bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ocular Chronic Graft Versus Host Disease after Bone Marrow Transplantation
Authors: Jeppesen H. , Sengeloev H. , Lindegaard J. , Julian H. , Prause J.U. , Heegaard S. 
Published: September 2015

PurposeAllogeneic bone marrow transplantation (BMT) is a curative therapy for a number of hematological diseases. Ocular chronic graft versus host disease (cGVHD) is a major contributor to long‐term morbidity after BMT. The purpose of this study was to report the frequency of ocular cGVHD after BMT and onset in relation to systemic cGVHD.MethodsRetrospective examination of medical records of patients who underwent consecutive allogeneic BMT from 1980‐2011 at Copenhagen University Hospital (Rigshospitalet). This study included adults (>16 years) with no dry eye disease prior to BMT. The patients were seen by an ophthalmologist before BMT and annually after BMT. The ophthalmological examination included tear break‐up time, Schirmers test, corneal fluorescein stain, slit lamp examination and ophthalmoscopy. The criteria proposed by the “International Chronic Ocular GVHD Consensus Group” was used to diagnose ocular cGVHD.ResultsOut of the 939 patients included, 222 patients (23.6%) developed ocular cGVHD. We found no significant difference between gender and the development of ocular GVHD (p = 0.67). Median age at time of BMT was 41 years (rage 16–73) and 46 years (17–68) in the group who developed ocular cGVHD. Median time of onset of ocular cGVHD was 20 months (0.4–196) after BMT. Diagnosis of ocular cGVHD preceded systemic cGVHD in 33 cases (15%). Twenty‐seven patients (12%) had ocular cGVHD without systemic cGVHD. Ocular cGVHD was significantly higher in patients with systemic cGVHD involving the skin (p < 0.001).ConclusionsOcular cGVHD is common after BMT. It can occur at any age, but is more common in elder patients. Ocular cGVHD can occur in patients without systemic cGVHD. We recommend ophthalmological examinations in all patients before and after allogeneic BMT due to the high frequency of ocular cGVHD.
The STZ‐induced diabetic rat as a model for studying neuronal pathologies of diabetic retinopathy
Authors: Herrmann R. , Zippel N. , Haller J. , Streicher R. 
Published: September 2015

PurposeDiabetic retinopathy (DR) is a sight‐threatening complication of diabetes and a leading cause of blindness in adults. Current therapies target late‐stage vascular dysfunction of DR. However, DR is not a vascular disease per se, but is also characterized by chronic neurodegeneration. To identify neuroprotective treatments, it is critical to utilize appropriate animal models reflecting a hyperglycemia‐dependent loss of retinal function. Here we report a comprehensive characterization of the STZ‐induced diabetic rat as a model for neuronal dysfunction in DR.MethodsHyperglycemia was induced in Brown Norway rats upon STZ treatment. Blood glucose levels were monitored regularly and insulin levels were measured at study termination. To investigate different aspects of retinal function, dark‐ and light‐adapted flash and flicker electroretinograms were recorded at 4 and 7 weeks post STZ application, respectively. One group of animals received insulin treatment for antagonizing the effects of hyperglycemia.ResultsSTZ treatment led to decreased insulin and increased blood glucose levels. Hyperglycemia caused functional impairments of both rod‐ and cone‐driven pathways on the level of the outer as well as the inner retina, which could be partially rescued by insulin treatment. Overall, the degree of functional impairments correlated with increasing blood glucose levels.ConclusionsThe STZ‐induced diabetic rat model is characterized by a hyperglycemia‐dependent dysfunction of retinal neurons. Thus, this model is an attractive tool for investigating novel mechanisms underlying DR.
Surface modification of intraocular lenses towards controlled drug delivery
Authors: Filipe H.P. , Bozukova D. , Pimenta A. , Vieira A.P. , Alves P. , Coimbra P. , Guiomar A.J. , Gil M.H. , Mata J.L.G. , Serro A.P. 
Published: September 2015

PurposeOcular drug delivery systems replacing or complementing the usual therapeutics after cataract surgery have been the focus of several studies. A possible solution could be implanting intra‐ocular lenses (IOLs) also acting as drug carriers. The main challenge is to obtain IOLs that besides providing the best refractive outcome release the drug at a suitable rate. The purpose of our research was to design an effective strategy to incorporate the drug and study the release profile.MethodsIOL surface was modified with PHEMA [poly(2‐hydroxyethyl methacrylate)] by treatment with argon plasma and subsequent immersion in a HEMA solution with moxifloxacin (MFX; Vigamox®), followed by a final immersion in an MFX solution. Drug release profiles were obtained in vitro under hydrodynamic conditions, which simulate those found in the eye for the aqueous humor. A microfluidic cell with a volume of 250 μL was designed and used with a continuous flow of saline solution, at 37°C, with a renovation rate similar to the physiological one.ResultsResults showed that MFX was released with concentrations above the minimum inhibitory concentrations for S. aureus, S. epidermidis and S. pneumoniae for 11 days.ConclusionsIn the conditions described, IOLs surface modification with PHEMA has allowed an extended drug release effective to prevent post cataract surgery endophthalmitis.
Surgically induced corneal astigmatism after fornix‐based trabeculectomy
Authors: Van Keer K. , Willekens K. , Abegão Pinto L. , Delbeke H. , Vandewalle E. , Stalmans I. 
Published: September 2015

PurposeTo evaluate the degree of surgically induced corneal astigmatism (SIA) following trabeculectomy and to investigate the relation of SIA with long‐term reduction of intraocular pressure (IOP).MethodsFourty‐four eyes of 44 patients undergoing fornix‐based trabeculectomy were included in this single center, prospective trial. IOP, visual acuity (VA), corneal astigmatism, medication use and adverse events were recorded preoperatively and at 1, 3, 6 and 18 months postoperatively. Changes in corneal astigmatism were analysed using vector analysis. Pre‐ and postoperative parameters were compaired using one‐sample t‐test. Correlation between SIA and IOP were assessed using Pearson correlation coefficients.ResultsVector analysis of corneal astigmatism revealed a significant increase in with‐the‐rule corneal astigmatism, reaching a maximum at 1 month postoperatively (1.15 ± 0.8 D, P < 0.001) followed by a gradual decline (0.87 ± 0.8 D, P < 0.001 at month 18). SIA at 1 month showed a borderline significant correlation with IOP reduction at 3 months (r = 0.315, P = 0.051). SIA at 3, 6 and 18 months did not correlate with reduction in IOP (P > 0.05). After a transient decline at 1 month after surgery, VA recovered to preoperative values at month 3 without need for adjustment of the optical correction.ConclusionsFornix‐based trabeculectomy induces statistically significant with‐the‐rule astigmatism without affecting long term VA. In our population, maximum SIA, measured at 1 month postoperatively, showed a borderline significant correlation with reduction of IOP at 3 months.
Sarilumab for the treatment of posterior segment non‐infectious uveitis (NIU): The SATURN (SARIL‐NIU) study
Authors: Heissigerova J. , Sundaram P.A. , Erickson K. , Varona R. , Corp‐dit‐Genti V. , Vitti R. , Buggage R. , Rihova E. , Nguyen Q.D. 
Published: September 2015

PurposeInterleukin‐6 (IL‐6) and/or its soluble receptor are detected in the vitreous and aqueous humors of patients with uveitis. Inhibition of IL‐6 signaling in a murine model of experimental autoimmune uveitis suppresses the development of uveitis. We designed an exploratory Phase 2 study to evaluate the efficacy and safety of sarilumab, a human monoclonal antibody directed against the alpha subunit of the IL‐6 receptor complex in the management of posterior segment NIU.MethodsSATURN is a 52‐week, multicenter, double‐masked, placebo‐controlled, parallel arm, randomized trial to evaluate the efficacy and safety of sarilumab (200 mg) administered subcutaneously every 2 weeks in patients with posterior NIU, who are treated with systemic steroids (as single therapy or with methotrexate). Efficacy and safety are assessed at each visit. The study primary endpoints are reduction from baseline in vitreous haze or systemic‐steroid sparing effects, both measured at week 16. Other key endpoints assessed at week 16 include the change from baseline in: central retinal thickness, best‐corrected visual acuity, and percentage of patients with retinal vessel leakage on fluorescein angiography.ResultsThe study has completed enrollment. As of April 6, 2015, 58 patients have been randomized and treated.ConclusionsThe SATURN study may help clarify the role of IL‐6 in the pathogenesis of NIU and the potential for IL‐6 inhibition in the management of posterior segment NIU.
Microfluidic in vitro Drug Release from Contact Lens Materials
Authors: Filipe H.P. , Paradiso P. , Valente A.R.B. , Mata J.L.G. , Saramago B. , Henriques J.M. , Serro A.P. 
Published: September 2015

PurposeOver 90% of ophthalmic drugs are commonly applied as eye drops. However, drug tear film residence time is less than 5 min, and only 5% of the administered drug is absorbed, leading to a final poor drug bioavailability and eventual side effects Efforts have been made to develop more effective drug delivery systems. Therapeutic contact lenses (CLs) have demonstrated to be a good vehicle for a controlled release of a variety of drugs owing to their biocompatibility, high degree of comfort, and prolonged contact with the eye.MethodsCLs materials were prepared as a) a conventional hydroxyethylmethacrylate (HEMA) based hydrogel and as b) a silicone based hydrogel. The different materials were loaded with an antibiotic‐ levofloxacin (LVF), and one of two non‐steroidal anti‐inflammatory drugs (NSAID) ‐diclofenac (DCF) and ketorolac (KET). To simulate physiological human eye conditions such as temperature, tear volume and flow rate, drug release tests were carried out in a novel microfluidic cell.ResultsResults showed that a) HEMA based hydrogel allows a drug release up to 10 hours with predicted concentrations in the eye as >129 µg/mL for LVF, >918 µg/mL for DCF and > 251 µg/mL for KET whereas b) Silicone based hydrogel releases both NSAID for at least 4 days, with concentrations >163 µg/mL for DCF and >31 µg/mL for KET.ConclusionsDrug eluted CLs biomaterials can be used as a platform for ocular drug delivery applications.
Management of acute submacular haemorrhage: Royal free hospital experience
Authors: Sim S.Y. , Elhousseini Z. , Maragkos I. , Asaria R. 
Published: September 2015

PurposeTo evaluate visual outcomes of patients presenting with acute submacular haemorrhage (SMH) secondary to neovascular Age Related Macular Degeneration (nAMD) treated with pars plana vitrectomy (PPV), subretinal recombinant tissue plasminogen activator (rTPA) and air.MethodsRetrospective, clinical case series. 7 patients with acute SMH secondary to nAMD, underwent PPV, instillation of 50 μg/0.1 ml subretinal alteplase and air tamponade. Data was obtained from Electronic Medical Records (EDRM) of the Royal Free Hospital from October 2013 to March 2015. Patient demographics (age, gender, and laterality), duration between onset and treatment, visual acuity (VA) and any concurrent treatment were recorded.Results7 patients were included in our study with mean age ‐ 69.1 years (Range: 60–87). 3 patients had cataract. No other ocular comorbidities. Mean period between onset of symptoms to treatment was 13.7 days (Range: 1–56). At presentation, six patients had hand movement (HM) VA and one patient had counting fingers (CF) VA. At one month post‐operatively, 6 patients (85.7%) demonstrated VA improvement ≥1 line, of whom 3 (42.9%) improved by ≥2 lines. At 6 months post‐operatively however, only 3 (42.9%) patients had sustained VA improvement. Post‐operative OCT demonstrated complete displacement of SMH in 4 patients (57.1%), while 3 patients had residual submacular organised blood.ConclusionsSubretinal rTPA following vitrectomy with air tamponade may be used to dissolve submacular blood mass enabling physicians to resume NHS funded anti‐VEGF therapy. Long‐term visual outcome is often limited by underlying disease progression.
Ocular Sarcoidosis Surgery as the most effective option to avoid blindness
Authors: Martinez M. , Del Buey M. , Perez I. , Idoate A. , Sánchez J.I. , Ascaso J. , Cristobal J. 
Published: September 2015

PurposeTo present the clinical evolution and diagnosis of a patient with binocular and no simultaneous affection of posterior synechiae, associated to bombe iris and neovascular glaucoma, without medical treatment response.MethodsClinical case: A 63 year‐old male is assisted in the ER because of progressive and painless visual loss in his left eye; visual acuity was only light perception. Anterior segment (AS) showed a synechia, ambarin atypical membranous tissue and neovascularization in the pupillary area, causing an iris bombe with no acute inflammatory signs and an IOP of 60 mmhg. Ocular sonogram and ultrasound bio microscopy didn't show tumor growth. The treatment with anti‐inflammatory, hypotensive and mydriatic eye drops could not break the synechiae nor reach normal IOP. One year later, the patient came to the ER because of right eye visual loss. AS showed a similar synechial tissue, no tyndall effect and IOP of 20 mmhg. Due to the left eye experience, we decided to practice surgery in the right eye.ResultsWe took aqueous humor sample + synechiotomy + iridian biopsy + phacoemulsification with IOL. 20/20 visual acuity after surgery. After many medical tests and the anatomopathological study, the patient was released from the hospital with probable pulmonary and ocular sarcoidosis.ConclusionsIf we have a patient with atypical progressive posterior synechiae without inflammatory signs and with no treatment response, we should think about sarcoidosis ocular as the diagnosis. Our experience shows that an early surgery is the most effective option to avoid blindness in these cases.
Immune Responses at the Ocular Surface
Authors: Saban D.R. 
Published: September 2015

SummaryImmune‐mediated diseases of the ocular surface are relatively broad in their respective etiologies, which can involve infection, autoimmunity, or allergy. Despite this range, immune responses often converge upstream at the level of the dendritic cell (DC)—a highly specialized group of antigen presenting cells required in the activation of naïve T cells. Our lab has established a novel mouse model of allergic eye disease (AED), which leads to severe clinical manifestations, sustained ocular inflammation, and eosinophilic infiltration at levels seen in patients with atopic keratoconjunctivitis. Use of the AED model has led to identification of classical CD11b+ DCs as the key subset responsible for activating allergen reactive T cells. In addition, the AED model has uncovered the importance of CCR7 as the master chemokine receptor in homing of ocular surface DCs to the regional lymph nodes. Additionally, CCR7 has recently been shown to contribute to activation of Th17 cells in the mouse model of dry eye disease. Likewise, similar to the dry eye disease model, AED involves corneal lymphangiogenesis—potentially suggesting a role for corneal DCs in allergic immune responses. Thus, efforts to progress the current understanding of DC biology holds tremendous promise for advancement of novel and effective medicines in immune mediated diseases of the ocular surface.
Study of Xailin night physical Properties versus marketed ocular lubricant products
Authors: Pilotaz F. , Pecout A. , Do M. 
Published: September 2015

PurposeXailin Night is a multi‐dose preservative free lubricating eye ointment for night‐time relief of dry eye sensations. It contains white soft paraffin 57.3% w/w, white mineral oil 42.5% w/w and lanolin alcohols 0.2% w/w. Comparative studies were performed with Xailin Night against other marketed products in the EU in order to assess its key physical properties.MethodsTested products cover the whole range of ocular lubricants from oily formula to aqueous compositions. The parameters studied were the following: Viscosity and rheological behaviour (25°C and 35°C), capacity to slow down evaporation at 40°C and 70°C, spreading capacity at room temperature and 35°C, long‐lasting assessment. The products marketed in the EU assessed in this study were: Viscotears liquid gel, Lipolac, Celluvisc 4 mg/0.4 mL, Siccafluid 2.5 mg/g, Bepanthen, Vismed multi, Hyabak 0.15%, Artelac Nighttime Gel.ResultsAt room temperature, Xailin Night viscosity shows an intermediate profile included between low viscosity gels (Siccafluid) and very highly viscous products (Bepanthen, Viscotears and Lipolac). As expected, temperature has an effect on the rheological behaviour of ointments but not on the other products. No evaporation is observed for Xailin Night whatever the temperature, while all the other tested products show a slight evaporation. Lipolac and Viscotears have a superior spreading capacity compared to pure aqueous‐based products but remain significantly lower than ointments. As an ointment, Xailin Night has a superior long‐lasting effect than aqueous products.ConclusionsXailin Night is an ocular ointment with a strong long lasting effect and shows no evaporation compared to aqueous based ocular lubricants.
New management of peri‐ocular basal cell carcinoma using in vivo and ex vivo confocal microscopes
Authors: Espinasse M. , Grivet D. , Perrot J.L. , Cinotti E. , Labeille B. , Forest F. , Gain P. , Thuret G. 
Published: September 2015

PurposeWe have been using a handheld dermatology in vivo reflectance confocal microscopy (IVCM) for the imaging of the whole ocular surface and ocular adnexa for more than two year (JAmAcadDermatol2014;71:912, AJO2015;159:324), mainly for noninvasive diagnosis before surgery. Ex vivo confocal microscopy (EVCM) is a new device that allows pseudo histology in freshly excised tissue. Aim: to assess a new management strategy for eyelids lesions suspected to be basal cell carcinoma (BCC) using these two complementary confocal microscopes (CM).MethodsIVCM and EVCM, both using vivascope CM (Lucid Inc, NY) were performed by 3 skilled dermatologists having more than 500 CM diagnoses each with pathology confirmation. Forty consecutive peri‐ocular BCC were diagnosed by IVCM. Two millimetre‐margin incisions were made during surgery. Freshly excised tissues were mounted, unstained, between two glass slides and analysed “en face” with EVCM to delimitated the tumour and the clearance of margins. Diagnosis and margins were confirmed by standard pathology and immunolabeling on fixed tissues.ResultsWe obtained the first “en face” EVCM to delimitated the tumour. The acquisition of the whole tumour took less than 3 minutes. Tissues were not damaged by flat mount nor by exposure to laser beam. Histology confirmed all IVCM diagnosis of BCC and all clear margins.ConclusionsAssociation of IVCM and EVCM allowed accurate management of peri ocular BCC, using micrographic surgery to reduced surgical margins. GRANT: project INNOVEYE GIRCI RAA.
Canaloplasty with the Stegmann Canal expander – two years results
Authors: Grieshaber M. , Schoetzau A. , Stegmann R. 
Published: September 2015

PurposeTo assess the safety and efficacy of circumferential viscocanalostomy (canaloplasty) using a new canal expander in Caucasians with primary open‐angle glaucoma (POAG).MethodsThirty‐five eyes of 35 consecutive patients with medically uncontrolled POAG underwent primary canaloplasty and implantation of the Stegmann Canal Expander into Schlemm's canal. Schlemm's canal was unroofed ab externo, and dilated with viscoelastic material and microcatheter. The Stegmann Canal Expander was implanted into the canal lumen, and the superficial scleral flap was closed watertight. Laser goniopuncture of the trabeculo‐Descemet's membrane window was performed if postoperative intraocular pressure (IOP) exceeded 16 mmHg.ResultsThe mean IOP dropped from 26.6 ± 4.2 mm Hg preoperatively to 12.1 ± 2.6 mm Hg at 1 month, 13.1 ± 1.9 mmHg at 6 months, 13.0 ± 1.9 mm Hg at 12 months, and 13.4 ± 2.4 mm Hg at 24 months (p < 0.001). Laser goniopuncture was performed on 5 eyes (14.7%) 6.4 months after surgery; the mean IOP was 19.1 mm Hg before and 14.1 mm Hg after goniopuncture. The number of medications dropped from 2.9 ± 0.3 before surgery to 0.08 ± 0.3 after surgery (p < 0.001). The postoperative BCVA at last visit (0.12 ± 0.09; range, 0–0.39) was comparable to preoperative values (0.16 ± SD 0.10; range, 0–0.39) (p = 0.35). Complications were minor and included microhyphema (14 eyes) and transient elevated IOP (steroid responder; 4 eyes), partial peripheral Descemet's membrane detachment (2 eyes).ConclusionsCanaloplasty with implantation of the Stegmann Canal Expander reduced IOP significantly in POAG with a low risk for complications.
The study of needle tip aspirates and entry sites after intravitreal injections with different needle types
Authors: Lytvynchuk L. , Savytska I. , Sergiienko A. , Binder S. , Petrovski G. 
Published: September 2015

PurposeTo compare the entry site and study the cellular content of different needle tip aspirates after transscleral intravitreal injection (IVI) on rat eyes.MethodsThe intravitreal injections (IVI) were performed on 20 white outbred rat eyes (10 IVI with 30‐gauge subcutaneous needles (SCN), 10 with 27‐gauge Pencan needle (PCN) (B.Braun)). The 1.0 cc syringes were preloaded with 0.02 cc of balanced salt solution (BSS) and connected to the needles. The penetration was performed 1 mm posterior to the limbus, followed by aspiration of 0.01 cc vitreous body. Aspirated material was evacuated onto glass slides and stained by Azure‐2‐Eosin. Enucleation and histological analysis of the IVI entry site was performed at magnification 100 and 400 times.ResultsCellular content of the aspirated material was revealed in all cases. The aspirated cells represented conjunctival epithelial‐, ciliary body non‐pigmented epithelial‐, sclerocyte‐like cells and vitreous crystallised specimens. The amount of conjunctival epithelial cells prevailed in 27‐gauge PCN IVI cases. The stained granular proteins were less significant in the case of 27‐gauge PCN tips. The entry sites after 30‐gauge SCN injection showed concrete cut of all tissues, while partial reassembling of the sclerocyte bindings was seen after 27‐gauge PCN injections.ConclusionsThe use of 30‐gauge SCN and 27‐gauge PCN needles for transscleral IVI has resulted in trauma of all layers of the rats’ eye wall. Histological analysis of the needle tip aspirates showed less tissue damage by 27‐gauge PCN; moreover, the SCN tips created complete cuts due to their sharp edges, in contrast to the PCN tips.