Herein, we report a case of nontraumatic bilateral rhegmatogenous retinal detachment (RRD) during... more Herein, we report a case of nontraumatic bilateral rhegmatogenous retinal detachment (RRD) during external beam radiotherapy for nonocular tumor, presented as an observational case study in conjunction with a review of the relevant literature. A 65-year-old male was referred to our hospital due to bilateral RRD. He underwent a biopsy for a tumor of the left frontal lobe 4 months prior to presentation, and the tumor had been diagnosed as primary central nerve system B-cell type lymphoma. He received chemotherapy and external beam radiotherapy for 1 month. There were no traumatic episodes. Bilateral retinal detachment occurred during a series of radiotherapies. Simultaneous nontraumatic bilateral retinal detachment is rare. The effects of radiotherapy on ocular functionality, particularly in cases involving retinal adhesion and vitreous contraction, may include RRD. Thus, it is necessary to closely monitor the eyes of patients undergoing radiotherapy, particularly those undergoing surgery for retinal detachment and those with a history of photocoagulation for retinal tears, a relevant family history, or risk factors known to be associated with RRD.
This study reviewed clinical data from dogs diagnosed with sudden acquired retinal degeneration s... more This study reviewed clinical data from dogs diagnosed with sudden acquired retinal degeneration syndrome (SARDS) in western Canada. Medical records from the Western College of Veterinary Medicine from 2002 to 2016 showed that 93 cases of SARDS were diagnosed based on presentation for sudden blindness and a bilaterally extinguished electroretinogram. The most common pure breeds were the miniature schnauzer, dachshund, and pug. The mean age at diagnosis was 8.1 years and males and females were equally affected. Most of the dogs were presented with normal non-chromatic, but abnormal chromatic pupillary light reflexes. The incidence of retinal degeneration as detected via ophthalmoscopy increased over time after SARDS diagnosis. Polyuria, polydipsia, polyphagia, weight gain, elevated liver enzyme values, isosthenuria, and proteinuria were common clinical and laboratory findings. Chromatic pupillary light reflex testing may be more valuable than non-chromatic pupillary light testing in detecting pupil response abnormalities in dogs with SARDS, although electroretinography remains the definitive diagnostic test.
Pectinate ligament dysplasia (PLD) is a common cause of canine glaucoma and the definitive clinic... more Pectinate ligament dysplasia (PLD) is a common cause of canine glaucoma and the definitive clinical diagnosis is based on gonioscopy. Although the histologic lesions of PLD have been described, it has not been determined whether these changes are specific for PLD or if similar histologic changes can develop as a consequence of secondary glaucoma. The filtration angles of 61 enucleated canine globes with chronic glaucoma were evaluated with light microscopy by 3 examiners who were masked to the clinical history, signalment, and gonioscopic results. A histologic diagnosis of PLD versus non-PLD was determined by each examiner based on previously reported morphologic criteria and compared with the clinical gonioscopic diagnosis. Of the 61 enucleated glaucomatous eyes, 40 were clinically diagnosed with PLD. For all 3 examiners, a histologic diagnosis of PLD corresponded poorly with the clinical diagnosis of PLD (range of kappa score: 0.149-0.269; range of AUC: 0.592-0.621). There was no difference between examiners in their ability to correctly diagnose PLD histologically (P ¼ .978). A fair degree of agreement was noted among examiners in obtaining their suspected histologic diagnosis of PLD (kappa score 0.256). No individual or sets of histologic ICA features were consistent with clinical PLD. The results indicate the histologic ICA changes proposed to be characteristic of PLD are also noted in canine globes affected with chronic secondary glaucoma. Therefore, using routine histologic evaluation, a histologic diagnosis of PLD is not possible in the face of chronic canine glaucoma.
Mitochondrial transcription factor A (Tfam) has been implicated in the pathogenesis of retinal dy... more Mitochondrial transcription factor A (Tfam) has been implicated in the pathogenesis of retinal dysplasia in miniature schnauzer dogs and it has been proposed that affected dogs have altered mitochondrial numbers, size, and morphology. To test these hypotheses the Tfam gene of affected and normal miniature schnauzer dogs with retinal dysplasia was sequenced and lymphocyte mitochondria were quantified, measured, and the morphology was compared in normal and affected dogs using transmission electron microscopy. For Tfam sequencing, retina, retinal pigment epithelium (RPE), and whole blood samples were collected. Total RNA was isolated from the retina and RPE and reverse transcribed to make cDNA. Genomic DNA was extracted from white blood cell pellets obtained from the whole blood samples. The Tfam coding sequence, 5' promoter region, intron1 and the 3' non-coding sequence of normal and affected dogs were amplified using polymerase chain reaction (PCR), cloned and sequenced. For electron microscopy, lymphocytes from affected and normal dogs were photographed and the mitochondria within each cross-section were identified, quantified, and the mitochondrial area (μm²) per lymphocyte cross-section was calculated. Lastly, using a masked technique, mitochondrial morphology was compared between the 2 groups. Sequencing of the miniature schnauzer Tfam gene revealed no functional sequence variation between affected and normal dogs. Lymphocyte and mitochondrial area, mitochondrial quantification, and morphology assessment also revealed no significant difference between the 2 groups. Further investigation into other candidate genes or factors causing retinal dysplasia in the miniature schnauzer is warranted.
To compare the scanning laser ophthalmoscopy (SLO), optical coherence tomography (OCT), and fluor... more To compare the scanning laser ophthalmoscopy (SLO), optical coherence tomography (OCT), and fluorescein angiography (FA) findings in retrievers with a single unilateral circular retinal plaque to those of an English springer spaniel with bilateral retinal dysplasia. Procedures: A retrospective record review identified three dogs with circular retinal plaques that underwent SLO and OCT; in two of the three dogs, FA was also completed. Morphologic changes, lesion measurements, and angiogram characteristics were documented. An English springer spaniel with bilateral retinal dysplasia that had undergone SLO, OCT, and FA was used for comparison. Results: Scanning laser ophthalmoscopy of the retriever dogs revealed circular retinal plaques with a dark periphery located in the tapetal retina. OCT revealed a thickening of the nerve fiber layer corresponding to the circular pattern observed on SLO. Within the circular plaque, the retina was predominantly of normal architecture. FA revealed variable hypofluorescence of both the rim and the center of the circular lesion throughout the early angiogram phases. In the late recirculation phase, small multifocal areas of hyperfluorescence were observed. OCT of geographic retinal dysplasia in the English springer spaniel revealed disorganization of both inner and outer retinal layers, and retinal detachment. Conclusions: Circular plaques observed in the tapetal retina are predominantly formed by a thickening of inner retina, while retinal dysplasia has disorganization of both inner and outer retinal layers. Further etiologic research is needed, including pedigree mapping to determine whether retinal plaques are an acquired or inherited condition.
Cavernous sinus syndrome is a unique constellation of cranial nerve deficits occurring typically ... more Cavernous sinus syndrome is a unique constellation of cranial nerve deficits occurring typically as a result of pathologic infiltration of the cavernous sinus, which is located in the lateral sellar compartment of the calvarium. This case report describes a polyneuropathy consistent with cavernous sinus syndrome as a result of a lesion outside of the cavernous sinus. The cat was presented with right internal and external ophthalmoplegia, loss of right corneal sensation, inspiratory stridor, dysphagia, dysphonia, tongue weakness, and weight loss. Magnetic resonance imaging identified a large nasopharyngeal mass along the base of, but without extension into, the calvarium. The histologic diagnosis was nasopharyngeal lymphoma. Focal extracranial masses should be considered as differential diagnoses for multiple cranial nerve deficits, including the constellation of clinical signs recognized as cavernous sinus syndrome.
Horner's syndrome arises from dysfunction of the oculosympathetic pathway and is characterized by... more Horner's syndrome arises from dysfunction of the oculosympathetic pathway and is characterized by miosis, enophthalmos, protrusion of the third eyelid, and ptosis. It has been recognized in a wide variety of breeds and ages in small animal patients. The oculosympathetic pathway is a 3-neuron pathway. The central/first order neuron arises from the hypothalamus and extends down the spinal cord. The preganglionic/second order neuron arises from the first 3 thoracic spinal cord segments and travels through the thorax and cervical region until it synapses at the cranial cervical ganglion. The postganglionic/third order neuron travels from this ganglion to the orbit. Topical application of cocaine is the gold standard for differentiating Horner's syndrome from other causes of miosis. Topical 1% phenylephrine allows for identification of a post-ganglion Horner's syndrome. Numerous etiologies have been reported for Horner's syndrome, but idiopathic disease is most common. Ancillary diagnostics include otoscopic examination, thoracic radiographs, or advanced imaging. Treatment and prognosis are determined by the etiology.
To describe the optical coherence tomography (OCT) and fluorescein angiography changes in dogs wi... more To describe the optical coherence tomography (OCT) and fluorescein angiography changes in dogs with sudden acquired retinal degeneration syndrome (SARDS). Methods: Retinal OCT was performed on 10 SARDS dogs and eight control dogs. Tomograms were collected in four quadrants around the optic nerve. Measurements were collected from the photoreceptor layer, the outer nuclear layer, the outer retina, the inner retina and the whole retina thickness in all quadrants. Sodium fluorescein was injected intravenously and serial fundic photographs were collected for a 5 minute period post-injection. Results: In all quadrants, the outer nuclear layer (dorsal temporal P = 0.0000, dorsal nasal P = 0.0001, ventral temporal P = 0.0002, ventral nasal P = 0.000) and outer retina (dorsal temporal P = 0.0001, dorsal nasal P = 0.0002, ventral temporal P = 0.0054, ventral nasal P = 0.0084) measurements were significantly decreased in SARDS dogs. The whole retina thickness was significantly decreased in the dorsal temporal (P = 0.0082) and ventral temporal (P = 0.0428) retina. There were no significant differences in the photoreceptor layer thickness or inner retinal thickness between SARDS and control dogs. All SARDS dogs had a loss of definition of all of the photoreceptor bands on OCT. Two SARDS dogs had multifocal small retinal detachments and one of these dogs exhibited fluorescein leaking at the detachment sites. Conclusions: The significant reduction in the outer nuclear layer and the loss of band signals in the photoreceptor layers in dogs with SARDS identified on OCT support the previous histopathology findings. Small detachments may occasionally be detected on OCT and they may leak fluorescein.
A 11-year-old neutered male Labrador retriever-cross dog was presented to the University of Misso... more A 11-year-old neutered male Labrador retriever-cross dog was presented to the University of Missouri-Columbia Veterinary Ophthalmology Service for subtle visual deficits. Indirect ophthalmoscopy revealed a smooth, bullous elevation in the superior-temporal retina OU. Optical coherence tomography (OCT) performed OU showed inner retinal separation consistent with retinoschisis. Electroretinography (ERG) revealed markedly reduced b-wave amplitudes in the more severely affected eye (OD) compared with the less severely affected eye (OS). The most notable reductions were in the rod response and 30-Hz flicker b-waves OD which were approximately 50% of the corresponding amplitudes OS. Implicit times, particularly the a-wave implicit times, were noticeably longer OD compared with OS. Lesions remained unchanged over 4 months at which time the dog was humanely euthanized for reasons unrelated to the ocular disease. Significant light microscopic ocular findings were bilateral superior temporal ...
Herein, we report a case of nontraumatic bilateral rhegmatogenous retinal detachment (RRD) during... more Herein, we report a case of nontraumatic bilateral rhegmatogenous retinal detachment (RRD) during external beam radiotherapy for nonocular tumor, presented as an observational case study in conjunction with a review of the relevant literature. A 65-year-old male was referred to our hospital due to bilateral RRD. He underwent a biopsy for a tumor of the left frontal lobe 4 months prior to presentation, and the tumor had been diagnosed as primary central nerve system B-cell type lymphoma. He received chemotherapy and external beam radiotherapy for 1 month. There were no traumatic episodes. Bilateral retinal detachment occurred during a series of radiotherapies. Simultaneous nontraumatic bilateral retinal detachment is rare. The effects of radiotherapy on ocular functionality, particularly in cases involving retinal adhesion and vitreous contraction, may include RRD. Thus, it is necessary to closely monitor the eyes of patients undergoing radiotherapy, particularly those undergoing surgery for retinal detachment and those with a history of photocoagulation for retinal tears, a relevant family history, or risk factors known to be associated with RRD.
This study reviewed clinical data from dogs diagnosed with sudden acquired retinal degeneration s... more This study reviewed clinical data from dogs diagnosed with sudden acquired retinal degeneration syndrome (SARDS) in western Canada. Medical records from the Western College of Veterinary Medicine from 2002 to 2016 showed that 93 cases of SARDS were diagnosed based on presentation for sudden blindness and a bilaterally extinguished electroretinogram. The most common pure breeds were the miniature schnauzer, dachshund, and pug. The mean age at diagnosis was 8.1 years and males and females were equally affected. Most of the dogs were presented with normal non-chromatic, but abnormal chromatic pupillary light reflexes. The incidence of retinal degeneration as detected via ophthalmoscopy increased over time after SARDS diagnosis. Polyuria, polydipsia, polyphagia, weight gain, elevated liver enzyme values, isosthenuria, and proteinuria were common clinical and laboratory findings. Chromatic pupillary light reflex testing may be more valuable than non-chromatic pupillary light testing in detecting pupil response abnormalities in dogs with SARDS, although electroretinography remains the definitive diagnostic test.
Pectinate ligament dysplasia (PLD) is a common cause of canine glaucoma and the definitive clinic... more Pectinate ligament dysplasia (PLD) is a common cause of canine glaucoma and the definitive clinical diagnosis is based on gonioscopy. Although the histologic lesions of PLD have been described, it has not been determined whether these changes are specific for PLD or if similar histologic changes can develop as a consequence of secondary glaucoma. The filtration angles of 61 enucleated canine globes with chronic glaucoma were evaluated with light microscopy by 3 examiners who were masked to the clinical history, signalment, and gonioscopic results. A histologic diagnosis of PLD versus non-PLD was determined by each examiner based on previously reported morphologic criteria and compared with the clinical gonioscopic diagnosis. Of the 61 enucleated glaucomatous eyes, 40 were clinically diagnosed with PLD. For all 3 examiners, a histologic diagnosis of PLD corresponded poorly with the clinical diagnosis of PLD (range of kappa score: 0.149-0.269; range of AUC: 0.592-0.621). There was no difference between examiners in their ability to correctly diagnose PLD histologically (P ¼ .978). A fair degree of agreement was noted among examiners in obtaining their suspected histologic diagnosis of PLD (kappa score 0.256). No individual or sets of histologic ICA features were consistent with clinical PLD. The results indicate the histologic ICA changes proposed to be characteristic of PLD are also noted in canine globes affected with chronic secondary glaucoma. Therefore, using routine histologic evaluation, a histologic diagnosis of PLD is not possible in the face of chronic canine glaucoma.
Mitochondrial transcription factor A (Tfam) has been implicated in the pathogenesis of retinal dy... more Mitochondrial transcription factor A (Tfam) has been implicated in the pathogenesis of retinal dysplasia in miniature schnauzer dogs and it has been proposed that affected dogs have altered mitochondrial numbers, size, and morphology. To test these hypotheses the Tfam gene of affected and normal miniature schnauzer dogs with retinal dysplasia was sequenced and lymphocyte mitochondria were quantified, measured, and the morphology was compared in normal and affected dogs using transmission electron microscopy. For Tfam sequencing, retina, retinal pigment epithelium (RPE), and whole blood samples were collected. Total RNA was isolated from the retina and RPE and reverse transcribed to make cDNA. Genomic DNA was extracted from white blood cell pellets obtained from the whole blood samples. The Tfam coding sequence, 5' promoter region, intron1 and the 3' non-coding sequence of normal and affected dogs were amplified using polymerase chain reaction (PCR), cloned and sequenced. For electron microscopy, lymphocytes from affected and normal dogs were photographed and the mitochondria within each cross-section were identified, quantified, and the mitochondrial area (μm²) per lymphocyte cross-section was calculated. Lastly, using a masked technique, mitochondrial morphology was compared between the 2 groups. Sequencing of the miniature schnauzer Tfam gene revealed no functional sequence variation between affected and normal dogs. Lymphocyte and mitochondrial area, mitochondrial quantification, and morphology assessment also revealed no significant difference between the 2 groups. Further investigation into other candidate genes or factors causing retinal dysplasia in the miniature schnauzer is warranted.
To compare the scanning laser ophthalmoscopy (SLO), optical coherence tomography (OCT), and fluor... more To compare the scanning laser ophthalmoscopy (SLO), optical coherence tomography (OCT), and fluorescein angiography (FA) findings in retrievers with a single unilateral circular retinal plaque to those of an English springer spaniel with bilateral retinal dysplasia. Procedures: A retrospective record review identified three dogs with circular retinal plaques that underwent SLO and OCT; in two of the three dogs, FA was also completed. Morphologic changes, lesion measurements, and angiogram characteristics were documented. An English springer spaniel with bilateral retinal dysplasia that had undergone SLO, OCT, and FA was used for comparison. Results: Scanning laser ophthalmoscopy of the retriever dogs revealed circular retinal plaques with a dark periphery located in the tapetal retina. OCT revealed a thickening of the nerve fiber layer corresponding to the circular pattern observed on SLO. Within the circular plaque, the retina was predominantly of normal architecture. FA revealed variable hypofluorescence of both the rim and the center of the circular lesion throughout the early angiogram phases. In the late recirculation phase, small multifocal areas of hyperfluorescence were observed. OCT of geographic retinal dysplasia in the English springer spaniel revealed disorganization of both inner and outer retinal layers, and retinal detachment. Conclusions: Circular plaques observed in the tapetal retina are predominantly formed by a thickening of inner retina, while retinal dysplasia has disorganization of both inner and outer retinal layers. Further etiologic research is needed, including pedigree mapping to determine whether retinal plaques are an acquired or inherited condition.
Cavernous sinus syndrome is a unique constellation of cranial nerve deficits occurring typically ... more Cavernous sinus syndrome is a unique constellation of cranial nerve deficits occurring typically as a result of pathologic infiltration of the cavernous sinus, which is located in the lateral sellar compartment of the calvarium. This case report describes a polyneuropathy consistent with cavernous sinus syndrome as a result of a lesion outside of the cavernous sinus. The cat was presented with right internal and external ophthalmoplegia, loss of right corneal sensation, inspiratory stridor, dysphagia, dysphonia, tongue weakness, and weight loss. Magnetic resonance imaging identified a large nasopharyngeal mass along the base of, but without extension into, the calvarium. The histologic diagnosis was nasopharyngeal lymphoma. Focal extracranial masses should be considered as differential diagnoses for multiple cranial nerve deficits, including the constellation of clinical signs recognized as cavernous sinus syndrome.
Horner's syndrome arises from dysfunction of the oculosympathetic pathway and is characterized by... more Horner's syndrome arises from dysfunction of the oculosympathetic pathway and is characterized by miosis, enophthalmos, protrusion of the third eyelid, and ptosis. It has been recognized in a wide variety of breeds and ages in small animal patients. The oculosympathetic pathway is a 3-neuron pathway. The central/first order neuron arises from the hypothalamus and extends down the spinal cord. The preganglionic/second order neuron arises from the first 3 thoracic spinal cord segments and travels through the thorax and cervical region until it synapses at the cranial cervical ganglion. The postganglionic/third order neuron travels from this ganglion to the orbit. Topical application of cocaine is the gold standard for differentiating Horner's syndrome from other causes of miosis. Topical 1% phenylephrine allows for identification of a post-ganglion Horner's syndrome. Numerous etiologies have been reported for Horner's syndrome, but idiopathic disease is most common. Ancillary diagnostics include otoscopic examination, thoracic radiographs, or advanced imaging. Treatment and prognosis are determined by the etiology.
To describe the optical coherence tomography (OCT) and fluorescein angiography changes in dogs wi... more To describe the optical coherence tomography (OCT) and fluorescein angiography changes in dogs with sudden acquired retinal degeneration syndrome (SARDS). Methods: Retinal OCT was performed on 10 SARDS dogs and eight control dogs. Tomograms were collected in four quadrants around the optic nerve. Measurements were collected from the photoreceptor layer, the outer nuclear layer, the outer retina, the inner retina and the whole retina thickness in all quadrants. Sodium fluorescein was injected intravenously and serial fundic photographs were collected for a 5 minute period post-injection. Results: In all quadrants, the outer nuclear layer (dorsal temporal P = 0.0000, dorsal nasal P = 0.0001, ventral temporal P = 0.0002, ventral nasal P = 0.000) and outer retina (dorsal temporal P = 0.0001, dorsal nasal P = 0.0002, ventral temporal P = 0.0054, ventral nasal P = 0.0084) measurements were significantly decreased in SARDS dogs. The whole retina thickness was significantly decreased in the dorsal temporal (P = 0.0082) and ventral temporal (P = 0.0428) retina. There were no significant differences in the photoreceptor layer thickness or inner retinal thickness between SARDS and control dogs. All SARDS dogs had a loss of definition of all of the photoreceptor bands on OCT. Two SARDS dogs had multifocal small retinal detachments and one of these dogs exhibited fluorescein leaking at the detachment sites. Conclusions: The significant reduction in the outer nuclear layer and the loss of band signals in the photoreceptor layers in dogs with SARDS identified on OCT support the previous histopathology findings. Small detachments may occasionally be detected on OCT and they may leak fluorescein.
A 11-year-old neutered male Labrador retriever-cross dog was presented to the University of Misso... more A 11-year-old neutered male Labrador retriever-cross dog was presented to the University of Missouri-Columbia Veterinary Ophthalmology Service for subtle visual deficits. Indirect ophthalmoscopy revealed a smooth, bullous elevation in the superior-temporal retina OU. Optical coherence tomography (OCT) performed OU showed inner retinal separation consistent with retinoschisis. Electroretinography (ERG) revealed markedly reduced b-wave amplitudes in the more severely affected eye (OD) compared with the less severely affected eye (OS). The most notable reductions were in the rod response and 30-Hz flicker b-waves OD which were approximately 50% of the corresponding amplitudes OS. Implicit times, particularly the a-wave implicit times, were noticeably longer OD compared with OS. Lesions remained unchanged over 4 months at which time the dog was humanely euthanized for reasons unrelated to the ocular disease. Significant light microscopic ocular findings were bilateral superior temporal ...
Uploads
Papers by Bruce Grahn