bluuebunny/crossref_metadata_2025 huggingface dataset:
Local steroidal treatments: what's new
Authors: Lowder C.
Published: September 2017

Local Steroidal Treatments

Severe vision loss occurs in 25%‐33% of all uveitis cases. Repeated bouts of inflammation increase risk of severe vision loss.

Local Treatment Options

Periocular steroids

Intravitreal steroids

Intravitreal drug delivery

Dexamethasone 700 ug implant (Ozurdex) up to 6 months – short term therapy

Fluocinolone acetonide 0.59 mg implant (Retisert) up to 36 months – long term therapy

Undergoing Clinical Trial

Fluocinolone acetonice 0.19 mg implant (Psivida) up to 36 months – long term therapy

How to choose the appropriate treatment?

If there is systemic disease that requires anti‐inflammatory therapy, maximize immunomodulatory therapy (IMT) rather than treating both locally and systemically for extended periods of time

“Breakthrough” cystoid macular edema in disease otherwise controlled with IMT may benefit from local therapy with Ozurdex, posterior subtenon Kenalog, intravitreal triesence or VEGF inhibition.

Disease that needs short term treatment should not be treated with long lasting implant (fluocinolone acetonide).

Disease likely to need many years of treatment should not be given repeated short lasting implant (dexamethasone) or intravitreal triamcinolone injections.
Red light provides partial protection against retinal ganglion cell degeneration in a mouse model of dominant optic atrophy through the activation of NFkB
Authors: Votruba M. , Beirne K. , Rozanowska M.
Published: September 2017

Purpose

Mutations in OPA1 are the leading cause of dominant optic atrophy, a disease in which a progressive loss of retinal ganglion cells (RGCs) leads to blindness. In the B6;C3‐Opa1Q285STOP mouse, an Opa1 mutation causes a decrease in ATP production and a progressive loss in visual acuity, which coincides with pruning of the predominantly ON‐centre RGC dendrites. Explanting the retina, initiates further dendritic pruning. Red light has been shown to increase ATP production and provide neuroprotection. We hypothesised that 670 nm light can delay ex vivo dendritic pruning in the B6;C3‐Opa1Q285STOP mouse.

Methods

We therefore monitored the effects of 670 nm light (radiant exposure of 26.4 J/cm2) on RGC dendritic pruning in retinal explants from B6;C3‐Opa1Q285STOP mice, after 16 hours ex vivo.

Results

The area under the Sholl curves, the peak of the Sholl curves and the total dendritic length of ON‐center RGCs showed statistically significant reductions by 28% (p<0.05), 27% (p<0.05) and 29% (p<0.05), respectively, from 0 to 16 hours ex vivo, with sham treatment but no statistically significant reductions were seen with 670 nm light treatment. An increase in the nuclear‐cytoplasmic ratio of transcription factor, NfkB, but not Nrf2, was found in the ganglion cell layer with 670 nm light treatment.

Conclusions

The results demonstrate the ability of 670 nm light to partially prevent ex vivo dendropathy in the B6;C3‐Opa1Q285STOP mouse retina, and that the transcription factor NfkB, but not Nrf2, plays a role. The findings suggests that 670 nm light may also delay the RGC dendritic pruning that occurs in vivo in the B6;C3‐Opa1Q285STOP mouse and ultimately provide neuroprotection against RGC degeneration in patients with dominant optic atrophy.
Attitudes of parents toward eye care in children under 7 years old in the Republic of Ireland
Authors: Conway M. , Subramanian A. , O Donoghue E. , Donaldson L.
Published: September 2017

Purpose

Various factors have been highlighted as affecting the uptake of eye care services around the world. We surveyed the parents and guardians of children under seven years old, in the Republic of Ireland, to investigate barriers to and knowledge of eye care. A secondary objective was to determine if either varies according to parent's socioeconomic status, ethnicity or level of education.

Methods

In 2015, one thousand surveys were distributed to the parents of 4 to 6 year old school children in the Republic of Ireland.

Results

446 surveys were completed (44.6% response rate). Chi‐square revealed a significant relationship between ethnicity and how to access eye care X2 (4, n = 437) =27.13, P < 0.001. Analysis of the raw data revealed that the majority of Asian parents, 6 out of 7 respondents (86%), did not know how to access eye care appropriate for their child's age. Thirty percent of parents/carers (n = 134) reported having at least one barrier to accessing eye care. Respondents were assigned a ‘barrier score’‐ zero barriers to a maximum of 10 reported barriers. A Mann‐Whitney U test disclosed that parents from lower income families n = 84 (19%) had significantly higher number of barriers to eye care (U = 12273, P = 0.002) than those from higher income households n = 356 (81%). Each respondent was assigned a ‘children's eye care knowledge score’. The maximum knowledge score was 5 and the minimum 0. Kruskal Wallis X2 (2, n = 438) =11.34, P = 0.003 revealed a significant relationship between knowledge of eye care and level of parental education. Inspection of the mean rank of groups suggest that those with higher levels of education n = 314 (77%) had the highest eye care knowledge score.

Conclusions

This research has shown that there are significant barriers to eye care in the Republic of Ireland which need to be addressed when designing future eye care pathways.
Schlemm canal stenting
Authors: KERR N.
Published: September 2017

In primary open‐angle glaucoma, the juxtacanalicular trabecular meshwork and inner wall of Schlemm canal are believed to be the site of greatest resistance to aqueous outflow. Recently several new minimally invasive devices have been developed to bypass this tissue and provide direct access to low resistance collector channels in the outer wall of Schlemm canal. These devices are inserted via an ab interno approach, usually at the time of cataract surgery, and are designed to lower intraocular pressure and reduce or eliminate the need for glaucoma medications. This Special Interest Symposium reviews the growing evidence base and covers techniques and pearls for the insertion of both the iStent and iStent Inject (Glaukos Corporation, Laguna Hills, CA, USA) as well as the Hydrus intracanalicular scaffold (Ivantis Inc., Irvine, CA, USA).
What to look for? Monitoring guidelines
Authors: Angi M.
Published: September 2017

Molecularly targeted agents are commonly used in oncology practice, and many new targeted agents are currently being tested in clinical trials. As many of the molecules targeted by anticancer agents are also expressed in ocular tissues, a wide spectrum of ophthalmologic toxicities has been reported, ranging from conjunctivitis and keratitis to sight‐threatening conditions such as retinal vein occlusion and optic neuritis. It is important for the Ophthalmologist to be aware of the adverse ocular events that have been reported for different drug types, in particular tyrosine kinase inhibitors and anti‐cytotoxic T‐cell lymphocyte antigen‐4 antibodies, as they may require dose reduction or interruption. A full ophthalmologic examination is recommended, including visual acuity, tonometry, and fundoscopy. For agents with the potential to cause retinal adverse effects, optical coherence tomography, retinography and visual field examination should also be considered. For agents with the potential to induce anterior segment pathology, a slit lamp examination with fluorescein staining and Schirmer test should be routinely performed.
Herpes and Zoster infections update
Authors: Labetoulle M.
Published: September 2017

Herpes Simplex Virus (HSV) and Varicella‐zoster Virus (VZV) are two leading causes of sight‐threatening keratitis. Following a period of latent infection in the trigeminal ganglia, the virus can reactivate, and new viral particles finally reach the ocular tissues.

Episodes of HSV keratitis may occur spontaneously or following a triggering factor like immunosuppression (including topical steroids), topical inflammation and nerve injuries. Ocular surgery, which combines several of these factors, is a strong risk factor of HSV keratitis recurrence. In case of exposure to one of these triggering factors, prevention with oral antiviral drugs reduces the risk of relapse of HSV keratitis. To date, there is no vaccine against HSV that has proved its clinical relevance.

For VZV, the main risk factor of keratitis is the occurrence of chickenpox or herpes zoster ophthalmicus (HZO) some days to weeks before. The prescription of oral antiviral drugs at the time of cutaneous rash is efficient for reducing the risk of ocular complications of HZO. However, the most efficient way to prevent VZV‐keratitis is probably to reduce the risk of chickenpox and eventually herpes zoster, by the mean of the existing vaccines dedicated to these both diseases.
Principles of wound healing – knowledge transfer to cornea
Authors: Järvinen T.
Published: September 2017

The closure of both corneal and skin wounds occurs when epithelial cells migrate from the edge of the wound and re‐epithelialize the injured area. Syndecan‐4 (SDC4) is a heparin sulfate proteoglycan (HSPG). A natural cell migration‐pathway triggered by SDC4 has been identified and proven to contribute to skin wound closure (Bass et al., Dev. Cell 2011). We have previously identified a wound‐homing peptide (CARSKNKDC; dubbed CAR; Järvinen & Ruoslahti, Am. J. Pathol. 2007) that requires HSPGs for its cell‐binding and penetrating activity. CAR peptide stimulates wound re‐epithelialization and its cell binding and internalization are both dependent on SDC4. Its wound healing‐promoting activity (stimulation of re‐epithelialization) is dependent on SDC4. Thus, CAR peptide subverts normal SDC4 function to promote wound healing by enhanced re‐epithelialization. CAR peptide may provide a new way of enhancing skin wound healing, and perhaps tissue regeneration in general. This therapeutic approach is dependent on the naturally occurring SDC4 dependent cell migratory pathway, which is up‐regulated in skin wounds. Whether the SDC4 ‐cell migratory pathway is available in corneal wound healing remains to be studied and could be therapeutic.
Choosing your fellowship and getting the most out of it ‐ advice from Fellows
Authors: Lukic M.
Published: September 2017

The aim of this lecture is to present young ophthalmologists the process of getting fellowship at Moorfields Eye Hospital in London, UK. The presentation will contain important facts and advice for application process, interview and opportunities when someone become a fellow. Likewise, it will be mentioned the procedure and requirements to get GMC registration and licence to practice which is mandatory to be able to apply for any fellowship in the UK and eventually to work in the UK as a medical doctor. Then, I will show the recent audit results about fellows’ opinion on MR fellowship at Moorfields Eye Hospital and show a few testimonials from my colleagues fellows. Lastly, I would like to give some additional information about finding out the accommodation and general costs of living in London which is important before someone decides to move in to London.
Segregation of novel p.(Ser270Tyr) MAF mutation and p.(Tyr56*) CRYGD variant in a family with dominantly inherited congenital cataracts
Authors: Liskova P. , Dudakova L. , Stranecky V. , Hlavova E. , Vincent A.
Published: September 2017

Purpose

To identify the molecular genetic cause in a three generation family with the occurrence of congenital cataracts, variably associated with iris colobomata and microcornea.

Methods

Whole‐exome sequencing was performed in three affected family members, one unaffected first degree relative, and one spouse. Sequence variants previously reported as disease‐causing, and novel sequence variants within genes listed in CatMap (http://cat-map.wustl.edu/) were given a priority for further evaluation. Verification of possibly pathogenic sequence variants was performed by conventional Sanger sequencing.

Results

Sequence variant c.168C>G; p.(Tyr56*) in CRYGD, previously reported as pathogenic, and a novel mutation c.809C>A; p.(Ser270Tyr) in MAF, were identified in two affected family members; the grandmother, and half‐brother of the proband. The proband inherited only the MAF mutation, whereas her clinically unaffected sister had the CRYGD change. In silico analysis supported a pathogenic role of p.(Ser270Tyr) in MAF, which was absent from publicly available whole‐exome datasets, and 1,161 Czech individuals. The frequency of CRYGD p.(Tyr56*) in the ExAC dataset was higher than the estimated incidence of congenital cataract in the general population.

Conclusions

Our study highlights that patients with genetically heterogeneous conditions may exhibit rare variants in more than one disease‐associated gene, warranting caution with data interpretation, and supporting parallel screening of all genes known to harbour pathogenic mutations for a given phenotype. The pathogenicity of sequence variants previously reported as cataract‐causing may require re‐assessment in light of recently released datasets of human genomic variation.

Supported by AZV 17‐30500A.
Tips and tricks in pediatric retina surgery
Authors: Ozdek S.O.
Published: September 2017

Pediatric vitreoretinal surgery has a different philosophy from adult surgery. It has its own rules, own complications, does not forgive faults, does not accept apologies. The eye is very small, there is a narrow space for maneuvers (15‐19mm). Lens is relatively large, vitreous‐retina relation is different, pars plana has not developed, sclera is thin and elastic. Posterior hyaloid is tightly attached. PFCL and Silicon oil is rarely used. They do not obey the head positioning! Retinal breaks usually ends up with surgical failure. PVR is frequent and severe! There is an additional amblyopia problem. We will talk about the details of these problems and the solution of them in ROP, PFV, Coats and FEVR cases.
Inflammatory markers but not symptoms are a strong predictor of temporal artery biopsy outcome – the Portsmouth experience
Authors: Meredith P.R. , Sepetis A. , Balendra S. , Jawed M. , Lockwood A.J. , Maclean H.
Published: September 2017

Purpose

To investigate the correlation of biopsy proven temporal arteritis with clinical symptoms and inflammatory markers.

Methods

Retrospective study of all patients (n = 89) referred for temporal artery biopsy (TAB) over a 30‐month period. Ten patients were excluded due to inconclusive biopsy or insufficient data. Correlation of presenting symptom (localised headache LH, jaw claudication JC, pain over temporal artery PTA, constitutional symptoms CS) and inflammatory marker level (ESR, CRP) with histological outcome (presence of giant cells) were assessed using a two‐tailed unpaired t‐test.

Results

50 cases had a negative (−ve) biopsy result and 29 positive (+ve). Mean age (SD) for each group was 71 yrs (10) and 77 yrs (6) respectively. No significant correlation was found between presenting symptom and biopsy result (−ve:+ve LH 88%:79%, PTA 46%:62%, CS 40%:59%) except for jaw claudication (36%:62%, p < 0.05). Inflammatory marker result was found to significantly correlate with biopsy outcome. Mean ESR (SD) was 23 (21) in the −ve and 34 (24) in the +ve (p < 0.05) and mean CRP (SD) was 33 (40) in the −ve and 98 (81) in the +ve group, (p < 0.001). Mean ESR+CRP (SD) was 55 (52) in the −ve and 132 (87) in the +ve (p < 0.0001). There were no significant differences in duration of steroid treatment prior to TAB or time to TAB between the two groups. One patient had normal ESR and CRP with a positive biopsy result.Treatment with steroids was continued for 48% of patients with −ve biopsy on clinical grounds.

Conclusions

Elevated ESR and CRP are strongly predictive of positive TAB outcome. Combining ESR+CRP increases the significance of the correlation. Further studies with larger patient numbers may identify an appropriate cut‐off level which, combined with age and clinical features, may provide a clinical score to aid decision making regarding which patients require TAB.
Submacular hemorrhage management
Authors: Pournaras C.
Published: September 2017

Submacular haemorrhage (SMH) is a sight threatening complication that can occur in exudative age related macular degeneration (AMD). Left untreated, SMH carries a grave visual prognosis. Diagnosis and effective management of this complication are important.

The treatment strategies for SMH include displacement of blood from the fovea, usually by injection of an expansile gas, pharmacologic clot lysis such as with recombinant tissue plasminogen activator (rtPA) and treatment of the underlying choroidal neovascularization (CNV), such as with antivascular endothelial growth factor (anti‐VEGF) agents. These three strategies have been employed in isolation or in combination, some concurrently and others in stages.

In cases presenting early, pneumatic displacement alone with anti‐VEGF may be sufficient. rtPA has demonstrable effect on the liquefaction of submacular clots but there are remaining uncertainties with regards to the dose, safety and the timing of initial treatment. Potential side effects of rtPA include pigment epithelial toxicity, increased risk of vitreous haemorrhage and systemic toxicity. Anti‐VEGF monotherapy is a treatment option particularly in patients with thinner SMH and those who are unable to posture.
Comparing anterior segment optical coherence tomography and ultrasound biomicroscopy with histopathology in measurement of corneal and bulbar conjunctival tumors depth
Authors: Lauwers N. , Janssens K. , Mertens M. , Mathysen D. , De Keizer R.J.W. , De Groot V.
Published: September 2017

Purpose

Corneal and bulbar conjunctival tumors can be visualized and measured by Anterior Segment Optical Coherence Tomography (A‐OCT) and Ultrasound Biomicroscopy (UBM). We compared tumor depth measured by histopathology (HP) with measurements by UBM and A‐OCT to investigate whether the two techniques are as accurate as HP.

Methods

35 patients with 42 corneal or conjunctival bulbar tumors were imaged with A‐OCT and UBM. 11 of the tumors were excised and analyzed on histopathology. The correlation of the depth measurements on HP versus A‐OCT and UBM was statistically analyzed. When the tumor was not excised, depth measurements on A‐OCT versus UBM were compared.

Results

Statistical analysis showed that UBM and HP measurements of tumor depth are positively correlated, as are UBM and A‐OCT measurements. It was not possible to obtain statistically significant data for the correlation between HP and A‐OCT measurements because of the small study population. Image quality was overall better with A‐OCT than with UBM, but in 12 tumors, depth measurement on A‐OCT was impossible because of tumor shadowing (thick or highly pigmented tumor).

Conclusions

UBM can measure tumor depth as accurately as HP. Tumor depth measurements on A‐OCT and UBM are positively correlated. A larger study is needed to investigate whether measurement of tumor depth with A‐OCT is as accurate as HP. Because of drawbacks of depth measurements on histopathology, we believe that A‐OCT and UBM could become the golden standard for measuring corneal and bulbar conjunctival tumor depth. We advise to use A‐OCT if the tumor is not too thick or too pigmented, and to use UBM in case of posterior tumor shadowing on OCT.
Role of GSK3 activity in optic nerve regeneration
Authors: Fischer D.
Published: September 2017

Retinal ganglion cells (RGCs) do not normally regenerate axons upon optic nerve injury. However, inflammatory stimulation (IS) significantly enables axon growth in the injured optic nerve. Here, we demonstrate that optic nerve crush strongly induces inhibitory phosphorylation of GSK3α and GSK3β in RGCs. To investigate the role of GSK3 in this context we tested IS induced regeneration and neuroprotection in conditional GSK3α and GSK3β knockout mice (GSK3α‐/‐, GSK3β‐/‐) as well as GSK3αS/A and GSK3βS/A mice expressing resistant GSK3 isoforms to this inhibitory phosphorylation. In contrast to GSK3α‐/‐, GSK3β‐/‐ markedly potentiated IS induced optic nerve regeneration. On the contrary, IS mediated regeneration was significantly reduced in GSK3S/A mice. These findings suggest that active GSK3 intrinsically limits the outcome of CNS axon regeneration. Thus, treatments activating the intrinsic growth state combined with GSK3β inhibition might be suitable to further improve the regenerative outcome after CNS injury.
Optic nerve sheath tumors
Authors: Kawasaki A.
Published: September 2017

Various neoplasms may originate from or secondarilry involve the meninges surrounding the optic nerve. This course will examine the more common of such neoplasms and review the clinical manifestations as well as management.
Contact lens and ocular surface ‐ After all, its still a foreign body
Authors: Knop E.
Published: September 2017

Contact lenses, as indicated by the name, are in direct contact with the ocular surface. CL are swimming within the tear film, between eye ball & palpebral conjunctiva ‐ in the middle of the Ocular Surface Unit. Interactions thus have direct impact on tear film & tissues with the risk of potential side effects (for details please see: WWW.OSCB‐BERLIN.ORG).

One main impact is increased mechanical friction by the ′additional structure′. Friction increases during eye movements and blinks when the lid border moves over the contact lens rim and along its anterior lens surface. Limited diffusion of nutritients can occur through the lens, particularly the supply with oxygen is critical for the cornea that depends on gas diffusion – Modern materials have meanwhile decreased this risk. Chemical impacts occur by the lens material or by solutions for lens cleaning & storing.
How to deal with Keratokonus – are there Contact Lens Related Problems in Sclerals?
Authors: NAU C. , Shorter E. , Nau A. , Harthan J. , Fogt J. , Schornack M.
Published: September 2017

Scleral lenses have become a popular early treatment choice for patients with keratoconus. In a recent SCOPE (Scleral Lenses in Current Ophthalmic Practice: an Evaluation) study group finding, 34% of practitioners, of 629 survey respondents, chose scleral lenses as their first treatment option for patients with corneal irregularity. Among all treatment choices for corneal irregularity, scleral lenses ranked second only to corneal rigid gas permeable lenses, from those responding. The SCOPE study group then polled a group of keratoconus patients wearing scleral lenses. Of 79 keratoconus patients reporting scleral lens wear in both eyes, 85% were somewhat or very satisfied with their vision. However, these patients also reported experiencing cloudy vision (59%), lens discomfort (67%), and difficulty with lens handling (63%) at some time over the previous two years.
Optical properties shape visual cortical population receptive fields after cataract surgery independently from subjective quality of vision
Authors: Rosa A. , Miranda Â. , Miguel P. , Harvey B.M. , Silva F. , Castelo‐Branco M.
Published: September 2017

Purpose

To study the impact of changed optical properties on cortical population receptive fields (pRF), psychophysical function and participant reported quality of vision after cataract surgery.

Methods

We studied 30 patients after recent bilateral sequential cataract surgery, using functional magnetic resonance imaging and pRF modelling methods to assess pRF sizes across early visual regions. Ophthalmological and psychophysical evaluation was also performed, and a quality of vision questionnaire was obtained.

Results

We found that subjects with worse optical properties had larger pRF sizes. pRF sizes in the primary visual cortex were also larger for operated subjects with worse contrast sensitivity (p = 0.038). Surprisingly, patients who were more bothered by dysphotic symptoms showed lower pRF size fitting interception (p = 0.012) and pRF size fitting slopes (p = 0.020), showing that objective and subjective quality of vision may dissociate.

Conclusions

Optical properties of the eye influence PRF sizes and both dissociate from subjective quality of vision, suggesting that patients with better cortical resolution may have augmented dysphotic perception, and consequently more visual complaints, in spite of improved optical quality.
“Inflammaging” in the zebrafish visual system
Authors: Moons L. , Bollaerts I. , Van houcke J. , Vanhunsel S. , Beckers A. , Lemmens K. , De Groef L.
Published: September 2017

Appropriate modulation of neuroinflammation upon central nervous system (CNS) damage is known to trigger a regenerative response, but the underlying cellular and molecular mechanisms remain elusive. Zebrafish possess high regenerative abilities, yet, also gradually age. They are ideally suited to study the contribution of neuroinflammation to successful regeneration, also in an aging context.

First, we followed the inflammatory response in fish subjected to optic nerve crush (ONC) and revealed a timed induction and resolution of microglia/macrophage (Mi/MΦ) activation. Next, both immunostimulatory/suppressive paradigms indicated that, as in mammals, axon regeneration is stimulated by an induced inflammatory response. Studies addressing Mi/MΦ activation and polarization state will provide further insights. In a second approach, we investigated whether an aged cellular environment affects neuronal survival/axonal regeneration. Detailed analyses in aged fish revealed altered numbers and distributions of Mi/MΦ, indicative of ‘inflammaging’, as well as a significant delay in axon outgrowth after ONC. Ongoing studies suggest phenotypic changes of senescent Mi/MΦ underlie this decelerated regeneration capacity in the aged zebrafish CNS.
The eye according to Byzantines medical writers
Authors: Trompoukis C.
Published: September 2017

The scientific foundation of ophthalmology as a medical specialty can be located in the Alexandrine period, since it is there we find evidence of diagnosis and therapy in the systematic knowledge of the eye. Many of the documents from that period have been lost, but the knowledge was preserved in the writings of Galen (129‐216 AD) and his successors. Byzantine medicine (324‐1453 AD) preserved ancient medical knowledge and transferred it either directly, or via an Arabic translation, into Latin. This was the natural connection between antiquity and the Renaissance, one that has been greatly appreciated in studies of the history of medicine. This study presents a detailed analysis of early Byzantine medical sources and the ancient medical tradition upon which they drew. There follows a discussion of knowledge relating to the eye, its clinical description, diagnosis and treatment.
The role of the Shh signaling pathway in radio‐induced cataractogenesis
Authors: De Stefano I. , Giardullo P. , Tanno B. , Leonardi S. , Pasquali E. , Babini G. , Saran A. , Mancuso M.T.
Published: September 2017

Besides the well‐known role in cancer, Shh signaling pathway direct cell proliferation, cell fate determination and EMT, remaining largely expressed in the stem cell compartment of adult tissues. Recently, we proposed Ptch1+/‐ mice as a relevant radiation‐induced cataract mouse model. These mice, develop cataract with a very high incidence (45.2%) and short latency after irradiation with 3 Gy of x‐rays, when radiation is delivered during the early stage of postnatal lens development. Molecular analyses suggest that Shh and TGF‐ß signaling cooperate to promote Ptch1‐associated cataract development by activating EMT and converging on Nanog. Furthermore, using a range of decreasing radiation doses to assess the cataract response in these mice, nonlinear biological responses were observed using doses ≤ 1 Gy, with a suggestion for borderline effects at 2 Gy, both for gross cataract development and for activation of the genetic pathways involved in the molecular pathogenesis of Shh‐associated cataract.

These findings highlight a novel function of Shh signaling unrelated to cancer and provide a new animal model to investigate the molecular pathogenesis of cataract formation.
Surgical management of diabetic macular edema – For
Authors: Pournaras J.A.
Published: September 2017

Diabetic retinopathy may require surgical management in case of vitreomacular interface disorders. Indications and prognostic factors will be discussed.Furthermore, after many anti‐VEGF without any reduction of diffuse macular edema, surgical approach may be proposed. In histopathological analysis, myofibroblasts have been detected and cause the contraction of vitreoretinal interface disorders affecting visual acuity. Removal of epiretinal membrane associated with ILM peeling is essential in these cases in order to eliminate the contractile elements.
Qualitative early signs of microglial activation in mice retinas contralateral to experimental glaucoma
Authors: Ramirez J.M. , Salobrar‐Garcia E. , Ajoy D. , Gonzalez‐Martin R. , de Hoz R. , Salazar J.J. , Rojas B. , Triviño A. , Ramirez A.I.
Published: September 2017

Purpose

To analyze qualitative retinal microglia signs of activation after 24 h of unilateral laser‐induced ocular hypertension (OHT) in OHT‐eyes and their contralateral eyes.

Methods

Albino Swiss mice were divided into two groups, naïve (n=6) and lasered (n=9). Retinal whole mounts were immunolabeled with antibodies against Iba‐ 1 and MHC‐II.

Results

Both in OHT eyes and in contralateral eyes Iba‐1+ cells: i)had morphological signs of activation, being these more intense in OHT eyes than in the contralateral eyes. Iba‐1+cells showed hypertrophy, soma displacement both in their own retinal layer and towards the nearest one and in some instances, reoriented microglial processes from being parallel to being perpendicular to the retinal surface. ii) were dystrophic in some instances in the photoreceptor layer (PRL); iii) in the outer plexiform layer sent processes to the PRL and this was mainly found in contralateral eyes; iv) overall, did not up‐regulate the expression of MHCII .

Only in OHT eyes MHCII+ rounded cells were observed in the nerve fiber layer‐ganglion cell layer, being more numerous in the peripheral superior zone of the retina and near the optic disc. These cells were surrounded and phagocyted by numerous ameboid Iba‐1+ cells. In addition, beneath the retinal areas where this event was occurring, microglial cells of the inner plexiform layer and outer plexiform layer oriented their processes towards those areas and surrounding them.

Conclusions

At 24 h after unilateral OHT, microglial features of activation were observed not only in OHT eyes but, interestingly, also in the contralateral untreated eyes. Whether this activation favors neuroprotection or neurodegeneration needs to be clarify.
Application of OCT in diagnosis and treatment of keratoconus patients
Authors: Wylegala E. , Dobrowolski D. , Wylegala A.
Published: September 2017

OCT optical coherence tomography is a noninvasive imaging modality. Morphological and morphometric data can be obtain using this technique. Cross‐linking is a method commonly used in reducing the progression of keratoconus and severe infectious diseases of the cornea. OCT can be useful in qualification patients for cross‐linking, during surgery and in the management of patients after cross‐linking. Different OCT systems (time‐domain, spectral domain and swept source) will be presented on the basis of clinical examples.
Crosslinking and corneal biomechanics
Authors: Fuchsluger T. , Brettl S. , Geerling G. , Philipp F.Z.
Published: September 2017

This presentation will demonstrate data on corneal biomechanics measured with the CORVIS ST (Oculus GmbH, Wetzlar, Germany) to evaluate normal corneas, non‐crosslinked and crosslinked corneas. Characteristics of biomechanical parameters are explained.
Preliminary results: Comprehensive national retinoblastoma cohort in Finland ‐ RB1 mutation spectrum
Authors: Nummi K. , Kivelä T.
Published: September 2017

Purpose

Retinoblastoma (Rb), a malignancy of developing retina, emerges almost always after biallelic mutation and inactivation of tumor suppressor gene RB1. In heritable Rb, a child carries germline RB1 mutation. Identifying this will help in future risk management and family planning. Recently, we have made an effort to create a comprehensive national register for Rb. DNA sequencing for mutations in RB1 is being offered to every patient not previously tested and the results are included in the register.

Methods

Of the 226 Rb patients registered in the Finnish Retinoblastoma Register until January 2016, 72 have so far underwent germline DNA testing and 40 patients from 32 unrelated families tested positive for mutation. RB1 mutation detection methods varied depending on the time period. Mutations were checked for pathogenicity from the Leiden Open Variation Database (http://rb1-lsdb.d-lohmann.de).

Results

RB1 mutations comprised 90% of heritable (bilateral, familial or both) Rb and 10% were sporadic unilateral tumors (unifocal or too advanced to assess focality). The distribution of mutation types was 46% nonsense, 15% frameshift, 15% splice site, 3% large indel, 8% missense, 13% chromosomal deletions and none promoter. Two novel mutations (c.1A>C and c.2042_2203+?del) were detected. Five mutations (13%) had been reported only once and nine mutations (23%) three times or less.

Conclusions

The frequencies of the type of mutation in the RB1 gene in the preliminary results of our national cohort expectedly follow the mutation spectrum described worldwide.
Adult orbital precursor B‐lymphoblastic lymphoma with involvement of the extraocular muscles
Authors: Mikkelsen L.H. , Ejstrup R. , Clasen‐Linde E. , Andersen M.K. , Gjerdrum M.L.R. , Heegaard S.
Published: September 2017

Purpose

To report a very rare case of a precursor‐B Lymphoblastic lymphoma (pre‐B‐LBL) with periocular muscle involvement in an adult. The clinical, histopathological, and genetic findings will be reported.

Methods

Case report, Immunohistochemistry, FISH, and ArrayCGH.

Results

A 56‐year‐old male experienced sudden onset of left sided ptosis and diplopia. Pain was not prominent. The patient had complete remission of an abdominal pre‐B‐LBL. On examination, proptosis and a left sided third cranial nerve palsy was found. After a few days, mydriasis without rapid afferent pupillary defect developed. MRI showed thickening of the medial and inferior rectus muscles. A biopsy of the inferior rectus muscle was obtained for histopathological examination. Histologically, an infiltrate of immature lymphocytic tumour cells was seen within the orbital skeletal muscle tissue. The tumour cells were small and presented with fine blastic nuclear chromatin along with small peripheral nucleoli. The tumour cells stained positively for CD10, CD79a, PAX5, and BCL‐2. The Ki‐67 proliferation index was 90%. These findings were consistent with a TdT‐negative pre‐B‐LBL relapse. FISH was negative for BCR/ABL, MLL‐rearrangement, and ETV‐6‐break. ArrayCGH was performed. A bone marrow biopsy confirmed systemic involvement. The patient was immediately started on NOPHO High Risk chemotherapy, followed by orbital radiation and awaits allogeneic bone marrow transplantation. The patient has no light perception in his left eye.

Conclusions

This is the first reported case of a very rare rapid growing orbital pre‐B‐LBL in an adult.
Method for assessing the impact of residual roughness after corneal ablation in perception and vision
Authors: Verma S. , Hesser J. , Arba‐Mosquera S.
Published: September 2017

Purpose

Despite theoretical models for achieving laser‐based ablation smoothness (Invest Ophthalmol Vis Sci. 2017;58:2021–2037), methods do not yet exist for assessing the impact of the residual roughness after corneal ablation, in perception and vision. As solution, we propose a method to convert wavefront aberrations with associated roughness, to a visual point spread function (PSF), to calculate the polychromatic retinal image.

Methods

Using SCILAB (Scilab Enterprises, Versailles, France) patient‐specific Zernike expansion coefficients and Pupil diameter were used to calculate the wavefront including chromatic compensation for the Red, Green and Blue channels (Optom Vis Sci 2003;80:6–14). Random noise was added to the calculated wavefront to simulate roughness in the cornea after laser ablation, within user‐defined limits. PSF of the eye was calculated for Red, Green and Blue channels and the retinal image was determined, as weighted combination of different color channels. Several corneal roughness conditions were compared in terms of the calculated perceived image quality based on metrics like Michelson Contrast, Weber Contrast and Modulation Transfer Function.

Results

For a constant roughness term, reducing the pupil size resulted in sharpening the PSF and perceived retinal image. The impact of varying roughness in ablation could be quantified through the calculated image quality metrics, deteriorating dramatically with increasing roughness.

Conclusions

The proposed model can be used for quantifying the impact of residual roughness in corneal ablation processes at relatively low cost. This method can help compare different refractive laser platforms in terms of their associated roughness in ablation, indirectly improving the quality of results after Laser vision correction surgery.
In vivo evaluation of voriconazole eye drops efficacy in a rat Acanthamoeba polyphaga keratitis model
Authors: Gueudry J. , Le Goff L. , Compagnon P. , Lefevre S. , Camille A. , Duval F. , Francois A. , Razakandrainibe R. , Favennec L. , Muraine M.
Published: September 2017

Purpose

Acanthamoeba keratitis is a sight‐threatening infectious disease. Its effective and safe medical therapy remains highly debated. The aim of this study is to test in vitro and in vivo voriconazole as a potential antiamoebic treatment for Acanthamoeba keratitis.

Methods

In vitro sensitivity of Acanthamoeba polyphaga to voriconazole was assessed using a commercially available viability assay. In vivo, Sprague‐Dawley male rats were injected in the left cornea stromal layer with trophozoites. Forty rats were divided into 3 groups, topically treated with 1% voriconazole eyedrop (hourly administrations for 3 days followed by every two hours for 11 days and followed every four hours for 7 days), orally treated with voriconazole (60 mg/kg/day), and control. At day 28, cornea and blood samples were collected and corneal scrapings were performed for bacterial and parasitological cultures and real‐time PCR analyses. Paraffin‐embedded corneas were analyzed. The plasma and corneal concentration of voriconazole was determined by high‐performance liquid chromatography.

Results

In vitro, voriconazole inhibited Acanthamoeba polyphaga trophozoites proliferation with IC90 value of 6 μg/ml, however no cystical activity was found. Mean intracorneal concentration of voriconazole eyedrops after three days treatment was 5.6 +/‐ 4.4 ng / mg; after seven days treatment was 2.38 + /1.6 ng/mg; and after twenty one days treatment was 0.32 +/‐ 0.15 ng / mg. Clinical infection worsened in fewer rats between the 7th and the14th day post infection in the voriconazole eye drops group (1/10 rats) and the control group (9/10 rats) (p = 0.001).

Conclusions

Our findings support the potential use of voriconazole as anti‐amoebic agents.
Prevalence of refractive errors and visual impairment in university students
Authors: Yekta A.A. , Hashemi H. , Khabazkhoob M. , Ali S.B. , Ostadimoghaddam H. , Heravian J. , Azimi A. , Momeni‐Moghaddam H.
Published: September 2017

Purpose

To determine the prevalence of refractive errors and visual impairment in a population of university students in Kazerun, south of Iran

Methods

Using multi‐stage sampling in all universities located in Kazerun, a number of university majors were selected as clusters. Then, proportional to the size, a number of students in each major were randomly selected to participate in the study. All participants underwent the measurement of visual acuity, non‐cycloplegic and subjective refraction, and corrected visual acuity. A spherical equivalent equal to or worse than −0.5 D and + 0.5 D was considered myopia and hyperopia, respectively. Astigmatism was defined as a cylinder power worse than −0.5 D. Visual impairment was defined as visual acuity worse than 20/60 in the better eye.

Results

Of 1595 students that were invited, 1462 participated in the study (response rate = 91.66%). The prevalence of visual impairment was 2.19% (95% CI: 1.48–3.23), of whom 1.92% (95% CI: 1.27–2.88) had low vision and 0.27% (95% CI: 0.12–0.62) were blind. Refractive errors comprised 75% of the causes of visual impairment. The prevalence (95% CI) of myopia, hyperopia and astigmatism was 42.71% (39.71–45.77), 3.75% (2.85–4.51) and 29.46% (27.50–31.50), respectively. Totally, 49.03% (95% CI: 46.39–51.68) of the participants had at least one refractive error. Myopia and hyperopia were not correlated with age and gender. The odds of astigmatism in participants aged 26–27 years (OR = 1.64; 95% CI: 1.03–2.61) was higher than subjects aged 18–19 years.

Conclusions

The prevalence of refractive errors, especially myopia is low in university students. Since refractive errors constitute a major part of visual impairment, university students should receive optical services to reduce their burden.
Clinical and genetic study of a new mutation in the choroidoremia gene
Authors: Idoate A. , Sanchez Marín J.I. , Bartolome Sese I. , Berniolles Alcalde J. , Lopez Sangros I. , Marco Monzon S. , Ascaso Puyuelo J. , Pinilla Lozano I. , Ibañez Alperte J.
Published: September 2017

Purpose

To describe retinal findings as well as spectral domain OCT and fundus autofluorescence in a new genetic mutation in a choroidoremia family.

Methods

An 11 year old boy was diagnosed with choroidoremia by his fundus changes. In his mother′s family there was another cousin with the same symptoms and his grandfather and great grandfather had an impaired vision. The family was studied.

Results

The boy has a reduced visual acuity of 20/40 in both eyes with ‐6D, reduced sensibility in his perimetry, and important retinal pigment changes in his fundus. SD‐OCT findings include changes in the external hyperreflective layers and hypofluorescence and hyperfluorescence changes in his fundus autofluorescence. His mother showed a normal OCT with hypofluorescence changes. His cousin, who was 13 years old, showed similar changes with a 20/20 vision and no myopic defect. The boys were hemizygous for a novel mutation c.1083_1084dupT of the CHM gene. The mutation was confirmed in heterozygosity in both carriers. The sister was not affected.

Conclusions

Clinical diagnosis and molecular analysis showed the new mutation leading to loss of function of the REP‐1 protein. Autofluorescence changes were presented in both patients and carriers. Myopia could increases the visual loss and pigment changes in choroidoremia.
Dexamethasone intravitreal implant combined with anti‐VEGF in patients with neovascular age related macular degeneration resistant to anti‐VEGF alone
Authors: Damico Ricci G. , Giancipoli E. , Boscia F. , Zasa G. , Sotgiu G. , Dore G. , Pinna A.
Published: September 2017

Purpose

To evaluate the efficacy and safety of a single intravitreal Dexamethasone implant (DXI) combined with anti‐vascular endothelial growth factor (anti‐VEGF) therapy, in patients with neovascular age related macular degeneration (wet‐AMD) resistant to the conventional treatment.

Methods

In this prospective, randomized, controlled pilot study 16 eyes of 15 patients, unresponsive to previous anti‐VEGF therapy, were enrolled. Patients were randomly assigned to three groups: DXI + Pro Re Nata (PRN) anti‐VEGF, DXI + monthly anti‐VEGF, and monthly anti‐VEGF alone. Each patient was treated at baseline, according to the assigned treatment, and followed up to 180 days. Primary outcomes were: complete regression of retinal fluid and best corrected visual acuity (BCVA) change. Secondary outcomes were: safety of the treatment, the change of median central foveal thickness (CFT) and macular volume. Correlations between anatomical features and visual function were also assessed.

Results

Eyes distribution was: 5 in DXI + anti VEGF PRN; 6 in DXI + monthly anti‐VEGF (treatment group), and 5 in monthly anti‐VEGF. BCVA showed no significant change from baseline in both the treatment and control group. Eight eyes (72.7%) in the treatment group showed complete retinal fluid resorption versus 2 eyes (40%) in the control group (p = 0.049). Both median CFT and macular volume showed a greater reduction from baseline in the treatment group. BCVA significantly correlated with the outer retinal layers status (rho = 0.82; p = 0.0001) and pattern of retinal fluid (rho = −0.59, p = 0.02). Several eyes in the treatment group experienced a transient increase of the intraocular pressure.

Conclusions

A combined approach with DXI and intravitreal anti‐VEGF may be a feasible option for those wet‐AMD patients with an incomplete response to anti‐VEGF therapy.
Bevacizumab‐treated diabetic macular edema: a pilot yearlong analysis of anatomic and functional outcomes from a referral center in Portugal
Authors: Leitão P. , Bettencourt S. , Trincão F. , Santos P. , SOUSA D.C. , Genro V. , Abegão Pinto L. , Raposo J.
Published: September 2017

Purpose

There is high quality evidence that antiangiogenic drugs are a valuable option on diabetic macular edema (DME) treatment. However, evidence under real‐world conditions is lacking. This paradigmatic pilot study aims to characterize and discuss the 1‐year functional and anatomic response of intravitreal bevacizumab in DME.

Methods

Observational retrospective study. Clinical charts from consecutive patients referred from the Lisbon and Tagus valley region (Portugal) between Jan‐2014 and Dec‐2015 were reviewed. All patients who underwent intravitreal injection of bevacizumab for DME were analyzed. Efficacy outcomes were i) visual acuity (VA) improvement (i.e. halving the visual angle or doubling the decimal value), and ii) a 10% or higher decrease in central macular thickness (CMT), both after a 12‐months follow‐up period. Statistical analysis were performed using STATA.

Results

A total of 107 eyes of 84 patients, with a mean age of 66.0 ± 8.8 years were studied. Mean time elapsed since diabetes diagnosis was 19.1 ± 7.9 years, and mean HbA1c levels were 8.1 ± 1.2%. Baseline VA improved from 0.35 ± 0.22 at baseline to 0.39 ± 0.25 after 12 months (P < 0.05). Also CMT significantly decreased from 464 ± 144 to 379 ± 144 μm one year after injection. The rate of VA and CMT improvement was 31% and 48%, respectively. A non‐statistically significant trend was observed for better outcomes in patients who were concomitantly treated with either focal laser or intravitreal triancinolone. No differences were noted considering the loading dose. No major complications were observed.

Conclusions

This pilot study suggests intravitreal bevacizumab was effective in the DME treatment of our cohort, with a good safety profile. A longer follow‐up and larger sample will help building better evidence to DME management.