Definition

Glaucoma remains one of the leading causes of irreversible blindness in the world. It is characterized by the gradual loss of retinal ganglion cells (RGC) and their axons, with anatomical repercussions on the entire optical path, from the lateral geniculate nucleus to the occipital cerebral cortex. The functional consequence of this is the gradual appearance, expansion, and merging of scotomatous areas (areas with reduced sensitivity to light) in the visual field, ultimately leading to the complete loss of vision.   

Epidemiology

IGlaucoma is a disease with a high social impact, being the most important cause of irreversible blindness in the world.  It has been estimated that about 60.5 million people worldwide were affected by glaucoma in 2010 and this number will rise to about 111.8 million in 2040.  In Italy about 800,000 people suffer from it, with a prevalence of about 2.5% in the ethnic Caucasian population over 40 years of age.

Prevention

In the primary, more widespread, form it is an asymptomatic disease: the patient does not realize that he is affected by it and complains extremely vague and absolutely non-specific symptoms (vision of halos, collision of objects). Therefore glaucoma has been called the “silent thief of sight” and today too many people are affected by it because of a lack of an early diagnosis (from 1/3 to half of patients with this disease do not know that they have it). Indeed, most of the time, glaucoma is diagnosed during eye examinations which are performed for other illnesses, and it is not rare for this to happen only once the patient is approaching blindness. Primary prevention of glaucoma prevention is not possible, because there are no externally influential disposable factors (except for some forms of secondary glaucoma). The pathways applicable are certainly those of a secondary prevention (recognition of risk factors in sensitive population groups) and a tertiary prevention (early identification of signs of worsening disease in those affected, in order to stem the evolution towards advanced forms)

Risk factors 

The cause of glaucoma is not yet known, and it pathogenesis has only partially been described. There are general and ocular risk factors for the development of glaucoma. Among the first ones, the most important is intraocular pressure (IOP), followed by reduced corneal thickness, pseudo-exfoliative and pigment syndrome, myopia and high hypermetropia. Other important risk factors include age, familiarity, ethnicity and geographical origin, genetic factors, and the use of drugs such as steroids.

The individual risk that a patient diagnosed with glaucoma will develop or worsen  loss of vision over the course of their life (including the risk of blindness) depends in large part of the seriousness of the condition at the time of diagnosis (importance of early diagnosis) and their age – in other words, their life expectancy. In this light, young patients with advanced glaucoma are the category most at risk of glaucoma-induced blindness. Another key element that needs to be taken into account in any risk assessment is the speed with which the disease progresses. 

The rate of progression can vary greatly from one patient to the next, and  even during unexpectedly early stages of the disease a glaucoma patient can experience a degree of vision loss that can affect their quality of life. Data from the literature provides important information on the speed of progression of the functional damage of glaucoma in the absence of  treatment. This data shows that while in most patients the field of view (median deviation, MD) worsens at a rate between  -1 and -2 dB/year (about 10 times faster than the normal loss of vision due to ageing), there is a significant subset of patients in which the disease worsens much faster, at a rate between -3 and -12 dB/year (which in the worst-case scenario is equivalent to the complete loss of vision within three years). These considerations have important implications for the clinical management of the disease in terms of both the choice of goals and  treatment options..

The classification of glaucoma 

In Caucasians, 80% of glaucoma cases refer to primary open-angle glaucoma, in which there is a gradual degeneration of the optic nerve combined with high ocular pressure, without macroscopic anatomic changes that can justify this increase in pressure.  A lower percentage of glaucoma can be classified as “normal pressure glaucoma”, in which there is a gradual degeneration of the optic nerve combined without high ocular pressure. Along with primary open-angle glaucoma, there are rarer forms known as primary closed-angle glaucoma, in which the increase in ocular pressure can be attributed to the partial  (chronic closed-angle glaucoma) or total (acute angle closure crisis) closure of the drainage passages for aqueous humour (a liquid that fills the anterior portion of the ocular globe). The term secondary glaucoma refers to all the forms of glaucoma in which a specific cause for the increase in ocular pressure can be identified. The many forms of secondary glaucoma include pseudoexfoliationglaucoma, pigmentary glaucoma, cortisone-induced glaucoma, post-traumatic glaucoma, and neovascular glaucoma (which is often associated with diabetes or vascular problems in the retina).

Ocular hypertension

Ocular hypertension occurs when there is an ocular pressure of more 21-22 mmHg in the absence of damage to the optic nerve or the field of vision. Can ocular hypertension lead to glaucoma? Individuals with high eye pressure have a higher chance of developing glaucoma. The decision of whether or not to begin treatment must be taken in consultation with one’s ophthalmologist on the basis of a full assessment of individual risk factors.

Diagnosing glaucoma

A glaucoma diagnosis is based on characteristic damage to the optic nerve and corresponding damage to the field of vision. In and of itself, high ocular pressure does not result in a glaucoma diagnosis, since there are forms of ocular hypertension that do not lead to glaucoma, and forms of glaucoma not associated with ocular hypertension.

The reference examination for the measurement of intraocular pressure is Goldmann Tonometry. Other forms of tonometry (e. g. air puff tonometer) do not have the same accuracy and therefore cannot be considered as a substitute for applanation tonometry.

Along with an assessment of the optic nerve and the field of vision, which represents the cornerstone of a glaucoma diagnosis, there are many other exams that can identify the type of glaucoma (primary, secondary, open-angle, closed-angle, etc.). These includegonioscopy,whose goal is to assess the anatomy of the iridocorneal angle, where the drainage passages for intraocular fluids (aqueous humour) are located. 

Pachymetry, i. e. the measurement of the central thickness of the cornea, is also very useful for a correct clinical framing of patients.The in-depth study of the optic nerve uses continuously evolving imaging techniques, such as Optical Consistency Tomography (OCT). These allow a computerized anatomical analysis of the optic nerve and the layer of nerve fibres that compose it. Recently, blood flow analysis at the head level of the optic nerve was also made possible thanks to the introduction of Angio-OCT.

Computerized examination of visual field instead measures the function of the optic nerve. The reference examination is the white on white perimeter able to detect the scotomatous areas, i. e. with reduced retinal sensitivity, corresponding to the damage of the optic nerve caused by the disease.

The evolution of perimeter evolution is represented by Fundus Automated Perimetry, able to integrate the imaging of the retina with automatic perimetry, allowing an accurate correlation between functional data and anatomical evidence.

Monitoring of the disease

Glaucoma is monitored through periodical optical examinations that include a direct examination of the aspect of the optic nerve, the measurement of optical pressure (tonometry), the carrying out of computerized examinations for the study of the optic nerve and the nerve fibres that constitute it (OCT) and an examination of the field of vision. The frequency of visits and other exams can vary greatly according to individual needs. We recommend at least 6 computerized analyses of the field of vision in the first 2 years following diagnosis, in order to assess the rate at which the disease is advancing in the patient, which is useful information for treatment and prognosis purposes.

Glaucoma treatment

Generally speaking, the goal of glaucoma treatment is to preserve the patient’s vision and their quality of life at a sustainable cost. The fundamental question that arises every time is decided to start hypotonizing therapy is how much IOP should be reduced, i. e. what IOP values should be achieved to prevent further damage to the optic nerve. Hence the concept of target IOP, i. e. the maximum value of IOP that is believed to reduce or slow down the progression of glaucomatous disease. In particular, the target IOP depends on: stage of the disease (the more advanced the diagnosis damage, the lower the target IOP should be), the value of IOP before the start of treatment (the lower this value is, the lower the target IOP should be), the rate of progression observed during follow-up, the age and life expectancy of the patient (youngest patients require a lower target IOP), the presence of other risk factors). Both in Europe and the United States, the first therapeutic choice for the treatment of glaucoma is of medical nature. The different guidelines suggest to start therapy with the prescription of a monotherapy which, in case it is not effective, must be changed with another monotherapy before adding other active principles. If this is necessary, it is always recommended to reduce the number of daily treatments using fixed combinations.

Medical therapy uses numerous active ingredients that, used alone or in association with each other, can reduce IOP, through the production of aqueous humor within the eye (beta-blockers, alpha-agonists, carbonic anhydrase inhibitors) through the promotion their outflow (prostaglandinic analogues, pilocarpine).

If the target IOP is not yet reached, parachirurgical treatments such as laser trabeculoplasty,when possible due to the iridocorneal angle structure, and surgical therapy can be considered.

However, this scheme can be subverted under special conditions. Laser trabeculoplasty can be considered the first therapeutic choice in selected cases when patient compliance and adherence to therapy do not guarantee the success of medical therapy (memory problems, difficulty with instillation of collyriums, intolerance to active ingredients).

To date, the choice of this treatment as a first therapeutic approach is also encouraged by the possibility of using lasers that are less invasive than argon, but equally effective, such as YAG lasers and micropulsed lasers, and is favoured by newly diagnosed patients for a lower impairment of the quality of life caused by chronic medical therapy.

Surgical therapy, such as all other glaucoma therapies, aims to reduce IOP by creating alternative outflow routes to intraocular fluids. The most common surgery is trabeculectomy, together with other techniques (for instance deep sclerectomy, viscocanalostomy, canaloplasty, etc.), each of which finds applications in certain patient groups. Drainage implants (such as Baerveldt, Ahmed, Molteno, etc.) are used in cases that are refractory to conventional surgical therapy, creating an artificial drainage route for intraocular fluids.

The European Guidelines suggest to consider filtering surgery by bypassing medical and laser therapy especially in patients with juvenile glaucoma, primary open angle glaucoma, pigmentary glaucoma and pseudoexfoliative glaucoma, especially if the diagnosis stage of the disease is already very advanced, IOP levels are very high and patient compliance is poor.

Thanks to the recent market introduction of new devices classified as minimally invasive glaucoma surgery (MIGS), the surgical choice is more easily considered already in the early stages of the disease. MIGS bridges the gap between medical therapy and more invasive surgical procedures such as trabeculectomy and draining implants. Unlike the latter, MIGS uses an ab-interior approach and have a low risk profile. In general, they share 5 important characteristics: an ab-interior approach, minimal surgical trauma, ability to reduce IOP, extremely high safety profile, rapid restoration of the initial clinical condition.