A closer look - Advances in glaucoma treatment and management

30 Oct 2019

Prof. Lai, Shiu-Ming Jimmy

Department of Ophthalmology,
The University of Hong Kong

Glaucoma affects more than 70 million people worldwide with approximately 10% being bilaterally blind, making it the leading cause of irreversible blindness in the world.1 In East Asia, it was the third leading cause of blindness in 2015.2 Glaucoma can remain asymptomatic until later stages, resulting in a high prevalence of undiagnosed glaucoma worldwide. During an interview, Prof. Lai, Shiu-Ming Jimmy from the Department of Ophthalmology, The University of Hong Kong, shared his insights on the etiology and the management of glaucoma.

What is glaucoma?

Glaucoma is a group of optic neuropathies characterized by progressive degeneration of retinal ganglion cells.3 These are central nervous system neurons that have their cell bodies in the retina and axons in the optic nerve.3 Degeneration of these nerves results in cupping, a characteristic appearance of the optic disc, and visual loss. The biological basis of glaucoma is poorly understood and the factors contributing to its progression have not been fully characterized.3

Glaucoma can be classified into two broad categories: Open-angle glaucoma (OAG) and angle-closure glaucoma (ACG).3 Although the majority of glaucoma cases are OAG, ACG is responsible for a higher number of patients with severe vision loss.4 Moreover, secondary glaucoma can result from trauma, certain medications such as corticosteroids, inflammation, tumor, or conditions like pigment dispersion or pseudo-exfoliation.5

Primary open-angle glaucoma (POAG)

Although the pathogenesis of glaucoma is not fully understood, the level of intraocular pressure (IOP) is principally related to the retinal ganglion cell death.6 The balance between secretion of aqueous humor by the ciliary body and its drainage through two independent pathways, the trabecular meshwork and uveoscleral outflow pathway, determines the IOP. In patients with OAG, there is an increased resistance to aqueous outflow through the trabecular meshwork leading to increased IOP.6

The risk of OAG is higher with an elevated IOP. IOP can cause mechanical stress and strain on the posterior structures of the eye, notably the lamina cribrosa and adjacent tissues. The sclera is perforated at the lamina where the optic nerve fibers (retinal ganglion cell axons) exit the eye.6 The lamina is the weakest point in the wall of the pressurized eye. Thus, IOP-induced stress and strain may result in compression, deformation, and remodeling of the lamina cribrosa with consequent mechanical axonal damage and disruption of axonal transport.6 Clinically this shows up as an increased cup-disk ratio (CDR).

POAG is more prevalent among patients with the known risk factors such as a family history of the disease, black race, high myopia, or advanced age.6 The primary care physicians should also be aware of the risk of developing glaucoma in patients being treated with systemic or topical corticosteroids.6

Primary angle-closure glaucoma (PACG)

The main feature distinguishing PACG from POAG is that the formation of an angle, the site of aqueous outflow in the eye, is obstructed by apposition of the iris, resulting in an anatomically closed angle (defined if at least 180° of the angle is occluded).4 Similar to POAG, PACG is predominantly an asymptomatic disease; individuals are often unaware of the disorder until advanced visual loss has occurred.4 In less than a third of the cases, patients may present with acute primary angle closure, a clinical condition characterized by marked conjunctival hyperemia, corneal edema, a mid-dilated unreactive pupil, a shallow anterior chamber, and very high IOP, usually greater than 30mmHg.4 Such patients may present with ocular pain, nausea, vomiting, and blurring of vision with halos noticed around lights.4

PACG is caused by the disorders of iris, lens, and retro-lenticular structures. Pupillary block is the most common mechanism of angle closure and is caused by the resistance to aqueous humor flow from the posterior to anterior chambers at the pupil.4 Aqueous humor accumulates behind the iris increasing its convexity causing angle closure. Additionally, plateau-like iris configuration may be responsible for a significant proportion of angle closure in Asian patients.4 PACG may also be caused by dynamic physiological factors, such as an increase in iris volume with pupil dilation and choroidal effusion. In addition, risk factors for angle closure include female sex, older age, and Chinese ethnicity.4

The goals of glaucoma management

The ultimate goal of glaucoma management is to preserve patients’ visual function and quality of life.7 The disease itself as well as the medical or surgical treatment can have an enormous impact on a patient’s quality of life. Even the mere diagnosis of a chronic, irreversible, potentially blinding disorder could trigger significant anxiety and adversely affect the patient’s sense of well-being and quality of life.7 Patients with POAG rarely present with visual symptoms, at least in the early course of the disease. Therefore, a better understanding of patient-reported QoL can improve patient-physician interaction and enhance treatment adherence by customizing treatment options based on individual patient profile, thus optimizing the long-term prognosis.7

Pharmacologic therapies for glaucoma

The standard first-line treatment for POAG includes eye drops that lower IOP (Figure 1).8 The eye drops are classified by the active ingredient chemical into five major classes, including prostaglandin analogues, beta-blockers, carbonic anhydrase inhibitors, cholinergic agonists, and alpha agonists.8 Among them, monotherapy with either prostaglandin analogues or twice daily dose beta-blockers is most commonly used. The prostaglandin analogues decrease IOP by reducing the outflow resistance, which results in increased aqueous humor flow through the uveoscleral pathway. On the other hand, beta-blockers reduce IOP by decreasing aqueous formation with a favorable ocular tolerability.8

If the monotherapy is not effective in controlling IOP, other drugs with different mechanisms of action can replace or be added in conjunction with beta-blockers or prostaglandin analogues.8 Commonly used second-line agents include alpha-agonists and topical carbonic anhydrase inhibitors. However, a major challenge faced with adding multiple types of drops is the patient compliance. Despite the existence of numerous treatments for glaucoma, there is currently no agent that effectively decreases a trabecular outflow. Currently, a new class of glaucoma medications, known as Rho kinase inhibitors, has emerged. Rho kinase inhibitors have been shown to increase the trabecular outflow by acting directly on the contractile tone of the trabecular meshwork.8


Laser therapies for glaucoma

At times, medical therapies are unsuccessful to reduce IOP to the target levels and some patients continue to experience the deterioration of optic nerve function despite receiving maximum medical therapy. Thus, argon laser trabeculoplasty was introduced as an effective treatment modality in OAG.8 Although the mechanism of trabeculoplasty is not completely understood, it is thought to be caused by the thermal energy directed towards the trabecular meshwork which causes focal scarring, thereby inducing inflammation. Subsequently, inflammation stimulates structural changes and improves outflow.8 The overall number of laser trabeculoplasty procedures and bilateral same-day laser treatments increased dramatically during the last decade due to the use of selective laser trabeculoplasty, which is considered a safer laser treatment today, without causing damaging effects to surrounding tissues.8

Surgery for glaucoma

In POAG, surgical management is indicated when there is inadequate IOP lowering or for those with progression of optic nerve or visual field damage despite medical and laser treatment.9 Trabeculectomy, either alone or in combination with lens extraction, is considered if the IOP remains too high despite laser and medical treatment, especially in late stages of POAG.9 Lens extraction is also performed when lens-related mechanisms predominate such as cataract-related vision loss. Finally, glaucoma drainage implants are considered in patients when trabeculectomy has failed to control IOP.9 Nowadays, minimally invasive glaucoma surgery (MIGS) for the treatment of glaucoma are currently gaining popularity among ophthalmologists and patients.9 In selected cases, they may be used as the primary treatment for POAG.

Message to the physicians

Glaucoma is becoming an increasingly important cause of blindness, and an early diagnosis and treatment can prevent the vision loss. Glaucoma diagnosis could be challenging in the presence of high myopia. The visual field defects caused by glaucoma and high myopia maybe similar and the clinicians must be aware of this. Therefore, primary care physicians should consider referring patients with glaucoma risk factors for a complete ophthalmologic examination. In addition, the evaluation of optic nerve by direct ophthalmoscopy may identify suspicious signs of optic nerve damage that should also prompt referral to an eye care specialist. Additionally, as glaucoma is a silent disease, the clinicians should consider enhancing patient awareness on glaucoma. It would help to diagnose the disease early and prevent blindness.


The glaucoma management has shown significant benefits in improving the IOP, visual fields, and decreasing the visual damage progression. Glaucoma is a life-long disease, thus minimizing disabilities among the patients with glaucoma remains a priority. Therefore, the ultimate goal of treating glaucoma patients is to maintain or improve their quality of life.

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