Chorioretinal Inflammatory Non-Infectious Diseases

Introduction

Uveitis includes a complex group of inflammatory eye diseases. Anatomically, there are four main groups of uveitis: anterior uveitis, which affects anterior segment of the eye; intermediate uveitis, which primarily involves the vitreous and peripheral retina; posterior uveitis, which involves the posterior segment of the globe (retina and choroid); and, finally, panuveitis, when more than one of the previous is involved. Posterior segment involvement may be secondary to infectious or noninfectious diseases. Noninfectious posterior uveitis comprise several entities, with different clinical history, prognosis, and treatment. However, all of them require imaging techniques to better visualize and monitor the disease. Some of these techniques, such as spectral domain optical coherence tomography (SD-OCT), fundus autofluorescence (FAF), and fluorescein angiography (FA), provide valuable information of vitreoretinal interface, retina, and retinal pigment epithelium (RPE). However, standard SD-OCT, FAF, and FA are not well suited for visualizing structures and pathologies involving choroid. Indocyanine-green angiography (ICGA) and newer and more advanced techniques, such as enhanced-depth imaging OCT (EDI-OCT), swept source OCT (SS-OCT), and OCT angiography (OCT-A), are capable of visualizing and monitoring choroid changes in posterior uveitis, becoming very valuable devices in the diagnosis and follow-up of these diseases. For example, clinically significant changes in subfoveal choroidal thickness (SFCT) have been reported in several posterior uveitis. Thus, SFCT data must turn indispensable in the management of posterior uveitis, considering that SFCT measurements obtained by EDI-OCT are reproducible in uveitis patients.

Macular edema (ME) is the most frequent structural complication of uveitis and the most common cause of visual impairment in patients with uveitis. OCT, mainly SD-OCT, is nowadays a fundamental tool in the analysis of uveitic ME (UME), with different morphologic patterns that may represent different stages in ME progression ( Fig. 13.1 ). Besides, the initial characteristics of UME could predict the clinical prognosis after treatment. Other studies have reported that subretinal fluid in UME is a marker for more responsive ME, with greater rates of edema resolution and visual acuity (VA) improvement after treatment ( Fig. 13.2 ).

Sarcoidosis

Sarcoidosis is an inflammatory multisystemic disease of unknown etiology that causes multifocal noncaseating granulomas in multiple organs (lung, lymph node, skin, liver, and eye).

Definitive diagnosis is made by biopsy. A sarcoid lesion is characteristically a well-defined granuloma with epithelioid cells arranged concentrically around multinucleate giant cells, without caseating necrosis.

Sarcoid is a truly protean disease, and it could be acute or chronic, widespread or localized, and self-limited or prolonged. The disease is slightly more frequent in women and with a higher rate of presenting uveitis. The peak incidence for men is about 40 years and for women is about 55 years.

A very high proportion (30%–60%) of patients with sarcoidosis develop ocular involvement, mainly bilateral granulomatous uveitis. Anyway, the uveitis of sarcoidosis can be of any type involving or not the posterior segment, being considered one of the great imitators. Clinical signs suggestive of ocular sarcoidosis have been recently summarized ( Table 13.1 ).

It is possible to observe an acute nongranulomatous anterior uveitis, specially in patients with classic Löfgren syndrome or more commonly chronic granulomatous anterior uveitis ( Fig. 13.3 ).

Intermediate uveitis with vitreous snowballs, pars plana exudates, and peripheral retinal vascular sheathing are also common manifestations ( Fig. 13.4 ).

Sarcoidosis predominantly affects retinal venules, which may be engorged and tortuous, surrounded by fluffy white plasma exudates. Some patients have a tendency to develop arterial ectasia, sometimes with macroaneurism formation, especially in older women with multifocal choroiditis.

Multifocal choroiditis is the hallmark of posterior segment sarcoidosis. Lesions usually are at different stages of evolution and are located at the inferior and nasal choroid ( Fig. 13.5 ).

Larger solitary lesions are unusual, but if present may raise the retina and even be associated with subretinal fluid. In such cases, differential diagnosis should include choroidal tuberculoma ( Fig. 13.6A and B ).

Chorioretinal involvement in sarcoidosis have been evaluated for many decades by clinical examination of the ocular fundus, because FA allowed better definition for retinal involvement and subtle choroidal changes might not been properly explored. Characteristics ICGA features in sarcoidosis include usually choroidal filling delay with punctate hypofluorescence. However, the technique is invasive, involves systemic administration of the dye, and there are overlapping of retinal and choroidal images which could be a confounding factor.

EDI-OCT reliably images the full thickness of the choroid and is capable of visualizing the extent and characteristics of a choroidal granuloma. EDI-OCT is a noninvasive and rapid technology that also allows one to monitor the evolution of the granuloma and the response to the treatment.

We have evaluated by means of EDI-OCT (Spectralis, Heidelberg) the characteristics of a presumed choroidal granuloma that appears as a localized hyporreflective choroidal thickening (620 μm) and an area of sensorial retinal detachment (RD) with subretinal fluid at the level of the choroidal granuloma The adjacent choroid has increased thickness and normal reflectivity. Three weeks after systemic corticosteroids, VA improved and the choroidal thickness (CT) decreased to 325 μm. After 3 months of corticosteroid therapy, CT was 247 μm ( Fig. 13.7A and B ).

On the other hand, it has been published that during the quiescent phase, patients with ocular sarcoidosis had thinner choroids than normal subjects. SFCT showed a positive correlation with VA and negative correlation with global disease duration and also with the duration of active disease, being a good indicator of inflammatory activity in sarcoidosis.

Sympathetic Ophthalmia

Sympathetic ophthalmia (SO) is a rare bilateral granulomatous uveitis that occurs after trauma or surgery to one eye (the exciting eye), which will lead to an inflammatory reaction in both eyes, being the nontrauma eye, the sympathizing eye. In the past, trauma was the main cause of SO. However, recent studies suggest that ocular surgery, particularly vitreoretinal surgery, is the major risk for this disorder. The occurrence of SO is estimated to be 0.4–1.4% of all uveitis and 0.1–0.3% of all traumatized eyes.

Posterior segment classical manifestations of OS include exudative RD, vasculitis, disc edema, and multiple white-yellow lesions, occasionally confluent, mainly in periphery, which are the clinical sign of Dalen-Fuchs nodules (DFN), which is a histopathological finding (collections of epithelioid cells below the RPE). OCT is a very valuable tool in the diagnosis and monitoring of retinal involvement in SO. A recent report describes the SD-OCT images of the characteristic DFN, revealed as hyperreflective lesions at the level of RPE, associated with disruption of the inner segment/outer segment (IS/OS) junction. After treatment and clinical improvement, DFN on SD-OCT went away, but abnormalities of the IS/OS and disruptions of the RPE persisted. SD-OCT image of RPE rip in a case of SO has also been reported. Other study analyzed the changes seen in the photoreceptor layer of the retina during the acute phase of SO. The outer retinal segment showed serous RD (SRD) and disruption of the IS/OS junctions in all the eyes, whereas elongation of photoreceptors occurred in 66% of eyes. Those abnormalities improved over the time after systemic corticosteroid therapy, with resolution of SRD, normal photoreceptor layer, and restoration of IS/OS junction in all the eyes 4 weeks later. A similar and more recent report describes the EDI-OCT findings in an acute phase of SO. Presenting EDI-OCT showed a diffuse increase of CT in both the sympathizing and exciting eyes. One month after corticosteroid therapy, a marked decrease in the CT was observed, especially in the sympathizing eye. At 15-month follow-up visit, in the convalescent phase, the CT had decreased but was thicker than normal. The authors conclude that EDI-OCT can be an accurate way of assessing disease activity and monitoring response to treatment in SO.

FA is of limited diagnostic value in SO. In the acute stage reflects an exudative process, with multiple areas of subretinal leakage as hyperfluorescent and hypofluorescent spots. DFN may block early (become hypofluorescent) and then stain late (i.e., hyperfluorescence). In chronic cases, FA shows irregular choroidal filling and patchy choroidal staining, whereas DFN appear as window defects.

FAF in a case of SO has been reported, showing hyperfluorescence in areas of SRD that will turn, after treatment and SRD resolution, into speckled areas of hyper- and hypoautofluorescence resembling leopard spots.

As the disease predominantly involves the choroid, ICGA is more useful in the diagnosis of SO. Two patterns of fluorescence have been observed in SO. First, a pattern of hypofluorescence dark dots in the intermediate phase that become isofluorescent at the late phase, representing active lesions. Second, a hypofluorescent pattern that persisted until the late phase, depicting a cicatricial or atrophic lesion. A more recent report found similar ICGA findings, well correlated to fundus ophthalmoscopy and FA, making the ICGA the most useful image technique in helping to monitor the response of SO to treatment. A histopathological correlation with ICGA findings showed that hypoflourescent areas did not correspond to nonperfusion areas, but they were secondary to inflammatory cell blockage and choriocapillaris edema.

In conclusion, EDI-OCT and ICGA seem to be nowadays, the best image techniques for diagnosis and monitor the SO, so both studies must be performed in the baseline and in the follow-up of SO patients.

Vogt–Koyanagi–Harada Syndrome

Vogt–Koyanagi–Harada (VKH) disease is a bilateral diffuse granulomatous panuveitis that involves the eyes, auditory system, meninges, and skin. VKH disease is more frequent in pigmented skin people. Women seem to be affected more frequently than men. VKH disease affects mainly those in their third to four decades of life. The prevalence of VKH disease depends on the studied population, being more common in Japan (10.1% of all uveitis referrals ) than in the United States (1–4%), India (2%), or Brazil (2.5%).

In 2001, the consensus of the “First International Workshop on Vogt–Koyanagi–Harada Disease” was published, in which the nomenclature and diagnostic criteria for VHK disease were established ( Table 13.2 ). VKH disease may have different clinical manifestations, which are presented in four stages, that include prodromal, acute uveitic, chronic, and chronic recurrent stages.