Observed genes

Polygenic score

Influential genes: CDKN2B-AS1,ARHGEF12,PLEKHA7

Variations in the CDKN2B-AS1 gene region have been linked to an increased risk of glaucoma.

Genetic variations in the ARHGEF12 gene have been associated with glaucoma susceptibility.

Variants in the PLEKHA7 gene have been strongly associated with primary open-angle glaucoma, the most common form of glaucoma.

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Overview

Glaucoma is a multifactorial optic degenerative neuropathy characterized by the loss of cells in the retina, which are responsible for the transmission of signals to the brain’s visual center. This condition consists of a group of diseases that may or may not be associated with concomitant IOP.

Major types of glaucoma include Primary Open-Angle Glaucoma (also called chronic glaucoma), Angle-Closure Glaucoma, and Congenital Glaucoma. All types are linked to the increased intraocular pressure. The fluid inside the eye, called aqueous humor, flows through a mesh-like channel. When this channel is blocked or if there is fluid overproduction, the buildup volume will raise the pressure inside the eye. 

Primary Open-Angle Glaucoma (POAG) is the most common type and usually related to  aging. It is often bilateral and associated with progressively increased intraocular pressure. This phenomenon will cause vascular compression and subsequently ischemia of the optic nerve. 

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Angle-Closure Glaucoma (ACG), on the other hand, appears with a sudden and sharp increase in intraocular pressure due to an obstruction of aqueous outflow in the eye. Primary ACG is due to anatomical variation of ocular structures, while Secondary ACG appears as a consequence of occlusion of the iridocorneal angle. It is important to notice that when acute, ACG is a medical emergency as it results in permanent vision loss if left untreated. 

Congenital glaucoma is mostly diagnosed within the first year of life and it is either Primary – sporadic or autosomal recessive – or Secondary – due to trauma, infection, or tumor.

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Prevalence & Risk factors

It is estimated that 57.5 million people worldwide are affected by Primary Open-Angle Glaucoma (POAG) and it is expected to linearly increase in the next few years to reach 111.8 million by 2040.^[1] The other types, angle-closure glaucoma and congenital glaucoma, are rather rare.

POAG is the most common and, while the primary cause is unclear, risk factors include age >40, European or African descent, diabetes mellitus, a family history of POAG, myopia, and chronic steroid therapy.

ACG is associated with anatomical variations predisposing to angle closure, advanced age, female sex, Asian ethnicity, eye trauma, rubeosis iridis (pathological neovascularization of the iris), and mydriasis, either drug-induced or due to stress response.

CG can be sporadic, with autosomal recessive pattern; or secondary due to trauma, infection, or tumors.  

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Genetics

Genes play an important role in the development of glaucoma, and research has identified several variants associated with an increased risk of glaucoma. However, genetics alone does not determine whether someone will develop glaucoma.  

Genetic studies have uncovered specific genes associated with different forms of glaucoma. Mutations in genes MYOC and OPTN are linked to primary open-angle glaucoma (POAG), a common subtype.

Increased intraocular pressure is also a significant contributor. High intraocular pressure puts a strain on the optic nerve and causes damage to it. Thus, the risk of each individual is determined by the interaction between genetic and other external factors.^[6-8]

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Congenital glaucoma (CG) is primarily caused by factors that often result from mutations in genes involved in the development of the outflow angle of the eye, such as CYP1B1 or LTBP2. It is usually transmitted by autosomal recessive inheritance (the child inherits one mutated copy of the gene from each parent). But the genetic basis in some familial cases remains unclear, and further research is needed.^[8]

Genetic testing allows us to detect whether you have the predisposition to develop this disease and therefore directs us to take steps toward prevention, monitoring, and possible treatment options. In Macromo, we use polygenic risk scores and causative evidence-based genetic variants for evaluation. The polygenic risk score (PRS) represents the total number of genetic variants that increase an individual's risk of developing a particular disease. All variants across their genome are summed and ranked according to their effect on disease development.

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Signs & Symptoms

Glaucoma, depending on the type, has an array of symptoms ranging from asymptomatic picture to progressive bilateral visual field loss in POAG. When considering ACG, it is important to distinguish acute form from chronic, as the acute form is a medical emergency. In acute ACG, there is a sudden onset of symptoms, often showing as an inflamed, reddened, and severely painful eye. It is associated with headaches, vomiting, nausea, and blurred vision. If left untreated, it leads to rapid and permanent vision loss. Chronic ACG resembles POAG by being asymptomatic in early stages, followed by gradual vision loss.

Congenital glaucoma exhibits specific signs and symptoms, these being buphthalmos (enlarged eyeball), corneal clouding, photophobia, and excessive tearing in newborns.

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Diagnosis

Diagnosis is made during an ophthalmological examination by tonometry measuring the intraocular pressure, by fundoscopy to observe the optic nerve, and by gonioscopy to differentiate from angle-closure glaucoma.

Visual field and acuity tests should be done as well to assess visual function.

Genetic testing and newborn screening are important when diagnosing congenital glaucoma.

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Therapy

Treatment is indicated in all patients, even if they are asymptomatic. The options include medical therapy, laser therapy, and open surgery.

The most common drugs used are prostaglandins to decrease IOP. In case pharmacological treatment fails, laser therapy is the next best option. It is gaining importance nowadays as it helps to lower IOP and facilitates drainage of aqueous humor.

Acute angle-closure glaucoma is an emergency and is treated with a combination of topical ophthalmic medications. Urgent surgery is considered when medical management fails.

In chronic ACG, therapy starts with laser surgery of the iris before moving to pharmacotherapy.

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Prevention

General screening for glaucoma is recommended to patients with diabetes mellitus, family history of glaucoma, or those of African descent aged 50 and over.

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Prognosis

If left untreated, glaucoma leads to permanent blindness. Even with treatment, 15% of the affected patients become blind in at least one eye within 20 years[3].

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Recommendations

• If you experience severe eye pain, reddening, and inflammation unilaterally, you should immediately visit an emergency room.
• Improve your health by exercising and controlling your diabetes.