Experimental evaluation of ophthalmic devices and solutions using rabbit models

OBJECTIVE: To analyze and compare the geometry of the anterior segment of rabbit and human eyes, with relevance for the evaluation of intraocular lenses, and to review rabbit models used in our laboratory for the evaluation of different ophthalmic devices and solutions. PROCEDURES: Fifteen rabbit and 15 human eyes (10 phakic and 5 pseudophakic/group) obtained postmortem were used. Anterior-posterior length, equatorial diameter, and white-to-white (corneal diameter) were measured with calipers. The eyes were then analyzed with a very high-frequency ultrasound (Artemis, Ultralink) for measurements of the anterior chamber depth, and anterior chamber and ciliary sulcus diameters. The capsular bag diameter was measured with calipers from a posterior view, and the diameter and thickness of the crystalline lenses were measured after their excision from the phakic eyes. RESULTS: Although the size of the rabbit eye is overall smaller than the size of the human eye, the dimensions of the anterior segment of rabbit eyes are generally larger. The differences between rabbit and human eyes were statistically significant (Wilcoxon rank sum test) in terms of anterior-posterior length, equatorial diameter, white-to-white measurements (P < 0.0001), anterior chamber diameter (P = 0.0004), ciliary sulcus diameter (P = 0.0012), and crystalline lens diameter and thickness (P = 0.0003). CONCLUSIONS: Experimental evaluation of design features of new phakic intraocular lenses in rabbit eyes may be inconclusive without adaptation of their size/design, contrary to the evaluation of new pseudophakic lenses by implantation in the capsular bag. The rabbit is a very valuable model for the experimental evaluation of different ophthalmic devices and solutions.     

The relationship of cataract maturity to intraocular pressure in dogs

Objective To determine the distribution of intraocular pressure, as measured by applanation tonometry, in dogs with cataracts, and compare these tonometric results to the different stages of cataract formation (incipient, immature, mature, and hypermature). Animals studied Retrospection study of canine clinical patients (86 dogs). Procedures All records of dogs presented from 1991 to 1996 to the university veterinary medical teaching hospital for diagnosis of cataracts and evaluation for cataract surgery were reviewed. The tonometric measurements from the initial ophthalmic examination were selected in cataractous and nonglaucomatous eyes either receiving no topical or no systemic medications. The stage of cataracts was based on the degree of opacification, tapetal reflection, clinical vision, and visibility of the ocular fundus by indirect ophthalmoscopy. The distribution of tonometric results were grouped by the cataract maturity, and compared by anova and Tukey’s general linear tests. Results Intraocular pressure with incipient cataracts ranged from 9 to 17 mmHg (mean 12.7 ± 1.2 mmHg). Intraocular pressure with immature cataracts ranged from 3 to 27 mmHg (mean 13.6 ± 0.6 mmHg). For the mature cataracts, IOP ranged from 5 to 22 mmHg (mean 11.9 ± 0.7 mmHg). For the hypermature cataract group, IOP ranged from 4 to 23 mmHg (mean 10.8 ± 0.6 mmHg). Comparison of the tonometric results among the different stages of cataract formation indicated a significant difference (P = 0.0086) between only the immature and hypermature groups. Conclusions Intraocular pressure in lens‐induced uveitis (LIU) is lowered but the relationship to the stage of cataract maturity is less clear. Significant tonometric differences were present between the immature and hypermature cataract groups, but these differences are too small to be clinically useful. Decreased intraocular pressure of dogs with all stages of cataract formation suggests concurrent LIU during all stages of cataract formation, especially with the mature and hypermature stages. The average tonometric measurements in dogs with these cataracts were about two standard deviations below the mean IOP reported in normal dogs.     

Phacofragmentation for morgagnian cataract in a horse

A 3‐year‐old Paint gelding was presented for sudden onset of cataract affecting the right eye. Ophthalmic examination revealed subtle to mild microphthalmia and a mature cataract affecting the right globe. The right eye was treated with an antibiotic‐corticosteroid ophthalmic ointment and phacofragmentation was recommended. On re‐examination 5 months later, resorption of the cortex of the right lens and a morgagnian cataract were evident. The nucleus was positioned ventronasally in the lens capsule. The right eye had light perception, and a menace response was present. Examination of the right fundus via binocular indirect ophthalmoscopy was not possible. Ophthalmic ultrasonography revealed that the right globe was 4 mm shorter in axial length when compared with the left globe. There was a marked reduction in the size of the right lens vs. the left lens, and the presence of a moderate amount of hyperechoic debris was identified within the vitreal compartment of the right globe. Phacofragmentation, irrigation and aspiration of the morgagnian cataract and an anterior vitrectomy were performed. On postoperative examination, the eye was comfortable and a menace response was present. The horse regained useful vision and continues to have a comfortable, visual eye 7 months postoperatively.     

Accuracy of data in abstracts of veterinary ophthalmology research articles published in peer-reviewed journals

Objective

Assess the accuracy of abstracts in published veterinary ophthalmology articles.

Procedures

Abstracts and contents of 204 original research articles in veterinary ophthalmology published in seven peer-reviewed journals between 2016–2020 were reviewed. Abstracts were considered inconsistent if they contained data that were either missing from or inconsistent with corresponding data in the article's body. Each abstract was graded between 0 (inaccurate) to 3 (accurate), and each inconsistency was subjectively classified as minor or major. The influence of selected variables was assessed: journal, impact factor, year of publication, number of words in abstract, study type (prospective/retrospective), and characteristics of the corresponding author [institution (academia/private practice), country of domicile (native/non-native English), number of publications].

Results

Most abstracts were accurate, with 1%, 4%, 9% and 86% receiving a score of 0, 1, 2 and 3, respectively. When detected, most inconsistencies were considered minor (77%). Although not statistically significant (p ≥ .130), the proportion of articles with a perfect score (=3) was higher in prospective (88%) vs. retrospective (81%) studies, academia (88%) vs. private practice (78%), and studies from corresponding authors domiciled in English (89%) vs. non-English (83%) speaking countries. A significant but very weak (r = −0.15 to −0.19; p ≤ .034) negative correlation was found between accuracy score and number of words, as well as 1-year and 5-year impact factors.

Conclusions

Although relatively uncommon, data in abstracts that are inconsistent or missing from the article's body do occur in veterinary ophthalmology articles, and could adversely influence a reader's interpretation of study findings.     

Evaluation of serum chondroitin sulfate and hyaluronan: biomarkers for osteoarthritis in canine hip dysplasia

Hip dysplasia (HD) is one of the most important bone and joint diseases in dogs. Making the radiographic diagnosis is sometime possible when the disease has markedly progressed. Chondroitin sulfate (CS) and hyaluronan (HA) are the most important cartilage biomolecules that are elevated in the serum taken from dogs with osteoarthritis. The serum CS and HA can be detected by an ELISA technique, with using monoclonal antibodies against CS epitope 3B3 and WF6 and the HA chain as the primary antibodies. The aim of this study was to compare the levels of serum CS (both epitopes) and HA in non-HD and HD dogs. All 123 dogs were categorized into 2 groups. The non-HD group was composed of 98 healthy dogs, while the HD group was comprised of 25 HD dogs. Blood samples were collected for analyzing the serum CS and HA levels with using the ELISA technique. The results showed that the average serum level of the CS epitope WF6 in the HD group (2,594 ± 3,036.10 ng/ml) was significantly higher than that in the non-HD group (465 ± 208.97 ng/ml) (p < 0.01) while the epitope 3B3 in the HD group (105 ± 100.05 ng/ml) was significantly lower than that in the non-HD group (136 ± 142.03 ng/ml) (p < 0.05). The amount of serum HA in the HD group (134.74 ± 59.71 ng/ml) was lower than that in the non HD group (245.45 ± 97.84 ng/ml) (p < 0.05). The results indicate that the serum CS and HA levels might be used as biomarkers for osteoarthritis in HD dogs.     

Phacoemulsification and acryl foldable intraocular lens implantation in dogs: 32 cases

This study evaluated the surgical outcome and complications of phacoemulsification and the implantation of an acryl foldable intraocular lens (IOL) with a squared edge in dogs with cataracts. Thirty-two eyes from 26 dogs were examined. The mean follow up period was 75.9 days ranging from 23 to 226 days. The complications after phacoemulsification were posterior capsular opacity (PCO) around the IOL (n = 11), ocular hypertension (n = 4), focal posterior synechia (n = 4), hyphema (n = 3) and corneal ulcer (n = 2). The complications associated with the IOL were decenteration of the optic (n = 2) and ventral haptic displacement (n = 1). Most cases of PCO were found only around the margin of the IOL, and all eyes had vision during the observation period. In conclusion, the implantation of an acryl-foldable lens with a squared edge at the time of phacoemulsification is an effective method for preserving the central visual field of dogs with cataract.     

Phacoemulsification and implantation of foldable +14 diopter intraocular lenses in five mature horses

Presently, intraocular lenses (IOLs) are not routinely implanted after equine cataract surgery. Subsequently, horses are visual but markedly farsighted (hyperopic). This report describes the surgical results and visual status after phacoemulsification and implantation of IOLs in mature horses with spontaneous cataracts. Six eyes of 5 mature horses underwent phacoemulsification and implantation of a +14 diopter (D) foldable IOL. Recheck ocular examinations were performed at 1, 4 and 24 weeks post operatively. Refractive error was recorded at 4 weeks post operatively. Visual status, refractive error and anterior chamber depth were recorded 24 weeks post operatively: 5 of 6 operated eyes remained visual and the average refractive error was +0.4 ± 1.1D. There was a significant difference between the 24 week post operative refractive error and the population mean of +10D (P<0.0001) for aphakic horses. The average post operative anterior chamber depth was 7.89 ± 1.55 mm. One globe was enucleated 2 months post operatively. Phacoemulsification with IOL implantation resulted in a significant reduction in post operative refractive error and restored vision to within 0.4D of emmetropia in 5 of 6 operated eyes. Implantation of a +14D IOL ameliorated the hyperopia documented in aphakic horses and improved the post operative visual acuity.     

Surgical margins in the veterinary cancer patient

In veterinary oncologic specimens, histopathology is the gold standard for determining adequacy of excision. Despite limitations of this technique, the pathologist's interpretation of margin status significantly impacts patient management, including indications for adjuvant therapy. This article aims to summarize peer‐reviewed literature as it relates to histologic margin evaluation in veterinary cancer patients. The value of histologic tumour‐free margins and technical factors influencing histopathologic margin outcomes are also discussed. We review alternative strategies for determining excisional status, and discuss how an evolving understanding of tumour biology might inform clinical and research perspectives on surgical margins. In doing so, we aim to provide context and a stimulus for future investigations into this important yet incompletely understood topic.     

Preliminary study of the gene expression of sulfation and degradation enzymes for chondroitin sulfate in glycerol-treated C2C12 myoblast cells

In this study, we induced chemical damage of C2C12 myoblasts that had differentiated into myotubes with glycerol, and four sulfation enzymes for chondroitin sulfate (CS) [carbohydrate sulfotransferase (Chst) 12, Chst15 and Chst3 and uronyl 2-O-sulfotransferase (UST)] and two CS degradation enzymes [hyaluronidase (Hyal) 1 and Hyal2] were examined for changes in gene expression. Treatment of myoblasts with 5% glycerol significantly increased the expression levels of the sulfation enzymes Chst12 and Chst15 and the degradation enzymes Hyal1 and Hyal2. However, the expression levels of the other two genes (Chst3 and Ust) showed no change. Differences in the expression levels of these enzymes may help to understand the difference in responsiveness of myoblasts to glycerol after muscle injury in vivo or in vitro.     

Effects of one-time and two-time intra-articular injection of hyaluronic acid sodium salt after joint surgery in dogs

Thirty-one dogs with patellar luxation (grades 2 and 3) were categorized into three groups. Group 1 (G.1; n = 12) had sodium hyaluronate (SHA) intra-articularly injected into the stifle joint that received surgery. Group 2 (G.2; n = 10) received SHA twice: first after surgery and then 1 week later. Group 3 (G.3; n = 9) served as a control, without injection. Blood was collected before injection and then once a week for 4 weeks after injection for evaluation of chondroitin sulfate (CS-WF6) and hyaluronan (HA). The results revealed significantly (p < 0.05) improved clinical scores by the end of week 4 in G.1 and G.2 relative to G.3; however, there was no significant difference between G.1 and G.2. There was a significant decrease (p < 0.05) in serum CS-WF6 levels beginning at week 2 in G.1 and G.2. At weeks 3 and 4, serum HA in G.1 and G.2 differed from that in G.3 (p < 0.05). No significant difference (p > 0.05) was observed in serum biomarkers between G.1 and G.2. In conclusion, intra-articular injection with SHA after joint surgery may improve homeostasis of the joint, retarding the process of OA.     

Efficacy of two chondroitin sulfate ophthalmic solutions in the therapy of spontaneous chronic corneal epithelial defects and ulcerative keratitis associated with bullous keratopathy in dogs

OBJECTIVE: To determine the efficacy of two antimicrobial-chondroitin sulfate ophthalmic solutions in the therapy of spontaneous chronic corneal epithelial defects (SCCED) and ulcerative keratitis associated with bullous keratopathy in dogs. ANIMALS STUDIED: Eighty dogs with SCCED and 14 dogs with ulcerative keratitis associated with bullous keratopathy. PROCEDURE: Following manual debridement of nonadherent epithelium, dogs were treated topically with a chondroitin sulfate ophthalmic solution containing either tobramycin or ciprofloxacin. Patients were re-evaluated at 2-week intervals for 4 weeks. RESULTS: After 2 weeks of treatment, 53.6% of eyes with SCCED and 17.6% of eyes with ulcerative keratitis associated with bullous keratopathy had healed. After 4 weeks of treatment, 81.0% of eyes with SCCED and 23.5% of eyes with ulcerative keratitis associated with bullous keratopathy had healed. There were no statistically significant differences in healing percentages between the tobramycin-chondroitin sulfate solution treatment groups and the ciprofloxacin-chondroitin sulfate solution treatment groups. Two dogs with SCCED, one treated with the tobramycin-chondroitin sulfate solution and the other treated with the ciprofloxacin-chondroitin sulfate solution, developed sterile corneal stromal abscesses during the study. CONCLUSIONS: Topical therapy with an antimicrobial-chondroitin sulfate ophthalmic solution combined with manual debridement of nonadherent epithelium compares favorably with other published medical and surgical therapies for SCCED; however, these compounds are only equivocally more effective than therapy with manual debridement alone. These solutions appear to be ineffective in the treatment of ulcerative keratitis associated with bullous keratopathy. The significance of the two cases of corneal stromal abscessation is unknown at this time and warrants further investigation.     

Secondary glaucomas in the dog in North America

OBJECTIVE: To determine the prevalence of secondary glaucomas in dogs associated with cataract formation, lens luxation or displacement, cataract surgery, uveitis, hyphema and intraocular neoplasia. METHODS: Information was obtained from the Veterinary Medical Data Base (VMDB) from all veterinary medical teaching hospitals in North America from March 1964 to March 2003. Secondary glaucomas were diagnosed at the same examination or after the primary diagnosis was made, and included those associated with cataract formation, lens luxation, cataract surgery, uveitis of unknown cause, hyphema of unknown cause, and intraocular neoplasia. The data were evaluated by decade, breed, gender and age of presentation. RESULTS: A total of 1 592 831 dogs were presented, and 9695 canine secondary glaucomas. Secondary glaucoma associated with cataract formation represented 81% of all the canine secondary glaucomas. Breeds (n = 7890 dogs) predisposed to secondary glaucoma and cataracts had an overall prevalence of 0.5%, but nearly 20% of all the cataractous dogs developed secondary glaucoma in at least one eye. For the years 1994-2003, these breeds included the American Cocker Spaniel; Boston Terrier; Toy, Miniature and Standard Poodle; English Springer Spaniel; Bichon Frise; and Labrador Retriever. The other forms of secondary glaucoma occurred less frequently, and included those glaucomas with lens luxation or displacement (779 dogs; 12.0%), postcataract surgery (528 dogs; 5.1%), with uveitis from unknown cause (399 dogs; 7.1%), with hyphema from unknown cause (117 dogs; 7.3%), and with intraocular neoplasia (19 dogs; 3.5%). The risk of the secondary glaucomas from 1984 to 2002 was highest after the intracapsular lens extraction (ICLE), less in the extracapsular technique (ECLE), and lowest for the phacoemulsification/phacofragmentation method. CONCLUSION: Prevalence of the canine secondary glaucomas ranges from 0.25% (1964-1973), 0.46% (1974-1983), 0.79% (1984-1993), to 0.80% (1994-2003) and are as frequent as the primary or breed-related glaucomas during these same time periods.     

Intraocular pressure development after cataract surgery: a prospective study in 50 dogs (1998-2000)

Objective To study the course of intraocular pressure (IOP) after cataract surgery in 50 dogs. Design Prospective study. Animals Fifty dogs without preoperative ocular hypertension were selected for cataract surgery. Methods All dogs underwent cataract surgery: 25 by manual extracapsular extraction and 25 by phacoemulsification. For each dog, intraocular pressure was measured before surgery, and 1, 3, 5, 18 h, 1 week and 1 month post surgery. Results No significant difference of mean intraocular pressure between the two surgical methods was observed for each time measurement. Nine dogs had postoperative hypertension (IOP > 25 mmHg) during the first 5 hours post surgery. Incidence of postoperative hypertension was not significantly different with manual extracapsular extraction (16%) vs. phacoemulsification (20%). A decrease of mean IOP was observed 1 h after surgery (8.49 mmHg vs. 10.91 mmHg), then an increase 3 and 5 h post surgery (12.3 and 13.32 mmHg, respectively). At 18 h, 1 week and 1 month post surgery, mean IOP decreased. Mean IOP was 10.38, 10.38 and 8.84 mmHg, respectively. Conclusion In this study incidence of POH is not high. However, a follow‐up of IOP in the first hours after cataract surgery is required to avoid complications of the retina and optic nerve and to administer hypotensive treatment if necessary.     

Phacoemulsification and +14 diopter intraocular lens placement in a Saddlebred foal

A 2‐month‐old, 110‐kg Saddlebred filly presented for evaluation of bilateral cataracts. A hypermature cataract in the left eye (OS) and an incipient nuclear cataract in the right eye (OD) were diagnosed. Electroretinography and ocular ultrasound revealed no contraindications for surgical removal of the cataractous lens OS. Phacoemulsification and implantation of a +14 diopter (D) intraocular lens (IOL) OS were performed at 4 months of age without complication, with the exception of a partial iridectomy performed on a small iris section that prolapsed through the corneal incision. Complete ophthalmic examinations, including ocular ultrasound and streak retinoscopy, were performed 1, 2, 6 weeks, 4 months, 1, and 2 years postoperatively. Diffuse corneal edema and a superficial corneal ulcer developed OS during the early postoperative period and resolved without complication. Dyscoria was identified owing to anterior synechia of the dorsomedial iris at the incision site. Two years after surgery, menace response, palpebral reflex, dazzle reflex, and pupillary light reflexes were present in both eyes (OU). The IOL remained centrally positioned within the capsule, with mild anterior tilting of the superior portion of the IOL and mild fibrosis of the lens capsule. The postoperative net refractive error was +0.31 D OS. Based on this report, a +14 D IOL may be the appropriate choice following lens extraction in a foal to achieve refraction near emmetropia at maturity. To our knowledge, this is the first report of phacoemulsification and IOL implantation in a foal with long‐term follow‐up.     

兽药广告审查申请材料中常见问题解析

当前,兽药广告已成为众多兽药生产、经营企业宣传推销产品的常用方法,兽药广告审查数量不断增长。本文对计划在全国重点媒体发布兽药广告的审查申请材料中常见的问题进行了分析与总结,并有针对性地提出建议,旨在为规范兽药广告、营造健康用药环境提供参考。