Glaucoma Comprehensive Clinical Review

Introduction

Glaucoma represents a group of progressive optic neuropathies characterized by retinal ganglion cell loss, optic nerve head cupping, and corresponding visual field deficits. Increased intraocular pressure (IOP) is the most significant modifiable risk factor, but glaucomatous damage can occur even at normal pressures. As the second leading cause of irreversible blindness worldwide, glaucoma demands timely recognition, accurate classification, and individualized management to preserve vision and quality of life.

Epidemiology

• Global prevalence is estimated at 80 million individuals in 2020, projected to exceed 111 million by 2040.
• Over 50% of cases remain undiagnosed globally, particularly in low-resource settings.
• Prevalence rises with age: approximately 2% of those over 40 and up to 10% over age 80.
• Primary open-angle glaucoma (POAG) predominates in individuals of African descent, whereas primary angle-closure glaucoma (PACG) is more common in East Asian populations.
• Family history confers a 7–10× increased risk, highlighting genetic predisposition (MYOC, OPTN, TBK1 genes).

Classification

1. Primary Open-Angle Glaucoma (POAG)
2. Chronic, insidious elevation of IOP with open anterior chamber angles on gonioscopy.
3. Normal-Tension Glaucoma (NTG)
4. Optic nerve damage occurs despite IOP within normal range; implicated in vascular dysregulation.
5. Primary Angle-Closure Glaucoma (PACG)
6. Narrow or occludable angles leading to intermittent or sustained IOP spikes; subdivided into acute, subacute, and chronic forms.
7. Secondary Glaucomas
8. Result from ocular or systemic pathology (e.g., pigment dispersion, pseudoexfoliation, uveitis, neovascularization, steroid-induced).
9. Congenital and Developmental Glaucoma
10. Early-onset glaucomas from trabeculodysgenesis, presenting in infancy or childhood.

Pathophysiology

• Aqueous Humor Dynamics: Produced by the ciliary epithelium, aqueous humor flows from the posterior chamber through the pupil into the anterior chamber, exiting via the trabecular meshwork (conventional outflow) and uveoscleral pathways (unconventional outflow).
• Elevated IOP: Increased resistance at the trabecular meshwork is the primary mechanism in POAG; angle closure obstructs outflow in PACG.
• Optic Nerve Damage: Mechanical compression and ischemia at the lamina cribrosa impair axoplasmic flow, leading to ganglion cell apoptosis.
• Pressure-Independent Factors: Vascular dysregulation, oxidative stress, mitochondrial dysfunction, and inflammatory mediators contribute to disease progression, particularly in NTG.

Clinical Presentation

POAG

• Often asymptomatic until advanced stages.
• Progressive peripheral visual field loss (arcuate scotomas, nasal steps) detectable on automated perimetry.

PACG

• Acute Attack: Sudden ocular pain, headache, nausea, vomiting, halos around lights, mid-dilated nonreactive pupil, corneal edema, IOP often >40 mm Hg.
• Chronic Forms: Subtle symptoms, intermittent pressure spikes, gradual visual field constriction.

Secondary and Developmental Glaucoma

• Presentation varies by cause: pigment dispersion may show transillumination defects; neovascular glaucoma presents with neovascularization of the iris and angle.

Diagnosis

• IOP Measurement: Goldmann applanation tonometry is the gold standard; non-contact and rebound tonometry useful for screening.
• Gonioscopy: Assess anterior chamber angle anatomy, presence of synechiae or pigment.
• Optic Nerve Evaluation: Fundoscopic examination of cup-to-disc ratio, neuroretinal rim thinning, disc hemorrhages.
• Visual Field Testing: Automated perimetry to document defects and track progression.
• Optical Coherence Tomography (OCT): Quantitative assessment of retinal nerve fiber layer thickness and ganglion cell complex.
• Anterior Segment Imaging: Ultrasound biomicroscopy or anterior segment OCT for angle evaluation in suspected angle closure.

Management

Target IOP

• Individualized based on disease severity; typical goal is a 20–30% reduction from baseline IOP.

Medical Therapy

• First-Line Agents:
• Prostaglandin analogs (latanoprost, bimatoprost) to increase uveoscleral outflow.
• Timolol or other beta blockers to reduce aqueous production.
• Second-Line Agents:
• Alpha-agonists (brimonidine), carbonic anhydrase inhibitors (dorzolamide), rho-kinase inhibitors.
• Fixed Combinations: Enhance adherence by reducing the number of instillations.

Laser and Surgical Interventions

• Selective Laser Trabeculoplasty (SLT): Promotes trabecular outflow; repeatable treatment option.
• Laser Peripheral Iridotomy (LPI): Standard for PACG prevention and acute management.
• Trabeculectomy: Filtration surgery for uncontrolled IOP; risk of bleb-related complications.
• Minimally Invasive Glaucoma Surgery (MIGS): Micro-stents and shunts for mild-to-moderate POAG with favorable safety profiles.
• Tube Shunt Devices: Preferred in refractory or neovascular glaucoma.

Patient Education and Follow-Up

• Emphasize the asymptomatic nature and chronic course of glaucoma.
• Instruct patients on proper eye drop technique and adherence strategies (timers, reminders).
• Schedule follow-up intervals based on stability: every 3–4 months for advanced or progressing cases, every 6–12 months for stable patients.
• Monitor IOP, visual fields, and optic nerve OCT regularly.

Conclusion

Glaucoma requires a proactive, multidisciplinary approach to minimize vision loss. Advances in pharmacologic, laser, and surgical therapies allow tailored treatment plans. Early detection, consistent IOP control, and patient engagement are key to preserving visual function and quality of life in this lifelong disease.