Tomas S Aleman

University of Pennsylvania, Philadelphia, PA, United States

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Publications (98)557.29 Total impact

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    ABSTRACT: To study the relationship between the appearance of the optic nerve and the retinal nerve fiber layer (RNFL) thickness determined by spectral domain optical coherence tomography (OCT).
    Translational vision science & technology. 10/2014; 3(6):4.
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    ABSTRACT: The purpose of this study was to determine if there is an association between obstructive sleep apnea (OSA) and central serous chorioretinopathy (CSCR).
    Retina (Philadelphia, Pa.) 08/2014; · 2.93 Impact Factor
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    ABSTRACT: Abstract Purpose: To describe the retinal structure in a patient with cobalamin C (cblC) disease. Methods: A 13-year-old male patient diagnosed with cblC disease during a perinatal metabolic screening prompted by jaundice and hypotony underwent ophthalmic examinations, electroretinography (ERG) and spectral domain optical coherence tomography (SD-OCT). Results: The patient carried a homozygous (c.271dupA) mutation in the methylmalonic aciduria and homocystinuria type C (MMACHC) gene. At age 3 months he had a normal eye exam. A pigmentary maculopathy progressed to chorioretinal atrophy from 5-10 months. ERG at 7 months was normal. A nystagmus remained stable since the age of 2 years. At age 13, visual acuity was 20/250 (right eye) and 20/400 (left eye), with a +5.00 D correction, a level of vision maintained since first measurable at age 5 years. SD-OCT showed bilateral macular coloboma-like lesions; there was also a thickened surface layer with ganglion cell layer thinning. Photoreceptor outer segment loss and thinning of the outer nuclear layer (ONL) transitioned to regions with no discernible ONL with a delaminated, thickened, inner retina. Conclusions: A thick surface layer near the optic nerve resembling an immature retina and an initially normal macula that rapidly developed coloboma-like lesions suggest there may be an interference with retinal/foveal development in cblC, a mechanism of maculopathy that may be shared by other early onset retinal degenerations. Photoreceptor loss and inner retinal remodeling confirm associated photoreceptor degeneration.
    Ophthalmic Genetics 02/2014; · 1.07 Impact Factor
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    ABSTRACT: To define the retinal structural abnormalities in a patient with vitamin A deficiency. The patient had a complete ophthalmic examination, electroretinography (ERG), short-wave fundus autofluorescence (SW-AF) and spectral domain optical coherence tomography (SD-OCT) imaging. Serum vitamin A levels were measured. A 63-year-old man with alcoholic cirrhosis, sclerosing cholangitis and chronic pancreatitis experienced blurred vision and nyctalopia for over a year. There was no family history of eye disorders or consanguinity. His best-corrected visual acuity was 20/20 in each eye; color vision as determined with Ishihara color plates was normal in each eye. Anterior segment examination was unremarkable. He was pseudophakic in both eyes. Standard ERGs showed non-detectable rod function, a cone-mediated dark-adapted response to the standard flash and borderline reduced cone function. Serum vitamin A levels were below 0.06 mg/L (normal 0.3-1.2 mg/L). Fundus examination revealed numerous round yellow-white lesions along the superior arcade and nasal to the optic nerve in both eyes. These lesions were hypoautofluorescent on SW-AF. SD-OCT cross sections demonstrated that they were focal disruptions distal to the ellipsoid band of the photoreceptors with hyperreflective images bulging up the ellipsoid and region. The retinal pigment epithelium and the inner retina appeared intact. Limited and gradual vitamin A supplementation for over a month (20 000 IU/day) led to a dramatic improvement in retinal function and to the resolution of the symptoms. The retinal lesions remained unchanged. Imaging of this patient with nyctalopia and severe rod dysfunction suggests that the retinal white lesions known to occur in vitamin A deficiency localize to the photoreceptor layer, particularly the outer segment. On OCT, they are reminiscent of lesions observed in genetic diseases with retinoid cycle dysfunction and of drusenoid subretinal deposits, an abnormality commonly associated with age-related macular degeneration.
    Documenta Ophthalmologica 07/2013; · 1.54 Impact Factor
  • Retina (Philadelphia, Pa.) 08/2012; 32(8):1687-8. · 2.93 Impact Factor
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    ABSTRACT: Hereditary retinal blindness is caused by mutations in genes expressed in photoreceptors or retinal pigment epithelium. Gene therapy in mouse and dog models of a primary retinal pigment epithelium disease has already been translated to human clinical trials with encouraging results. Treatment for common primary photoreceptor blindness, however, has not yet moved from proof of concept to the clinic. We evaluated gene augmentation therapy in two blinding canine photoreceptor diseases that model the common X-linked form of retinitis pigmentosa caused by mutations in the retinitis pigmentosa GTPase regulator (RPGR) gene, which encodes a photoreceptor ciliary protein, and provide evidence that the therapy is effective. After subretinal injections of adeno-associated virus-2/5-vectored human RPGR with human IRBP or GRK1 promoters, in vivo imaging showed preserved photoreceptor nuclei and inner/outer segments that were limited to treated areas. Both rod and cone photoreceptor function were greater in treated (three of four) than in control eyes. Histopathology indicated normal photoreceptor structure and reversal of opsin mislocalization in treated areas expressing human RPGR protein in rods and cones. Postreceptoral remodeling was also corrected: there was reversal of bipolar cell dendrite retraction evident with bipolar cell markers and preservation of outer plexiform layer thickness. Efficacy of gene therapy in these large animal models of X-linked retinitis pigmentosa provides a path for translation to human treatment.
    Proceedings of the National Academy of Sciences 02/2012; 109(6):2132-7. · 9.81 Impact Factor
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    ABSTRACT: To measure macular visual function in patients with unstable fixation, to define the photoreceptor source of this function, and to estimate its test-retest repeatability as a prerequisite to clinical trials. Patients (n = 38) with ABCA4-associated retinal degeneration (RD) or with retinitis pigmentosa (RP) were studied with retina-tracking microperimetry along the foveo-papillary profile between the fovea and the optic nerve head, and point-by-point test-retest repeatability was estimated. A subset with foveal fixation was also studied with dark-adapted projection perimetry using monochromatic blue and red stimuli along the horizontal meridian. Macular function in ABCA4-RD patients transitioned from lower sensitivity at the parafovea to higher sensitivity in the perifovea. RP patients had the inverse pattern. Red-on-red microperimetric sensitivities successfully avoided ceiling effects and were highly correlated with absolute sensitivities. Point-by-point test-retest limits (95% confidence intervals) were ±4.2 dB; repeatability was not related to mean sensitivity, eccentricity from the fovea, age, fixation location, or instability. Repeatability was also not related to the local slope of sensitivity and was unchanged in the parapapillary retina. Microperimetry allows reliable testing of macular function in RD patients without foveal fixation in longitudinal studies evaluating natural disease progression or efficacy of therapeutic trials. A single estimate of test-retest repeatability can be used to determine significant changes in visual function at individual retinal loci within diseased regions that are homogeneous and those that are heterogeneous and also in transition zones at high risk for disease progression.
    Investigative ophthalmology & visual science 01/2012; 53(2):841-52. · 3.43 Impact Factor
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    ABSTRACT: Autosomal recessive retinitis pigmentosa (RP), a heterogeneous group of degenerations of the retina, can be due to mutations in the MFRP (membrane-type frizzled-related protein) gene. A patient with RP with MFRP mutations, one of which is novel and the first splice site mutation reported, was characterized by noninvasive retinal and visual studies. The phenotype, albeit complex, suggested that this retinal degeneration may be a candidate for gene-based therapy. Proof-of-concept studies were performed in the rd6 Mfrp mutant mouse model. The fast-acting tyrosine-capsid mutant AAV8 (Y733F) vector containing the small chicken β-actin promoter driving the wild-type mouse Mfrp gene was used. Subretinal vector delivery on postnatal day 14 prevented retinal degeneration. Treatment rescued rod and cone photoreceptors, as assessed by electroretinography and retinal histology at 2 months of age. This AAV-mediated gene delivery also resulted in robust MFRP expression predominantly in its normal location within the retinal pigment epithelium apical membrane and its microvilli. The clinical features of MFRP-RP and our preliminary data indicating a response to gene therapy in the rd6 mouse suggest that this form of RP is a potential target for gene-based therapy.
    Human gene therapy 12/2011; 23(4):367-76. · 4.20 Impact Factor
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    ABSTRACT: To determine the safety and efficacy of subretinal gene therapy in the RPE65 form of Leber congenital amaurosis using recombinant adeno-associated virus 2 (rAAV2) carrying the RPE65 gene. Open-label, dose-escalation phase I study of 15 patients (range, 11-30 years of age) evaluated after subretinal injection of the rAAV2- RPE65 vector into the worse-functioning eye. Five cohorts represented 4 dose levels and 2 different injection strategies. Primary outcomes were systemic and ocular safety. Secondary outcomes assayed visual function with dark-adapted full-field sensitivity testing and visual acuity with Early Treatment Diabetic Retinopathy Study charts. Further assays included immune responses to the vector, static visual fields, pupillometry, mobility performance, and optical coherence tomography. No systemic toxicity was detected; ocular adverse events were related to surgery. Visual function improved in all patients to different degrees; improvements were localized to treated areas. Cone and rod sensitivities increased significantly in the study eyes but not in the control eyes. Minor acuity improvements were recorded in many study and control eyes. Major acuity improvements occurred in study eyes with the lowest entry acuities and parafoveal fixation loci treated with subretinal injections. Other patients with better foveal structure lost retinal thickness and acuity after subfoveal injections. Gene therapy for Leber congenital amaurosis caused by RPE65 mutations is sufficiently safe and substantially efficacious in the extrafoveal retina. There is no benefit and some risk in treating the fovea. No evidence of age-dependent effects was found. Our results point to specific treatment strategies for subsequent phases. Gene therapy for inherited retinal disease has the potential to become a future part of clinical practice. clinicaltrials.gov Identifier: NCT00481546.
    Archives of ophthalmology 09/2011; 130(1):9-24. · 3.86 Impact Factor
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    ABSTRACT: PURPOSE. To determine the disease course in Usher syndrome type IB (USH1B) caused by myosin 7A (MYO7A) gene mutations. METHODS. USH1B patients (n = 33, ages 2-61) representing 25 different families were studied by ocular examination, kinetic and chromatic static perimetry, dark adaptometry, and optical coherence tomography (OCT). Consequences of the mutant alleles were predicted. RESULTS. All MYO7A patients had severely abnormal ERGs, but kinetic fields revealed regional patterns of visual loss that suggested a disease sequence. Rod-mediated vision could be lost to different degrees in the first decades of life. Cone vision followed a more predictable and slower decline. Central vision ranged from normal to reduced in the first four decades of life and thereafter was severely abnormal. Dark adaptation kinetics was normal. Photoreceptor layer thickness in a wide region of central retina could differ dramatically between patients of comparable ages; and there were examples of severe losses in childhood as well as relative preservation in patients in the third decade of life. Comparisons were made between the mutant alleles in mild versus more severe phenotypes. CONCLUSIONS. A disease sequence in USH1B leads from generally full but impaired visual fields to residual small central islands. At most disease stages, there was preserved temporal peripheral field, a potential target for early phase clinical trials of gene therapy. From data comparing patients' rod disease in this cohort, the authors speculate that null MYO7A alleles could be associated with milder dysfunction and fewer photoreceptor structural losses at ages when other genotypes show more severe phenotypes.
    Investigative ophthalmology & visual science 08/2011; 52(11):7924-36. · 3.43 Impact Factor
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    ABSTRACT: To investigate the human disease due to CRB1 mutations and compare results with the Crb1-mutant rd8 mouse. Twenty-two patients with CRB1 mutations were studied. Function was assessed with perimetry and electroretinography (ERG) and retinal structure with optical coherence tomography (OCT). Cortical structure and function were quantified with magnetic resonance imaging (MRI). Rd8 mice underwent ERG, OCT, and retinal histopathology. Visual acuities ranged from 20/25 to light perception. Rod ERGs were not detectable; small cone signals were recordable. By perimetry, small central visual islands were separated by midperipheral scotomas from far temporal peripheral islands. The central islands were cone mediated, whereas the peripheral islands retained some rod function. With OCT, there were small foveal islands of thinned outer nuclear layer (ONL) surrounded by thick delaminated retina with intraretinal hyperreflective lesions. MRI showed structurally normal optic nerves and only subtle changes to occipital lobe white and gray matter. Functional MRI indicated that whole-brain responses from patients were of reduced amplitude and spatial extent compared with those of normal controls. Rd8 mice had essentially normal ERGs; OCT and histopathology showed patchy retinal disorganization with pseudorosettes more pronounced in ventral than in dorsal retina. Photoreceptor degeneration was associated with dysplastic regions. CRB1 mutations lead to early-onset severe loss of vision with thickened, disorganized, nonseeing retina. Impaired peripheral vision can persist in late disease stages. Rd8 mice also have a disorganized retina, but there is sufficient photoreceptor integrity to produce largely normal retinal function. Differences between human and mouse diseases will complicate proof-of-concept studies intended to advance treatment initiatives.
    Investigative ophthalmology & visual science 07/2011; 52(9):6898-910. · 3.43 Impact Factor
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    ABSTRACT: Mutations in the MYO7A gene cause a deaf-blindness disorder, known as Usher syndrome 1B. In the retina, the majority of MYO7A is in the retinal pigmented epithelium (RPE), where many of the reactions of the visual retinoid cycle take place. We have observed that the retinas of Myo7a-mutant mice are resistant to acute light damage. In exploring the basis of this resistance, we found that Myo7a-mutant mice have lower levels of RPE65, the RPE isomerase that has a key role in the retinoid cycle. We show for the first time that RPE65 normally undergoes a light-dependent translocation to become more concentrated in the central region of the RPE cells. This translocation requires MYO7A, so that, in Myo7a-mutant mice, RPE65 is partly mislocalized in the light. RPE65 is degraded more quickly in Myo7a-mutant mice, perhaps due to its mislocalization, providing a plausible explanation for its lower levels. Following a 50-60% photobleach, Myo7a-mutant retinas exhibited increased all-trans-retinyl ester levels during the initial stages of dark recovery, consistent with a deficiency in RPE65 activity. Lastly, MYO7A and RPE65 were co-immunoprecipitated from RPE cell lysate by antibodies against either of the proteins, and the two proteins were partly colocalized, suggesting a direct or indirect interaction. Together, the results support a role for MYO7A in the translocation of RPE65, illustrating the involvement of a molecular motor in the spatiotemporal organization of the retinoid cycle in vision.
    Human Molecular Genetics 07/2011; 20(13):2560-70. · 7.69 Impact Factor
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    ABSTRACT: To determine the human retinal phenotype caused by mutations in the gene encoding AIPL1 (Aryl hydrocarbon receptor-interacting protein-like 1) now that there are proof-of-concept results for gene therapy success in Aipl1-deficient mice. Leber congenital amaurosis (LCA) patients (n = 10) and one patient with a later-onset retinal degeneration (RD) and AIPL1 mutations were studied by ocular examination, retinal imaging, perimetry, full-field sensitivity testing, and pupillometry. The LCA patients had severe visual acuity loss early in life, nondetectable electroretinograms (ERGs), and little or no detectable visual fields. Hallmarks of retinal degeneration were present in a wide region, including the macula and midperiphery; there was some apparent peripheral retinal sparing. Cross-sectional imaging showed foveal cone photoreceptor loss with a ring of minimally preserved paracentral photoreceptor nuclear layer. Features of retinal remodeling were present eccentric to the region of detectable photoreceptors. Full-field sensitivity was reduced by at least 2 log units, and chromatic stimuli, by psychophysics and pupillometry, revealed retained but impaired rod function. The RD patient, examined serially over two decades (ages, 45-67 years), retained an ERG in the fifth decade of life with abnormal rod and cone signals; and there was progressive loss of central and peripheral function. AIPL1-LCA, unlike some other forms of LCA with equally severe visual disturbance, shows profound loss of foveal as well as extrafoveal photoreceptors. The more unusual late-onset and slower form of AIPL1 disease may be better suited to gene augmentation therapy and is worthy of detection and further study.
    Investigative ophthalmology & visual science 01/2011; 52(1):70-9. · 3.43 Impact Factor
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    ABSTRACT: A single founder mutation resulting in a Ser163Arg substitution in the C1QTNF5 gene product causes autosomal dominant late-onset retinal macular degeneration (L-ORMD) in humans, which has clinical and pathological features resembling age-related macular degeneration. We generated and characterised a mouse "knock-in" model carrying the Ser163Arg mutation in the orthologous murine C1qtnf5 gene by site-directed mutagenesis and homologous recombination into mouse embryonic stem cells. Biochemical, immunological, electron microscopic, fundus autofluorescence, electroretinography and laser photocoagulation analyses were used to characterise the mouse model. Heterozygous and homozygous knock-in mice showed no significant abnormality in any of the above measures at time points up to 2 years. This result contrasts with another C1qtnf5 Ser163Arg knock-in mouse which showed most of the features of L-ORMD but differed in genetic background and targeting construct.
    PLoS ONE 01/2011; 6(11):e27433. · 3.53 Impact Factor
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    ABSTRACT: To investigate whether mutations in NPHP5 can cause Leber congenital amaurosis (LCA) without early-onset renal disease. DNA samples from 276 individuals with nonsyndromic LCA were screened for variations in the NPHP5 gene. Each had been previously screened for mutations in 8 known LCA genes without identifying a disease-causing genotype. Nine of the 276 LCA probands (3.2%) harbored 2 plausible disease-causing mutations (7 different alleles) in NPHP5. Four of these have been previously reported in patients with Senior-Loken syndrome (F141del, R461X, H506del, and R489X) and 3 are novel (A111del, E346X, and R455X). All 9 patients had severe visual loss from early childhood but none had overt renal disease in the first decade of life. Two patients were diagnosed with nephronophthisis in the second decade. Retinal imaging studies showed retained photoreceptor nuclei and retinal pigment epithelium integrity mainly in the cone-rich central retina, a phenotype with strong similarities to that of NPHP6 disease. Mutations in NPHP5 can cause LCA without early-onset renal disease. Abnormalities observed in the photoreceptor outer segments (a cilial structure) may explain the severe visual loss in NPHP5 -associated LCA. Clinical Relevance The persistence of central photoreceptor nuclei despite severe visual loss in NPHP5 disease is encouraging for future therapeutic interventions.
    Archives of ophthalmology 01/2011; 129(1):81-7. · 3.86 Impact Factor
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    ABSTRACT: Leber congenital amaurosis (LCA), a severe autosomal recessive childhood blindness, is caused by mutations in at least 15 genes. The most common molecular form is a ciliopathy due to NPHP6 (CEP290) mutations and subjects have profound loss of vision. A similarly severe phenotype occurs in the related ciliopathy NPHP5 (IQCB1)-LCA. Recent success of retinal gene therapy in one form of LCA prompted the question whether we know enough about human NPHP5 and NPHP6 disease to plan such treatment. We determined that there was early-onset rapid degeneration of rod photoreceptors in young subjects with these ciliopathies. Rod outer segment (OS) lamination, when detectable, was disorganized. Retinal pigment epithelium lipofuscin accumulation indicated that rods had existed in the past in most subjects. In contrast to early rod losses, the all-cone human fovea in NPHP5- and NPHP6-LCA of all ages retained cone nuclei, albeit with abnormal inner segments and OS. The rd16 mouse, carrying a hypomorphic Nphp6 allele, was a good model of the rod-dominant human extra-foveal retina. Rd16 mice showed normal genesis of photoreceptors, including the formation of cilia, followed by abnormal elaboration of OS and rapid degeneration. To produce a model of the all-cone human fovea in NPHP6-LCA, we generated rd16;Nrl-/- double-mutant mice. They showed substantially retained cone photoreceptors with disproportionate cone function loss, such as in the human disease. NPHP5- and NPHP6-LCA across a wide age spectrum are thus excellent candidates for cone-directed gene augmentation therapy, and the rd16;Nrl-/- mouse is an appropriate model for pre-clinical proof-of-concept studies.
    Human Molecular Genetics 01/2011; 20(7):1411-23. · 7.69 Impact Factor
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    ABSTRACT: The history of the North African Jewish community is ancient and complicated with a number of immigration waves and persecutions dramatically affecting its population size. A decade-long process in Israel of clinical-molecular screening of North African Jews with incurable autosomal recessive blindness led to the identification of a homozygous splicing mutation (c.95-2A > T; IVS2-2A > T) in RPE65, the gene encoding the isomerase that catalyzes a key step in the retinoid-visual cycle, in patients from 10 unrelated families. A total of 33 patients (four now deceased) had the severe childhood blindness known as Leber congenital amaurosis (LCA), making it the most common cause of retinal degeneration in this population. Haplotype analysis in seven of the patients revealed a shared homozygous region, indicating a population-specific founder mutation. The age of the RPE65 founder mutation was estimated to have emerged 100-230 (mean, 153) generations ago, suggesting it originated before the establishment of the Jewish community in North Africa. Individuals with this RPE65 mutation were characterized with retinal studies to determine if they were candidates for gene replacement, the recent and only therapy to date for this otherwise incurable blindness. The step from molecular anthropological studies to application of genetic medicine was then taken, and a representative of this patient subgroup was treated with subretinal rAAV2-RPE65 gene therapy. An increase in vision was present in the treated area as early as 15 days after the intervention. This process of genetically analyzing affected isolated populations as a screen for gene-based therapy suggests a new paradigm for disease diagnosis and treatment.
    Human gene therapy 12/2010; 21(12):1749-57. · 4.20 Impact Factor
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    ABSTRACT: To quantify the retinal disease in Rpe65-deficient mice across a wide age span and compare the results to those in humans with Leber congenital amaurosis (LCA) caused by RPE65 mutations. Full-field electroretinograms (ERGs) were recorded from wild-type (C57BL/6; Rpe65(+/+)) and Rpe65(-/-) mice at ages ranging from ∼1 month to 2 years. A physiologically based model of rod phototransduction activation was used to determine photoreceptor (P3) cell components of ERG photoresponses. A bipolar (P2) cell component was also derived. Photoreceptor and inner retinal thickness measurements were made by using optical coherence tomography in human RPE65-LCA. Age-related declines in ERG photoreceptor and bipolar amplitudes were present in the Rpe65(-/-) mouse. The loss of photoresponse amplitude with age in the mutant mice paralleled reported losses of photoreceptor nuclear layer thickness over the same age range. Unexpectedly, the early activation phase of photoresponses in Rpe65(-/-) mice accelerated with age as amplitude decreased; this was not a feature of Rpe65(+/+) mice. Inner retinal dysfunction increased with age in the mutant mice. Human RPE65-LCA patients had retinal degeneration and loss of photoreceptors in the first decade of life. Unlike the mouse model, there were no examples of a normal photoreceptor complement. Abnormal thickening of the inner retina occurred with increasing loss of photoreceptors. The differences in time course of murine and human RPE65-deficiency diseases suggests that preclinical efficacy testing of therapeutic modalities would be most informative when the murine disease becomes comparable to early human disease, toward the end of the first year of life in Rpe65(-/-) mice.
    Investigative ophthalmology & visual science 10/2010; 51(10):5304-13. · 3.43 Impact Factor
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    ABSTRACT: To correlate visual acuity of patients with Leber's congenital amaurosis (LCA) and early childhood-onset retinitis pigmentosa (RP) with mutations in underlying LCA genes. Multicentered retrospective observational study. After exclusion of 28 subjects, 169 patients with the diagnosis of LCA and 27 patients with early childhood-onset RP were included in the study because the underlying mutations in AIPL1, GUCY2D, RDH12, RPE65, CRX, CRB1, RPGRIP1, CEP290, LCA5, and TULP1 genes could be identified in this cohort of patients. We collected data on best-corrected visual acuity as recorded at the time of the patient's most recent visit to one of the participating ophthalmology departments. The median and range of visual acuities for each genetic subtype were calculated separately for the LCA and early childhood-onset RP groups. The range and median best-corrected visual acuities for each genetic subtype and age-related mean visual acuities for each genetic subtype. A wide variation in visual acuity was observed in patients with LCA and RPE65, RDH12, and CRB1 mutations, whereas AIPL1, GUCY2D, CRX, and RPGRIP1 gene mutations were associated with severely decreased visual acuities beginning within the first year of life. It was also noted that patients with either an RPE65 or CRB1 mutation have progressive visual loss with advancing age. Onset of visual symptoms after infancy was associated with a relatively better visual prognosis. The data obtained from this study will help clinicians provide counseling on visual prognosis to patients with known mutations in LCA genes and be of value in future studies aimed at the treatment of LCA and early childhood-onset RP.
    Ophthalmology 06/2010; 117(6):1190-8. · 5.56 Impact Factor
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    Journal of Vision 12/2009; 9(14):27-27. · 2.48 Impact Factor

Publication Stats

5k Citations
557.29 Total Impact Points

Institutions

  • 1999–2013
    • University of Pennsylvania
      • • Department of Ophthalmology
      • • Scheie Eye Institute
      Philadelphia, PA, United States
  • 2001–2012
    • Hospital of the University of Pennsylvania
      • Department of Ophthalmology
      Philadelphia, Pennsylvania, United States
  • 2011
    • University of Iowa
      • Department of Ophthalmology and Visual Sciences
      Iowa City, IA, United States
  • 2009–2011
    • University of California, Los Angeles
      • Department of Ophthalmology
      Los Angeles, California, United States
    • Case Western Reserve University
      • Department of Pharmacology
      Cleveland, OH, United States
  • 2008–2011
    • University of Florida
      • Department of Ophthalmology
      Gainesville, FL, United States
  • 2010
    • University of Illinois at Chicago
      • Department of Ophthalmology and Visual Sciences (Chicago)
      Chicago, IL, United States
  • 2007
    • Howard Hughes Medical Institute
      Ashburn, Virginia, United States
    • Treatment Research Institute, Philadelphia PA
      Philadelphia, Pennsylvania, United States
  • 2006
    • University of Michigan
      • Department of Ophthalmology and Visual Sciences
      Ann Arbor, MI, United States
  • 2001–2006
    • Cornell University
      • College of Veterinary Medicine
      Ithaca, New York, United States
  • 2004
    • Western General Hospital
      Edinburgh, Scotland, United Kingdom