Feline primary open angle glaucoma

Objectives We have documented the histomorphological features of feline primary open angle glaucoma. Design A retrospective morphologic study of eight affected eyes from eight cats, from 1992 to 2006 extracted from a pathology collection, which includes 4000 feline submissions and 1100 cases of feline glaucoma. Procedure Sections of affected globes, stained with H&E or with alcian blue were examined with a light microscope. Eyes that did not fulfill the criteria for primary open angle glaucoma were excluded from the study. Results The mean age was 9.1 years. Five cats were female and three cats were male. The breeds included five DSH, two Burmese, and one DLH cat. Significant histomorphological findings included an open irido‐corneal angle with an open ciliary cleft in all cases, loss of ganglion cells in eight of eight cases, cupping and gliosis of the optic nerve head in four of four cases in which the optic nerve was adequately sampled, and myxomatous changes of the stroma surrounding the vortex veins in seven of eight cases. Conclusions Primary open angle glaucoma in cats is a rare disease that should be taken into consideration when investigating cases of feline glaucoma. The pathogenesis of aqueous outflow obstruction in these cases is not known. This study describes eight additional cases of feline primary open angle glaucoma in cats without an identified cause.     

Comparative Doppler imaging of the ophthalmic vasculature in normal Beagles and Beagles with inherited primary open-angle glaucoma

The objective of this study was to compare orbital and ocular vasculature velocity, measured by Doppler imaging, in normal Beagles and Beagles with inherited primary open-angle glaucoma. Eight normal Beagles and 13 Beagles with different stages of primary open-angle glaucoma were evaluated twice with a 2–4-week period between measurements. Doppler imaging was performed with the dogs anesthetized, and the Doppler transducer applied directly on the corneal surface. The majority of the orbital vasculature (external ethmoidal artery; internal ophthalmic artery and vein; and external ophthalmic artery and vein) and ocular blood vessels (anterior ciliary artery and veins; long posterior ciliary arteries; short posterior ciliary arteries; primary retinal arteries; and the vortex veins) were identified and Doppler blood velocity parameters were determined. The glaucomatous dogs demonstrated significant differences in the Doppler velocity parameters of several orbital vessels (external ethmoidal, external ophthalmic, and internal ophthalmic arteries), and several ocular vessels (anterior ciliary, short posterior ciliary, and long posterior ciliary arteries). These differences included decreased blood velocities, and increased pulsatility and resistive indexes. The Doppler blood flow velocities of the primary retinal arteries were unchanged between the normal and glaucomatous dogs. In the glaucomatous dogs, the Doppler imaging suggests increased vascular resistance downstream in both the orbital and ocular vasculature. These blood velocity parameter changes may be primary or secondary, and may offer therapeutic opportunities to increase perfusion, prolong the retina and optic nerve head function, and maintain vision in the canine glaucomas.     

Cullen frontal sinus valved glaucoma shunt: preliminary findings in dogs with primary glaucoma

PURPOSE: To evaluate the efficacy of a novel, professionally manufactured, frontal sinus valved glaucoma shunt in maintaining normal intraocular pressure (IOP) and vision in dogs with primary glaucoma. METHODS: Three eyes of three dogs diagnosed with primary glaucoma were included in this prospective clinical study. A Cullen frontal sinus valved glaucoma shunt was implanted into each glaucomatous globe. Dogs were treated postoperatively with topical neomycin/polymyxin B/0.1% dexamethasone and 0.03% flurbiprofen every 6 h tapered over 8-12 weeks, and meloxicam at 0.1 mg/kg orally every 24 h for 7-10 days. IOP, intracameral shunt position and apparent patency, and vision were assessed twice daily for up to 4 (n= 3 eyes) and 10 (n= 2 eyes) days postoperatively, and then at re-examination periods of up to 36 weeks (n= 1 eye). Postoperative complications were recorded and documented photographically. RESULTS: Normal IOP was maintained in all shunted globes (range 10-29 mmHg; mean = 16.7 mmHg at 24 h; IOP = 23 mmHg at 36 weeks) postoperatively for 2 days (3/3 eyes), 8 weeks (2/2 eyes), and 36 weeks (1/1 eye) without additional antiglaucoma therapies. Photopic vision and shunt position and patency were maintained in all shunted globes for all follow-up periods. Postoperative complications included mild aqueous flare and fibrin (n= 3 eyes for 3-10 days postoperatively); intracameral shunt occlusion with fibrin (n= 1 eye at days 2 and 4); partial anterior chamber tube extrusion (n= 1 eye at day 4), and focal corneal edema (n= 1 eye at 18 weeks). Tissue plasminogen activator injected intracamerally through the silicone tube near the frontal sinus effectively resolved the fibrinous shunt occlusion. CONCLUSIONS: The Cullen frontal sinus valved glaucoma shunt shows promise for the management of canine primary glaucoma.     

Morphologic changes in the lamina cribrosa of beagles with primary open-angle glaucoma

Optic nerve axoplasmic flow is known to be impaired at the scleral lamina cribrosa in Beagles with hereditary primary open-angle glaucoma and is similar to the condition in human beings. Trypsin and detergent digestion to remove all neural, vascular, and glial cellular tissue revealed a well-developed scleral lamina cribrosa in the normal dog in this study. Beagles with primary open-angle glaucoma had signs of mechanical distortion of the anterior lamina cribrosa prior to the detection of ophthalmoscopic changes in the optic nerve head. This change in the supporting architecture of the optic nerve began early and increased in severity as the disease process progressed.     

Ultrastructural changes in laminar optic nerve capillaries of beagles with primary open-angle glaucoma

Ultrastructural examination of optic nerve capillaries in the canine lamina cribrosa revealed many spherical, membrane-bound, electron-dense inclusions that closely resembled Weibel-Palade bodies, in pericytes and endothelial cells of preglaucomatous, early, moderately, and advanced affected Beagles with hereditary primary open-angle glaucoma. This ultrastructural difference between the laminar capillary endothelial cells of normal and glaucomatous Beagles could represent a functional vascular disorder, because Weibel-Palade bodies are associated with microcirculatory abnormalities.     

Progressive changes in ophthalmic blood velocities in Beagles with primary open angle glaucoma

Objective To measure changes in the ocular and orbital blood flow velocities by color Doppler imaging (CDI) in beagles with primary open angle glaucoma as the disease progressed from early to advanced stages. Methods CDI measurements were performed periodically on 13 glaucomatous Beagles during the nontreated mild, moderate and advanced stages of POAG over the course of 4 years. CDI was performed with the dogs lightly anesthetized (butorphanol 0.1 mg/kg IV, acepromazine maleate 0.02 mg/kg IV, and atropine sulfate 0.05 mg/kg) while the CD transducer was placed directly on the cornea anesthetized with 0.5% tetracaine hydrochloride. Intraocular pressure (IOP) by pneumatonography or TonoPen XL, heart rate and mean arterial blood pressure were measured at the beginning, middle and end of each study. The ophthalmic vessels examined included: external ophthalmic arteries and veins, long and short posterior ciliary arteries, anterior ciliary arteries and veins, primary retinal arteries, and vortex veins. Recordings of each vessel included peak systolic velocity (PSV), end diastolic velocity (EDV) and time averaged velocity (TAV), and when possible the resistive index (RI) and pulsatility index (PI) were computed. Results CDI abnormalities were present before intraocular pressure exceeded the normal range. As the animals aged, and the glaucoma progressed with higher levels of IOP, significant changes occurred in nearly all vessels, and generally included a major increase in RI (P < 0.001) and an increase in the PI (P < 0.001). Mean arterial blood pressure (105 ± 18 mmHg) and heart rate (118 ± 33/min) remained reasonably constant. The IOP gradually increased as the disease progressed (early and normotensive: 19.4 ± 3.9 mmHg; moderate: 29.7 ± 2 mmHg; and advanced: 44.5 ± 6 mmHg). The ocular veins seemed most influenced early on in the disease. Late in the disease, ocular venous blood flow could not be consistently demonstrated. An increase in the PI of ocular veins occurred in the moderately and severely affected glaucomatous Beagles. As the IOP increased, there were trends of increasing resistive index and pulsatility index in most arteries, and periods of marked decreased velocities of the vortex and external ophthalmic veins in severe cases. Conclusion CDI measurements in Beagles with primary open angle glaucoma during the course of 4 years indicate easily measurable and repeatable progressive blood flow abnormalities before the elevation of IOP and, thereafter, with gradually increased levels of IOP.     

The effect of dorzolamide 2% on circadian intraocular pressure in cats with primary congenital glaucoma

Objective To determine the extent of fluctuation in circadian intraocular pressure (IOP) and the efficacy of topical dorzolamide 2% q 8 h in lowering IOP and blunting circadian fluctuation in IOP in glaucomatous cats. Animals studied Seven adult cats with primary congenital glaucoma (PCG). Procedures Measurements of IOP and pupil diameter were obtained for both eyes (OU) of each cat q 4 h for 12 days. Cats were housed in a laboratory animal facility with a 12‐h light:dark cycle. Baseline values were established for 2 days. For the next 5 days, placebo (1.4% polyvinyl alcohol) was administered OU q 8 h. Dorzolamide 2% was then administered OU q 8 h for a further 5 days. A multivariate mixed linear model was fitted to the data, with parameters estimated from a Bayesian perspective. The 4 am time point was selected as the reference for the purposes of comparisons. Results Estimated mean IOP for the reference time point pre‐treatment was symmetric (about 33 mmHg OU). In all cats, IOP was significantly lower during the diurnal phase, relative to the 4 am measurements, with highest IOP observed 2–6 h after the onset of the dark phase. Circadian fluctuations in IOP were dampened during the treatment period. There was a significant decrease in IOP in all cats during the dorzolamide treatment period (estimated mean for the treatment period reference = 17.9 mmHg OU). Conclusions Topical dorzolamide 2% q 8 h is effective in reducing IOP and IOP fluctuation in cats with PCG.     

Loss of glutamine synthetase immunoreactivity from the retina in canine primary glaucoma

Purpose Changes in retinal glutamate distribution occur in primary glaucoma (PG) in dogs. Although the redistribution resembles that induced by ischemia, decreases in glutamine synthetase (GS) activity may also induce a similar glutamate redistribution. We examined the distribution of GS, glutamate, and glial fibrillary acidic protein (GFAP), a marker for reactive glia, in PG retinas by immunohistochemistry to determine whether decreases in GS and formation of reactive glia are associated with glutamate redistribution and neuronal damage. Animals Sections from 14 control dog eyes and 22 eyes from dogs with PG. Methods Sections from 14 control and 22 glaucomatous globes were immunohistochemically stained for GS, glial fibrillary acidic protein or glutamate. Results In semiquantitative immunogold studies, decreases in GS staining density were strongly correlated with glutamate redistribution and neuronal damage. In less quantitative immunoperoxidase staining of acute (≤ 5 days after clinical signs) and chronic PG retinas, GS immunoreactivity was decreased in focal regions of some acute PG retinas, and there were widespread decreases in chronic PG retinas. GFAP immunoreactivity was increased in Müller cells primarily in severely damaged regions of chronic PG retinas. Conclusions Decreases in GS immunoreactivity were associated with glutamate redistribution. These decreases in GS occurred even in mildly damaged regions of retina before retinal thinning. Reactive Müller cells were seen primarily in chronic PG in severely damaged regions. Decreases in GS may potentiate ischemia‐induced early glutamate redistribution and neuronal damage in canine PG.     

Effect of birth weight,gender and litter characteristics on summer mortality in lambs of Norwegian breeds

Abstract

This study describes how birth weight, gender, litter size, and age of dam affect lamb mortality during the summer period, using data on lambs of the breeds Spælsau (N ≈ 110 000) and Norwegian White Sheep (N ≈ 450 000) during 1994 to 2005. A general mixed linear model was used for the analysis. Birth weight affected summer mortality non-proportionally: an increase in weight from very small towards the breed mean strongly deflated mortality risk; weigh increase above breed means had little effect. Male lambs had a higher mortality than females, and lambs born by 12-months-old dams were in greater risk than those having older dams. Increasing litter size resulted in increased mortality. The results are discussed and recommendations for future research, with focus on breeding and genotype by environment interaction effects are made.     

Pectinate ligament dysplasia (PLD) and glaucoma in Flat Coated Retrievers. I. Objectives, technique and results of a PLD survey

Pectinate ligament dysplasia (PLD) in dogs is a congenital ocular abnormality affecting the iridocorneal angle, the presence of which may be associated with adult-onset primary glaucoma. This paper describes the objectives, methods and results of a survey of PLD in Flat Coated Retrievers in the UK, including the technique used for gonioscopic assessment of the degree of PLD. In a random sample of 389 Flat Coated Retrievers, 34.7% were found to have a degree of PLD. In a 'target' sample of 48 Flat Coated Retrievers (close relatives of dogs from the random sample with high degrees of PLD, or dogs presented with primary glaucoma), 83.3% were found to have a degree of PLD. The percentage of animals with a degree of PLD was only 6.0% in a 'control' sample of 100 dogs from other breeds. The relationship between PLD and canine glaucoma is discussed.     

Posterior lens luxation with associated glaucoma in a pony

Secondary lens luxation is an infrequent consequence of equine recurrent uveitis (ERU). This Case Report describes a pony with posterior lens luxation with associated glaucoma, thought to be secondary to ERU.     

Combined transscleral diode laser cyclophotocoagulation and Ahmed gonioimplantation in dogs with primary glaucoma: 51 cases (1996-2004)

OBJECTIVE: To evaluate the combined diode laser cycloablation procedure and adjunctive Ahmed gonioimplant use in dogs with primary glaucoma. DESIGN: Retrospective study. ANIMALS: 48 dogs, 51 eyes with primary glaucoma. PROCEDURE: Medical records from two large private clinical ophthalmology services were reviewed. Signalment, duration of glaucoma, gonioscopic evaluation, laser power and duration settings, immediate postoperative and final intraocular pressure and visual results, short and long-term visual outcome, and surgical complications were recorded. RESULTS: The age range of affected dogs was 3.0-14.0 years, with a mean age of 7.5 +/- 2.6 years. Eleven pure breeds were represented, with the most common being the American Cocker Spaniel. The sex distribution was 22 neutered males, 1 intact male, 23 spayed females, and 2 intact female dogs. The right eye was affected in 33 cases, and the left eye in 18 cases. The average total joules, which was administered with the diode laser, was 109.6 +/- 23.6 J. Immediate surgical complications included fibrin formation in the anterior chamber (15), corneal ulcers (4), hyphema (7), and focal retinal detachment (1). Long-term complications included cataract formation (8 total, 2 of which were significant, vision-threatening), elevated intraocular pressure (IOP) (6), unstable gonioimplant (1), and glaucoma recurrence (14). Additional surgeries performed on the eyes over the course of study included: intrascleral prosthesis (4), enucleation (1), resection of fibrotic scar tissue (5), and repeat laser cycloablation (8). The dogs were examined for a mean follow-up time of 17.6 months (range: 2-83 months postoperatively). Twenty-nine cases were followed greater than one year. Vision was maintained in 42/51 eyes (82%) in the immediate short-term of this study. In all cases included in the study, good control of IOP was achieved in 39/51 (76%) of eyes, and IOP was poor or uncontrolled in 12/51 (24%) of eyes. Twenty out of 41 eyes (49%) maintained fair to excellent vision six months after surgery. Twelve months postoperative observations demonstrated that 12/29 (41%) of the eyes were still visual. CONCLUSIONS: In primary glaucoma, the combined procedure of laser diode cyclophotocoagulation and Ahmed valve implant was associated with return or maintenance of vision in 42/51 eyes (82%) in the immediate short-term of this study, and a long-term IOP control in 39/51 (76%) of the cases, with 12/29 eyes (41%) visual after 12 months.     

Aqueous humor myocilin protein levels in normal, genetic carriers, and glaucoma Beagles

Objective The gene (myocilin: MYOC) has been attributed to be involved in over 6% of inherited types of human glaucoma, the highest correlation for any gene to date. This study determines myocilin protein levels in the aqueous humor (AH) of normal laboratory quality, genetic carrier (offspring of normal laboratory quality and POAG Beagles), and primary open angle glaucoma (POAG) Beagles. Materials and methods Eighteen dogs were used and classified as either normal, carrier or having mild, moderate or advanced POAG. A 0.1‐mL sample of AH was drawn from the anterior chamber of each dog in the study and frozen on dry ice. A modified Coomassie stain and Western blot, using a polyclonal rabbit antihuman myocilin antibody (Santa Cruz Biotechnologies, Santa Cruz, CA), was run on each sample to compare the myocilin levels. A purified human trabecular meshwork excreted myocilin protein sample was used as a control (Alcon Research Laboratories, Fort Worth, TX) and its band/densitometry measurement was defined as one unit of myocilin for comparisons. Results Comparisons of AH myocilin levels differed among normal laboratory quality, genetic carrier, and POAG Beagles at different stages of the disease. In the normal laboratory, Beagles the AH myocilin measured 0.817 ± 0.075 units (mean ± SEM); in the carrier Beagles the AH myocilin was 3.117 ± 0.290 units. As POAG progressed, myocilin protein levels also increased to 6.097 ± 0.810, 8.844 ± 1.079, and 17.228 ± 1.198 units in the early, moderate, and advanced forms, respectively. Overall comparisons between normal, carrier and all POAG Beagles combined showed significant differences (P < 0.0010). Individual comparisons between normal and carrier eyes showed significant differences (P < 0.0193). Comparisons between normal and all POAG eyes also showed significant differences (P < 0.0426). Conclusion This study shows myocilin protein is present in normal Beagles, markedly increased in POAG Beagles, and mildly increased in genetic carrier Beagles. There is a strong correlation between amounts of AH myocilin protein and the presence and severity of POAG. The exact role of AH myocilin levels in the genesis of ocular hypertension remains unresolved, but myocilin may adversely affect AH outflow.     

Across-country genomic predictions in Norwegian and New Zealand Composite sheep populations with similar development history

The goal of this study was to assess the feasibility of across-country genomic predictions in Norwegian White Sheep (NWS) and New Zealand Composite (NZC) sheep populations with similar development history. Different training populations were evaluated (i.e., including only NWS or NZC, or combining both populations). Predictions were performed using the actual phenotypes (normalized) and the single-step GBLUP via Bayesian inference. Genotyped NWS animals born in 2016 (N = 267) were used to assess the accuracy and bias of genomic estimated breeding values (GEBVs) predicted for birth weight (BW), weaning weight (WW), carcass weight (CW), EUROP carcass classification (EUC), and EUROP fat grading (EUF). The accuracy and bias of GEBVs differed across traits and training population used. For instance, the GEBV accuracies ranged from 0.13 (BW) to 0.44 (EUC) for GEBVs predicted including only NWS, from 0.06 (BW) to 0.15 (CW) when including only NZC, and from 0.10 (BW) to 0.41 (EUC) when including both NWS and NZC animals in the training population. The regression coefficients used to assess the spread of GEBVs (bias) ranged from 0.26 (BW) to 0.64 (EUF) for only NWS, 0.10 (EUC) to 0.52 (CW) for only NZC, and from 0.42 (WW) to 2.23 (EUC) for both NWS and NZC in the training population. Our findings suggest that across-country genomic predictions based on ssGBLUP might be possible for NWS and NZC, especially for novel traits.