Glaucoma and genetics
Glaucoma is a group of eye conditions characterized by increased intraocular pressure (IOP) that can lead to optic nerve damage and vision loss. The condition can be categorized into primary and secondary forms, where primary open-angle glaucoma (POAG) is the most common, affecting approximately 1% of the global population. Genetic factors play a significant role in glaucoma's development, with various genes associated with different types. For instance, primary congenital glaucoma (PCG) has autosomal recessive inheritance linked to specific genes, while POAG and juvenile open-angle glaucoma (JOAG) typically follow autosomal dominant patterns. Risk factors for glaucoma include ethnicity, family history, age, and various health conditions. Symptoms may range from unnoticed vision loss in early stages to more severe manifestations like tunnel vision. Early detection through routine screenings is crucial, as there is no cure for glaucoma, but treatment options such as eye drops, laser surgery, and possibly conventional surgery can help manage the condition and prevent vision loss.
Glaucoma and genetics
DEFINITION Glaucoma is a group of eye conditions, typically presenting with increased intraocular pressure (IOP) or buildup of aqueous humor (fluid in the space between the lens and the cornea) that cause diminished vision primarily as a result of optic nerve damage. In secondary glaucomas, elevated IOP is attributable to concurrent ocular conditions; in primary glaucomas, it is not. In primary open angle glaucoma (POAG), the corneal-iris angle is open but the trabecular meshwork drainage system is obstructed, inhibiting the efflux of aqueous humor. The corneal-iris angle is closed in primary closed angle glaucoma (PCAG), preventing access to the trabecular meshwork. Glaucoma is the consequence of a complex interplay of multiple genetic and environmental factors.
Risk Factors
The likelihood of glaucoma increases when the IOP climbs above the mid-twenties (mmHG). However, glaucomatous damage may occur in the absence of high IOP (low tension or normal tension glaucoma) or above-normal IOP may not result in glaucoma. Loss of neurons or abnormalities in the optic nerve is a better predictor of glaucoma than is IOP.
POAG affects 1 percent of the global population. The of glaucoma is positively associated with ethnicity and family history. People of African descent are more likely to develop POAG than are those of Caucasian origin; those of Asian origin have the highest risk of developing PCAG. Other risk factors include increasing age, abnormal blood pressure, heavy alcohol use, myopia, diabetes, corticosteroid use, and eye trauma or malformations.
Etiology and Genetics
Glaucoma is genetically heterogeneous, with late-onset forms having a more complex, basis. Numerous genetic locations have been linked with diverse types of glaucoma.
Open angle glaucoma is the most prevalent form of the disease, typically beginning in adulthood but sometimes present at birth (primary congenital glaucoma, or PCG) or developing in childhood (juvenile open angle glaucoma, or JOAG). PCG inheritance is primarily autosomal recessive and has been linked to two genes, CYP1B1 and LTBP2, and two loci, GLC3B at 1p36 and GLC3C at 14q24.3. Primarily autosomal dominance characterizes JOAG and POAG inheritance. Two loci have been linked with JOAG (9q22/GLC1J, 20p12/GLC1K); one with JOAG and POAG (1q23–q24/GLC1A); and several with POAG (2cen-q13/GLC1B, 2p16.3–p15/GLC1H, 3q21–q24/GLC1C, 5q22.1/GLC1G, 7q35–36/GLC1F, 8q23/GLC1D, 10p14–15/GLC1E, 15q11–q13/GLC1I). Defects in the myocilin gene (MYOC, 1q23–q24) appear to be a significant factor in causing increased IOP in JOAG and POAG. Optineurin (OPTN) variations have been linked with POAG and the rarer low tension forms of the disease. The WDR36 gene (formerly known as GLC1G) is thought to be a modifier gene that influences the severity of glaucoma.
Among the secondary glaucomas, the most common form is pseudoexfoliation syndrome, in which cells of the lens are deposited in the trabecular meshwork, obstructing drainage. Defects called single nucleotide polymorphisms (SNPs) in the lysil oxidase-like 1 (LOXL1 ) gene (15q24/G153D) are associated with the disorder. Pigmentary glaucoma is another “shedding” disorder (iris cells into aqueous humor), and defects at the GLC1F locus on chromosome 7q35–36 have been linked with the condition.
Several disorders that cause abnormalities in the anterior part of the eye are associated with glaucoma. Several loci and genes have been linked to a number of these conditions, collectively called anterior segment dysgenesis syndromes, including: B3GALTL (Peters plus); 4q25–26/RIEG1, PITX2 and 6p25/IRID1, FOXC1 (Axenfeld-Reiger, iridogoniodysgenesis); 11p13/PAX6, PAX6 (anirida, Axenfeld-Reiger); and 13q14/RIEG2 (Axenfeld-Reiger syndrome). Inheritance appears to be primarily autosomal dominant for all these conditions.
Symptoms
The early stages of POAG typically have no noticeable symptoms. As POAG progresses, small spots of diminished vision appear, followed by loss of peripheral vision that advances to tunnel vision in later stages of the disease. In contrast, the symptoms of PCAG may appear suddenly with blurred vision, seeing halos around lights, eye pain, nausea, headaches, and/or reddening of the eyes.
Screening and Diagnosis
Initial glaucoma screening typically includes tonometry to measure IOP, pachymetry to measure corneal thickness (thicker corneas may inflate IOP readings, while thinner corneas may deflate IOP readings), visual field testing to evaluate peripheral vision, and assessment of risk factors. More detailed diagnostic methods used include gonioscopy to determine drainage angle and imaging techniques to inspect the optic nerve for damage or abnormalities.
Treatment and Therapy
Glaucoma treatment usually begins with eye drops. Prostaglandin-like compounds (such as Lumigan), cholinergic agents (such as Pilopine), and epinephrine compounds (such as Propine) increase aqueous humor outflow; beta blockers (such as Betagan), carbonic anhydrase inhibitors (such as Trusopt) decrease aqueous humor production; alpha-a agonists (such as Lopidine) do both. Orally, carbonic anhydrase inhibitors, cannabinoids, and serotonin agonists are efficacious.
Laser surgery is usually the second line of treatment. Common procedures include trabeculoplasty, which opens the trabecular meshwork; iridotomy, in which a hole is made in the iris; and cycloablation, in which ciliary body oblation decreases fluid production. If laser surgery fails, then conventional surgical procedures such as trabeculectomy, in which a portion of the trabecular meshwork is removed, or the insertion of drainage implants may be used.
Prevention and Outcomes
People with a family history of glaucoma and who are over the age of forty-five should be tested for glaucoma at least once a year. Although glaucoma has no cure, keeping IOP down can prevent visual loss and blindness. Vigorous exercise, chronic head-down postures, drinking large amounts of fluid in a short time, and tight clothing around the neck can elevate IOP.
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