bluuebunny/crossref_metadata_2025 huggingface dataset:
Investigation of tear protein composition in healthy and dry eye subjects using trapped ion mobility spectrometry coupled with quadrupole time of flight
Authors: Kolman Ioannis , Kessal Karima , Chardonnet Solenne , Mélik Parsadaniantz Stéphane , Baudouin Christophe , Brignole‐Baudouin Françoise
Published: December 2019

Purpose

Proteomic composition of tears is not yet fully characterized and has a great potential to be used as source for discovery of disease‐specific protein biomarkers. The present work is a preliminary evaluation of tear proteome using timsTOF Pro®, a new highly sensitive mass spectrometry technology.

Material and Methods

Three tear samples from 3 healthy subjects (HS) and 2 from a dry eye (DE) patient were collected using plastic micropipettes and Schirmer’s strips respectively. After protein elution from the strips, all samples were treated under the same conditions. Proteins were reduced and alkylated then digested in solution with LysC and Trypsin prior to nanoLC‐MS/MS analysis (nanoElute and timsTOF Pro®, Bruker). Protein identification was performed with Xtandem.

Results

In total, 1191 proteins were identified in both analytical groups with at least 1 specific peptide: 446 proteins in HS and 1034 proteins in the DE; 802 proteins were exclusively identified in DE (e.g. A2M, HPX, ALDH3A1, PKM, MYH14, ALDH3A1) while 157 were expressed only in controls (e.g. PLOD1, DNAJC3, GOLM1, RNASE4, SDF4, HYOU1). In DE cell structural associated proteins as well as proteins highly correlated with inflammatory and apoptotic processes were detected. Finally, among the proteins that are common to both groups 122 were upregulated in DE vs HS (e.g. ALB, TF, ENO1, ANXA1, GSTP1, S100A9) while 88 were downregulated (e.g. LTF, LCN1, LPO, CST4, LACRT, AZGP1). The upregulated proteins are associated with a blood‐lachrymal barrier failure, inflammatory & immune responses while the downregulated ones sign a lachrymal gland dysfunction.

Conclusions

Differences in the protein expression between HS and DE arise due to the pathological conditions but also due to the different sampling methods used. This preliminary study could offer a roadmap for designing further studies for the in‐depth characterization of the tear protein profile expression under physiological and pathological conditions.
Clinical impact of drug monitoring in non‐infectious uveitis treated with adalimumab
Authors: Mortelé Augustijn , Mortelé Marie , Potvin Arnaud , De Schryver Ilse
Published: December 2019

Purpose

To assess the relationship between adalimumab (ADA) trough levels and clinical efficacy and to evaluate the importance of quantification of ADA serum in combination with clinical data of the patient.

Methods

A retrospective study of patients with non‐infectious uveitis (NIU) treated with ADA for at least 6months who had ADA trough and antibody levels measured during maintenance therapy. Disease activity was evaluated by changes in best‐corrected visual acuity (BCVA), degree of anterior chamber cells, central macular thickness and imaging findings.

Results

Twenty‐four patients were included. The median age was 36 years and 50% were women. The most common diagnosis was idiopathic uveitis (50%), followed by sarcoidosis (17%) and Birdshot (8%). All patients received 40 mg adalimumab every other week and showed an initial clinical benefit. Mean follow‐up was 39.5 months. The median trough level of adalimumab was higher in patients in clinical remission (11.02 μg/mL) than in patients with active disease (4.22 μg/mL). Adalimumab cut‐off value was calculated to discriminate clinical remission from disease activity. A cut‐off drug level of 7.95 μg/mL yielded optimal sensitivity and specificity. Only 2 of 25 patients (8%) had undetectable adalimumab trough levels with antibodies against adalimumab which correlated with loss of clinical response. None of the responders had antibodies.

Conclusion

Despite the limited number of cases, our data suggest that in NIU clinical efficacy improves with increasing adalimumab serum levels. Clinical remission is more likely to occur in those patients who achieve an adalimumab trough level of at least 7.95 μg/mL The development of anti‐adalimumab‐antibodies was associated with undetectable trough adalimumab levels and worse uveitis outcome. Since there is variability in the range for its clinical applicability, controlled prospective studies are required to determine the optimal therapeutic window of ADA serum levels.
Reduced pattern electroretinogram signal in affected patients with Leber Hereditary Optic Neuropathy
Authors: Lalonde Melanie , Kantungane Ange‐Lynca , Sadun Alfredo , Coupland Stuart , Karanjia Rustum
Published: December 2019

Purpose

The pattern electroretinogram (PERG) signal has been reported to be a sensitive tool for the detection of retinal ganglion cell (RGC) dysfunction in both animal models and patients suffering from optic neuropathies. This study investigated whether functional PERG can detect different levels of RGC dysfunction in both carriers and affected patients with Leber Hereditary Optic Neuropathy (LHON).

Methods

PERG signals were recorded using both checkerboard (0.8° check size, 2 reversals/sec) and bars (0.5 cycles/deg) stimuli with mean luminance of 300 cd/m2 and 100% contrast. PERG signals were measured against functional full field Photopic Negative Response (PhNR) recordings (red flashes at 5 cd s/m2 stimulus intensity on blue rod saturating background) and subjective measures of retinal sensitivity (mean deviation [MD] via 30‐2 automated visual fields) and structural metrics (both ganglion cell complex [GCC] and retinal nerve fiber layer [RNFL] thickness from optical coherence tomography [OCT] scans).

Results

PERG P50 amplitudes were similar across controls, carriers, and LHON affected patients. P50 implicit times were significantly reduced in LHON affected patients (CHECKS: 45.8 ± 1.1 ms; BARS: 43.5 ± 0.8 ms; n = 32) compared to controls (CHECKS: 49.3 ± 0.5 ms; BARS: 48.1 ± 0.4 ms; n = 72). N95 amplitudes elicited by the checkerboard stimulus were significantly reduced and implicit times significantly increased in LHON affected patients (−3.4 ± 0.4 µV; 93.6 ± 2.2 ms; n = 32) compared to controls (−5.9 ± 0.5 µV; 85.3 ± 0.8 ms; n = 72). No differences were seen in PERG signals between control or LHON affected patients and carriers. Although PERG parameters were significantly different in LHON affected patients, the measurements were not correlated with PhNR signals, MD and RNFL thickness in all four quadrants around the optic disc. On the other hand, PhNR amplitudes, which were significantly reduced in LHON affected (−16.3 ± 3.4 µV; n = 32) and in carriers (−21.8 ± 3.0 µV; n = 30) compared to controls (−34.2 ± 2.5 µV; n = 28), were correlated with MD (r = −0.611, p < 0.0005; n = 28), average GCC (r = −0.618, p < 0.0001; n = 32) and average RNFL thickness (r = −0.553, p < 0.001; n = 31) in affected patients.

Conclusions

Significant differences in PERG recordings were measured between control and LHON affected patients. However, no significant differences were seen in carriers and PERG metrics were not correlated with functional PhNR parameters and other subjective and objective measurements tested. Our results suggest that PERG may not be as sensitive as PhNR to discriminate different levels of RGC dysfunction between LHON affected patients and carriers.
Extraction of hyaluronic acid and chondroitin sulfate from marine biomass for their application in the treatment of the dry eye disease
Authors: Abdallah Maha
Published: December 2019

Purpose

Tear film instability, hyperosmolarity and neurosensory abnormality are the key etiological contributors to the pathophysiological process of the Dry Eye Disease (DED).1 Hyaluronic acid (HA) and Chondroitin sulfate (CS) have shown improvements in the corneal epithelial barrier in patients with DED.2 Moreover they are used in pharmaceutical applications due to their biocompatibility, viscoelasticity, lubricity and immunostimulatory effects. In this study, they are extracted from marine wastes and will be evaluated as possible DED treatment using natural, green and novel Deep Eutectic Solvents (DES) to replace time‐consuming and expensive conventional methods and maintaining the quality and purity of the isolated HA and CS. Natural compounds such as menthol and trehalose, are used in DES preparation and have shown to be effective in DED treatment.3,4

Methods

HA and CS are isolated from marine wastes using conventional methods and DES as low‐cost alternative technique. DES are prepared by heating and mixing the components at certain ratios. They are mixed with the marine sources at specific extraction conditions. The extracts are then enzymatically hydrolyzed and analyzed by HPLC and capillary electrophoresis to quantify HA and CS.

Results

HA and CS are extracted from mussels, codfish bones and furtherly tuna eyeballs and shark fins using DES. Several DES were tested such as menthol:borneol, menthol:camphor, trehalose:glycerol, and significant amounts of HA and CS were extracted with high specificity. For example, 37.92 µg/gdry codfish bones CS disaccharide (ΔHexAβ1‐3GalNAc4S) were extracted using menthol:borneol.

Conclusion

DES are effective compounds for the extraction of valuable biopolymers HA and CS. The isolated HA and CS, as well as their therapeutic mixture with DES will be studied in vitro on conjunctival and corneal epithelial human cell lines to assess their toxicity, biocompatibility, muco‐adhesion and anti‐oxidant effects for the treatment of the DED.

References

Craig, Jennifer P., et al. “TFOS DEWS II report executive summary.” The Ocular Surface 15.4 (2017): 802‐812.

Limberg, Michael B., et al. “Topical application of hyaluronic acid and chondroitin sulfate in the treatment of dry eyes.” American journal of ophthalmology 103.2 (1987): 194‐197.

Arita, Reiko, et al. “Effects of a warm compress containing menthol on the tear film in healthy subjects and dry eye patients.” Scientific reports 7 (2017): 45848.

Fondi, Klemens, et al. “Effect of Hyaluronic Acid/Trehalose in Two Different Formulations on Signs and Symptoms in Patients with Moderate to Severe Dry Eye Disease.” Journal of ophthalmology 2018 (2018).
Automatic classification and triage of diabetic retinopathy from retinal images based on a convolutional neural networks (CNN) method
Authors: Galdran Adrian , Chakor Hadi , Alrushood Abdulaziz A. , Kobbi Ryad , Christodoulidis Argyrios , Chelbi Jihed , Racine Marc‐André , Benayed Ismail
Published: December 2019

Purpose

Diabetic retinopathy (DR) is one of the leading causes of adult vision loss in the developed countries. Epidemiological and demographic factors, including the rising rates of diabetes related to obesity and an aging population, are driving the incidence of diabetic eye complication inexorably higher.

Method

Deep learning emerges as a powerful tool for analyzing and classifying retinal images in an automatic way, but the classification results depend greatly on the availability of large datasets. As the number of categories and the imbalance ratio increase, the performance of deep learning models diminishes. In the context of DR grading, minority classes (mild and severe DR) are critical to diagnose. Experiments were performed on a real dataset developed at local hospital and at different hospitals around the world. Overall, 42 179 retinal images were obtained from Diagnos database. All images were graded by 3 retinal experts using the early treatment diabetic retinopathy study severity scale (ETDRS). The dataset was built by expanding on 4 categories: R0 or normal, R1 or mild DR, R2 or moderate DR, and R3&R4 or severe and proliferative DR. The data was split 90/10 for training and testing respectively, and an ensemble of Convolutional Neural Networks was trained to perform DR grading.

Results

The proposed method achieves high accuracy in predicting DR grades, with the R1 class showing lower performance, in line with recently proposed methods. An area under the ROC curve of 0.96 (0.95–0.96) for R0, 0.70 (0.65–0.75) for R1, 0.95 (0.94–0.95) for R2 and 0.92 (0.89–0.96) for R34.

Conclusion

Comparable to the score of human experts, the deep learning techniques in this study were effective to be applied in clinical use as primary care setting and could be a valuable tool to help primary care triage. Improvement in detection of R1 subjects is needed for further progressing in this area.

References

1. He K, Zhang X, Ren S & Sun J (2016): Deep Residual Learning for Image Recognition. In 2016 IEEE Conference on Computer Vision and Pattern Recognition (CVPR) 770–778.

2. Krause J et al. (2018): Grader variability and the importance of reference standards for evaluating machine learning models for diabetic retinopathy. Ophthalmology 125: 1264–1272.
Giant squamous cell carcinoma of the conjunctiva: a clinical case report
Authors: Lopes Diogo , Loureiro Tomás , Carreira Rita , Barros Sandra , Machado Inês , Campos Paul , Campos Nuno
Published: December 2019

Purpose

Conjunctival Squamous cell carcinoma (SCC) represents a malignant disease that, if untreated, can cause irreversible loss of vision or even death. It is a rare disease, which is why the diagnostic and therapeutic approaches are not always linear. To report a case of a giant conjunctival SCC, including its diagnostic and therapeutic approach.

Methods

A 82 years old man, with history of basal cell carcinoma in situ of the upper eyelid, was referred to the emergency department by a conjunctival lesion of the right eye with 3 months of evolution and rapid growth. Examination revealed a whitish, conical‐shaped temporal conjunctival lesion (16 x 18 x 6.5mm) in the right eye with no mobility relative to the scleral plane and staining with 1% toluidine blue. Orbital magnetic resonance imaging identified the temporal conjunctival lesion in the right eye, without unequivocal signs of scleral and other intraocular structures invasion.

Results

This lesion was excised with a 4 mm margin, using 1% toluidine blue dye, through a no‐touch technique. As adjuvant therapy, we performed cryotherapy of the conjunctival margins and scleral bed, which was covered with amniotic membrane. Histological examination confirmed the presence of a well differentiated conjunctival SCC. One month after surgery, he started treatment with mitomycin‐c 0.04 mg/mL. Three months later, there were no signs of relapse.

Conclusion

Clinical observation allows, in some cases, a high clinical suspicion. The vital staining with topical toluidine blue is an excellent aid in diagnosis, staining most lesions with high sensitivity, and in treatment, allowing to delineate surgical margins. Surgical treatment alone is associated with recurrence rates of up to about 70%, which is why adjuvant therapy, in particular cryotherapy and topical mitomycin‐c, is advocated. Although less common in the daily practice of an ophthalmologist, conjunctival SCC is potentially fatal and, therefore, deserves particular attention.
Visual acuity and structure‐function relationships in acute and chronic LHON patients treated with idebenone
Authors: Pemp Berthold , Kircher Karl , Reitner Andreas
Published: December 2019

Purpose

Leber's hereditary optic neuropathy (LHON) is a mitochondrial disease characterised by a subacute and progressive impairment and subsequent degeneration of macular retinal ganglion cells and their nerve fibres causing permanently reduced visual acuity (VA) in most cases. Idebenone is currently the only approved treatment for LHON. This study aims to evaluate the course of VA and its correlations with inner retinal layer morphology in LHON patients treated with idebenone.

Methods

42 eyes of 21 genetically confirmed LHON patients treated with idebenone were examined in regular intervals. VA was measured using logMAR charts. Macular ganglion cell layer volume (GCLV) and peripapillary retinal nerve fibre layer thickness (pRNFLT) were measured by spectral domain OCT. Patients were divided into three groups according to their time from LHON onset until treatment start including acute patients (<1 year, 12 eyes), chronic group 1 (1 to 5 years, 14 eyes) and chronic group 2 (>5 years, 16 eyes).

Results

A significant increase of VA compared to minimum VA was observed in all groups (acute: ‐0.25 logMAR, chronic 1: −0.29 logMAR, chronic 2: −0.31 logMAR; p < 0.001 all groups). VA at baseline was similar between groups, but 6 eyes of 4 acute patients showed a marked decline during the first year reaching a minimum after 9 months. Minimum VA of all patients was significantly correlated with final pRNFLT (r = 0.48, p = 0.002) and GCLV (r = 0.40, p = 0.008), but OCT and maximum VA during continued treatment showed stronger correlations (pRNFLT: r = 0.50, p = 0.001; GCLV: r = 0.43, p = 0.004). VA gain was not associated with OCT and not different between all groups.

Conclusions

VA in LHON patients with recent disease onset can decrease during the first months of treatment with idebenone. The increase of VA after this nadir is comparable to the treatment effects observed in chronic patients and may be the result of a reactivated signal transduction in surviving dysfunctional ganglion cells.
Clinical outcomes after intracorneal ring segment implantation for keratoconus management in corneas with apical haze
Authors: Reinhold Aja , Panos Georgios D. , Khine Aye , Elalfy Mohamed , Hamada Samer , Scholl Hendrik , Gatzioufas Zisis
Published: December 2019

Purpose

Intracorneal ring segment implantation represents a safe and effective treatment option for visual improvement in patients with keratoconus. The presence of corneal scarring is considered to be an exclusion criterion for the use of intracorneal ring segments. The aim of this retrospective cohort study was to evaluate the clinical outcomes after intracorneal ring segment implantation for keratoconus in patients with corneal apical haze.

Methods

Six eyes from 6 patients with keratoconus and corneal apical haze, who underwent femtosecond laser‐assisted Keraring implantation for keratoconus, were included in this study. All patients have had corneal crosslinking in the past. Uncorrected visual acuity (UCVA), corrected visual acuity (CDVA), Kmax, Kmean and thinnest corneal pachymetry have been evaluated preoperatively and 6 months after the Keraring implantation. Wilcoxon test was applied for statistical analysis with calculation of median value (lowest value – highest value). P values less than 0.05 were considered statistically significant.

Results

Six eyes of 6 patients (4 males and 2 females) were included in the study. Median age (years) was 33 (28 ‐ 38). UCVA (logMAR) and CDVA (logMAR) improved significantly from 1.05 and 0.75 preoperatively to 0.9 and 0.4 at 6 months postoperatively, respectively (p=0.03). Kmax (diopters) and Kmean (diopters) decreased from 54.5 and 47.85 preoperatively to 53.45 and 46.42 postoperatively, respectively (p=0.3). Changes in thinnest corneal pachymetry were not statistically significant (p=1.0). No complications occurred peri‐ or postoperatively.

Conclusion

Our study showed significant keratometric amelioration and visual improvement after intracorneal ring segment implantation for in patients with keratoconus and mild corneal apical haze at 6 months postoperatively. No complications occurred. These results suggest that the presence of mild corneal apical haze should not necessarily exclude the use of intracorneal ring segments in patients with keratoconus.
Cell Based Therapy for Corneal Endothelial Regeneration
Authors: Niazi Sana , Sanginabadi Azad
Published: December 2019

Cell based treatment, as an option in contrast to ordinary donor corneal transplantation, is foreseen to give a not so much intrusive but rather more successful helpful methodology for corneal endothelial dysfunction. The proliferative capacity of human corneal endothelial cells is seriously controlled, in this way making the foundation of ideal conditions for the development of human corneal endothelial cells a basic perspective for the clinical utilization of a cell based treatment. As of late, effective development convention of human corneal endothelial cells for clinical application which incorporates the utilization of Rho kinase (ROCK) inhibitor and the restraint of changing development factor beta flagging were accounted for to advance the cell multiplication and to help human corneal endothelial cell societies that show high cell thickness. Creature tests demonstrated that a cell‐infusion treatment joined with the utilization of a ROCK inhibitor advances developed corneal endothelial cell bond onto the back cornea, at last bringing about the recuperation of corneal straightforwardness. A pilot clinical examination was as of late started in Japan to research the viability of a cell‐infusion treatment for patients with bullous keratopathy.
A historical form of adenoid cystic carcinoma orbital: about a case
Authors: Abdi Rhizlane , Chariba Siham , Maadane Asmae , Sekhsoukh Rachid
Published: December 2019

Introduction

Adenoid Cystic Carcinoma is a slow growing, locally invasive tumor of epithelial origin, mainly from the lacrimal gland. It is a rare tumor and the mortality rate has been found to be quite high (> 50%). Its usual development is done on salivary glands. Its orbital location on lacrimal glands is exceptional. We report the 55‐year‐old patient with advanced orbital cystic adenoid carcinoma.

Case Report

A 55 years old female presented to our clinic with complaints of insidious onset, gradually worsening frontal region headache of 6 years duration, proptosis associated with decreased visual acuity, the evolution was marked 3 years ago by the appearance extended orbital mass to the frontal and maxillary region. The evolution was marked 3 years ago by the appearance of an extended orbital mass towards the frontal and maxillary region. The patient came to consultation at a very advanced stage with visual acuity at no light perception,at the inspection we observe an enormous frontoorbitofacial mass taking half of the left hemiface. The slit lamp examination exhibited exposure keratitis and the fundus: optic atrophy and retinal folds. Tomography computed scan revealed: the presence of an intra‐orbital tissue mass which includes the oculomotor muscles and the lacrimal gland measuring 67 * 16 mm pushing back the optic and infiltrating nerve in front of the left periorbital and left frontal palpebral soft tissues, with the presence of bone lysis of the different walls of the orbit . The assessment of extension found: pulmonary micronodules and vertebral lesions. A biopsy was performed and the histo pathological study revealed an adenoid cystic carcinoma. The patient was referred oncology for possible radio chemotherapy.

Conclusion

Cystic adenoid carcinomas of the lacrimal gland are rare, they are malignant tumors that have a very high recurrence rate, and require early diagnosis and early management.
Bilateral anterior ischaemic optic neuropathy with macular star as first manifestation of Henoch‐Schönlein purpura (IgA vasculitis)
Authors: Kontou Evgenia , Bontzos Georgios , Ragkousis Antonis , Gkoumas Evangelos , Triantafyllou Dionysios , Bitza Penelope , Xirou Tina
Published: December 2019

Purpose

To report a case of bilateral anterior ischaemic optic neuropathy with macular star in a patient with Henoch–Schönlein purpura (HSP).

Methods

A 46‐year‐old man was referred to our clinic complaining of progressive decrease in visual acuity of the right eye (OD) since the last 10 days, and since 3 days in his left eye (OS). His visual acuity was ‘hand motion’ OD and 4/10 OS. Anterior segment examination was insignificant, while fundus examination revealed optic disc edema, and bilateral macular star. A relative afferent pupillary defect was present in his right eye with normal pupillary reflexes in the left eye. Laboratory analysis showed: Hematocrit: 22.1%, ESR: 140 mm/hr, CRP: 64.80 mg/dl, Creatinine: 4.4 mg/dl. Physical examination revealed presence of erythematous rash on the trunk and the extremities. The patient was admitted to the Nephrology department for treatment of his azotemia.

Results

During his hospital course we performed complete laboratory and imaging examinations for autoimmune diseases, vasculitis and infectious diseases, which were negative. Histologic findings of renal biopsy were compatible with IgA glomerulonephritis and thus HSP was diagnosed. The patient received oral methylprednisolone and intravenous cyclophosphamide therapy. Six months later his renal function had improved, the rash had subsided and his visual acuity was ‘counting fingers’ OD and 10/10 OS. Standard automated perimetry showed peripheral visual field depression bilaterally.

Conclusions

Henoch–Schönlein purpura (HSP) is a small vessel vasculitis which is more common in children. Based on literature, ophthalmic manifestations of HSP usually involve the anterior segment and less frequently the posterior segment. Systemic vasculitis should be included in the differential diagnosis of bilateral optic disc edema.
Impact study of polarized light on the eye in a experimental model of dry eye disease
Authors: Shargorodska Iryna , Rykov Sergiy , Denysiuk Liubov , Liemienieva Anastasiia
Published: December 2019

Now dry eye disease (DED) influences each tenth inhabitant of the planet. Current question of modern ophthalmology are the search for new therapies, one of which is the application of BIOPTRON‐PILER therapy.

Purpose

To study of pathophysiological mechanisms of action and clinical efficacy of poly‐ and monochromatic BIOPTRON‐PILER‐light of dry eye disease.

Methods

Here, we used rats with an experimental model of the dry eye induced by inflammation of eye anterior surface. BIOPTRON‐PILER therapy was performed using the red filter of the BIOPTRON (Bioptron AG, Zepter Group, Swiss) at 1 day after induction of DED. Only the right eye was treated from the distance of 30 cm for 3 min. Each animal received a course of treatment for 10 days.

Results

Are showed that a fluorescein test carried out immediately after alkali application and on 1, 5 and 10 days demonstrated a gradual increase in corneal epithelization and vascularization. We observed substantial and statistically significant increase of lacrimation in experimental rats on a 1 day after induction of inflammation compared to naïve animals. By the 7 day, the lacrimation decreased to a level with subsequent tendency to further decreased tear production. At the same time, there was no significant reduction in tear production on 7th day in a group of rats with the anterior surface inflammation that received polarized red light treatment, which may indicate a possible anti‐inflammatory effect of such treatment.

Conclusion

Obtained evidence of the positive anti‐inflammatory effect of BIOPTRON‐PILER‐light in experimental model of the dry eye disease.
Contact lens wearers and dry eye symptoms: Ocular surface conditioning with Thealoz Duo
Authors: Peral Assumpta , Fernández Elena , Diz Elena
Published: December 2019

Purpose

Contact lens use is associated with dry eye symptoms in approximately 50% of patients and can lead to discontinuation of their use. The aim of this study was to assess the effects of a combination of hyaluronic acid/trehalose eye drops on signs and symptoms of dry eye in contact lens wearers. Patient and care provider satisfaction were also evaluated

Methods

Prospective, non‐controlled, pilot treatment trial was carried out in contact lens wearers with pre‐enrolement OSDI scores over 18. Following a week long washout period with sodium chloride eye drops 33 patients with contact lens related dry eye symptoms were recruited to receive 4 daily drops of a hyaluronic acid/trehalose eye drop for 12 weeks. TBUT, corneal and conjunctival staining, meniscus height and symptom questionnaires OSDI, DEFC and CLDEQ‐8 were performed at baseline, 5 weeks and 12 weeks.

Results

Treatment with hyaluronic acid/trehalose improved dry eye symptoms significantly as evidenced in reduction of questionnaire scores. Signs of dry eye improved most significantly for corneal fluorescein staining.

Conclusions

Hyaluronic acid/trehalose eye drops reduce the signs and symptoms of dry eye in contact lens wearers and are safe to use.
XEN in extreme cases
Authors: Djavanmardi Shirin , Milla Elena
Published: December 2019

Purpose

The Xen implant allows to perform a filtering procedure using a collagen tube of 6 mm in length and 45 microns of lumen usually placed in the upper nasal quadrant. Its main indication is primary open angle glaucoma, however, its versatility has allowed it to be used in other types of glaucoma cases. The aim of this communication is to present some cases in which the Xen implant has been used to treat complex situations.

Methods & Results

Case 1 ‐ A 31‐year‐old woman with congenital glaucoma, a history of goniotomy and a drainage device carrier of double‐plate glaucoma who presented intraocular pressure (IOP) of 17 mmHg with maximum topical and oral treatment and severe toxic ocular disease. As the upper nasal quadrant was occupied, a XEN device was implanted in the inferior nasal quadrant. During the postoperative period, displacement of the implant towards the anterior chamber was evident, but no endothelial cell loss was observed and control of the IOP was maintained at 1 year of follow‐up with a significant reduction in medication and improvement of the ocular surface. Case 2 ‐ A 34‐year‐old man presented with contusive trauma in his left eye complicated by 2‐mm hyphema and (IOP > 40 mmHg ) that could not be controlled with maximum medication. After performing a drainage of the hyphema a XEN implant was placed in the upper nasal quadrant. Since then, IOP was controlled and the visual acuity completely reestablished. Case 3 ‐ A 58‐year‐old woman with severe scleromalacia affecting all four quadrants. She had a history of trabeculectomy in the upper quadrant and a superior nasal sector of healthy conjunctiva that was normocolored and mobilizable was observed. After placing the Xen in the upper nasal sector, the patient has remained with an IOP of 16 mmHg with a beta‐blocker medication.

Conclusions

1. The Xen implant can be useful in the management of glaucoma in some challenging situations. 2. The inferior nasal location of the Xen is raised exceptionally. It can make it more susceptible to displacement, although this does not necessarily affect its functioning. 3. The Xen device can be useful in acute uncontrolable ocular hypertension (ex trauma) in the context of an open angle.
Electrical synapses interconnecting axons in the optic nerve head–a novel model of optic nerve function
Authors: Pietrucha‐Dutczak Marita , Akhtar Saeed , Liu Xiaonan , Podracka Lucia , Toropainen Elisa , Alkanaan Aljoharah , Ruponen Marika , Urtti Arto , Varjosalo Markku , Kaarniranta Kai , Lewin‐Kowalik Joanna , Smedowski Adrian
Published: December 2019

Purpose

Axons in the optic nerve are arranged in bundles and conducting action potential with resistance related to their membrane. Here, we aim to characterize the function of newly identified gap junctions coupling optic nerve axons with each other’s.

Methods

Proximal and distal rat optic nerve stumps were processed for immunostainings, electron microscopy (EM), RT‐PCR and western blots (WB). Additional 20 animals were deeply anesthetized, and stainless‐steel screw electrodes were drilled in skulls in standard locations to record fVEPs. Recordings were performed in untouched animals, after retrobulbar injection of saline (negative control) or meclofenamic acid solution (gap junctions’ blocker). Human paraffin cross‐sections of eyeballs for immunostainings were obtained from the Human Eye Biobank for Research, University of Toronto, Canada.

Results

Immunostaining of rat and human samples revealed presence of Cx45 and 36 in axonal membranes, colocalizing with β3‐tubulin, but not with GFAP. In WB, Cx36 content in optic nerve was approximately halved when compared with retina (0.58 ± 0.005 ‐ proximal stump; 0.44 ± 0.02 ‐ distal stump), Cx45 showed higher levels (0.68 ± 0.0003 ‐ proximal stump; 0.9 ± 0.07 ‐ distal stump). Additionally, we detected transcript of Cx45 and Cx36 in RT‐PCR analysis of optic nerve homogenates. In immunogold‐EM of optic nerve sections, we found electric synapses (formed mostly by Cx45) that are directly coupling neighboring axons. In fVEPs, blocking of gap junctions’ with meclofenamic acid resulted in prolongation of the latency of P1 wave up to 140% after 5 min from retrobulbar injection of this blocker (p < 0.001) and 170% after 30 min (p < 0.001).

Conclusions

Optic nerve axons do not form absolutely independent conductive channels. They are directly coupled by gap junctions formed in majority by neuronal Cx45. Coupling of axons allows to reduce axonal membrane resistance and accelerates transduction of visual signal.
Unilateral unifocal advanced intraocular retinoblastoma: is reasonable to adopt intra‐arterial chemotherapy as single therapeutic choice?
Authors: De Francesco Sonia , Leonini Sara , Galluzzi Paolo , Bracco Sandra , Gennari Paola , Maria Pinto Anna , Neri Giovanni , Barchitta Matteo , Renieri Alessandra , Hadjistilianou Doris
Published: December 2019

Purpose

To report the outcome of 30 naive unilateral unifocal retinoblastoma cases treated with intra‐arterial chemotherapy alone.

Methods

From 2008 to 2019, 192 eyes affected with retinoblastoma have been treated with intra‐arterial chemotherapy (IAC). 100 out of 192 (52%) eyes were naive advanced unilateral unifocal retinoblastoma (Group B‐E). 30 out of 100 (30%) received intra‐arterial chemotherapy alone. All patients underwent genetic testing at diagnosis. MR was performed at diagnosis, during treatment (when necessary), 3 months after last infusion and annually to evaluate eyeball growth.

Results

Tumor control and globe salvage was achieved in 100% of the reported cases (follow‐up ranged from 11 years to 9 months). New tumors or relapse have not been detected. No further local or systemic therapies were necessary. Procedure complications and local and systemic effects are reported. No intraocular or orbital tumor recurrence or metastatic disease have been observed observed.

Conclusions

The outcome will be correlated to genetic analysis, doses and drugs used (alone or in combination) and number of infusions received.
Length and width of the peripapillary scleral flange in relation to axial length
Authors: Jonas Shefali , Panda‐Jonas Songhomitra , Jonas Jost
Published: December 2019

Purpose

The peripapillary scleral flange is the continuation of the posterior sclera after separating from the optic nerve dura mater and serves as the biomechanical anchor for the lamina cribrosa from which it is separated by the peripapillary border tissue of Elschnig. In view of its biomechanical importance for the optic nerve head, we determined the dimensions of the peripapillary scleral flange and its associations with axial length.

Methods

The study included human globes which had been enucleated due to malignant melanomas or end‐stage secondary angle closure glaucoma. Histologic slides were histomorphometrically examined.

Results

The study included 202 eyes of patients with a mean age of 61.7 ± 13.7 years (range: 24–89 years) and a mean axial length of 24.9 ± 2.5 mm (range: 20.0–35.0 mm). The mean thickness of the peripapillary scleral flange was 0.37 ± 0.10 mm (median: 0.38 mm; range: 0.10–0.76 mm), and a mean length of 0.54 ± 0.43 mm (range: 0.05–2.14 mm). Peripapillary scleral flange thickness was inversely correlated with longer peripapillary scleral flange length (p = 0.001; standardized regression coefficient β: −0.46) and longer axial length (p = 0.001; β = −0.23). Correspondingly, peripapillary scleral flange length increased with longer axial length (p < 0.001; β = 0.49).

Conclusions

Axial elongation is associated with a marked elongation and corresponding thinning of the peripapillary scleral flange. With the PSF being the biomechanical anchor of the lamina cribrosa, the findings may be of interest for the biomechanics of the optic nerve head in axial myopia.
ARREST BLINDNESS: a brief overview from the project coordinator
Authors: Lagali Neil
Published: December 2019

ARREST BLINDNESS was the first cornea research project funded under the EU Horizon 2020 program, with the goal of developing advanced next‐generation corneal regenerative and restorative therapies, offering hope to patients where no suitable therapy exists. Here, a brief summary will be given of the main goals, deliverables and milestones of the project. Work packages within the project were aimed at developing next‐generation regenerative and restorative therapies to treat corneal pathologies focusing on technologies applied at the molecular, cell, and tissue levels. Molecular‐level therapies include novel topical neuro‐regenerative and anti‐angiogenic agents, cell therapy includes xenogenic‐free cultivated limbal stem cell transplantation for unilateral and bilateral limbal stem cell insufficiency and cultivated endothelial cell sheet development for endothelial transplantation, while tissue‐level therapies include a collagen‐derived biopatch, collagen‐based stromal replacement implants, and angio‐ablative strategies. Within the past four years all technologies have advanced from laboratory testing through preclinical stages, where further development continues or the technologies have progressed to first‐in‐man clinical studies, where four such clinical studies were undertaken during the project. Milestones achieved, technology status, and clinical study updates will be given in six separate talks, each focusing on a specific project work package aimed at developing and translating a novel advanced regenerative therapy into eventual clinical application.
Indocyanine green angiography for identifying telangiectatic capillaries in diabetic macular edema
Authors: Castro Farías Daniela
Published: December 2019

Aims

During diabetic macular edema (DME), a spectrum of capillary abnormalities is commonly observed, ranging from microaneurysms to large microvascular abnormalities. Clinical evidence suggests that targeted photocoagulation of large microvascular abnormalities may be beneficial, but their detection is not done in a routine fashion. It was reported that they are better identified by indocyanine green angiography (ICGA) than by fluorescein angiography. Here, we investigated the prevalence and ICGA and OCT features of large microvascular abnormalities in a group of patients with DME.

Methods

Observational study. The fundus photographs, ICGA and structural and angiographic OCT charts of 35 eyes from 25 consecutive patients with DME were reviewed.

Results

Twenty‐two eyes (63%) had at least one focal area of microvascular abnormalities showing prolonged ICG staining (i.e. beyond 10 min after injection). In particular, all eyes with circinate hard exudates (n = 9) showed foci of late ICG staining in the center of exudates. These areas appeared either as isolated globular capillary ecstasies or as a cluster of ill‐defined capillary abnormalities. They were located at a median distance of 2708 µm from the fovea (range: 1064–4583 µm). Their diameter ranged from 153 to 307 µm. During ICGA, 94% of such large lesions showed an increase in their contrast and apparent size in late frames relative to early frames, while 77% of microaneurysms showed reduced contrast on late frames. OCTA appeared as poorly contributive for the detection of ICG stained lesions.

Conclusion

Late ICG staining revealing large microvascular abnormalities is commonly observed during DME. Because of their specific angiographic and OCT features relative to microaneurysms, we propose to name them telangiectatic capillaries.
The London Project at 10 years: Have we found a cure?
Authors: Coffey Pete
Published: December 2019

The London Project to Cure Blindness is a collaboration between Professor Pete Coffey and Dr Lyndon da Cruz from University College London and Moorfields Eye Hospital. The project aims to use Stem Cell technology to restore sight, prevent progression and ultimately improve the quality of life for patients with Age‐Related Macular Degeneration (AMD) and other retinal and macular disorders, combining cutting edge knowledge and technology from the laboratory, clinic and operating theatre.
Intraoperative OCT guided peeling of ERM
Authors: Georgiadis Odysseas
Published: December 2019

The integration of Optical Coherence Tomography (OCT) into the automated operating microscope has introduced a new era for the operating viewing systems in ophthalmic surgery. By adding a real‐time cross‐sectional visualization to the traditional en face operating view it has been reported to improve the efficacy and safety of both the anterior and posterior segment intraocular surgeries. Furthermore, it has opened the field for novel techniques and experimental surgical approaches with enhanced operative precision. Numerous vitreoretinal procedures have been described utilizing intraoperative OCT (iOCT), with the epiretinal membrane (ERM) peeling being amongst the most common. From the early studies with hand‐held iOCT prototypes that led to the discovery of residual membranes after the initial peeling, to the recent multi‐surgeon prospective studies with microscope‐integrated scanners that involved hundreds of operations, the use of the iOCT has been demonstrated to affect or even alter the surgeon’s decisions in a significant percentage of the studies cases. Specifically for ERM, iOCT‐guided peeling seems to have resulted in a significant improvement of post‐operative visual acuity, reduction in macular thickness and lower rates of recurrence. Preliminary results are encouraging; nevertheless further investigation with randomized comparative trials is still required to determine the probable advantages of the iOCT‐guided ERM surgery over the standard visualization techniques.
Treatment paradigms for mitochondrial optic neuropathies
Authors: La Morgia Chiara
Published: December 2019

The most common mitochondrial optic neuropathies are Leber’s Hereditary Optic Neuropathy (LHON) and Dominant Optic Atrophy (DOA). Both diseases are characterized by retinal ganglion cell loss resulting in optic atrophy and are characterized by a complex I defect. The current available therapeutic option for LHON is the recently approved in Europe Idebenone‐©Raxone for patients with a disease duration of 1 year or less. Moreover, gene therapy trials for patients carrying the 11778/ND4 LHON mutation are ongoing in Europe, US and China. Potential therapeutic options for LHON include also EPI‐743, elamipretide, estrogens and drugs aimed at increasing mitochondrial biogenesis and anti‐apoptotic agents such as cyclosporine A. Moreover, the possibility of mitochondrial replacement therapy for female LHON carriers of childbearing age can be offered to prevent the maternal transmission of pathogenic mtDNA mutations. The current active clinical trials on LHON will be presented. For DOA there is no approved drug available at the moment. A potential beneficial effect of idebenone has been suggested, but randomized controlled trials are still needed to confirm these preliminary data. Interestingly, for DOA, a gene therapy approach has been recently successfully used to alleviate retinal ganglion cell loss in a OPA1‐mouse model.
Treatment of dry eye disease
Authors: Jacobi Christina
Published: December 2019

The major goal of dry eye disease (DED) therapeutic management is to restore homeostasis of the ocular surface by breaking the vicious cycle of the disease and offering long‐term treatment options.

TFOS DEWS II Report recommends a specific evidence‐based treatment approach:

Step 1: education regarding DED, modification of local environment, potential dietary modifications, identification and modification of offending medications (systemic/topical), ocular lubricants, lid hygiene, warm compresses.

Step 2: non‐preserved ocular lubricants, tea tree oil treatment for Demodex, tear conservation (e.g. punctal occlusion), overnight treatments (ointment, moisture chamber devices), in‐office physical heating and expression of the Meibomian glands, device‐assisted therapies, in‐office intense pulsed light therapy, prescription drugs: topical corticosteroids (limited duration), topical antibiotics or antibiotic/steroid combinations applied to the lid margins for blepharitis, topical secretagogues, topical non‐glucocorticoid immunomodulatory drugs (e.g. cyclosporine), topical LFA‐1 antagonist drugs, oral macrolide or tetracycline antibiotics.

Step 3: oral secretagogues, autologous serum eye drops, therapeutic contact lenses.

Step 4: topical corticosteroids (longer duration), amniotic membrane grafts, surgical punctal occlusion, other surgical approaches (e.g. tarsorrhaphy).

Careful follow‐up strategies are important to monitor changes in patients` symptoms and signs and to ensure that patients are applying the recommended management options successfully. Moreover, therapies should be applied over a certain period of time before it can be concluded that no improvement will occur. It is essential to understand the multiple pathogenetic processes in dry eye patients to select effective therapies, especially as DED is a complex condition that varies in severity and character from patient to patient.
Autologous cell regeneration of the crystalline lens
Authors: Michael Ralph
Published: December 2019

Regeneration of ocular tissues using stem cells is currently under investigation for the cornea and the retina. Some more recent studies focus also on the regeneration of the crystalline lens. The lens consists of only two cell types, epithelial cells, which can differentiate and act as progenitor cells to the other cell type, fiber cells. Lens epithelial cells are very active, and due to this it is difficult to prevent their proliferation, migration and differentiation when they develop posterior capsule opacification (PCO) after cataract surgery. We have compared the morphology and histopathology of PCO developed in‐vivo with a PCO model of in‐vitro tissue culture. Our in‐vitro tissue culture showed some volumetric growth of cells which expressed the potential to form lens fiber cells. Some, but not all in‐vivo formed PCO showed doughnut shaped lens like structures with anterior epithelial cells, a lens bow and lens fiber like cells, very similar to the natural lens. Special surgical procedures of lens removal have been applied in rabbits and tested to treat human congenital cataract. Both were capable of regenerating the lens to some extent. These studies on PCO and in‐vivo surgery, demonstrate the potential to regenerate the crystalline lens in humans.
Disease penetrance in LHON ‐ unravelling the puzzle
Authors: Karanjia Rustum
Published: December 2019

Lebers Hereditary Optic Neuropathy (LHON) is the most common hereditary mitochondrial optic neuropathy. The reported incidence is about 1:50 000 but the risk of conversion from the carrier to affected state is in part dependent on the sex of and age of the patient. The proposed reasons for this apparent skewed rate of conversion will be discussed in this presentation.
The role of vitrectomy in uveitis
Authors: Krepler Katharina
Published: December 2019

In uveitis patients therapy usually depends on the aetiology of the disease and a correct diagnosis is therefore important. A diagnostic vitrectomy with laboratory workup of vitreous specimens can improve the likelyhood of diagnosis. In therapeutiv vitrectomy, removing infiltrated vitreous helps in diagnosis by restoring fundus view and removes potentially harmful inflammatory and infectious material from the eye. Visual acuity has been reported to improve in 70%‐90% of cases depending on aetiology. Secondary retinal problems such as Epiretinal membranes with macular traction, macular holes or retinal breaks and detachment can be successfully treated. Additional treatment with intravitreal steroids can be considered.

Combining modern microincisional vitrectomy surgery with phacoemulsification is a safe option.