Publications by authors named "Naheed W Khan"

Importance: The association of race and detection of pathogenic variants using wide-panel genetic testing for inherited retinal diseases (IRD), to our knowledge, has not been studied previously.

Objective: To investigate the genetic detection rates of wide-panel testing in Black and non-Hispanic White patients with IRDs.

Design, Setting, Participants: This 2-group comparison used retrospective patient data that were collected at the University of Michigan (UM) and Blueprint Genetics (BG).

View Article and Find Full Text PDF

The use of vectors for gene supplementation has achieved spectacular success as a treatment for individuals with autosomal recessive retinal disease caused by biallelic mutations in the visual cycle gene . However, the efficacy of this approach in treating autosomal dominant retinitis pigmentosa (adRP) associated with a monoallelic mutation encoding a rare D477G RPE65 variant has not been studied. Although lacking a severe phenotype, we now find that knock-in mice heterozygous for D477G RPE65 (D477G KI mice) can be used to evaluate outcomes of gene supplementation.

View Article and Find Full Text PDF

We previously identified a homozygous G178R mutation in human () through whole-exome analysis responsible for early onset retinal degeneration (RD) in patients with cone-rod dystrophy. The mutant G178R ASRGL1 expressed in Cos-7 cells showed altered localization, while the mutant ASRGL1 in lacked the autocatalytic activity needed to generate the active protein. To evaluate the effect of impaired ASRGL1 function on the retina in vivo, we generated a mouse model with c.

View Article and Find Full Text PDF

Background: Self-determination theory (SDT) of human motivation was used to examine associations between different forms of motivation in Argus II retinal prosthesis users and their engagement and satisfaction with the Argus device.

Materials And Methods: Nine subjects were administered: 1) a Situational Motivation Scale (SIMS) questionnaire to measure intrinsic motivation, identified regulation, external regulation, and amotivation, and 2) the Argus questionnaire (AQ) which was organized into 5 categories to measure 'Decision to get an Argus implant,' 'Self-perception as an Argus user', 'Utility of Argus,' 'Perceived competence,' and 'Family support.' Spearman correlations () were used to find associations between measures from SIMS and AQ.

View Article and Find Full Text PDF

Patients with inherited retinal dystrophies (IRDs) were recruited from two understudied populations: Mexico and Pakistan as well as a third well-studied population of European Americans to define the genetic architecture of IRD by performing whole-genome sequencing (WGS). Whole-genome analysis was performed on 409 individuals from 108 unrelated pedigrees with IRDs. All patients underwent an ophthalmic evaluation to establish the retinal phenotype.

View Article and Find Full Text PDF

: Several novel treatments of inherited retinal degenerations have undergone phase I/IIa clinical trials with limited sample size, yet investigators must still determine if toxicity or an efficacy signal occurred or if the change was due to test-retest variability (TRV) of the measurement tool.: Synthetic datasets were used to compare three types of TRV estimators under different sample sizes, mean drift, skewness, and number of baseline measurements.: Mixed effects models underestimated the standard deviation of measurement error (SDEM); the unbiased change score estimator method (UBS) was more accurate.

View Article and Find Full Text PDF

Photoacoustic microscopy (PAM) has significant potential as a promising diagnostic method for eye diseases and can provide anatomic and functional information of the retinal and choroidal vasculature. However, there are no FDA-approved PAM systems for ophthalmic imaging. In this study, a comprehensive safety evaluation was performed to evaluate the safety of PAM retinal imaging and whether PAM causes damage to retinal structure or function in rabbit eyes.

View Article and Find Full Text PDF

Purpose: The purpose of this study was to evaluate baseline best corrected visual acuity (BCVA), full-field electroretinography (ERG), full-field stimulus thresholds (FST), and their relationship with baseline demographic and clinical characteristics in the Rate of Progression in Usher syndrome type 2 ()-related Retinal Degeneration (RUSH2A) multicenter study.

Methods: Participants had Usher syndrome type 2 (USH2, = 80) or autosomal recessive nonsyndromic retinitis pigmentosa (ARRP,  = 47) associated with biallelic variants in the gene. Associations of demographic and clinical characteristics with BCVA, ERG, and FST were assessed with regression models.

View Article and Find Full Text PDF

Major advances in the study of inherited retinal diseases (IRDs) have placed efforts to develop treatments for these blinding conditions at the forefront of the emerging field of precision medicine. As a result, the growth of clinical trials for IRDs has increased rapidly over the past decade and is expected to further accelerate as more therapeutic possibilities emerge and qualified participants are identified. Although guided by established principles, these specialized trials, requiring analysis of novel outcome measures and endpoints in small patient populations, present multiple challenges relative to study design and ethical considerations.

View Article and Find Full Text PDF

Purpose: To report a case of pituitary adenoma in a patient with retinitis pigmentosa (RP) and consequent rapid constriction of the visual field in each eye, which is atypical for either of these pathologies.

Observations: A 45-year old male, with a long-standing history of RP, presented with rapid vision loss over 3 months. Examination revealed a severe drop in visual acuity and significant progression of concentric visual field constriction in each eye compared to 3 months prior.

View Article and Find Full Text PDF

Background: Monoclonal gammopathy of undetermined significance (MGUS) is a plasma cell dyscrasia and precursor to multiple myeloma. It has known ocular manifestations, but has not previously been shown to have an association with autoimmune retinopathy.

Case Presentation: A 57 year-old female presented with 1 year of progressive, bilateral, peripheral vision loss, photopsias, and nyctalopia.

View Article and Find Full Text PDF

Purpose: X-linked retinitis pigmentosa can manifest in female carriers with widely variable severity, whereas others remain unaffected. The contribution of X-chromosome inactivation (XCI) to phenotypic variation has been postulated but not demonstrated. Furthermore, the impact of genotype and genetic modifiers has been demonstrated in affected males but has not been well established in female carriers.

View Article and Find Full Text PDF

Purpose: To compare retinal function by using fundus-guided microperimetry (MP) and multifocal electroretinography (mfERG) for detecting hydroxychloroquine (HCQ) maculopathy.

Methods: Forty-six eyes of 25 patients referred to our clinical practice for HCQ maculopathy assessment and 3 groups of normal control subjects were evaluated by mfERG and MP. Macular structure was assessed using spectral-domain optical coherence tomography (SD-OCT).

View Article and Find Full Text PDF

Early-onset severe retinal dystrophy (EOSRD) is a genetically heterogeneous group of diseases resulting in serious visual disability in children. A significant number of EOSRD cases, often diagnosed as Leber congenital amaurosis (LCA13), are associated with mutations in the gene encoding retinol dehydrogenase 12 (RDH12). RDH12 is a member of the enzyme family of short-chain dehydrogenases/reductases.

View Article and Find Full Text PDF

Background: Stargardt disease (STGD) and age-related macular degeneration (AMD) share clinical and pathophysiological features. In AMD, macular hyperpigmentary changes are associated to a worse prognosis. The purpose of this study was to characterize macular hyperpigmentary changes in patients with STGD and associate them with the severity of phenotype.

View Article and Find Full Text PDF

Background: Defects in retinol dehydrogenase 12 () account for 3.4%-10.5 % of Leber congenital amaurosis and early-onset severe retinal dystrophy (EOSRD) and are a potential target for gene therapy.

View Article and Find Full Text PDF

Background: Patients with retinal diseases frequently complain of poor visual function even when visual acuity is relatively unaffected. This clinical finding has been attributed to deficits in contrast sensitivity (CS). The purpose of our study was to evaluate the CS in patients with clinical and genetic diagnosis of inherited retinal degeneration (IRD) and relatively preserved visual acuity.

View Article and Find Full Text PDF
Article Synopsis
  • - Whole genome sequencing (WGS) identified specific genetic variants linked to inherited retinal degeneration (IRD) in a Caucasian family, particularly focusing on mutations in the IFT88 gene.
  • - The study confirmed that the mutations p.Arg266* and p.Ala568Thr in IFT88 lead to abnormal ciliary structures, indicating a disruption in cellular function.
  • - Results showed that the p.Arg266* mutation causes significant loss of IFT88 mRNA due to nonsense-mediated decay, highlighting its role in retinal disease mechanisms.
View Article and Find Full Text PDF

Mutations in the genes necessary for the structure and function of vertebrate photoreceptor cells are associated with multiple forms of inherited retinal degeneration. Mutations in the gene encoding RHO (rhodopsin) are a common cause of autosomal dominant retinitis pigmentosa (adRP), with the Pro23His variant of RHO resulting in a misfolded protein that activates endoplasmic reticulum stress and the unfolded protein response. Stimulating macroautophagy/autophagy has been proposed as a strategy for clearing misfolded RHO and reducing photoreceptor death.

View Article and Find Full Text PDF

The International Society for Clinical Electrophysiology of Vision (ISCEV) standard for full-field electroretinography (ERG) describes a minimum procedure, but encourages more extensive testing. This ISCEV extended protocol describes an extension to the ERG standard, namely the photopic On-Off ERG, and outlines common clinical applications. A light stimulus duration of 150-200 ms is used in the presence of a rod-suppressing background to elicit cone-driven On- and Off-system ERG components.

View Article and Find Full Text PDF

Neurodegeneration is a central aspect of the early stages of diabetic retinopathy, the primary ocular complication associated with diabetes. While progress has been made to improve the vascular perturbations associated with diabetic retinopathy, there are still no treatment options to counteract the neuroretinal degeneration associated with diabetes. Our previous work suggested that the molecular chaperones α-crystallins could be involved in the pathophysiology of diabetic retinopathy; however, the role and regulation of α-crystallins remained unknown.

View Article and Find Full Text PDF

We report an unusual phenotype in a child with a clinical diagnosis of recessive Stargardt disease (STGD1) and two pathogenic variants in the ABCA4 gene. Typically, the diagnosis of early-onset STGD1 is challenging because children may present with a variety of fundus changes and a variable rate of progression. At the time of his initial visit, the 6-year-old boy presented with 20/200 OD (right eye) and 20/150 OS (left eye), symmetrical mild foveal atrophy without flecks on fundus exam, and foveal hypoautofluorescence surrounded by a homogeneous hyperautofluorescent background on wide-field fundus autofluorescence.

View Article and Find Full Text PDF

Purpose: Kinetic visual field testing is used to monitor disease course in retinal dystrophy clinical care and treatment response in treatment trials, which are increasingly recruiting children. This study investigates Goldmann visual field (GVF) changes in young children with mutation-proven retinal dystrophies as they age and with progression of the retinal degeneration.

Methods: Retrospective review of children ≤ 17 years old with a mutation-proven retinal dystrophy.

View Article and Find Full Text PDF

Autophagy is a lysosomal degradation pathway critical to preventing the accumulation of cytotoxic proteins. Deletion of the essential autophagy gene Atg5 from the rod photoreceptors of the retina (atg5 mouse) results in the accumulation of the phototransduction protein transducin and the degeneration of these neurons. The purpose of this study is to test the hypothesis that autophagic degradation of visual transduction proteins prevents retinal degeneration.

View Article and Find Full Text PDF

A PHP Error was encountered

Severity: Notice

Message: fwrite(): Write of 34 bytes failed with errno=28 No space left on device

Filename: drivers/Session_files_driver.php

Line Number: 272

Backtrace:

A PHP Error was encountered

Severity: Warning

Message: session_write_close(): Failed to write session data using user defined save handler. (session.save_path: /var/lib/php/sessions)

Filename: Unknown

Line Number: 0

Backtrace: