bluuebunny/crossref_metadata_2025 huggingface dataset:
Ranibizumab in patients with neovascular age‐related macular degeneration: results from the real‐world LUMINOUS™ study
Authors: Souied E. , Clemens A. , Macfadden W.
Published: September 2017

Purpose

LUMINOUS(NCT01318941) was designed to evaluate the long‐term safety, effectiveness, and treatment patterns with ranibizumab 0.5 mg in clinical practice across all licensed indications. We report, the effectiveness and safety of ranibizumab treatment in patients with neovascular age‐related macular degeneration (nAMD) from the final analysis of LUMINOUS.

Methods

LUMINOUS is a recently‐completed, 5‐year, global, observational study. Consenting adult patients were treated as per the local ranibizumab label. Reported are the 1‐year visual acuity (VA, primary treated eye), and injection pattern for the treatment‐naïve nAMD patients. The incidence of adverse events (AEs) and serious AEs (SAEs) for the total treatment‐naïve nAMD cohort is also presented.

Results

Baseline and 1‐year VA data were available for 2701 treatment‐naïve nAMD patients. At baseline, the mean (SD) age was 75.9 (9.7) years, 58.4% were female, and 78.4% were Caucasian. VA (letters) gains at 1‐year in treatment‐naïve patients receiving <3, 3–6, and >6 injections were 2.1 (n = 372), 3.6 (n = 1499), and 4.3 (n = 830), from baseline of 45.0, 52.5, and 54.9, respectively. In all treatment‐naïve nAMD patients, the mean (SD) gain in VA of 3.6 (16.2) at 1 year from 52.2 (20.8) at baseline was achieved with a mean (SD) of 5.3 (2.7) ranibizumab injections and 9.3 (3.3) monitoring visits. Across all treatment‐naïve nAMD patients (n = 6241), the incidence of ocular/non‐ocular AEs and SAEs were 8.2%/12.8% and 0.9%/7.4%, respectively.

Conclusions

This analysis from LUMINOUS confirms the effectiveness of ranibizumab in treatment‐naïve nAMD, and shows a relationship between VA improvement and the number of ranibizumab injections each patient received.
Changes of anterior chamber morphometry with age in children using hand‐held spectral domain optical coherence tomography
Authors: Edawaji B. , Proudlock F. , Gottlob I.
Published: September 2017

Purpose

To identify the change of anterior chamber measurements with age in children using Hand‐Held Spectral Domain Optical Coherence Tomography (HH‐SDOCT).

Methods

A cross‐sectional study involved 93 normal children (mean age = 5.19 ± 4.1 years, range: 2 days to 15 years). HH‐SDOCT (Leica Microsystems Ltd) was used to image anterior chamber angle. B‐scan showing both clear nasal and temporal angles were analysed using ImageJ. The iridocorneal angle landmarks: scleral spur (SS), Schwalbe`s line (SL) and angle recess (AR) were identified and used to calculate trabecular meshwork length (TML), scleral spur angle opening distance (SSAOD), Schwalbe`s line angle opening distance (SLAOD), trabecular iris surface area (TISA), TISA500, SS limbal distance (SSLD) and SL limbal distance (SLLD), nasal SS to temporal SS distance (SS‐SSD), nasal SL to temporal SL distance (SL‐SLD) and pupil diameter (PD). Linear mixed models were used to determine the correlation between ocular parameters and demographic data with log age.

Results

All measured parameters were significantly influenced by age (all P values <0.05). The changes of parameters per age were measured in 591 angle images. In the first year, TML increased by 159.6 μm (30.5%), SSAOD 120.4 μm (112.4%), SLAOD 347.4 μm (95.7%), TISA 0.19 mm² (133.4%), TISA500 0.13 mm² (96.4%), SSLD 33.7 μm (4.2%), SLLD ‐ 30.3 μm (3.9%), SS‐SSD 2.4 mm (23.3%), SL‐SLD 2.0 mm (21.4%) and PD 2.4 mm (114.3%). No significant changes were detected with gender or between both eyes (P values > 0.05).

Conclusions

HH‐SDOCT can be an effective technique in understanding the morphometric changes of anterior chamber in children from birth. Our findings highlight the need for normative age adjusted data to detect abnormalities in angle measures clinically.
Laboratory work‐up and specialized investigations
Authors: khairallah M. , Khochtali S. , Jelliti B.
Published: September 2017

Making the correct diagnosis of a specific uveitic entity is critical to appropriate management. The likely diagnosis can be derived from medical history, anatomic type and clinical characteristics of uveitis, and results of ocular imaging in selected cases. Laboratory testing then is performed to look for an infectious cause or an underlying systemic disease, that cannot be identified on a clinical basis. A comprehensive work‐up is costly and unnecessary. It may also give misleading positive results. Laboratory investigations should rather be tailored to epidemiological data and clinical findings. In cases of suspected intraocular infections, intraocular fluids may be evaluated for specific antibody production or polymerase chain testing. In case of negative history and absence of findings suggestive of a particular diagnosis, a minimal work‐up should be performed, including complete blood count, erythrocvyte sedimentation rate, Mantoux test, interferon‐gamma release assay, chest X‐ray, and serology of syphilis. A more extensive work‐up may be required in cases of severe uveitis, recurrences, resistance to treatment or worsening under therapy.
Therapeutic management of uveitis
Authors: Dick A.
Published: September 2017

This talk will overview the contemporary therapeutic approaches to treatment of noninfectious non‐infective ocular inflammatory disease. Treatment of non‐infectious uveitis has over past 15 years expanded from the use of traditional therapies including corticosteroids and immunosuppressants to the deployment of targetting the immuneresponse with biologic therapies with monoclonal antibodies and immunoadhesins. Such use will be exemplified with case reports during the talk. Evidence of efficacy of immunosuppressants in the treatment of uveitis, the role of predicting steroid responsiveness, the use of monotherapy with immunosuppression and finally the pathways and evidence of success of biologic therapy will be provided.
Neural crest FGF signaling controls lacrimal gland development
Authors: Garg A. , Zhang X.
Published: September 2017

Neural crests are multipotent progenitors that migrate from the neural tube to populate the entire body, differentiating into diverse cell types in many organs. FGF signaling is one of the key regulators of neural crest development, but the downstream signaling mechanism is not well understood. Here we show that conditional knockout of Shp2 disrupted migration, survival and differentiation of neural crests, culminating in the loss of Fgf10 into the periocular mesenchyme. This results in abrogation of lacrimal gland development. These phenotypes are reproduced by genetic ablation of Fgfr, adaptor protein Frs2 and downstream kinases Mek and Erks in the neural crest, and rescued by constitutive activation of Kras, establishing a FGFR‐Frs2‐Shp2‐Ras‐MEK‐ERK cascade. By RNAseq analysis, we showed that Shp2 deficiency causes significant changes in the neural crest transcriptome and identified critical regulator of Fgf10 expression in the periocular mesenchyme. These results demonstrate that neural crest FGF signaling is essential for lacrimal gland induction.
Optical coherence tomography – basic optical principles
Authors: Irsch K.
Published: September 2017

Optical Coherence Tomography (OCT) is an optical analogue to ultrasound imaging. The much higher speed of light compared with sound allows for finer cross‐sectional views of the retina and anterior segment. Since it is extremely difficult to directly detect the shorter “echo” times it takes light to travel from different structures at axial distances within the eye, interferometry is used. Incident light is thus split into two beams, and the beam backscattered from the ocular tissue is then compared (“interfered”) with the beam that has traveled a known time from the reference mirror. Broadband (i.e., low “coherence”) light sources are used, because they produce a wider band of wavelengths, and thereby enable greater sensitivity in comparing the travel time differences of the two beams. In time‐domain OCT, the reference mirror position is altered, so that interference patterns are generated whenever the two beams have traveled almost the same amount of time. In spectral‐domain OCT, the reference mirror position is fixed and the mixed interference patterns are separated via spectral wavelength analysis. This lecture will explain underlying concepts of OCT with a discussion of cutting‐edge technological developments.
Optical coherence tomography – machine learning
Authors: Bernardes R. , Castelo‐Branco M.
Published: September 2017

Machine learning is a method of data analysis. It gives computers the ability to learn from data and to build models from which predictions can be made. Even though OCT is mainly used to visualize retinal structures and compute thickness maps, it conveys information on subtle changes within the retina before structural ones can be identified. Exposing the machine learning model to a set of examples allows it to build a model from which predictions can be made on new data and explain differences between groups. This lecture will explain the underlying principles of machine learning and discuss potential applications in ophthalmology and CNS disorders through the imaging of the retina.
27‐Gauge vitrectomy – the smaller the better?
Authors: Falkner‐Radler C. , Bukaty E. , Krebs I.
Published: September 2017

Purpose

To evaluate anatomic, functional and refractive outcomes after 27‐gauge vitrectomy in a prospective study.

Methods

The study was designed to include patients presenting with vitreoretinal disorders (epiretinal membrane [ERM], macular holes, asteroid hyalosis and vitreomacular traction [VMT]) with or without coexisting significant cataract. Exclusion criteria were (a) patients with rhegmatogenous or tractional detachment, (b) previous vitreoretinal surgery, and (c) the need for silicone oil tamponade. Surgical conditions using a scaled questionnaire, complication rates, IOP, functional and refractive outcomes were evaluated. All surgeries were performed by one surgeon (F‐R CI).

Results

Up to now, 60 patients, 41 females and 19 males with a mean age of 72 years, have completed the 3 months follow‐up. The vitreoretinal diagnosis was ERM in 36 eyes, macular holes in 9 eyes, VMT in 2 eyes, and asteroid hyalosis in 13 eyes. In 47 eyes cataract surgery was combined with vitrectomy. Intraoperative conditions were graded good to excellent. However, a slightly increased time needed for core vitrectomy was noted and particularly in hyperopic and left eyes the 27 gauge instruments were graded to be more flexible. No wound leakage was found and the IOP was stable in all eyes. Complication rates included a mild postoperative vitreous hemorrhage in one patient which spontaneously resolved during follow‐up. Visual acuity improved in all patients and the refractive results in the combined cases were excellent.

Conclusions

These results suggest that 27 gauge vitrectomy with or without combined cataract surgery results in excellent wound architecture and offers promising functional and refractive results.
Bidirectional cross talk between uveal melanoma cells and hepatic myofibroblasts promotes inflammation‐induced chemokines expression
Authors: Babchia N. , Landreville S. , Clement B. , Coulouarn C. , Mouriaux F.
Published: September 2017

Purpose

Uveal melanoma (UM) is the most common primary ocular neoplasm in adults. Its cause is largely unknown, and no risk factors have yet been identified. The metastatic disease develops in up to 50% of patients, usually involving the liver. Treatment only rarely prolongs survival, because metastases are highly resistant to most chemotherapeutic agents. Tumor cells may modulate the functions of surrounding cells to facilitate their own growth, survival, invasion, and metastasis. This study was conducted to investigate the role of hepatic microenvironment on UM cells (UMC).

Methods

Here, we utilized metastatic (Omm2.3) and non‐metastatic (Mel270) UMC in coculture with hepatocyte‐stellate cells (HSC) LX2. The transcriptomic study was performed by microarray assay. Expression of relevant genes was measured by qPCR. Cytokines were quantified by Elisa test. Cell proliferation was assessed by MTT staining. Extracellular matrix components were evaluated by quantitative cell adhesion assay.

Results

Hepatic microenvironment increased the expression of numerous genes. However, the number of genes overexpressed in metastatic co‐cultures is three‐times higher than in non‐metastatic cocultures, demonstrating that hepatic microenvironment has more impact on metastatic UMC. Over‐expressed genes in coculture were linked to inflammation and included several interleukins. In addition, UMC‐HSC crosstalk generated expression of cell adhesion receptors, particularly by increasing fibronectin. In contrast, hepatic microenvironment had no effect on cell proliferation.

Conclusions

Our results provide evidence for an important role of inflammation in the progression of metastatic UM. Therefore, the inflammatory characteristics of the tumor microenvironment might offer therapeutic opportunities.
Principles and techniques; pearls and pitfalls
Authors: Lupidi M. , Coscas G. , Coscas F.
Published: September 2017

The contrast generated between static and non‐static tissue results in a vascular signal. This principle stands at the base of OCT‐Angiography (OCT‐A), a novel imaging technique that allows to visualize the retinal and choroidal perfusion in a depth‐resolved approach. Clinical investigations of OCT‐A have demonstrated its potential in a wide variety of retinal and macular diseases. Dye angiographies maintain several advantages mainly related to the larger imaging field. Moreover OCT‐Angiography needs some learning time to interpret the images, in order to distinguish new imaging features of a well know clinical entity from artifacts. Motion errors, improper software correction or shadowgraphic flow projection can lead to severe artifacts, which influence and sometime interfere with the imaging assessment.

Purpose of this lecture is to highlight the role of OCT‐A in clinical practice: describing its principles, pearls and pitfalls may help the clinician to integrate this innovative approach in common patient care.
OCT‐A and VRO
Authors: COSCAS F. , Coscas G. , Souied E.H.
Published: September 2017

Correlations in retinal vein occlusion (RVO) patients between macular vascular densities in the superficial and deep capillary plexuses obtained using OCT‐Angiography (OCTA) and the data from conventional examination (visual acuity and peripheral retinal non perfusion on fluorescein angiography) might reveal new insights in the pathogenesis of vascular damage. Through a retrospective, observational study of RVO patients with who underwent a comprehensive ophthalmic examination including FA and OCTA a significant correlation between automatically quantified macular vascular density on OCTA and peripheral non‐perfusion on FA was demonstrated; OCTA could help in identifying high‐risk RVO patients who may benefit from further evaluation using FA.
OCT‐A A in CSC and in MacTel type 2
Authors: Mauget‐Faysse M. , Wolff B. , Vasseur V. , De Bats F.
Published: September 2017

OCT‐A with OCT « en face » allow a good imaging and location of vessel abnormalities in MacTel2. OCT‐A reflects the progressive transformation of the perifoveolar capillaries and detects the presence of CNVs. There are still difficulties to analyse the link between the different layers of the retina & the choroid due to the frontal section of OCT‐A. There is a need for 3D imaging. A new symptomatology is described on OCT A in CSC as abnormal dark and white lesions. OCT B, C and multimodal imaging are mandatory in addition to OCT A to diagnose non neovascular retinal and choroidal CSC lesions. However, OCT A is very helpfull in the detection of abnormal choroidal neovascular membrane in CSC patients. In CSC, signs on OCT‐A must be interprete with caution and compare with multimodal imaging OCT « En‐Face ». The main contribution in CSC of OCT‐A is for CNV detection.
OCT‐A in ocular oncology
Authors: Zografos L.
Published: September 2017

OCT‐A allows the visualization of various capillary plexusses located in front of the retinal pigmented epithelium. In case of partial depigmentation or metabolic modifications of the retinal pigmented epithelium, vascular networks located in the choroid can also be observed. This new imaging technique is currently used mainly in the diagnosis, the follow‐up and the prognostication of irradiation induced maculopathy. The presence of a vascular network in pigmented and unpigmented small choroidal tumors visible in selected cases on OCT‐Angiography offers new diagnostic perspectives which are currently under investigation.
Mouse case
Authors: Roux M. , Amiot C. , Maréchal D. , Hérault Y.
Published: September 2017

The retina of Down syndrome (DS) patients is thicker than the one from controls, an anomaly reproduced in two murine models of the disease, Ts65Dn and Tg(Dyrk1a) and attributed to the increased dosage of Dyrk1a (Laguna et al. 2013), considered as one of the key genes in the apparition of DS symptoms. As HSA21 genes not triplicated in Ts65Dn may affect the expression/function of DYRK1A, we have analyzed by optical coherence tomography (OCT) the retina of Ts65Dn and Tg(Dyrk1a) mice, and compared the results to those obtained on various additional models, notably Dp(16)1 Yeh mice, which have a triplicated segment of MMU16 longer than Ts65Dn, and crosses between Tg(Dyrk1a) and Dp1 Yah, which carries a triplication of the MMU17 genes orthologue to HSA21. In parallel, we have started to analyze by immunohistochemistry the retinal neuron populations in Tg(Dyrk1a) mice, showing an increase in dopaminergic amacrine cells when Dyrk1a is triplicated. Mirror results were obtained on the retina of Dyrk1a+/‐, a model of Mental Retardation 7.

Laguna et al. (2013 ): Triplication of DYRK1A causes retinal structural and functional alterations in Down syndrome. Hum Mol Genet 15;22(14):2775‐84.
Inflammation in relation to retinal diseases
Authors: Dick A.
Published: September 2017

Maintaining tissue and cellular health to preserve vision requires active immune responses to prevent damage and respond to danger. Macrophage polarisation may determine the result of the immune response and subsequent tissue health and TNF–alpha is a central regulator. With respect to an insidious degeneration in atrophic AMD or in neovasular AMD, the ability to attenuate pathogenic immune responses is observed despite known inflammasome activation. The result of immune cell activation is environmentally dependent, for example on retinal cell bioenergetics status, autophagy and oxidative stress, alterations in which skew interaction between macrophages and retinal pigment epithelium (RPE). For example, dead RPE eliciting macrophage VEGF secretion but exogenous IL‐4 liberates an anti‐angiogenic macrophage sFLT‐1 response. Impaired autophagy or oxidative stress drives inflammasome activation, increases cytotoxicity and accentuation of neovascular responses, yet exogenous inflammasome derived cytokines such as IL‐18 and IL‐33 attenuate responses.
Elevation of intraocular pressure in relation to retinal diseases
Authors: Vidal‐Sanz M. , Valiente‐Soriano F.J. , Rovere G. , Nadal‐Nicolás F.M. , Salinas‐Navarro M. , Agudo‐Barriuso M. , Villegas‐Pérez M.P.
Published: September 2017

Intraocular pressure remains the only modifiable risk factor in glaucoma, a disease characterized by progressive loss or retinal ganglion cells (RGCs) and visual field deficits leading to blindness. Using two rat models of chronic (COH) or acute (AOH) ocular hypertension we study the response of the general population of RGCs responsible for image‐forming visual information and the intrinsically photosensitive population of RGCs responsible for nonimage‐forming visual information, identified with Brn3a and melanopsin antibodies, respectively. For AOH the anterior chamber of the left eye was cannulated and connected to saline elevated 1½ meters for 75 minutes. COH was induced by laser‐photocoagulation of limbar tissues. In both models prior to OH a single intravitreal injection of brain derived neurotrophic factor (5 μg BDNF in 1% albumin PBS) or vehicle was administered. Re retinas were examined at 12 or 15 days after COH or 3, 7, 14, or 45 days after AOH to identify surviving Brn3a+RGCs and m+RGCs. COH induced comparable loss of RGCs but only Brn3a+RGCs responded to BDNF. After AOH, Brn3a+RGCs died progressively while m+RGCs did not, and BDNF induced a permanent protection up to 45 days after AOH in both types of RGCs.
Mitochondrial impairment regulates inflammasome activation in human retinal pigment epithelial cells
Authors: Korhonen E. , Piippo N. , Hytti M. , Kaarniranta K. , Kauppinen A.
Published: September 2017

Purpose

Dysfunctional mitochondria and excessive inflammasome activation have been shown to play a role in age‐related macular degeneration. The aim of the present study was to investigate whether release of mitochondrial reactive oxygen species (ROS) by impaired mitochondria leads to inflammasome activation and further secretion of IL‐1β in human retinal pigment epithelial cells.

Methods

ARPE‐19 cells were primed with IL‐1α and exposed to mitochondrial electron transport chain III inhibitor, Antimycin A, after pretreatment with caspase‐1 inhibitor, Ac‐YVAD‐CMK or mitochondrion‐specific ROS scavenger, mito‐TEMPO. Pro and mature forms of IL‐1β were measured from cell lysates and cell culture supernatants by enzyme linked immunosorbent assay (ELISA) method. Cytotoxicity was determined by commercial lactate dehydrogenase (LDH) assay.

Results

Antimycin A induced secretion of mature form of IL‐1β in IL‐1α primed ARPE‐19 cells. However, secretion of IL‐1β was significantly declined by Ac‐YVAD‐CMK and further by pretreating cells with mito‐TEMPO. AC‐YVAD‐CMK or mito‐TEMPO had no impact to the cell viability.

Conclusions

In conclusion, the present study reveals that impaired mitochondria increases release of bioactive IL‐1β through the inflammasome activation in human retinal pigment epithelial cells.
Inner retina changes in hydroxychloroquine patients
Authors: Barata A. , Leal I. , Sousa F. , Teixeira F. , Pinto F.
Published: September 2017

Purpose

To study if hydroxychloroquine (HCQ) patients with apparent no retinal toxicity will show lower retinal thickness in inner layers as compared to healthy controls.

Methods

Retrospective study of 43 patients (86 eyes) evaluated for HCQ macular toxicity with spectral‐domain OCT (SD‐OCT) and with no OCT signs of maculopathy were subdivided into two groups: (1) no blunting of the foveal contour (foveal splaying), (2) with foveal splaying. Age and sex‐matched controls were used for comparison. Automated retinal layer segmentation at the center of fovea and at a radius of 3 (parafoveal) to 6mm (perifoveal) from the superior, inferior, temporal and nasal sectors was performed. Statistical analysis using two sample t‐test was made to calculate significant results between groups.

Results

Center macular and internal retinal layers thickness in all parafoveal sectors, particularly in the retinal nerve fibre (RNFL) and ganglion cell layer (GCL), was statistically reduced when compared to control group (p < 0.05) and differed between group 1 and 2. RNFL thickness was also reduced in all perifoveal sectors but temporal sector (p < 0.05) and inner plexiform layer and inner nuclear layer thickness showed only significant reduction in foveal and nasal parafoveal sector (p < 0.05) in HCQ eyes. No significant differences in outer layers was observed between groups.

Conclusions

Small changes in inner retinal layers thickness have been described with HCQ use and conflicting correlation with HCQ toxicity is present in the literature. This study supports that inner retina at the fovea and parafovea is thinner in patients with no outer retinal OCT signs of HCQ toxicity. Further investigation is needed to assess if an inner retinal thickness reduction threshold could serve as valuable tool for identifying patients with increased risk of HCQ maculopathy.
Idiopathic retinal vasculitis, arteriolar macroaneurysms and neuroretinitis (IRVAN): case series of three patients with multimodal imaging
Authors: Yu Jeat C. , Logeswaran A. , Damato E.
Published: September 2017

Purpose

To describe the clinical presentation, disease progression, treatment and complications of IRVAN.

Methods

Retrospective review of three patients with a diagnosis of IRVAN seen at the Birmingham and Midland Eye Centre between 2010 and 2017. Multimodal imaging investigations included wide‐field fluorescein angiography, optical coherence tomography, and indocyanine green angiography.

Results

A total of 6 eyes from 3 patients with bilateral disease were included. All six eyes were treated with panretinal photocoagulation (PRP). One eye received a dexamethasone implant for refractory macular oedema and exudation. One eye was treated with Avastin injections for persistent optic disc neovascularization. All 3 patients were treated with oral steroids at some point in the course of their disease and one was subsequently immunosuppressed with mycophenolate mofetil. Visual outcomes varied. One patient maintained excellent visual acuity of 6/6 in both eyes at 72‐months follow‐up. The second patient experienced progressive visual loss from 6/9 right eye, 6/6 left eye at presentation; to 6/18 right eye, 6/60 left eye at 12 months follow‐up due to macular exudation despite aggressive PRP and intravitreal Ozurdex. The third patient deteriorated from 6/5 right eye, 6/4 left eye at presentation to 6/60 right eye at 6 months, despite aggressive PRP. He had recurrent vitreous haemorrhages in the right eye secondary to NVD despite further interventions with Avastin injections; seven years after presentation, vision remained at 6/60 right eye and 6/18 left eye.

Conclusions

The cadence of progression of IRVAN can vary greatly, despite aggressive treatment with PRP, intravitreal steroids, and anti‐VEGF agents. We observed variation in disease progression both among patients as well as within the same individual, supporting an individualized approach to therapy.
Sicca syndrome ‐ disease continnum. Anatomical, functional and systemic assessment
Authors: CARDIGOS J. , Crisostomo S. , Costa L. , Vaz Patto J. , Maduro V. , Barcelos F. , Alves N.
Published: September 2017

Purpose

To evaluate objective findings in the ophthalmologic examination and search for patterns of association with the clinical and laboratory characteristics in patients with Sicca Syndrome (SiS).

Methods

Cross‐sectional study of 80 eyes of 80 patients with SiS divided into four groups. 20 patients with pSS for more than 10 years (group1), 20 patients with pSS for less than 2 years (group 2), 20 patients with SiS associated to undifferentiated connective tissue disease (UCTD) (group 3) and 20 patients with SiS without UCTD (group 4). Demographic, clinical and immunologic data were recorded. Ophthalmologic examinations included Schirmer test, break up time (BUT), Corneal Staining Score (CSS), tear meniscus evaluation in Anterior Segment – Optical Coherence Tomography (AS‐OCT) and corneal sub‐basal nerve plexus (CSNP) measurements with in vivo Confocal Microscopy (IVCM).

Results

Group 1 had an early diagnosis when compared with group 2. Group 1 presented a higher frequency of positivity for anti‐SSA, anti‐SSB, Rheumatoid Factor and ANA titers compared to groups 2‐4 (p<0.05). Patients in group 1 presented more frequently systemic manifestations compared to groups 2‐4 (p<0.05). Sjogren Syndrome Activity Index (SSDAI) correlated positively with positive anti‐SSA (r=0.470, p<0.0005). Group 1 showed a higher CSS and a lower BUT, tear meniscus height and area compared to group 2 and 3 (p<0.005). CSNP's length and density were significantly smaller in group 1 compared to group 2 and 3 (p<0.05).

Conclusions

CSNP's density and length, as well as tear meniscus area and height are smaller in advanced pSS compared to pSS with recent diagnostic and SiS‐UCTD. AS‐OCT and IVCM may be useful for risk stratification in SiS.
Preclinical validation of an innovative corneal bioreactor versus organ culture for long term storage: a randomized controled study
Authors: Garcin T. , Forest F. , Verhoeven P. , Pugniet J.L. , Peyragrosse T. , Rogues F. , Herbepin P. , Perrache C. , Acquart S. , He Z. , Gain P. , Thuret G.
Published: September 2017

Purpose

The organ culture (OC) is a passive corneal storage, gold standard in Europe for decades. The bioreactor (BR) is a sterile transparent device that allows active storage: transcorneal pressure gradient and fluid renewal. Aim: To compare quality of human corneas stored for 1 month in our BR versus (vs) OC.

Methods

Randomized controled preclinical study, authorized by the French Biomedicine Agency and an IRB, including only fresh scientific paired human corneas >2000cells/mm2 and <10% difference between both corneas at day (D)2. Immediately at retrieval, one cornea was randomized and stored in OC and the other in BR, both with the same commercial medium (CorneaMax). At D26 only OC corneas were transferred to a deswelling medium (CorneaJet). We calculated that 49 pairs were needed to show a difference of 500 viable cells/mm2 between groups. Assessments were performed at D2, 26, 28. Main criterion: viable ECD (vECD) determined by triple staining Hoechst/Ethidium/Calcein at D28, blind of storage method. Secondary criteria: average transparency (T), central corneal thickness (CCT) and microbiology.

Results

We retrieved 60 pairs, included 52 pairs at D2, analyzed 50 pairs (1 contamination per group). At D2 ECD in BR was 2607±340 vs 2576±357cells/mm2 in OC (p=0.243). At D26 ECD was >2000cells/mm2 for 92% of corneas in BR vs 58% in OC (p<0.001). At D28 vECD was higher in BR 2188±379 vs 1687±389cells/mm2 in OC, with 76% of corneas >2000 viable cells/mm2 in BR vs 22% in OC (p<0.001); T didn't differ and CCT was higher in BR with 684±52 vs 608±53μm in OC (p<0.001).

Conclusions

Restoring IOP and renewing medium significantly improves endothelial cell survival while avoiding deleterious deswelling necessary in OC: after 1 month‐storage, the BR provides much more corneas suitable for transplantation and higher quality grafts that could survive longer in recipients.
Protective effects of sulforaphane on STZ‐induced diabetic retinopathy via activation of Nrf2/HO‐1 antioxidant pathway and inhibition of NADPH oxidase
Authors: He M. , Luan L. , Zhang Y. , Nan Y.
Published: September 2017

Purpose

To investigate the protective effects of sulforaphane, an Nrf2 activator, on streptozotocin (STZ)‐induced diabetic retinopathy.

Methods

8 wk male C57BL/6 mice were intraperitoneally injected with streptozotocin (STZ, 45 mg/kg) for 5 consective days. Animals with fasting blood glucose higher than 13.89 mmol/L were considered diabetes and used for further study. Two weeks after STZ injection, animals were intraperitoneally injected with sulforaphane (12.5 mg/kg) for 8 wks, 3 times per week and retinas were harvested at the tenth‐week. Reactive oxygen species (ROS) in retina were detected by DHE staining. The expression of heme oxygenase‐1 (HO‐1) and Nox2 in retina was detected by Western blotting. Immunofluorescent staining was used to detect the expression of RNA binding protein with multiple splicing (RBPMS)and choline acetyl transferase (ChAT), which could specifically mark the retinal ganglion cells (RGCs) and amacrine cells (ACs), respectively. Acellular capillaries in retina were observed by using periodic acid‐Schiff and hematoxylin staining.

Results

The fasting blood glucose of the mice injected with STZ was increased rapidly, accompanied by significantly decreased body weight. STZ‐injection induced increased ROS generation, increased RGCs and ACs loss, and increased formation of acellular capillaries, which could all be reversed by SF treatment. Meanwhile, HO‐1 and Nox2 expression were increased by STZ‐injection. SF treatment could further enhance STZ‐induced HO‐1 expression, whereas decreased STZ‐induced Nox2 expression.

Conclusions

SF treatment could protect mice retina from STZ‐induced oxidative stress and cellular damage, possibly through the activation of Nrf2 antioxidant pathway and inhibition of Nox2 expression.
OCT‐A based management and treatment of RVO
Authors: Coscas F. , Coscas G. , Souied E.H.
Published: September 2017

Correlations in retinal vein occlusion (RVO) patients between macular vascular densities in the superficial and deep capillary plexuses obtained using OCT‐Angiography (OCTA) and the data from conventional examination (visual acuity and peripheral retinal non perfusion on fluorescein angiography) might reveal new insights in the pathogenesis of vascular damage. Through a retrospective, observational study of RVO patients with who underwent a comprehensive ophthalmic examination including FA and OCTA a significant correlation between automatically quantified macular vascular density on OCTA and peripheral non‐perfusion on FA was demonstrated; OCTA could help in identifying high‐risk RVO patients who may benefit from further evaluation using FA.
ECP ‐ limbal & pars plana techniques
Authors: Bloom P.
Published: September 2017

Cyclo‐photocoagulation is a well‐recognised and powerful therapeutic modality for the reduction of intraocular pressure. Externally applied laser treatment (TransScleral Cyclo‐Photocoagulation, TSCP) may cause collateral destruction of local tissue and can induce considerable inflammation so until recently the use of diode laser cyclo‐photocoagulation was restricted to poorly sighted eyes.

Endoscopically applied diode laser (Endoscopic Cyclo‐Photocoagulation, ECP) is a newer, more controlled, titratable, minimally destructive treatment that treats only the target tissue. One of the first MIGS procedures, ECP allows for a quick and simple additional step to be added to routine cataract surgery (Phaco‐ECP), offering the potential to treat cataract and glaucoma simultaneously.

In addition, ECP is of considerable value in treating cases of advanced, refractory glaucoma; this area will be discussed in detail during this part of the symposium, via both limbal and pars plana approaches. ECP may be used before or instead of drainage device surgery, or afterward to further augment IOP control.
Molecular techniques in ocular pathology
Authors: Moulin A.
Published: September 2017

With the advancement of imaging modalities in ophthalmology encompassing OCT, angio‐OCT, confocal microscopy, high definition MRI, the correct diagnosis can often be reached without a biopsy. In ocular oncology, ocular biopsy remains however crucial not only for the diagnosis, but also to assess the possible response to specific therapy. This course will review the recent development in diagnostic and molecular pathology. It will be based on practical routine examples and clinico‐pathologic correlations of adnexal, orbital, conjunctival and intra‐ocular biopsies.
Novel roles for voltage sensitive ion channels in retinal pigment epithelium and phagocytosis
Authors: Nymark S. , Johansson J. K. , Skottman H. , Ihalainen T.O.
Published: September 2017

Photoreceptors of the retina undergo a daily renewal process where they shed 10% of their outer segment disks that are then digested by the retinal pigment epithelium (RPE). Recent work demonstrated that L‐type calcium channels in RPE are important for the diurnal regulation of this process. We investigated the regulatory role of several ion channels of the RPE in phagocytosis using human embryonic stem cell (hESC)‐derived RPE and freshly isolated mouse tissue. The ion channels were first characterized by patch clamp recordings. The localization of photoreceptor outer segments (POS) and different ion channels during phagocytosis were studied by incubating hESC‐derived RPE with purified POS particles or by dissecting mouse RPE during the physiological peak of POS shedding. Our phagocytosis assays and subsequent immunolabeling showed a promising co‐localization between certain voltage sensitive ion channels, opsin and proteins involved in the phagocytosis pathway. Moreover, blocking the activity of these channels significantly reduced the efficiency of the process. Overall, several types of ion channels appear to be involved in the phagocytosis pathway. Yet, more work is required to assess their specific role.
Vitrectomy with fibrovascular membrane delamination for proliferative diabetic retinopathy with or without preoperative Avastin
Authors: Garnavou‐Xirou C. , Papavasileiou E. , Velissaris S. , McHugh D. , Jackson T.L.
Published: September 2017

Purpose

To describe and compare 1. the changes in intraretinal microstructure using serial spectral domain optical coherence tomography (SD‐OCT) preceding and following pars plana vitrectomy and delamination of fibrovascular membranes and 2. Intraoperative and postoperative complications in patients with proliferative diabetic retinopathy (PDR) who had preoperative Avastin (group A) or not (group B).

Methods

This retrospective, interventional case series includes 113 eyes. Outcome measures included LogMAR distance best‐corrected visual acuity (BCVA), SD‐OCT integrity of photoreceptor inner and outer segments junction (IS/OS), and integrity of external limiting membrane (ELM), intraoperative and postoperative complications.

Results

Pre‐operative central macular thickness (CMT) was significantly correlated with the final post‐operative LogMAR BCVA in group A. Both groups were also categorised into three sub‐groups based on post‐operative IS/OS integrity (group 0: IS/OS intact; group 1: IS/OS irregular but not completely disrupted; group 2: IS/OS completely disrupted). Mean BCVA improved significantly and IS/OS integrity and ELM integrity postoperatively, were significantly and positively correlated with final BCVA in group A. Intraoperative complications such as iatrogenic tears and haemorrhage and postoperative such as vitreous haemorrhage and neovascular glaucoma where significantly less in group A compared to group B.

Conclusions

Pre‐operative Avastin reduces the risk of intraoperative and postoperative complications and results in better postoperative anatomic and functional outcomes in fibrovascular delamination surgery for patients with PDR.
Uveitic macular edema: efficacy and safety of subconjonctival triamcinolone injections
Authors: Vermuso L. , Gueudry J. , Ngo C. , Portmann A. , Muraine M.
Published: September 2017

Purpose

Triamcinolone acetonide is a prolonged‐release corticosteroid with a maximum effect until approximately 3 months. The aim of this work is to evaluate its effectiveness and side‐effects in uveitic macular edema treatment.

Methods

This is a single institution retrospective study. From October 2014 to September 2016, 44 eyes of 44 patients who had subconjunctival triamcinolone acetonide injections for an uveitic macular oedema were included. The main outcome measures were the best corrected visual acuity and the central macular thickness measured in optical coherence tomography (OCT). These parameters were evaluated at baseline, 1 month, 3 months, 6 months and 10 months after first injection. Intraocular pressure, introduction of anti glaucoma medication, and appearance of cataract during follow‐up were also noted

Results

A statistically significant improvement of visual acuity was observed as early as one month, and the benefit continuing up to 10 months. Initial visual acuity was 0.59 ± 0.49 logMAR and 0.35 ± 0.43 logMAR at 10 months. Initial macular central thickness was 460 ±124 μm, it significantly decreased to 333 ±78 μm at 1 month. Macular thickness was rapidly reduced to 1 month, and then seems relatively stable up to 10 months. The mean intraocular pressure at baseline was 14.8 ± 3.6 mmHg and significantly increased at 1 month to 17.6 ± 6 mmHg and to 17.2 ± 4,3 mmHg at 3 months. There were 9 intra ocular hypertension cases (20%) treated with glaucoma medication. No filtration surgery was required. There was one case of cataract but no surgery.

Conclusions

Subconjonctival triamcinolone acetonide injections thus provide a visual acuity gain and a decrease of uveitic macular oedema. They appear to be an alternative to intravitreal and subtenon injections, less invasive and easier to achieve.
Uveal melanoma biopsy or not (pro)
Authors: Shields C.
Published: September 2017

There will be a debate on fine needle aspiration for uveal melanoma cytogenetic testing. Dr. Carol Shields will argue for biopsy. There are several reasons that biospy is important in identifing tumor cell type, genetic profile and understading risks for metastasis. If high risk, systemic therapies can be effective for reducing risk. If low risk, the patient is comfortable with piece of mind. To not do needle biopsy for melanoma is like living in the Dark Ages and never knowing what the future holds. Fine needle aspiration biopsy for uveal melanoma cytogenetic profile is smart medicine.
Suspicious naevi: observe
Authors: Zografos L.
Published: September 2017

Differential diagnosis of large choroidal nevi and small choroidal melanomas may be challenging. The diagnostic approach is guided by various clinical criteria including tumor thickness, presence or absence of subretinal fluid, orange pigment, presence or absence of symptoms, presence or absence of drusen and pin points. In case of doubt, a periodical observation can confirm the correct diagnosis. Taking in account that an irradiation treatment of tumors located close to the macula or the optic disk can produce major irradiation induced complications and visual loss, a carefull periodic observation in selected cases appears as the best diagnostic option.
Nanoparticle delivery for diabetic macular edema
Authors: Stefansson E.
Published: September 2017

Nanotechnology solves the main obstacles in topical drug delivery and delivers drugs by eye drop to posterior segment of the eye.

Cyclodextrin nanoparticles containing dexamethasone increase solubility of dexamethasone in tear fluid 30 fold and the drug stays in tear film for 6 hours compared with minutes for conventional eye drops. The high concentration gradient from tear film into eye wall creates a flux which is active for many hours following eye drop application. This delivers approximately 10 times more drug into the eye and reaches the posterior segment in significant concentration. At the same time relatively less drug is absorbed systemically.

Several clinical trials have demonstrated the efficacy of the cyclodextrin nanoparticle platform both for posterior and anterior segment use. Two clinical trials in 41 patients have shown significant improvement in visual acuity and retinal structure in diabetic macular edema. The clinical effect of the eye drops is similar to that of intravitreal anti‐VEGF injections and steroid implants. Two reports show compelling effect on intermediate/posterior uveitis with cystoid macular edema.

Nanotechnology has broken the age old dogma that eye drops cannot reach the retina.
SOS – Simulated Ocular Surgery website and applications
Authors: Mcnaught A.
Published: September 2017

There is growing interest in simulation training for learning surgery: there are huge benefits to patient safety if trainees can gain essential skills before they attempt surgery on real patients. In ophthalmology, traditional simulation attempts have included practicing simple surgical techniques on animal eyes, or perhaps cadaveric human tissue. These approaches, whilst undoubtedly useful, have some disadvantages e.g inability to practice in a completely realistic surgical environment, which would ideally be the trainee surgeon's own operating theatre, also, cadaveric human tissue, whilst excellent, is expensive to obtain, and store. In the last few years, advances in virtual reality, and plastics technology have stimulated widespread interest in more realistic, and less expensive surgical simulation systems, many of which, especially plastic eyes, allow the surgeon to practice in their own operating theatre, in the office using table‐top binocular microscopes, or even practice at home using loupes. I present our experiences with the ‘Simulated ocular surgery’ (SOS) system, across the full range of ocular surgery, with supporting videos of trainees using this system. For further information: simulatedocularsurgery.com.
Simulation in Mainland Europe – the present and future
Authors: Abegao Pinto L.
Published: September 2017

Surgical training in Europe is very different according to each region. National regulations, different settings and allocated resources allow for a great heterogeneity in surgical opportunities.

The equation of providing adequate training and performance levels to the surgeon while upholding the best possible practices of maximizing patient safety is a difficult task. Throughout Europe, surgeons are increasingly resorting to solutions that allow them to train in simulated scenarios before being confronted with a real life scenario. From wet‐labs to electronic simulations, there is a wide range of solutions that could be adapted to each reality. We will explore these options, its applicability, its advantages and drawbacks, in order to promote a discussion on the validity of each option in each setting.
Biologic therapy: let the Copernican revolution begin!
Authors: Neri P. , Gorgoni F. , Gennari G. , Cesari C.
Published: September 2017

Non‐infectious uveitis can be a potentially sight‐threatening disease. The advent of biologic drugs has represented a Copernican revolution for ocular inflammatory diseases therapies: biologic treatments are a great opportunity for those patients affected by severe, non‐responder, sight threatening uveitis. The availability of such drugs has significantly improved the uveitis outcome. Several publications have reported the efficacy of biologic agents in a progressively larger number of refractory uveitides, suggesting a central role for biologic drugs in selected cases. On the other hand, the medical literature has not provided yet significant numbers and most of the biologic drugs available have been reported in small case series. The anti‐tumor necrosis factor (TNF)‐α is the category with the most consistent medical literature in uveitis and, very recently, Adalimumab has recently obtained the indication for the treatment of non‐infectious posterior, intermediate, pan‐uveitis, representing the first on label biologic agent used in ophthalmology for the therapy of uveal inflammation.
Pediatric tumors of the iris
Authors: Hadjistilianou T.
Published: September 2017

The Author in this report provides an overview of the clinical features and frequency of iris tumors in children. Iris tumors are broadly classified into cystic or solid lesions. Cystic lesions are generally benign. Solid lesions are most often melanocytic. Iris nevus is the most common solid iris tumor in all age groups .

The most common diagnoses in the pediatric group include iris nevus,IPE cyst, iris stromal cyst,juvenile xanthogranuloma,and melanoma. The author report the personal experience and presents rare tumors like melanocytoma,medulloepithelioma and choristoma of the iris.
Update in CHED
Authors: Bremond‐Gignac D.
Published: September 2017

Corneal dystrophies refer to a group of corneal diseases and that are genetically determined. Our understanding of corneal phenotype has improved with improving anterior segment imaging and early genotype‐phenotype correlations. Primary corneal disease includes endothelial dystrophies, corneal dermoids, cornea plana, and kerato‐irido‐lenticular dysgenesis (also known as Peters anomaly, types 1 and 2). Other secondary developmental corneal diseases may include Axenfeld‐Rieger syndrome, Aniridia, and primary congenital glaucoma, with specific genotype. The new molecular information is challenging the traditional thinking that was usually guided by the histopathological findings. Other secondary causes are acquired and include infection, trauma, and metabolic disorders. The new molecular information is challenging the traditional thinking that was usually guided by the histopathological findings. An overview of the innovating diagnosis and treatment are summarized.