INTRODUCTION

THE RETINA

It is a thin and sensitive membrane with an extremely complex internal structure, composed of ten layers each with specialized functions. In the first layers there are the light-sensitive cells, the photoreceptors. There are photoreceptors sensitive to light and others sensitive to different colors. Each photoreceptor reads a point in the image (brightness, color, or both) and generates electrical impulses that it transmits to the next layers, where these are encoded for transmission through the optic nerve. The distribution of photoreceptors is not uniform. They have the maximum concentration in the central part of the retina, called the macula; as you move towards the periphery of the retina, the density of the photoreceptors decreases and they are more distant from each other. There is a precise reason for this: the macula is used for distinct vision and for reading, the periphery (the “tail of the eye”) is more sensitive to things in motion. To function and feed the retina must be adherent, i.e. attached at all points to the pigment epithelium (which is the layer of cells immediately below). There is no "glue" at the base of the retinal adhesion but a mechanism of aspiration by the pigment epithelium, by which it is "sucked" towards the wall.

 THE VITREOUS

The vitreous (also called vitreous body, or vitreous gel) is a transparent, gelatinous tissue inside the eye, constituting 2/3 of the entire volume. It is composed 99% of water and 1% of collagen and hyaluronate fibrils that constitute its "scaffold".

The network of collagen fibrils forms a solid structure that is supported by the hyaluronic acid, creating the actual vitreous morphology. Comparing the vitreous to a wet sponge, the fibrous component is the sponge itself in whose interior spaces the watery part is trapped. The result is a compact and perfectly transparent gelatin. Over time, however, this balance tends to alter and thickening and gaps can form, resulting in the loss of perfect transparency. Moving bodies can thus begin to appear in the visual field, particularly visible in full brightness and/or on a light background. Thanks to its high viscosity, the vitreous has the purpose of cushioning ocular traumas, protecting the surrounding ocular tissues; its elasticity allows the antero-posterior displacements of the lens helping the process of accomodation.

VITREOUS DETACHMENT

The detachment of the vitreous occurs due to a sudden break in the balance between the fibrous and aqueous components, so that they separate from each other. If we take the sponge from the previous example, squeeze it and let it dry, it will shrink considerably. In the same way, the fibrous component of the vitreous, separating from the aqueous one, undergoes a marked reduction in volume. Since the volume of the eye does not change, the consequence of this phenomenon is the detachment of the vitreous fibrous component from the inner surface of the eye, i.e. from the retina. Vitreous detachment typically begins in the upper part of the eye and progresses downward. At the end of the process, the vitreous (it would be more correct to say: the fibrous component) remains adherent to the retina only in the front of the eye, where the vitreous-retinal connection is more tenacious. Although in most cases it runs without serious consequences, the detachment of the vitreous is a critical event for the eye, because it could produce retinal lesions: from the rupture of a small capillary (harmless) to the occurrence of retinal break, the first reason for the detachment of the retina itself.

Symptomatology

The symptoms of vitreous detachment are usually quite impressive: you suddenly notice numerous moving bodies accompanied by light sensations and flashes; the latter linked to the mechanical stress of the retina. It is difficult to ignore these symptoms: most people go to the emergency room or to an urgent specialist visit and this is of the utmost importance since, as we will see, an initial retinal detachment can still be repaired, at this stage, without resorting to surgery.

EXTRAMACULAR RETINAL ALTERATIONS

RETINAL BREAKS

It is important to note that a retinal break is not the same as a retinal detachment, although it is often the precursor. With rare exceptions, retinal breaks are always caused by vitreous and in most cases occur in coincidence with vitreous detachment; less often they accompany less important vitreous modifications.

There are various types of retinal breaks, which are distinguished from each other by shape, location and size. It ranges from retinal holes (round), to horseshoe tears (from the characteristic U-shape) to giant breaks or lacerations, which affect entire sectors of the retinal periphery. The symptoms of a retinal break are usually confused with those of the detachment of the vitreous that caused it; only the eye examination can resolve the doubt.

RETINAL DETACHMENT

Retinal detachment occurs because, passing through the retinal break or breaks, a certain amount of vitreous fluid insinuates itself below the retina and begins to dislodge it. A retinal detachment may remain circumscribed, but it typically tends to extend and affect larger and larger portions of the retina. At this point a dark curtain appears that extends from the periphery towards the central part of the visual field. If the detachment progresses to affect the macula, there is also a sharp decrease in vision. The rate of progression of retinal detachments is very variable: in some cases, we see total detachment in a few hours, in other cases the detachment tends to be self-limiting and to remain more circumscribed. This is influenced by numerous factors, including rest: for this reason, patients with retinal detachment are kept in bed waiting for surgery. Laser treatment is not applicable in case of retinal detachment: any "glue" requires that the parts to be glued are perfectly adherent, and this is not the case. Those who have a retinal detachment must, unfortunately, have surgery. There are several reasons why retinal detachment surgery should be performed with some urgency. First, the detachment of retina left to itself usually tends to extend, requiring a heavier treatment; second, the detached retina progressively loses vitality. Third, the detached retina tends to stiffen and wrinkle, making surgery difficult and reducing the chances of success.

Predisposing factors

There are several predisposing factors that can promote retinal detachment. Among the local (i.e. eye-related) factors there are the so-called "peripheral retinal degenerations", i.e. areas of localized abnormality that spontaneously arise in one or more peripheral sectors of the retina. Myopia, especially elevated myopia, is a condition in which the eyeball is elongated (rather than spherical) and shares numerous risk factors: thinner retina, vitreous alterations, higher incidence of degenerative areas. Still remaining among the local factors, it is well known how cataract surgery, however correctly performed, leads to a considerable increase in the incidence of retinal detachment, especially in young subjects. The higher incidence of retinal detachments in the warmer months has led us to believe that the heat, favoring dehydration, acts by inducing or precipitating the detachment of the vitreous. A very important role can be played by trauma, both direct and indirect. The first are direct blunt trauma on the eyeball (for example, a fist); the second include head trauma (for example, a headshot) and blows in general (a classic example is the one from road collision). These act by causing displacements of the vitreous within the eyeball, causing tractions on the retina at the line of action of the trauma.

Vitreous Hemorrhage

The vitreous hemorrhage consists of a blood shedding inside the posterior portion of the eyeball, or at the level of the vitreous. The blood of this jelly that fills the eye has important consequences from the visual point of view.

Epidemiology

The frequency of vitreous hemorrhage is proportional to its related diseases, so the most frequent causes are advanced diabetic retinopathy (31-54% of cases in the United States, depending on the studies), retinal breaks (11-44%), trauma (12-19%), posterior vitreous detachment (3.7-11.7%) and age-related macular degeneration (0.6-4.3%).

Symptomatology

When a vitreous hemorrhage occurs, the associated disorders depend on the extent of the hemorrhage: in the mildest cases there is a "smoky" vision, with the increase in the amount of blood, mobile bodies, black stripes, increasingly severe clouding until the uncertain perception of light are perceived.

Diagnosis

The diagnosis is made following an eye examination with eye fundus examination; in the less severe cases it is possible to glimpse the retina and the optic nerve and the vitreous structures, in the most severe cases neither the ophthalmologist nor the patient can see anything, so a ocular ultrasound must be used which represents the fundamental examination to understand the severity of the situation and allows you to set therapeutic options.

THERAPY OF EXTRAMACULAR RETINAL ALTERATIONS

RETINAL BREAKS THERAPY

Early diagnosis is of great importance, since a retinal break without detachment lends itself to an outpatient treatment with the laser that can prevent surgery.

The principle of laser treatment of a retinal break is to form a barrier around it, isolating it from the rest of the retina. By means of the laser, a series of close "spots" are produced that are nothing but small burns of the retina, the pigmented epithelium, and the underlying choroid. The spots are practiced as to draw a barrier of two, three and sometimes four rows around the retinal break. In the days following the treatment, these microscopic burns give rise to a scarring which represents a permanent "glue" and constitutes a definitive barrier around the retinal break. In practice, the laser treatment of retinal tears is an extremely simple outpatient procedure: as in the eye examination, the patient is placed in front of the instrument, drops are instilled for surface anesthesia (more than sufficient for the purpose) and a particular contact lens is applied to the eye. When treatment begins, the patient perceives brief flashes of blue-green color (if the laser is visible light) each of which corresponds to a spot on the retina. Treatment is usually not painful.

PREVENTIVE THERAPY OF RETINAL DETACHMENT

Prevention of retinal detachment is based on attenuation or elimination of predisposing factors. The retinal degenerations can be surrounded by a laser barrier, following the same principle used in the treatment of simple retinal breaks: isolate the dangerous area. There is a wide debate about the appropriateness of such treatment in relation to the possible side effects, and it is not uncommon to find conflicting opinions among the various specialists: the result is a confused and disoriented patient. The state of things can be summarized in the following points: not all degenerative areas are equally dangerous, some are not at all, others are proportional to their extent and others are dangerous. The potential danger of a degenerative area also depends on the context in which it is inserted: high myopia, presence of cataracts (which may require surgery), presence of vitreous detachment, age and habits of the patient and so on. Laser treatment can have negative effects, essentially related to the overheating of the vitreous. It is mainly a question of balancing between positive and negative effects, a balance that also weighs on the previous experiences and beliefs of the operator. It should be borne in mind that many degenerative areas tend to spontaneous healing, which can help explain different opinions over time. Many people wonder if correcting myopia does not have a preventive effect towards retinal detachment. The answer is unfortunately negative, since laser treatment (PRK or Lasik) corrects the curvature of the cornea, adapting it to the longer bulb, but does not change the internal condition of the eyeball. Absolutely counterproductive is, from this point of view, the removal or replacement of the crystalline lens that some specialists practice for the treatment of high myopia: it is equivalent to cataract surgery and exposes the patient to the relative risks, already mentioned above. A series of hygiene and behavioral rules can limit the action of general predisposing factors. People who have an established predisposition for retinal detachment (for example, potentially dangerous retinal degenerations) should avoid exposure to heat in the hottest periods, supplementing their diet with water and mineral salts, and should avoid suffering trauma or blow to the skull: this is the case for many athletes (head shots, dives).

SURGICAL THERAPY OF RETINAL DETACHMENT

There are basically two techniques for the surgical treatment of retinal detachment: the "ab-externo" technique, also called episcleral, and the "ab-interno" technique, called vitrectomy.

Episcleral surgery

The term "episcleral" means "above the sclera", in other words above that thick white membrane that constitutes the outer shell; it is the classic intervention for retinal detachment, developed (with numerous variants) for several decades but still current. The principle of this surgery is to resolve the detachment by pushing the wall of the eye towards the detached retina, to close the retinal breaks and neutralize the vitreous tractions. In practice, suitable implants of biocompatible materials are sutured to the sclera in such a way as to be pushed towards the centre of the eye, deforming its wall and causing a sort of rigid and permanent imprint. At the same time, the subretinal fluid is released to the outside through a small hole made in the sclera itself. Once the retinal adhesion is obtained, it is consolidated through the application of cryogenic treatments, which have the same meaning as laser applications: to cause burns (in this case, from cold) that will stimulate the subsequent scarring, that is, welding.

The main advantages of episcleral surgery are its simplicity and the less trauma it induces on the retina and intraocular structures in general since it does not provide for entry into the eyeball. For this reason, it is still the technique of choice for the treatment of uncomplicated forms of retinal detachment. Among the disadvantages, we recall the myopia of the operated eye (on average 2-3 diopters) and the possibility of developing abnormalities of ocular motility, linked to silicone implants that can interfere with the normal activity of the muscles responsible for eye movements. Rejection of implanted material is very rare.

VITRECTOMY

The 1970s saw the progressive development of vitrectomy and intraocular surgery techniques. The principle is, in this case, to enter the eye through tiny holes with microsurgical instruments and to intervene directly on the retina and vitreous. There are pincers, scissors, spatulas, cannulas, and optical fibers able to pass through a hole of 1 mm in diameter. The term "vitrectomy" indicates the removal of the vitreous, which in fact is only one of the steps in this type of intervention; however, its use to indicate the entire procedure is widespread. Vitrectomy successfully addresses complicated forms of retinal detachment: long-standing retinal detachments, forms accompanied by intraocular hemorrhagic effusion, forms accompanied by fibrous epiretinal membranes (as in diabetic retinopathy) and macular pucker and so on. There are many cases in which it is associated with episcleral surgery. The main disadvantage is represented by the greater trauma to the internal structures of the eye; manipulated directly and dazzled, the retina - which is still a very delicate nerve tissue - often shows signs of post-operative suffering and resumes functioning more slowly. In addition, vitrectomy can promote the development of cataract. The greater complexity and the need for sophisticated equipment means that it can only be carried out in highly qualified centres. Both ab-external and ab-internal techniques have advantages and disadvantages. These are different and complementary procedures, each with its own indications.

VITREOUS HEMORRAGE TREATMENT

Therapy depends on the cause and extent of the hemorrhage. In milder cases it can wait, usually up to a month, for the vitreous to clear spontaneously. If this does not happen or in the presence of tractions that cause lifts of the retina, surgical therapy must be used, represented by the vitrectomy with correction of the triggering causes.

MACULAR RETINAL ALTERATIONS

INTRODUCTION

Surgically treatable macular diseases are mainly represented by those forms of alteration of the macular region caused by mechanical phenomena. At the level of this region of the retina it is possible to form membranes at the area located in contact with the vitreous body. The vitreous body is bounded by an outer film called the cortical vitreous. In correspondence of the macula there is a region in which due to specific anatomical particularities it is possible the formation of thin abnormal membranes originated sometimes from residues of the vitreous cortex, sometimes from the same retina. These membranes, called "epiretinal", contract relations with the macular retina, adhering to the internal retina. If the cells that make up the membranes are not contractible and therefore, they do not tend to exert traction on the points of contact, the visual disturbances caused by the epiretinal membranes are moderate. The disturbances in these cases are generally limited to an image distortion, due to a modest wrinkling of the macular region subject to traction by the membrane (figs. 2, 3). If, on the other hand, the tractions are more marked (fig. 4), the retinal tissue suffers due to the strong deformation caused by the membrane and the visual reduction becomes more marked, being able to hesitate in severe reductions of vision if not intervened surgically.

Diseases associated with macular epiretinal membrane

The main macular diseases related to the presence of epiretinal membranes are:

the macular pucker (which means "wrinkling") (figs. 2, 3, 4, 5), characterized by the presence of an epiretinal membrane attached to the macular and contracted region (figs.), therefore associated with image distortion and, in the most severe cases, with the formation of blind spots in vision (scotomas). Surgery can lead to a resolution, not always total, of visual diseases, and especially to a reduction in image deformation.

the vitreomacular traction (figs. 6, 7, 8), in which the cortical vitreous remains attached to the central portion of the macula, called the fovea. The resulting traction over such a small area can cause a noticeable visual lowering.

The macular hole, characterized by the formation of an opening in the central part of the macular region, which mainly in eyes with high myopia can be associated with a posterior retinal detachment.

Epidemiology

Epiretinal membranes as a pathology were first described by Iwanoff in 1865. They may be associated with other eye problems, such as posterior vitreous detachment, retinal breaks, retinal detachment, inflammatory and vascular eye diseases, and vitreous hemorrhages. In most cases, however, they can also occur without association with other diseases, in which case they are called idiopathic membranes.

These membranes represent a rather frequent disease since large-scale studies in the past have shown them to be present in 7% of the population, with frequency increasing with advancing age, but with the advent of new diagnostic techniques (optical coherence tomography, OCT) in a 2016 study it was found that the prevalence in the population can reach 34.1%.

Evolution

The disorders caused by the disease depend on the characteristics of the membranes, such as thickness, position, and contractile capacity, as mentioned above. Initially they cause poor distubes, when they progress, they cause vague disorders and difficult to describe by the patient, the most frequent disturbance is the distortion of the images, followed then by blurry vision and reduction of visual acuity. In a 2016 study it was observed that in 5 years 29% of epiretinal membranes progress, 26% regress and 39% remain stable.

Diagnosis

A key role in the therapy of these diseases affecting the macular region is played by Optical Coherence Tomography (OCT), a new method of visualizing the macular region developed in the mid-1990s. This technique uses a low optical coherence light beam, not monochromatic, which "brushes" the macular region with a series of numerous parallel lines, the reflected light is captured by a detector that analyzes it and establishes through a computer the optical density of each retinal point, reconstructing a three-dimensional map of the area of tissue analyzed. The result is high-resolution 3D images of the macular region and the vitreous in front of it, which make it possible to visualize the shape of the membranes, the relationships they have with the retina and the damage they are causing. The OCT technique has undergone a considerable evolution over the years: initially a technology called "Time Domain" was used, that is, the analysis of the signal was carried out in the time domain, with a mirror that moved to follow the depth of the various points analyzed, then a method called "Spectral Domain" was developed in which there are no moving parts for which the precision of the analysis is increased, up to the last and most accurate system that is called "Swept Source", in which the precision is increased by the fact that the light source consists of a modulated laser, with a wavelength in the infrared field, allowing in addition to the production of extreme detail also a deeper penetration into the tissues, for which even the deepest structures are displayed.

DIABETIC RETINOPATHY

Diabetic retinopathy is a subtle and insidious disease, provoked by circulatory impairment caused by diabetes itself followed by reduced oxygenation of tissues. Non-proliferative diabetic retinopathy presents with small hemorrhages, deposits (called exudates), and other abnormalities of the retinal circulation. Fundamental, at this stage, is the fluorescein angiography, which allows to visualize in detail such anomalies, which must be treated with the laser. In the later stages, diabetic retinopathy becomes proliferative. This term means that membranes containing abnormal vessels form inside the eye. The membranes arise from the retina and optic nerve and grow as climbing plants, causing retinal detachments and massive hemorrhages.

TREATMENT OF MACULAR DISEASES

SURGERY

The most frequently used surgical technique is vitrectomy with removal of epiretinal membranes. In these cases it is a complex intervention because it involves an action on extremely delicate ocular structures, consider that the entire macular region is 1.5 mm large and consists of a tissue composed of high-density nerve cells with a critical disposition for the maintenance of visual acuity, so it must be used only after an accurate morphological and functional evaluation of the patient that allows to establish if the benefit/risk ratio is favorable.

Vitrectomy surgery has also proved to be of great importance in the treatment of the most severe cases of retinopathy that occur in diabetic patients. Diabetes, in fact, in the most advanced cases, which currently thanks to the improvement of preventive care have become increasingly rare, can hesitate in intraocular hemorrhages and in retinal detachments with tractions also at the macular level. The vitrectomy, removing the vitreous infusion of blood and the tractions that this exerts on the retina, allows the resolution of cases that in the past led to blindness.

ENZYMATIC VITREOLYSIS

In the case of localized tractions on the macula, the solution, in addition to surgical, in which the vitreous-macular traction and the vitreous are removed, can be simpler thanks to the introduction of new therapies that, in selected cases, resolve the traction on the retina. Enzymes are used that, injected from the eyeball can "digest" the adhesion point, separating the vitreous cortex from the retina and resolving traction without having to resort to more invasive surgeries.

Figure 1. Schematic representation of the eyeball and its component structures.

Figure 2. Photograph of the fundus of the eye of a myopic patient. The green line indicates the slice of which the section with OCT is made (figs. 4, 8 and 9).

Figure 3. Normal situation (right eye). Map in false colors that highlights the thickness of the macular retina, the warm colors indicate a greater thickness, the cold ones a smaller thickness. Scanning with Swept-Source OCT. The normal profile of the macular region (right) and the end portion of the optic nerve (left) can be observed. It is also evident the profile of the main blood vessels that depart from the optic nerve and surround part of the macula.

Figure 4. Macular Pucker. Section of the central macula with Swept-Source OCT. The formation of folds in the inner retina produced by the contracted membrane (at the top), partially separated from the retina, is noted, which cause a distortion of the images.

Figure 5. Macular pucker (left eye). Map in false colors that highlights the thickness of the macular retina. Scanning with Swept-Source OCT. The lower macular region is thickened due to the epiretinal membrane, retinal folds between macula and optic nerve are evident.

Figure 6. Macular pucker in a more advanced stage than in fig. 3. Map in false colors that highlights the thickness of the macular retina. Scanning with Swept-Source OCT. The macular region is all thickened due to the epiretinal membrane, there are evident retinal folds with radial distribution.

Figure 7. Macular pucker with a "pseudohole" appearance. At the top, image of the macular retina, at the bottom selective map of the innermost layer of the retina, scanning with Swept-Source OCT. The epiretinal tissue and the folds it determines at the level of the retina are clearly visible. Around the central part of the macula (fovea) there is a ring of tissue attached to the retina that gives the membrane a hole-like appearance.

Figure 8 Vitreomacular traction in myopic eye. Section with Swept-Source OCT. The profile of the eye is deformed due to the typical elongation of myopic eyes.

Figure 9. Vitreomacular traction in the non-myopic eye. Section of the central macula with Spectral Domain OCT. The central macular region undergoes the traction of the vitreous cortex, for which the formation of liquid collections is detected at the level of the central macular region, causing visual damage.