Retrospective investigation of perioperative risk factors for immediate postoperative corneal erosions in dogs undergoing phacoemulsification.

OBJECTIVE: To characterize the incidence, contributing risk factors, and healing characteristics of immediate postoperative corneal erosions (IPCE) in dogs undergoing routine phacoemulsification. ANIMALS STUDIED: Medical records of 313 canine eyes (159 dogs) undergoing routine phacoemulsification surgery. PROCEDURES: Medical records of dogs undergoing planned cataract surgery at UW Veterinary Care were retrospectively reviewed. Patient-related variables including age, skull conformation, diabetes status, and cataract stage at the time of surgery were recorded. Intraoperative variables per eye were also recorded including surgical technique, surgeon expertise level, average phacoemulsification power, and phacoemulsification time. Diagnosis of IPCE ≤ 24 h after completion of surgery and time to IPCE healing were recorded where follow-up data were available. RESULTS: Immediate postoperative corneal erosions were observed in 48/313 (15.3%) operated eyes. The presence of diabetes mellitus or brachycephalic skull conformation, preoperative Schirmer tear test (STT) value, surgical technique and surgeon experience level, phacoemulsification time, and absolute phacoemulsification time were not statistically significant risk factors for IPCE. Average phacoemulsification power was associated with IPCE (RR 1.52, p = .001). Time to IPCE healing was similar in diabetic and non-diabetic dogs (median [IQR] 8 [6-11] days and 8 [6-15] days, respectively). Diabetes mellitus, brachycephaly, and phacoemulsification parameters were not associated with IPCE healing at 7 or 14 days postoperatively. CONCLUSIONS: Higher average phacoemulsification power may be associated with the development of IPCE in canine eyes. The presence of diabetes mellitus or brachycephaly are not risk factors for the development of IPCE, nor are they factors that influence IPCE healing.

Retrobulbar lidocaine injection via the supraorbital fossa is safe in adult horses but produces regionally variable periocular anaesthesia.

BACKGROUND: Injection techniques for retrobulbar anaesthesia are published in horses, but neither safety nor anaesthetic efficacy and duration have been evaluated objectively in vivo. OBJECTIVE: To characterise the safety and efficacy of one published technique for retrobulbar anaesthesia. STUDY DESIGN: Randomised, controlled descriptive experiment. METHODS: Unilateral retrobulbar injection with 10 mL lidocaine (2%) was performed in eight sedated adult mares. Contralateral eyes served as untreated controls. Neurophthalmic parameters, intraocular pressure (IOP), and corneal and periocular sensation were measured awake, post-sedation and at periodic time points for 24 hours following injection. Adverse effects were documented. RESULTS: Injection of 10 mL lidocaine significantly increased IOP for up to 2 hours (P < .05) maximally at 30 min (mean [95% CI]: 6.0 [2.7, 9.2] mm Hg, P < .001). Six of the eight treated eyes developed mild to moderate reversible chemosis for 2 to 24 hours. One eye developed severe chemosis and superficial corneal ulceration at 24 and 48 hours following injection respectively. Corneal sensitivity significantly decreased for 6 hours (P < .05), maximally at 10 min (-44.4 [-34.6, -54.1] mm, P < .001). Periocular sensitivity (measured as increase in applied force) significantly decreased dorsally and medially for up to 2 hours (maximal at 2 hours (367.1 [238.5, 495.7] g, P < .001, and at 30 min: 345.8 [202.6, 488.9] g, P < .001) respectively). Ventral and lateral sensitivity were not effectively decreased beyond 30 min. Optic nerve function was not consistently reduced following injection. MAIN LIMITATIONS: Investigators were not masked to the treated eye. CONCLUSIONS: Retrobulbar injection using 10 mL lidocaine is safe in normal eyes of adult horses, but carries risk in structurally compromised or glaucomatous eyes due to transient IOP increase. Reversible chemosis commonly develops 2-4h following injection, and may be severe in some horses with risk for corneal ulceration. Corneal anaesthesia is rapid and prolonged, but all periocular regions are not consistently anaesthetised. Retrobulbar injection should be combined with other local anaesthetic injections for eyelid surgeries or enucleations.

Medical anti-glaucoma therapy: Beyond the drop.

Barriers to effective medical therapy are numerous and include difficulties with effective and sustained control of intraocular pressure (IOP) and adherence to prescribed anti-glaucoma drop regimens. In an effort to circumvent these challenges, a number of new anti-glaucoma therapies with sustained effects have emerged. Methods for sustained delivery of prostaglandin analogs are being intensely investigated and many are in human clinical trials. Intracameral devices include the following: Allergan's Durysta™ Bimatoprost SR, Envisia Therapeutics' ENV515 travoprost implant, Glaukos' iDose™ , Ocular Therapeutix's OTX-TIC travoprost implant, and Santen's polycaprolactone implant with PGE2-derivative DE-117. Other prostaglandin-based technologies include Allergan's bimatoprost ring (placed in the conjunctival fornix), Ocular Therapeutics' OTX-TP intracanalicular travoprost implant, subconjunctival latanoprost in a liposomal formulation, and the PGE2 derivative PGN 9856-isopropyl ester that is applied to the periorbital skin. Exciting breakthroughs in gene therapy include using viral vectors to correct defective genes such as MYOC or to modulate gonioimplant fibrosis, CRISPR technology to edit MYOC or to alter aquaporin to reduce aqueous humor production, and siRNA technology to silence specific genes. Stem cell technology can repopulate depleted tissues or, in the case of Neurotech's Renexus® NT-501 intravitreal implant, serve as a living drug delivery device that continuously secretes neurotrophic factors. Other unique approaches involve nanotechnology, nasal sprays that deliver drug directly to the optic nerve and noninvasive alternating current stimulation of surviving cells in the optic nerve. Over time these modalities are likely to challenge the preeminent role that drops currently play in the medical treatment of glaucoma in animals.

The SPOTS System: An Ocular Scoring System Optimized for Use in Modern Preclinical Drug Development and Toxicology.

PURPOSE: To present a semiquantitative ocular scoring system comprising elements and criteria that address many of the limitations associated with systems commonly used in preclinical studies, providing enhanced cross-species applicability and predictive value in modern ocular drug and device development. METHODS: Revisions to the ocular scoring systems of McDonald-Shadduck and Hackett-McDonald were conducted by board-certified veterinary ophthalmologists at Ocular Services On Demand (OSOD) over the execution of hundreds of in vivo preclinical ocular drug and device development studies and general toxicological investigations. This semiquantitative preclinical ocular toxicology scoring (SPOTS) system was driven by limitations of previously published systems identified by our group's recent review of slit lamp-based scoring systems in clinical ophthalmology, toxicology, and vision science. RESULTS: The SPOTS system provides scoring criteria for the anterior segment, posterior segment, and characterization of intravitreal test articles. Key elements include: standardized slit lamp settings; expansion of criteria to enhance applicability to nonrabbit species; refinement and disambiguation of scoring criteria for corneal opacity, fluorescein staining severity, and aqueous flare; introduction of novel criteria for scoring of aqueous and anterior vitreous cell; and introduction of criteria for findings observed with drugs/devices targeting the posterior segment. A modified Standardization of Uveitis Nomenclature (SUN) system is also introduced to facilitate accurate use of SUN's criteria in laboratory species. CONCLUSIONS: The SPOTS systems provide criteria that stand to enhance the applicability of semiquantitative scoring criteria to the full range of laboratory species, in the context of modern approaches to ocular therapeutics and drug delivery and drug and device development.

Slit Lamp-Based Ocular Scoring Systems in Toxicology and Drug Development: A Literature Survey.

PURPOSE: To present a survey of the features of published slit lamp-based scoring systems and their applicability in the context of modern ocular toxicology and drug development. METHODS: References describing original or modified slit lamp-based scoring systems for human or veterinary clinical patients or in investigative or toxicologic research were collected following a comprehensive literature review using textbooks and online publication searches. Each system's indications and features were compiled to facilitate comparison. RESULTS: Literature review identified 138 original or modified scoring systems. Most (48%) were published for evaluation of the ocular surface, 34% for the general anterior segment, and 18% for the lens. Most systems were described for assessment of human patients (50%) and small albino laboratory species such as rabbits (19%), rats (12%), and mice (8%). Systems described for pigmented laboratory species and for larger species such as dogs, cats, pigs, and nonhuman primates (NHPs) were comparatively underrepresented. No systems described a lens scoring scheme specific to the dog, cat, pig, or NHP. Scoring schemes for aqueous and vitreous cells were infrequently described for laboratory species. CONCLUSIONS: Many slit lamp-based scoring systems have been published, but the features of each differ and complicate translation of findings between different species. Use and interpretation of any scoring system in toxicology and drug development must be done with awareness of the limitations of the system being used.

Ocular Adverse Events Associated with Antibody-Drug Conjugates in Human Clinical Trials.

This article reviews ocular adverse events (AEs) reported in association with administration of antibody-drug conjugates (ADCs) in human clinical trials. References reporting ocular toxicity or AEs associated with ADCs were collected using online publication searches. Articles, abstracts, or citations were included if they cited ocular toxicities or vision-impairing AEs with a confirmed or suspected association with ADC administration. Twenty-two references were found citing ocular or vision-impairing AEs in association with ADC administration. All references reported use of ADCs in human clinical trials for treatment of various malignancies. The molecular target and cytotoxic agent varied depending on the ADC used. Ocular AEs affected a diversity of ocular tissues. The most commonly reported AEs involved the ocular surface and included blurred vision, dry eye, and corneal abnormalities (including microcystic corneal disease). Most ocular AEs were not severe (≤ grade 2) or dose limiting. Clinical outcomes were not consistently reported, but when specified, most AEs improved or resolved with cessation of treatment or with ameliorative therapy. A diverse range of ocular AEs are reported in association with administration of ADCs for the treatment of cancer. The toxicologic mechanism(s) and pathogenesis of such events are not well understood, but most are mild in severity and reversible. Drug development and medical professionals should be aware of the clinical features of these events to facilitate early recognition and intervention in the assessment of preclinical development programs and in human clinical trials.

Equine protozoal myeloencephalitis due to Neospora hughesi and equine motor neuron disease in a mule.

CASE DESCRIPTION: A 23-year-old female mule was presented for bilateral ocular abnormalities and an abnormal pelvic limb gait. CLINICAL FINDINGS: Anisocoria, unilateral enophthalmos, medial strabismus, ptosis, pupillary light reflex deficits, and bilateral reticulated pigmentary retinopathy were observed on ophthalmic examination. Neurologic abnormalities included right-sided facial nerve paralysis, extensive symmetric muscle atrophy, and asymmetric pelvic limb ataxia with an abnormal pelvic limb gait. A positive titer (1:40) for equine protozoal myeloencephalitis (EPM) associated with Neospora hughesi was obtained from cerebrospinal fluid with minimal (<1 red blood cell/microL) blood contamination. Muscle biopsies of the sacrocaudalis dorsalis medialis muscle revealed predominantly type I neurogenic muscle atrophy, consistent with a diagnosis of equine motor neuron disease (EMND). TREATMENT AND OUTCOME: Treatment included a 2-month course of ponazuril (5 mg/kg PO q24 h), vitamin E (8000 IU PO q24 h), and selenium (2 mg PO q24 h). Clinical improvement was not observed after 2 months although the mule remained stable. Clinical deterioration was reported upon discontinuation of the ponazuril after a 2-month course. CONCLUSION: Concurrent disease with EPM associated with N. hughesi and EMND should be considered in cases demonstrating cranial nerve abnormalities, pronounced symmetric muscle atrophy, unusual asymmetric gait abnormalities, and reticulated pigmentary retinopathy.