The pathophysiology and treatment of glaucoma: a review

Abstract

Importance: Glaucoma is a worldwide leading cause of irreversible vision loss. Because it may be asymptomatic until a relatively late stage, diagnosis is frequently delayed. A general understanding of the disease pathophysiology, diagnosis, and treatment may assist primary care physicians in referring high-risk patients for comprehensive ophthalmologic examination and in more actively participating in the care of patients affected by this condition.

Objective: To describe current evidence regarding the pathophysiology and treatment of open-angle glaucoma and angle-closure glaucoma.

Evidence review: A literature search was conducted using MEDLINE, the Cochrane Library, and manuscript references for studies published in English between January 2000 and September 2013 on the topics open-angle glaucoma and angle-closure glaucoma. From the 4334 abstracts screened, 210 articles were selected that contained information on pathophysiology and treatment with relevance to primary care physicians.

Findings: The glaucomas are a group of progressive optic neuropathies characterized by degeneration of retinal ganglion cells and resulting changes in the optic nerve head. Loss of ganglion cells is related to the level of intraocular pressure, but other factors may also play a role. Reduction of intraocular pressure is the only proven method to treat the disease. Although treatment is usually initiated with ocular hypotensive drops, laser trabeculoplasty and surgery may also be used to slow disease progression.

Conclusions and relevance: Primary care physicians can play an important role in the diagnosis of glaucoma by referring patients with positive family history or with suspicious optic nerve head findings for complete ophthalmologic examination. They can improve treatment outcomes by reinforcing the importance of medication adherence and persistence and by recognizing adverse reactions from glaucoma medications and surgeries.

Conflict of interest statement

Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Weinreb reported that he has worked as a consultant for Alcon, Allergan, Anakem, Aquesys, Bausch and Lomb, Carl Zeiss Meditec, Quark, Sensimed, Solx, Topcon and has received research support from National Eye Institute, Nidek, Genentech, Quark, and Topcon. Dr Aung reported that he has worked as a consultant for Alcon, Allergan, Bausch and Lomb, MSD, and Quark; has received research support from Alcon, Allergan, Aquesys, Carl Zeiss Meditec, Ellex, and Ocular Therapeutics; and has received lecture fees from Alcon, Allergan, Carl Zeiss Meditec, Ellex, Pfizer, and Santen. Dr Medeiros reported that he has received research support from the National Eye Institute, Alcon, Allergan, Merck, Carl-Zeiss Meditec, Heidelberg Engineering, Sensimed, and Reichert.

Figures

Figure 1

Aqueous Humor Drainage Pathways of Healthy and Glaucomatous Eyes

Figure 2. Schematic Illustration of Normal Anatomy and Neurodegenerative Changes Associated With Glaucomatous Optic Neuropathy

A, The optic disc is composed of neural, vascular, and connective tissues. The convergence of the axons of retinal ganglion (RG) cells at the optic disc creates the neuroretinal rim; the rim surrounds the cup, a central shallow depression in the optic disc. Retinal ganglion cell axons exit the eye through the lamina cribrosa (LC), forming the optic nerve, and travel to the left and right lateral geniculate nucleus, the thalamic relay nuclei for vision. B, Glaucomatous optic neuropathy involves damage and remodeling of the optic disc tissues and LC that lead to vision loss. With elevated intraocular pressure, the LC is posteriorly displaced and thinned, leading to deepening of the cup and narrowing of the rim. Distortions within the LC may initiate or contribute to the blockade of axonal transport of neurotrophic factors within the RG cell axons followed by apoptotic degeneration of the RG cells. Strain placed on this region also causes molecular and functional changes to the resident cell population in the optic nerve (eg, astrocytes, microglia), remodeling of the extracellular matrix, alterations of the microcirculation and to shrinkage and atrophy of target relay neurons in the lateral geniculate nucleus.

Figure 3. Normal, Glaucomatous, and Severe Glaucomatous Optic Nerve Heads and Visual Field Test Results

A, The pink area of neural tissue forms the neuroretinal rim, whereas the central empty space corresponds to the cup. B, Glaucomatous optic nerve showing loss of superior neural retinal rim (thinning) and excavation with enlargement of the cup. The arrowheads point to an associated retinal nerve fiber layer defect, which appears as a wedge-shaped dark area emanating from the optic nerve head. The superior neural losses correspond to the inferior defect (black scotoma) seen on the visual field. There is also a small retinal nerve fiber layer defect inferiorly, but the corresponding hemifield of the visual field remains within normal limits. C, More extensive neural tissue loss from glaucoma with severe neuroretinal rim loss, excavation, and enlargement of the cup. There is severe loss of visual field both in the superior as well as in the inferior hemifield.

Figure 4. Imaging Assessment of the Optic Nerve and Retinal Nerve Fiber Layer Using Spectral-Domain Optical Coherence Tomography

A, The arrowheads point to a retinal nerve fiber layer (RNFL) defect. B, Areas of thicker RNFL appear in yellow and red. Arrowheads point to the RNFL defect. A deviation map compares the RNFL thickness values with a normative database and highlights the defect. E, Arrowheads point to a visual field defect.

Figure 5. Gonioscopic Imaging and Optical Coherence Tomographic Imaging of Open-Angle and Closed-Angle

A lens with a prism is placed on the eye during gonioscopy, a process during which the examiner is able to examine the angle configuration and assess for the presence of angle closure. A, The arrowhead points to the lack of contact between the iris and angle. Image on the right shows the anterior segment captured by optical coherence tomography. The arrowheads point to visible trabecular meshwork. B, The angle is closed with the trabecular meshwork not visible due to apposition of the iris to the angle. In the right image, the arrowheads indicate apposition of the iris to the angle wall; the anterior chamber is shallow and the iris has a slightly convex configuration. This is more noticeable in the region of the iris on the right.

Figure 6. Closed-Angle Glaucoma Treatment by Laser Peripheral Iridotomy

C, Arrowhead points to the full-thickness hole in the iris.