What is Glaucoma?

Glaucoma refers to a heterogeneous group of optic neuropathies characterized by the progressive degeneration of retinal ganglion cells (RGCs) and their axons, leading to visual field loss. The condition is commonly associated with elevated intraocular pressure (IOP), but it can also occur with normal or even low IOP, known as normal-tension glaucoma (NTG).

Pathophysiology

The optic nerve damage in glaucoma is primarily due to the mechanical compression of axons at the lamina cribrosa, combined with ischemic and excitotoxic mechanisms that lead to RGC apoptosis. The following factors play a critical role in the development of glaucoma:

• Intraocular Pressure (IOP): Elevated IOP is the most significant risk factor for glaucoma. It results from impaired aqueous humor outflow through the trabecular meshwork and Schlemm's canal. The buildup of aqueous humor increases pressure inside the eye, leading to mechanical stress and damage to the optic nerve.
• Vascular Dysregulation: Altered blood flow to the optic nerve head can lead to ischemia and contribute to glaucomatous optic neuropathy. This is particularly relevant in NTG, where IOP is not significantly elevated.
• Genetics: Genetic predisposition plays a critical role, with several genes such as MYOC (myocilin), OPTN (optineurin), and TBK1 (TANK-binding kinase 1) being implicated in the development of various forms of glaucoma.
• Neurodegeneration: Glaucoma shares similarities with other neurodegenerative diseases, where excitotoxicity, mitochondrial dysfunction, and oxidative stress contribute to the progressive loss of RGCs.

Types of Glaucoma

• Primary Open-Angle Glaucoma (POAG): The most common form, characterized by a wide and open anterior chamber angle. The exact cause is unknown, but it is associated with reduced aqueous humor outflow and increased IOP.
• Angle-Closure Glaucoma (ACG): Caused by the mechanical blockage of the trabecular meshwork by the iris, leading to a rapid increase in IOP. It can be acute, presenting as a medical emergency, or chronic.
• Normal-Tension Glaucoma (NTG): A subtype of POAG where optic nerve damage occurs despite normal IOP levels, often associated with vascular dysregulation and increased susceptibility of the optic nerve to damage.
• Secondary Glaucoma: Arises due to an underlying condition such as uveitis, trauma, or steroid use, leading to increased IOP and optic nerve damage.

Symptoms and Diagnosis

Glaucoma is often asymptomatic in the early stages, with vision loss occurring gradually. By the time symptoms such as peripheral vision loss or "tunnel vision" become noticeable, significant optic nerve damage may have already occurred. Acute angle-closure glaucoma can present with sudden onset of severe ocular pain, headache, nausea, vomiting, and blurred vision.

Diagnosis is based on a combination of clinical findings:

• Tonometry: Measurement of IOP using devices such as Goldmann applanation tonometry.
• Ophthalmoscopy: Evaluation of the optic nerve head for signs of glaucomatous damage, including increased cup-to-disc ratio and optic disc hemorrhage.
• Gonioscopy: Examination of the anterior chamber angle to differentiate between open and closed-angle glaucoma.
• Perimetry: Visual field testing to assess the extent of visual field loss.
• Optical Coherence Tomography (OCT): Imaging of the retinal nerve fiber layer (RNFL) to detect early glaucomatous changes.

Treatment

The primary goal of glaucoma treatment is to lower IOP to a level that prevents further optic nerve damage. Treatment options include:

• Pharmacologic Therapy: Topical medications such as prostaglandin analogs, beta-blockers, alpha agonists, and carbonic anhydrase inhibitors to reduce aqueous humor production or increase outflow.
• Laser Therapy: Procedures such as laser trabeculoplasty or iridotomy to improve aqueous outflow or create an alternate drainage pathway.
• Surgical Interventions: Trabeculectomy, glaucoma drainage devices, or minimally invasive glaucoma surgery (MIGS) to lower IOP in patients who do not respond to medical or laser therapy.
• Neuroprotective Strategies: Emerging therapies aimed at protecting RGCs and preserving vision, though these are still under investigation.

Early detection and consistent management are crucial to preventing irreversible vision loss in patients with glaucoma.