Journal of Clinical Medicine

Editorial

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3 pages, 143 KiB

Open AccessEditorial

Novel Therapies for Inherited Retinal Dystrophies

by Christine Nichols Kay

J. Clin. Med. 2024, 13(23), 7358; https://doi.org/10.3390/jcm13237358 - 3 Dec 2024

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Abstract

With the approval of the first retinal gene therapy, voretigene neparvovec [...] Full article

(This article belongs to the Special Issue Clinical Diagnosis and Treatment of Retinal Degeneration)

Research

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10 pages, 627 KiB

Open AccessArticle

Microperimetry Sensitivity Correlates to Structural Macular Changes in Adolescents with Achromatopsia Unlike Other Visual Function Tests

by Eleonora Cosmo, Elisabetta Pilotto, Enrica Convento, Federico Parolini and Edoardo Midena

J. Clin. Med. 2024, 13(19), 5968; https://doi.org/10.3390/jcm13195968 - 8 Oct 2024

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Abstract

Objectives: Achromatopsia (ACHM) is a rare autosomal, recessively inherited disease that is characterized by cone dysfunction, for which several gene therapies are currently on trial. The aim of this study was to find correlations between the morphological macular changes identified using optical coherence [...] Read more.

Objectives: Achromatopsia (ACHM) is a rare autosomal, recessively inherited disease that is characterized by cone dysfunction, for which several gene therapies are currently on trial. The aim of this study was to find correlations between the morphological macular changes identified using optical coherence tomography (OCT) and some visual functional parameters. Visual acuity (VA), contrast sensitivity (CS), and macular sensitivity obtained by means of microperimetry were assessed. Methods: Adolescents with ACHM underwent macular microperimetry (S-MAIA device) in mesopic condition, macular OCT, best corrected visual acuity (BCVA), low luminance visual acuity (LLVA), near vision acuity (NVA), and CS measurement. Results: Eight patients (15 eyes) with ACHM were analyzed. The mean age was 17 ± 2.7 years, and genetic variants involved the CNGA3 gene (37.5%) and CNGB3 gene (62.5%). OCT staging significantly correlated with microperimetry sensitivity parameters, namely the sensitivity of the central foveal point (p = 0.0286) and of the first and second perifoveal rings (p = 0.0008 and p = 0.0014, respectively). No correlations were found between OCT staging and VA measurements, nor with CS value. Conclusions: Among the extensive evaluated visual function tests, only microperimetry sensitivity showed a correlation with morphological macular changes identified at OCT. Microperimetry sensitivity may thus represent a useful visual function tool in natural ACHM history studies considering the upcoming research on gene therapies for the treatment of ACHM. Full article

(This article belongs to the Special Issue Clinical Diagnosis and Treatment of Retinal Degeneration)

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11 pages, 4416 KiB

Open AccessArticle

Novel and Previously Known Mutations of the KCNV2 Gene Cause Various Variants of the Clinical Course of Cone Dystrophy with Supernormal Rod Response in Children

by Almaqdad Alsalloum, Ilya Mosin, Kristina Shefer, Natalia Mingaleva, Alexander Kim, Sofya Feoktistova, Boris Malyugin, Ernest Boiko, Shamil Sultanov, Olga Mityaeva and Pavel Volchkov

J. Clin. Med. 2024, 13(16), 4592; https://doi.org/10.3390/jcm13164592 - 6 Aug 2024

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Abstract

Background/Objectives: Cone dystrophy with supernormal rod response (CDSRR) is a rare autosomal recessive retinal disorder characterized by a delayed and markedly decreased photoreceptor response. In this article, we aim to describe the clinical course and associated molecular findings in children with cone [...] Read more.

Background/Objectives: Cone dystrophy with supernormal rod response (CDSRR) is a rare autosomal recessive retinal disorder characterized by a delayed and markedly decreased photoreceptor response. In this article, we aim to describe the clinical course and associated molecular findings in children with cone dystrophy with supernormal rod response associated with recessive mutations in the KCNV2 gene, which encodes a subunit (Kv8.2) of the voltage-gated potassium channel. Methods: The genetic testing of two patients included the next-generation sequencing of a retinal dystrophy panel and direct Sanger sequencing to confirm KCNV2 gene variants, in addition to an electroretinogram (ERG) and spectral domain optical coherence tomography (SD-OCT). Results: Cone dystrophy with supernormal rod response is associated with identified variants in the KCNV2 gene. The genetic analysis of the first case identified a compound heterozygous mutation in the KCNV2 gene, including a de novo nonsense duplication at cDNA position 1109, which led to the premature termination of the p.Lys371Ter codon in the second extracellular domain of the protein. Two patients showed changes in the full-field electroretinogram, especially in the first case, which demonstrated a close to supernormal total electroretinogram amplitude. This study increased the range of the KCNV2 mutation database, added an unreported de novo substitution pattern to KCNV2 gene variants, and linked it to the evaluated clinical studies. Conclusions: The initial clinical manifestations were varied, but both patients presented with hypermetropia and slight exotropia. The ERG findings are characteristic of KCNV2 mutations, and patients exhibited an increased b-wave latency in DA3.0 ERG (combined rod–cone response). Full article

(This article belongs to the Special Issue Clinical Diagnosis and Treatment of Retinal Degeneration)

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9 pages, 223 KiB

Open AccessArticle

Comparison of The Results of Sponsored Genetic Testing Panels for Inherited Retinal Diseases

by Yicheng K. Bao, Betty A. Situ, Margaret Runner, Andrew Moshfeghi and Hossein Ameri

J. Clin. Med. 2024, 13(11), 3118; https://doi.org/10.3390/jcm13113118 - 26 May 2024

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Abstract

Background/Objectives: Gene therapy’s emergence has made molecular diagnosis for inherited retinal diseases clinically significant. Free genetic testing panels have improved testing access in clinical practice, yet the interpretation of results, especially variants of unknown significance (VUS), remains challenging and requires expertise. This [...] Read more.

Background/Objectives: Gene therapy’s emergence has made molecular diagnosis for inherited retinal diseases clinically significant. Free genetic testing panels have improved testing access in clinical practice, yet the interpretation of results, especially variants of unknown significance (VUS), remains challenging and requires expertise. This study shares our experience in utilizing sponsored IRD panel tests by Invitae and Blueprint Genetics (BG), reporting their positivity rates, and comparing their reclassification of variants through amendments. Methods: This retrospective study analyzed genetic test reports from patients who underwent testing via Invitae or BG panels. A positive test was determined if there was a pathogenic mutation in an autosomal dominant gene, two pathogenic mutations in an autosomal recessive gene, or a pathogenic mutation in an X-linked gene in a male patient. Results: The testing positivity rates were 34.9% for Invitae (n = 109) and 42.1% for BG (n = 107). Invitae had more pathogenic variants per report (0.87 vs. 0.58 variants, p = 0.0038) and issued more amendments than BG (0.54 vs. 0.03 amendments; p < 0.01). Of the Invitae variant classification changes, 66.2% switched a VUS to benign. In the BG group, 75% of variant reclassifications changed a VUS to pathogenic. As a result of the Invitae amendments, 88% did not change the overall report result. Conclusions: While free-of-charge genetic testing panels offer valuable insights for diagnosing IRD, limitations such as low diagnostic yield and variant classification discrepancies persist between Invitae and BG. VUS should not be considered pathogenic in the clinical decision-making process. Careful interpretation of genetic testing is required. Full article

(This article belongs to the Special Issue Clinical Diagnosis and Treatment of Retinal Degeneration)

16 pages, 3109 KiB

Open AccessArticle

Retinitis Pigmentosa Masquerades: Case Series and Review of the Literature

by Abinaya Thenappan, Arjun Nanda, Chang Sup Lee and Sun Young Lee

J. Clin. Med. 2023, 12(17), 5620; https://doi.org/10.3390/jcm12175620 - 28 Aug 2023

Cited by 4 | Viewed by 3608

Abstract

Retinitis pigmentosa (RP) displays a broad range of phenotypic variations, often overlapping with acquired retinal diseases. Timely recognition and differentiation of RP masquerades is paramount due to the treatable nature of many such conditions. This review seeks to present examples of pseudo-RP cases [...] Read more.

Retinitis pigmentosa (RP) displays a broad range of phenotypic variations, often overlapping with acquired retinal diseases. Timely recognition and differentiation of RP masquerades is paramount due to the treatable nature of many such conditions. This review seeks to present examples of pseudo-RP cases and provide a comprehensive overview of RP masquerades. We first present two pseudo-RP cases, including comprehensive clinical histories and multimodal retinal imaging, to highlight the important role of accurate diagnoses that subsequently steered effective intervention. Subsequently, we conduct an in-depth review of RP masquerades to provide valuable insights into their key distinguishing features and management considerations. The recent approval of ocular gene therapy and the development of investigational gene-based treatments have brought genetic testing to the forefront for RP patients. However, it is important to note that genetic testing currently lacks utility as a screening tool for inherited retinal diseases (IRDs), including RP. The integrity of a precise clinical assessment remains indispensable for the diagnosis of both RP and RP masquerade conditions, thereby facilitating prompt intervention and appropriate management strategies. Full article

(This article belongs to the Special Issue Clinical Diagnosis and Treatment of Retinal Degeneration)

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10 pages, 213 KiB

Open AccessArticle

Current Assistive Devices Usage and Recommendations for a Future Artificial Vision Prosthesis among Patients with Severe Visual Impairment Due to Inherited Retinal Diseases

by Sophia Sidhu, Patrice J. Persad, Byron L. Lam, Kasey L. Zann and Ninel Z. Gregori

J. Clin. Med. 2023, 12(16), 5283; https://doi.org/10.3390/jcm12165283 - 14 Aug 2023

Cited by 1 | Viewed by 1580

Abstract

Patients with inherited retinal diseases (IRDs) utilize various adaptive techniques and devices designed to assist them with activities of daily living (ADLs). The purpose of this study was to assess the assistive devices used by patients with IRDs, the difficulties they face despite [...] Read more.

Patients with inherited retinal diseases (IRDs) utilize various adaptive techniques and devices designed to assist them with activities of daily living (ADLs). The purpose of this study was to assess the assistive devices used by patients with IRDs, the difficulties they face despite these devices, and their recommendations for a future visual prosthesis. In collaboration with blind patients, an online survey was developed and administered to adults with IRDs and visual acuities of 20/400 to no light perception in the better-seeing eye. We analyzed data from 121 survey respondents (aged 18 to >80 years). Five respondents were Argus II prosthesis recipients. The most commonly used aids were cellular phones/tablets for reading (63.6%) as well as a sighted guide (75.0%) and a cane (71.4%) for mobility. Despite current assistive devices, participants reported continued difficulty with ADLs. Improved navigation, reading, and facial recognition were ranked the most desirable features for future visual prostheses. Argus II recipients suggested technology with improved ability to recognize objects and obstacles, detect movement, and cut out busy backgrounds. These insights are valuable in shaping the design of future prosthetic devices tailored to the needs of IRD patients. Full article

(This article belongs to the Special Issue Clinical Diagnosis and Treatment of Retinal Degeneration)

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Review

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23 pages, 7315 KiB

Open AccessReview

Retinal Imaging Findings in Inherited Retinal Diseases

by Giulia Corradetti, Aditya Verma, Jasaman Tojjar, Louay Almidani, Deniz Oncel, Mehdi Emamverdi, Alec Bradley, Sophiana Lindenberg, Muneeswar Gupta Nittala and SriniVas R. Sadda

J. Clin. Med. 2024, 13(7), 2079; https://doi.org/10.3390/jcm13072079 - 3 Apr 2024

Cited by 1 | Viewed by 2446

Abstract

Inherited retinal diseases (IRDs) represent one of the major causes of progressive and irreversible vision loss in the working-age population. Over the last few decades, advances in retinal imaging have allowed for an improvement in the phenotypic characterization of this group of diseases [...] Read more.

Inherited retinal diseases (IRDs) represent one of the major causes of progressive and irreversible vision loss in the working-age population. Over the last few decades, advances in retinal imaging have allowed for an improvement in the phenotypic characterization of this group of diseases and have facilitated phenotype-to-genotype correlation studies. As a result, the number of clinical trials targeting IRDs has steadily increased, and commensurate to this, the need for novel reproducible outcome measures and endpoints has grown. This review aims to summarize and describe the clinical presentation, characteristic imaging findings, and imaging endpoint measures that are being used in clinical research on IRDs. For the purpose of this review, IRDs have been divided into four categories: (1) panretinal pigmentary retinopathies affecting rods or cones; (2) macular dystrophies; (3) stationary conditions; (4) hereditary vitreoretinopathies. Full article

(This article belongs to the Special Issue Clinical Diagnosis and Treatment of Retinal Degeneration)

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19 pages, 4746 KiB

Open AccessFeature PaperReview

Updates on Emerging Interventions for Autosomal Recessive ABCA4-Associated Stargardt Disease

by Liang Wang, Serena M. Shah, Simran Mangwani-Mordani and Ninel Z. Gregori

J. Clin. Med. 2023, 12(19), 6229; https://doi.org/10.3390/jcm12196229 - 27 Sep 2023

Cited by 4 | Viewed by 3335

Abstract

Autosomal recessive Stargardt disease (STGD1) is an inherited retinal degenerative disease associated with a mutated ATP-binding cassette, subfamily A, member 4 (ABCA4) gene. STGD1 is the most common form of juvenile macular degeneration with onset in late childhood to early or [...] Read more.

Autosomal recessive Stargardt disease (STGD1) is an inherited retinal degenerative disease associated with a mutated ATP-binding cassette, subfamily A, member 4 (ABCA4) gene. STGD1 is the most common form of juvenile macular degeneration with onset in late childhood to early or middle adulthood and causes progressive, irreversible visual impairment and blindness. No effective treatment is currently available. In the present article, we review the most recent updates in clinical trials targeting the management of STGD1, including gene therapy, small molecule therapy, and stem cell therapy. In gene therapy, dual adeno-associated virus and non-viral vectors have been successful in delivering the human ABCA4 gene in preclinical studies. For pharmaceutical therapies ALK-001, deuterated vitamin A shows promise with preliminary data for phase 2 trial, demonstrating a decreased atrophy growth rate after two years. Stem cell therapy using human pluripotent stem cell-derived retinal pigment epithelium cells demonstrated long-term safety three years after implantation and visual acuity improvements in the first two years after initiation of therapy. Many other treatment options have ongoing investigations and clinical trials. While multiple potential interventions have shown promise in attenuating disease progression, further exploration is necessary to demonstrate treatment safety and efficacy. Full article

(This article belongs to the Special Issue Clinical Diagnosis and Treatment of Retinal Degeneration)

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