Clearly defining glaucoma will help advance research findings

Investigators must reach consensus on diagnosis of glaucoma.

ByClive Migdal, MD, FRCS, FRCOphth

Clive Migdal

Glaucoma continues to be one of the most widely researched ophthalmologic disorders, and important new data are published regularly. Although these data add to the knowledge and understanding of this debilitating disease, the definition of glaucoma and its anatomic effects are inconsistently reported in the literature.

Investigators’ definitions of glaucoma varies in their research results but often may refer only to specific symptoms associated with the disease such as increased IOP. Without a common definition, researchers risk difficulties in the interpretation and understanding of their data.

Lack of a diagnosis also limits the ability to assess epidemiologic studies, carry out reliable meta-analyses, calculate prevalence estimates, and document the efficacy and safety of investigational treatments. Most critical, the lack of a definition for glaucoma contributes to the risk of late or misdiagnosis that can result in vision loss.

The current edition of the European Glaucoma Society Guidelines defines open-angle glaucoma as “chronic, progressive optic neuropathies that have in common characteristic morphological changes at the optic nerve head and retinal nerve fibre layer, in the absence of other ocular disease or congenital anomalies.” The definition further notes that these changes are associated with progressive retinal ganglion death and visual field loss.

The European Glaucoma Society definition has been modified to reflect ongoing research, most notably excluding IOP in the diagnosis.

There are also diagnoses of glaucoma based on biological and clinical presentations. The biological definition is glaucomatous optic neuropathy resulting from precise pathophysiologic alterations in the retinal ganglion cell axons, whereas clinically, the disease is described as progressive optic neuropathy with characteristic structural damage often seen in tandem with a particular type of field defect such as an arcuate scotoma.

Glaucomatous optic neuropathy is the final common pathway of a group of conditions that share common biological properties and clinical characteristics. Unlike other optic neuropathies, it develops via a cellular cascade of events resulting in apoptosis of the retinal ganglion cell. Mechanical effects, such as compression and posterior displacement of the lamina cribrosa, cause blockade of orthograde and retrograde axonal transportation, resulting in selective degeneration of the optic nerve fibers and eventual development of glaucomatous optic nerve damage.

Such damage is caused by a number of factors, either singly or in combination. These include elevated IOP, impaired microcirculation, altered immunity, and excitotoxicity.

IOP and individual risk

Although IOP is a leading risk factor associated with glaucoma damage, no concrete threshold for the onset of primary open-angle glaucoma has been established. Data from population-based analyses have indicated glaucoma-characteristic disc/field damage in patients with IOP readings in the normal range. Similarly, individuals with statistically high IOP measures are often not diagnosed with glaucoma, even after extensive long-term follow-up.

Although IOP is a leading risk factor associated with glaucoma damage, no concrete threshold for the onset of primary open-angle glaucoma has been established.

—Clive Migdal, MD, FRCS, FRCOphth

Although raised IOP is still an important diagnostic sign, these data suggest that diagnostic analysis should be as specific to the patient as possible in order to identify who is at risk for glaucomatous damage. IOP is a risk factor, but the level of pressure that causes glaucoma damage varies among patients, and therefore ophthalmologists should diagnose glaucoma accordingly.

Other important variables to consider include age, family history, gender, perfusion, and ischemia.

Proper diagnosis also includes monitoring the structural and functional changes commonly seen in patients with glaucoma.

Future directions

Although the diagnosis and treatment of glaucoma are limited by the lack of consensus regarding its definition, emerging research offers greater understanding of this condition.

There is still considerable research to be conducted on the diagnosis and treatment of glaucoma. Currently, most treatment approaches focus on lowering IOP, but as ophthalmologists learn more about the pathology of glaucoma, it will become possible to develop treatments to target other aspects of the disease through genetics, neuroprotection, or other evolving therapies.

Clive Migdal MD, FRCS, FRCOphth, is a consultant ophthalmologist and head of the Glaucoma Service at the Western Eye Hospital, London, England.