Tubercular SLC can be clinically differentiated from SC by the frequent presence of vitritis and multifocal choroiditis lesions in posterior pole and periphery, often sparing the juxtapapillary region [3]. The lesions in SC are, however, usually around the optic disk and spread contiguously to the macula. People with SLC are from areas endemic for tuberculosis, have positive uveitis work-up for tuberculosis, and respond favorably to antitubercular therapy with oral corticosteroids.
The main histological findings described in SC are atrophy of the choriocapillaries, the RPE, and the photoreceptors [4, 7]. While the choriocapillaries was reported to be the most affected layer that appeared acellular, the large choroidal vessels were unremarkable. Moderate, diffuse lymphocytic infiltration of the choroid has been reported, with predominant RPE atrophy. Occasionally, RPE hypertrophy has been seen correlating with areas of pigment clumping clinically [4, 7]. On the other hand, clinicopathological correlation in tubercular SLC is still not known. Clinically, SLC appears to involve primarily the inner choroid and the RPE. However, isolation of Mycobacterium tuberculosis from the RPE in an eye with tubercular panuveitis has strongly suggested preferential localization of the mycobacteria in the RPE, even in eyes with panuveitis or related intraocular inflammation, including multifocal choroiditis or serpiginouslike choroiditis [8].
High-speed, high-resolution OCT, by providing unprecedented details, has enhanced our understanding of the ultrastructure of the retina [9]. Distinct scattering bands correspond to photoreceptor IS/OS junction, photoreceptor outer segment tips, and the RPE and represent the thick scattering bands of outer retina [9]. The SD-OCT changes in healed scars of SLC have shown disruption of the outer retina at the site of scars with loss of junction between the inner and outer segments of photoreceptors and thinning of RPE/Bruch membrane complex and a correspondent increase in light reflectivity from the choroid [3]. Areas of thickening of RPE/Bruch membrane complex have also been shown in the regions of scars. However, there is no report of SD-OCT changes in any active and healing stages of SLC lesions.
All eyes with active lesions of SLC in our patients illustrate the progressive changes in the outer retinal layers on OCT scans that correlated with the FAF changes. The FAF images obtained simultaneously demonstrated the transition from initial hyperautofluorescent of acute lesions to predominant hypoautofluorescent in the healed stage. Absence of any demonstrable changes in the inner choroid during the active stage of the lesion on OCT scans may suggest a primary involvement of the RPE and not the choroid in tubercular SLC lesions. The FAF signals provide a strong clue to the status of RPE cells in various degenerative, inflammatory, and neoplastic disease processes. The FAF is increased (hyperautofluorescence) in the presence of increased metabolic activity of the RPE and decreased (hypoautofluorescence) when there is loss of the RPE.
We observed that the structural changes on OCT scans occurring during the course of SLC followed a stepwise orderly sequence, similar to those as seen on the FAF images. Increased autofluorescence in the acute lesions seen as diffuse, subtle, feeble hyperautofluorescent probably reflects retinal edema which was structurally evident as hyperreflectivity spreading into the outer retinal layers in the OCT scans of our patients. This possibly suggests cellular infiltration or extracellular fluid accumulation in these layers due to inflammation. As the lesions started healing, hyperautofluorescence decreased and hypoautofluorescence increased due to loss of RPE. The outer retinal layers on OCT scans of our patients showed attenuation and progressive loss in the affected areas as the lesions healed. The FAF becomes increasingly hypoautofluorescent which indicates severe damage to RPE and photoreceptors. This was seen as an irreversible, collective loss of the outer retinal layers involving the RPE, photoreceptor outer and inner segments, and the ELM in OCT scans.
Acute inflammatory lesions involving the RPE often cause a thickening at the level of RPE. It is believed that the lesions in SC arise deep in the retina, and the overlying retina appears edematous. The edema subsides as the lesions heal, and the RPE–choriocapillaries undergo atrophy. There is loss of photoreceptor–RPE complex with variable degrees of RPE hyperplasia. Yeh et al. have hypothesized that RPE may be the site of primary insult and hence, more severely damaged in presumed tuberculosis-associated serpiginouslike choroidopathy [10]. Increased autofluorescence in acute phase may be due to a number of factors. The size, number, or content of the fluorophores in the RPE cells may be altered by inflammation which increases the fluorophores content by inducing certain prooxidative pathways. Increased autofluorescence in other inflammatory conditions also such as White Dot Syndromes has been correlated with areas of RPE elevation on OCT image during active disease [10]. Once healed, the hypoautofluorescent areas showed resolution of RPE abnormalities on OCT scan.
The FAF abnormalities (hyperautofluorescent in active stage progressively becoming hypoautofluorescent in healed stage) have been well recognized (unpublished data). We observed that in the very initial stages of disease occurrence, when there was feeble hyperautofluorescence in the areas of new lesions, the OCT showed hyperreflectivity in the outer retinal layers that was fuzzy and ill defined. The choroid did not show any reflectance. This is an important OCT finding during the acute stage of SLC that may reflect the site of primary insult in SLC. However, SD-OCT technology is not yet able to image the choroid similarly to the retina, and hence, the absence of choroid changes on SD-OCT is not enough to definitely exclude its primary involvement in SLC.
Hyperreflectivity in the outer retinal layers in an active SC lesion is believed to be suggestive of acute inflammation involving deeper retinal and choroidal structures. From the OCT findings of our patients, we speculate that in an acute lesion of SLC, there is an increased metabolic activity caused by primary inflammation of the RPE cells. Release of inflammatory mediators into the retinal layers adjacent to the RPE causes a fuzzy, hyperreflective appearance on SD-OCT. Following an acute inflammatory episode, the RPE cells undergo hyperplasia and hypertrophy which is evident as hyperautofluorescence on FAF due to increased collection of lipofuscin. This corresponds to the localized, knobbly elevations of the outer retinal layers which represents clumping of the inflamed RPE cells. Once these damaged RPE cells undergo atrophy, there is an irreversible loss of photoreceptors giving rise to the loss of the outer retinal layers on OCT. The simultaneous increased hypoautofluorescence depicts the atrophied RPE cells. The late pigmentation of the retinal scar associated with RPE hypertrophy or hyperplasia also leads to a decreased FAF signal (especially when photoreceptors are disrupted), as can also be seen in Figs. 1 and 2. The baring of choroidal vessels in healed lesions of SC in contrast to their masking by hyperpigmentary changes of the RPE in SLC may also be due to entirely different entities affecting the inner choroid and the RPE cells, respectively.
The limitations of our study include a small number of cases and lack of clinicopathologic correlation. The outer retinal bands on SD-OCT, particularly IS/OS junction and POST, have not been so far correlated to the histological structures, and such correlation is still mostly presumed. However, the sequential ultrastructural changes in the outer retinal morphology on SD-OCT scans as seen in our patients provide important information that may add a new dimension in understanding the primary site of pathology in inflammatory conditions affecting the choroid and the RPE–photoreceptor complex.