Operating in the Dark: A Night-Vision System for Surgery in Retinas Susceptible to Light Damage

A standard operating microscope was modified with a bandpass infrared filter in the light path and infrared image intensifiers for each of the 2 eyepieces. We evaluated this system for subretinal injections in normal control dogs and those with a mutation in the rhodopsin gene. Rhodopsin-mutant dogs are a model for human autosomal dominant retinitis pigmentosa, and their retinas degenerate faster when exposed to modest light levels as used in routine clinical examinations. We showed that the mutant retinas developed severe generalized degeneration when exposed to the standard operating microscope light but not the infrared light. The modified operating microscope provided an excellent view of the ocular fundus under infrared illumination and allowed us to perform subretinal injections in the retinas of the rhodopsin-mutant dogs without any subsequent light-induced retinal degeneration. The first description of light-induced retinal damage showed that exposure of albino rats to visible light intensities ordinarily encountered in the laboratory led to irreversible retinal damage.1 This finding soon was extended to other species, including rabbits2 and monkeys.3 Studies in animal models of retinal degeneration (eg, Royal College of Surgeons rats, ABCA4-mutant mice, or rhodopsin-mutant mice and dogs) have emphasized the interplay between the gene mutation and environmental light and demonstrated acceleration of the disease process by light.4- 10 The effect of environmental light on disease severity in humans with retinitis pigmentosa has been suggested by case reports,11 although definitive proof is lacking. However, patients with class B1 rhodopsin mutations may be at risk of accelerated vision loss with increased light exposures because they have defects in dark (bleaching) adaptation similar to those found in rhodopsin-mutant dogs that demonstrate a high susceptibility to retinal light damage.8,12,13 Many of the emerging therapies for retinal degeneration require the intraocular placement of a reagent or device with the use of an operating microscope.14,15 The damaging effect of the microscope light on the normal retina, even with the appropriate filtering of UV light, has been described previously,16,17 and there is increased emphasis on reducing the intensity and duration of the exposures. Herein, we describe a modification of an operating microscope with an infrared bandpass filter and a night-vision system to perform surgical interventions in the posterior segment of the eyes of rhodopsin-mutant dogs without the risk of photochemical retinal damage. This modification prevents acceleration of the photoreceptor degeneration that occurs with exposure to modest light levels as used in routine clinical practice.8 If humans with retinitis pigmentosa are shown to have similar light damage susceptibility, this microscope modification could be considered for surgical procedures such as the subretinal application of gene therapy vectors

Electroretinography in Dogs and Cats. Part I. Retinal Morphology and Physiology

Electroretinography is an important objective procedure that is used to assess the outer retina and follow the progression of and recovery from retinal disorders. This procedure is more sensitive than other diagnostic techniques, such as ophthalmoscopy, for determining subtle or early alterations in the outer retina. Electroretinography cannot, however, assess vision because an electroretinograpn (ERG) may be normal in dogs and cats with cortical blindness or early stages of glaucoma. If retinal dysfunction is known or suspected, an ERG may be necessary. This two-part presentation provides general practitioners with information about this relatively noninvasive electrodiagnostic procedure in order to assist them in assessing the need for referral to a veterinary ophthalmologist or neurologist. Part I reviews the morphologic and physiologic characteristics of the retina; Part II will examine electroretinographic technique, interpretations, and indications

Electroretinography in Dogs and Cats. Part II. Technique, Interpretation, and Indications

Electroretinography, a technique that objectively assesses the function of the retina, is used to evaluate the progression of retinal disorders. Part I of this two-part presentation discussed the morphologic and physiologic characteristics of the retina. The information presented in Part II can help practitioners determine when an electroretinogram (ERG) is recommended. In addition to the standard flash ERG, visual evoked potentials (VEPs) are useful for evaluating disorders that lead to blindness. The most common indications for electroretinography are presurgical evaluation of patients with cataracts, characterization of disorders that cause blindness, and identification of the extent of retinal damage caused by glaucoma. A flash ERG can only show changes that occur to the retina in advanced stages of glaucoma; whereas a pattern ERG (PERG) can record early, selective damage to ganglion cells in the retina

Primary Adenocarcinoma of the Gland of the Nictitating Membrane in a Cat

An 11-year-old, neutered, male domestic shorthair was presented with a five-month history of recurrent, unilateral, seromucoid discharge from the right eye. A verrucous mass extended from the posterior aspect of the nictitating membrane. Adenocarcinoma of the gland of the nictitating membrand (GNM) was diagnosed upon biopsy. The cat subsequently developed metastases to the lungs, pleura, mediastinum, liver, and kidneys and died six months after clinical signs first were observed. Little is known about the biological behavior of adenocarcinoma of the GNM in cats. This is the first report that describes the natural progression of this disease

Intraocular Nematodiasis in a Llama (\u3cem\u3eLama glama\u3c/em\u3e)

This report describes a unique case of presumed migration of Parelaphastrongylus tenuis through the spinal cord into the eye of a llama where it survived and matured within the ocular environment. Blindness of the eye was most likely attributable to migration of the parasite through the central nervous tissue. Résumé Infestation par les nématodes intraoculaire chez un lama (Lama glama). Ce rapport décrit un cas unique de migration présumée de Parelaphastrongylus tenuis dans la colonne vertébrale jusque dans l’œil d’un lama où il a survécu et est parvenu à maturité dans l’environnement oculaire. La cécité de l’œil a été le plus probablement attribuable à la migration du parasite dans les tissus du système nerveux central. (Traduit par Isabelle Vallières

Application of a New Subretinal Injection Device in the Dog

The use of a new subretinal injection device (RetinaJect™ Subretinal Cannula, SurModics, Inc., Eden Prairie, MN) to access the subretinal space in the canine model was evaluated. Subretinal injections were performed in 33 mongrel dogs between 2 and 52 months of age (median = 9 months). In 5 normal dogs the injection of 150 μl saline or India ink occurred by using a conventional subretinal injection device (CSID) with a 30-gauge anterior chamber irrigating cannula. The sclera had to be surgically exposed and penetrated before the subretinal injection with the CSID could occur. After removing the CSID, the conjunctiva over the sclerotomy site had to be closed. In a second group of 28 dogs [16 normals, 10 RPE65 mutants, and 2 with progressive rod cone degeneration (prcd)], the 25-gauge needle of the RetinaJect™ was used to penetrate the conjunctiva and the sclera. Once the tip of the needle was close to the retinal surface, a 39-gauge polyimide cannula was extended and brought into apposition with the retina for the subsequent subretinal injection of 150 μl saline, India ink, or adeno-associated virus (AAV). No closure of the conjunctiva was required. The animals were clinically monitored between 1 and 59 weeks after surgery. From this second group 25 eyes were harvested for routine histological analysis either immediately after surgery or after a clinical observation time of between 1 and 40 weeks. Both devices provided equally successful access to the subretinal space. The main advantage of the RetinaJect™ was that no surgical dissection was required; this led to a shorter procedure time and milder postoperative conjunctival swelling. In summary, the use of the RetinaJect™ can be recommended as an alternative to the CSID for subretinal injections in dogs

Hyphema. Part II. Diagnosis and Treatment

The clinical appearance of hyphema is variable and is influenced by the volume of blood and the amount of time erythrocytes are present in the anterior chamber. When hyphema is evident, a complete history should be obtained and a thorough physical examination performed to direct the initial selection of diagnostic tests. Secondary complications of hyphema include glaucoma, synechiae, cataract formation, blood-staining of the cornea, and blindness. Frequent measurement of intraocular pressure is recommended. The two primary management issues in animals with hyphema are prevention of secondary hemorrhage (by treating the underlying disease) and control of secondary glaucoma

Hyphema. Part I. Pathophysiologic Considerations

Hemorrhage in the anterior chamber of the eye, or hyphema, results from a breakdown of the blood-ocular barrier (BOB) and is frequently associated with inflammation of the iris, ciliary body, or retina. Hyphema can also occur by retrograde blood flow into the anterior chamber via the aqueous humor drainage pathways without BOB breakdown. Hyphema attributable to blunt or perforating ocular trauma is more common than that resulting from endogenous causes. When trauma has been eliminated as a possible cause, it is prudent to assume that every animal with hyphema has a serious systemic disease until proven otherwise

Hyphema. Part II. Diagnosis and Treatment

The clinical appearance of hyphema is variable and is influenced by the volume of blood and the amount of time erythrocytes are present in the anterior chamber. When hyphema is evident, a complete history should be obtained and a thorough physical examination performed to direct the initial selection of diagnostic tests. Secondary complications of hyphema include glaucoma, synechiae, cataract formation, blood-staining of the cornea, and blindness. Frequent measurement of intraocular pressure is recommended. The two primary management issues in animals with hyphema are prevention of secondary hemorrhage (by treating the underlying disease) and control of secondary glaucoma

Targeting Gene Expression to Cones With Human Cone Opsin Promoters in Recombinant AAV

Specific cone-directed therapy is of high priority in the treatment of human hereditary retinal diseases. However, not much information exists about the specific targeting of photoreceptor subclasses. Three versions of the human red cone opsin promoter (PR0.5, 3LCR-PR0.5 and PR2.1), and the human blue cone opsin promoter HB569, were evaluated for their specificity and robustness in targeting green fluorescent protein (GFP) gene expression to subclasses of cones in the canine retina when used in recombinant adeno-associated viral vectors of serotype 5. The vectors were administered by subretinal injection. The promoter PR2.1 led to most effective and specific expression of GFP in the long- and medium-wavelength-absorbing cones (L/M cones) of normal and diseased retinas. The PR0.5 promoter was not effective. Adding three copies of the 35-bp LCR in front of PR0.5 lead to weak GFP expression in L/M cones. The HB569 promoter was not specific, and GFP was expressed in a few L/M cones, some rods and the retinal pigment epithelium. These results suggest that L/M cones, the predominant class of cone photoreceptors in the retinas of dogs and most mammalian species can be successfully targeted using the human red cone opsin promoter