Glaucoma: Types, Causes, and Risk Factors

• Glaucoma is a group of ocular diseases causing progressive optic neuropathy.
• This leads to vision loss related to a specific pattern of visual field (VF) loss.
• Glaucoma is a chronic, progressive disease presenting with optic nerve damage, retinal nerve fiber layer defects, and subsequent VF loss.
• VF loss is significantly specific in glaucoma diagnosis.
• It is the second leading cause of bilateral blindness worldwide, with open-angle glaucoma being the most common type.
• Primary open-angle glaucoma is about 7 times more prevalent among African Americans.
• In African Americans, glaucoma begins approximately 10 years earlier compared to Caucasians.
• Older Latinos have similar risk of developing open-angle glaucoma as African Americans, particularly after age 60

Glaucoma Classifications

• Open-angle
• Closed-angle.
• Primary glaucoma is not related to another underlying condition.
• Secondary glaucoma results from another ocular or systemic disease, trauma, or drug use.
• Developmental glaucoma.

Open-Angle Glaucoma

• Secondary open-angle glaucoma can arise from inflammatory conditions.
• It can further arise from lens-induced issues, tumors, cysts, trauma, surgery, or iridoschisis.

Angle-Closure Glaucoma

• Pupillary block
• Plateau iris syndrome
• Malignant glaucoma (misdirection)
• Synechial
• Neovascularization (NV)
• Iridocorneal endothelial (ICE) syndrome
• Fuchs' endothelial dystrophy
• Posterior polymorphous corneal dystrophy
• Ciliary body swelling

Open-Angle Glaucoma Characteristics

• Optic nerve head (ONH) damage, loss of nerve fiber layer, and VF loss.
• Primarily affects adults and is generally bilateral but not symmetrical.
• Most patients with primary open-angle glaucoma have IOP > 21 mmHg.
• Ocular hypertension (OHT) patients have IOPs above 21 mmHg without ONH damage or vision loss.
• Normal (or low) tension glaucoma (NTG) patients have OAG with IOP below 21 mmHg.

Aqueous Humor

• It is produced by the nonpigmented ciliary epithelium of the ciliary processes.
• Production involves diffusion, ultrafiltration, and active secretion

Aqueous Humor Composition and Function

• Compared to plasma, it has 20x more ascorbate concentration.
• It has 200x less protein in order to maintain transparency of the AH.
• It also contains amino acids, lactate, and Cl(-) to maintain fluid balance.
• It nourishes the posterior cornea, anterior vitreous, lens, and trabecular meshwork (TM).
• It collects metabolic waste and clears inflammatory products.
• Serves to provide a clear media for light refraction.

Aqueous Outflow

• Trabecular outflow accounts for 80% of the drainage.
• Trabecular outflow includes the trabecular meshwork, Schlemm’s canal, collector channels, and episcleral venous system.
• Uveoscleral outflow accounts for 20%.
• AH reaches the ciliary muscle, flows across the sclera, through emissarial vessels into uveal vessels and vortex veins, and possibly ciliary processes.

Autonomic Nervous System Regulation

• The sympathetic nervous system regulates AH production through β (β1 and β2) and α (α1 and α2) receptors.
• The parasympathetic nervous system also regulates AH production through muscarinic receptors.

Aqueous Humor Production

• 80% by nonpigmented epithelium of ciliary processes of the ciliary body.
• Production decreases due to drugs, hypoxia, hypothermia.
• 20% depends on blood pressure in the ciliary body, plasma pressure, and IOP.
• Normal AH secretion is at a rate of 20 uL/min, with an equal amount drained.
• IOP usually ranges from 11-21 mmHg, with an average of 15 mmHg.
• Diurnal variation: IOP increases in the morning and decreases in the evening, with changes of about 5 mmHg.

Factors Influencing IOP

• Increased age
• Pupillary block
• TM block

Decreased Outflow Resistance

• Accommodation
• Drugs like miotics, prostaglandins, sympathomimetics, adrenaline.

AH Formation Rate

• Uveitis affects the ciliary body, decreasing AH production.
• Persistent inflammation increases IOP due to cells blocking the TM.
• Acidosis and hyperosmolarity affect plasma, decreasing AH production.

Conditions Affecting Outflow

• Neovascularization of the angle from capillaries due to hypoxia, as seen in central vein occlusion and proliferative diabetic retinopathy.
• Inflammation, such as uveitis, can cause trabeculitis, disrupting the angle.
• Hyphema
• Pigment dispersion, where pigment dislodges and goes to the angle.
• Exfoliation, where zonules degenerate and accumulate.
• Angle recession due to trauma, leading to posterior insertion and increased IOP.
• Glaucomatocyclitic crisis (Schlossman Posner Syndrome), related to a mild form of uveitis with a sudden increase in IOP.

Additional IOP Influences

• High blood pressure may induce IOP but is not consistently proven.
• Resistance in outflow causes resistance in IOP, potentially leading to high IOP.
• IOP measurements can be artificially high or low depending on central corneal thickness.
• Supine position gives the highest IOP reading due to less gravity effect on aqueous circulation.

Increase in IOP

• Usually due to decreased aqueous outflow caused by resistance within the TM due to aging changes.
• Loss of TM endothelial cells.
• Increase in pigment accumulation/deposition within these endothelial cells.
• Thickening of trabecular lamellae.
• Thickening of the collagen can be expressed more in other people
• Thickening of scleral spur.
• Increased extracellular amyloid plaques in the anterior chamber angle.
• Loss of endothelial cells lining of Schlemm’s canal to form giant vacuoles.

Glaucoma Etiology

• Mechanical, compression of axons by the elevated IOP, causing axonal death.
• Vascular, reduced blood flow (ischemia) to the posterior pole, leading to axonal necrosis.
• Compromise of the ganglion cell axons at the level of the lamina cribosa leads to apoptosis.

Glaucomatous Damage

• Axonal necrosis leads to cupping.
• Loss of supporting glial tissue

Etiology of Primary Mechanism of Damage

• Incited by elevated IOP, causes compression and ischemia/hypoxia.
• Incited by ocular blood pressure (OPP and vascular regulation dependent), causes ischemia/hypoxia.
• Both mechanism leads to ischemia which in turn may provoke hypoxia.

Etiology of Secondary Mechanism of Damage

• Cellular damage by ischemia/hypoxia and compression to NFL and ONH affect cellular proteins that control expression of at least 2 genes.
• One that inhibits apoptosis (bcl-2) – underexpression.
• One that promotes cell death (bax) – overexpression.
• This result in GC death at the NFL and ONH.
• Causes an intracellular overload calcium overload and possible calcium dysregulation that activates nitric oxide synthase (NOS), causing excess levels of nitric oxide(NO) and finally death of GC.
• Increased levels of nitric oxide in ONH and NFL and high levels of glutamate in vitreous in patient with POAG.

IOP Lowering

• May remove the mechanical or the vascular insult to the GC axons.

Glaucoma is an eye disease that damages the optic nerve, leading to vision loss. Primary open-angle glaucoma is the most common type. Certain populations, like African Americans and older Latinos, have a higher risk.