Long-term effect of gene therapy on Leber's congenital amaurosis.

Background: Mutations in RPE65 cause Leber's congenital amaurosis, a progressive retinal degenerative disease that severely impairs sight in children. Gene therapy can result in modest improvements in night vision, but knowledge of its efficacy in humans is limited.

Methods: We performed a phase 1-2 open-label trial involving 12 participants to evaluate the safety and efficacy of gene therapy with a recombinant adeno-associated virus 2/2 (rAAV2/2) vector carrying the RPE65 complementary DNA, and measured visual function over the course of 3 years.

Scotopic and Photopic Microperimetry in Patients With Reticular Drusen and Age-Related Macular Degeneration.

Importance: Clinical observations suggest that patients with age-related macular degeneration (AMD) have vision problems, particularly in dim light conditions. Previous studies on structural-functional analysis in patients with AMD with reticular drusen (RDR) have focused on photopic sensitivity testing but have not specifically assessed scotopic function.

Objective: To evaluate retinal function by scotopic and photopic microperimetry in patients with AMD and a well-demarcated area of RDR.

A longitudinal study of Stargardt disease: quantitative assessment of fundus autofluorescence, progression, and genotype correlations.

Purpose: We characterized subtypes of fundus autofluorescence (AF) and the progression of retinal atrophy, and correlated these findings with genotype in Stargardt disease.

Methods: Full clinical examination and AF imaging was undertaken in 68 patients with Stargardt disease. The baseline data were compared to those at follow-up.

Comparison of fundus autofluorescence with photopic and scotopic fine matrix mapping in patients with retinitis pigmentosa: 4- to 8-year follow-up.

Purpose: To assess the significance and evolution of parafoveal rings of high-density fundus autofluorescence (AF) in 12 patients with retinitis pigmentosa (RP).

Methods: Twelve patients with autosomal recessive RP or Usher syndrome type 2 were ascertained who had a parafoveal ring of high-density AF and a visual acuity of 20/30 or better at baseline. Photopic and scotopic fine matrix mapping (FMM) were performed to test sensitivity across the macula.

Early onset retinal dystrophy due to mutations in LRAT: molecular analysis and detailed phenotypic study.

Purpose: To report novel variants and characterize the phenotype associated with the autosomal recessive retinal dystrophy caused by mutations in the lecithin retinol acyltransferase (LRAT) gene.

Methods: A total of 149 patients with Leber's congenital amaurosis (LCA) or early onset retinal dystrophy were screened for mutations in LCA-associated genes using an arrayed-primer extension (APEX) genotyping microarray (Asper Ophthalmics). LRAT sequencing was subsequently performed in this 148-patient panel.

Serial imaging and structure-function correlates of high-density rings of fundus autofluorescence in retinitis pigmentosa.

Purpose: To document the evolution and functional and structural significance of parafoveal rings of high-density fundus autofluorescence (AF) in patients with retinitis pigmentosa and preserved visual acuity.

Methods: Fifty-two patients with nonsyndromic retinitis pigmentosa or Usher syndrome, who had a parafoveal ring of high-density AF and a visual acuity of 20/30 or better, were ascertained. All had international standard full-field electroretinography and pattern electroretinography.

Retinal specific measurement of dark-adapted visual function: validation of a modified microperimeter.

Background: Scotopic function is an important marker of many retinal diseases and is increasingly used as an outcome measure in clinical trials, such as those investigating gene therapy for Lebers congenital amaurosis. Scotopic visual function has traditionally been measured using an adapted perimetry system such as the Humphrey field analyser (HFA). However this system does not control for fixation errors or poor fixation stability.

Localisation and significance of in vivo near-infrared autofluorescent signal in retinal imaging.

Aim: To evaluate near-infrared (NIR) autofluorescence (AF) in patients with geographic atrophy (GA) secondary to age-related macular degeneration and to investigate the origin of the signal by in vivo and histological analysis in rats and in a human donor eye.

Methods: Confocal scanning laser ophthalmoscopy in vivo imaging, including blue (excitation: 488 nm, emission 500-700 nm) and NIR (excitation: 790 nm, emission >810 nm) AF was performed in 21 eyes of 18 GA patients. Pigmented and albino rats underwent with the same device both in vivo and post-mortem imaging.

Structural and functional changes over time in MacTel patients.

Purpose: To investigate functional and morphologic alterations over a 1-year review analysis in patients with type 2 idiopathic juxtafoveal retinal telangiectasia (MacTel).

Methods: Nine eyes of 9 patients with MacTel underwent repeated scotopic and photopic fine matrix mapping (FMM), 10-2 photopic microperimetry, and imaging studies.

Results: Early Treatment Diabetic Retinopathy Study visual acuity assessment showed a median difference between examinations of 1.

Post-capsulotomy dysphotopsia in monofocal versus multifocal lenses.

Purpose: To compare the photic symptoms experienced by patients with the monofocal SI30 intraocular lens (IOL) with the refractive multifocal SA40 Array IOL after capsulotomy.

Methods: In this prospective cohort study, 49 eyes of 49 patients (20 multifocal, 29 monofocal IOLs) were assessed following uncomplicated cataract extraction and Nd:YAG capsulotomy equal to the scotopic pupillary diameter. Subjects with post-operative refraction of +/-1.

Effect of gene therapy on visual function in Leber's congenital amaurosis.

Early-onset, severe retinal dystrophy caused by mutations in the gene encoding retinal pigment epithelium-specific 65-kD protein (RPE65) is associated with poor vision at birth and complete loss of vision in early adulthood. We administered to three young adult patients subretinal injections of recombinant adeno-associated virus vector 2/2 expressing RPE65 complementary DNA (cDNA) under the control of a human RPE65 promoter. There were no serious adverse events.

Correlation of functional impairment and morphological alterations in patients with group 2A idiopathic juxtafoveal retinal telangiectasia.

Objective: To correlate functional impairment with morphological alterations in patients with group 2A idiopathic juxtafoveal retinal telangiectasia.

Methods: As part of the Macular Telangiectasia Project, a cohort of 10 patients underwent additional functional testing and imaging studies including photopic and scotopic fine matrix mapping, microperimetry, reflectance, and autofluorescence imaging with scanning laser ophthalmoscopy.

Results: From clinical stage 2 to 5, scotopic central function was reduced, which corresponded to depletion of macular pigment density.

Macular and retinal dysfunction of unknown origin in adults with normal fundi: evidence for an autoimmune pathophysiology.

Here we report the discovery of and phenotypic characterization of a retinal disorder of unknown origin in adults using clinical, electrophysiological and psychophysical techniques, and to seek the presence of circulating retinal autoantibodies in the sera of these patients. Sixteen patients were identified with progressive bilateral visual loss over a period of months. Ten of the patients were male, and the average age was 55.

Functional characteristics of patients with retinal dystrophy that manifest abnormal parafoveal annuli of high density fundus autofluorescence; a review and update.

Purpose: To examine the presence and functional significance of annular fundus autofluorescence abnormalities in patients with different retinal dystrophies.

Methods: Eighty one patients were ascertained who had a parafoveal ring of high density on fundus autofluorescence imaging. Sixty two had had a clinical diagnosis of retinitis pigmentosa (RP) or Usher syndrome with normal visual acuity.

Complement factor H deficiency in aged mice causes retinal abnormalities and visual dysfunction.

Age-related macular degeneration is the most common form of legal blindness in westernized societies, and polymorphisms in the gene encoding complement factor H (CFH) are associated with susceptibility to age-related macular degeneration in more than half of affected individuals. To investigate the relationship between complement factor H (CFH) and retinal disease, we performed functional and anatomical analysis in 2-year-old CFH-deficient (cfh(-/-)) mice. cfh(-/-) animals exhibited significantly reduced visual acuity and rod response amplitudes on electroretinography compared with age-matched controls.

Xanthophyll accumulation in the human retina during supplementation with lutein or zeaxanthin - the LUXEA (LUtein Xanthophyll Eye Accumulation) study.

The xanthophylls lutein (L) and zeaxanthin (Z) form the macular pigment with the highest density in the macula lutea. We investigated Macular Pigment Optical Density (MPOD) responses to supplementation with identically formulated (Actilease) L or Z (OPTISHARP) or L+Z over 6-12 months using doses of 10 or 20mg/day. MPOD as well as blue light sensitivity in fovea and parafovea were measured monthly by heterochromatic flicker photometry.

Maculopathy due to the R345W substitution in fibulin-3: distinct clinical features, disease variability, and extent of retinal dysfunction.

Purpose: To determine (1) clinical features that distinguish maculopathy due to the R345W substitution in fibulin-3 from other forms of inherited or early-onset drusen, (2) the phenotypic variability, and (3) the extent of retinal disease in those with a positive molecular diagnosis.

Methods: Affected individuals underwent ophthalmic examination, digital color fundus photography, fundus autofluorescence (AF) imaging, and psychophysical testing with automated photopic and dark-adapted perimetry and fine matrix mapping. Blood samples were taken for DNA extraction and screening for the R345W mutation in fibulin-3.

Assessment of neuroprotective effects of glutamate modulation on glaucoma-related retinal ganglion cell apoptosis in vivo.

Purpose: To assess the neuroprotective effects of different glutamate modulation strategies, with a nonselective (MK801) and a selective (ifenprodil) NMDA receptor antagonist and a metabotropic glutamate receptor agonist (mGluR Group II, LY354740), in glaucoma-related in vivo rat models of retinal ganglion cell (RGC) apoptosis.

Methods: RGC apoptosis was induced in Dark Agouti (DA) rats by staurosporine (SSP) treatment. Single agents MK801, ifenprodil, or LY354740, or MK801 and LY354740 combined, were administrated intravitreally at different doses.

Pars plana vitrectomy with and without peeling of the inner limiting membrane for diabetic macular edema.

Purpose: A prospective, comparative, nonrandomized study to evaluate the efficacy of pars plana vitrectomy (PPV) with and without inner limiting membrane (ILM) peeling for persistent diffuse clinically significant macular edema.

Methods: Eighteen patients with persistent diffuse clinically significant macular edema despite laser photocoagulation were recruited for the study. Clinical assessment included determination of best-corrected visual acuity, fundus fluorescein angiography, optical coherence tomography, and perifoveal cone function testing.

Central retinal thickness is positively correlated with macular pigment optical density.

Macular pigment (MP) has been suggested to have a protective role in age-related macular degeneration by reducing the amount of oxidative stress on the retina. MP levels peak at the foveal center, where it is found predominantly in the receptor axon and inner plexiform layers of the retina. The purpose of this study was to investigate the relationship between central retinal thickness and macular pigment optical density in a group of healthy subjects.

Heritability of macular pigment: a twin study.

Purpose: Several studies have reported higher levels of macular pigment (MP) in association with reduced risk for age-related macular degeneration (ARMD), a disease to which there is a genetic predisposition. A classic twin study was performed to determine the heritability of MP in the healthy eye.

Methods: One hundred fifty twin pairs (76 monozygotic [MZ] and 74 dizygotic [DZ]), aged 18 to 50 years, participated.

Autofluorescence imaging of choroidal neovascularization due to age-related macular degeneration.

Objective: To describe the autofluorescence (AF) characteristics of choroidal neovascularization (CNV) in patients with age-related macular degeneration.

Methods: Autofluorescence images of 65 consecutive eyes with CNV at various stages of evolution were analyzed. Twenty images were of recent-onset CNV (group 1), 8 were of eyes 1 to 6 months after CNV diagnosis (group 2), and 37 were late-stage CNV (group 3).

Magnification changes in scanning laser tomography.

Purpose: It is important when evaluating glaucomatous optic disc progression in longitudinal images that image magnification remains unchanged. We studied the effect of changed lens power on magnification in scanning laser tomography. The relative contribution to magnification of axial length, eye-scanner distance, and image-to-image scaling was also assessed.

Reducing noise in suspected glaucomatous visual fields by using a new spatial filter.

Visual field testing with automated perimetry is hampered by the amount of noise present in the readings. Here, we derive a physiologically accurate spatial filter to be applied to the data after patient examination. The filter was tested by a Virtual Eye computer simulation.