bluuebunny/crossref_metadata_2025 huggingface dataset:
The effect of trehalose 3% as adjuvant therapy on Lasik procedure
Authors: Mateo Orobia A.J. , Cristobal J. , Casas Pascual P. , Lafuente Ojeda N. , Perez Garcia D. , Peiro Embid C. , Korobko Kulikova V. , Del Buey M. , Lavilla L.
Published: September 2015

Purpose

The majority of all Lasik patients experience dry eye. Usually temporary it also could last for months or years. Patients with no or mild dry eye symptoms but high risk factors have better post‐LASIK outcomes when being preoperatively treated with lubricants. Surgical outcome of patients, with neither symptoms nor risk factors of having dry eye, could be maximized by optimizing the ocular surface before surgery. This study evaluated the effect of trehalose 3% eye drops (Thealoz), pre and post‐surgery use, on the postoperative ocular surface status of the patient.

Methods

Clinical study including 26 eyes from 13 patients, mean age of 35, having no dry eye signs or symptoms, who were scheduled for a LASIK procedure. Patients were randomly assigned to use trehalose 3% 48 h before surgery (G1; 1 drop tid) or no treatment (G2). After LASIK surgery, G1 used trehalose 3% 1 drop q4 h in association with artificial tears (hyaluronic acid ‐HA‐ 1 drop q4 h) and G2 used only artificial tears (1 drop q4 h) for 90 days, as corneal hydrating treatment.

Results

OSDI score obtained during follow‐up period showed a positive evolution in G1 compared to G2 (no statistical significance). Frequency and severity of the symptoms from first day after surgery were significantly lower in G1 (p < 0.05). Other clinical test (osmolarity, TBUT, lissamine staining) also showed positive evolution in G1 but it was not observed statistical differences between treatments. Corneal staining (NIE and Oxford scales) showed lower scores in G1. Results were statistically significant at D30 and at D90 (NIE scale) and at D90 for Oxford scale.

Conclusions

Addition of trehalose to the standard treatment using HA eye drops after LASIK surgery at pre and post‐surgery period, it has been revealed as a positive therapeutic strategy to control and reduce dry eye symptoms and corneal staining score.
New generation analysis of thrombin generation in retinal vein thrombosis
Authors: Fruschelli M. , Capozzoli M. , Scapellato C. , Calzoni P. , Puccetti L.
Published: September 2015

Purpose

To investigate potential mechanisms involved in retinal vein occlusion (RVO) we evaluated thrombin generation and soluble CD40 ligand (sCD40L) with respect to other known thrombophilic factors.

Methods

68 patients affected by RVO (28 central, 40 branch) and 60 healthy controls were evaluated for endogenous thrombin potential (ETP) by a chromogenic method and sCD40L by ELISA technique. Polymerase chain reaction (PCR) was employed for genetic polymorphisms and coagulative/chromogenic methods for othe coagulation factors.

Results

Independently of genetic polymorphisms ETP was increased in patients with CRVO whereas sCD40L was higher in the whole cohort.

Conclusions

Our data indicate an involvement of global coagulative activation in CRVO patients as suggested by ETP.
Electrophysiological ON and OFF responses in Autosomal Dominant Optic Atrophy
Authors: Morny E. , Margrain T. , Binns A. , Votruba M.
Published: September 2015

Purpose

To assess the effect of ADOA on the ON and OFF components of the photopic negative response (PhNR).

Methods

Twelve participants from 6 families with OPA1 ADOA and 16 age matched controls were recruited. Electrophysiological assessment involved long flash focal (20o) and full field ERGs using red flash (664 nm, 250 msec, 55 cd/m2, 2 Hz) on a rod saturating blue background (454 nm, 100 scot cd/m2); and brief xenon flash ERGs using red filter (Lee Filter “Terry Red”, max 300 µs flash duration, 1.69 cd.s.m‐2, 4 Hz) over a continuous rod saturating blue background (Schott Glass Filter BG28, 206 scot cd/m2). Amplitudes (from peak and baseline to fixed time point) and implicit times of the ERG components were analysed.

Results

Mean amplitude (peak to fixed time) of the focal PhNR‐ON were significantly (p < 0.05) reduced by 40% while the focal PhNR‐OFF was completely eliminated. In the long duration full field ERG, the PhNR‐ON and –OFF were reduced by 21% and 57% respectively. Subtraction of the grand averaged ERG of ADOA participants from that of the controls produced a difference plot with a nearly symmetrical loss in the PhNR‐ON and OFF components of the focal ERG. ROC curve analysis showed focal PhNR‐ON and OFF amplitudes performed better than their full field counterparts.

Conclusions

We show that OFF components of the photopic ERG were more severely affected in ADOA than ON components. Additionally, the focal PhNR‐ON and –OFF components were more effective in assessing ADOA than their full field components.
Ophthalmic insert for pupillary mydriasis in neonates
Authors: Bremond‐Gignac D. , Jacqz‐Aigrain E. , Abdoul H. , Beresniak A. , Baud O. , Alberti C.
Published: September 2015

Purpose

To study efficacy and tolerance of ophthalmic insert Mydriasert® versus standard treatment phenylephrine and tropicamide eye drops for fundus examination in neonates.

Methods

Prospective, randomised, single‐blinded non‐inferiority study of 80 premature and full‐term babies and infants treated for fundus examination. Mydriasis was obtained with two groups randomly assigned. The eye drop group received three instillations of 2.5% phenylephrine and 0.5% tropicamide and the insert group received Mydriasert® containing phenylephrine and tropicamide. the mydriasis was evaluated 75 minutes after the introduction of the mydriatic agents.

Results

The mydriasis was successfully achieved in both eyes in 97.5% of infants in the insert group and 90% in the eye drop group at 75 minutes after dispensation. The efficacy of the insert was non‐inferior compared to the eye drops. To reach effective mydriasis, the insert group required fewer nursing interventions for one patient comparing to the eye drop group. Good general and local tolerance was observed in the two groups. However two patients reported an adverse event as bradycardia and gastro‐oesophageal reflux that could be related to neonate pathology.

Conclusions

Mydriasis obtained with the ophthalmic insert Mydriasert® was not inferior compared to standard eye drop treatment. Insert reduced the number of nursing interventions to obtain mydriasis for a fundus examination.
New insights into the proliferative capacities of rabbit corneal endothelial cells
Authors: Crouzet E. , He Z. , Forest F. , Perrache C. , Piselli S. , Peoc'h M. , Gain P. , Thuret G.
Published: September 2015

Purpose

Rabbits are known to have highly proliferative corneal endothelial cells (CECs) with excellent wound healing properties. Yet, little evidence of these capacities is available, except for 2 papers dating back to 1977 (PMID: 873721) and 1984 (PMID: 6511225).

Aim

To better characterize the proliferative capacity of rabbit CECs using labelling of mitosis and DNA synthesis and to search for potential stem cells.

Methods

Central corneal freezing (CF) was used on the right eye of young rabbits (4 weeks) with a brass bar soaked in liquid nitrogen. The thymidine analogue, 5‐ethynyl‐2′‐deoxyuridine (EdU) was injected intraperitonealy at 0, 24 and 48 hours after CF. The corneal opacity was monitored using a slit lamp and corneal thickness using an AS‐OCT. Rabbits were euthanatized 5 or 40 days after CF to label proliferating and slow cycling cells (presumed stem cells) using a Click‐It EdU kit combined with Ki67 labeling. Both analyses were performed on flat mounted whole corneas to observe all CECs.

Results

Corneal opacity and thickness increased within 24 h after the CF. Both parameters returned to normal after 5 days. At 5 and 40 days the central endothelial cell density was normal. 266 ± 17 (1.7%) EdU positive CECs and/or 1532 ± 34 (5%) Ki67 positives CECs were observed, often grouped by pairs, in the endothelial periphery of the right eye as well as in the control eye. 14 ± 4 Ki67 positive cells (0.3%) were observed grouped by pairs in the central endothelium of the right eye.

Conclusions

In rabbit cornea, a few CECs are continuously spontaneously cycling at the periphery of the endothelium and all CECs may have the capacity to proliferate in response to injury, even in the centre.
Improving the overall diagnosis of eyelid margin tumours with in vivo reflectance confocal microscopy
Authors: Grivet D. , Singer A. , Forest F. , Cinotti E. , Douchet C. , Labeille B. , Perrot J.L. , Cambazard F. , Dumollard J.M. , Peoc'h M. , Gain P. , Thuret G.
Published: September 2015

Purpose

The clinical diagnosis of eyelid margin tumours is often challenging and surgical excision in this area may have both functional and aesthetic consequences. Aim: to assess the role of handheld in vivo reflectance confocal microscopy (IVCM) in the diagnosis of eyelid margin tumours.

Methods

We prospectively evaluated and characterized 130 eyelid margin lesions using a handheld dermatology IVCM (Vivascope 3000, Mavig/Lcid, NY). Patients were referred to our multidisciplinary consultation from may 2013 to april 2015. All lesions were first clinically characterized as benign or malignant and then evaluated under IVCM by 3 skilled Dermatologists. Surgical excision was decided for 79 of them, based on both clinical and IVCM features. The 51 remaining lesions with no signs of malignancy were under followed up for at least 6 months. Clinical, IVCM, and histopathology diagnoses were compared.

Results

Considering the 79 excised lesions: IVCM showed a sensitivity (Se) of 90% and a specificity (Sp) of 57% for malignant tumours (basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and melanoma) as compared to the histopathology. Clinical evaluation had Se of 81% and Sp of 50%. IVCM showed Se and Sp of respectively 89% and 62% for BCC; 60% and 100% for SCC; 100% and 45% for melanoma. None of the non‐excised lesions had clinical progression at 6 months and all these lesions were considered as benign.

Conclusions

IVCM is an important tool in the management of eyelid margin tumours by improving the global sensitivity and specificity of the clinical diagnosis GRANT: AP jeune chercheur GIRCI RAA.
Altered micro‐RNA21 expression correlates with enhanced peripheral IL‐23p19 levels patients with primary Sjögren's syndrome
Authors: Ni Gabhann J. , Pilson Q. , Jefferies C. , Murphy C.
Published: September 2015

Purpose

Sjögren's syndrome (SS) is a systemic autoimmune disorder characterized by inflammation that affects mucous membranes particularly those of the exocrine glands, causing dry eyes and dry mouth. Previous investigations have suggested that dysregulated systemic inflammation contributes to the development and pathogenesis of SS. This study aimed to investigate potential mechanisms responsible for over production of pathogenic cytokines in SS patients.

Methods

Peripheral blood mononuclear cells and serum were prepared from whole blood taken from both healthy controls and pSSpatients. Gene induction and micro‐RNA expression were analysed by real‐time PCR. Cytokine levels were determined by ELISA.

Results

We observed significantly enhanced expression of the pro‐inflammatory micro‐RNA, miR‐155 (p ≤ 0.05) and significantly reduced levels of the IL‐10 promoting miR, miRNA‐21 (p ≤ 0.05) compared to healthy controls. In keeping with this altered pattern of miR expression we observed significantly increased serum levels of pro‐inflammatory cytokines (IL‐6, IL‐8 and TNF‐a) as well as the Th17 promoting cytokine, IL‐23p19 (p ≤ 0.05). Altered expression of previously identified targets of miR‐155 (SHIP‐1, SOCS1 – potent anti‐inflammatory regulators) and miR‐21 (IL12p35 and PDCD4, positive regulators of inflammation) was also observed. Significantly a moderate negative correlation (r = −0.657, p ≤ 0.05) was observed between reduced miR‐21 expression and increased peripheral IL‐23p19 levels in pSS patients, suggesting a link between altered miR expression and disease pathogenesis.

Conclusions

Our data suggest that abnormal expression or regulation of miRs and consequently miR regulated genes in innate immunity may contribute to the initiation and progression of SS via overproduction of pathogenic cytokines.
Evaluation of intraocular pressure, choroidal and retinal thickness measurements using optical coherence tomography in non‐diabetic haemodialysis patients
Authors: Strupaite R. , Skvarciany I. , Noreikyte M. , Mockeviciute E. , Galgauskas S. , Rimsevicius L. , Cimbalas A. , Asoklis R.
Published: September 2015

Purpose

The purpose of this study was to evaluate the ocular findings in non‐diabetic patients with chronic renal disease undergoing haemodialysis (HD).

Methods

We performed a pilot study in Vilnius University Hospital Santariskiu Klinikos departments of Nephrology and Ophthalmology. In this study 7 patients (14 eyes) with chronic renal disease undergoing haemodialysis underwent an ophthalmic examination including visual acuity (VA), intraocular pressure (IOP), central foveal thickness (CFT) and subfoveal choroidal thickness (SFCT) measurements using high‐definition optical coherence tomography (OCT, Spectralis; Heidelberg Engineering) line scans with the activated enhanced depth imaging mode, (central corneal thickness (CCT) and endothelial cell density (CD). Each patient underwent examination 30 minutes before and 30 minutes after a HD session.

Results

14 eyes of 7 patients with chronic renal failure (CRF) undergoing HD were included. 5 males (35.5 %) and 2 females (14.3 %) participtated. Patients mean age was 72.71 ± 7.67 years. The mean VA was 0.83 ± 0.16. The mean IOP increased from 12.28 ± 1.89 to 14.14 ± 4.75 mmHg (p = 0.1). The change was statistically insignificant. The mean central foveal thickness decreased statistically insignificant from 227.07 ± 15.71 to 225.57 ± 14.10 μm (p = 0.69). The mean subfoveal choroidal thickness before HD was 207.57 ± 50.71 μm, after HD – 194.85 ± 55.39 μm (p = 0.016). There was a statistically significant decrease in the choroidal thickness before and after haemodialysis (p = 0.016). The mean CCT was 529.77 ± 32.12 μm. The mean CD 2777.11 ± 380.15 cells/mm2.

Conclusions

Haemodialysis with a high ultrafiltration volume did not alter the retinal thickness and IOP but caused a significant choroidal thinning in non‐diabetic end‐stage CRF patients.
Evaluation of the retinal nerve fiber layer thickness and its relation to visual evoked potentials in multiple sclerosis
Authors: Strupaite R. , Mockeviciute E. , Kizlaitiene R. , Budrys V. , Liveikiene A. , Mamontovaite G. , Cimbalas A. , Asoklis R.
Published: September 2015

Purpose

To evaluate the retinal nerve fiber layer (RNFL) thickness by optical coherence tomography (OCT) in Lithuanian patients with multiple sclerosis (MS) and to assess the relationship between RNFL thickness and visual evoked potentials (VEP).

Methods

From 2013 till 2014 a prospective study involving 71 patients with multiple sclerosis was conducted in Vilnius University Hospital Santariškių Clinic Center of Neuroscience and Eye Diseases. The epidemiological, clinical, laboratory and instrumental data was assessed: gender, age, oligoclonal bands, IgG index in cerebrospinal fluid (CRF), visual evoked potentials (VEP), OCT. RNFL and papilomacular bundel (PMB) thicknesses were performed with SD‐OCT.

Results

The distribution of gender for patients with MS was as follows: men n = 22 (31%), women n = 49 (69%); average age −40.7 ± 10.7 years. OCT results were as follows: RNFL average thickness: right eye 85.5 ± 15.6 μm, left eye 86.3 ± 13.2 μm. According to the t‐test: the upper nasal (NS) segment averages of right and left eyes differed statistically significant −6.6 ± 14.7 μm (p < 0.05). There was significant negative correlation between VEP P100 latency and RNFL thickness of the right eye TI segment (r = −0.57; p = 0.01) and the left eye PMB segment (r = −0.52; p = 0.02). The most damaged segment was the temporal (T) one: right eye 84.5% (n = 60), left eye −90.1% (n = 64). RNFL of both eyes revealed statistically significant mean differences with the IgG index.

Conclusions

The most vulnerable segment of the retina is the temporal. If VEP gets prolonged thinning of RNFL is also observed. The CSF index is increased by immunologically more active multiple sclerosis. We think that more active form of MS may be associated with retinal segments violation. Hence we may conclude that RNFL thinning could be related with irreversible progression of the disease.
Nrf2‐ and PGC‐1α‐deficient mice: A novel animal model for impaired autophagy in AMD?
Authors: Paterno J.J. , Smedowski A. , Hytti M. , Bjørkøy G. , Amadio M. , Levonen A.L. , Tavi P. , Kauppinen A. , Kaarniranta K.
Published: September 2015

Purpose

To clarify the complex role of impaired autophagy in RPE damage, we analysed mice deficient in both Nrf2 and PGC‐1α. Increasing evidence of impaired autophagy as a contributor to AMD has raised the importance of animal models that fundamentally mimic autophagy decline in RPE.

Methods

We analysed morphological and immunohistochemical changes in the retina of aged Nrf2 and PGC‐1α double knock‐out (dKO) mice and wild‐type controls. The Keap1‐Nrf2 pathway, an essential system involved in oxidative stress response, is regulated by proteasomes and autophagy. PGC‐1α is a master regulator of ROS‐scavenging enzymes, and it has a role in inducing autophagy/mitophagy. We performed immunostaining of proteins related to oxidative stress and autophagy (4‐HNE, Beclin‐1, HuR, LC3, p62, and ubiquitin).

Results

RPE degeneration was prominent in dKO mice and it was associated with changes in autophagy and oxidative stress.

Conclusions

Our findings suggest Nrf2 and PGC‐1α deficiency increases oxidative stress and affects autophagy. This coincides with the retinal degeneration observed in the promising new AMD mouse model.
Differential molecular signature of ectatic and non‐ectatic areas from Keratoconus patient corneas
Authors: Pahuja N. , Rajiv Kumar N. , Shetty R. , Shroff R. , Ghosh A.
Published: September 2015

Purpose

To evaluate if the gene expression profile of corneal epithelium from the cone area in Keratoconus (KC) differs from the peripheral non‐ectatic areas.

Hypothesis

The ectasia in Keratoconic cornea is localized to the cone while the peripheral areas are apparently normal. Hence we hypothesized that within the cone of a KC patient cornea, the structural weakness may be a function of localized gene expression differences.

Methods

Study group contained 54 KC patients undergoing epithelium off corneal collagen crosslinking (CXL) and 9 non‐ectatic subjects undergoing photo refractive keratectomy (PRK) as controls. The cone vs periphery distinction is based on keratometry and location of the cone based on elevation map. Using a 4.5 mm trephine centered on the cone, epithelium was scraped separately for cone and rest as periphery. In non‐ectatic controls, the central 4.5 mm area was taken as cone. Gene expression profiling was performed for each pair of cone and periphery samples by quantitative PCR.

Results

Lysyl oxidase levels were significantly reduced in the cone of KC patients (p = 0.002). Structure related genes COL1 (p = 0.01) and COL4 (p = 0.008) were also reduced significantly in KC patient cones. The cytokines IL6, TGFβ and TNFα did show an increased trend; regulatory cytokine IL10 did not show significant trend. Matrix remodeler MMP9 showed an increasing trend at the cone while its inhibitor TIMP1 showed a reducing trend that was not significant(p = .09).

Conclusions

Ectasia in KC may be driven by local molecular factors at the cone that possibly spreads to other parts of cornea as disease progresses.
Self‐complementary vectors for optimization of AAV2‐mediated gene‐therapy of corneal endothelial cells
Authors: Gruenert A. , Buening H. , Schnoedt M. , Schmeer M. , Schleef M. , Kruse F.E. , Fuchsluger T.
Published: September 2015

Purpose

Recombinant adeno‐associated viruses 2 (rAAV2) represent a nonpathogenic and safe alternative to other viral delivery systems. However, their transduction efficiency in corneal endothelial cells (CEC) is limited. As the level of transgene expression is dependent on the conversion of single‐stranded (ss)‐ into double‐stranded (ds)‐DNA, self‐complementary (sc)‐AAV vectors have been developed to circumvent this problem. The aim of this study was to evaluate the use of scAAV2 in terms of transduction efficiency in CEC. Additionally, the impact of transduction on cell viability was investigated.

Methods

A human corneal endothelial cell line (HCEC‐12) as well as organ‐cultured human donor corneas were transduced with different titers of ss‐ or sc‐AAV2. Transduction efficiencies were compared by means of GFP‐transgene expression. GFP‐expression in HCEC‐12 cells was evaluated by flow cytometry over a period of 28 days. GFP‐expression in human donor corneas was analyzed by confocal microscopy on day 6. 7‐AAD staining and flow cytometry as well as MTT‐assay were performed to determine cell viability after transduction.

Results

GFP‐expression was significantly higher in cells transduced with scAAV2 than in cells transduced with ssAAV2. The difference in transduction efficiency decreased with increasing vector titer. The highest transgene expression rate using scAAV2 was 86.9% compared to 80.5 % using ssAAV2. In human donor corneas GFP‐expression was observed in 72.2% (scAAV) and 44.1% (ssAAV) of CEC respectively. There was no significant difference between viability of transduced and untreated cells.

Conclusions

ScAAV2 vectors are an effective tool to enhance transduction efficiency in CEC. Allowing higher transduction rates with lower vector titers, this could improve AAV2‐mediated gene therapy to protect CEC in corneal allografts.
Uveal melanoma in Finnish patients with congenital ocular melanocytosis
Authors: Mamunur R. , Kivelä T.
Published: September 2015

Purpose

To described the characteristics of uveal melanoma in congenital ocular melanocytosis in Finland.

Methods

For this retrospective observational case series, we identified all 15 of 867 (1.7%; 95% CI 1.0–2.8) uveal melanoma patients (5 male, 10 females) with congenital ocular melanocytosis during January 2000‐May 2015 at the Ocular Oncology Service, Helsinki University Hospital. The patient was followed up at 3 and 6 months, every 6 months for 3 years, and thereafter annually. The diagnosis of uveal melanoma was based on clinical and ultrasonographic features, and metastases were screened with annual abdominal ultrasonography and liver function tests.

Results

The mean age at diagnosis was 55 years as compared with 64 years for all 867 patients. The mean thickness and basal diameter of the tumours were 6.5 (SD 3.6) and 13.1 (SD 4.4) mm, respectively, as compared to 5.1 (SD 3.9) and 12.5 (SD 4.5) among all patients, respectively. The melanoma involved the ciliary body in 6 patients (40%). The tumours represented TNM stages I in 4 (27%) patients, II in 5 (33%), III in 5 (33%) and IV (metastases at the time of diagnosis) in 1 patient. Enucleation was done in 2 cases, I‐125‐brachytherapy in 7 cases, and 5 patients were treated with Ru‐106. Recurrent tumour growth was observed in 2 patients. Overall 5‐ and 10‐year survival was 68% (95% CI 35–87) and 13% (95% CI 1–43). Survival was associated with TNM stage: 100%, 80%, 33% and 0% at 5 eyars for stages I‐IV, respectively. One patient survived for 10 years without metastasis.

Conclusions

In our data set, uveal melanoma patients with congenital ocular melanocytosis are on average 9 years younger than uveal melanoma patients in general, and have a tendency to die of metastases.
Glaucoma patient satisfaction regarding tolerance to their prostaglandin treatment: results from the GOAL (Glaucoma patients treated with prOstaglandins; sAtisfaction evaLuation) survey in Europe
Authors: Clarke J. , Stalmans I. , Lemij H. , Baudouin C.
Published: September 2015

Purpose

The high prevalence of ocular surface diseases (OSD) in patients treated for OHT/glaucoma is expected to displease them. To evaluate this, a survey was conducted in three European countries: the Netherlands, Belgium and United Kingdom.

Methods

In this multicentre epidemiological survey, the following data were recorded during a visit to the ophthalmologist: glaucoma history, previous treatments and reasons for any change, tolerance, patient satisfaction, ocular signs and the presence of OSD.

Results

The data of 793 patients treated with prostaglandins were analysed (168 from the Netherlands, 253 from Belgium and 372 from England). Only 9% of the treatments were preservative‐free.

A very large number (93.7%) of patients declared to be satisfied or very satisfied with their current glaucoma treatment. The mean score of tolerance evaluated on a Visual Analog Scale (VAS) was 82.7 ± 16.1 mm (range from 0 mm: very bad tolerance to 100 mm: very good tolerance).

At the same time, the survey revealed (displayed in percentage of all patients):

OSD was diagnosed in 42.5%

symptoms upon instillation in 31.4%

symptoms between instillations in 57.3%

a conjunctival hyperaemia in 32%

frequent use of artificial tears in 25.1%

The presence of hyperaemia, ocular signs, and symptoms upon or between instillations, positive conjunctival staining and frequent use of tear substitutes was statistically significantly linked to patient satisfaction (p ≤ 0.006).

Conclusions

A high percentage of satisfied patients (94%) was found in this survey, despite OSD signs and symptoms. Tear film substitutes are commonly prescribed to treat these side effects. Alternative treatment regimes such as preservative free treatments may reduce local side effects and encourage ophthalmologists to convince their patients that local intolerance is no longer inevitable.
Clinical characteristics and surgical outcomes of mesectodermal leiomyoma of the ciliary body and choroid
Authors: Park H.J. , Lee J.H. , Lee S.C.
Published: September 2015

Purpose

Mesectodermal leiomyoma is a rare tumor that can arise from smooth muscle tissue in the iris or ciliary body or from heterotopic smooth muscle in the choroid. The purpose of this study was to describe the clinical characteristics and surgical outcomes of mesectodermal leiomyoma of the ciliary body and choroid.

Methods

Retrospective observation case series of 8 patients who were diagnosed with mesectodermal leiomyoma with histopathologic and immunohistochemical confirmation.

Results

The median age at presentation was 37.5 years. The median follow‐up period was 27 months. Ultrasonography showed dome‐shaped smooth surface with low to medium internal reflectivity and regular internal structure in all tumors. The tumor had a median largest base diameter of 10.4 mm and a median thickness of 7.7 mm. They revealed pinkish colored surface and vessels that more developed than other intraocular tumors. The tumors located on ciliary body only in 4 eyes, on choroid only in 2 eyes, and on ciliochoroid in 2 eyes. 6 patients who had tumors on ciliary body only or ciliochoroid underwent lamellar sclerouvectomy. 2 patients who had choroidal tumor received enucleation or partial excision for biopsy each. On immunohistochemistry, all the tumors were stained positively for smooth muscle actin and desmin. After lamellar sclerouvectomy, the tumor did not show recurrence in follow up period. But the patient that underwent partial removal of tumor on choroid showed irregularly changing surface with increasing size.

Conclusions

Mesectodermal leiomyoma did not show the recurrence after lamellar sclerouvectomy and malignant change of tumor. However these tumors are difficult to differentiate from other intraocular tumor and to conclude definitely that they do not develop malignant change because they have heterogeneity from benign leiomyoma of other body organs.
Changes in choroidal thickness after intraocular pressure reduction following trabeculectomy
Authors: Kadziauskiene A. , Kuoliene K. , Galgauskas S. , Asoklis R.
Published: September 2015

Purpose

To evaluate changes of choroidal thickness (CT) after an acute reduction in intraocular pressure (IOP) following trabeculectomy.

Methods

Subfoveal and peripapillary CT and IOP were measured in 40 glaucomatous eyes (40 patients) 1 day before, 1 week and 1 month after the trabeculectomy. The choroid was evaluated using spectral domain optical coherence tomography enhanced depth imaging at the fovea and 1.7 mm superior, temporal, inferior and nasal to a optic nerve head centre. Biometry was performed preoperatively.

Results

The mean IOP was significantly reduced after trabeculectomy at both follow‐up visits (P < 0.001). The mean subfoveal CT (±SD) increased from 216.1 (±86.1) µm at baseline to 260.3 (±86.9) µm after one week and 243.1 (±87.1) µm after one month postoperatively (P < 0.001). The mean CT significantly increased one week after trabeculectomy at all peripapillary locations (P < 0.01), however, the thickening of choroid was significant only temporally after one month. There was positive correlation between the magnitude of change in subfoveal CT and the IOP reduction (r = 0.518, P < 0.001 for the 1‐week follow‐up; r = 0.290, P = 0.034 for the 1‐ month follow‐up). The preoperative axial length correlated positively with the magnitude of thickening of subfoveal CT after one week (r = 0.451, P = 0.002).

Conclusions

The subfoveal and peripapillary CT increased with the IOP reduction following trabeculectomy, however, choroidal thickening around the optic nerve disc appeared to be short‐term. The thickening of subfoveal CT was found to be related to the greater IOP reduction and longer axial length.
Lack of collagen XVIII in mice evokes age‐dependent deficiency in retinal pigment epithelium proteostasis
Authors: Kivinen N. , Felszeghy S. , Aikio M. , Pihjalaniemi T. , Kaarniranta K.
Published: September 2015

Purpose

Collagen XVIII is a unique component of basement membranes (BMs) with the structural properties of both a collagen and a proteoglycan. It has been found at the basement membrane/stromal interface and is thought to mediate their attachment. Proteolytic cleavage within its C‐terminal domain releases a fragment, endostatin, which has been reported to have anti‐angiogenesis effects. Age‐dependent loss of vision in the collagen XVIII mutant mice is associated with pathological accumulation of deposits under the retinal pigment epithelium. We have recently shown that impaired proteasomal and autophagy clearance associate with the pathogenesis of age‐related macular degeneration (AMD). In this study, staining levels of proteasomal and autophagy markers were studied in different ages of the Col18a1−/− mice.

Methods

Enucleated eyes from 3, 12 and 18 months old mice were embedded in paraffin according to a routine protocol. Serial 5 μm‐thick parasagittal samples were immunostained for proteasomal ubiquitin (Ub) and autophagy markers SQSTM1/p62 and Beclin. The extent of immunopositivity in the retinal pigment epithelial cells was evaluated during confocal microscopic analysis.

Results

Lack of collagen XVIII in mice evoked age‐dependent retinal pigment epithelium (RPE) degeneration and drusen‐like deposit accumulation. Proteasomal Ub protein conjugate staining was prominent in both RPE cytoplasm and extracellular space. Autophagy markers SQSTM1/p62 and beclin stainings were prominent in the basal part of RPE cell cytoplasm in the Col18a1−/− mice.

Conclusions

Disturbed proteostasis regulated by collagen XVIII may induce RPE degeneration, increase protein aggregation and finally predispose to the choroidal neovascularization.
Pore size assessment during corneal endothelial cell permeabilization by femtosecond laser‐activated carbon nanoparticles
Authors: Jumelle C. , Mauclair C. , Houzet J. , Bernard A. , He Z. , Piselli S. , Perrache C. , Gain P. , Thuret G.
Published: September 2015

Purpose

Therapeutic molecules delivery represents a promising solution to maintain human corneal endothelial cells (HCECs) viability, but transport across cell membrane must be facilitated. A new delivery method consists in ephemerally permeabilizing cell membranes using a photo‐acoustic reaction produced by carbon nanoparticles (CNPs) and femtosecond laser (FsL). The aim of this work is to investigate the size of pores formed at cell membrane by this technique.

Methods

To induce cell permeabilization, HCECs (B4G12 cell line) were put in contact with CNPs and irradiated with a 500 µm diameter Ti:Sa FsL focalized spot. Four sizes of fluorescent reporter molecules were delivered into HCECs to investigate pore sizes: calcein (1.2 nm), FITC‐Dextran 4 kDa (2.8 nm) and FITC‐Dextran 70 kDa (12 nm) and FITC‐Dextran 2MDa (50 nm). Uptake of each molecule was assessed by flow cytometry immediately after irradiation.

Results

The delivery rate was dependent of their size. Calcein was delivered in 56 ± 8% of HCECs, FITC‐Dextran 4 kDa in 42 ± 4%, FITC‐Dextran 70 kDa in 22 ± 3% and finally FITC‐Dextran 2MDa in 13 ± 2%, suggesting that a large number of pores in the size ranging from 1.2 to 2.8 nm were formed. However, 12 nm and larger pores were almost half more infrequent.

Conclusions

Pore sizes formed at cell membrane by the technique of cell permeabilization by FsL activated CNPs were investigated for the first time. This innovative non‐viral method is characterized by pore sizes large enough for the efficient delivery of small, medium and big therapeutic molecules on HCECs. GRANT: Fondation des Aveugles de France, Fondation de l'Avenir, Fondation Visaudio (ET1‐638).
Transfer of molecules into the endothelial cells of whole human corneas using carbon nanoparticles activated by femtosecond laser
Authors: Jumelle C. , Mauclair C. , Houzet J. , Barnard A. , He Z. , Piselli S. , Perrache C. , Gain P. , Thuret G.
Published: September 2015

Purpose

The targeted delivery of drugs and genes represents a promising solution to modify human corneal endothelial cells (HCECs), however, it remains limited by the difficulty to efficiently cross cell membranes without altering their integrity. Aim: to adapt an innovative technique of macromolecules delivery in corneal endothelium using carbon nanoparticles (CNPs) activated by femtosecond laser (FsL).

Methods

HCECs of 35 whole human corneas stored in organ culture were permeabilized by photo‐acoustic reaction induced by irradiation of CNPs by FsL beam. The uptake of dextran AlexaFluor 488, a 3000‐Da fluorescent macromolecule, was assessed using fluorescent microscopy. Three fluences (20, 30 and 40 mJ/cm2) and protective additives (ROCK inh and Poloxamer 407) were tested in order to increase uptake efficiency while limiting cell mortality (ethidium +). Dextan uptake and cell mortality rates were quantified using the CorneaJ plugin for ImageJ.

Results

Dextran delivery significantly increased with fluence, reaching a mean of 13% of HCECs for 40 mJ/cm2. Induced mortality varied from 0 to 53% and was more dependent of the cornea itself than on fluence. Treatment by either protective additive did significantly enhance the delivery rate, nor HCECs viability.

Conclusions

For the first time, ex vivo HCECs of whole corneas were permeabilized by mediated‐nanoparticles laser perforation. Even if the delivery rate was lower than for viral vectors, it remained high for a non‐viral technique. Mortality was variable according to corneas tested even with the use of protective additives. GRANT: Fondation des Aveugles de France, Fondation de l'Avenir, Fondation Visaudio (ET1‐638).
Retinal vein occlusion in a patient with jugular vein compression by metastasis of carcinoma of the oral tongue
Authors: Navarro Perez , Ascaso F.J. , Sánchez J.I. , Esteban O. , Martinez M. , Del Buey M.Á. , Núñez E.
Published: September 2015

Purpose

Retinal Vein Occlusion (RVO) is the second retinal vascular disease after the diabetic retinopathy. It has been associated with multiple factors both systemic (arterial hypertension, diabetes mellitus, hemoglobinopathy, …) and local (glaucoma, hyperopia, …). We report the very uncommon case of a central RVO that appeared after the patient suffered an internal jugular vein compression syndrome secondary to metastases of squamous cell carcinoma of the oral tongue (SCCOT).

Methods

Spectral‐domain optical coherence tomography (SD‐OCT) and fluorescein angiography (FA) were used in the diagnosis and follow‐up of the visual disorder and PET‐CT and cervical ultrosonography were used in the diagnosis of jugular compression.

Results

A 48‐year‐old male complained with decreased visual acuity on his right eye. Best‐corrected visual acuity (BCVA) was 0.2 in the RE and 0.63 in the LE. Fundus examination revealed image of impending CRVO. FA showed severe bilateral venous stasis especially on the RE. He had been diagnosed with a SCCOT. PET‐ CT revealed a tongue neoplasia with right anterior jugular adenopathy. A cervical ultrosonography showed a compression on both uptown jugular veins and more constricted in high area on the right one. The tumor was considered unresectable. The patient underwent palliative chemotherapy and the ophthalmological symptoms and signs significantly improved. VA improved to 0.5 in the right eye and 0.8 in the left eye after chemotherapy.

Conclusions

Ophthalmologists should be aware of internal jugular vein compression as a possible cause of CRVO in patients suffering from metastases of cervicofacial neoplasies.
Efficacy and safety of ranibizumab in diabetic macular edema: real life study
Authors: Hrarat L. , Fajnkuchen F. , Sarda V. , Grenet T. , Buffet S. , Chaine G. , Giocanti‐auregan A.
Published: September 2015

Purpose

To evaluate the efficacy and safety of ranibizumabin patients with vision loss secondary to diabetic macular edema (DME).

Methods

Retrospective analysis of a cohort of patients withvision loss (VA) due to DME and treated by ranibizumab. Patients were examined before treatment and during treatment every 4–6 weeks. Ophthalmologic examination included:measure of the best corrected visual acuity (BCVA) on the ETDRS scale, examination at the slit lamp, fundus, and SD‐OCT (Cirrus 5000, Carl Zeiss Meditec). All patients receiveda loading dose of 3 monthly injections followedby re‐treatments on an as‐needed basis (PRN regimen) The primary endpoint was the change in visual acuity at 12 months. The other criteria assessed were central retinal thickness (CRT) after loading dose, and at 12 months, and the number ofintravitreal injections (IVT) during the first year of follow‐up.

Results

109 eyes of 79 consecutive patients treateded since November 2012 have been included. At baseline the mean BCVA was 48.77 letters, the CRT was 517 microns. At 12 months the average BCVA was of 60.80 letters (p < 0.05), with an average VA gain of +14.67 letters and 25% of patients had a BCVA> 70 letters. The mean CRT after 3 injections was 344.32 microns (p < 0.05) and 332 microns (p < 0.05) at 12 months, with 57.23% of patients with CRT ≤ 300 microns. At 12 months the average VA in patients with CRT ≤ 300 microns was 63.51 letters (p < 0.05) and the average AV in patients with ERC> 300 .microns was 57.39 letters (p < 0.05). The average number of IVT performed during the first year of follow up was 5.59. No serious adverse event was noted.

Conclusions

Pivotal studies have clearly shown the benefit of ranibizumab treatment of vision loss due to DME. This study in a “real life” setting confirms the results obtained in randomized trials.
Corneal surface temperature and tear secretion in young and adult aqueous tear deficient guinea pigs
Authors: Gallar J. , Luna C. , Alonso E. , Revert R. , Quirce S. , Aracil A. , Belmonte C. , Acosta M.C.
Published: September 2015

Purpose

To evaluate changes in ocular surface temperature and tear secretion in young and adult control and tear‐deficient (DE) guinea‐pigs.

Methods

Tearing rate (TR) was measured using phenol red threads (30s). Tear break‐up time (TBUT) was measured after fluorescein instillation. Corneal surface temperature (CST) was recorded continuously in the full open eye during 30s after the eye opening using an infrared thermal camera (InfRec R300SR, Nippon Avionics). Images were analyzed using dedicated software.

Results

Tearing rate was significantly higher and TBUT was significantly lower (p < 0.05) in adult (12‐18 months) compared with young (2‐4 months) animals (p < 0.001). CST immediately after the eye opening had a value around 36.5°C in control eyes in young and adult animals. Most tear deficient eyes had initial CST over 37°C. The slope of temperature decrease during the interblink period was similar for all ages. As expected, DE animals had significantly lower TR (p < 0.001) and TBUT (p < 0.01) than intact animals, although their initial CST and the slope of interblink temperature decrease were similar to age‐matched control eyes.

Conclusions

Tear‐deficient eyes show higher CST values immediately after blink suggesting the presence of inflammation. Temperature reduction during the interblink period was not modified in DE, despite the reduced stability of tear film.
Insulin‐induced dilatation of porcine retinal vessels in vitro is most pronounced in precapillary arterioles
Authors: Jensen P.S. , Bek T.
Published: September 2015

Purpose

Impaired retinal blood flow is involved in the pathophysiology of diabetic retinopathy, and it has been shown that the smaller and larger retinal vessels may contribute differently to these flow changes. Diabetes mellitus is accompanied with changes in a number of metabolic parameters including a reduced effect of insulin. However, the vasoactive effects of insulin on retinal vessels with different calibers have not been studied in detail.

Methods

Porcine hemiretinas were mounted in a newly established experimental model specifically developed for studying diameter changes of retinal vessels with different caliber. Changes in the diameter of larger arterioles (25 μm or larger), pre‐capillary arterioles (10‐25 μm) and capillaries (smaller than 10 μm) were studied after intravascular and extravascular addition of insulin in retinal vessels preconstricted with the prostaglandin analogue U46619 from altogether 6 hemiretinas from different animals.

Results

Insulin dilated preconstricted arterioles and pre‐capillary arterioles significantly after both intravascular and extravascular application (p < 0.01 for all comparisons), but had no significant effect on the diameter of capillaries after intravascular (p > 0.07) and extravascular (p > 0.31) application. The dilating effect of insulin was significantly more pronounced for pre‐capillary arterioles than for the two other vessel types after extravascular application (p < 0.01).

Conclusions

Insulin dilates preconstricted retinal vessels, but the effect is most pronounced in pre‐capillary arterioles. This may have importance for understanding disturbances in retinal blood flow in diabetic retinopathy.
The Effect of Ikervis® (1 mg/mL Ciclosporin cationic emulsion) on severe keratitis in patients with dry eye disease participating in a phase III study
Authors: Leonardi A. , Labetoulle M. , Ismail D. , Garrigue J.S. , Rancho L. , Brignole‐Baudouin F. , Amrane M. , Baudouin C.
Published: September 2015

Purpose

The treatment of severe keratitis in Dry eye disease (DED) represents a real therapeutic challenge. The effect of Ikervis®, an unpreserved 1 mg/mL ciclosporin A cationic emulsion, in this condition was evaluated.

Methods

Sansika study was a 12 month phase III, multicenter, double‐masked, vehicle controlled, in which 246 DED patients with severe keratitis (corneal fluorescein staining, CFS, grade 4 on modified Oxford scale), were randomised to one drop of Ikervis® or vehicle daily at bedtime for 6 months. Vehicle patients switched to Ikervis® after 6 months.

Results

The proportion of patients achieving by M6 at least a two‐grade improvement in CFS and a 30% improvement in symptoms [Ocular Surface Disease Index (OSDI)] was 28.6% with Ikervis® vs 23.1% with vehicle, p = 0.326. There was a greater improvement in Ikervis® treated patients over vehicle in mean CFS change from baseline (CFB) at M6 (−1.81 vs −1.48, p = 0.037). The mean OSDI CFB was −13.6 with Ikervis® and −14.1 with vehicle at M6, p = 0.858. There was a reduction in the ocular surface inflammation assessed with Human Leukocyte Antigen‐DR (HLA‐DR) expression in favour of Ikervis® at M6 (p = 0.021). Post hoc analysis showed a greatest proportion of patients achieving a 3‐grade improvement in CFS with Ikervis® over vehicle (28.8% vs 9.6%) at M6.

Conclusions

This study confirmed the positive benefit/risk ratio of Ikervis® for the treatment of severe keratitis in DED. The availability in Europe of Ikervis® represents a significant progress in the management of this disease.
Treatment of peripheral exudative hemorrhagic chorioretinopathy by intravitreal injections of Aflibercept: report of 4 cases
Authors: Malcles A. , Russo A. , Agard E. , El‐Chehab H. , Dot C.
Published: September 2015

Purpose

Peripheral exudative hemorrhagic chorioretinopathy (PEHCR) is a rare disorder characterized by subretinal or sub‐pigment epithelial hemorrhage and exudation localized outside the macular region.Some authors consider PEHCR as the peripheral version of age‐related macular degeneration while others believe PEHCR is a specific variant of polypoidal choroidal vasculopathy (PCV).

Methods

We report 4 cases of PEHCR (3 women and 1 man) treated by intravitreal injections of Aflibercept. The mean age was 78 years (range 62–83 years). In all cases the presence of PCV was confirmed with indocyannine green angiography. Examination revealed peripheral subretinal or sub‐pigment epithelial hemorrhage with exudation extented into the macula in all patients. After 2 or 3 intravitreal injections of Aflibercept, PEHCR lesions and submacular exudation significantly regressed.

Results

Generally PEHCR has a favorable prognosis, hovewer vision can be threated because of subretinal hemorrhage and fluid extension into the macula. In cases in which the macula appears threatened, intravitreal antivascular endothelial growth factor therapy and/or laser‐based therapies may be indicated. Peripheral lesion can be difficult to reach with photodynamic therapy. Intravitreal Aflibercept, with its mechanism of action, may be an effective treatment option to reduce subretinal fluid.

Conclusions

PEHCR is not well‐recognized by the ophthalmologist and is often misinterpreted as a choroidal melanoma. To our knowledge this is the first report of Aflibercept use and efficacy in this indication.
3D Sphere cultures of uveal melanoma reveal a molecular signature with a potential target for cancer therapy
Authors: Ness C. , Garred Ø. , Eide N. , Bærland T. , Nicolaissen B. , Moe M. , Noer A.
Published: September 2015

Purpose

Uveal melanoma (UM) is the most common intraocular malignancy and is fatal in approximately 50% of the cases. Cancer relapse can be seen years after treatment. Diverse mechanisms have been proposed to explain the late relapse of UM e.g cancer dormancy and the presence of cancers stem cells (CSCs). UM has the disadvantage of being difficult to culture, thus a limited number of cell lines are available. 3D sphere cultures of early passages offer a lower degree of clonal selection and perhaps a more accurate reflection of the primary tumours. The propagation of cells as spheres is believed to enrich for a CSC‐like population.

Methods

2D cultures were expanded in RPMI 1640 with 10% FBS, while 3D sphere cultures were expanded in hESC + MEF for 7–10 days.

We compared UM primary tumours fresh frozen vs. 2D culture and 3D sphere culture of the same donors by microarray, qRT‐PCR, transmission electron microscopy (TEM), immunohistochemistry (IHC) and chromatin immunoprecipitation (ChIP).

Results

3D sphere cultures induce signalling pathways that enhance survival and increase oncogenic activity. They show ultrastructural resemblance to in vivo UMs. The metabolic shift seen in 3D cultures could reflect the survival patterns of pre‐metastatic cancer cells.

Conclusions

The molecular signature of the 3D cultures reveals the presence of attractive targets for future epigenetic modulation or cancer cell vaccines.