Macular Degeneration: Duncan JL

Duncan JL. · No affiliation provided · Br J Ophthalmol. · Pubmed #16299127 links to  free full text

This publication has no abstract.

Paskowitz DM, LaVail MM, Duncan JL. · Medical Scientist Training Program and Beckman Vision Center, UCSF School of Medicine, San Francisco, CA 94143-0730, USA. · Br J Ophthalmol. · Pubmed #16707518 links to  free full text

Abstract: Light deprivation has long been considered a potential treatment for patients with inherited retinal degenerative diseases, but no therapeutic benefit has been demonstrated to date. In the few clinical studies that have addressed this issue, the underlying mutations were unknown. Our rapidly expanding knowledge of the genes and mechanisms involved in retinal degeneration have made it possible to reconsider the potential value of light restriction in specific genetic contexts. This review summarises the clinical evidence for a modifying role of light exposure in retinal degeneration and experimental evidence from animal models, focusing on retinitis pigmentosa with regional degeneration, Oguchi disease, and Stargardt macular dystrophy. These cases illustrate distinct pathophysiological roles for light, and suggest that light restriction may benefit carefully defined subsets of patients.

Duncan JL, Aleman TS, Gardner LM, De Castro E, Marks DA, Emmons JM, Bieber ML, Steinberg JD, Bennett J, Stone EM, MacDonald IM, Cideciyan AV, Maguire MG, Jacobson SG. · Department of Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, PA 19104, USA. · Exp Eye Res. · Pubmed #12014918 No free full text.

Abstract: Choroideremia is an incurable X-linked retinal degeneration caused by mutations in the gene encoding Rab escort protein-1. A group of clinically defined and genotyped patients were studied to determine: (1) the degree of rod and cone dysfunction and structural abnormality in the central retina and the level of macular pigment; and (2) the response of macular pigment and foveal vision to a 6 month trial of supplementation with oral lutein (at 20 mg per day). Rod and cone-mediated function was measured with dark-adapted static perimetry; in vivo retinal structure was determined with optical coherence tomography; and macular pigment optical density was measured with heterochromatic flicker photometry. In this cohort of patients (ages 15-65 years), both rod- and cone-mediated central function declined with age as did central retinal thickness. Macular pigment levels did not differ between patients and male control subjects. Supplementation of oral lutein in a subset of patients led to an increase in serum lutein and macular pigment levels; absolute foveal sensitivity did not change. It is concluded that macular pigment density can be augmented by oral intake of lutein in patients with choroideremia. There was no short-term change in the central vision of the patients on the supplement, but long-term influences of lutein supplementation on disease natural history warrant further study.

Duncan JL, Zhang Y, Gandhi J, Nakanishi C, Othman M, Branham KE, Swaroop A, Roorda A. · Department of Ophthalmology, University of California, San Francisco School of Medicine, San Francisco, California 94143-0730, USA. · Invest Ophthalmol Vis Sci. · Pubmed #17591900 links to  free full text

Abstract: PURPOSE: To investigate macular photoreceptor structure in patients with inherited retinal degeneration using high-resolution images and to correlate the findings with clinical phenotypes and genetic mutations. METHODS: Adaptive optics scanning laser ophthalmoscopy (AOSLO) images of photoreceptors were obtained in 16 eyes: five with retinitis pigmentosa (RP), three with cone-rod dystrophy (CRD), and eight without retinal disease. A quadratic model was used to illustrate cone spacing as a function of retinal eccentricity. Cone spacing at 1 degrees eccentricity was compared with standard measures of central visual function, including best-corrected visual acuity (BCVA), foveal threshold, and multifocal electroretinogram (mfERG) amplitude and timing. Intervisit variations were studied in one patient with RP and one patient with CRD. Screening of candidate disease genes identified mutations in two patients, one with RP (a rhodopsin mutation) and the other with CRD (a novel RPGR-ORF15 mutation). RESULTS: Cone spacing values were significantly different from normal for patients with RP (P = 0.01) and CRD (P < 0.0001) and demonstrated a statistically significant correlation with foveal threshold (P = 0.0003), BCVA (P = 0.01), and mfERG amplitude (P = 0.008). Although many RP patients showed normal cone spacing within 1 degrees of fixation, cones could not be unambiguously identified in several retinal regions. Cone spacing increased in all CRD patients, even those with early disease. Little variation was observed in cone spacing measured during two sessions fewer than 8 days apart. CONCLUSIONS: AOSLO images can be used to study macular cones with high resolution in patients with retinal degeneration. The authors present the first report of cone structure in vivo in patients with mutations in rhodopsin and RPGR-ORF15 and show that macular cones display distinct characteristics, depending on the underlying disease. AOSLO imaging, therefore, can provide new insight into possible mechanisms of cone vision loss in patients with retinal degeneration.

Roorda A, Zhang Y, Duncan JL. · UC Berkeley School of Optometry, University of California, Berkeley, Berkeley, California 94720-2020, USA. · Invest Ophthalmol Vis Sci. · Pubmed #17460294 links to  free full text

Abstract: PURPOSE: To use high-resolution and contrast imaging techniques to reveal microscopic retinal structures, including individual retinal pigment epithelial (RPE) cells, in human eyes with inherited retinal disease. METHODS: Adaptive optics scanning laser ophthalmoscopy (AOSLO) was used to image the macular region in patients with retinal degenerative diseases, including two patients with cone-rod dystrophy and one with bilateral progressive maculopathy. Images were processed, and the microscopic details were analyzed. Fundus-related microperimetry was used to assess visual function within retinal regions where no cones were visible. RESULTS: In addition to patches of intact cone photoreceptors, AOSLO images revealed mosaics of RPE cells in regions where it appeared that cones were missing. In cone-rod dystrophy (CRD), the RPE cells were visualized in an annular region surrounding a cone-preserved central area. RPE cell shape, size, and distribution compared well with measurements from the literature. Fundus-related microperimetry results indicated scotomas that corresponded to the locations where RPE cells were visible. CONCLUSIONS: For the first time, the mosaic of RPE cells has been directly visualized by AOSLO. Patients with hereditary retinal degenerations causing cone loss in the macula allowed visualization of RPE cells in areas where cones were missing. Regions with visible RPE cells demonstrated loss of visual function measured using microperimetry.

Duncan JL, Paskowitz DM, Nune GC, Yasumura D, Yang H, Matthes MT, Zarbin MA, LaVail MM. · University of California, San Francisco, California 94143, USA. · Adv Exp Med Biol. · Pubmed #17249587 No free full text.

This publication has no abstract.

Paskowitz DM, Nune G, Yasumura D, Yang H, Bhisitkul RB, Sharma S, Matthes MT, Zarbin MA, Lavail MM, Duncan JL. · Department of Ophthalmology, University of California, San Francisco, 94143-0730, USA. · Invest Ophthalmol Vis Sci. · Pubmed #15505074 links to  free full text

Abstract: PURPOSE: Verteporfin photodynamic therapy (PDT) is the most effective treatment for age-related macular degeneration, using laser activation of a photosensitizing dye to achieve closure of choroidal neovascularization. Although PDT preferentially affects pathologic vessels, it can also cause collateral damage to the overlying retina. In the current study, it was found that the neuroprotective agent brain-derived neurotrophic factor (BDNF) reduces this retinal damage. METHODS: Normal adult rats received intravitreal BDNF in one eye and PBS or no injection in the other eye 2 days before PDT. RESULTS: Control eyes exhibited choroidal hypofluorescence, moderate to severe photoreceptor loss, and depression of local retinal function measured using multifocal ERG in the laser-treated area. BDNF-injected eyes had more surviving photoreceptors and improved multifocal ERG responses 1 week after PDT. BDNF did not diminish the effect of PDT on the choroidal circulation as assessed by fluorescein angiography, and there was no evidence of retinal toxicity due to BDNF treatment. CONCLUSIONS: These results suggest that adjunctive neuroprotective therapy may reduce collateral damage to photoreceptors and improve visual outcome after PDT.

Wilson HL, Schwartz DM, Bhatt HR, McCulloch CE, Duncan JL. · Department of Ophthalmology, UCSF School of Medicine, San Francisco, CA 94143, USA. · Am J Ophthalmol. · Pubmed #15059698 No free full text.

Abstract: PURPOSE: To investigate the relationship between statin and aspirin use and the risk of choroidal neovascularization (CNV) in patients with age-related macular degeneration (AMD). DESIGN: Retrospective consecutive case series. METHODS: All patients 60 years and older with AMD who were seen between January 1, 1990, and March 1, 2003, at the San Francisco Veterans Affairs Hospital Eye Clinic with fundus photographs were included. Patients with other diagnoses predisposing to CNV or incomplete medical records were excluded. The main outcome measure was angiographically evident CNV. Diagnosis was based on review of fundus photographs and fluorescein angiograms in masked fashion; medical records were reviewed for variables possibly predisposing to CNV or statin use. For patients with CNV, age of onset was recorded; those without CNV were treated as censored. Age-related macular degeneration disease status and time of onset of CNV was compared between patients treated or not treated with statins for at least 6 months. RESULTS: Of 326 patients with AMD, 104 had CNV, 204 had dry AMD, and 18 had geographic atrophy (GA). Of CNV subjects, 21 (20%) used statins, compared with 77 (38%) of dry AMD subjects without GA and 6 (33%) of controls with GA (hazard ratio = 0.51, 95% confidence interval (CI) = 0.31-0.86, P =.01). Aspirin use was also significantly associated with decreased rates of CNV; 62 CNV subjects (60%) used aspirin, compared with 154 (75%) dry AMD subjects without GA or 12 (67%) with GA (hazard ratio = 0.63, 95% CI = 0.40-0.98, P =.04). CONCLUSIONS: Therapy with statins or aspirin is associated with decreased rates of CNV among AMD patients. Additional study with a prospective and/or randomized trial of statin and aspirin use in AMD patients is warranted.

Aleman TS, Duncan JL, Bieber ML, de Castro E, Marks DA, Gardner LM, Steinberg JD, Cideciyan AV, Maguire MG, Jacobson SG. · Department of Ophthalmology, Scheie Eye Institute, 51 N. 39th Street, University of Pennsylvania, Philadelphia, PA 19104, USA. · Invest Ophthalmol Vis Sci. · Pubmed #11431456 links to  free full text

Abstract: PURPOSE. To determine macular pigment (MP) in patients with inherited retinal degeneration and the response of MP and vision to supplementation of lutein. METHODS. Patients with retinitis pigmentosa (RP) or Usher syndrome and normal subjects had MP optical density profiles measured with heterochromatic flicker photometry. Serum carotenoids, visual acuity, foveal sensitivity, and retinal thickness (by optical coherence tomography [OCT]) were quantified. The effects on MP and central vision of 6 months of lutein supplementation at 20 mg/d were determined. RESULTS. MP density in the patients as a group did not differ from normal. Among patients with lower MP, there was a higher percentage of females, smokers, and light-colored irides. Disease expression tended to be more severe in patients with lower MP. Inner retinal thickness by OCT correlated positively with MP density in the patients. After supplementation, all participants showed an increase in serum lutein. Only approximately half the patients showed a statistically significant increase in MP. Retinal nonresponders had slightly greater disease severity but were otherwise not distinguishable from responders. Central vision was unchanged after supplementation. CONCLUSIONS. Factors previously associated with lower or higher MP density in normal subjects showed similar associations in RP and Usher syndrome. In addition, MP in patients may be affected by stage of retinal disease, especially that leading to abnormal foveal architecture. MP could be augmented by supplemental lutein in many but not all patients. There was no change in central vision after 6 months of lutein supplementation, but long-term influences on the natural history of these retinal degenerations require further study.