bluuebunny/crossref_metadata_2025 huggingface dataset:
In vivo modified peripheral glia enhance regenerative capacity in a rat retina
Authors: Smedowski A. , Pietrucha‐Dutczak M. , Kaarniranta K. , Lewin‐Kowalik J.
Published: September 2015

Purpose

To investigate impact of transplanted peripheral glia on neurites outgrowth and synaptogenesis in adult rat retina associated with ongoing optic neuropathy.

Methods

In this study we used two models of retinal neurodegeneration – degeneration of denervation represented by retinal explants culture and glaucomatous degeneration represented by rat model of ocular hypertension. Retinal explants were cultured in standard supplemented Neurobasal A medium (n = 48). Ocular hypertension has been induced using beads occlusive model (n = 10). In both ex vivo and in vivo approaches we applied transplantation of peripheral glia, prepared as previously described (Marcol et al. 2015), of density 104/5 µl for ex vivo and 106/5 µl for in vivo. PBS treatment was used as a control. After proper follow‐up time (10 days for retinal explants and 6 weeks for glaucoma model), tissue was fixed and processed for immunostaining (GAP43, synaptophysin, mGlu2/3R) and stereological analyses.

Results

There were visible differences in GAP43, synaptophysin and mGlu2/3R staining between experimental groups. Treatment with peripheral glia increased expression of above proteins both ex vivo and in vivo. Synaptic proteins expression was increased in glial cells treated glaucomatous retinas with mostly within inner plexiform layer, however punctate staining appeared also in ganglion cells layer and retinal nerve fiber layer that might be associated with synaptic plasticity induced by our treatment. Retinal explants analyzed in stereology revealed significant differences expressed in parameters of neurites outgrowth (U‐Mann Whitney test, p < 0.05).

Conclusions

Transplantation of in vivo modified peripheral glia support regeneration and might have impact on synaptogenesis and synaptic plasticity within inner rat retina.
Human choroidal nevi histopathology revisited
Authors: Madigan M.c. , Vader M. , Ton H. , Van der Velden P. , Jager M.J.
Published: September 2015

Purpose

Choroidal nevi are relatively common lesions seen in normally asymptomatic eyes. They show low potential for progression to melanoma but may produce visual effects depending on location. We investigated vasculature and macrophages in pigmented choroidal nevi using histopathology and immunohistochemistry.

Methods

340 fixed post mortem adult human eyes with no history of choroidal melanoma were examined. Paraffin sections of eyes were subsequently cut, stained with hematoxylin & eosin or Periodic acid Schiff reagent and histopathology examined. We assessed localisation and distribution of macrophages immunolabelled with CD163 or CD68 antibodies.

Results

Thirteen eyes (aged 54–90 years) with 16 pigmented lesions were found. Of these, 15/16 lesions occurred within the posterior pole region. H&E and PAS staining confirmed pigmented choroidal nevi, with a diameter of 1.5–6.8 mm, and thickness <1.5 mm. Lesions were located at varying depths within the choroid, comprised of densely pigmented nevi cells, and with a predominantly oval or dome shape (15/16). Overlying drusen were observed for 8/16 nevi. Large choroidal vessels bordered 11/16 nevi, and normal vessels were seen within nevi, however no microvascular patterns typically associated with melanoma were observed. Larger nevi located just beneath Bruch's membrane were more often associated with choriocapillaris (CC) thinning and RPE disruption. Nevus cells were seen within the CC pillars, abutting Bruch's membrane. Compared to surrounding choroid, numerous CD163+ and CD68+ macrophages (CD163+ >CD68+) were localised within and around nevi, often associated with vessels.

Conclusions

These findings indicate that choroidal nevi can affect normal choroidal vessels including CC integrity. Nevi also share some histopathological characteristics with melanoma, including infiltrating macrophages.
Assessment of the size spectrum of epithelial lesions of punctuate superficial keratitis during dry eye
Authors: Courrier E. , Lepinet T. , Hor G. , He Z. , Chikh M. , Thuret G. , Gain P.
Published: September 2015

Purpose

Quantification of staining of the ocular surface by fluorescein and lissamine green is important for diagnosis and follow up of dry eye syndromes, especially in clinical trials. Analysis of digital pictures may help improving the reliability of this quantification but require objective data on the basic lesions constitutive of punctuate superficial keratitis (PSK) to develop adequate algorithms. Aim: to evaluate the size spectrum of epithelial lesions of PSK during dry eye to improve the existing diagnosis tools.

Methods

Fluorescein was instilled to six patients suffering from dry eye graded according to the Oxford scheme. Pictures (3008x1960px) were taken using a Topcon slit‐lamp using the Cobalt blue light without barrier filter. Two magnifications (x10 and x16) were used and calibrated using a certified standard reference grating. It allowed determining the size of observed objects with the software ImageJ. The most visible and isolated PSK lesions (green dots) were selected. The size of 180 different PSK lesions (30/patient, 15/magnification) were measured by tracing the light intensity profile and manually measuring the width at half maximum.

Results

All patients combined, the mean was 21.6 ± 4.8 μm (15.2‐30 μm, 10°‐90° percentile). Lesion diameters ranged between 11.4 and 30.4 μm.

Conclusions

Lesions seem to be smaller than epithelial cells (approximatively 25 μm×50 μm for superficial cells) and might correspond to the beginning of cell detachment with fluorescein retained between cells. These new quantitative data will help developing automatic recognition algorithm to obtain reliable objective classification of the corneal staining.
The inhibitory effect of Itraconazole on Corneal neovascularization in Rabbits
Authors: Won J.Y. , Chung S.K.
Published: September 2015

Purpose

To evaluate the inhibitory effect of itraconazole on corneal neovascularization in rabbits.

Methods

Corneal neovascularization was induced in 36 eyes of 18 rabbits by suture placement in the corneal stroma. Seven days after suture placement, all rabbits were randomly divided into 4 groups and were treated four times daily with balanced salt solution (Group 1, 4 rabbits), topical 0.5% itraconazole (5 mg/mL, Group 2, 4 rabbits), topical 1% itraconazole (10 mg/mL, Group 3, 6 rabbits), and topical 2% itraconazole (20 mg/mL, Group 4, 4 rabbits). After one week, the surface area of corneal neovascularization was assessed on the digital photographs. In the corneal specimens, the concentration of VEGF A (vascular endothelial growth factor), VEGF R2, and PLGF (placental growth factor) mRNAs was measured by RT‐PCR, and the concentration of ERK, p‐ERK, Flk, and p‐Flk was measured by Western Blotting.

Results

The surface area of induced corneal neovascularization was significantly smaller in Groups 2, 3, and 4 compared to the control group on day 14 (p < 0.05). RT‐PCR analysis showed that the mean concentration of VEGF and PLGF in Groups 2, 3, and 4 was significantly lower than that in the control group after 7 days of treatment. Western Blotting analysis showed that the mean concentration of p‐ERK, Flk, and p‐Flk in Group 3 was significantly lower than that in the control group after 7 days of treatment.

Conclusions

Topical itraconazole application was useful for effective inhibition of experimental corneal neovascularization.
Anatomic features of choroidal naevi: Swept‐source optical coherence tomography vs Enhanced depth imaging tomography. Preliminary results in 31 patients
Authors: Papastefanou V. , Vázquez‐Alfageme C. , Xirou T. , Degli‐Esposti S. , Patel P. , Sagoo M.S.
Published: September 2015

Purpose

To assess the anatomic retinal and choroidal features of choroidal naevi using swept‐source optical coherence tomography (SS‐OCT) and enhanced‐depth optical coherence tomography (EDI‐OCT).

DESIGN

Observational case series.

Methods

Patients with choroidal lesions underwent clinical examination, B‐scan ultrasound and imaging with SS‐OCT and EDI‐OCT. Location, dimensions, clinical and OCT retinal and choroidal features were recorded. Descriptive statistics were used.

Results

Case series included 31 patients. 27/31 naevi imaged were melanotic and 4/31 amelanotic with a an overall median thickness of 0.7 mm. Naevus configuration was plateau in 17/31 cases, dome in 10/31 cases and mixed in 4/31 cases. RPE and photoreceptor layer disruption were noted in 14/31 cases and 13/31 had no retinal changes. Subretinal fluid was noted in 6/31 cases. Bruch`s membrane was found intact in 26/31 cases on both modalities. Intrinsic hyperreflectivity was noted in 29/31 cases on EDI‐OCT and 30/31 cases on SS‐OCT with less optical shadowing. The posterior margin of the naevus was visualized in 11/31 cases with SS‐OCT and in 6/31 cases with EDI‐OCT. Intratumour vessels were visualized in 28/31 cases with SS‐OCT and 23/31 cases with EDI‐OCT. For both modalities choriocapillaris appeared compressed and abnormal in 20/31 cases.

Conclusions

These preliminary results indicate that imaging of choroidal naevi with SS‐OCT enables better visualization of intratumour vessels and the posterior margin.
Comparability and reproducibility of four wavefront aberrometers for measuring lower and higher order aberrations in pseudophakic eyes
Authors: Nguyen P.M. , Hirnschall N. , Doeller B. , Schuschitz S. , Varsits R. , Findl O.
Published: September 2015

Purpose

To compare measurements of lower and higher order aberrations (HOA) obtained with four different wavefront aberrometers and to assess their reproducibility.

Methods

This prospective study included pseudophakic otherwise healthy patients. Four wavefront aberrometers were compared. Three of the aberrometers in this study are combined with coneal topographers. Two of the devices use a Hartmann‐Shack sensor (WASCA, Carl Zeiss Meditec AG; iDesign Advanced WaveSan aberrometer, Abbott Medical Optics), one device works on the basis of ray tracing (iTrace, Tracey Technologies), one device utilizes automated retinoscopy (OPD‐ScanIII; NIDEK Co. Ltd.). All patients are measured with an autorefractometer (Topcon, Japan) and also a subjective refraction has been performed. In addition a Purkinjemeter measurement has been done.

Results

In total, 51 eyes of 51 patients were included. No patient was lost to follow‐up. Mean difference concerning root mean square of all higher order aberrations was 0.013 µm between Wasca and iDesign and 0.113 µm between Wasca and OPD, respectively. Reproducibility was found to be between 0.09 µm (SD:0.06) (iDesign) and 0.41 µm (SD: 0.12) (iTrace). Details for higher order aberrations will be presented at the meeting.

Conclusions

Feasibility was found to be excellent for Wasca and iDesign and was high for iTrace but for the OPD Scan there was a flat learning curve. Reproducibility was found to be good for all devices but slightly weaker for the iTrace device.
Assessment of interlinked double staircase acuity test
Authors: Giulvezan S. , Gallagher K. , Davies N.
Published: September 2015

Purpose

To compare a novel visual acuity threshold algorithm using a predictive double staircase method with standard ETDRS logMAR chart.

Methods

Software was written in MATLAB to generate a computerised visual acuity test. The algorithm uses a randomly presented double staircase method, the staircases are interlinked using a prediction of threshold based on each prior response. This reduces test duration and increases accuracy. The screen was calibrated using a Vernier scale and there solution of the test was 0.02 log units. Ten threshold measurements were made for each test, the results expressed as the mean and standard deviation. The test was performed by three observers each with an induced range of refractive errors and compared with the result ofETDRS logMAR acuity using a chart generated with the same screen calibration.

Results

Mean stair cased acuities were −0.13, 0.02, 0.22, 0.36, 0.56 log unitsfor 0, 0.5, 1, 1.5 and 2 dioptres of defocus respectively. The mean single letter score logMAR acuities were −0.08, 0.01, 0.17, 0.38, 0.58 log units. The mean error in the stair cased test was 0.02 (SD 0.01) log units forall defocus values. The mean difference between the two tests was −0.01 log units (SD 0.09). Bland‐Altmann plots showed no systematic difference. The mean time to perform the staircased test was 93 seconds (SD 19s).

Conclusions

The interlinked double staircase method gives a fast and accurate assessment of visual acuity which compares well with ETDRS logMAR.Ten threshold measures allow error estimation which is not available in a logMAR test. Other advantages over logMAR include a true resolution of 0.02 log units rather than interpolation and random letter generation with no memory effect.
Quantification of total retinal blood flow via dual‐beam bidirectional Doppler optical coherence tomography for the assessment of neurovascular coupling
Authors: Aschinger G. , Werkmeister R. , Garhöfer G. , Schmetterer L.
Published: September 2015

Purpose

In recent years, the reliability of dual‐beam Doppler optical coherence tomography (DOCT), a method for measuring absolute retinal blood flow velocities, has been proven. A simultaneous determination of retinal vessel diameters allows calculating total retinal blood flow. The combined measurement of both parameters also offers the ability to quantify perfusion of the retina under different stimuli conditions and by this getting insight into the mechanisms of neurovascular coupling.

Methods

Total retinal blood flow was measured in four healthy subjects at baseline condition (constant illumination of the fundus) and 20 min after this during stimulation with diffuse luminance flicker light at 12 Hz.

Results

The average increase in total retinal blood flow during flicker stimulation was about 40%, which is assumed to be caused by an increased firing rate of the retinal ganglion cells. However, when comparing the blood flow in single retinal vessels under both baseline condition and flicker stimulus, the individual increase varied vastly.

Conclusions

We think the observed phenomena are caused by resistance changes of the vasodilated vascular network which cause non‐linear flow changes in single vessels. Our results show that the measurement of a single retinal vessel alone is not adequate for assessing neurovascular coupling in the retina. To conclude, for gaining insight into the mechanisms and functioning of neurovascular coupling, total retinal blood flow must be assessed.
Corneal lenticules as an ex‐vivo model to study keratocyte biology
Authors: Shroff R. , Shetty R. , Kumar D. , Ghosh A. , Kumar S. , Pahuja N. , Ghosh A.
Published: September 2015

Purpose

Keratocytes show differential gene expression in culture media; and are extensively used to study wound healing, corneal disease biology and response to topical drugs. However, mono‐layer culture cannot replicate the 3‐dimensional biological environment of corneal stroma. Hence, we propose to establish corneal lenticule as an ex‐vivo model to study keratocyte biology for corneal diseases, drug response studies and in wound healing experiments.

Methods

SMILE surgery was performed using the VisuMax femtosecond laser system (Carl Zeiss Meditec AG, Jena, Germany). After the refractive lenticule of intra‐stromal corneal tissue was created using the femtosecond cutting procedure, it was dissected and separated through the side‐cut opening and removed manually. SMILE lenticules from patients were obtained in MK media and were transferred to DMEM F12 with 10% FBS and 1% PSA. The media was replenished every 24 h and lenticules were harvested at 0 h, 24 h, 48 h, 78 h and 96 h. Gene Expression analysis was performed for pro‐fibrotic genes (fibronectin, ɑ‐sma, vimentin, TGF‐β and TGF‐βR2), pro‐inflammatory (IL‐6 and TNF‐ɑ) and structural genes (Col1‐A1, Col4‐A1and Col5‐A1).

Results

Our results demonstrate that lenticules remain metabolically active in culture media for long periods of time as evident from the varying expression of different pro‐fibrotic, pro‐inflammatory and structural genes after 0 h, 24 h, 48 h, 78 h and 96 h of culture. Furthermore, linear regression analyses show that clinical parameters like lenticule thickness do not affect the expression profile of the various genes by the keratocytes contained in the lenticule.

Conclusions

In conclusion, lenticule can be used as an ex‐vivo model to study keratocyte biology in various corneal diseases and for drug testing.
Visual Acuity (VA) Outcomes and Impact of Baseline (BL) Perfusion Status in VIBRANT
Authors: Feltgen N. , Asmus F.
Published: September 2015

Purpose

Report additional VA outcomes from VIBRANT.

Methods

VIBRANT was a phase 3 study of intravitreal aflibercept (IVT‐AFL) vs laser for macular edema (ME) due to branch retinal vein occlusion (BRVO). Patients received IVT‐AFL 2 mg every 4 weeks to week 24 (W24) and every 8 weeks thereafter or macular grid laser at BL. Eligible laser patients received IVT‐AFL rescue beginning at W24. Primary endpoint was the proportion of eyes gaining ≥15 letters in best corrected VA (BCVA) at W24. Retina was considered perfused for patients with ≤10 disc areas of capillary nonperfusion at baseline.

Results

The proportion of eyes gaining ≥15 letters from BL to W24 and W52 was 52.7% vs 26.7% (P < 0.001) and 57.1% vs 41.1% (P < 0.03), for IVT‐AFL vs laser; 36.3% and 49.5% of eyes receiving IVT‐AFL gained ≥15 letters by W4 and W12. Overall mean BCVA gain from BL to W24 and W52 was 17.0 vs 6.9 letters (P < 0.0001) and 17.1 vs 12.2 letters (P < 0.004), for IVT‐AFL vs laser. W52 results for laser group include patients who received IVT‐AFL rescue. In the laser group, 80.7% received rescue IVT‐AFL between W24 and W48. In perfused patients, mean BCVA gain from BL to W24 and W52 was 14.3 vs 5.7 and 13.7 vs 11.9 letters; in nonperfused patients, it was 19.1 vs 11.3 and 20.0 vs 15.6 letters. The most common ocular AE, conjunctival hemorrhage, occurred in 24.2% (IVT‐AFL) and 15.2% (laser) of patients. Two APTC‐ATEs occurred, both in the laser group.

Conclusions

Here, IVT‐AFL provided statistically and clinically significant VA benefits over laser at W24 that were maintained at W52. Benefits with AFL treatment were not dependent on baseline perfusion status.
SQSTM1/p62 depletion leads to the Rab7 accumulation and inflammatory response in ARPE‐19 cells
Authors: Piippo N. , Hyttinen J. , Hytti M. , Korhonen E. , Kaarniranta K. , Kauppinen A.
Published: September 2015

Purpose

SQSTM1/p62 is a central player in the selective autophagy directing ubiquitinated protein aggregates, mitochondria, and bacterial pathogens to autophagosomes. Autophagy culminates into the fusion of matured autophagosomes with lysosomes that contain degradative enzymes. One regulator of the fusion is Rab7, which also has a role in the movement of autophagosomes along microtubules. In this study, we have investigated the significance of SQSTM1/p62 in the functionality of human retinal pigment epithelial (RPE) cells and its possible role in the regulation of Rab7.

Methods

SQSTM1/p62 was blocked in ARPE‐19 cells using spesific siRNA. Proteasomes were inhibited with MG‐132, which has been shown to induce autophagy flux by providing more substrate to the autophagic machinery. Additionally, AMPK‐activator AICAR (5‐aminoimidazole‐4‐carboxamide ribonucleotide) was used to induce autophagy. Rab7 protein levels were determined with western blot and the secretion of inflammatory cytokines using the ELISA method.

Results

According to our results, interference of autophagy by SQSTM1/p62 depletion, especially in the presence of other stimuli, such as MG‐132 or AICAR, leads to the accumulation of Rab7. Along with higher amounts of Rab7, increased inflammatory response was observed.

Conclusions

Our results emphasize the importance of SQSTM1/p62 in the regulation of autophagy and inflammation in RPE cells that play the principal role in the pathogenesis of age‐related macular degeneration (AMD).
Uveal melanoma and renal cell carcinoma both metastatic to the liver
Authors: Turunen J. , Markkinen S. , Wilska R. , Kivelä T.
Published: September 2015

Purpose

Germline mutations in the BRCA1‐associated protein‐1 gene (BAP1) predispose carriers to several types of cancer, including uveal and cutaneous melanoma, mesothelioma, renal cell cancer, and possibly other diverse tumor types. Approximately 2% of consecutive Finnish uveal melanoma patients harbor a germline mutation in BAP1.

Methods

Case report.

Results

A 53‐year‐old man was diagnosed with renal cancer in 2006. No metastasis was detected during a 5‐year follow‐up after surgery. In 2011, he noted decreased vision in his left eye. Ophthalmological examination revealed a suspicious choroidal mass and the patient was referred to the ocular Oncology service, Helsinki University Eye Clinic. A choroidal melanoma with a largest basal dimension of 15.5 mm and thickness of 11.1 mm and no metastases was detected (T3aN0M0, stage IIB). He received brachytherapy with an iodine plaque. Three years later he had liver metastases, and biopsies indicated the presence of both uveal melanoma and renal carcinoma metastases. Further, a sister of his father also has had uveal melanoma. Given that the patient was a candidate to harbor a germline BAP1 mutation we sequenced the gene. No mutation was found in the coding regions or adjacent intronic sequences. Further, we carried out whole exome sequencing, and no mutations or mosaicism were found in BAP1, BRCA1, SF3B1, or EIF1AX.

Conclusions

Not all familial uveal melanoma patients even with history of renal cell cancer harbor an obvious BAP1 germline mutation. Currently, we are analyzing histological samples to further investigate the possible role of BAP1 in tumor tissue and genetic data to find or exclude indirect effect on BAP1 function.
Increased Uptake of Intracameral Antibiotic Prophylaxis in Europe
Authors: Barry P.
Published: September 2015

Purpose

To determine the use of intracameral cefuroxime at the end of cataract surgery across Europe since the beneficial results were first reported by the ESCRS Endophthalmitis Study Group in 2007 and examine the reasons for the different practice patterns identified.

Methods

The ESCRS conducted a survey of 250 ophthalmic surgeons across Europe regarding their awareness of the ESCRS study and seeking the reasons for their current use or non‐use of i/c antibiotics in their cataract surgery. Simultaneously, data on practice patterns for prophylaxis were searched in the main European countries concentrating on the uptake of the i/c route and the reasons for the switch.

Results

In the ESCRS survey, 74% always/usually use i/c antibiotics and 82% of these use cefuroxime. Lack of need, protocol, or concerns re adverse events related to the absence of an approved product, accounted for non‐use. Only 8% would not use i/c cefuroxime whether commercially available or not. Germany has the lowest use and the highest cataract volume whilst France has the next highest volume and the most rapid conversion due to Government guidelines introduced in 2011. The approval of a product of i/c cefuroxime for use in cataract surgery by the EMA (European Medicines Agency) in 2012 eliminated the risks of errors of dilution, diluent, contamination or TASS and is largely responsible for the major shift to the i/c route.

Conclusions

The landmark ESCRS Study results of 2007 heralded a worldwide increase in the use of i/c antibiotic for the prevention of postoperative endophthalmitis following cataract surgery. Subsequent studies all over the world have validated these results ‐ where the rate was high it got much lower, where it was low it got even lower with almost no adverse events.
Three‐dimensional structure of the mammalian limbal stem cell niche
Authors: Borderie V. , Grieve K. , Ghoubay D. , Georgeon C. , Thouvenin O. , Bouheraoua N. , Pâques M.
Published: September 2015

Purpose

Although the existence of the limbal stem cell (LSC) niche is accepted, precise knowledge of its 3D architecture remains incomplete.

Methods

The LSC niche was explored on freshly excised corneoscleral rims from human donors (n = 47), pigs (n = 15) and mice (n = 27) with full‐field optical coherence microscopy (FFOCM).

Results

Limbal crypt features were detected in 90% of human corneoscleral rims, extending between the palisades of Vogt as radial (74%) and/or rounded (23%) forms, often branching off to or becoming interconnected by sub‐scleral radially or circumferentially oriented crypts (56%). [kg1] Mean crypt volume represented 16% of sampled limbal volume on the vertical axis and 8% on the horizontal axis. In pigs, palisades were finer and crypts wider with relatively uniform distribution around the eye, and radial orientation, connecting to numerous narrow criss‐crossing invaginations beneath the sclera. In mice, only a circumferential limbal trough was detected. Mean crypt volume represented 13% of limbal volume in humans, 9% in pigs and 7% in mice. FFOCM combined with fluorescence showed presence of p63‐α+ cells and cytokeratin‐3 +  cells in the limbal crypts. LSC density increased with percentage limbal volume occupied by crypts. Colony Forming Efficiency increased with limbal crypt volume. [kg1] See how to rephrase all this.

Conclusions

Crypt architecture in the three species appears associated with eye exposure to light. Clone production correlated strongly with the limbal crypt volume in humans indicating that limbal crypts constitute a niche for adult limbal stem cells. FFOCM imaging could assist in assessment of the richness of the limbal crypts and targeted biopsy for cell culture.
Presbyopia compensation: looking for cortical predictors
Authors: Imbeau L. , Majzoub S. , Thillay A. , Bonnet‐Brilhault F. , Pisella P.J. , Batty M.
Published: September 2015

Purpose

New surgical techniques have recently been developed in order to compensate for visual impairment for presbyopic patients. However, the follow‐up results are still variable, depending on the correction modality used and/or the patient. The main purpose of this study was to identify predictive electrophysiological markers of post‐correction visual comfort for presbyopic patients.

Methods

Thirteen presbyopic patients received randomized presbyopia compensation with contact lenses successively by monovision, and by multifocality, for 3 weeks with a break of two weeks without any presbyopia compensation in between. Follow‐up examinations were performed at entry (T0) and after each correction modality (Tmono and Tmulti). They included testing for near and distance visual acuity, stereoacuity (TNO test), binocular contrast sensitivity and electrophysiological recordings (monocular and binocular patterns Visual Evoked Potentials).

Results

A significant correlation was found between the TNO score difference (monovision‐multifocallity) and the P100 latency evoked by the binocular pattern at T0, suggesting that late P100 latency could be associated with a lesser decrease in stereoacuity with monovision.

Conclusions

While our findings do not permit decisions regarding the superiority of f one type compensation over another, these preliminary results support using the P100 latency evoked by binocular patterns as a predictor of post‐compensation stereoacuity.
Contribution of Optical Coherence Tomography (OCT) with real‐time OCT of the Femtosecond laser, and per operative OCT of the microscope in deep anterior lamellar keratoplasty (DALK) for keratoconus: a new technique
Authors: Nguyen D.T. , Stephan S. , Gleize S. , Cochereau I. , Gabison E.
Published: September 2015

Purpose

Deep anterior lamellar keratoplasty (DALK) is a treatment of choice for keratoconus. We evaluate the contribution of a new technique associating femtosecond laser with real‐time OCT, and per‐operative OCT on the microscope, in DALK surgeries for keratoconus.

Methods

After training on artificial anterior chambers of corneal grafts to evaluate the reproducibility of cuts, pre‐cuts of human anterior corneal lamellae during DALK of keratoconus were realized using the femtosecond laser (Victus, Bausch and Lomb) with real‐time OCT and a curved applanation's surface. The depth was caculated around 60% of the thinnest pachymetry. Surgeries were realized using the per‐operative OCT with the Rescan system of the microscope (Lumera 700, Zeiss).

Results

Curved applanation and visualization with real‐time OCT of the cuts’ depth enabled the realization of reproducible lamellar cuts on 200 µ thick corneas, without modifying the laser‐cornea interface neither using masking agents. Femtosecond laser cuts allowed the big‐bubble formation on 10/10 ex‐vivo corneas. In human surgeries, real‐time OCT visualization allowed controlling non‐penetrating cuts, and the curved applanation limited folds formation on the residual stroma. Each surgical step was controlled by per‐operative OCT, with visibility of tissues’ structure and thickness, and instruments in cross section. The Anwar‐air dissection technique permitted the “big‐bubble” formation in 7/7 case, clearly visible on OCT, with only 1 or 2 injections of air. Residual posterior stroma was resected realizing pre‐descemetic lamellar grafts.

Conclusions

This new technique, femtosecond laser associated with per‐operative OCT, appears to be safe, effective, reproducible and time‐saving in DALK surgeries, facilitating the “big‐bubble” formation. It may be proposed for the management of keratoconus and other indications.
In‐vitro anti angiogenic effects of cryo‐preserved amniotic membrane
Authors: Faraj L. , Stewart E. , Albert R. , Allen C. , Petrovski G. ,  Dua H. ,  Amoaku W.
Published: September 2015

Purpose

Amniotic membrane (AM) has long been used as a biological substrate in Ophthalmology. It has a valuable role in ocular surface burns, ulcers, and nonhealing epithelial defects. AM is non‐immunogenic and has anti‐inflammatory and anti‐fibrotic properties. AM is also supports epithelial cells proliferation and migration.These effects are mediated through a host of growth factors and cytokines. Despite its clinically accepted role in reducing corneal vascularisation when applied on the eye, there have been contradicting reports on its in‐vitro anti angiogenic effect. The purpose of this study was to establish the effect of clinically prepared AM on angiogenesis and to identify the factors responsible for this role.

Methods

The effect of clinically prepared cryo‐preserved AM on human umbilical cord endothelial cells (HUVEC) proliferation was quantified using. The amniotic membrane effect on angiogenesis was quantified on matrigel. Responsible anti‐angiogenic factors were identified using searchlight protein analysis and immun‐blocking experiments.

Results

AM had a profound and significant direct effect on angiogenesis. A gradient effect was observed where HUVEC closer to the AM failed completely to migrate and form any tubules. HUVEC also failed to survive directly on the AM. proliferation was reduced significantly when exposed to AM conditioned medium. Analysis of the soluble factors released by the AM included high levels of anti‐angiogenic factors,Thrombospondin and tissue inhibitors of metalloproteinase 1 and 2.

Conclusions

The AM in‐vitro has significant anti‐angiogenic properties. This effect is attributable to an array of soluble anti angiogenic factors. This can opens a new field of using AM conditioned solutions for ocular surface vascularisation if the physical presence of the AM over prolonged period of time is not desired.
Optic nerve Drüsens in black patients: a case series of 16 patients
Authors: Sustronck P. , Jean‐Charles A. , Benzekri R. , Merle H.
Published: September 2015

Purpose

Optic nerve Drüsens are rare among black patients. The goal of our study was to describe the characteristics of ophthalmological findings in this population.

Methods

We carried out a descriptive prospective study from June 2006 to October 2014 on 19 eyes of Afro‐Caribbean patients from Martinique with optic nerve Drüsens diagnosed by fundoscopy and B‐Scan ultrasonography. Patients underwent clinical exam, Optical coherence tomography (OCT), colour vision, and visual field. Three eyes were excluded from visual acuity and paraclinic analysis due to an anterior optic ischemic neuropathy (AOIN), a penetrating eye injury and an epimacular membrane.

Results

11 Afro‐Caribeean patients were included: four men and seven women with age ranking from 11 to 68 years with a mean age of 41. Nine of the 11 patients (69%) had bilateral optic nerve Drüsens. Only 2 patients (12%) were symptomatic including the AOIN. Mean ETDRS visual acuity was 56 at 4 meters (min 31, max 68, sd 7.0). Three of 16 eyes (19%) had an ETDRS vision loss. Four of 16 (25%) had a Pellirobson contrast vision loss due to cataracts. Four patients (25%) had a dyschromatopsy. The average OCT RNFL was 94 µm (min 57, max 150, sd 18.7). Mean foveal threshold was 34 db (min 22, max 39; sd 2.8). 11 of 16 eyes (69%) showed a visual field defect: Nine had an enlarged blind spot and nine had an arcuate scotoma. None of the patients had a pathology associated with optic nerve Drüsens such as pigmentary retinopathy or angioïd streaks.

Conclusions

This study is the largest case series carried out on optic nerve Drüsens in black patients. It shows that the majority of them is asymptomatic but campimetric defects are common. Some rare but severe complications can occur such as AION.
Repeatability of retinal nerve fiber layer reflectance intensity measurement in glaucoma
Authors: Gardiner S. , Demirel S. , Reynaud J. , Fortune B.
Published: September 2015

Purpose

Decreased reflectance within the retinal nerve fiber layer (RNFL), observable using optical coherence tomography (OCT), appears to be related to functional loss in glaucoma. In order to investigate this in a quantitative manner, reliable measurements of reflectance intensity are needed. However, reflectance may not only be affected by pathophysiological changes in tissue properties but also confounded by other effects of ocular media and image quality. This study assesses the repeatability of intensity measurements, before and after normalization aimed to reduce test‐retest variability.

Methods

Data were taken from participants with glaucoma in a test‐retest study. Each had peripapillary circle scans acquired from both eyes 5 times within 10 weeks. For each scan, the following were extracted: average RNFL thickness; RNFL intensity, defined as the mean reflectance intensity of pixels within the delineated RNFL; sub‐RNFL intensity, defined as the mean intensity of pixels between the outer boundary of the RNFL and Bruch's Membrane; and intensity ratio, defined as RNFL intensity divided by sub‐RNFL intensity. For each parameter, deviations from the per‐eye mean were calculated. The intra‐eye standard deviations (SD) were expressed as percentage of the width of the range of observed measurements.

Results

The intra‐eye SD of RNFL intensity was 12.5% of the range. Normalization reduced the intra‐eye SD of intensity ratio to 4.9% of the range, representing a significant reduction in absolute deviations with p < 0.0001 (Wilcoxon signed rank test). RNFL thickness was more repeatable, with intra‐eye SD 0.8% of its range.

Conclusions

RNFL reflectance intensity varies substantially between scans. However, dividing by the intensity of sub‐RNFL tissue greatly reduces this variability. Such normalization allows useful measurements to be obtained.
Posterior corneal anatomy in a newborn baby
Authors: Faraj L. , Yeung A. , Said D. , Branch M. , El Alfy M. , Dua H.
Published: September 2015

Purpose

In view of the recent developments in our understanding of posterior corneal anatomy and the description of a unique layer and zone in adults, we investigated two corneas from a three‐week‐old baby.

Methods

both corneas were subjected to intra stromal air injection using a 30G needle. The type of big bubble formed was identified. The wall of the big bubble and the posterior stromal interface with Descemet membrane was studied using light microscopy, electron microscopy and immune‐histological studies.

Results

Intra stromal injection of air resulted in the formation of characteristic type 1 big bubble in one cornea and another characteristic type II big bubble in another. The wall of the type I big bubble bubble was made of endothelial cells, Descemet's membrane and a thin collagen layer anteriorly (previously described as Dua's layer [DL]).

DL was made of 7‐8 collagen lamellae of compactly opposed collagen. This was made of predominantly type I collagen with abundance of collagen VI. Thrombospondin was characteristically seen along the posterior surface of DL extending to the trabecular meshwork. The interface between DL and DM was not distinct but presented a transition zone. The wall type II big bubble was made of Descemet membrane only, which was extremely thin.

Conclusions

We demonstrated here that the human infant cornea behaves similarly to adult cornea when subjected to air injection (dissection). We also demonstrated the presence of DL in a 3 week old baby and presented its histological characteristics.
Glaucomatocyclitic crisis, a rare cause of unilateral ocular hypertension
Authors: Ozcan A.A. , Sariyeva A.
Published: September 2015

Purpose

To report a case of glaucomatocyclitic crisis which is a rare cause of ocular hypertension.

Methods

A 40 ‐year‐ old immunocompetent male patient admited, with the complaints of blurry vision, photophobia,red eye, and severe pain in the left eye for the last 2 days.Examination revealed mild anterior chamber reaction, corneal oedema, appearance of keratic precipitates and a very high intraocular pressure (52 mmHg) with an unresponsive, semi‐dilated pupil in the same eye. Gonioscopy revealed open angles in both eyes.

Results

He was treated with topical steroids and topical pressure‐lowering agents with oral acetazolamide. The patient was also evaluated for systemic causes of red eye. Investigations carried out included routine blood tests and ESR, the results of which were all within normal limits. In the following 24 month period, the patient had two further episodes of unilateral IOP spikes associated with cyclitis.

Conclusions

This is an interesting and a rare uveitic condition. Although the list of differential diagnoses is long, the condition is relatively quickly identifiable by the presence of remarkable signs and symptoms. Medical and surgical treatments are indicated to reduce inflammation and to prevent long‐term glaucomatous optic nerve damage related to the high intraocular pressure.
Influence of intraocular pressure in anterior lamina cribrosa depth – a prospective observational study in a healthy Portuguese population
Authors: Cordeiro Sousa D. , Leal I. , Pinto Ferreira N. , Pinto J. , Abegao Pinto L. , Pinto F. , Marques‐Neves C.
Published: September 2015

Purpose

To investigate the association between anterior lamina cribrosa depth (ALCD) determined with enhanced depth imaging spectral‐domain optical coherence tomography (EDI‐OCT) and IOP in a healthy Portuguese population.

Methods

Prospective observational study conducted between January and April 2015 of 44 subjects with a irrelevant ophthalmologic history. EDI‐OCT of optic nerve head (ONH) was performed in all participants (2 cross scans: vertical and horizontal). ALCD was defined as the perpendicular distance between the line connecting both edges of Bruch's membrane and the anterior border of the lamina cribrosa, at the maximum depth point. An experienced operator manually segmented ALCD and a mean of the two consecutive blinded measurements was computed. To guarantee observations’ independence, only one eye was considered per subject. Only high‐quality images were accepted. The tenets of the Declaration of Helsinki were followed. Statistical analyses were performed using STATA 13.0.

Results

Studied population included 44 subjects (26 women), with a mean age of 62.9 ± 14.3 years. Mean vertical and horizontal maximum ALCD was 453.3 ± 88 μm and 436.1 ± 78.7 μm, respectively. Neither gender nor age were associated with these ALCD scans (p > 0.05). When controlling for gender, age and spherical equivalent, maximum vertical and horizontal ALCD increased, respectively, by 8.8 μm (95% confidence interval [CI], 0.6–17.0 μm; p = 0.04) and 8.1 μm (95% CI, 0.4–15.7 μm; p = 0.04) per mmHg increase in IOP.

Conclusions

Our sample of healthy subjects presented a statistically significant positive linear relation between IOP and ALCD, when controlling for possible confounding factors. Our results may trigger furthers studies to better elucidate the role of IOP in morphological and functional dynamics of the ONH.
Long‐Term Safety of Intravitreal Sirolimus for the Treatment of Non‐infectious Uveitis (NIU) of the Posterior Segment: 12‐Month SAKURA Study 1 Results
Authors: Bodaghi B. , Pavesio C. , Alfredo A.C. , Valentine M.E.
Published: September 2015

Purpose

Intravitreal sirolimus significantly reduced inflammation in subjects with NIU of the posterior segment and provided clinically relevant visual benefit, with an acceptable incidence of ocular adverse events (AEs), in the double‐masked period of SAKURA Study 1, the first of 2 phase 3 randomized trials. Here, we report the long‐term (12 month) safety findings from the combined double‐masked and open‐label treatment periods.

Methods

Subjects with active NIU of the posterior segment (N = 347) were randomized to 44 μg (active control), 440 μg, or 880 μg injections of intravitreal sirolimus, administered every 2 months. At M6, all subjects transitioned to 880 µg injections every 2 months.

Results

287 subjects entered the open‐label treatment period and completed the M12 Vitreous Haze assessment. Of these, 211 received ≥1 intravitreal sirolimus injections. Through M12, the most common serious ocular AEs (study eye) occurring in ≥2% of subjects were ocular inflammation (2.9–5.8%), cataract (3.8%), and medication residue (transient drug depot in the visual axis; 2.3%). The mean change in intraocular pressure was <2 mm Hg. The incidence of confirmed endophthalmitis was 0.06%/injection.

Conclusions

There was a low incidence of serious ocular AEs over 12 months with intravitreal sirolimus in this heterogeneous group of subjects with NIU of the posterior segment.
Fundus photography as a screening method of diabetic retinopathy in children and adolescents with type 1 diabetes Outcome of the first fundus photography at the age of 9–17 years
Authors: Gräsbeck T. , Gräsbeck S. , Miettinen P.J. , Summanen P.A.
Published: September 2015

Purpose

To study the success of fundus photography in screening of diabetic retinopathy (DR) in children <18 years with type 1 diabetes (T1D) in producing gradable images.

Methods

Photographic success of black‐and‐white macula and optic disc‐centered fundus images of both eyes of each patient was graded by one observer (TG) using a slightly modified classification of ARIC. All images were taken with a digital 60° Canon CF‐60UD camera. Photography as a whole was graded as ‘complete success’ if the images of both eyes were at minimum of fairly good quality (i.e. gradable), and ‘partial success’ if the images of only one eye reached this level.

Results

Of the 213 patients photographed for the first time in 2009–2013 at the Department of Pediatrics, 121 (57%) were males. The median age of diagnosis was 8 (range, 1–16) years and at the first photography 11 (9–17) years. At the first photography, the median duration of T1D was 2.3 (range, 0.2–9.6) years and the median HbA1c was 8.5% (range, 6.3–13.8).

At least partial success was reached in 153 (72%; 95%CI, 65–78) patients and complete success in 97 (46%; 95%CI, 39–52) patients. Complete success was equally common among those aged 9–10, 11–12, and 13–17 years (45%, 46% and 47%). The macula‐centered images of 177 (83%; 95%CI, 77–88) patients, and the optic‐disc centered images of 103 (48%; 95%CI, 41–55) patients were gradable in both eyes. Age at the first photography was not associated with success (p = 0.20).

Conclusions

Less than half of the first fundus images achieved complete success, but over 70% achieved at least partial success when photography was performed at the age of 9–17 years. No significant associations were identified. Photography is a reliable method for screening of DR also in pediatric setting.
Two‐year, Prospective, Multicenter Study of the Use of Dexamethasone Intravitreal Implant for Treatment of Macular Edema Secondary to Retinal Vein Occlusion in France
Authors: Gualino V. , Korobelnik J.F. , Kodjikian L. , Delcourt C. , Leaback R. , Pinchinat S. , Velard M.E.
Published: September 2015

Purpose

To characterize patterns of use, efficacy, and safety of dexamethasone intravitreal implant (DEX) in treatment of macular edema (ME) due to retinal vein occlusion (RVO) in the French clinical setting.

Methods

A 24‐month, observational, prospective, epidemiological study conducted at 48 randomly selected sites in France enrolled consecutive patients with ME due to RVO who were treated with DEX at baseline. DEX re‐treatment and use of other RVO treatments was at the physician's discretion. The primary endpoint was change in best‐corrected visual acuity (BCVA) from baseline to month 6. Secondary endpoints included BCVA change from baseline and adverse events through month 24.

Results

Patients (n = 375) received a mean of 2.6 DEX injections (range, 1–7) over 2 years; 167 received DEX only and 208 also received other types of RVO treatment. Mean (SD) change from baseline BCVA was +5.1 (19.0) ETDRS letters at month 6 (P < 0.001) and +4.6 (22.3) letters at month 24 (P < 0.001). For patients treated only with DEX during the study, mean (SD) change from baseline BCVA was +8.1 (20.9) letters (P < 0.001) at 24 months, compared with +2.5 (23.0) letters (P = 0.092) for patients moved to other treatments. BCVA improved significantly from baseline at 6 and 24 months in subgroups defined by diagnosis (branch RVO, central RVO), previous treatment, duration of ME, and pattern of DEX use. The most common adverse events were ocular hypertension and cataract.

Conclusions

Patients with RVO‐related ME treated with DEX in the French clinical setting had efficacy and safety outcomes similar to those seen in the phase 3 registration trials. BCVA gains were maintained over 2 years and largest in patients with recent onset (<3 months) ME, confirming the benefit of early treatment.