bluuebunny/crossref_metadata_2025 huggingface dataset:
A variant rs613872 in TCF4 gene is responsible for the higher risk for Fuchs endothelial corneal dystrophy development‐ the results of study in Polish patients
Authors: Udziela M. , Oldak M. , Ruszkowska E. , Sciezynska A. , Binczyk E. , Ploski R. , Szaflik J.P.
Published: September 2015

Purpose

The aim of the study was to investigate the connection between rs613872 polymorphism in TCF4 gene and Fuchs Endothelial Corneal Dystrophy (FECD), and evaluation of TCF4 gene expression within corneas of patients with FECD and individuals of Polish population control group.

Methods

Genomic DNA was extracted from peripheral blood. Polymorphism rs613872 was genotyped in 227 subjects with FECD and 312 controls using real‐time PCR and TaqMan sonds. Total RNA was isolated from Descemet's membranes, which were stripped during endothelial keratoplasty performed in patients with FECD (n = 24) and from fragments of donors’ corneas unused for transplantation (n = 22). The difference in TCF4 gene expression was estimated by quantitative method PCR.

Results

The distribution of genotypes TT, GT, GG in control group was 74%, 23.4%, 2.6% and in FECD patients 21.6%, 64.8%, 13.7%, respectively. The rate of alleles T and G in patients’ group was 245/454 (54%) and 209/454 (46%). In control subjects the results were 535/624 (85.7%) and 89/624 (14.3%). Allele G was much more common in patients with FECD compared to control group (OR = 5.13, 95%CI: 3.84–6.86, χ2 = 132.63, p < 0.0001). Within corneas from patients with FECD the tendency to increased TCF4 gene expression was observed in comparison to the control group, but the disparity was not statistically significant.

Conclusions

The results of our investigations revealed the rs613872 variant in TCF4 gene to be significant associated with FECD in Polish patients. The influence of changing expression of TCF4 gene for FECD development requires the further studies.
Apparent Contradictions in Pupillomotor, Sensory Visual and Electrodiagnostic Findings in Chiasmal Compression
Authors: Krastel H. , Landauer M. , Diehm T. , Kubarko A. , Schlichtenbrede F.
Published: September 2015

Purpose

To improve the understanding of pupillomotor and electrodiagnostic findings in correlation to visual sensory defects in chiasmal compression.

Methods

Full and half field VEPs were recorded by the Roland Retiport system. Stato‐kinetic dissociation in visual field findings was demonstrated by Goldmann kinetic and Twinfield static perimetry. Low luminance conditions are applied with both kinetic and static perimetry. In addition, the he swinging flashlight pupil test was applied in different variants, to solve apparent contradictions in functional findings. Analyzed are two cases of chiasmal compression by aneurysms of the internal carotid artery and one case of a tuberculum sellae meningeoma, in which visual symptoms were the presenting ones.

Results

Despite sensory symptoms may be confined to one eye, contralateral involvement due to chiasmal compression may show up in perimetry – more early by static than by kinetic examination. Low luminance perimetry produces more significant field defects in chiasmal lesins than standard perimetry. The swinging flash comparison of pupil responses may miss the unilateral relative afferent defect, depending on the direction of the light stimulus. Comparing not only responses to OD and to OS stimulation but also pupil responses to upper and lower half field stimulation helps to not overlook relative afferent pupil defects. Comparing, on the other hand, upper and lower half field VEPs has to consider physiological differences in these responses.

Conclusions

In chiasmal compression, apparent contradictions in results of functional examinations may lead to false diagnostic conclusions or even to doubts concerning the somatic origin of visual complaints. The above mentioned extended toolbox of functional exams improves the diagnostic reliability.
Double‐hump sign on gonioscopy: definitive plateau iris? A cross‐sectional study using ultrasound biomicroscopy
Authors: Cordeiro Sousa D. , Leal I. , Caiado F. , Goncalves I. , Reina M. , Marques‐Neves C. , Prior Filipe H. , Abegao Pinto L.
Published: September 2015

Purpose

Plateau iris configuration (PIC) is a rare condition involving an angle closure unrelated to pupillary block. It may be defined by a narrow angle and a double‐hump configuration on gonioscopy. Plateau iris syndrome (PIS) may lead to acute angle‐closure glaucoma due to an anterior displacement and rotation of the ciliary body. It has been proposed that ultrasound biomicroscopy (UBM) is helpful in PIC/PIS diagnosis. Our work aims to describe UBM quantitative and qualitative findings in patients whose gonioscopy suggested a PIC/PIS

Methods

Cross‐sectional study involving patients with a double hump gonioscopic finding. UBM was then performed by a blinded observer and evaluated for the presence of following ultrasonographic (US) criteria: (1) a thick and flat iris, (2) a sharp, square root angulation on its insertion, (3) an anterior rotation of the ciliary body, (4) irido‐ciliary sulcus narrowing, (5) iris‐trabecular apposition and (6) a relatively normal anterior chamber (AC) depth. Only high‐quality images were accepted

Results

From September 14 to May 15, 35 patients (59 eyes) were recruited. Only 3 eyes presented the six US criteria, 23 eyes filled five of the criteria, 13 satisfied four criteria, 16 presented three criteria and 4 two criteria. The most commonly verified criteria (over 95% of them) were a thick and flat iris and a square root insertion. There was no association between any of these criteria and sex nor age (p > 0.10). Furthermore, the presence/absence of these criteria did not correlate with either anterior chamber depth, lens vault and lens length (p > 0.10)

Conclusions

The majority of patients presenting with clinical iris plateau syndrome do not fulfill the entire US criteria for this condition. However, the US‐based iris morphological parameters seem to be present in nearly all iris plateau patients.
The Liverpool Uveal Melanoma Prognosticator Online (LUMPO) for prognosing metastasis free survival in the absence of cytogenetic data after ruthenium brachytherapy for uveal melanoma
Authors: Rospond‐Kubiak I. , Wroblewska‐Zierhoffer M. , Twardosz‐Pawlik H. , Kociecki J.
Published: September 2015

Purpose

Liverpool Uveal Melanoma Prognosticator Online (LUMPO) is a tool developed by Eleuteri et al. to establish the prognosis for uveal melanoma patients according to the initial tumour characteristics and cytogenetic data. It has been validated with two separate cohorts of patients in United Kingdom and more recently in US. The aim of this study was to test the prognosticator in a homogenous group of patients treated with ruthenium brachytherapy where genetic analysis was not performed.

Material and methods

The records of the patients treated with ruthenium brachytherapy for uveal melanoma at the Department of Ophthalmology, Poznan University of Medical Sciences between 1994 and 2012 were retrospectively reviewed. The probability of 3‐, 5‐ and 10‐year metastasis free survival were obtained for each patient using the LUMPO accessed online and then compared with the existing follow‐up data.

Results

We identified 102 patients, 60 women, 42 men in a mean age of 59 years. Mean largest basal diameter of the treated tumours was 9.29 (range: 4.04–18.9) mm, mean tumour thickness: 4.8 (range: 2.6–7.01) mm. Follow‐up ranged from 3 to 22 years, mean: 7.55 years. 33 patients died, 18 (17.65%) out of metastatic disease. The metastatic death was not related to patients’ age (p = 0.6866), LBD (p = 0.3049) or tumour thickness (p = 0.7063) alone. The probability of metastasis free survival according to LUMPO was significantly lower for the metastatic group comparing to the surviving group at 3 years (p = 0.0017) and 5 years post treatment (p = 0.0001).

Conclusions

LUMPO is a useful tool for prognostication for uveal melanoma patients. However, the use of cytogenetic data makes this prognosis more precise.
Ophthalmologic manifestations of the granulomatosis with polyangiitis (Wegener)
Authors: Toutée A. , Touitou V. , Bodaghi B. , Lehoang P. , Saadoun D. , Hie M. , Schoindre Y.
Published: September 2015

Purpose

Wegener's granulomatosis (WG) is a severe focal granulomatous inflammation with variable ophthalmic manifestations

Methods

Patients with a confirmed WG, seen in a single tertiary center between 2008 and 2014 were included retrospectively. WG was proven based on biological or histological analysis

Results

Five patients (3W/2M) aged 26–55 years, were included. Clinical features included one scleritis with dacryoadenitis, one bilateral episcleritis complicated with uveo‐scleritis, one bilateral Mooren's ulcer and two orbital inflammatory pseudotumor. Time between the onset of symptoms and the diagnosis was 100 months (range: 1–276 months). All patients had anti‐cytoplasm antibodies to polynuclear neutrophils and underwent biopsies. Histological features included vasculitis inflammatory necrotizing granulomas. Extraocular features were pulmonary lesions (100%), rhinosinusal involvment (80%), renal disease (40%), neurological injury (40%). All patients were initially treated with high‐dose corticosteroids, wich were progressively decreased and received maintenance immunosupressive drugs. Immunosuppressive treatment was initiated on average 64 months after the onset of signs (range: 1–276 months)

Conclusions

WG‘s ophthalmologic symptoms are variable. Scleritis remains the most common manifestation, followed by orbital inflammation. Atypical manifestations such as Mooren's ulcer or uveitis can delay the diagnosis. A multidisciplinary approach is mandatory to control this life threatening condition. WG should be considered in all cases of chronic orbital inflammation, scleritis or keratitis to ensure prompt diagnosis and improve the systemic prognosis.
Hospital prevalence of visual of visual impairment caused by diabetic retinopathy
Authors: Rocha De Sousa A. , Tavares‐Ferreira J. , Perestrelo S.P. , Lima‐Ramos P. , Batista A.M. , Santana R. , Macedo A.F.
Published: September 2015

Purpose

To investigate cases of visual impairment caused by diabetic retinopathy (DR) in a hospital population.

Methods

As part of an observational study to estimate the prevalence and costs of visual impairment in Portugal (PCVIP study), clinical records of all patients attending the ophthalmology department of a tertiary hospital were analysed looking for patients meeting the inclusion criteria. Inclusion criteria were: (i) presenting visual acuity in the better eye <5/10 (20/40) and/or (ii) visual field <20°. Diagnosis of cases with VI were classified according with ICD9. Results reported here were selected from the total number of patients with VI by filtering ICD9 codes staring by 362.

Results

In 12 weeks, 1920 cases of VI were detected, 586 (31%) caused by any type of DR. From those: 54% were caused by non‐proliferative‐DR, 40% by proliferative‐DR and 6% by diabetic macular oedema. The mean age of the patients with VI caused by DR was 69.4 (sd = 9.5) years and 57% were female. The estimated hospital prevalence (for 52 weeks) of VI caused by DR is 39% (95%CI = 38–41).

Conclusions

Our results show that DR remains the leading cause of VI in the population attending our hospital. Information about the number of patients reaching VI will be fundamental to assess the cost‐benefits of treatments and public health campaigns to reduce the burden of diabetic retinopathy in Portugal.
The Four Seasons of Dry Eye Disease Seasonal Variations in Presenting Symptoms and Signs of Dry Eye Disease in Norway
Authors: Eidet J.R. , Ræder S. , Chen X. , Badian R. , Utheim Ø. , utheim T.P.
Published: September 2015

Purpose

To investigate the seasonal variations of presenting symptoms and signs of dry eye disease (DED) in Norway

Methods

930 DED patients examined between August 2012 and May 2015 at the Norwegian Dry Eye Disease Clinic in Oslo, Norway, were consecutively included. All patients underwent a comprehensive ophthalmological examination. Presenting symptoms and signs were related to the season according to when each patient had been examined. Weather report data from the exact day of examination in Oslo, including mean temperature, relative humidity, hours of sunshine, and mean wind, from the Norwegian Meteorological Institute, were also compared with the presenting symptoms and signs.

Results

Mean seasonal temperatures for Oslo during spring, summer, fall and winter were 7°C, 16°C, 7°C, and −2°C, respectively. Compared to the rest of the year, tear film break‐up time (TFBUT) was highest during summer (P < 0.001), ocular protection index (OPI) lowest during winter (P = 0.013), Schirmer I lowest during summer (P = 0.004), tear meniscus height was highest during winter (P = 0.004), meibum quality least pathological during winter (P = 0.001), the percentage of patients being diagnosed with meibomian gland dysfunction lowest during winter (P < 0.001), and intraocular pressure highest during winter (P = 0.001). Weather report data correlated the strongest with meibum quality and intraocular pressure, which both were associated with mean temperature (r = 0.24; P < 0.001 and r = −0.21; P < 0.001). Self‐reported symptom load and dry eye severity level (DESL) did not differ between seasons.

Conclusions

Parameters for assessing DED show seasonal variations, which are important to consider when examining patients with DED. Moreover, contrary to common belief, our results suggest that meibomian gland function appears to improve during winter and with low temperatures.
Homonymous hemimacular thinning in retrochiasmal lesions
Authors: Cunha J.P. , Proença R. , Dias‐Santos A. , Vicente A. , Anjos R. , Costa L. , Cardigos J. , Ferreira J. , Amado D.
Published: September 2015

Purpose

To evaluate the thickness of macular retina and determine which retinal layers are most affected by retrochiasmal visual pathways lesions.

Methods

Mean retinal thickness utilizing automated intraretinal layer segmentation of spectral domain optical coherence tomography scans was performed in 40 eyes of 40 patients with retrochiasmal visual pathways lesions and compared with 60 eyes of control subjects.

Multiple linear regression analysis was used to determine the relationship between retinal thickness and follow‐up, age and gender.

Results

Ganglion cell and inner plexiform layer was thinner in the temporal hemiretina ipsilateral and in the nasal hemiretina contralateral than in healthy controls.

The mean thickness was significantly reduced in lesions over 6 months of duration, with no differences in correlations with age or gender.

Conclusions

This study demonstrate ganglion cell and inner plexiform thinning in the hemimacular area. These results support the concept that transneuronal retrograde degeneration of the retinal ganglion cells can be detected by OCT in humans with retrochiasmal visual pathways lesions.

This homonymous hemimacular thinning in OCT represents an imaging biomarker that can be of valu in diagnosis, prognosis and clinical trials of neuroprotectives therapies.
Anterior chamber and refractive parameters in diabetic patients according to metabolic status
Authors: Costa L. , Cardigos J. , Vicente A. , Borges B. , Ferreira J. , Cunha J.P. , Amado D.
Published: September 2015

Purpose

Diabetes Mellitus is associated with changes in refractive parameters. Some aspects already studied were the corneal biomechanics and lens thickness. Although, the discussion about anterior chamber angle and depth is still open.

The author objective was to analyze and correlate the anterior chamber depth, lens vault and lens thickness with disease duration and metabolic status.

Methods

Prospective case–control study. The anterior chamber and refractive parameters were studied using the Visante OCT and the differences between diabetic patients with metabolic control and disease stability were determined (group 1), without (group 2) and group‐control (3). The metabolic control is based on HbA1c levels. The cut‐off considered was 7%.

Results

A total of 64 patients were evaluated (group 1 – n = 21; group 2 – n = 20; group 3 – n = 23). The mean age was 64.32 ± 7.55 years and approximately 5 years of disease duration. In both groups of diabetic patients we found thicker lens, narrow anterior chamber and higher lens vault compared to control group. There was a difference between diabetic groups exists, but it was not statistically significant.

Conclusions

The anterior chamber angle and lens vault are influenced by the serum glucose levels. Further studies will be necessary to clarify the physiopathology mechanism responsible for the anterior segment modifications.
Therapautic options: how does it work?
Authors: Pournaras C.J.
Published: September 2015

Visual acuity, in diabetic patients, is decreased due to the development of macular edema (DMO), capillary non‐perfusion, and vitreous hemorrhage secondary to retinal neovascularization. Clinical therapeutical approaches using focal photocoagulation and intravitreal treatments offer new insights for the managmenet of DMO and the preservation of vision. The inhibition of the endothelial growth factor (VEGF) and the inflammatory factors, alone or in association to focal laser, have an important impact on the reversal of the inner blood‐retina barrier (BRB) diabetic abnormalities. Laser photocoagulation induces in addition, an improvement of the macular hemodynamics, a reversal of tissue hypoxia, a downregulation of the VEGF and inflammatory factors expression and an occlusion of the permanent microvascular abnormalities.
Genotype and phenotype correlation of monogenic corneal dystrophies in population of central Poland
Authors: Udziela M. , Oldak M. , Sciezynska A. , Ploski R. , Szaflik J.P.
Published: September 2015

Purpose

To assess the genotype‐phenotype correspondence in monogenic corneal dystrophies caused by KRT,TGFBI and UBIAD1 genes mutation.

Methods

61 patients from 30 Polish families with clinically diagnosed epithelial and stromal corneal dystrophies participated in the study.

Corneal phenotypes were assessed by slit lamp, AS‐OCT,and confocal microscopy in vivo. Genomic DNA was obtained from blood samples and respective exons (hot spots) were PCR amplified and sequenced on both strands.

Results

Molecular genetic testing revealed heterozygous missense p.E498V mutation (exon 7) of KRT3 in one family with Meesmann corneal dystrophy phenotype, p.R555W (exon 12) mutation in 19 patients diagnosed with granular type I dystrophy (GCD1). In two patients p.R124H mutation (GCD2, Avellino) was found. In three patients (2 families) heterozygous p.R124L (exon 4) mutation was identified and diagnosed as Reis‐Buecklers dystrophy. In two unrelated patient p.R555Q (exon 12) mutation typical for Thiel‐Behnke dystrophy was found. Heterozygous p.R124C (exon 4), p.T538R (exon 12) and p.H626R (exon 14) mutations were identified, respectively, in 10 patients diagnosed with lattice corneal dystrophy (LCD1). A novel p.L565P mutation was found in one family with late‐onset LCD.

Among 18 idividuals (4 families) suffering from stromal Schnyder corneal dystrophy (SCD) molecular genetic testing revealed 3 different UBIAD1 gene mutations: p.N102S, p.D112N, p.T120R.

Conclusions

The genotype typical for monogenic corneal dystrophies caused by KRT and UBIAD1 genes mutation corresponds with its clinical phenotype. TGFBI is associated with phenotype heterogenity and in some cases only genetic tests may confirm the proper diagnosis.

This indicates that a relatively straightforward molecular analysis can be a practical use in diagnosis of these conditions and associated genetic counseling.
Healing of a resistant neurotrophic corneal ulcer using a new matrix therapy agent (RGTA): A case report
Authors: Zghal I. , Zahaf A. , Fekih O. , Zayani M. , Bouguila H. , Nacef L.
Published: September 2015

Purpose

We report a case of a resistant neurotrophic corneal ulcer successfully treated by the matrix regenerating agent (RGTA) Cacicol(®).

Methods

We report a case of an 18‐year‐old female patient, who developed a persistent epithelial ulcer after cataract surgery complicated by endophthalmitis, with no improvement despite 4 weeks of artificial tears. A new ophthalmologic solution based on a regenerating agent (RGTA, Cacicol20®) was then used, with a dosage of two eye drops per week for 8 weeks.

Results

Improvement was observed in 2 weeks, and complete healing was obtained in <5 weeks, with no side effects.

Conclusions

This heparin mimetic, which may stimulate extracellular matrix healing, may be a possible alternative therapy to autologous serum or amniotic membrane transplantation in severe neurotrophic ulcer. However, randomized studies are necessary to confirm this encouraging result.
Upgrading wide field contact specular microscope
Authors: Hor G. , Gavet Y. , Gain P. , Thuret G. , Bernard A. , Pinoli J.C.
Published: September 2015

Purpose

Non‐contact specular microscopes (SM) developed 25 years ago highly facilitated image acquisition while eliminating contaminations risk. Nevertheless their very small field of observation (SM Topcon SP2000: 0.1 mm2) constitute major limitations for the assessment corneas.

Aim

To upgrade a wide field contact SM with a digital camera and dedicated software.

Methods

The original camera film was replaced by a digital camera (Canon EOS 6D with full‐frame 35 mm sensor) connected to a computer. The new camera was fixed on the SM (Konan SP5500, ×40 zoom) with 3D print custom adaptor and uses its optics. After acquisition of wide field images (0.6 mm2), they were processed using a segmentation algorithm (watershed with markers method). Software, using several libraries (ITK, OpenCV, Qt, MySQL), has been developed allowing the acquisition of images (camera control), image processing, and storage of results in a database.

Results

A segmented image showing only cell borders in black over white background and document which presents ECD number (1000 cells counted) and cell's characteristics showing quality of cells (regarding their size). Stored in a database, these results are available for operators.

Conclusions

The upgraded wide field contact SM counts a great number of cells. Consequently, it estimates the ECD with less bias than other methods. Also, it can be used for the assessment of heterogeneous endothelium like in Fuchs corneal endothelial diseases for which noncontact SM are obviously unsuited. GRANT: ANR 2012 CORIMMO project.
Clinical cases
Authors: Creuzot C.
Published: September 2015

Clinical cases of diabetic retinopathy will be considered: diabetic retinopathy with macular edema, macular edema and cataract surgery, proliferative diabetic retinopathy, diabetic retinopathy and pregnancy.
Therapeutics course of childhood noninfectious uveitis
Authors: Tarfaoui N. , Lala E. , Uettwiller F. , Marot Y. , Hoarau C. , Lelez M.L. , Arsene S. , Pisella P.J.
Published: September 2015

Purpose

Childhood noninfectious uveitis is a relatively uncommon but severe disease. All cases seen at the Tours's Hospital were included in this study and were equally followed by the multidisciplinary consultation to evaluate our practice over time.

Methods

44 children followed from 2003 to 2013 were included. Demographic criteria (gender, age, type of uveitis, initial and final clinical description) and therapeutic outlines were recorded. A vision quality questionnaire Eye–Q associated with a tolerance questionnaire were sent to all patients.

Results

66% were girls, the average age of diagnosis is 6.5 years and 48% of cases were JIA. Average final visual acuity was approximately 20/20. The initial treatment was topical corticotherapy alone in 47% of cases, and 42% associated with oral corticosteroids. Since the introduction of our multidisciplinary consultation, the delay in determining the change in treatment has been decreased (p = 0.001) without modifying neither the duration nor the dose of corticosteroid therapy. 16% developed new ocular complication during average follow‐up of 39 months. 60% of the ocular complications de novo could be topical corticosteroid related. The response rate was 62% and 66% with preserved quality of vision. The Eye – Q score was correlated with the visual acuity but not with the duration or the doses of any treatments.

Conclusions

Our population showed similarity to that of the literature, except for the early support. Our Visual and inflammatory results were satisfactory, which could be explained by the introduction of our multidisciplinary consultation allowing a faster adaptability of therapeutics.
Evolution of hiperreflective points after intravitreal dexamethasone implant injection in patients with macular edema associated with retinal vein occlusion
Authors: Almenara Michelena C. , Ascaso F.J. , Idoate A. , Caramello C.M. , Sánchez J.I. , Berniolles J. , Cristobal J.
Published: September 2015

Purpose

To analyse the evolution of macular hyperreflective points (HRP) detected by spectral‐domain optical coherence tomography (SD‐OCT) in eyes with macular edema secondary to retinal vein occlusion (RVO), following treatment with intravitreal dexamethasone implant (Ozurdex®).

Methods

Retrospective observational study of 45 consecutive cases of RVO‐associated macular edema: 13 central RVO and 32 branch RVO treated with Ozurdex®. The relationship between best corrected visual acuity (BCVA), central macular thickness (CMT) and the presence of HRD in SD‐OCT before treatment and two months post‐injection was determined.

Results

CMT decreased significantly following treatment (527.7 μm vs 308.3 μm, p < 0.001). Although there was a visual acuity improvement in 18 of the 45 eyes (40%), the mean BCVA difference was not statistically significant (p = 0.373). Numerous HRP were detected in 24 patients (53.3%), disappearing in 10 of them (41.7%) after corticosteroid intravitreal therapy.

Conclusions

Disappearance of HRP after an intravitreal dexamethasone impant would support the hypothesis that HRP could represent some inflammatory cells.
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‐β (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.
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.
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 2 and 6 months after the ischemic event. The OCT device was set to image a 15 × 10° 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.
Epiretinal membrane peeling for eyes with asteroid hyalosis: a case–control study
Authors: Mouna A. , Conaert J.B. , Kurun S. , Ameloot F. , Berrod J.P.
Published: September 2015

Purpose

To evaluate anatomical and functional results of epiretinal membrane peeling for patients with asteroid hyalosis (AH) comparing with those of a control population without AH.

Methods

Retrospective, case–control study, of a cohort of 1104 patients operated from an epiretinal membrane (EM) between January 2002 and February 2014. Forty‐four consecutive patient were included in the EM associated with AH group and were compared to 44 control patient without AH, matched for: age, sex, date of surgery, and axial length. The best corrected visual acuity (BCVA) and central macular thickness on OCT (CMT) were measured at baseline and postoperatively at 1, 6 and 12 months. Intraoperative and/or postoperative complications were also analyzed.

Results

34 men and 10 women were included in the AH group. Respectively, the mean initial BCVA was 0.49 ± 0.21 logMar for the AH group vs 0.44 ± 0.21 logMAR for the control group (p = 0.2), and the mean initial CMT was 415 ± 71 µm vs 422 ± 73 µm (p = 0.6). No significant difference was found regarding the final BCVA, with respectively a mean of 0.37 vs 0.24 logMAR (p = 0.26) at 1 month, 0.27 vs. 0.23 logMAR (p = 0.5) at 6 months, and 0.17 vs 0.2 logMAR (p = 0.26) at 12 months. Also, no difference was found regarding the evolution of CMT, with respectively a mean of 368 vs 353 µm (p = 0.5) at 1 month, 347 vs 358 µm (p = 0.61) at 6 months, 345 vs 349 µm (p = 0.87) at 12 months. Only a single macular hole was recorded in the AH group in the follow up.

Conclusions

The presence of asteroid hyalosis does not constitute a factor of poor prognosis for visual recovery after epiretinal membrane peeling.
Imaging of intravitreal injected solution dispersion
Authors: Willekens K. , Reyns G. , Jonckx B. , Feyen J. , Yewei L. , Coudyzer W. , Yicheng N. , Stalmans P.
Published: September 2015

Purpose

The extent of activity of an intravitreal injected drug is linked to its dispersion within the vitreous body. Researchers have been trying to visualize dispersion of intravitreal injected solutions using Indian ink or fluorescein, either with subsequent dissection or with endoillumination, both invasive methods that could influence the dispersion pattern. Therefore, this pilot study aims at investigating and identifying the best minimal invasive imaging method for visualizing the dispersion of an intravitreal injected solution.

Methods

To determine the optimal imaging concentration, a series of 5 enucleated porcine eyes were injected with 0.1 cc of 100%, 50%, 25%, 20% and 10% standard iodium contrast medium, respectively. Injections were made using a standard 1 cc syringe and 30 gauge needle at 3.5 mm from the limbus aiming at the center of the globe. Subsequently, the dispersion of the contrast agent was monitored using high resolution imaging methods: mammography and ultra high resolution computed tomography (UHRCT). For the latter, 3D reconstructions were rendered.

Results

A 1:10 dilution mixture combined optimal visualization contrast with low viscosity of the injection solution using radiographic ultrahigh resolution mammography. Both mammography and UHRCT images were taken from two eyes; one with a slow injection, the other with a fast injection.

Conclusions

3D reconstructed UHRCT images were favored over 2D mammography images for dynamic imaging of the intravitreal solution dispersion.
Anterior lens epithelium in cataract patients with retinitis pigmentosa – scanning and transmission electron microscopy study
Authors: Andjelic S. , Draslar K. , Hvala A. , Hawlina M.
Published: September 2015

Purpose

In retinitis pigmentosa (RP) patients, relatively minor lens opacity posteriorly centrally may cause disproportionate functional symptoms requiring cataract operation. To investigate possible structural reasons for this opacity development, we studied the structure of the lens epithelium of RP patients.

Methods

The anterior lens capsule (aLC: basement membrane and associated LECs) were obtained from cataract surgery and prepared for scanning and transmission electron microscopy (SEM and TEM).

Results

Both SEM and TEM show the holes in the anterior lens epithelium of cataract patients with RP. Mainly, the holes appear as thinning and degradation of the epithelium, with the dimensions from <1 μm to more than 10 ηm and covering the region of several aLECs. A step towards the formation of denuded regions with the dimensions even bigger than 50 ηm may be the detachment of the lens epithelium. Other type of holes in size up to 20 ηm, may be formed by gradual stretching of the lens epithelium. Another type of holes is formed between adjacent LECs where lateral connections are absent, with dimensions 0.1‐2 ηm × up to 10 ηm.

Conclusions

Showing of holes in the anterior lens epithelium supports the hypothesis that disturbed structure of the lens epithelium plays a role in water accumulation in the RP cataractous lens. We suggest that the lens epithelium has a role in the development of the cataract in RP patients.
Microbiology of conjunctiva sac in intravitreal injections
Authors: Grzybowski A. , Gaca‐Wysocka M. , Paluch M.
Published: September 2015

Purpose

To evaluate the conjunctival sac flora before and after intravitreal injection (IVI) in eyes with no prophylactic antibiotic use.

Methods

37 eyes of 37 patients not using systemic or local antibiotics for at least 30 days were included. Microbiological culture from conjunctiva sac to nutrient media was taken twice: before IVI and before any topical medications were given and 30 minutes after anty‐VEGF IVI. Topical antibiotics were not used neither before, nor after IVI. Shortly before IVI conjunctival sac was rinsed with 5% povidone‐iodine (PVI). Control group constituted eyes not treated with IVI of the same patients.

Results

Negative microbiological cultures before and after IVI were noted in the studied group in 15 patients (40.5%) and in 9 control eyes (24.3%). Coagulase‐negative Staphylococci (CNS) were cultured in 13 eyes (35.1%) before IVI and in 8 eyes (21.6%) after IVI. In 3 eyes (8.1%) Staphylococcus aureus was shown before IVI, with subsequent negative cultures. In the control group CNS was shown in 14 eyes (37.8%) before IVI and in 7% (18.9%) after IVI. Microbiological flora was identical in studied and control groups in 14 cases (37.8%). There was no case of post‐IVI endophthalmitis.

Conclusions

About 50% of cultures were negative, in 35% – CNS, and in 15% – other bacteria were cultured, including Staphylococcus aureus in 8%. The number of negative cultures after IVI (the use of PVI) was higher than before IVI, and all Staphylococcus aureus were eliminated. The eye antisepsis based on PVI in IVI is an effective and efficient prophylaxis method.
Systemic immunosuppression with mycophenolate mofetil to prevent corneal graft rejection after high risk penetrating keratoplasty: a 2‐year follow‐up study
Authors: Szaflik J.P. , Major J. , Izdebska J. , Lao M. , Szaflik J.
Published: September 2015

Purpose

The study aimed to evaluate the efficacy and safety of systemic immunosuppression with mycophenolate mofetil (MMF) to prevent corneal graft rejection after high risk penetrating keratoplasty.

Methods

One hundred ninety‐six consecutive patients who underwent high risk penetrating keratoplasty defined as the presence of deep vascularization in more than two quadrants, keratouveitis, emergency keratoplasties, and retransplantations were enrolled in the study. Ninety‐eight prospectively followed‐up patients were treated with MMF (with dose adjustment based on mycophenolic acid [MPA] serum concentration), and 98 patients were in the non‐MMF‐treated retrospectively assessed control group.

Results

During a mean of 24 months’ observation, immune reactions occurred in 8 cases (8%) and graft rejection with subsequent graft failure occurred in 3 cases (3%) in the MMF group. In the control group, graft rejection occurred in 76 cases (78%) and failure due to graft rejection occurred in 30 cases (31%). Kaplan–Meier analysis showed that after a year 93% of the grafts in the MMF‐treated group and 47% in the control group showed no immune rejection (p < 0.01, log‐rank test). Cox regression analysis showed that MMF treatment decreased the risk of graft rejection 11 times (RR = 11, 95.0% CI 4.8–25, p < 0.0001). Among 98 MMF‐treated patients, 13 had gastric discomfort, 3 developed leucopenia, and 2 had anemia that resolved after MMF dose reduction.

Conclusions

MMF treatment after high risk penetrating keratoplasty is safe and reduces the incidence of immune graft rejection and graft failure. Side effects were rare and reversible in all but one case.
Receptor‐targeted liposome‐peptide‐siRNA nanoparticles represent a novel and efficient siRNA delivery system to prevent conjunctival fibrosis
Authors: Yu‐Wai‐Man C. , Tagalakis A. , Manunta M. , Hart S.L. , Khaw P.T.
Published: September 2015

Purpose

Glaucoma is the leading cause of irreversible blindness worldwide and fibrosis is the main cause of failure of glaucoma surgery. We have previously described how the Myocardin‐related transcription factor/Serum response factor (MRTF/SRF) pathway is intricately linked to all the key pathways in ocular fibrosis. Our aim was to develop a novel liposome‐peptide‐siRNA (LYR) nanoparticle as an efficient delivery system for MRTF siRNA in conjunctival fibrosis.

Methods

The LYR nanoparticles were characterised with regard to particle size and zeta potential. Real‐time qPCR and western blotting were used to compare the silencing efficiency in human Tenon's fibroblasts using different MRTF siRNA concentrations, targeting peptides, and liposomes. The cytotoxicity of the LYR nanoparticles was assessed using the MTT cell assay. Three‐dimensional fibroblast‐populated collagen matrices were also used as a functional assay to measure contraction in vitro.

Results

All LYR nanoparticles were strongly cationic with sizes around 100 nm and PDIs < 0.4. The LYR nanoparticles efficiently silenced the MRTF gene by 76% and 84% using 50 nM and 100 nM siRNA respectively. The MRTF gene was also efficiently silenced by 76% and 75% using the targeting peptides Y and ME27 respectively. The MRTF protein expression was significantly decreased by the LYR nanoparticles. The non‐PEGylated liposome formulations showed higher silencing efficiency than the cationic PEGylated formulations. The MRTF nanoparticles were also not cytotoxic at 50 nM siRNA concentration and prevented matrix contraction after a single transfection treatment.

Conclusions

This is the first study to show that receptor‐targeted liposome‐peptide‐siRNA nanoparticles represent an efficient and safe siRNA delivery system that could be used to prevent fibrosis after glaucoma surgery.
The study of needle tip aspirates and entry sites after intravitreal injections with different needle types
Authors: Lytvynchuk L. , Savytska I. , Sergiienko A. , Binder S. , Petrovski G.
Published: September 2015

Purpose

To compare the entry site and study the cellular content of different needle tip aspirates after transscleral intravitreal injection (IVI) on rat eyes.

Methods

The intravitreal injections (IVI) were performed on 20 white outbred rat eyes (10 IVI with 30‐gauge subcutaneous needles (SCN), 10 with 27‐gauge Pencan needle (PCN) (B. Braun)). The 1.0 cc syringes were preloaded with 0.02 cc of balanced salt solution (BSS) and connected to the needles. The penetration was performed 1 mm posterior to the limbus, followed by aspiration of 0.01 cc vitreous body. Aspirated material was evacuated onto glass slides and stained by Azure‐2‐Eosin. Enucleation and histological analysis of the IVI entry site was performed at magnification 100 and 400 times.

Results

Cellular content of the aspirated material was revealed in all cases. The aspirated cells represented conjunctival epithelial‐, ciliary body non‐pigmented epithelial‐, sclerocyte‐like cells and vitreous crystallised specimens. The amount of conjunctival epithelial cells prevailed in 27‐gauge PCN IVI cases. The stained granular proteins were less significant in the case of 27‐gauge PCN tips. The entry sites after 30‐gauge SCN injection showed concrete cut of all tissues, while partial reassembling of the sclerocyte bindings was seen after 27‐gauge PCN injections.

Conclusions

The use of 30‐gauge SCN and 27‐gauge PCN needles for transscleral IVI has resulted in trauma of all layers of the rats’ eye wall. Histological analysis of the needle tip aspirates showed less tissue damage by 27‐gauge PCN; moreover, the SCN tips created complete cuts due to their sharp edges, in contrast to the PCN tips.
The added value of undiluted vitreous biopsy samples processed by the Cellient® tissue processor (Hologic) in unsolved uveitis
Authors: Van Calster J. , Van Ginderdeuren R.
Published: September 2015

Purpose

In this prospective study, the added value of undiluted vitreous biopsy samples in the diagnosis of unsolved uveitis was evaluated. Vitreous biopsies are difficult to handle because of the paucity of cells and the gelatinous structure of the vitreous. Histopathological analysis of the vitreous is useful in challenging cases to differentiate uveitis from lymphoma or infection and to define the type of cellular reaction.

Methods

97 consecutive undiluted vitreous samples were isolated in patients with unsolved intermediate or posterior uveitis. A 1.5–2.5 cc sample was taken through a single 23G or 27G port using the EVA vitrectomy platform (DORC) with a twin duty cycle high speed cutter. The samples were analysed with the Cellient® tissue processor (Hologic). This machine is a fully automated processor starting from a specified container with PreservCyt® (fixative fluid) with cells to paraffin. Routine histochemical and immunostainings were evaluated.

Results

In 94.8% of the cases, sufficient material was found to provide an added value in the diagnostic workup. In 34%, a Cytolyt® mucolytic wash was necessary to prevent clotting of the tubes in the Cellient® tissue processor due to the viscosity of the sample. In 7% the diagnosis was an acute inflammation (presence of granulocytes), in 42% chronic active inflammation (presence of T‐lymphocytes), in 36% low‐grade inflammation (presence of CD68 cells, with <5% T‐lymphocytes); and in 9% a malignant process (lymphoma). In 5% no diagnosis was found. In the chronic active inflammation group 39% was a granulomatous inflammatory process.

Conclusions

This standardized protocol for sampling and handling undiluted vitreous biopsies gives a superior result in morphology, number of cells, and possibility of immuno‐histochemical stainings. The diagnosis can be established or confirmed in 94.8% of cases.