Elsevier

The Lancet

Volume 390, Issue 10108, 11–17 November 2017, Pages 2183-2193
The Lancet

Seminar
Glaucoma

https://doi.org/10.1016/S0140-6736(17)31469-1Get rights and content

Summary

Glaucoma is a heterogeneous group of diseases characterised by cupping of the optic nerve head and visual-field damage. It is the most frequent cause of irreversible blindness worldwide. Progression usually stops if the intraocular pressure is lowered by 30–50% from baseline. Its worldwide age-standardised prevalence in the population aged 40 years or older is about 3·5%. Chronic forms of glaucoma are painless and symptomatic visual-field defects occur late. Early detection by ophthalmological examination is mandatory. Risk factors for primary open-angle glaucoma—the most common form of glaucoma—include older age, elevated intraocular pressure, sub-Saharan African ethnic origin, positive family history, and high myopia. Older age, hyperopia, and east Asian ethnic origin are the main risk factors for primary angle-closure glaucoma. Glaucoma is diagnosed using ophthalmoscopy, tonometry, and perimetry. Treatment to lower intraocular pressure is based on topical drugs, laser therapy, and surgical intervention if other therapeutic modalities fail to prevent progression.

Introduction

The term glaucoma includes a panoply of diseases that differ in their cause, risk factors, demographics, symptoms, duration, treatment, and prognosis. Glaucoma has become the most frequent cause of irreversible blindness worldwide.1, 2, 3 From a pathophysiological and therapeutic point of view, intraocular pressure is the primary modifiable risk factor, since progression of glaucoma usually stops if this pressure is lowered by 30–50% from baseline. This association suggests that intraocular pressure in glaucoma is too high in relation to the pressure susceptibility of the optic nerve head, at which glaucomatous optic-nerve damage occurs.

The common feature for all forms of glaucoma is loss of retinal ganglion cells, thinning of the retinal nerve fibre layer, and cupping of the optic disc (figure 1; figure 2). According to the morphology of the anterior chamber angle, glaucoma can be divided into open-angle glaucoma and angle-closure glaucoma. The anterior chamber angle contains Schlemm's canal, which is located between the peripheral cornea and the peripheral iris; the aqueous humour leaves the eye through Schlemm's canal (figure 3). In many patients, intraocular pressure (as the most important risk factor for glaucoma) either is increased only slightly or is within the normal range, and the rise in pressure—if present at all—is usually painless. Since chronic glaucoma can progress unnoticed by the patient until central visual acuity and reading ability are affected late in the disease, early detection is important before subjective symptoms develop. In this Seminar, we aim to outline the epidemiology, pathophysiology, symptoms, diagnosis, and treatment of glaucoma, and we discuss potential future developments in this area.

Section snippets

Epidemiology

In 2010, of 32·4 million blind individuals worldwide, glaucoma was the cause of blindness in 2·1 million (6·5%) people.4 Glaucoma caused visual impairment—defined as visual acuity in the better eye between less than 6/18 and 3/60 or greater—in 4·2 million (2·2%) of 191 million visually impaired individuals worldwide.4 Because of the association with older age, the overall prevalence of glaucoma was lower in regions with younger populations than in high-income regions with relatively old

Anatomy and pathophysiology

Intraocular pressure (normal range 10–21 mm Hg) is regulated by a balance between secretion of aqueous humour by the ciliary body in the posterior chamber and drainage of aqueous humour from the anterior chamber angle, either through the trabecular meshwork and Schlemm's canal or via the uveoscleral outflow pathway through the iris root into the uveoscleral interface (figure 3). Increased intraocular pressure is due to a decreased outflow facility of aqueous humour.

In open-angle glaucoma, the

Risk factors

The main risk factors for both development and progression of glaucoma are older age,3, 43, 44, 45, 46 an intraocular pressure too high in relation to the pressure sensitivity of the optic nerve head,7, 47, 48, 49, 50, 51 ethnic background,44, 52 a positive family history for glaucoma, stage of disease, and high myopia.53, 54, 55 Findings of a randomised placebo-controlled trial showed that medical lowering of intraocular pressure resulted in preservation of visual field in patients with

Genetics

Based on findings of genome-wide association studies, primary open-angle glaucoma is associated with several genes: CDKN2B-AS1, CAV1 and CAV2, TMCO1, ABCA1, AFAP1, GAS7, TXNRD2, ATXN2, the chromosome 8q22 intergenic region, and SIX1 and SIX6.36, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89 In particular, myocilin, optineurin, and WDR36 are linked to adult glaucoma,77, 78, 79 CYP1B1 to glaucoma in children and younger adults,90 and LOXL1 to exfoliative glaucoma.80, 81, 91, 92 This

Screening

A large proportion (50–90%) of patients with glaucoma remain undiagnosed in developed, developing, and underdeveloped regions of the world.59, 99 Although screening for glaucoma in the entire population would be an option, it is not considered logistically feasible. Because of the fairly low prevalence of glaucoma (about 3·5% in individuals aged 40 years or older), and since diagnostic measures with sufficient precision are not yet available, general screening for glaucoma would result in an

Diagnosis

Because chronic forms of glaucoma are painless, measurable visual-field defects do not develop at an early stage of glaucoma, and defects generally do not occur at homonymous locations in both visual fields, self-detection of glaucoma by affected individuals usually occurs at a late stage of the disease. The mainstay of detection of glaucoma is examination of the optic nerve head and retinal nerve fibre layer.102, 103, 104, 105, 106 Glaucomatous changes of the optic nerve head include loss of

Open-angle glaucoma

The only proven and generally accepted treatment to reduce the risk of further progression of glaucomatous optic neuropathy is to lower intraocular pressure.49, 51, 115 Reduction of intraocular pressure is achieved by drug treatment, laser therapy, or surgery. The goal is to lower the intraocular pressure towards an individual target level at which further progression of glaucomatous optic nerve damage is unlikely. The target intraocular pressure for a particular eye is estimated based on the

Future developments

The noted growth in prevalence of cataract surgery and the increase in prevalence of axial myopia, in particular in Asia, might decrease the occurrence of angle-closure glaucoma in the future.125 Ongoing studies that investigate the benefits of iridotomy in patients with angle closure from east Asia will provide guidance on the efficacy of this treatment in these populations, in which angle-closure is fairly prevalent among adults.126

Topically applied ρ kinase inhibitors might become an

Search strategy and selection criteria

We searched the Cochrane library, MEDLINE, and Embase between January, 2000, and December, 2016, with the terms: “glaucoma”, “primary open-angle glaucoma”, “secondary open-angle glaucoma”, “angle-closure glaucoma”, “intraocular pressure”, “optical coherence tomography”, “perimetry”, “optic disc”, “optic nerve head”, “retinal nerve fiber layer”, “trabecular meshwork”, “glaucoma therapy”, and “glaucoma surgery”. We largely selected publications from the past 5 years, but we did not exclude

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