seems to be an effective and well‐tolerated method to reduce IOP in patients with open‐angle glaucoma without previous filtering surgery.
Primary open angle glaucoma treated by high intensity focused ultrasound (HIFU) with the 2nd generation probe
Authors: Rouland J.F. , Aptel F.
Published: September 2015

Purpose

To assess the safety and efficacy of Ultrasound Ciliary Plasty (UCP procedure) using HIFU (high intensity focused ultrasound) with a second‐generation probe which increases the treatment surface area and the firing duration in patients with primary open angle glaucoma.

Methods

Prospective clinical series performed in two University Hospitals, on eighteen eyes of eighteen patients with primary open‐angle glaucoma, treated with the EyeOP1 medical device equipped with six miniaturized cylindrical piezoelectric transducers of a new generation with an increased lesion volume. All eyes were treated with an 8‐second exposure time per transducer. The main assessment criteria were safety and efficacy measured by the incidence of complications and IOP reduction. Ophthalmic examination and ultrasound biomicroscopy were performed before treatment and during clinical follow‐up at D7, M1, M3, M6 and M12.

Results

The mean intraocular pressure was significantly reduced from 28.4 ± 5.4 mmHg before treatment to 17.4 ± 3.8 mmHg at last follow‐up. Complete success rate, as defined by an IOP reduction >20% and IOP > 5 mmHg after one UCP procedure was 84%. The mean IOP reduction achieved in responding patients was 42%. No major intra‐ or post‐operative complications were observed. Clinical examination showed no lesions of ocular structures other than the ciliary body and no or few signs of intraocular inflammation after treatment.

Conclusions

Coagulation of the ciliary body using high intensity focused ultrasound carried out with the new‐generation of miniaturized transducers is a simple, well‐tolerated procedure which enables to significantly reduce the intraocular pressure in patients with Open Angle Glaucoma.
Real Time, In Vivo Analysis of the Onset of Retinogenesis: Assessment of the Retinal Vascular Plexus, Electrophysiological Response and Architecture in Neonatal Mice
Authors: Deniro M. , AlQahtani A. , AlAhmar S. , AlMohanna F.
Published: September 2015

Purpose

To evaluate the retinal vascular network in P0 and P1 neonates in vivo in real time.

Methods

C57Bl/6J neonates were dark‐adapted overnight. Animals were subjected to clinical investigation by using electroretinography (ERG) and spectral domain optical coherence tomography (SD‐OCT) coupled to fluorescein angiography (FA).

Results

FA in P0 neonates revealed that vascularization starts as ring‐shaped vascular sprouts growing radially from the optic nerve head, becoming progressively interconnected by a capillary plexus between them. OCT data indicated that neonatal retina consisted of three layers; ganglion cell, inner plexiform and neuroblastic. The retinal thickness in P0 and P1 pups were 45 ± 7 μm, 50.2 ± 2 μm, respectively. ERG recordings were observed as early as day 0; however they exhibited a nearly abolished b‐waves and relatively preserved a‐waves. This suggests that synaptic functionality develops at the onset of postnatal retinogenesis.

Conclusions

We report here for the first time the imaging of the developing retina in real time as early as P0, which was coupled to focal‐ERG and OCT measurements. Our data indicated that despite the nearly abolished b‐wave, the retina was responsive to light stimuli. Our data also suggest that the positive‐going b‐wave of the dark‐adapted ERG response is generated by the precursor neuronal cells within the developing NBL and the response to light stimulation occurs long before the appearance of the rods and cones in the developing photoreceptor layer.
Development of Diabetic Retinopathy in a 22‐Week Old Homozygous Ins2Akita Mouse: A Case Study
Authors: Deniro M. , AlQahtani A. , AlAhmar S. , AlMohanna F.
Published: September 2015

Purpose

Mice homozygous for Ins2Akita develop type 1 diabetes mellitus. These animals die by 12 weeks old age due to rapid and severe hyperglycemia, which leaves the mice with a short window period to manifest diabetic retinopathy (DR). Here we report the rare development of DR in a 22 week‐old male Akita mouse.

Methods

Electroretinography (ERG) and spatial‐domain optical coherence tomography (SD‐OCT) imaging as a measure of visual function, which was coupled to fluorescein angiography (FA) and trypsin digestion (TD).

Results

The homozygous mouse exhibited hyperglycemia and retinal complications including early signs of vascular damage consistent with DR. TD demonstrated the presence of pericyte ghosts, whereas FA exhibited the manifestation of retinal neovascularization, vascular leakage and microaneurysm formation. ERG recording and OCT imaging were sensitive in detecting the degree of retinal degeneration and RPE tear as compared to the wildtype control. The RPE tear created an area where photoreceptors have no RPE support. Scotopic ERG analysis exhibited significantly faster b‐wave responses as compared to wildtype control. Further analysis using b/a‐wave ratio revealed a strikingly disproportionate reduction in the b‐ and a‐wave amplitudes. SD‐OCT demonstrated a reduction in the overall retinal thickness (OS‐NFL) of homozygous Ins2Akita mouse but not age‐matched control.

Conclusions

Our study reports and for the first time the rare development of full‐blown clinical expression of diabetic retinopathy in a 22‐week old homozygous Akita.
Genotypes & Phenotypes in Belgian Patients with Albinism
Authors: De Bleser E. , Tack M. , De Baere E. , Leroy B.P.
Published: September 2015

Purpose

To study the different genotypes and phenotypes in Belgian patients with albinism.

Methods

Phenotypes and genotypes in a cohort of 89 patients were studied in detail. These patients were then grouped according to genotype.

Results

A total of 40 patients with isolated oculocutaneous (OCA), and 11 with XL ocular albinism (XLOA) were molecularly confirmed. Nine syndromic OCA patients were identified. Genotypes of 29 patients were unknown at the time of study. Although not statistically significant due to small sample size, patients with a proper TYR mutation in combination with a temperature sensitive variant (TS) generally showed milder characteristics. A study of one specific family showed 3 affected siblings with this genotype. However, 2 normal children, each of a different patient, also had this genotype. There was perfect concordance between fundoscopic identification of lyonization in 15 female carriers of XLOA, and molecular confirmation of heterozygosity. Two adult patients with Chediak‐Higashi syndrome showed OCA in combination with neurodegeneration. Systemic abnormalities in 7 Hermansky‐Pudlak syndrome patients were very variable.

Conclusions

Molecular analysis is essential to confirm clinical phenotyping in albinism. A causal relationship between a combination of a TYR mutation and the TS variant is as yet uncertain and requires more in depth analysis.
Seasonal variation of the pupil light reflex
Authors: Kourti P. , Münch M. , Collomb S. , Kawasaki A.
Published: September 2015

Purpose

Variation of retinal light sensitivity between winter and summer seasons may be a marker for seasonal affective disorder and the basis for response to phototherapy. As the pupil is a marker of retinal light sensitivity and shows a 24‐hour variation that reflects circadian rhythm, we used the pupil as proxy to assess light sensitivity of rods, cones and melanopsin as a function of seasonal light in healthy adults.

Methods

37 adults were tested during the short (January‐February) and long (July‐August) annual photoperiods. All subjects completed standardized questionnaires of seasonality and sleep. Pupil responses to blue (470 nm) and red (622 nm) light were recorded under dark and light adapted conditions using an automated pupillometer. Main outcome parameters were maximal contraction amplitude and post‐stimulus contraction amplitude.

Results

All but two subjects reported good sleep quality. One subject was an extreme morning type. Twelve subjects reported a global seasonal variation in sleep, mood and appetite but without dysfunction or disability. Baseline pupil size of light adapted eyes was greater in summer compared to winter. Maximal contraction amplitudes to scotopic and photopic light stimuli were greater in summer. The post‐stimulus pupil contraction was also greater in summer, but only after light adaptation.

Conclusions

Baseline pupil size and pupil responses derived from rods, cones and melanopsin photoreception were greater in summer in healthy adults. This seemingly greater retinal sensitivity to light when the photoperiod (daylength) is long suggests a more central basis for seasonal regulation of the pupil light reflex.
Ex vivo porcine corneal storage using an innovative bioreactor
Authors: Guindolet D. , HE Z. , Bernard A. , Rageade D. , Piselli S. , Perrache C. , Forest F. , Peoc'h M. , Gain P. , Gabison E. , Thuret G.
Published: September 2015

Purpose

There is no animal model of medium‐long‐term corneal storage for easily available animals because, contrary to human, ex vivo, animal corneas rapidly and dramatically swell and loose their transparency. As intraocular pressure and optimal function of endothelial cells are critically important for corneal homeostasis, we suppose that the passive eye banking technique is not adapted for corneas of young animals with high stromal swelling pressure. We therefore reproduce physiological parameters to improve storage of animal corneas.

Methods

We designed a bioreactor (BR) that restores a pressure equivalent to the intra ocular pressure in the endothelial chamber while allowing continuous renewing of media in both epithelial and endothelial chambers. Epithelial side underwent alternating air‐lifting and medium immersion to reproduce blinking. Porcine eyeballs were obtained from a local slaughterhouse within 4 hours after death. Corneas were stored either in a BR or in conventional vials, both in standard organ culture medium. Transparency, thickness, histological structure and immunohistological staining (ABCB5, PAX6, 5‐ethynyl‐2′‐deoxyuridine, K3‐K12, Laminin‐5) were compared to conventionally stored corneas after 2 weeks.

Results

Porcine corneas stored in bioreactor were more transparent and thinner. Increased endothelial cell viability was observed in the BR and epithelial layer was preserved and mature. Epithelial stem cells also survived.

Conclusions

The porcine version of our BR mimics physiological condition and improves corneal storage. It could be a new model of eye banking and a powerful experimental platform to study corneal physiopathology. Grant: UJM, ANSM.
Mineralocortycoid receptor's antagonists in treatment of central serous chorioretinopathy
Authors: Romanowska Dixon B. , Karska‐Basta I. , Pociej‐Marciak W. , Ozog‐Baran J. , Kubicka‐Trzaska A.
Published: September 2015

Purpose

To evaluate the influence of eplerenon on the function and morphology of the macula in patients with central serous chorioretinopathy (CSC).

Methods

The study included 17 eyes in 16 patients with central serous chorioretinopathy treated in the Department of Ophthalmology at the University Hospital in Krakow. There were 13 males, 3 women at the age of 32 to 66 years, mean age 41.71 years. The duration of symptoms was ranging from 4 to 24 months, an average of 8 months. The patients were treated with eplerenone according to the scheme: 25 mg/day for a week, then 50 mg/day by 3 months. The baseline examination and two controls (after 1–1.5 month and after 3–4 months) included best corrected visual acuity, central retinal thickness in optical coherence tomography and visual central disturbances in Amsler test.Results

The values for CRT decreased from 367 (± 70) µm to 264 (± 50) µm (the first control) and to 248 (± 50) (the second control), the difference was an average of 112.71 microns (p = 0.00001). The average BCVA improved from 0.61 (± 0.25) to 0.67 (± 0.28) (the first control) and to 0.72 (± 0.28) (the second control). 10 patients (58.8%) reported improvement of Amsler test while in the 7 patients (41.2%) deterioration in central vision stayed unchanged during the first control. During the second control 7 patients (50%) reported improvement of Amsler test while in the 7 patients (50%) deterioration in central vision stayed unchanged.

Conclusions

The results of our observations indicate that eplerenone can provide an alternative treatment CSC especially in cases where there are contraindications for the use of other therapeutic methods such as laser photocoagulation of the retina. Further investigation is needed.
Age Macular Degeneration‐Lipidomic Study: Relevance and interest of Lipidomic study in screening, follow‐up and etiopathogeny of AMD
Authors: Gonzalez C. , Bertrand‐Michel J.
Published: September 2015

Purpose

To evaluate the lipidomic study impact on AMD diagnosis, screening, etiopathogenie and interrelations,correlations between those 2 entities.

Methods

AMD: 30 AMD patients. 3 Groups: A:10 first stage AMD patients,B:10 Atrophy AMD patients, C:10 Neovascular AMD patients. Ophthalmologic exam:ETDRS visual acuity (VA), complete ophthalmic examination,Fundus examination, autofluorescence imaging (FAF), optical coherence tomography (Spectral Domain OCT) and fluorescein angiography (FA) and ICG when Neovascular complication.Lipidomic Study: Blood tests and analysis, all lipids qualitative, quantitative analysis, all the same for all patients, whatever group. Blood test is done during ophthalmologic exam. Plasma congelation “snap frost” in liquid nitrogen after total blood centrifugation, then liquid‐liquid extraction for lipids analysis:neutral lipid by GC, as well as fatty acid but after BF3 methanol derivation,phospholipids by LC‐MS directly,as sphingolipids but firstly hydrolysed. Polyinsatured fatty acids metabolites preparation: protein precipitation then pre‐concentration by SPE(solid phase extraction) before m'analyses by LC‐MS.

Results

Analysis will determine qualitative,quantitative lipids values in each patients group, each of them proportion, characterization, singularity; so, characterization, prevalence, specifics of and for each group. Lipidomic study’ evaluation, identification, classification in AMD patients groups allow AMD screening,follow‐up, particularly according to AMD type and stage. Lipidomic study have biomarker feature, let AMD prevention, etiopathogenic concept.

Conclusions

Lipidomics study and so better AMD characterization allow better diagnosis, follow‐up, screening of AMD. Interrelations and correlations between AMD and Lipidomics lead to better etiopathogenie understanding and therapeutics prospects.
Comparisons of retinal sensitivity obtained by microperimetry with two different fixation targets in normal individuals
Authors: Nizawa T. , Kitahashi M. , Yamamoto S.
Published: September 2015

Purpose

To determine the retinal sensitivities obtained by microperimetry with an one degree single cross (Cr) or an one degree circular (Ci) fixation target in normal individuals.

Methods

The retinal sensitivity within the central 2 degrees was measured in 32 eyes of 16 healthy volunteers (mean age 28.9 ± 1.4, range 24–44) with Microperimeter 3 (MP‐3, Nidek, Italy) using two fixation targets. The retinal sensitivity of the central 0 degree and mean central 2 degrees consisting of 8 points were measured with the two fixation targets. The Goldmann III stimuli were presented for 200 msec on a white background with a luminance of 31.5 asb.

Results

The mean central retinal sensitivity (0 degrees) was 24.4 ± 0.8 dB with the Cr and 29.8 ± 0.6dB with the Ci targets. The central retinal sensitivity with the Ci target was significantly higher than that with the Cr. (P = 1.2 × E‐5). The mean retinal sensitivity of the central 2 degrees was 32.0 ± 0.3 dB with the Cr target and 31.4 ± 0.3 dB with the Ci target. The mean central 2 degrees retinal sensitivity with the Cr was significantly higher than that with the Cr target (P = 0.006).

Conclusions

The differences in the retinal sensitivity is probably because the fixation targets overlap the stimuli. These results indicate that the size and shape of the fixation target must be considered when evaluating the central retinal sensitivity.
Changes in lamina cribrosa and prelaminar tissue in anterior ischemic optic neuropathy
Authors: Munoz‐Negrete F.J. , Rebolleda G. , García‐Montesinos J. , Oblanca‐Llamazares N. , De Juan V. , De Dompablo E.
Published: September 2015

Purpose

To determine changes in lamina cribrosa (LC) and prelaminar tissue in patients with unilateral non‐arteritic anterior ischemic optic neurophaty (NAION) using enhanced depth imaging (EDI) spectral domain optical coherence tomography (SD‐OCT).

Methods

Seventeen eyes of 17 patients with NAION were prospectively studied. SD‐OCT scans using EDI technology were obtained at the acute episode and at two and six months after the ischemic event. The OCT device was set to image a 15x10 degree vertical rectangle centered on the optic disc. The scan in LC was seen clearliest was selected for analysis. The vertical distances from three equidistant points on the reference line (Bruch's membrane opening‐BMO) to the anterior prelaminar tissue surface, and to the anterior and posterior surfaces of the LC were measured.

Results

At diagnosis, mean prelaminar tissue was significantly thicker and anterior LC surface more posteriorly placed in NAION eyes than in non‐involved eyes. During the follow‐up, in NAION eyes there was a significant prelaminar thinning and an anterior LCreversal (P = 0.001 and P = 0.002 at 2 and 6 months respectively). BMO significantly reduced during follow‐up (P = 0.008 and P = 0.034 at 2 and 6 months respectively). Both prelaminar tissue thickness and BMO changes correlated with retinal nerve fiber layer thickness measurements.

Conclusions

OHN is a dynamic structure that undergoes biomechanical changes in eyes suffering NAION. A significant prelaminar tissue thickening and posterior lamina cribrosa displacement occurred during the acute ischemic optic neuropathy, that reverse as the edema resolves.
Evidence for a new model of the human eye ‐ a holographic laser system, biophotonics. The holographic view
Authors: Manu M.D. , Plesu G.
Published: September 2015

Purpose

The authors proposed to verify the eyes structure and function as laser system, position of the image on retina, and properties of bio‐luminescence (BL) of the eye, with help of multidisciplinary studies, biophotonic and bionic tests.

Methods

Methods demonstrated that the eyes are laser bifocal systems, with nonlinear medium, through multidisciplinary studies up to date in medicine, biochemistry and physics, original biophotonic tests, delayed luminescence DL, self‐emission SE tests, and two original models of bionic eye.

Results

We detected: errors of the photographic mechanism of human vision; other properties of human eye as holographic laser system, a laser bifocal system; the eye is initiating BL tract as laser phenomenon, due to internal source of light as phosphate ‐ water; a right position of the images on retina; the amplification of BL along nervous tract, from the eye till to bones and muscles; the BL sense of propagation is reverse nighttime, from brain‐retina‐cornea, show a right position too, as dream; BL properties are: monochromatic, coherent, directionality, rotary polarization, amplified power and information along the nervous system; every color has oscillation plans; nonlinear medium of the cells and organs apply Stokes and anti‐Stokes rule; so it was done the first step for psychic processes (vision, memory, thinking, speech) and bionics.

Conclusions

The eye is a bifocal laser system that initiates a biological laser phenomenon, BL, a coherent monochromatic, polarized and amplified radiation, and renders holograms in right position on retina, due to eye itself, not to brain. Important applications are in medicine, physics, teaching, bionics etc.