bluuebunny/crossref_metadata_2025 huggingface dataset:
An unusual germ responsible for fungal keratitis: Metarrhizium Anisopliae
Authors: Zaidi M. , Bazard M.C. , Dorin J. , Machouart M. , Angioi K.
Published: September 2015

Purpose

Fungal keratitis remain rare, and often have a poor visual prognosis. About 30% require a keratoplasty. Many fungal agents may be involved. We report the first case of Metarrhizium Anisopliae keratitis in Europe.

Methods

A 39‐years old man complained about pain and redness in his right eye 15 days after having received earth on his face. His ophtalmologist diagnosed a corneal abscess and initiated a local treatment by Ciprofloxaxin. The patient was referred to our clinic 2 days later for worsening of local abscess. Visual acuity was limited to 2/10 RE and 10/10 LE. Slit‐lamp examination revealed diffuse conjunctival redness, and a 3‐mm diameter corneal abscess surrounded by diffuse corneal edema. After realization of a corneal scraping (which results happened to be negative), we introduced local antibiotherapy (Vancomycin‐Ceftazidim), associated with Amphotericin B and Hexamidin. Despite these treatments and the realization of a therapeutic ptosis for persistent ulcer, the abscess enlarged and a deep stromal infiltration developed. As we suspected a fungal etiology, systemic Voriconazole was added. Despite all these treatments the abscess worsened dramatically and a transfixiant keratoplasty was performed.

Results

Microbiological analysis of the cornea revealed neither bacteria nor amoeba or viruses, but presence of a filamentous fungus secondary identified as Metarrhizium Anisopliae by molecular biology.

Conclusions

Metarrhizium anisopliae is usually known as an entomopathogenic fungus. It was first described in human pathology 18 years ago and only 9 cases have been reported worldwide, including 4 cases of keratitis. Our patient is the first case of Metarrhizium Anisopliae keratitis described in Europe. This report also shows that transfixiant keratoplasty is often the only treatment that allows visual rehabilitation in such dramatic cases.
Evaluation of the influence of corneal biomechanical properties on the central corneal curvature after a SUPRACOR procedure
Authors: Delbarre M. , Rambaud C. , Berguiga M. , Sendon D. , Graber M. , Froussart‐Maille F.
Published: September 2015

Purpose

SUPRACOR™, performed with the Technolas Excimer Workstation 217P (Bausch + Lomb Technolas), creates a small zone of high refractive power in the central cornea, the « bump », to facilitate near focus. The aim of this study is to evaluate the influence of corneal biomechanics on this « bump ».

Methods

This retrospective study included 46 eyes of 23 patients. The Supracor ablation pattern was applied, to create hyperprolate shape resulting about 2 D near addition. The periphery was treated with hyperopic ablation in a 6 mm zone, using 9.5 mm suction ring, under 120 µm flap created by the IntraLase FS60 femtosecond laser (AMP, USA). Every patient underwent a corneal topography (Pentacam, Oculus, Germany) before and 1 month after surgery to evaluate the importance of the “bump”, and a biomechanical evaluation with the Ocular Response Analyser (ORA, Reichert, NY). CH (Corneal Hysteresis) and CRF (Corneal Resistance Factor) were evaluated. Spearman's rank correlation coefficient was used to analyze the relationship between the parameters of the ORA and the « bump ».

Results

The mean patient age was 55.5 ± 3.94, ranging from 50 to 62 years. Pre‐operative spherical equivalent were 1.57 ± 0.77 D. Mean corneal thickness was 548 ± 44 µm. CH and CRF were respectively 10.53 ± 1.63 mmHg and 10.90 ± 2.12 mmHg. Mean “bump” was 2.25 ± 0.98 D, ranging from 0.50 to 4.64 D. A correlation was found between the CH and the bump (r = 0.34; p = 0.022) and also between the pachymetry and the bump (r = 0.45; p = 0.004). A strong correlation was found between corneal thickness and the CH (r = 0.62; p = 0.001).

Conclusions

In this study, the “bump” is correlated with the corneal thickness and the CH. The corneal thickness appears to be sufficient to predict the “bump” in hyperopic patients undergoing Supracor. These results should be confirmed in a larger sample of patients.
Gender specific IOP measurement using induced corneal vibration analysis ‐ a multicenter clinical trial
Authors: Bitoun P. , Bouafia K. , Khoueir Z. , Haouchine B. , Hammoud S. , Chapelle P. , Chambard J.P. , Jourot P. , Lachkar Y. , Benzacken L.
Published: September 2015

Purpose

Novel non‐contact, non‐invasive Vibration Tonometry using analysis of induced corneal vibrations and their correlation to GAT IOP was tested in a large multicenter clinical trial.

Methods

470 eyes in 236 volunteers from various ethnic origins at Paris area hospital eye clinic and Glaucoma Institute were studied. History, vibration tonometry measurements in triplicate GAT, NIDEK air puff IOP, refractometry, keratometry and non‐contact pachymetry. Algorithm discovery was performed by random draw splitting runs into a discovery sample and a separate validation sample performed 10 times separately in men and women

Results

In 236 patients, 34.6% of eyes had glaucoma, 51% of which women. 1311/1772 (76%) vibration tonometry measurements were in correct position. Population aged 20–92 yo with 48.7% females with mean of 62.1(± 13.5) in women and 62.5 (± 12.7) in men. CCT mean was 531.2 μ (± 37.3) in women and 534.8 μ (± 38.5) in men. 207 patients AL mean was 23.29 mm (± 1.68) in women and 23.73 mm (± 1.68) in men. GAT IOP ranged from 5.3 to 34 mm Hg, mean was 15.2 mm Hg (± 3.1) in women and 15.2 (± 3.52) in men ‐No significant differences. No adverse events during or post trial. Algorithm for women yielded 98.6% of IOP mean within 5 mm Hg of mean GAT IOP and 86% within 3 mm Hg. For men 96.4% of IOP mean was within 5 mm Hg of mean GAT IOP and 84.2% within 3 mm Hg from GAT IOP mean. Using the mean of 2 closest measures was used .

Conclusions

Current algorithm shows no influence of CCT on IOP. Gender Specific algorithm concurrs with previous publications of different corneal hysteresis (lower) in women. Vibration tonometry is a valuable method for measurement of IOP without contact with precision and reproducibility independently of CCT. It may be a valuable tool for IOP measurement in thin and surgical corneas.
Relapsing Polychondritis and its Orbital Manifestations
Authors: Teo L. , Choo C.T.
Published: September 2015

Purpose

We describe a 73 year old Chinese Gentleman with bilateral relapsing, remitting orbital inflammatory disease associated with Relapsing Polychondritis (RP).

Methods

We reviewed the current literature available on the diagnosis and management of orbital inflamamtory disease in RP.

Results

Our patient first presented with right orbital inflammation that did not improve despite antibiotic treatment. Computer tomography (CT) of the orbits showed a soft tissue mass along the roof of the orbit, which was biopsied, revealing acute on chronic inflammation. There was complete resolution of his orbital inflammation within 2 weeks of initiating systemic steroid treatment. He subsequently developed recurrent bouts of left orbital inflammation. One year later, he was diagnosed with relapsing polychondritis and subsequently developed multiple myeloma seven years later.

Conclusions

In summary, recurrent orbital inflammatory disease should prompt the Oculoplastics surgeon to exclude a systemic autoimmune disease and hematological malignancy. The course of orbital inflammation in RP can be relapsing and remitting. Co‐managementwith a rheumatologist will be helpful to achieve control of the disease with judicious use of immunosuppression. Long‐term follow‐up of the patient will be necessary to monitor for malignant transformation of the orbital lesion, as well as the development of hematologic malignancies.
Lack of correlation between calcium activity in perivascular cells and prostaglandin induced changes in the tone of porcine retinal arterioles in vitro
Authors: Kudryavtseva O. , Bek T.
Published: September 2015

Purpose

Recently, a population of perivascular cells (PVCs) was identified external to the vascular smooth muscle cells in retinal arterioles. However, it is unknown whether the pattern of Ca2+ activity in the PVCs can support the role of these cells in the regulation of tone in retinal arterioles. Therefore, the purpose of the present study was to identify whether Ca2+ activity in PVCs correlated with contraction of porcine retinal arterioles induced by prostaglandin F2a (PGF2a)and relaxation of these vessels induced by prostaglandin E2 (PGE2).

Methods

Porcine retinal arterioles were mounted in a confocal myograph and loaded with the Ca2+‐sensitive fluorophore Oregon Green. Ca2+ activity in the PVCs was studied after pre‐constriction with U46619 (10–6 M) followed by relaxation induced by PGE2 (10–5 M), or constriction induced by PGF2a (10–5 M). Arteriolar tone and fluorescence from PVCs were recorded in the absence and in the presence of the Ca2+ channel blockers (ryanodine, nifedipine, LOE908, CPA and 2‐APB).

Results

PGE2 induced significant relaxation and PGF2a significant contraction of retinal arterioles in vitro, but the PVC Ca2+ responses were similar during the two interventions. The percentage of active PVCs and the number of Ca2+ waves were significantly reduced by CPA and 2‐APB for both prostaglandins, while the tone responses were unaffected.

Conclusions

The effects of PGE2 and PGF2a on the tone of retinal arterioles involve other cell types than PVCs or is active downstream of the PVC pathway, e.g. by a direct effect on the vascular smooth muscle cells.
Proton beam irradiation of choroidal hemangiomas after unsuccessful photodynamic therapy
Authors: Zografos L. , Schalenbourg A.
Published: September 2015

Purpose

To study the outcome of patients treated for a choroidal hemangioma with proton beam irradiation following unsuccessful PDT and compare the therapeutic results with that of a control group that received proton therapy as a primary treatment.

Methods

Proton beam irradiation was applied to twelve cases of choroidal hemangioma that had been unsuccessfully treated with PDT (N of sessions: 1–5). Their functional results were compared to those of a control group of 48 cases treated only with proton therapy. The latter were matched (4 to 1) for the duration of symptoms before primary treatment, extent of retinal detachment as well as distance to the macula.

Results

The mean follow‐up following proton beam irradiation therapy was 28 months [range: 6 months‐5 years] in the PDT group and 41 months [range: 6 months‐10 years] in the control group. In all patients, the retinal detachment and macular edema disappeared following proton therapy. In the study group, final visual acuity was ≤0.1 in 25%, 0.2–0.5 in 25% and ≥0.6% in 50% of cases. Visual acuity improved in 50%, remained stable in 42% and decreased in 8% of cases. In the control group, final visual acuity was ≤0.1 in 4%, 0.2‐0.5 in 38% and ≥0.6 in 58% of cases. Visual acuity improved in 65%, remained stable in 29% and decreased in 6% of cases.

Conclusions

Proton beam irradiation is a valid therapeutic option after inconclusive results following PDT for choroidal hemangioma. Within the limits of this study, therapeutic results were slightly better for those patients that received proton therapy as a primary treatment.
Effects of optic's shape for contraction of anterior capsulorhexis
Authors: Mayumi N. , Hiroyuki M. , Tadashi S.
Published: September 2015

Purpose

Evaluation of capsulorhexis contraction in two different shapes of hydrophobic acrylic intraocular lenses (IOLs).

Methods

The study was conducted on 69 eyes that had undergone cataract surgery. FY‐60AD (HOYA) or ZCB00V (AMO) were randomly selected and implanted after phacoemulsification. The FY‐60AD has usual shapes of optics; however, the ZCB00V has rim at peripheral of optics. Anterior retro illumination images were photographed using slit lamp and EAS1000 (NIDEK) at 1 weeks, 1 month, 3 months and 6 months postoperatively. Capsulorhexis opening area were analyzed and the reduction ratios of capsulorhexis area were compared. After that, fibrosis in anterior capsule were also measured using area analysis software (Area Q, S‐Tech) after 3 months postoperatively.

Results

Reduction rate of capsulorhexis opening area were 5.44 ± 10.15% (FY‐60AD) and 0.25 ± 2.36 μ (ZCB00V) after 6 months postoperatively. There were statistically significance (P < 0.01). The area of fibrosis in anterior capsule were 62.24 ± 21.32% (FY‐60AD) and 16.90 ± 8.34% (ZCB00V). There were statistically significance, too (P < 0.01).

Conclusions

The ZCB00V prevent the contraction of capsulorhexis opening area. And the increase of fibrosis is also prevented at the same time. The shape of optics may be an important factor to prevent the contraction of capsulorhexis.
Treg‐based immunotherapy of non‐infectious uveitis (NIU)
Authors: Asnagli H. , Jacquin M. , Belmonte N. , Gertner‐Dardenne J. , Hubert M.F. , Sales A. , Foussat A.
Published: September 2015

Purpose

Col‐Treg is a T‐cell immunotherapy composed of autologous type‐1 regulatory T (Treg) cells specific for collagen‐II. Col‐Treg are tested in NIU mice as collagen‐II is present in the eye, allowing the triggering of their activity in situ. NIU is one of the most common cause of blindness in the developed world.

Methods

Col‐Treg cells are produced from blood of healthy volunteers or splenocytes of mice transgenic for collagen‐II‐specific TCR. Cells are characterized for marker expression using FACS and for in‐vitro immuno‐modulatory function. NIU model was induced by IRPB immunization. In‐vivo efficacy was evaluated with ophthalmoscopy histology, pro‐inflammatory cytokines analysis. In‐vivo tracking was performed using a Col‐Treg TCR specific quantitative PCR.

Results

Col‐Treg secrete IL10, IL13 and express GITR, CD39 and Granzyme B, molecules involved in the control of inflammation. Col‐Treg hydrolyse ATP, kill myeloid cells and inhibit T effector cell IL17 and IFNg secretion. Intravenous administration of Col‐Treg inhibited ocular inflammation in NUI mice with reduction of cellular infiltrates, IL1β, IL6, TNFα. In‐vivo‐tracking demonstrated a tropism of Col‐Treg for inflammatory eyes. In‐vivo GLP toxicity study in healthy mice did not revealed Col‐Treg related adverse events. Characterization of human Col‐Treg GMP batches demonstrated comparability with mouse Col‐Treg for marker expression and in vitro function.

Conclusions

These data demonstrate the safety and efficacy of Col‐Treg administration for the treatment of NIU in mice, suggesting that Col‐Treg could be used as a therapeutic tool for patients with non‐infectious uveitis refractory to approved medications.
3D model of pterygium and corneal limbus: Investigating histopathology and stem cell distribution
Authors: Blom N. , Andreasen A. , Heegaard S. , Hjortdal J. , Nielsen K.
Published: September 2015

Purpose

This study aims to create a complete histological 3D computer model of pterygium in situ, mapping the anatomy of the disease tissue, its relation to the corneal limbus and the distribution of limbal stem cells.

Methods

One human eye affected with pterygium was obtained from a cornea donor post mortem. The anterior part of the eye was cut into 900 consecutive horizontal sections. Every other section was stained with HE to be digitized, aligned and 3D reconstructed using interactive 3D visualization software. Immunohistochemistry targeting CK19, MMP‐1, p63 and VEGF was performed on the remaining sections alternating across the structure so as to create evenly distributed overlaying models.

Results

Using the sections a high‐resolution model of the pterygium and limbus was created, and in aligning the immunostained sections to the model, a spatial map of the staining was created.Analyzsing the model we found a mostly normal temporal limbus with intact architecture, however nasally the limbus was found to be buried under the pterygial mass and only partly intact, showing a number of pathological changes.

Conclusions

The limbal degeneration underneath the pterygium appears to be a precondition for or a consequence of the pterygial growth.
Bioluminescence – Biological Laser Phenomenon initiated by eye. Biophotonic tests
Authors: Manu M.D.
Published: September 2015

Purpose

The study of the characteristics of bio‐luminescence (BL) in eyes, optic nerves, brain, spinal cord, muscles, bones, phosphate, water.

Methods

Multidisciplinary studies, biophotonic and electronic tests performed at the International Institute of Biophysics Neuss, on biological samples Onchorynchus mykiss (rainbow trout), with photo‐multiplier PMS1 and PMS2. The samples optical axis is oriented parallel, obliquely, 90°C and 180°C angels to optical stimulus.

Results

BL transmission is present all biological systems studied; energy values are the maximum when the optical axis BL of the sample is parallel to the direction of the external stimuli; appear an optical amplification from the eye to the brain ‐bones and muscles, and two optical paths cross over the nervous system.

Conclusions

In your eyes, like in bifocal and confocal laser system, any color simultaneously reach from one pole to another. The sense of BL is from outside to inside daytime,and reverses direction nighttime.The presence of the laser active substance LAS (phosphate, water, liquid crystals) in cells, allows stimulation and the propagation of light, step by step, as thermodynamic cycles, but reduce the light speed. By overlapping the ocular optical axis over the object axis, begins conversion non‐coherent light into coherent light In the cornea, when on the surface of the cornea appears a geometric place of coherent points, that dispersed light in color components, rotary polarization and separation dextro, levo‐gyrate radiation.The BL amplification on the route of the nervous system is produced by interference (ventre) as digital optical pulses and by adding visible and caloric energy. BL energy is ultra‐weak but has large effects due to energy transformation of each stimulus, as four secondary effects: biochemical; electrical; magnetic; optic (holographic, laser heat).
Anatomic and functional follow‐up of foveal microstructures after macula‐off retinal detachment surgery
Authors: Deschasse C. , Kauffmann Y. , Frérot M. , Chiquet C. , Berrod J. , Le Mer Y. , Arndt C. , Tadayoni R. , Korobelnik J.F. , Weber M. , Gaucher D. , Delbosc B. , Bron A.M. , Creuzot C.
Published: September 2015

Purpose

To describe the course of functional and anatomical damage after successful repair of macula‐off rhegmatogenous retinal detachment (RRD).

Methods

This was a prospective multicenter study including patients with successful surgery for macula‐off RRD between October 2011 and April 2014. Patients with pre‐existing macular diseases or with surgery failures were excluded. Each patient underwent a complete ophthalmologic exam at baseline and at one, three and six months after the surgery (M1, M3, M6), with an assessment of the best‐corrected visual acuity (BCVA) at 4 m using the standard Early Treatment Diabetic Retinopathy Study chart, and with Spectral‐Domain Optical Coherence Tomography (SD‐OCT) macular imaging.

Results

One hundred and three eyes of 103 patients from ten French centers, with a 63‐years median age (IQR: [58; 69]), were included. The median BCVA increased significantly from 63 [46; 73] letters at M1 to 73 [62; 80]) at M6, p < 0.01). SD‐OCT morphologic lesions in the outer retina significantly improved between M1 and M6: irregular hyporeflectivity of the photoreceptor outer segments (76.7% vs 61.5%, p < 0.01) and disruption of the inner/outer segment junction line (51.5% vs 26.2%, p < 0.01). The rate of epiretinal membrane did not significantly increase between M1 and M6 (9.7% vs 20.4%, p < 0.67).

Conclusions

These preliminary results of the study “DécOllement de REtine: Fonction et Anatomie (DOREFA)” show a slow recovery of the external retinal layers after a successful RRD surgery. These observations seem to be parallel to the progressive recovery of the visual function after the intervention. A better knowledge of functional and anatomical kinetics after macula‐off RRD constitutes a preliminary step to the study of factors influencing the visual prognosis.
Prevalence of age‐related macular diseases in an old French population (the MONTRACHET Study)
Authors: De lazzer A. , Dossarps D. , Gabrielle P.H. , Pallot C. , Daniel S. , Binquet C. , Tzourio C. , Bron A.M. , Creuzot C.
Published: September 2015

Purpose

To describe the prevalence of age‐related macular diseases in a French population‐based study (the Montrachet study) older than 74 years.

Methods

The Three City study (3C) was a prospective study including 9294 patients aged of 65 years or more from three French cities (Dijon, Bordeaux, and Montpellier) at enrolment in 1999. After 10 years of follow‐up, an eye examination was proposed to participants of the 3C cohort in Dijon and 1153 participants were included in the so‐called Montrachet study. All patients underwent a complete eye examination including nonmydriatic color retinal photographs. The photographs were classified according to the type of abnormality (intermediate soft drusen, large soft distinct or indistinct drusen, reticular drusen or large area of soft drusen reaching 500 µm in diameter, hyperpigmentation or hypopigmentation), and their location (central or pericentral) using the classification of the Multi‐ethnic Study of Atherosclerosis (MESA) and that used in the Rotterdam Study. Patients were then classified into 3 categories: early age‐related macular degeneration (AMD), late AMD (atrophic or neovascular).

Results

Data were available for 1069 patients: 396 men (37.0%) and 673 women (63.0%). The mean age was 82.2 ± 3.8 years. The prevalence of healthy subjects was 56.0%. Stages 1, 2 and 3 accounted for 32.6%, 7.7% and 1.5%, respectively. The late AMD stages represented 2.2% (24 patients). Smoking was not significantly associated with AMD categories.

Conclusions

The prevalence of AMD grading in our population is consistent with the literature. The classification of participants according to different macular abnormalities may predict the populations at risk of developing an advanced grade and can help to adapt the management. The relationship with other risk factors will be the next step of this analysis.
A high oxygen demand in normal tension glaucoma
Authors: Turksever C. , Todorova M. , Orguel S.
Published: September 2015

Purpose

To evaluate relationship between vascular dysregulation and retinal oxygen demand in normal tension glaucoma (NTG).

Methods

Retinal vascular responses of 27 eyes of 18 Caucasian (10♀ :8♂) individuals with NTG were measured. Subjects were grouped based on their median vascular responsiveness. In each group, retinal vessel oxygen saturation was measured in arterioles (A‐SO2) and in venules (V‐SO2) within the peri‐papillary annulus with the oximetry tool of Retinal Vessel Analyser (IMEDOS Systems UG, Jena, Germany).Retinal nerve fiber layer thickness (RNFL) was measured with spectral domain optical coherence tomography (Carl Zeiss Meditec, Dublin, CA, USA) and visual field (VF) with Octopus perimeter (Haag‐Streit International, Switzerland). Retinal oxygen concentration per micron of nerve fiber layer thickness (O2‐C) was calculated as follows; the difference of aretrio‐venous oxygen saturation (A‐V SO2) was divided to the mean RNFL thickness. A linear mixed‐effects model was applied (IBM SPSS®)

Results

The eyes were grouped based on their vascular responsiveness (group1 ≤ 2.90%; n = 13, group 2 > 2.90%; n = 14). In group1 and in group2, mean A‐ SO2, V–SO2  and A‐V SO2 were 96.50%(±4.38); 97.77% (±3.03) (p=0.517), 62.89% (±6.23); 60.71% (±6.28) (p = 0.391), 34.64%(±4.51); 36.68% (±5.27) (p = 0.294), respectively. Subjects in group 1 showed higher O2‐C 0.488%/µ (±0.0848) than in group2 0.434%/µ (±0.0551) (p = 0.027). Mean age (65.45 y (±11.7)) and VF(dB) defect (4.7 dB (± 3.6), 3.4 dB (±5.2) were not statistically different between groups (p = 0 > 141). In group 1, RNFL thickness was significantly less than in group 2 (72.23 µm (±12.1); 85.31 µm (±13.67) (p=0.014).

Conclusions

Oxygen demand was increased in patients with excessive vascular dysregulation, while mean SO2 values were not related to age and/or flicker responses. This conclusion remains to be conformed in further studies.
Our experience with anti‐VEGF treatment on central serous retinopathy
Authors: Papavasileiou E. , Younis S.
Published: September 2015

Purpose

To evaluate the short‐term efficacy of intravitreal anti‐VEGF for the treatment of subretinal fluid (SRF) and/or pigment epithelium detachment (PED) secondary to chronic central serous chorioretinopathy (CSR).

Methods

Sixteen patients were treated with intravitreal injections of anti‐VEGF at 6‐ to 8‐week intervals until SRF and/or PED resolved. Main outcomes were Best‐Corrected Visual Acuity (BCVA), central retinal thickness (CRT) measured with optical coherence tomography (OCT), performed at 6‐ to 8‐week intervals and number of injections. Fluorescein angiography was performed at baseline visit and thereafter depending on clinical and OCT findings.

Results

Patients received 3.16 (range: 1–15) intravitreal injections of anti‐VEGF on average during a follow‐up of 22 +/‐ 2 weeks. Mean BCVA increased by 11.2 letters and mean CRT decreased significantly over follow‐up from 396.68 µm at baseline to 250.36 µm on last visit. 5 patients (31.25%) showed complete resolution of subretinal fluid and PED, 6 patients (37.5%) had persistent SRF and 5 patients (31.25%) had persistent PED.

Conclusions

Anatomic and functional improvement following intravitreal anti‐VEGF injections suggest that vascular endothelial growth factor (VEGF) may be involved in fluid leakage in patients with chronic CSR. The results suggest a possible role for anti‐VEGF agents in the treatment of chronic CSR.
Risk of trabeculectomy with an initial diagnosis of glaucoma versus ocular hypertension in Gloucestershire, UK
Authors: McNaught A. , Turner S. , Ivanova K. , Crabb D.
Published: September 2015

Purpose

Gloucestershire is a rural county in the UK, with a population of ~300,000 > 40 years. Importantly, almost all glaucoma and OHT patients attend the Gloucestershire Eye Unit, under the care of one of two glaucoma specialists. Those treated privately will also be treated by the same clinicians: any audit of all the clinical activity of both might reasonably be extrapolated across the whole county. We use this approach to estimate risk of trabeculectomy in patients with an initial diagnosis of glaucoma versus OHT.

Methods

An audit of the case notes of all trabeculectomies performed between 2010 and 2012 was undertaken. The initial clinical diagnosis at presentation was recorded e.g. whether POAG, NTG, ACG, secondary glaucoma or OHT, as was the initial untreated IOP/severity of visual field loss (MD). Time elapsed between initial diagnosis and eventual surgery was calculated.

Results

Considering only open‐angle glaucomas and OHT, there were 127 trabeculectomies in 119 patients over the two years of the audit. Secondary glaucomas (n = 14) were excluded. Annual risk of trabeculectomy in POAG was 2% per year based on an estimate of ~3000 glaucoma patients in the eye clinic. Median time from diagnosis to trabeculectomy: OHT (n = 4) 131 months, POAG (n = 93), 112 months, NTG (n = 14) 89 months, and PEX (n = 8) 55 months. Relative risk of trabeculectomy was 70 times higher in POAG compared with OHT, assuming prevalence of 2% POAG, 5% OHT in people >40 years (95% CI of RR 20‐290).

Conclusions

When compared with POAG, people with an initial diagnosis of OHT are 70 times less likely to need surgery. Patients with PXF had surgery much sooner than those with OHT. This audit provides prognostic predictions for glaucoma and OHT patients, and further, might suggest more resources be directed to patients with glaucoma, perhaps at the expense of patients with OHT.
Frequency‐Doubling Perimetry in Type2 Diabetes without Retinopathy
Authors: Aldaham S. , Martín‐Ridura M.D.C. , Pérez‐Carrasco M.J. , Palomo‐Álvarez C. , Carballo‐Álvarez J. , Puell M.
Published: September 2015

Purpose

Frequency Doubling Technology (FDT) perimetry has been utilized to detect visual field (VF) changes in type 1 diabetics with no retinopathy. However, it has not been tested in type 2 diabetes. The purpose was to assess FDT perimetry and its diagnostic capacity in type 2 diabetics without retinopathy.

Methods

This comparative cross‐sectional study included thirty‐one controls and nineteen age‐matched patients with type 2 diabetes without retinopathy, well controlled glucose level and onset duration >4 years. Full threshold C‐20 program was used for VF testing in the FDT perimeter. Mean sensitivities for each VF location, mean deviation (MD), pattern standard deviation (PSD), and test duration were compared. Area under the curve (AUC) of a Receiver Operating Characteristic (ROC) was calculated to assess the diagnostic value of the FDT perimetry.

Results

Mean sensitivities for some VF locations were significantly lower in the diabetic group. The mean MD was worse in diabetics (−3.35 ± 2.02 dB) than controls (−1.95 ± 1.70 dB) (p < 0.05). Neither the mean PSD nor the testing time was significantly different between the two groups. AUC values for MD and PSD were 0.29 and 0.69, respectively, (standard error = 0.076, p = 0.024).

Conclusions

FDT perimetry has a diagnostic capacity as a clinical tool for the detection of early retinal dysfunction in Type 2 diabetics before the onset of retinopathy.
Clinical cases (all)
Authors: Creuzot C.
Published: September 2015

Clinical cases to illustrate diseases related to degenerative myopia will be discusses with the audience. Diagnosis, outcome and treatment will be considered.
Cataract surgery in adult patients with uveitis
Authors: Bacquet J.L. , Fel A. , Butel N. , Remond A.L. , Le Hoang P. , Bodaghi B.
Published: September 2015

Purpose

To determine current challenges and visual results in patients with uveitis who underwent cataract surgery in 2013.

Methods

We retrospectively collected data from every consecutive uveitis patient who underwent cataract surgery during the year 2013 and studied demographic data (age, gender) along with uveitis etiology and therapeutic management. Pre and post operative anterior chamber flare was evaluated by laser flare photometry. Postoperative rate of macular edema (ME), ocular hypertension, epiretinal membrane (ERM) was also evaluated. Every patient was operated by the same surgeon (BB) and received a subconjunctival injection of dexamethasone at the end of the procedure. Use of perioperative oral prednisone was noted.

Results

Twenty eight eyes of 24 patients were operated. The mean age was 57.6, and 24 were female (85.6%). Preoperative mean best corrected visual acuity (BCVA) was 0.90 logMar. A week after surgery mean BCVA was improved to 0.26 logMar. A month later, mean BVCA was 0.26 logMar. BCVA was 0.38 logMar at 6 months and 0.27 logMar at one year. The mean preoperative flare value was 26.4 ph/ms. It increased to 42.8 ph/ms at one day and 35.0 ph/ms at one week. ME was noted postoperatively in 11 eyes (39%), of which 4 were preexistant. Four eyes (14.3%) had inflammatory glaucoma and ERM was noticed on OCT examination in 6 eyes (21.4%). Oral prednisone was used prior to surgery in 6 patients (25%) and after surgery in 10 patients (41.6%).

Conclusions

Cataract surgery in adult patients with uveitis has a satisfactory outcome in most of the cases. It is important to achieve a strict preoperative control of ocular inflammation. The incidence of complications such as macular edema, epiretinal membrane or glaucoma has been dramatically reduced by an appropriate management of the disease.
Angiotensin Receptor Blockade in Retinopathy of Prematurity: An Experimental Study
Authors: Nath M. , Kumar A. , Chandra P. , Singh B. , Deorari A.K. , Velpandian T.
Published: September 2015

Purpose

Retinal renin angiotensin (RRAS) system has been reported to play a vital role in the retinal angiogenesis pathway. Present study was conducted to evaluate the modulation of RRAS components by quantitative gene expression studies in retina and to evaluate the effect of angiotensin receptor1 (AT1) blockade in the oxygen induced retinopathy (OIR) experimental model.

Methods

Neonatal Wistar rat pups were exposed to high oxygen saturation (75% ±2%) chamber, from postnatal day (PD) 7th to postnatal day 12th. On PD 12th the pups were randomised into four groups (n = 9) viz. disease control (saline treated), AT1 receptor blocker (ARB) treated (telmisartan), antibody against VEGF (AAV) treated positive control (bevacizumab) and pups grew up in normoxia. On Day 17th Rat pup retina was assessed through fundus imaging and electroretinogram (ERG) by MICRON III. Rat pups were then sacrificed and retinas were extracted to study the gene expression of RAS components (renin, angiotensinogen, AT1 receptor & ACE), VEGF and HIF 1α in various test groups. Flat mounted ADPase stained retinas were subjected for light microscopy. Rat pups plasma, vitreous and retina were subjected for LC‐MS/MS.

Results

Examination of rat pup retina through fundus imaging, ADPase staining and ERG showed the reduction in tortousity index,vessel density of the retinal vasculature and improved “b” wave. Gene expression analysis revealed that treatment with ARB was able to normalise the expression of all the genes to a significant level except renin levels. ARB concentration in the retina was found to be therapeutically effective.

Conclusions

Present study shows Intervening in the over activated RRA system through angiotensin receptor 1 blockade was able to regulate this system in experimental model of ROP. Further studies are in progress to understand the RRAS mechanisms involved in ROP.
Evaluation of a cyclosporine A ophthalmic ointment in an experimental mouse model of dry eye
Authors: Cimbolini N. , Antonelli S. , Mauro V. , feraille L. , Elena P.P.
Published: September 2015

Purpose

Dry eye syndrome is a common disease with multifactorial causes. Symptoms typically include irritation, dryness, burning and decreased or fluctuating vision. Anti‐inflammatory drugs are widely used for the treatment of the inflammation produced by the disease with corticoid or cyclosporine A (CsA). Restasis® (Allergan), a CsA emulsion, was approved by the FDA but is not available in Europe. Here we propose to show the action of Optimmune® (MSD Animal Health) a marketed veterinary ophthalmic ointment that contains CsA in an experimental mouse model of dry eye induced by scopolamine, a tropane alkaloid drug with muscarinic antagonist effects.

Methods

Animals were divided in three groups of ten pigmented mice: Two groups were exposed to desiccating conditions (relative humidity <25%, air‐flow 15 L/min, temperature 20‐22°C) with transdermal scopolamine administration (0.5 mg/72 h) for 14 days. Animals were treated topically three times a day with 0.2% CsA ointment or vehicle. Controls were saline‐treated animals placed in a normal environment. Tear production was measured with the phenol red thread test, corneal defects were examined by slit‐lamp observation using blue light after 0.5% fluorescein eye drop. These examinations were performed in both eyes before exposure and on days 3, 7 and 14. A histological study was performed at the end of the study.

Results

Cyclosporine A eye ointment appeared to show efficacy in this model.

Conclusions

Cyclosporine A eye ointment significantly reduced clinical signs of dry eye by decreasing corneal defect more than cyclosporine A ophthalmic emulsion (internal studies).
Switching to ranibizumab for diabetic macular edema with persistent fluid on bevacizumab: Who is likely to benefit from the switch?
Authors: Lee J.H. , Lee W.K.
Published: September 2015

Purpose

To evaluate the efficacy of switching from bevacizumab to ranibizumab in patients with diabetic macular edema (DME).

Methods

The medical records of 41 DME eyes which showed persistent fluid after at least three monthly bevacizumab injections, and switched to ranibizumab injection were reviewed. Each patient received a single ranibizumab injection and followed up at 1 month. Anatomic responders to ranibizumab were followed up monthly and given ranibizumab injections on an as‐needed basis until 3 months.

Results

At 1 month, the mean central foveal thickness (CFT) decreased from 431 μm to 349 μm (P < .001), and mean best‐corrected visual acuity (BCVA) improved from 20/53 to 20/48 (P = .062). Twenty‐six eyes (65.9%) were classified as anatomical responders, and the mean CFT improved and maintained until 3 months (439 μm to 320 μm, P < .001) after repeated injections (mean number: 2.8), while the mean BCVA stabilized (20/59 to 20/54, P = .075) in these eyes. Dry macula were achieved in 9 of 26 eyes at least once during the follow‐up period. Favorable anatomic response to ranibizumab at month 1 was related with previous partial response to bevacizumab.

Conclusions

Switching to ranibizumab may present an alternative option in the treatment of DME with persistent fluid after repeated bevacizumab injections, and the switch was more effective in eyes that showed partial response to previous bevacizumab.
Ocular fundus changes in patients with Down syndrome and pulmonary hypertension
Authors: Leys A. , Delcroix M. , Willems A. , Wirix M. , Nijs I.
Published: September 2015

Purpose

The ocular and visual problems in Down syndrome are due to refractive errors, poor accomodation, strabismus, keratoconus, cataract, optic disc and retinal structural anomalies and brain changes. Pulmonary hypertension (PH) is associated with high mortality and morbidity and ocular complications may occur. PH associated central serous choroidopathy‐like maculopathy, venous thrombosis and neovascular glaucoma have been described in case reports but no large studies of ocular complications are available. Improved non‐invasive imaging with optical coherence tomography (OCT), enhanced depth OCT and OCT angiography without dye allow a detailed study of the retinal and optic disc changes.

Methods

A cross sectional study of 180 adult patients with PH included 9 Down patients with congenital heart disease. Age of the Down patients was 25–44 years. The fundus changes included PH associated and Down associated anomalies.

Results

PH associated mild changes included episcleral and retinal vein dilation and a thick choroid. None of the Down patients had severe complications of PH. The Down associated fundus changes included absence of optic disc cup, supranumerary optic cisc vessels,and structura lmacular anomalies with small capillary free zone. Two eyes were functionally lost due to complications of hydrops keratoconus.

Conclusions

Non‐invasive imaging with OCT allows a detailed analysis of fundus changes in Down patients with or without PH.
Clinical experience with Idebenone (Raxone®) in the treatment of patients with Leber's Hereditary Optic Neuropathy (LHON)
Authors: Metz G. , Klopstock T. , Gallenmüller C. , Catarino C. , von Livonius B. , Lob F. , Meier T.
Published: September 2015

Purpose

LHON is an orphan mitochondrial disorder affecting the retinal ganglion cells leading to permanent blindness from which recovery is rare. An increasing body of evidence indicates that idebenone has therapeutic potential for the treatment of LHON. Data from a randomized placebo‐controlled study (RHODOS), from a number of case reports and retrospective cohort studies demonstrate that patients with established vision loss may benefit from idebenone treatment and recover visual acuity (VA).

This study reports VA outcomes for patients with recent onset of vision loss who received idebenone treatment under an ongoing global Expanded Access Program (EAP) where currently 82 patients are enrolled and have been treated for an average of 15 months. The outcomes will be compared with findings of the RHODOS study and a Case Record Survey collecting VA data from untreated patients.

Methods

Analyses are performed to assess recovery from the VA nadir. Clinically relevant recovery was defined as (i) improvement from nadir by at least 10 letters on the ETDRS chart or (ii) improvement from “off‐chart” at nadir to being able to read at least 5 letters on‐chart. Furthermore, the prevention of vision loss for patients with residual vision below 1.0 logMAR (20/200) at start of therapy was analysed.

Results

A high proportion of patients (about 50% at submission of the abstract) treated with idebenone under this global EAP experienced a clinically meaningful recovery of vision. In addition, in patients with residual vision below 1.0 logMAR at start of therapy, loss of VA to above this level could be prevented in a large number of patients (about 60% at submission of the abstract).

Conclusions

The therapeutic potential of idebenone in the treatment of LHON is further demonstrated by the clinical experience in a large cohort of patients under a global EAP.
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 less than 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.
SRPK1 inhibitors as novel anti‐angiogenic therapeutics for wet age‐related macular degeneration (wAMD)
Authors: Batson J. , Toop H. , Rowlinson J. , Allen C. , Gibbons B. , Zhang J. , Wearmouth S. , Knapp S. , Morris J. , Bates D.
Published: September 2015

Purpose

Anti‐angiogenic VEGF inhibitors are the standard of care for wAMD but must be administered by intraocular injection and non‐specifically inhibit all VEGF isoforms. We aim to develop SRPK1 inhibitors as eye drops that specifically inhibit pro‐angiogenic VEGF‐A isoform‐driven angiogenesis underlying wAMD.

Methods

Novel compounds, synthesized based on the structure of SRPK1, were tested in kinase assays, thermal shift binding assays and immunoprecipitation, immunoblotting and immunofluorescent assays. Retinal toxicity and efficacy were evaluated by Ganzfeld ERG and laser‐CNV. PK was evaluated in vivo and in ex vivo penetration assays using mass spectrometry.

Results

Novel compounds selectively bind to SRPK1 and dose‐dependently inhibit SRPK1 kinase activity (IC50s<10 nM), SRSF1 phosphorylation and nuclear localization and increase anti‐angiogenic VEGF‐A165b levels. SRPK1 inhibitors did not inhibit retinal function yet potently inhibited laser‐CNV following eye drop administration in mice (EC50s<0.5 µM, n = 6‐8, P < 0.05, One‐way ANOVA). Compounds were detected in the sclera, choroid and retina following eye drop administration in vivo in rat and mouse and in ex vivo penetration assays in human, pig and rabbit eyes.

Conclusions

We developed SRPK1 inhibitors that specifically target pro‐angiogenic VEGF‐A‐driven choroidal neovascularization and can be delivered to the retina following eye drop administration. These compounds potentially offer more specific, efficacious and safer therapeutics for patients with wAMD.
Late ocular changes after closantel (Flukiver) poisoning
Authors: Asoklis R. , Augyte A. , Cimbalas A.
Published: September 2015

Purpose

To describe late ocular changes in 5 women after harmful use of donated closantel (Flukiver).

Methods

The study included 5 women from the report published by Hoen and Hodgkin in The Lancet journal in 1993 about 11 cases of donated veterinary drug closantel use in Lithuania. We analysed medical records from 1993 to 2015 and performed eye examination of 5 suffered patients 22 years after the event.The study was conducted at the Centre of Eye Diseases,Vilnius University Hospital Santariškių Klinikos,it adhered to the tenets of the Declaration of Helsinki.Eye examination included best corrected visual acuity (BCVA), perimetry, colour vision(CV), tonometry, slit lamp evaluation, fundus photography and optical coherent tomography.

Results

In 2015 the mean age of the patients was 49.4 years In 1993 BCVA varied from 0.08 to 1.0.Right eye (RE)in average‐ 0.66, left eye(LE) – 0.68. In 2015 BCVA varied from 0.1 to 1.0.RE in average – 0.7 and LE – 0.6.22 years after the event average visual field defect in the right eye was 24.13 dB and in the left eye ‐ 23.85 dB.CV Ishihara test showed decreased green color perception in 3 patients and 2 were not able to perform it, because of the visual field defects.The average central macular thickness 216.0 ± 36.1 µm in RE and 196.0 ± 42.0 µm in LE, retinal nerve fiber layer respectively 86.0 ± 11.0 µm and 93.2 ± 5.4 µm. Ophthalmoscopy showed atrophy of the optic nerve and changes of the retina reminding those in retinitis pigmentosa.

Conclusions

Closantel is veterinary drug causing decades lasting damage of the optic nerve and retina in humans. Visual functions don't correlate with central macular and retinal fiber layer thickness.Fundus photography and perimetry reveal changes similar to retinitis pigmentosa. To our knowledge this is the first report about the late outcomes of closantel toxicity in humans.
A Fresh Look at Tear Film Structure and Dynamics
Authors: Bron A.J. , Yokoi N. , Georgiev G.
Published: September 2015

Purpose

To determine the structure of the precorneal tear film from its behaviour during blinking and eye movements.

Methods

The tear film lipid layer (TFLL) and the fluorescein‐stained mucoaqueous subphase (MAS) were studied during spontaneous blinking and after vertical or horizontal saccades, using the DR‐1TM video‐interferometer and video‐biomicroscope, respectively.

Results

During horizontal saccades, the TFLL and MAS behave as a ‘fluid shell’, that moves with the cornea (Yokoi et al. Ocul Surf 2014). This cohesion is lost during blinking. In the downstroke, the TFLL is stripped from the MAS and compressed. In the upstroke it spreads, driven by a surface tension gradient, dragging with it the newly deposited MAS. As these layers spread, they are transiently dissociated and also, the MAS is dissociated from the glycocalyx. Cohesion is restored as the tear film stabilises before the next blink. When the tear film forms in the upstroke of the blink, the menisci draw fluid from the tear film until they are separated by a zone of meniscus‐induced thinning (MIT) – the “black line” seen in the fluorescein‐stained tear film. During pauses at the end of any saccade, this MIT is imprinted onto the MAS and made visible in the fluorescein‐stained tear film as dark arcs on return from horizontal saccades, and dark bands after vertical saccades. Their persistence in the blink interval, implies that the MAS has viscous, gel‐like properties.

Conclusions

Just prior to each blink there is cohesion between the tear film and glycocalyx and between each layer of the tear film. Cohesion is broken transiently by blinking. Most of the water intervening between the gel‐like MAS and TFLL is drawn off into the menisci at the time of tear film formation.