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Proceedings of the National Academy of... Feb 2020One of the major questions in human genetics is what percentage of individuals in the general population carry a disease-causing mutation. Based on publicly available...
One of the major questions in human genetics is what percentage of individuals in the general population carry a disease-causing mutation. Based on publicly available information on genotypes from six main world populations, we created a database including data on 276,921 sequence variants, present within 187 genes associated with autosomal recessive (AR) inherited retinal diseases (IRDs). Assessment of these variants revealed that 10,044 were categorized as disease-causing mutations. We developed an algorithm to compute the gene-specific prevalence of disease, as well as the mutational burden in healthy subjects. We found that the genetic prevalence of AR-IRDs corresponds approximately to 1 case in 1,380 individuals, with 5.5 million people expected to be affected worldwide. In addition, we calculated that unaffected carriers of mutations are numerous, ranging from 1 in 2.26 individuals in Europeans to 1 in 3.50 individuals in the Finnish population. Our analysis indicates that about 2.7 billion people worldwide (36% of the population) are healthy carriers of at least one mutation that can cause AR-IRD, a value that is probably the highest across any group of Mendelian conditions in humans.
Topics: Africa; Asia; Europe; Gene Frequency; Genes, Recessive; Heterozygote; Humans; Mutation; Pedigree; Prevalence; Retinal Diseases
PubMed: 31964843
DOI: 10.1073/pnas.1913179117 -
Clinical & Experimental Optometry May 2021Inherited retinal diseases (IRDs) comprise a heterogeneous group of genetic disorders affecting the retina. Caused by mutations in over 300 genes, IRDs result in visual... (Review)
Review
Inherited retinal diseases (IRDs) comprise a heterogeneous group of genetic disorders affecting the retina. Caused by mutations in over 300 genes, IRDs result in visual impairment due to dysfunction and degeneration of photoreceptors, retinal pigment epithelium, or the choroid. Important photoreceptor IRDs include retinitis pigmentosa and Leber congenital amaurosis. Macular dystrophies include Stargardt and Best disease. Currently, IRDs are largely incurable but the landscape of treatment options is rapidly changing for these diseases which, untreated, result in severe visual impairment and blindness.Advances in DNA delivery to the retina and improved genetic diagnosis of IRDs have led to a new era of research into gene therapy for these vision-threatening disorders. Gene therapy is a compelling approach due to the monogenic nature of most IRDs, with the retina being a favourable target for administering genetic vectors due to its immunoprivileged environment, direct visibility, and multiple methods to assess sensitivity and function. Generally, retinal gene therapy involves a subretinal or intravitreal injection of a viral vector, which infects target cells to deliver a therapeutic gene, or transgene. A gene augmentation strategy introduces a functioning copy of a gene to restore expression of a mutated gene, whereas a gene-editing strategy aims to directly edit and correct the mutation. Common delivery vectors include adeno-associated virus (AAV) and lentivirus.Voretigene neparvovec-rzyl (Luxturna) became the first FDA-approved direct gene therapy in December 2017, and the Australian TGA followed suit in August 2020. More are projected to follow, with clinical trials underway for many other IRDs.This review provides an overview of gene therapy for IRDs, including current progress and challenges. A companion article in this issue details target patient populations for IRD gene therapy, and how optometrists can assist in assessing individuals who may be eligible for current and future therapies.
Topics: Australia; Genetic Therapy; Humans; Leber Congenital Amaurosis; Retina; Retinal Diseases
PubMed: 33689657
DOI: 10.1080/08164622.2021.1880863 -
Eye (London, England) Jan 2015Familial exudative vitreoretinopathy (FEVR) is a rare inherited disorder of retinal angiogenesis. Cases can be autosomal dominant, autosomal recessive, or X-linked. FEVR... (Review)
Review
Familial exudative vitreoretinopathy (FEVR) is a rare inherited disorder of retinal angiogenesis. Cases can be autosomal dominant, autosomal recessive, or X-linked. FEVR patients have an avascular peripheral retina which, depending on the degree of ischaemia, causes the secondary complications of the disease. Expressivity may be asymmetric and is highly variable. Five genes have been identified that when mutated, cause FEVR; NDP (X-linked), FZD4 (autosomal dominant and recessive), LRP5 (autosomal dominant and recessive), TSPAN12 (autosomal dominant and recessive), and ZNF408 (autosomal dominant). Four of these genes have been shown to have a central role in Norrin/Frizzled4 signalling, suggesting a critical role for this pathway in retinal angiogenesis. In addition to the ocular features, LRP5 mutations can cause osteopenia and osteoporosis. All FEVR patients in whom molecular testing is not easily accessible should have dual energy X-ray absorptiometry (DEXA) scans to assess bone mineral density, as treatment can be initiated to reduce the risk of bone fractures.
Topics: DNA-Binding Proteins; Eye Diseases, Hereditary; Eye Proteins; Familial Exudative Vitreoretinopathies; Frizzled Receptors; Humans; Low Density Lipoprotein Receptor-Related Protein-5; Mutation; Nerve Tissue Proteins; Retinal Diseases; Tetraspanins; Transcription Factors; Vitreoretinopathy, Proliferative
PubMed: 25323851
DOI: 10.1038/eye.2014.70 -
Indian Journal of Ophthalmology Sep 2020Autoimmune retinopathy (AIR) refers to a group of rare autoimmune retinal degenerative diseases presumably caused by cross-reactivity of serum autoantibodies against... (Review)
Review
Autoimmune retinopathy (AIR) refers to a group of rare autoimmune retinal degenerative diseases presumably caused by cross-reactivity of serum autoantibodies against retinal antigens. The pathogenesis of AIR remains largely presumptive and there are a significant number of antiretinal antibodies that have been detected in association with AIR. The diagnosis of AIR is largely based on the demonstration of antiretinal antibodies in the serum along with suggestive clinical features and ancillary investigations. A high index of suspicion along with early diagnosis and treatment may play a critical role to lower the risk of irreversible immunological damage to the retinal cells in these patients. A multi-disciplinary approach for complete management and evaluation is helpful in such conditions. Various therapeutic options have been described for the treatment of AIR, though there is no consensus on standard treatment protocol.
Topics: Autoantibodies; Autoantigens; Autoimmune Diseases; Humans; Retina; Retinal Diseases
PubMed: 32823399
DOI: 10.4103/ijo.IJO_786_20 -
Progress in Retinal and Eye Research Mar 2019Myopia is a highly frequent ocular disorder worldwide and pathologic myopia is the 4th most common cause of irreversible blindness in developed countries. Pathologic... (Review)
Review
Myopia is a highly frequent ocular disorder worldwide and pathologic myopia is the 4th most common cause of irreversible blindness in developed countries. Pathologic myopia is especially common in East Asian countries. Ocular alterations associated with pathologic myopia, especially those involving the macular area-defined as myopic maculopathy-are the leading causes of vision loss in patients with pathologic myopia. High myopia is defined as the presence of a highly negative refractive error (>-6 to -8 diopters) in the context of eye elongation (26-26.5 mm). Although the terms high myopia and pathologic myopia are often used interchangeably, they do not refer to the same eye disease. The two key factors driving the development of pathologic myopia are: 1) elongation of the axial length and 2) posterior staphyloma. The presence of posterior staphyloma, which is the most common finding in patients with pathologic myopia, is the key differentiating factor between high and pathologic myopia. The occurrence of staphyloma will, in most cases, eventually lead to other conditions such as atrophic, traction, or neovascular maculopathy. Posterior staphyloma is for instance, responsible for the differences between a myopic macular hole (MH)-with and without retinal detachment-and idiopathic MH. Posterior staphyloma typically induces retinal layer splitting, leading to foveoschisis in myopic MH, an important differentiating factor between myopic and emmetropic MH. Myopic maculopathy is a highly complex disease and current classification systems do not fully account for the numerous changes that occur in the macula of these patients. Therefore, a more comprehensive classification system is needed, for several important reasons. First, to more precisely define the disease stage to improve follow-up by enabling clinicians to more accurately monitor changes over time, which is essential given the progressive nature of this condition. Second, unification of the currently-available classification systems would establish standardized classification criteria that could be used to compare the findings from international multicentric studies. Finally, a more comprehensive classification system could help to improve our understanding of the genetic origins of this disease, which is clearly relevant given the interchangeable-but erroneous-use of the terms high and pathologic myopia in genetic research.
Topics: Choroidal Neovascularization; Humans; Myopia, Degenerative; Retinal Detachment; Retinal Diseases; Retinal Neovascularization; Tomography, Optical Coherence
PubMed: 30391362
DOI: 10.1016/j.preteyeres.2018.10.005 -
BioMed Research International 2015
Topics: Choroid; Diagnostic Techniques, Ophthalmological; Humans; Ophthalmologic Surgical Procedures; Retina; Retinal Diseases; Software
PubMed: 25705650
DOI: 10.1155/2015/193561 -
Indian Journal of Ophthalmology Jul 2022Inherited retinal diseases (IRDs) are a group of phenotypically diverse disorders with varied genetic mutations, which result in retinal degeneration leading to visual... (Review)
Review
Inherited retinal diseases (IRDs) are a group of phenotypically diverse disorders with varied genetic mutations, which result in retinal degeneration leading to visual impairment. When a patient presents to a clinician who is not an IRD expert, establishing a correct diagnosis can be challenging. The patient and the family members are often anxious about further vision loss. They are eager to know the prognosis and chance of further worsening of the vision. It is important for every eye specialist to educate himself/herself about the basics of IRD. It would help to familiarize oneself about how to approach a patient with an IRD. An early and accurate diagnosis can help predict the vision loss and also help the patient plan his/her education and choose appropriate career choices. An updated knowledge about the genetic mutations, mode of inheritance, and possible therapies would empower the eye specialist to help his/her patients. This article gives a broad plan of how to approach a patient with IRD with regards to characterization and diagnosis of the disorder, visual rehabilitation, and possible therapy.
Topics: Female; Humans; Male; Mutation; Retina; Retinal Degeneration
PubMed: 35791111
DOI: 10.4103/ijo.IJO_314_22 -
Romanian Journal of Ophthalmology 2020Retinal migraine is usually defined by transitory attacks of fully reversible monocular visual loss, mostly with aura. An accurate diagnostic can be completed based upon... (Review)
Review
Retinal migraine is usually defined by transitory attacks of fully reversible monocular visual loss, mostly with aura. An accurate diagnostic can be completed based upon the International Classification of Headache Disorders-2 (ICHD-2) criteria. In view of this, we summarized some clinical features, treatment principles, complications, prognosis and prophylaxis.
Topics: Disease Management; Humans; Migraine Disorders; Prognosis; Retinal Diseases; Retinal Vessels; Vision, Monocular
PubMed: 32685773
DOI: No ID Found -
Indian Journal of Dermatology,... 2019
Topics: Humans; Hyperpigmentation; Macula Lutea; Retinal Diseases; Vision Disorders
PubMed: 30516169
DOI: 10.4103/ijdvl.IJDVL_843_18 -
The Western Journal of Medicine Nov 1992Radiation therapy is effective against many cancerous and noncancerous disease processes. As with other therapeutics, side effects must be anticipated, recognized, and... (Review)
Review
Radiation therapy is effective against many cancerous and noncancerous disease processes. As with other therapeutics, side effects must be anticipated, recognized, and managed appropriately. Radiation retinopathy is a vision-threatening complication of ocular, orbital, periorbital, facial, nasopharyngeal, and cranial irradiation. Factors that appear important in the pathogenesis of radiation retinopathy include total radiation dosage, fraction size, concomitant chemotherapy, and preexisting vascular disorders. Clinical manifestations of the disorder include macular edema and nonproliferative and proliferative retinopathy, similar to changes seen in diabetic retinopathy. Argon laser photocoagulation has proved efficacious for managing macular edema and fibrovascular proliferation in some of these patients. Ongoing basic laboratory and clinical research efforts have led to a better understanding of the pathogenesis, natural history, and treatment response of radiation retinopathy. The ultimate goal of this knowledge is to improve the prevention, recognition, and management of this vision-threatening complication.
Topics: Fluorescein Angiography; Humans; Radiation Injuries; Radiotherapy; Retina; Retinal Diseases
PubMed: 1441494
DOI: No ID Found