Medical Management versus PACK-CXL in Dogs with Infectious Keratitis: A Randomized Controlled Trial Protocol

Infectious keratitis is a common and painful disease, usually caused by bacteria in dogs. Brachycephalic breeds are at increased risk. Despite medical therapy, enzymatic corneal melting can lead to ulcer perforation and globe loss. Treatment alternatives are needed due to an increase in antibiotic resistance and growing popularity of brachycephalic dogs. Photoactivated Chromophore for Keratitis-Corneal Cross-linking (PACK-CXL) reduces enzymatic collagenolysis and damages multiple targets within microorganisms, resulting in corneal tissue stabilization and elimination of bacteria, irrespective of their antibiotic resistance status. A randomized controlled trial providing evidence of PACK-CXL effectiveness in dogs is lacking. We aim to determine whether PACK-CXL is a viable alternative to conventional medical therapy for canine infectious keratitis. Two hundred-and-seventy client-owned dogs with presumed infectious keratitis will be allocated to two equally sized treatment groups (PACK-CXL or medical therapy) in a masked, randomized, controlled, multicenter trial in eleven clinics. The primary outcome measure is treatment success defined as complete epithelial closure within 28 days. The sample size is based on a group sequential design with two interim analyses, which will be overseen by a Data Safety and Monitoring Board. Ethical approvals have been obtained. The study protocol is preregistered at preclinicaltrials.eu. Publishing trial protocols improves study reproducibility and reduces publication bias

Seasonal effects on the corneoconjunctival microflora in a population of Persian cats in Iran

This study was performed to determine the normal seasonal aerobic and an-aerobic corneoconjunctival bacterial flora in cats. Thirty eyes of 15 clinically normal client-owned Persian cats were evaluated. All cats lived in a similar indoor/outdoor home environment being fed the same diet for the entire year. The cats did not receive any medications and were found to be clinically healthy 1 week prior to each microbial sampling. The cats were not exposed to other cats during the study period. Microbial samples were collected at the same time of day on the first day of the second month of each of the four seasons. During sample collection, a sterile swab was rolled over the corneoconjunctival surface avoiding contact with surrounding skin or hair. Immediately after sample collection, microbiologic aerobic and anaerobic cultures were initiated. Gram-positive bacteria were the most prevalent isolates. The most commonly isolated bacterial organisms across all seasons were Staphylococcus epidermidis (41/95; 43.2%), β-hemolytic streptococcus (18/95; 18.9%), Staphylococcus aureus (17/95; 17.9%), and Escherichia coli (11/95; 11.5%). Twenty-five cultures of a total of 120 (20.8%) were negative. One negative culture was collected in the summer, while 21 cultures were negative in fall and winter. Gram-positive bacteria were the predominant micro-organisms of the normal ocular surface of healthy cats in all seasons in this study. This result is in agreement with previous publications

Growth factors and mechano-regulated reciprocal crosstalk with extracellular matrix tune the keratocyte–fibroblast/myofibroblast transition

Improper healing of the cornea after injury, infections or surgery can lead to corneal scar formation, which is associated with the transition of resident corneal keratocytes into activated fibroblasts and myofibroblasts (K–F/M). Myofibroblasts can create an extracellular matrix (ECM) niche in which fibrosis is promoted and perpetuated, resulting in progressive tissue opacification and vision loss. As a reversion back to quiescent keratocytes is essential to restore corneal transparency after injury, we characterized how growth factors with demonstrated profibrotic effects (PDGF, FGF, FBS, TGFβ1) induce the K–F/M transition, and whether their withdrawal can revert it. Indeed, the upregulated expression of αSMA and the associated changes in cytoskeletal architecture correlated with increases in cell contractility, fibronectin (Fn) and collagen matrix density and Fn fiber strain, as revealed by 2D cell culture, nanopillar cellular force mapping and a FRET-labeled Fn tension probe. Substrate mechanosensing drove a more complete K–F/M transition reversal following growth factor withdrawal on nanopillar arrays than on planar glass substrates. Using decellularized ECM scaffolds, we demonstrated that the K–F/M transition was inhibited in keratocytes reseeded onto myofibroblast-assembled, and/or collagen-1-rich ECM. This supports the presence of a myofibroblast-derived ECM niche that contains cues favoring tissue homeostasis rather than fibrosis

Corneal collagen cross-linking (CXL) for the treatment of melting keratitis in cats and dogs: a pilot study

Objective UV-A/riboflavin cross-linking (CXL) of corneal collagen fibers is an established, highly promising therapy for corneal melting in physician-based ophthalmology. A prospective pilot study was conducted to demonstrate proof of principle of this novel method for the treatment of melting corneal ulcers in dogs and cats. Procedures After obtaining owner consent, CXL was performed in three cats and three dogs with corneal melting, which either affected the entire corneal surface or was resistant to conventional antibiotic and anticollagenolytic therapy, or affected parts or all of the corneal surface. Medical therapy was continued in all patients. The available follow-up ranged from 2 to 22.5 months and involved slit-lamp examination, fluorescein staining, and photographic documentation during all rechecks. Results Surgical stabilization of the cornea was not necessary in any case, because progression of corneal melting was arrested in all cases within 1–20 days of CXL treatment. Corneal re-epithelization occurred within 7–40 days in all eyes. At 40 days after CXL, all eyes presented a quiescent corneal state without signs of active inflammation and with beginning scar formation. The complications observed in three of the six animals included a corneal sequestrum, superficial corneal stromal pigmentation, and bullous keratopathy. Conclusions This study shows the feasibility of CXL to treat progressive corneal melting in veterinary patients. CXL may represent a cost-efficient and safe alternative therapy in the treatment for corneal melting in veterinary ophthalmology. More investigations comparing the effectivity and complication rate of CXL to those of standard medical treatment are necessary

Outer retinal thickness and visibility of the choriocapillaris in four distinct retinal regions imaged with spectral domain optical coherence tomography in dogs and cats

Purpose: To evaluate the outer retinal band thickness and choriocapillaris (CC) visibility in four distinct retinal regions in dogs and cats imaged with spectral domain optical coherence tomography (SD-OCT). To attempt delineation of a fovea-like region in canine and feline SD-OCT scans, aided by the identification of outer retinal thickness differences between retinal regions. Methods: Spectralis® HRA + OCT SD-OCT scans from healthy, anesthetized dogs (n = 10) and cats (n = 12) were analyzed. Scanlines on which the CC was identifiable were counted and CC visibility was scored. Outer nuclear layer (ONL) thickness and the distances from external limiting membrane (ELM) to retinal pigment epithelium/Bruch's membrane complex (RPE/BM) and ELM to CC were measured in the area centralis (AC), a visually identified fovea-like region, and in regions superior and inferior to the optic nerve head (ONH). Measurements were analyzed using a multilevel regression. Results: The CC was visible in over 90% of scanlines from dogs and cats. The ONL was consistently thinnest in the fovea-like region. The outer retina (ELM-RPE and ELM-CC) was thickest within the AC compared with superior and inferior to the ONH in dogs and cats (p < .001 for all comparisons). Conclusions: The CC appears a valid, albeit less than ideal outer retinal boundary marker in tapetal species. The AC can be objectively differentiated from the surrounding retina on SD-OCT images of dogs and cats; a fovea-like region was identified in dogs and its presence was suggested in cats. These findings allow targeted imaging and image evaluation of these regions of retinal specialization

Ocular manifestations of a metastatic adenocarcinoma in a horse

A 10-year-old German Warmblood gelding was referred to the Equine Department of the Vetsuisse Faculty, University of Zurich, Switzerland, for an iris mass OD, lethargy, intermittent fever, and coughing. Ophthalmic examination revealed a 7 × 9 mm raised, fleshy, whitish to pinkish, vascularized iris mass at the 2 o`clock position OD. Fundic examination showed multifocal round, brown to black, slightly raised lesions with indistinct margins and a surrounding hyperreflective zone OU. Physical examination revealed a temperature of 39.2 °C, sinus tachycardia, preputial and ventral edema, and an enlarged right mandibular lymph node. Results of a complete blood count and plasma biochemical profile showed mild anemia, leukocytosis, and thrombocytopenia. Severe splenopathy, moderate splenomegaly, and severe pulmonary pathology with nodules and large areas of consolidated lung parenchyma were observed on abdominal ultrasound and thoracic radiographs, respectively. Fine needle aspirates of the enlarged mandibular lymph node showed malignant epithelial neoplastic cells. The horse was euthanized because of the poor prognosis and subsequently underwent postmortem examination. Macroscopic necropsy and histopathology revealed an adenocarcinoma of suspected pulmonary origin with involvement of eyes, heart, liver, kidneys, spleen, diaphragm, skeletal muscles, mandibular, pulmonary, and internal iliac lymph nodes. Metastatic adenocarcinoma should be considered as a differential diagnosis in horses with iris masses, multifocal chorioretinal infiltrates, and clinical signs that conform to a paraneoplastic syndrom

Corneal collagen cross-linking as treatment for infectious and non-infectious corneal melting in cats and dogs: results of a prospective, non-randomized, controlled trial

OBJECTIVE. UV-A/Riboflavin crosslinking of corneal collagen fibers (CXL) is a highly promising therapy for corneal melting in humans. A prospective interventional, non-randomized, controlled study was conducted to compare the stabilizing effect of CXL treatment on melting keratitis in dogs and cats and the complication rate of CXL to those of standardized intensive medical treatment. PROCEDURES. Forty-nine eyes with melting keratitis were included in the study between October 2009 and October 2012. All eyes were treated according to the same medical treatment protocol. Nineteen eyes were CXL-treated and 30 eyes were not. Follow-up included slit-lamp examination, fluorescein staining, ulcer size measurement, stromal stability evaluation, photographic documentation and documentation of complications. RESULTS. Five of 19 eyes in the CXL group and 9/30 eyes in the control group required rescue stabilization due to continued melting. Seven of the 9 control group corneas stabilized after rescue CXL treatment. At initial presentation, the ulcers in the canine CXL group were significantly deeper and larger than in the control group. Ulcer deepening during follow-up was more pronounced in the canine control group than in the canine CXL group. CXL treatment related complications were not observed. CONCLUSIONS. Based on the similar failure rates in the control and CXL treatment groups despite the poorer initial situation in the CXL group, the tendency for the ulcers in the control group to deepen and the stabilization of all corneas receiving CXL rescue treatment, we believe that CXL has its place as an adjunctive therapy for melting keratitis in veterinary ophthalmology

Protective coatings for intraocular wirelessly controlled microrobots for implantation : corrosion, cell culture, and in vivo animal tests

Grup: Gnm3 FundingDiseases in the ocular posterior segment are a leading cause of blindness. The surgical skills required to treat them are at the limits of human manipulation ability, and involve the risk of permanent retinal damage. Instrument tethering and design limit accessibility within the eye. Wireless microrobots suturelessly injected into the posterior segment, steered using magnetic manipulation, are proposed for procedures involving implantation. Biocompatibility is a prerequisite for these procedures. This paper investigates the use of cobalt-nickel microrobots coated with polypyrrole, and gold, which has been used as an ocular implant material. Polypyrrole has well-established biocompatibility properties, but no reports concerning its ocular implantation is available. Coated and uncoated microrobots were investigated for their corrosion properties, and solutions that had contained coated and uncoated microrobots for one week were tested for cytotoxicity by monitoring NIH3T3 cell viability. None of the microrobots showed significant corrosion currents and corrosion potentials were as expected in relation to the intrinsic nobility of the materials. NIH3T3 cell viability was not affected by the release medium, in which coated/uncoated microrobots were stored. In vivo tests inside rabbit eyes were performed using coated microrobots. There were no significant inflammatory responses during the first week after injection. An inflammatory response detected after two weeks was likely due to a lack of longer-duration biocompatibility. The results provide valuable information for those who work on implant technology and biocompatibility. Coated microrobots have the potential to facilitate a new generation of surgical treatments, diagnostics and drug-delivery techniques, when implantation in the ocular posterior segment will be possible