Definition

Glaucoma is a progressive chronic optic neuropathy in which morphological alterations characteristic of the optic nerve head and the retinal nerve fiber layer are documented in the absence of other ocular pathologies. Glaucoma involves the entire optic pathway, from the retinal ganglion cell to the visual cortex.

The pathogenesis of glaucoma is not well known. The main pathogenic theories are vascular and mechanical.

According to vascular theory, optic neuropathy is a consequence of an inability of the vessels of the optic nerve head to ensure a constant blood supply due to reduced blood flow resulting from increased intraocular pressure or other risk factors that interfere with local self-regulation.

According to mechanical theory, intraocular pressure causes stress on the posterior structures of the eye resulting in compression, deformation and remodeling of the cribriform plate with damage to the axons that make up the optic nerve that cross it and impairment of axonal transport of neurotrophic factors critical for the survival of retinal ganglion cells.

Glaucoma is one of the leading causes of irreversible blindness in the world.

It has been estimated that about 60 million people are affected by glaucoma worldwide, with a prevalence of 2.2%, and this number will increase to about 112 million by 2040. In Europe, 7.8 million people are affected by glaucoma and the prevalence is 2.5%. In Italy, about 800,000 people suffer from it, with a prevalence of about 2.5% in the Caucasian population over the age of 40.

Risk factors for the development of the disease can be divided into general and ocular. Among the first are advanced age, familiarity with glaucoma, ethnicity, diabetes mellitus, hypertension and systemic hypotension, vasospasm, migraine, topical or systemic steroid use.

Among the ocular risk factors, the most important is intraocular pressure. Other ocular risk factors are reduced corneal thickness,  pseudoexfoliation  and pigmentary syndrome, high myopia and hyperopia.

Symptomatology

In the primary, most widespread form, it is an asymptomatic disease: the patient does not notice that he is affected and complains of extremely vague and absolutely non-specific symptoms (vision of halos, collision of objects).
The pathology of glaucoma is therefore called “the silent thief of sight” and to date many people are affected by it due to a lack of early diagnosis (1/3 to half of affected patients do not know they have the disease).

The cause of glaucoma is not yet known and its pathogenesis has only been partially characterized.

There are ocular and general risk factors for the development of glaucoma; among the first the most important is intraocular pressure (IOP), followed by a reduced corneal thickness, pseudoexfoliation and pigmentary syndrome, myopia and high hyperopia.
Other important risk factors are represented by age, familiarity, ethnicity and geographical origin, genetic factors, intake of drugs such as steroids.

A further fundamental element to consider in estimating individual visual risk is the rapidity with which the disease progresses in the individual. The rate of progression can be very variable from patient to patient and, even in unexpectedly early stages of the disease, the glaucomatous patient may experience a decline in visual function that alters his quality of life.

Diagnosis

In most cases the diagnosis of glaucoma is made completely randomly during a visit made for other disorders, and it is not uncommon for this to happen when the situation is close to blindness.

Monitoring of the disease is carried out through periodic eye examinations that include direct examination of the appearance of the optic nerve, measurement of eye pressure (tonometry), computerized examinations for the study of the optic nerve and the nerve fibers that constitute it (OCT) and examination of the visual field.

The frequency of visits and other examinations can vary greatly depending on individual needs. It is recommended to perform at least 6 computerized visual field tests in the first 2 years from diagnosis to frame the speed with which the disease tends to progress in the individual patient, useful information for prognostic and therapeutic purposes.

The most frequent form of glaucoma in the Caucasian population is primary open-angle glaucoma, in which the progressive loss of nerve fibers leading to damage to the optic nerve and visual field is caused by an increase in intraocular pressure. There is also a more difficult clinical form to diagnose which is normal pressure glaucoma, characterized by the same clinical picture as primary open-angle glaucoma, but in the absence of high intraocular pressure values. Another form of glaucoma widespread especially in the Asian population is primary narrow-angle glaucoma, characterized by a reduction in the anatomical spaces that allow the physiological outflow of the aqueous humor (intraocular fluid that determines the pressure of the eye).

Secondary glaucomas are all those forms, both open-angle and narrow-angle, in which a precise cause responsible for the increase in intraocular pressure is identifiable. These include pseudoesfoliative glaucoma, pigmentary glaucoma, cortisone glaucoma, post-traumatic glaucoma and neovascular glaucoma (often associated with diabetes or retinal vascular problems).

Ocular hypertension affects those patients who have an increase in intraocular pressure without morphological or functional damage to the optic nerve. These patients have an increased risk of developing glaucoma and this risk increases in the presence of the other general and ocular factors mentioned above.

Therapy

The only evidence-based treatment strategy that can slow or stop the progression of glaucoma is to reduce intraocular pressure. 

The first therapeutic approach is generally medical, based on eye drops with different hypnotic active ingredients, able to reduce the production of aqueous humor (beta-blockers, alpha-agonists, inhibitors of carbonic anhydrase) or to promote outflow (prostaglandin analogues, pilocarpine).

Medical therapy is not without side effects, both systemic and local. The latter are linked not only to the active ingredients, but also to the preservatives contained in eye drops. Symptoms such as irritation, itching, burning, foreign body sense, photophobia, dry eye, fluctuating vision, are attributable to alterations of the ocular surface present in about 60% of patients with glaucoma, resulting in reduced compliance and adherence to treatment.

If medical therapy is insufficient to ensure good control of the pressure and progression of the disease, or if there is widespread intolerance to the different eye drops, other para-surgical strategies, such as laser trabeculoplasty, or surgical should be considered.

Surgical therapy aims to reduce intraocular pressure by creating alternative outflow pathways to intraocular fluids or by implementing physiological outflow pathways. Surgical techniques are divided into filtering and non-filtering, and the choice depends on the type of patient. Among the filtering techniques, the most common intervention is Trabeculectomy. In cases refractory to conventional surgical therapy, drainage implants that provide for the creation of an artificial drainage pathway for intraocular fluids are applicable.

Recently, new devices classified as “minimally invasive glaucoma surgery” (MIGS) have been placed on the market, thanks to which the surgical choice is more easily considered already in the early stages of the disease, having a low risk profile.