Drusen-Associated Degeneration in the Retina

Johnson, P.T.; Lewis, Geoffrey P.; Talaga, K.C.; Brown, Meghan N; Kappel, Peter J.; Fisher, Steven K.; Anderson, Don H.; Johnson, Lincoln V.

doi:10.1167/iovs.03-0436

Cited by 181 publications

(142 citation statements)

References 35 publications

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“…It has been shown that photoreceptor cells in areas impacted by drusen exhibit morphologic and biochemical signs of degeneration, including decreased expression of synapse-associated proteins and increased expression of stress-response molecules. There are also drusen-associated reductions in photoreceptor cell densities, thus suggesting that degenerative changes in photoreceptors ultimately lead to cell death (151,152).…”

Section: Physiological Correlates Of Early Amdmentioning

confidence: 99%

“…Other drusen components including vitronectin (160), clusterin, complement receptor 1 (CR1), and membrane cofactor protein (MCP-1) (163) are known complement regulatory proteins. Still others include known activators of the complement cascade including cholesterol (168), C-reactive protein (154), and the amyloidogenic peptide amyloid β (152,169). Metallic zinc, an amyloid β binding molecule, is also a drusen constituent (170).…”

Section: Inflammation and Amdmentioning

confidence: 99%

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Age‐related macular degeneration—emerging pathogenetic and therapeutic concepts

et al. 2006

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Today, the average life expectancy in developed nations is over 80 years and climbing. And yet, the quality of life during those additional years is often significantly diminished by the effects of age-related, degenerative diseases, including age-related macular degeneration (AMD), the leading cause of blindness in the elderly worldwide. AMD is characterized by a progressive loss of central vision attributable to degenerative and neovascular changes in the macula, a highly specialized region of the ocular retina responsible for fine visual acuity. Estimates gathered from the most recent World Health Organization (WHO) global eye disease survey conservatively indicate that 14 million persons are blind or severely visually impaired because of AMD. The disease has a tremendous impact on the physical and mental health of the geriatric population and their families and is becoming a major public health burden.Currently, there is neither a cure nor a means to prevent AMD. Palliative treatment options for the less prevalent, late-stage 'wet' form of the disease include anti-neovascular agents, photodynamic therapy and thermal laser. There are no current therapies for the more common 'dry' AMD, except for the use of antioxidants that delay progression in 20%-25% of eyes. New discoveries, however, are beginning to provide a much clearer picture of the relevant cellular events, genetic factors, and biochemical processes associated with early AMD. Recently, compelling evidence has emerged that the innate immune system and, more specifically, uncontrolled regulation of the complement alternative pathway plays a central role in the pathobiology of AMD. The complement Factor H gene-which encodes the major inhibitor of the complement alternative pathway-is the first gene identified in multiple independent studies that confers a significant genetic risk for the development of AMD. The emergence of this new paradigm of AMD pathogenesis should hasten the development of novel diagnostic and therapeutic approaches for this disease that will dramatically improve the quality of our prolonged lifespan.

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Section: Physiological Correlates Of Early Amdmentioning

confidence: 99%

Section: Inflammation and Amdmentioning

confidence: 99%

Age‐related macular degeneration—emerging pathogenetic and therapeutic concepts

et al. 2006

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“…Both types of drusen have been shown to damage cone and rod inner and outer segments. 24 Table 1 shows the characteristics of each ARM subject and the AREDS fundus grading 23 results at baseline and after 1 year.…”

Section: Subjectsmentioning

confidence: 99%

Monitoring retinal function in early age-related maculopathy: visual performance after 1 year

Feigl

Brown

Lovie‐Kitchin

et al. 2004

Eye

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Purpose To monitor visual performance in early age-related maculopathy (ARM). Methods We measured monocular visual functionFhigh-contrast visual acuity (HC-VA), central visual fields (mean sensitivity, MS), colour vision (desaturated Panel D-15), Pelli-Robson (P-R), and coneand rod-mediated multifocal electroretinograms (mfERG) in 13 ARM subjects and 13 age-matched control subjects with normal fundi at baseline and after 1 year. All had visual acuity of 6/12 or better. The mfERG data were compared to templates derived from the control group at baseline. We analysed the mfERG results by averaging the central and peripheral fields and the superior and inferior fields (CP and SI methods) and by calculating the local responses. Results The mean rod-mediated responses were significantly delayed in the ARM group for the CP (P ¼ 0.04) and the SI methods (P ¼ 0.03) at baseline compared to the control group. This did not change significantly after 1 year, whereas the mean cone-mediated responses were within the normal range at both times. Although the local analysis revealed lower amplitudes for the cone-and rod-mediated responses at baseline this was not found after 1 year and only the local rodmediated latencies were delayed at both times (Po0.01). HC-VA, desaturated Panel D-15 and P-R were significantly worse in the ARM group (Pp0.01) at baseline but did not show further significant deterioration. Progressive fundus changes were found in only two subjects (18%).

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“…Both types of drusen have been shown to damage cone and rod inner and outer segments. 32 We divided our subjects into two groups (ARM1 and ARM2) according to the AREDS AMD levels 31 (ARM1 ¼ AREDS ARM levels 1 and 2; ARM2 ¼ AREDS ARM level IIIa-c) ( Table 1). The ARM1 group (less advanced) consisted of 11 eyes with drusen size less than 125 mm and RPE abnormalities, and the ARM2 group (more advanced) included six eyes with indistinct drusen greater than 125 mm and/or a total area 372 mm determined 'by mentally moving all drusen together' 31 and comparing this area with those of the standard circles of the Wisconsin grading system.…”

Section: Subjectsmentioning

confidence: 99%

Cone- and rod-mediated multifocal electroretinogram in early age-related maculopathy

Feigl

Brown

Lovie‐Kitchin

et al. 2004

Eye

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Purpose To investigate the cone-and rodmediated multifocal electroretinograms (mfERG) in early age-related maculopathy (early ARM). Methods and subjects We investigated the cone-and rod-mediated mfERG in 17 eyes of 17 subjects with early ARM and 16 eyes of 16 age-matched control subjects with normal fundi. All subjects had a visual acuity of 6/12 or better. We divided the ARM subjects into two groups based on drusen size and retinal pigment epithelium abnormalitiesFa less advanced (ARM1) and a more advanced (ARM2) group. The mfERG data were compared to templates derived from the control group. We analysed the mfERG results for the central and peripheral fields (CP method) and the superior and inferior fields (SI method). Results While the mean cone results showed no statistically significant difference between the groups, the rods showed significantly delayed responses in the ARM1 group for the CP and the SI methods, but not in the ARM2 group, although there was a trend of longer latencies compared to the control group. Conclusion Our results show a functional impairment of the rods in early ARM subjects. As there is histopathological evidence showing earlier rod than cone impairment in early ARM, following the rod function with the mfERG might be helpful in diagnosis or for monitoring the progression of early ARM.

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Drusen-Associated Degeneration in the Retina

Cited by 181 publications

References 35 publications

Age‐related macular degeneration—emerging pathogenetic and therapeutic concepts

Age‐related macular degeneration—emerging pathogenetic and therapeutic concepts

Monitoring retinal function in early age-related maculopathy: visual performance after 1 year

Cone- and rod-mediated multifocal electroretinogram in early age-related maculopathy

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