FUNCTIONAL ASSESSMENT OF MACULAR DEGENERATIONS
Michael A Sandberg
Harvard University (medical School)
medical School Campus
boston, Ma 02115
Grant 5R01EY008398-04 from National Eye Institute IRG: VISB
Abstract: Patients with advanced age-related macular degeneration in one eye and early age-related macular degeneration in their fellow eye will have their fellow eye evaluated over a three year interval with computer-assisted maps of macular malfunction, Amsler grid testing, blue-cone thresholds in the fovea, and foveal cone electroretinograms. Results will be compared with the appearance of the macula in the fellow eye quantified from optically- scanned fundus photographs and fluorescein angiograms to determine to what extent changes in these macular function tests correspond with changes seen in the fundus on the same or subsequent visits and precede the development of exudative maculopathy and/or loss of visual acuity. In separate sets of patients with early stages of either age-related or juvenile macular degeneration, cone and rod dark adaptation kinetics will be assessed with long and short duration bleaches in regions of the macula outside the foveola to help determine if the retinal pigment epithelium or the photoreceptors, or both, are primarily involved, and to evaluate whether rod malfunction precedes cone malfunction in these regions. This research should provide a better understanding of pathophysiological mechanisms that may be involved in these conditions. In the case of age-related macular degeneration, macular degeneration, demonstration of the usefulness of one or more of the functional tests under study in detecting more patients with impending exudative maculopathy and loss of visual acuity may increase the number of patients who would subsequently benefit from laser therapy
Keywords: diagnosis quality /standard, eye disorder diagnosis, longitudinal human study, macular degeneration, pathologic process, vision disorder, vision test computer assisted diagnosis, cone cell, dark adaptation, electroretinography, eye fundus photography, eye laser therapy, fluorescein angiography, human age group, retinal pigment epithelium, rod cell, visual perception, visual photoreceptor human subject, image processing, mathematical model, statistics /biometry
Project start date: 1990-05-01
Project end date: 1995-04-30
5R01EY008398-04 (1993): $178041
Sponsored Links Excellgen http://Excellgen.com
FUNCTIONAL ASSESSMENT OF MACULAR DEGENERATION
Michael A Sandberg
Ophthalmologyharvard University (medical School)
medical School Campus
boston, Ma 02115
Grant 5R01EY008398-05 from National Eye Institute IRG: VISB
Abstract: Patients with advanced age-related macular degeneration in one eye and early age-related macular degeneration in their fellow eye will have their fellow eye evaluated over a three year interval with computer-assisted maps of macular malfunction, Amsler grid testing, blue-cone thresholds in the fovea, and foveal cone electroretinograms. Results will be compared with the appearance of the macula in the fellow eye quantified from optically- scanned fundus photographs and fluorescein angiograms to determine to what extent changes in these macular function tests correspond with changes seen in the fundus on the same or subsequent visits and precede the development of exudative maculopathy and/or loss of visual acuity. In separate sets of patients with early stages of either age-related or juvenile macular degeneration, cone and rod dark adaptation kinetics will be assessed with long and short duration bleaches in regions of the macula outside the foveola to help determine if the retinal pigment epithelium or the photoreceptors, or both, are primarily involved, and to evaluate whether rod malfunction precedes cone malfunction in these regions. This research should provide a better understanding of pathophysiological mechanisms that may be involved in these conditions. In the case of age-related macular degeneration, macular degeneration, demonstration of the usefulness of one or more of the functional tests under study in detecting more patients with impending exudative maculopathy and loss of visual acuity may increase the number of patients who would subsequently benefit from laser therapy
Project start date: 1990-05-01
Project end date: 1996-04-30
5R01EY008398-05 (1994): $185228
Grants awarded to Michael A Sandberg
Melanopsin-based Form Vision In Photoreceptor Disease
Michael A Sandberg
Harvard University (medical School) Medical School Campus Boston, Ma 02115
Grant 5R03EY016350-03 from National Eye Institute IRG: ZEY1
Abstract: The long-term objective of this program is to use melanopsin gene therapy to restore useful form vision and visual field to patients blind due to photoreceptor degeneration. Melanopsin is an invertebrate-like opsin present in rare, intrinsically-photosensitive, large-field ganglion cells of the mammalian retina not involved in the processing of spatial information. This pilot study is intended to demonstrate proof of principle with the following sequence of specific aims (1) to express melanopsin in typical, small-field ganglion cells of mice with advanced photoreceptor degeneration, (2) to show that these modified ganglion cells have become intrinsically light-sensitive and to describe their stimulus-response characteristics, and (3) to show that melanopsin treatment improves the pattern discrimination of these mice. We will inject a recombinant adeno-associated virus (AAV) carrying the melanopsin gene and the GFP reporter gene (as a marker) into the vitreous of one eye of 1-month-old retinal degeneration (rd/rd) mice and use light microscopy to assess the level, extent, and persistence of transgene expression in ganglion cells. We will then use a microelectrode array on the retinal surface to record extracellular action potentials from ganglion cells of melanopsin-treated versus untreated eyes to demonstrate the photosensitivity and response characteristics of the transduced cells. We will then infer the visual acuity for melanopsin-treated versus untreated eyes by recording monocular pattern visually evoked potentials in response to an alternating stripe pattern of varying spatial frequency. If this pilot program is successful, then transfection of the melanopsin gene into typical, small-field ganglion cells of patients with hand-motions or worse vision and markedly constricted fields due to photoreceptor degeneration could be a future consideration to improve their visual acuity to ~20/100 and widen their visual field to enhance mobility. Restoration of useful form vision to some 4,000 such patients in the United States would facilitate their functioning independently in society and improve the long-term outlook of approximately 100,000 patients with generalized photoreceptor degeneration in this country who have not yet become blind.
Keywords: gene therapy, nonhuman therapy evaluation, retina degeneration, rhodopsin, visual perception, visual photoreceptor, action potential, calcium channel blocker, evoked potential, form /pattern perception, ganglion cell, gene expression, glutamate, visual field, visual photosensitivity, green fluorescent protein, histochemistry /cytochemistry, laboratory mouse, light microscopy, microelectrode, transfection
Project start date: 2005-04-01
Project end date: 2009-02-28
5R03EY016350-03 (2007): $164590
5R03EY016350-02 (2006): $165517
1R03EY016350-01 (2005): $169500
MODIFIABLE RISK FACTORS FOR CME IN RETINITIS PIGMENTOSA
Michael A Sandberg
Massachusetts Eye And Ear Infirmary, 243 Charles St, Boston, Ma 02114-3096
Grant 5R21EY019767-02 from National Eye Institute
Abstract: Retinitis pigmentosa is a hereditary retinal degeneration that leads to loss of night vision, side vision, and eventually most of central vision. Cystoid macular edema (CME), a complication involving swelling of the central retina and reduction in visual acuity, occurs in at least 25% of patients with retinitis pigmentosa, often before their central vision has become impaired due to the primary disease process. Some patients with retinitis pigmentosa have CME that is poorly responsive to treatment with eye drops or injections into the eye, while other patients may show a reduction in swelling with only an incomplete recovery of visual acuity following treatment. Iodine supplementation has been suggested as a way to reduce edema in different tissues. We have evidence that taking an iodine supplement reduces the risk for CME in patients with retinitis pigmentosa. Since an iodine supplement may constitute only a small fraction of total dietary intake of iodine, the main purpose of the present study is to determine whether the likelihood of having CME in retinitis pigmentosa is related to iodine concentration in the urine, as a measure of the total dietary iodine intake. Since gamma linolenic acid (GLA) has also been suggested as a way to reduce edema, we will determine whether the risk of CME is inversely related to dietary GLA as a secondary goal. To address these issues, we will use optical coherence tomography to detect CME, quantify urinary iodine concentration as a measure of total dietary iodine intake, and measure GLA intake based on food frequency questionnaires in 200 patients with retinitis pigmentosa. If the risk of CME is found to be inversely related to urinary iodine concentration and/or GLA intake in this population, then a clinical trial could be considered to determine whether higher dietary iodine and/or GLA intake will help protect patients with retinitis pigmentosa from developing CME or, possibly, reduce CME in those who already have it
Keywords: 6, 9, 12-Octadecatrienoic acid, (Z, Z, Z)-; Address; Adhesions; Body Tissues; Capillary Endothelial Cell; Central Retinal Edema, Cystoid; Clinical Trials; Clinical Trials, Unspecified; Complication; Cystoid Macular Edema; Diet Supplement; Dietary Iodine; Dietary Supplements; Dietary intake; Disease; Disorder; Doppler OCT; Dropsy; Edema; Endothelial Cells; Epithelial; Eye; Eye Drops; Eyeball; Eyedrops; Food; Frequencies (time pattern); Frequency; Goals; Hereditary; Hydrops; I- element; Inherited; Injection of therapeutic agent; Injections; Intake; Iodine; Logistic Regressions; Macular Edema, Cystoid; Measures; Modeling; Nutrient; Nutritional Supplement; OCT Tomography; Occluding Junctions; Optical Coherence Tomography; Outer pigmented layer of retina; Patients; Permeability; Pigment cell layer of retina; Pigmentary Retinopathy; Pigmented layer of retina; Population; Process; Questionnaires; Recovery; Reporting; Research; Retina; Retinal; Retinal Degeneration; Retinal Pigment Epithelium; Retinal pigment epithelial cells; Retinitis Pigmentosa; Risk; Risk Factors; Rod-Cone Dystrophy; Sampling; Side; Sight; Structure of retinal pigment epithelium; Supplementation; Swelling; Tapetoretinal Degeneration; Testing; Tight Junctions; Tissues; Tomography, Optical Coherence; Urinary System, Urine; Urine; Vision; Visual Acuity; Zonula Occludens; base; clinical investigation; disease/disorder; gamma-Linolenic Acid; modifiable risk; retina degeneration; retinal degenerative; urinary
Relevance: At least 25% of patients with retinitis pigmentosa have cystoid macular edema (CME), a complication involving swelling of the central retina and reduction in visual acuity. We have evidence that the likelihood of having CME in this disease is reduced in patients taking iodine supplements. The main purpose of the present study is to determine whether higher iodine in the urine, as a measure of total dietary iodine intake, is associated with a reduced risk of CME in retinitis pigmentosa
Project start date: 2009-09-01
Project end date: 2011-08-31
Budget start date: 1-SEP-2010
Budget end date: 31-AUG-2011
PFA/PA: PA-06-181
5R21EY019767-02 (2010): $194046
1R21EY019767-01 (2009): $228293
MODELS OF PHOTORECEPTOR DISEASE
Michael A Sandberg
Harvard University (medical School), Medical School Campus, Boston, Ma 02115
Grant 5R01EY010309-14 from National Eye Institute
Abstract: Hereditary photoreceptor degeneration is a group of blinding retinal diseases with diverse genetic origins. We propose to perform functional studies of several proteins known or postulated to have essential roles in photoreceptors. Emphasis is placed on the connecting cilium and the mammalian equivalent of a periciliary ridge complex, and their roles in membrane protein transport to the outer segment and disc morphogenesis. The proposed research will study RPGR, RPGRIP and Tubby-like proteins, hypothesized to function in the above processes. Our approaches are based on analyses of in vivo genetic models complemented by in vitro cell biological studies. The proposed efforts should contribute to our understanding of disease mechanisms underlying photoreceptor degeneration, and advance our knowledge concerning important and lesser understood aspects of photoreceptor cell biology
Keywords: Actins; Binding; Binding (Molecular Function); Biological; Cell membrane; Cells; Cellular Matrix; Cellular biology; Chromosome Pairing; Cilia; Complement; Complement Proteins; Complex; Cytoplasmic Membrane; Cytoskeletal System; Cytoskeleton; Data; Defect; Diffusion; Disease; Disorder; Docking; Frog; GDP Dissociation Factor; GDP Dissociation Stimulators; GDP Exchange Factors; GDP-GTP Exchange Protein; GDP-GTP Reversing Factors; GEF; GTP GDP exchange factor; Genetic; Genetic Models; Guanine Nucleotide Exchange Factors; Guanine Nucleotide Exchange Protein; Guanine Nucleotide Releasing Factors; Guanyl-Nucleotide Exchange Factor; Guanyl-Nucleotide Releasing Factor; Hereditary; In Vitro; Inherited; Investigators; Knowledge; Lateral; Membrane; Membrane Proteins; Membrane Transport Proteins; Membrane Transporters; Membrane-Associated Proteins; Modeling; Models, Genetic; Molecular Interaction; Morphogenesis; N-terminal; NH2-terminal; Nuclear Pore; Occluding Junctions; Opsin; Pathway interactions; Phenotype; Photoreceptor Cell; Photoreceptors; Photosensitive Cell; Physiologic; Physiological; Plasma Membrane; Process; Programs (PT); Programs [Publication Type]; Proteins; RP3 protein; RP3 protein, human; RPGR protein; RPGR protein, human; Rana; Rana (genus); Recruitment Activity; Research; Research Personnel; Researchers; Retinal Diseases; Retinal Disorder; Rod-Opsin; Role; Role Playing; Role Playings; Role playing therapy; Running; Site; Structure; Surface Proteins; Synapses; Synapsis; Synapsis, Chromosomal; Synaptic; Tight Junctions; VESCL; Vesicle; Visual Receptor; Zonula Occludens; base; cell biology; disease/disorder; exchange factor; experiment; experimental research; experimental study; gene product; human RPGR protein; in vivo; intracellular skeleton; membrane structure; pathway; photoreceptor degeneration; plasmalemma; programs; protein function; recruit; research study; retina disease; retina disorder; retinitis pigmentosa 15, cone dystrophy 1 (X-linked); retinitis pigmentosa GTPase regulator, human; retinopathy; role playing (psychodrama); social role; transcription factor
Project start date: 1994-02-01
Project end date: 2010-03-31
Budget start date: 1-APR-2008
Budget end date: 31-MAR-2010
5R01EY010309-14 (2008): $0
Reading Enhancement For Patients With Visual Field Loss
Michael A Sandberg
Harvard University (medical School) Medical School Campus Boston, Ma 02115
Grant 5R03EY013769-03 from National Eye Institute IRG: ZEY1
Abstract: Applicant s ) According to The National Advisory Eye Council, a program goal is to "Develop assistive devices ... and rehabilitation strategies to minimize the impact of visual impairment in everyday life, and reduce disability and societal limitations among visually impaired persons" (Vision Research-A National Plan 1999-2003, National Eye Institute). In accordance with this guideline, the proposed pilot study will measure and attempt to correct the reading disability of patients who retain only a small central island of vision due to advanced retinal degeneration or glaucoma, or only the left or right visual field due to stroke. These patients, who number in the thousands in the United States, are handicapped for reading standard, stationary text because they lack adequate parafoveal visual cues for smoothly shifting fixation from word to word and from line to line, and because some have reduced visual acuity as well. We plan to evaluate 150 patients with different forms of retinal degeneration or glaucoma and 30 patients with stroke. This program will quantify their reading speeds to standard, stationary text and relate reading speed to conventional measures of vision to develop a quantitative clinical frame of reference for their reading disability. We will explore whether their reading speeds to stationary text can be improved by tailoring the letter spacing, letter size, page width, and contrast polarity to their disease type and stage. Testing will also involve measuring their reading speed to text presented serially to the same location of the visual field, a format that minimizes the need for eye movements, and that should, therefore, little depend upon the absence of parafoveal cues; this format has been reported to result in up to four-fold faster reading by normal subjects. Since software is available for presenting text serially to the same location, either on-line or off-line, and since palmheld wireless devices are commercially available, a serial mode of presentation could be a practical, mobile solution for patients with these types of visual field loss.
Keywords: assistive device /technology, glaucoma, reading, retina degeneration, stroke, vision aid, visual field, computer program /software, longitudinal human study, rehabilitation, scotoma, vision disorder, visual perception, behavioral /social science research tag, human subject, ophthalmoscopy, patient oriented research, perimetry, questionnaire, vision test
Project start date: 2001-08-01
Project end date: 2004-12-31
5R03EY013769-03 (2004): $129000
5R03EY013769-02 (2003): $129000
1R03EY013769-01 (2001): $128869