Optic nerve head neuroretinal rim blood flow differences in monkeys with laser-induced glaucoma

INTRODUCTION: The blood flow of the neuroretinal rim (NRR) of the optic nerve head (ONH) of the rhesus monkey with laser-induced glaucoma was examined. METHODS: Argon laser photocoagulation of the trabecular meshwork to induce elevated intraocular pressure (IOP) was performed in one eye of nine normal male rhesus monkeys. The nasal and temporal NRR of the monkey ONH were examined by the Heidelberg retina tomograph/flowmeter (HRT/HRF) under neuromuscular blockade. A mixed effect analysis of variance was used to determine significant differences between eyes and between locations in the eyes. RESULTS: The average IOP in the hypertensive glaucoma and normal eyes was 34.8 +/- 7.2 and 16.0 +/- 1.9 mmHg, respectively. The HRT determined average overall cup to disc (C/D) area ratio in the glaucoma and normal eyes, which was 0.49 +/- 0.28 and 0.22 +/- 0.16, respectively. The mean temporal NRR HRF flow in the hypertensive eyes was significantly greater than in the normotensive eyes (P < 0.0001), than in the nasal NRR of the hypertensive eyes (P < 0.0001) and than in the nasal NRR of the normotensive eyes (P < 0.01). The mean nasal NRR HRF flow in the hypertensive eyes was significantly less than in the nasal NRR of the normotensive eyes (P < 0.01). There was no statistical difference between the mean HRF flow of the temporal and nasal NRR of the normotensive eyes. The elevated IOP positively influenced the flow values in the hypertensive eye (r = 0.724). CONCLUSIONS: The capillary microcirculation of the temporal NRR of the rhesus monkey ONH with laser-induced glaucoma has significantly increased blood flow, and the nasal NRR significantly reduced blood flow compared to blood flow in the NRR of normal normotensive monkey eyes.     

Spectral domain optical coherence tomography (SD-OCT) assessment of the healthy female canine retina and optic nerve

Objective To provide normative data for canine whole retinal thickness (WRT), nerve fiber layer thickness (NFL), photoreceptor layer thickness (PR), and outer nuclear layer thickness (ONL) using spectral domain optical coherence tomography. Animal studied: Twelve healthy adult intact female beagles. Procedure Horizontal volume scans through the area dorso‐temporal from the optic nerve (superior retina), and the area ventro‐temporal from the optic nerve (inferior retina) were used to evaluate the thickness of retinal NFL, PR, ONL, and WRT. Peripapillary circular scans were used to evaluate NFL thickness. Statistical analyses were performed to compare the thickness of the individual layers between the superior and inferior retina (paired t‐test). One‐way analysis of variance (ANOVA) was used to compare the thickness of peripapillary NFL between the superior, inferior, temporal and nasal quadrants of the circle scan. Results The WRT, PR, and NFL thickness were greater in the superior than in the inferior retina (198.7 ± 9.6 μm vs. 164.4 ± 6.4 μm, P < 0.0001; 95.5 ± 6.5 μm vs. 78.8 ± 7.4 μm, P < 0.0001; and 26.4 ± 1.6 μm vs. 25.0 ± 1.9 μm, P = 0.0236, respectively). No statistical difference was found between the ONL thickness of the superior and inferior retina (50.1 ± 6.4 μm vs. 44.3 ± 3.6, P = 0.0578). Peripapillary NFL thickness showed a similar tendency as the linear scans, with the superior quadrant having the greatest thickness (91.26 ± 7.0 μm) and the inferior quadrant being the thinnest (76.42 ± 9.2 μm) (P < 0.001). Conclusions Results of our in vivo studies showed significant differences between thickness values for the superior (tapetal) and inferior (nontapetal) retinal regions.     

Comparative optic nerve physiology: implications for glaucoma, neuroprotection, and neuroregeneration

The axoplasm of optic nerve axons moves bidirectionally at various speeds along an intra-axonal pressure gradient from the retinal ganglion cell (RGC) somata toward its synapse, and from the synapse towards the RGC somata. The axoplasmic flow of optic nerve axons is precarious even at normal intraocular pressures (IOP) as it moves from the intraocular optic nerve through the scleral lamina cribrosa to the intraorbital optic nerve. The scleral lamina cribrosa is not simply a porous region of the sclera but a specialized extracellular matrix of the central nervous system whose movement during fluctuations in IOP can affect optic nerve axoplasmic flow. The abundant optic nerve blood supply maintains adequate optic nerve head perfusion through a process of vascular autoregulation. Glaucoma is associated with reduced optic nerve axoplasmic flow and compromised optic nerve circulation such that RGC death due to glutamate excitotoxicity and neurotrophin deprivation result.     

Rapid diagnosis of retina and optic nerve abnormalities in canine patients with and without cataracts using chromatic pupil light reflex testing

Objective To develop fast and reliable testing routines for diagnosing retina and optic nerve diseases in canine cataract patients based on chromatic properties of the pupillary light reflex response. Procedures Seventy‐seven canine patients with a history of cataract and decreased vision (43 patients with cataracts and no evidence of retina or optic nerve disease, 21 patients with cataracts and retinal degeneration [RD], 13 patients with cataracts and retinal detachment [RDT]), 11 canine patients with optic neuritis (ON) and 23 healthy dogs were examined using chromatic pupillary light reflex (cPLR) analysis with red and blue light and electroretinography. Results Electroretinography analysis showed statistically significant deficits in a‐ and b‐wave amplitudes in dogs with cataracts and RD, or cataracts and RDT, when compared to dogs with cataracts without evidence of retinal abnormalities. Evaluation of b‐wave amplitudes showed that presence of 78.5‐μV (or lower) amplitudes had high sensitivity of 100% (95% CI: 87.2–100%) and high specificity of 96.7% (95% CI: 88.4–100%) in RD and RDT. Evaluation of cPLR responses using red light showed that presence of the pupil end constriction diameter of 5.5 mm (or higher) had moderately high sensitivity of 76.5% (95% CI: 50.1–93.2%) and high specificity of 100% (95% CI: 91.2–100%) in detecting RD and RDT. Optic neuritis patients had absent cPLR responses, regardless of the visual status. Conclusions and Clinical Relevance Chromatic evaluation of the pupillary light reflex is a rapid and accurate test for diagnosing retina and optic nerve diseases in canine patients.     

Distinctive histopathologic features of canine optic nerve hypoplasia and aplasia: a retrospective review of 13 cases

Canine optic nerve hypoplasia (ONH) and aplasia (ONA) are significant neuro-ophthalmologic disorders that have been reported in several species. The purpose of this study was to describe the distinctive histopathologic features of ONH and ONA in canine patients identified from a collection of 20 000 ocular submissions at the comparative ocular pathology laboratory of Wisconsin from 1989 to 2006. The following information about ONH and ONA cases was collected: signalment, and clinical and gross findings, including unilateral vs. bilateral involvement. Microscopic evaluation was performed, with attention to optic nerve malformation, retinal ganglion cell (RGC) and nerve fiber layer (NFL) loss, and retinal disorganization. The distribution of retinal vasculature was recorded and a search for unusual findings of ONH and ONA was performed. Information and histologic documentation was available for 13 cases. Eight cases of ONH and five cases of ONA were identified. The average group age was 20.2 months and 16.1 months, respectively. The most common breed was the Shih Tzu (3/13). ONH usually presented bilaterally (7/8); all ONA cases presented as a unilateral disease (5/5). The morphologic findings in the optic nerve (ON) in ONH included variable degrees of ON hypoplasia and gliosis, as well as ectopic vestigial ON remnants within orbital nerves and connective tissues. The NFL was detected in the majority of the ONH cases; however, RGCs were rare or absent. Mild retinal disorganization was seen occasionally. Most cases of ONH were associated with regional peripheral retinal blood vessel extension into the vitreous, leaving the peripheral retina avascular. In ONA cases the retinal blood vessels, NFL and RGCs were totally absent and retinal disorganization was severe. Distinctive microscopic features encountered in ONA included anterior segment dysgenesis in some cases. The retina in these cases was stretched across the posterior lens capsule, never making contact with the posterior pole of the globe. The current study reviews the human and veterinary literature pertaining to ONH and ONA, compares ONH and ONA in dogs, and presents related ophthalmic histopathologic findings that have not been reported previously.     

The future of canine glaucoma therapy

Canine glaucoma is a group of disorders that are generally associated with increased intraocular pressure (IOP) resulting in a characteristic optic neuropathy. Glaucoma is a leading cause of irreversible vision loss in dogs and may be either primary or secondary. Despite the growing spectrum of medical and surgical therapies, there is no cure, and many affected dogs go blind. Often eyes are enucleated because of painfully high, uncontrollable IOP. While progressive vision loss due to primary glaucoma is considered preventable in some humans, this is mostly not true for dogs. There is an urgent need for more effective, affordable treatment options. Because newly developed glaucoma medications are emerging at a very slow rate and may not be effective in dogs, work toward improving surgical options may be the most rewarding approach in the near term. This Viewpoint Article summarizes the discussions and recommended research strategies of both a Think Tank and a Consortium focused on the development of more effective therapies for canine glaucoma; both were organized and funded by the American College of Veterinary Ophthalmologists Vision for Animals Foundation (ACVO‐VAF). The recommendations consist of (a) better understanding of disease mechanisms, (b) early glaucoma diagnosis and disease staging, (c) optimization of IOP‐lowering medical treatment, (d) new surgical therapies to control IOP, and (e) novel treatment strategies, such as gene and stem cell therapies, neuroprotection, and neuroregeneration. In order to address these needs, increases in research funding specifically focused on canine glaucoma are necessary.     

Light-microscopy evaluation of zonular fiber morphology in dogs with glaucoma: secondary to lens displacement

Lens displacement resulting in secondary glaucoma is common in terrier breeds. This study was carried out to evaluate whether light microscopy was useful in detecting abnormal patterns in zonular fiber protein. Eyes from 63 dogs with glaucoma secondary to lens displacement were evaluated for the presence of abnormal zonular fiber morphology using the following stains: hematoxylin and eosin, periodic acid Schiff (PAS), Masson's trichrome and Verhoeff's elastin stains. Two distinct forms of abnormal zonular fiber morphology were recognized and designated as zonular fiber dysplasia (ZFD) and zonular fiber collagenization (ZFC). ZFD protein morphology was characterized by being tightly adherent to the nonpigmented ciliary body epithelium, exhibiting a distinct lamellar and cross-hatched pattern and staining strongly positive with PAS and trichrome stains, and staining negative with elastin stains. ZFD was predominant in terrier breeds (18 of 29) and Shar-Pei dogs (4 of 29). ZFC abnormality was characterized by excessive zonular fiber that was not tightly adherent to the ciliary body epithelium and staining positive with PAS, trichrome (blue for collagen) and elastin stains. Only 7 of 19 dogs with ZFC changes were terrier breeds, and there was no pattern in the breeds affected. Fifteen of the 63 dogs used in the study had normal appearing zonular fibers. The staining pattern in these dogs matched normal controls by staining positive with PAS and Verhoeff's elastin stains and had only minimal positive staining with Masson's trichrome stain. Results suggest that light microscopy is useful in detecting breed-related changes in zonular fiber morphology in cases of glaucoma secondary to lens displacement. These changes may correlate with the presence of abnormal zonular fiber proteins and might be important in the pathogenesis of primary lens displacement in terrier and Shar-Pei dogs.     

Unilateral invasive intraocular melanoma with choroidal and optic nerve involvement resulting in bilateral vision loss in a Labrador Retriever

A 10-year-old male castrated Labrador Retriever cross was referred for evaluation of acute vision loss. Ophthalmic examination revealed mild left sided exophthalmos, bilateral resting mydriasis, an absent direct and reduced consensual PLR in the left eye and reduced direct and absent consensual PLR in the right eye. Examination of the cornea and anterior segment with slit lamp biomicroscopy was unremarkable. Indirect fundoscopy revealed a left optic nerve head obscured by a darkly pigmented lesion. Fundic examination in the right eye was unremarkable. Magnetic resonance imaging revealed a smoothly marginated, lobulated cone to irregularly shaped, strongly T1 hyperintense, T2 and T2 fluid-attenuated inversion recovery hypointense, strongly contrast enhancing mass closely associated with the entire left optic nerve, extending across the optic chiasm and into the right optic nerve ventrally. Full clinical staging revealed no evidence of metastasis. Exenteration of the left eye was performed. Histopathology revealed an unencapsulated, poorly demarcated, multilobulated and infiltrative pigmented mass that was effacing the posterior choroid and optic nerve. The mass was composed of a moderately pleomorphic population of heavily pigmented polygonal cells arranged in sheets and clusters, displaying moderate anisocytosis and anisokaryosis. The population of cells contained moderate amounts of abundant brown-black granular pigment consistent with melanin within the cytoplasm. Mitotic figures averaged approximately three per ten 400× fields (2.37 mm²). This is the first report of a melanocytic tumor invading along the optic nerve and tract to result in contralateral vision loss.     

Quantitative studies of the optic nerve fiber layer in the chicken retina.

The optic nerve fiber layer (NFL) of the chicken retina was studied quantitatively and morphologically at 17 positions along seven radially arranged bands from the dorsal tip of the pecten oculi using electron microscopy. The number of nerve fibers was counted in areas 6 microm in width x the full thickness of the NFL. Myelinated nerve fibers in the NFL were also identified immunohistochemically using anti-myelin basic protein serum. The dorsal area (dorsal, dorso-temporal and dorso-nasal bands) in the retina had thin NFL and contained the largest number of nerve fibers, which were mainly thin and unmyelinated. The ventral area (ventral and ventro-temporal bands) had a thick NFL and contained a relatively small number of nerve fibers, many of which were myelinated. The nasal band had the thickest NFL and contained as many nerve fibers as the dorsal area, with the temporal band showing a high ratio of myelinated fibers. The band had a thick NFL and contained many nerve fibers with a relatively low ratio of myelinated fibers. The relationship between the number and composition of nerve fibers in the NFL to the chicken visual characteristics was discussed. Although the myelin in the chicken retina was loose type, the myelin-forming cells were similar in appearance to dense oligodendrocytes. retina, morphometry, myelinated fiber, nerve fiber layer.     

Bilateral traumatic optic nerve avulsion in a Thoroughbred gelding

This report describes an unusual case of acute blindness following traumatic head injury in a mature horse. The horse fell over backwards and subsequently presented with bilateral blindness and epistaxis. Vision did not return following medical supportive therapy and euthanasia was elected. Post mortem findings revealed a basisphenoid fracture and bilateral optic nerve avulsion rostral to the optic chiasm, an uncommon presentation of traumatic blindness not previously reported in the horse.     

Magnetic resonance imaging of the femoral head of normal dogs and dogs with avascular necrosis.

The purpose of this study was to describe the appearance of the femoral head of normal, young, small breed dogs, and dogs with avascular necrosis using low-field (0.3 T) magnetic resonance (MR) imaging. Images of the femoral heads were obtained in the dorsal plane, and included T1-weighted spin-echo, T2-weighted fast spin-echo, fast spin echo-inversion recovery, and fluid attenuated inversion recovery pulse sequences. MR imaging features of the asymptomatic femoral heads and necks included uniform high signal intensity compared with muscle on T1- and T2-weighted images. There was either uniform enhancement or no enhancement on postcontrast T1-weighted images. The MR imaging findings of dogs affected with avascular necrosis differed from those of asymptomatic dogs. Typically, the affected dogs had inhomogeneous intermediate to low-signal intensity within the femoral head and neck compared with muscle on T1-weighted images, inhomogeneous enhancement of the femoral head and/or neck on postcontrast T1-weighted images, and inhomogeneous low- to high- signal intensity within the femoral head and neck on T2-weighted images.     

Genetic analysis of optic nerve head coloboma in the Nova Scotia Duck Tolling Retriever identifies discordance with the NHEJ1 intronic deletion (collie eye anomaly mutation)

Collie eye anomaly (CEA) encompasses a spectrum of different ophthalmic phenotypes from clinically inconsequential choroidal hypoplasia to blindness from coloboma of the optic nerve head (ONH). A previous study found a 7.8‐kb deletion in intron 4 of the NHEJ1 gene to be associated with CEA. A genetic test based on this association is recommended for many breeds, including the Nova Scotia Duck Tolling Retriever (NSDTR). Collection of ONH coloboma‐affected NSDTR showed lack of concordance of the NHEJ1 intronic deletion with ONH coloboma. Using genomewide single nucleotide polymorphism (SNP) genotyping in 7 ONH coloboma‐affected NSDTR cases and 47 unaffected NSDTR controls with no ophthalmic signs, one SNP, located on chromosome 7, demonstrated genomewide significance. However, high genomic inflation may have confounded the results. Therefore, the genomewide association study was repeated using EMMAX to control for population structure in the cohort of 7 cases and 47 controls. However, no regions of the genome were significantly associated with ONH coloboma. These results failed to document significant association with the CEA locus. Due to the complex genetic etiology of ONH coloboma, the NHEJ1 intronic deletion test results should be carefully considered when making breeding decisions. If the goal is to select for visually competent dogs, our data suggest that eye examinations of puppies would be more effective as a guide in selection of breeding pairs than relying solely on currently available genetic tests.     

Quantitative study of the optic nerve in buffaloes (Bos bubalis)

The total number, distribution and size of the optic axons of the buffalo (Bos bubalis) were studied in five optic nerves using light and transmission electron microscopes. Semithin sections were cut at 0.40 μm with an ultramicrotome and stained with 0.3% toluidine blue for light microscopic analysis. The ultrathin sections were cut at 70 nm, mounted on copper mesh grids (No. 200) and stained with saturated solution of uranyl acetate dihydrate and examined with the transmission electron microscope. The optic axons were assessed in 10 regions of roughly equal area. The total number of optic fibers was estimated on semithin and ultrathin sections. The measurements of the axonal diameters were made on electron micrographs taken from various regions across the optic nerve. The mean value of the total number of optic axons calculated was 1 397 099 ± 10 995 and 1 584 255 by light and electron microscopes, respectively. There was very little difference in the density of the optic fibers between the 10 regions of the optic nerve. The optic nerve area ranged from 18.2 to 22.4 mm² (mean, 21.3 mm²). The diameters of the optic axons ranged from 0.5 to 12.3 μm (mean, 3.3 μm).     

Assessment of the pigeon (Columba livia) retina with spectral domain optical coherence tomography

BackgroundTo assess the normal retina of the pigeon eye using spectral domain optical coherence tomography (SD-OCT) and establish a normative reference.MethodsTwelve eyes of six ophthalmologically normal pigeons (Columba livia) were included. SD-OCT images were taken with dilated pupils under sedation. Four meridians, including the fovea, optic disc, red field, and yellow field, were obtained in each eye. The layers, including full thickness (FT), ganglion cell complex (GCC), thickness from the retinal pigmented epithelium to the outer nuclear layer (RPE-ONL), and from the retinal pigmented epithelium to the inner nuclear layer (RPE-INL), were manually measured.ResultsThe average FT values were significantly different among the four meridians (p < 0.05), with the optic disc meridian being the thickest (294.0 ± 13.9 µm). The average GCC was thickest in the optic disc (105.3 ± 27.1 µm) and thinnest in the fovea meridian (42.8 ± 15.3 µm). The average RPE-INL of the fovea meridian (165.5 ± 18.3 µm) was significantly thicker than that of the other meridians (p < 0.05). The average RPE-ONL of the fovea, optic disc, yellow field, and red field were 91.2 ± 5.2 µm, 87.7 ± 5.3 µm, 87.6 ± 6.5 µm, and 91.4 ± 3.9 µm, respectively. RPE-INL and RPE-ONL thickness of the red field meridian did not change significantly with measurement location (p > 0.05).ConclusionsMeasured data could be used as normative references for diagnosing pigeon retinopathies and further research on avian fundus structure.