The Retinitis Pigmentosa (RP) is a clinically and genetically heterogeneous group of retinal degenerations inherited from a person’s parents of primary incidence with autosomal dominant and recessive transmission modality, X-\linked and mitochondrial. It was described for the first time by Donders in 1857. The definition is per se misleading since it refers to an inflammatory process that does not play a primary role in this pathology. It is a progressive disorder that entails the death of the rods followed by the loss of the cones; however, the loss of both types of photoreceptors can also occur simultaneously.
The retinitis pigmentosa occurs less frequently as part of syndromes affecting other organs and tissues of the body. These forms of the disease represent 20-30% of the cases and are described as syndromic. The most common form of Syndromic Retinitis Pigmentosa is the Usher syndrome, with a prevalence that ranges from 1.8 to 6.2 every 100,000 and is characterized by the combination of loss of vision and loss of hearing since the beginning of life. Other genetic syndromes are the Bardet-Biedl syndrome, Refsum Disease, and the Neuropathy-Ataxia-Retinitis Pigmentosa (NARP syndrome).
Even though the course and progression of the disease show a significant variation among individuals, the pathology is typically characterized by certain initial symptoms such as the night blindness, with onset in the first or second decade of life, loss of the peripheral vision and, with the worsening of the disease, loss of the central vision, which can lead to full blindness or serious visual disability. In the “classic” RP presentation, the difficulty in adjusting to the darkness begins in adolescence and the loss of the medium-peripheral visual field becomes noticeable in the young adult age. However, the age of onset among patients with RP varies broadly; some patients develop the loss of sight in early childhood, whilst others can remain relatively asymptomatic until the third/fourth decade of life. The exact age of onset is often difficult to determine, since many patients, in particular children, are able to compensate with research the loss of the peripheral vision. Moreover, the difficulty to adjust to the darkness can remain unobserved by the patient because of an artificially well lighted night environment. In general the sub-types of RP which appear early in the course of life have a tendency to progress more rapidly. Furthermore, the severity of the pathology is related to the Mendelian inheritance and family tree building of the disease.
Prior to the typical RP anomalies, some patients can present non-specific anomalies such as irregular reflexes of the internal limiting membrane, an enlargement of the foveal reflex and numerous lesions at the RPE level. An arteriolar shrinkage is also found whose etiology is not fully clear. Initially, this clinical characteristic was ascribed to a reduced metabolic demand being a consequence of the degeneration of the ganglion cells secondary to a cellular loss of the photoreceptors. An alternative assumption ascribes the loss of the photoreceptors that consume oxygen to a hyperoxia condition of the remaining internal retina, which leads to the vasoconstriction and reduction of the blood flow of the retinal vessels. Coarse pigmentary perivascular rearrangements can be observed in the medium retinal periphery, in the form of bone spicules that gradually increase of density spreading in the anterior and posterior direction. The bone spicules consist in cells of the RPE, which detach from the Bruch membrane and migrate towards intraretinal perivascular sites, where they form melamine pigment deposits. In particular, what causes the migration of the RPE cells is still unknown, considering the high level of dynamic interaction between choriocapillaris, RPE and photoreceptors. The mosaic aspect of the fundus is due to the atrophy of the retinal pigment epithelium and the visualization of the no longer disguised large choroidal vessels, with severe caliber reduction of the arteries; the macula can present atrophy, macular cellophane formation (pucker) and cystoid macular edema (CME).
DIAGNOSIS
For those patients who report the typical symptoms of the Retinitis Pigmentosa, it is necessary to submit to an in-depth eye examination associated to specific functional and morphological instrumental tests. The Computerized Perimetry shows the progressive loss of the field of vision (FV) that is typical of the RP. This loss of the field of vision has a high bilateral symmetry and typically starts with isolated scotomas in the medium-peripheral areas, which gradually join one another and form an anular scotoma in the medium periphery. With the worsening of the disease, this anular scotoma extends both to the outside and, even if more slowly, to the inside. In addition to anular scotomas, other models of progression of the FV were reported, including the concentric loss of the field of vision without a previous anular scotoma and loss of the field of vision progressing from the superior to the inferior retina. The Electroretinogram (ERG) appears to be an early indicator of the loss of the function or the cones and rods in the RP and a decrease in the responses to the ERG can be evident in the early years of life, even if the symptoms appear much later. The Optical Coherence Tomography (OCT), shows a progressive loss of the external retinal layers and an altered distribution of lipofuscin. The first hystopathological change in the RP is the shortening of the external segments of the photoreceptors. This change determines a disarrangement of the external retinal layers, initially in the interdigitation area, followed by the ellipsoidal area and finally by the outer limiting membrane (OLM). With the progressing of the RP, the thinning of the outer segments is accompanied by a decrease in the thickness of the outer nuclear layer, which contains the nuclei of the photoreceptors. The last phases of the RP are characterized by the complete loss both of the layer of outer segments and of the outer nuclear layer. Conversely, the layers of the inner retina, including the inner nuclear layer and the layer of ganglion cells remain relatively well preserved. As a matter of fact, a decrease in the thickness of the outer segments of the photoreceptors can also be accompanied by a thickening of the inner layers of the retina; even if the cause of this thickening is not fully clear, it may be considered due to the formation of an edema in the retinal fiber layer and/or to the retinal remodeling of the glial cells as a response to the reduction of the outer retina. The Fluorescence Angiography with Fluorescein (FAG) is not commonly used for the RP. The chorioretinal atrophy can be easily observed, initially in the periphery and/or medium retinal periphery, and later in the posterior pole. Even though there is usually no delay in the filling of the retinal blood vessels, these appear to be attenuated and a few losses of coloring material (leakage) can be observed.
