Topical Administration of a Nanoformulation of Chitosan-Hyaluronic Acid-Epoetin Beta in a Rat Model of Glaucoma.

The present work investigates the effects of chitosan-hyaluronic acid-epoetin beta (CS/HA-EPOß) nanoparticles after topical ocular administration in a rat glaucoma model. Wistar Hannover rats (n = 24) were submitted to a complete ophthalmological examination and electroretinography, followed by glaucoma induction in their right eye on day 1 of the study. Treatment group (T) received CS/HA-EPOß nanocarriers (n = 12), while the control group (C) received only empty ones. Electroretinography was repeated on day 3 (n = 24) and before euthanasia on day 7 (n = 8), 14 (n = 8), and 21 (n = 8), followed by bilateral enucleation and histological assessment. The animals showed good tolerance to the nanoformulation. Maximum IOP values on the right eye occurred shortly after glaucoma induction (T = 62.6 ± 8.3 mmHg; C = 63.6 ± 7.9 mmHg). Animals from the treated group presented a tendency for faster recovery of retinal electrical activity (p > 0.05). EPOß was detected on the retina of all treated eyes using immunofluorescence. Control animals presented with thinner retinas compared to the treated ones (p < 0.05). Therefore, topical ocular administration of CS/HA-EPOß nanoparticles enabled EPOß delivery to the retina of glaucomatous rats and promoted an earlier retinal recovery, confirming EPOß's neuroprotective effects. The encouraging results of this preclinical study pave the way for new strategies for topical ocular administration of neuroprotective compounds.

Diagnostic approach and grading scheme for canine allergic conjunctivitis.

BACKGROUND: In humans, allergic conjunctivitis is a well described disease. In contrast, allergic conjunctivitis has not received much attention from the veterinary community so far. Canine allergic conjunctivitis (cAC) is one of the possible manifestations associated with canine atopic dermatitis (cAD), being often underdiagnosed and undertreated. Our aim is to contribute to disease characterization and clinical stagingfor cAC severity. RESULTS: A retrospective observational study including 122 dogs that underwent a complete ophthalmological and dermatological examinations and diagnosed with allergic conjunctivitis was conducted. A total of six ophthalmic clinical signs were considered for disease characterization and clinical staging: conjunctival hyperemia, chemosis, ocular pruritus, epiphora, seromucoid to mucopurulent discharge and keratitis, classified from 0 (absent) to 3 (severe). Scores comprised between 1-5 were considered mild, 6-10 moderate and 11-18 severe. The majority of dogs (64%) presented with moderate cAC followed by 24% of mild stages and only 12% of severe presentations. The severity of allergic conjunctivitis was not correlated to sex or age at the time of diagnosis and all presented with a bilateral form of the disease. Chemosis (84%), hyperemia (83%) and ocular pruritus (79%) was observed in 55% of the cases. Seromucoid to mucopurulent discharge (62%) and epiphora (69%) were less frequent, with keratitis being the least encountered clinical sign (15%). The degree of keratitis showed a positive correlation with both severity and chronicity of cAC (rho = 0.21-0.29, p ≤ 0.02)). Severity of cAD and cAD were not significantly correlated (p-value = 0.4). DISCUSSION AND CONCLUSION: The triad hyperemia, chemosis and ocular pruritus, already known in human medicine to be a reliable way of diagnosing human allergic conjunctivitis, also proved to be important in cAC Mild forms of the disease may pass unnoticed, ocular pruritus being hard to assess in canine patients.The proposed standardized diagnostic approach and novel grading scheme for cAC may be of value for both veterinary ophthalmologists and dermatologists, as well as general practitioners.

Topical ocular delivery of nanoparticles with epoetin beta in Wistar Hannover rats.

Topical instillation of drugs targeting the posterior ocular segment is an expanding area of research. Chitosan and hyaluronic acid have remarkable mucoadhesive properties and potentially enhance pre-corneal retention time after topical instillation. Bearing this in mind, we explored the possibility of delivering epoetin beta (EPOß) to the posterior segment of the eye in a chitosan-hyaluronic acid (CS/HA-EPOß) nanoparticulate system using the topical route of administration. Complete ophthalmological examinations, electroretinography and microhematocrit evaluations were performed in Wistar Hannover (WH) rats, before and after topical administration of nanoparticles. The right eye received CS/HA-EPOß and the left eye received only empty nanocarriers (control). Animals were split into 6 groups and at designated timepoints, all animals from each group (n = 3) were euthanized and both eyes enucleated. Retinal morphology and EPOß ocular distribution were assessed, respectively, through hematoxylin and eosin (HE) and immunofluorescence staining. After topical administration, no adverse ocular signs were noted and no significant changes either in microhematocrits nor in electroretinographies were detected. During the study, intraocular pressure (IOP) was always kept within physiological range bilaterally. No histological changes were detected in any of the ocular globes. Immunofluorescence enabled the identification of EPOß in the retina 12 h after the administration, its presence still being detectable at day 21. In conclusion, CS/HA nanoparticles could efficiently deliver EPOß to the retina of WH rats after topical instillation, being considered biologically safe. Topical administration of this nanoformulation could be a valuable tool for retinal neuroprotection, decreasing risks associated with more invasive routes of administration, being cost effective and also increasing long-term patients' compliance.

Chitosan and Hyaluronic Acid Nanoparticles as Vehicles of Epoetin Beta for Subconjunctival Ocular Delivery.

Neuroprotection in glaucoma using epoetin beta (EPOß) has yielded promising results. Our team has developed chitosan-hyaluronic acid nanoparticles (CS/HA) designed to carry EPOß into the ocular globe, improving the drug's mucoadhesion and retention time on the ocular surface to increase its bioavailability. In the present in vivo study, we explored the possibility of delivering EPOß to the eye through subconjunctival administration of chitosan-hyaluronic acid-EPOß (CS/HA-EPOß) nanoparticles. Healthy Wistar Hannover rats (n = 21) were split into 7 groups and underwent complete ophthalmological examinations, including electroretinography and microhematocrit evaluations before and after the subconjunctival administrations. CS/HA-EPOß nanoparticles were administered to the right eye (OD), and the contralateral eye (OS) served as control. At selected timepoints, animals from each group (n = 3) were euthanized, and both eyes were enucleated for histological evaluation (immunofluorescence and HE). No adverse ocular signs, no changes in the microhematocrits (≈45%), and no deviations in the electroretinographies in both photopic and scotopic exams were observed after the administrations (p < 0.05). Intraocular pressure remained in the physiological range during the assays (11-22 mmHg). EPOß was detected in the retina by immunofluorescence 12 h after the subconjunctival administration and remained detectable until day 21. We concluded that CS/HA nanoparticles could efficiently deliver EPOß into the retina, and this alternative was considered biologically safe. This nanoformulation could be a promising tool for treating retinopathies, namely optic nerve degeneration associated with glaucoma.

Colloidal nanosystems with mucoadhesive properties designed for ocular topical delivery.

Over the last years, the scientific interest about topical ocular delivery targeting the posterior segment of the eye has been increasing. This is probably due to the fact that this is a non-invasive administration route, well tolerated by patients and with fewer local and systemic side effects. However, it is a challenging task due to the external ocular barriers, tear film clearance, blood flow in the conjunctiva and choriocapillaris and due to the blood-retinal barriers, amongst other features. An enhanced intraocular bioavailability of drugs can be achieved by either improving corneal permeability or by improving precorneal retention time. Regarding this last option, increasing residence time in the precorneal area can be achieved using mucoadhesive polymers such as xyloglucan, poly(acrylate), hyaluronic acid, chitosan, and carbomers. On the other hand, colloidal particles can interact with the ocular mucosa and enhance corneal and conjunctival permeability. These nanosystems are able to deliver a wide range of drugs, including macromolecules, providing stability and improving ocular bioavailability. New pharmaceutical approaches based on nanotechnology associated to bioadhesive compounds have emerged as strategies for a more efficient treatment of ocular diseases. Bearing this in mind, this review provides an overview of the current mucoadhesive colloidal nanosystems developed for ocular topical administration, focusing on their advantages and limitations.

Clinical signs of brachycephalic ocular syndrome in 93 dogs.

BACKGROUND: Brachycephalic breeds have anatomical skull changes that are responsible for ocular clinical signs, known as the brachycephalic ocular syndrome (BOS). Their popularity has increased in recent years but the excessive pressure of selection lead to extreme conformation of skull shapes, resulting in facial alterations that can put these dogs' vision at risk. OBJECTIVES: This study aimed to analyse the ocular disorders in a sample of 93 brachycephalic dogs to better characterize the disease complex BOS. MATERIAL AND METHODS: Brachycephalic dogs were submitted to a complete ophthalmological examination. The studied parameters included animal's sex, age and breed, age, ophthalmological tests performed, results of complementary exams, clinical signs, ocular disorders, treatment protocols and their outcomes. Data were organized using Microsoft Office Excel 2007® and statistical analysis was performed with IBM SPSS Statistics 20®. RESULTS: The studied population included 93 brachycephalic dogs 45 males (48%) and 48 females (52%) from different breeds: French Bulldog (n = 38), Shih-Tzu (n = 22), Pug (n = 17), English Bulldog (n = 5), Pekingese (n = 4), Boxer (n = 4) and Boston Terrier (n = 3), aged between 0.2-16 years, median 4.65 years. The most frequent ocular abnormalities were corneal ulcers in 44%, corneal pigmentation in 36%, corneal fibrosis in 25% and entropion in 22% of the animals. There was a higher incidence of corneal pigmentary keratitis in Pugs (53%) and corneal fibrosis in Shih Tzus (36%). The most common surgical techniques were medial canthoplasty in 22%, conjunctival flap in 10% and electroepilation in 7% of the cases, without post-operative complications. CONCLUSIONS: This study contributed to a better characterization of the disease complex brachycephalic ocular syndrome. The percentage of ocular disorders like entropion, corneal pigmentation, fibrosis and ulcers was high, highlighting the importance of a regular ophthalmological check-up, and early diagnosis of the primary disorders. A higher incidence of corneal pigmentation was noticed in Pugs and corneal fibrosis in Shih Tzus, which suggests that some brachycephalic breeds may be predisposed to certain ocular abnormalities. A responsible reproductive strategy should be implemented to avoid undesired transmission of the abnormal traits to the offspring.

Congenital ocular malformations in dogs and cats: 123 cases.

OBJECTIVE: Provide epidemiological data regarding the prevalence of congenital ocular malformations in dogs and cats. ANIMALS STUDIED: A population of 32 974 dogs and 13 977 cats that presented for consultation at the veterinary teaching hospital. PROCEDURES: Medical records from 2011 to 2018 were reviewed. A retrospective and prospective epidemiological clinical study addressing congenital ocular malformations was conducted. Signalment, medical history, reason for presentation, clinical findings, vision impairment, and treatment options were analyzed. RESULTS: From the total of cases analyzed, 103 dogs (0.3%) and 20 cats (0.1%) met the inclusion criteria. The majority of dogs were mixed breed, the most common breed being the French Bulldog, while the majority of cats were European domestic shorthair. The median age of diagnosis was 12 months for dogs and 6 months for cats. Sex predisposition was not found. The most frequently identified abnormalities were as follows: congenital cataract (dogs: 31.1%; cats: 30.0%), microphthalmia (dogs: 35.0%, cats: 25.0%), and persistent pupillary membrane (dogs: 27.2%, cats: 40.0%). Some of the concurrently observed malformations were significantly associated. A statistically significant association was found between ocular dermoids and the French Bulldog breed (P < .001). CONCLUSIONS: Even though congenital ocular malformations are uncommon, knowledge about their prevalence is important, since they can cause vision impairment or even blindness. Moreover, some human ocular disease phenotypes are similar to the ones presented by dogs and cats, so they can be used as models to investigate pathophysiology and therapeutic approaches.

Topical chemotherapy with mitomycin C in a feline corneal squamous cell carcinoma.

CASE SUMMARY: A 9-year-old cat was presented with a right globe lesion of 6 months' duration. A large pink elevated mass covering two-thirds of the right cornea was detected. The corneal mass was surgically removed by superficial keratectomy and diagnosed by histopathology as a squamous cell carcinoma (SCC). The surgical procedure led to a relatively transparent cornea, but recurrence was likely. To avoid relapse, 1 month after surgery three cycles of mitomycin C 0.04% eye drops were applied q8h for 15 days on/15 days off. No local or systemic side effects were seen, and no recurrence was detected after 1 year of follow-up. Topical mitomycin C was successfully used as adjuvant local chemotherapy agent and prevented relapses owing to its cytostatic effect. RELEVANCE AND NOVEL INFORMATION: SCCs are relatively common in feline patients, especially in the non-pigmented extremities of the nose, ears and eyelids, but with the cornea being a rare location. They rarely metastasise and they seldom relapse locally after surgical excision. Surgical-free margins of 2 cm are advisable to prevent relapses. Corneal tumours are rare, as the cornea is avascular; corneal transparency is essential to assure clear vision. In corneal SCC this margin is impossible to achieve without enucleation. In the present report, surgical removal of the neoplasm was combined with topical administration of the anticancer drug mitomycin C and a good prognosis was obtained. This combined treatment may be an appropriate therapeutic option for feline corneal SCC.

Selected cytokine expression in dogs with alergic conjunctivitis: Correlation with disease activity.

INTRODUCTION: Canine allergic conjunctivitis (cAC) is described as the most frequent ocular manifestation associated with canine atopic dermatitis (cAD). OBJECTIVES: Clinical and immunological characterization of cAD through IL-6, TNF-α and IL-12 mRNA expression quantification in canine conjunctivae. PROCEDURES: Twenty client-owned dogs with both cAC and cAD and twenty-one healthy controls were enrolled and clinician assessed CADESI-04 and grade of ocular signs were calculated. Conjunctival biopsies were performed on all animals and relative quantification of the interleukins mRNA expression performed by qRT-PCR. The correlation between cytokine gene expression and cAC score was evaluated, as well as CADESI-04 values. RESULTS: The qRT-PCR showed a significant gene upregulation of respectively 291.48 (p = 1.306e-09) and 4.85 (p = .00033) folds on IL-6 and IL-12 in dogs with allergic conjunctivitis compared to the control group. Regarding the average expression of TNF-α there were no statistical significant differences between both groups (p = .18). Higher cAC scores were associated with enhanced gene expression of TNF-α and IL-12. No correlation was found between the cytokine gene expression levels and the CADESI-04 values. CONCLUSION: An increase of IL6 and IL12 in cAC was found in the studied population. These two cytokines may be potential immunotherapy targets cAC classification.

New nanoparticles for topical ocular delivery of erythropoietin.

Erythropoietin (EPO) is known for its neuroprotective and neuroregenerative properties. EPO topical ocular administration has not been tested yet and its bioavailability could be improved by mucoadhesive hydrogels. Thus, this study aimed to develop and evaluate a chitosan (CS) and hyaluronic acid (HA) nanoparticulate system for topical ocular delivery of EPO. Nanoparticles were prepared by ionotropic gelation using six different HAs (HA1-HA6), and characterized by size, zeta potential (ZP), polydispersity index (Pdi), cytotoxicity and mucoadhesion. Encapsulation efficiency and drug loading capacity were also determined. Ex vivo permeation was tested using fresh porcine corneas, scleras and conjunctivas. The permeated EPO was quantified by ELISA, and its presence in the membranes was confirmed by immunohistochemistry. Nanoparticles (NPs) presented size ≤300 nm, ZP around +30 mV and low Pdi (0.167-0.539) at a 1:1 CS:HA mass ratio. The most suitable HA was HA6 (300 kDa - Eye), which had the best mucoadhesive properties. CS/HA6-EPO nanoformulation permeated more rapidly through porcine conjunctiva, followed by sclera and thirdly by cornea, as assessed by immunohistochemistry. All formulations were noncytotoxic on ARPE-19 and HaCaT cell lines, as evaluated by metabolic and membrane integrity tests. In conclusion, CS/HA6-EPO NPs could be a promising formulation for increasing EPO ocular bioavailability by enhancing its retention time and permeation through the different ocular membranes.

Granulomatous rhinitis secondary to feline leishmaniosis: report of an unusual presentation and therapeutic complications.

CASE SUMMARY: A 12-year-old male neutered domestic shorthair cat underwent rhinoscopy due to inspiratory dyspnoea and stertor. Rhinoscopy showed signs of chronic rhinitis and a multinodular nasopharyngeal mucosa. A marked infiltrate of macrophages that contained intracellular parasitic forms morphologically compatible with Leishmania amastigotes were observed on histopathological examination of nasal and nasopharyngeal biopsies. PCR from nasal tissue was positive for Leishmania infantum DNA, confirming the diagnosis of granulomatous rhinitis secondary to this parasite. Two eyelid nodules were identified 2 weeks later. Fine-needle aspiration revealed Leishmania amastigotes within macrophages and in the background. Allopurinol therapy was started, but 5 days later the cat developed dermatological signs compatible with a cutaneous adverse drug reaction. The drug was discontinued and meglumine antimoniate prescribed. Twenty-five days later, the cat presented with acute kidney injury and meglumine antimoniate was discontinued. Despite clinical improvement after fluid therapy, mild azotaemia persisted. The cat was subsequently treated with nucleotides and active hexose correlated compounds (N-AHCC). Four months later upper respiratory signs were exacerbated. A relapse of granulomatous rhinitis was suspected and miltefosine therapy started. Chronic kidney disease (CKD) worsened during miltefosine treatment, having improved under fluid therapy. Since then, the cat has been treated with N-AHCC and renal diet and at the time of writing shows stable CKD with no recurrence of respiratory signs. RELEVANCE AND NOVEL INFORMATION: This case describes Leishmania infantum as a cause of granulomatous rhinitis in a cat without cutaneous lesions, reporting the alternative use of N-AHCC and miltefosine when allopurinol seemed to have induced a cutaneous rash and there was acute kidney injury (AKI) after meglumine antimoniate therapy.

Functional and Structural Effects of Erythropoietin Subconjunctival Administration in Glaucomatous Animals.

PURPOSE: The present study aimed to assess functional and structural benefits of erythropoietin (EPO) when administered subconjunctivally in the retina of glaucomatous rats using electroretinography (ERG) and retinal thickness (RT) measurements. METHODS: Glaucoma was experimentally induced in 26 Wistar Hannover albino rats. Animals were divided into 2 groups of 13 animals each: a treated group receiving a unique subconjunctival injection of 1,000 IU of EPO and a control group receiving a saline solution. In each group, 7 animals were used for retinal function evaluation (ERG) and 6 animals were used for retinal structural evaluation (histology). RT was measured, dorsally and ventrally, at 500 µm (RT1) and at 1,500 µm (RT2) from the optic nerve. RESULTS: Retinal function evaluation: for both scotopic and photopic conditions, ERG wave amplitudes increased in the treated group. This increase was statistically significant (p < 0.05) in photopic conditions. Structural evaluation: for both locations RT1 and RT2, the retinas were significantly (p < 0.05) thicker in the treated group. CONCLUSION: Subconjunctival EPO administration showed beneficial effects both on retinal structure and on retinal function in induced glaucoma in albino rats. This neuroprotective effect should be applied in other animal species.

Ex vivo permeation of erythropoietin through porcine conjunctiva, cornea, and sclera.

The aim of this study is to test the permeation of human recombinant erythropoietin (rHuEPO) across conjunctiva, cornea, and sclera in an ex vivo model. Thirty fresh pig eyes were collected from a slaughterhouse. Conjunctivas (n = 10), corneas (n = 10), and scleras (n = 10) were surgically dissected from surrounding tissues. Ocular membranes were placed into Franz diffusion cells and rHuEPO was administered into the donor phase of each cell, except for control samples. Samples were collected from the receptor phase at seven time points, from 30 min to 6 h of incubation. Erythropoietin (EPO) was quantified by enzyme-linked immunosorbent assay (ELISA) technique. Ocular membranes immunohistochemistry was also performed at the end of the study. EPO was detected in all test samples. After 6 h of incubation, conjunctiva was the most permeable membrane to rHuEPO (509.3 ± 89.8 mIU/cm2, corresponding to 0.52% of the total rHuEPO administered on the donor phase), followed by sclera (359.1 ± 123.7 mIU/cm2, corresponding to 0.35%) and finally cornea (71.0 ± 31.8 mIU/cm2, corresponding to 0.07%). Differences between ocular membranes' permeation were statistically significant (p < 0.001). EPO immunostaining signal was positive for the three ocular membranes. We have demonstrated in an ex vivo model that porcine conjunctiva, cornea, and sclera are permeable to rHuEPO protein. These are promising results concerning ocular EPO administration.

Late prostatic metastasis of an uveal melanoma in a miniature Schnauzer dog.

This manuscript describes a previously unreported clinical case of canine uveal melanoma in a miniature Schnauzer dog with an unusual location of metastasis (prostate) and delayed occurrence (3 years after primary tumor diagnosis and enucleation). Immunohistochemical labeling of both tumors with Melan A, Ki-67, and c-kit added some valuable information.

Ocular Erythropoietin Penetration after Subconjunctival Administration in Glaucomatous Rats.

PURPOSE: The present study aimed to determine whether the subconjunctival administration of recombinant human erythropoietin (rHuEPO) reached the retina in glaucoma conditions. After subconjunctival rHuEPO administration, in a rat glaucoma model, erythropoietin (EPO) distribution in the rat's retina was studied by immunohistochemistry. METHODS: Female Wistar Hannover albino rats (n = 15) were divided into 2 groups, control (n = 3) and treated (n = 12). The animals' unilateral glaucoma was induced by coagulation of episcleral veins, under general anaesthesia. After vein coagulation, 1,000 IU of rHuEPO were administered by the subconjunctival route to the treated group (n = 12). The control group (n = 3) received only a subconjunctival saline injection. The contralateral eye of each animal remained untouched. Treated group animals were euthanized at different time points, i.e. days 1, 3, 7 and 14. Bilateral enucleation was performed, and EPO distribution in the rat's retina was assessed by immunohistochemistry. RESULTS: Glaucoma was confirmed by results of repeated intraocular pressure measurements over the experimental period. In the test group, EPO was identified in different neuroretinal cells, showing a stronger immunostaining signal during the first 2 time points in the retinal ganglion cell (RGC) layer. EPO protein was still present on day 14 after the subconjunctival injection. EPO was not detected in any of the control eyes or in any contralateral eye of the treated group. CONCLUSION: When administered subconjunctivally to glaucomatous eyes, rHuEPO reached the RGC layer and was still present at least 14 days after administration. The subconjunctival route was shown to be a promising alternative for ocular EPO delivery in glaucomatous conditions in a rat animal model.

Ajuste en la práctica clínica de las directrices treat-to-target para la artritis reumatoide: resultados del estudio ToARCan / Adjustment in the clinical practice of treat-to-target guidelines for rheumatoid arthritis: results of the ToARCan study

Objetivo. Analizar el cumplimiento de las directrices t2t en la práctica clínica. Métodos. Estudio observacional transversal en pacientes consecutivos con artritis reumatoide (AR) de 5 hospitales canarios. Los pacientes cumplimentaron escalas de actividad, el HAQ y respondieron si el médico les había explicado el objetivo del tratamiento. El médico recogió además: visitas en el último año, empleo de índices y HAQ, DAS28 de la visita actual y fecha de la siguiente consulta. Se analizó el porcentaje de cumplimiento de las recomendaciones t2t (R) 1, 3, 5-7 y 10. Resultados. Se reclutó a 343 pacientes, 77% mujeres, con edad promedio de 57 años y duración de la AR de 10 años. La mediana de visitas en el último año fue de 3 y el promedio de meses entre la visita anterior y la actual de 5,6. El 93% estaba en tratamiento con FAME y el 44% en remisión por DAS (R1). Se había realizado recuento articular en la visita previa al 85%, HAQ al 19%, EVA actividad del paciente al 41% y DAS28 al 35% (R6). La siguiente visita se programó en un promedio entre uno y 3 meses (R5) al 64% de los pacientes con DAS28>3,2. El 96% de los pacientes dijo haber sido informado del objetivo del tratamiento (R10). La variabilidad entre centros era moderada, pero existía. El único factor que determinaba la realización de un DAS28 en la última consulta era el centro de procedencia del paciente. Conclusiones. Los centros canarios estudiados logran altas cotas de remisión y baja actividad en sus pacientes; la realización de índices compuestos y la frecuencia de seguimiento recomendado por el t2t se cumplen, aunque hay oportunidad de mejora (AU)

Objective. To analyze compliance with t2t clinical practice guidelines. Methods. Cross-sectional observational study in consecutive patients with rheumatoid arthritis (RA) in 5 hospitals in the Canary Islands. Patients filled out activity scales, HAQ and answered the question of whether the doctor had explained the treatment target. The rheumatologist also collected: visits in the past year, use of activity indices and HAQ, DAS28 of current visit and date of the next visit. The percentage of compliance to indicators based on the t2t recommendations (R) 1, 3, 5-7 and 10 was analyzed. Results. A total of 343 patients were recruited, 77% female, mean age 57, RA duration of 10 years. Median visits in the last year were 3 and mean time between last and current visit was 5.6 months. A total of 93% of the patients were treated with DMARDs and 44% were in remission by DAS (R1). In the previous visit, documented joint count was present in 85%, a HAQ in 19%, patient VAS in 41%, and a DAS28 in 35% of the patients (R6). The next visit was scheduled at an average of 4.3 months (R5). In 64% of patients with DAS28> 3.2 a visit between one and 3 months was scheduled (R5). A total of 96% of patients said they had been informed of the treatment target (R10). Variability between centers existed but was moderate. The only factor determining the performance of a DAS28 in the last visit was the patient's center of origin. Conclusions. The Canary Island centers studied achieved high levels of remission and low activity in their patients. The performance of composite indices and follow-up frequency recommended by the t2t are met, although there is room for improvement (AU)

Adjustment in the clinical practice of treat-to-target guidelines for rheumatoid arthritis: Results of the ToARCan study.

OBJECTIVE: To analyze compliance with t2t clinical practice guidelines. METHODS: Cross-sectional observational study in consecutive patients with rheumatoid arthritis (RA) in 5 hospitals in the Canary Islands. Patients filled out activity scales, HAQ and answered the question of whether the doctor had explained the treatment target. The rheumatologist also collected: visits in the past year, use of activity indices and HAQ, DAS28 of current visit and date of the next visit. The percentage of compliance to indicators based on the t2t recommendations (R) 1, 3, 5-7 and 10 was analyzed. RESULTS: A total of 343 patients were recruited, 77% female, mean age 57, RA duration of 10 years. Median visits in the last year were 3 and mean time between last and current visit was 5.6 months. A total of 93% of the patients were treated with DMARDs and 44% were in remission by DAS (R1). In the previous visit, documented joint count was present in 85%, a HAQ in 19%, patient VAS in 41%, and a DAS28 in 35% of the patients (R6). The next visit was scheduled at an average of 4.3 months (R5). In 64% of patients with DAS28> 3.2 a visit between one and 3 months was scheduled (R5). A total of 96% of patients said they had been informed of the treatment target (R10). Variability between centers existed but was moderate. The only factor determining the performance of a DAS28 in the last visit was the patient's center of origin. CONCLUSIONS: The Canary Island centers studied achieved high levels of remission and low activity in their patients. The performance of composite indices and follow-up frequency recommended by the t2t are met, although there is room for improvement.

Factors associated with the intensification of treatment in rheumatoid arthritis in clinical practice.

The aim of the present study was to analyse the patterns of treatment adjustment in rheumatoid arthritis (RA) patients with active disease in routine clinical care. This was a cross-sectional study of consecutive patients with RA conducted in five hospitals. Activity scales (DAS28-ESR) and function (HAQ) were measured, as well as whether ultrasound was performed as part of the assessment. Treatment decision (no changes/reduction/intensification) and time to the next scheduled visit were the outcomes variables. Associated factors were analysed by multilevel regression models. A total of 343 patients were included (77 % women, mean age 57 years, mean RA duration 10 years), of whom 44 % were in remission by DAS28. Treatment was continued in 202 (59 %) patients, reduced in 57 (16 %), and intensified in 83 (24 %). In the 117 patients with active RA (DAS28 ≥ 3.2), treatment was intensified in 61 (52 %). Factors associated with treatment intensification were physician and patient VAS, and DAS28, but not the centre. In the multilevel regression analysis with intensification of treatment as dependent variable, the following factors were significantly associated: DAS28 [OR 3.67 (95 % CI 2.43-5.52)], patient VAS [OR 1.04 (95 % CI 1.01-1.08)], and have performed an ultrasound [OR 3.36 (95 % CI 1.47-7.68)]. Factors associated with time to the next scheduled visit (an average of 4.3 months) were patient and physician VAS, DAS28, and centre. In clinical practice, half of the patients with active RA maintain or reduce the treatment. The decision to intensify treatment in active RA as recommended by a treat-to-target strategy is complex in practice.

Endophthalmitis due to an intra-ocular linear foreign body in a cat.

CASE SUMMARY: An unusual case of an intraocular linear foreign body that migrated from the oral cavity, causing a severe endophthalmitis, in a cat is described. A 2-year-old female domestic shorthair cat presented with signs of infection from the left eye that had begun 2 weeks previously. Despite having been prescribed oral and topical antibiotics, there was a progressive worsening of the clinical signs. On ophthalmic examination the cat presented with severe endophthalmitis, secondary glaucoma and exposure keratitis of the left eye. Radiography demonstrated the presence of an intraocular linear metallic foreign body compatible with a sewing needle. During enucleation, when the globe was extracted, the sewing needle stayed in the orbit. When the needle was pulled away, a piece of thread was also retrieved, which demonstrated that the linear foreign body had migrated retrogradely from the oral cavity to the orbit through the pterygopalatine fossa. Surgical recovery was uneventful. RELEVANCE AND NOVEL INFORMATION: Intraocular foreign bodies may present in a variety of ways, which may hinder their clinical detection. The management and prognosis depend on the composition and location of the foreign body, as well as the possible presence of secondary infection. To the author's knowledge, this is the first time that a case of severe endophthalmitis following retrograde intraocular migration of a linear foreign body from the oral cavity to the orbit through the pterygopalatine fossa in a cat has been reported.

Alternative route for erythropoietin ocular administration.

PURPOSE: This study aimed to find an alternative route for erythropoietin (EPO) ocular administration because of its neuroprotective and neuroregenerative known properties. Ocular penetration of EPO after subconjunctival injection was assessed, and potential side-effects on the haematocrit for a 28-day period were also evaluated. METHODS: Wistar Hannover female albino rats (n = 42) divided into seven groups of six were used. One group (n = 6) served as control. Six groups (n = 36) received 1,000 UI of EPO through the subconjunctival route in one of the eyes. According to the group, animals were humanely killed at 12 h (n = 6), 24 h (n = 6), 36 h (n = 6), 48 h (n = 6), and 60 h (n = 6), after EPO administration, in a total of 30 animals. Enucleation of both eyes was performed, and EPO protein distribution in the rat's retina was analyzed by immunohistochemistry. Another group of animals (n = 6) was used to collect blood samples and perform haematocrit analysis at 0, 7, 14, 21, and 28 days after unilateral EPO subconjunctival administration. RESULTS: The evaluation of EPO expression in the animals' retinas after subconjunctival administration yielded a strong immunostaining signal. Among the retina's layers, EPO expression was more evident in the RGC layer 24 h after the administration, and was still present on that layer till the end of the study (60 h). When administered subconjunctivally EPO reached several neuronal cells, in all retinal layers. The subconjunctival EPO administration did not cause significant changes in the haematocrit values over a 28-day period. CONCLUSION: In this study, it was demonstrated that EPO reached the retinal ganglion cell layers when administered subconjunctivally. EPO reached the retina 24 h after the subconjunctival administration, and was still present 60 h after the administration. Furthermore, it was also proved that EPO subconjunctival administration did not cause any haematopoietic significant side-effects. The subconjunctival route was shown to be a promising alternative for EPO ocular delivery.