The pathogenesis of uveitis entails changes in the structural morphology of the macula, choroid, and choroidal perfusion. Documentation of these pathologic alterations is pivotal in making a proper diagnosis and in follow-up of outcomes of therapy. The newly-introduced swept-source optical coherence tomography (SS-OCT) and optical coherence tomography angiography (SS-OCTA) were harbingers of a whole new era of noninvasive in vivo layer-to-layer dissection of macular and choroidal structural changes in uveitis and of disease-related vascular profile patterns. This new information unraveled new aspects of the underlying pathogenetic mechanisms in different uveitides and added to our understanding of the disease process. Monitoring choroidal thickness was introduced as a novel sensitive index for evaluation and titration of treatment response. Moreover, the ensuing complications of uveitis as poor pupillary dilatation due to posterior synechiae and mild to moderate opacities due to cataract or vitritis that frequently posed pertinacious impediments for reproducible imaging were overcome by SS-OCT features notably long-wavelength scanning laser and reduced sensitivity roll-off features. In the current manuscript we present our experience in diagnosis and management of selected posterior uveitides using SS-OCT and SS-OCTA.
- swept-source OCT in uveitis
- swept-source OCTA in uveitis
- serpiginous choroiditis
- multifocal choroiditis
- punctate inner choroidopathy
Traditionally, management of posterior segment inflammation secondary to uveitis relied on fundus fluorescein angiography (FFA) and indocyanine green angiography (ICG) for assessment of the pathological alteration of the inner- and outer-blood-retina-barriers (BRB), disturbances in choroidal perfusion, and the structural sequelae of inflammation in the macular area and elsewhere in the retina and the choroid [1, 2]. These tests offered indirect biological clues to evaluate the quality of the retinal and choroidal circulations in terms of patterns of leakage and grades of perfusion; henceforth, determination of disease evolution through remissions and exacerbations, titration of posology and monitoring tissue response to therapy [3, 4].
1.1 Limitations of conventional angiographic modalities
Despite the invaluable input of these diagnostic tools, they had inherent limitations that posed major impediment to full exploration of the pathological events in the posterior segment secondary to different uveitides. Firstly, the profuse leakage of the sodium fluorescein molecule from the choriocapillaris, and the optical scattering of incident light by the retinal nerve fiber layer confined the utility of FFA mostly to single-layered evaluation of the pathological cascade of events developing at the level of superficial capillary plexus (SCP) and left the observer with vague deductions regarding the ongoing pathology in the deep capillary plexus (DCP), the choriocapillaris and the choroidal stroma [5, 6, 7, 8, 9]. Secondly, the inflammatory by-products of uveitides and the associated pathological features included intra-, sub-retinal and sub-retinal pigment epithelium (RPE) fluid and/or lipoproteinaceous deposits, sub-retinal and sub-RPE fibrosis, RPE thickening and pigment epithelial detachment (PED). These features shared common FFA leakage and ICG fluorescence properties among themselves and with choroidal neovascular membrane (CNV) that might complicate posterior segment inflammation, which made these entities virtually indistinguishable from each other and subsequently delayed diagnosis and prompt intervention for treating CNV. Thirdly, the longevity of uveitis disease process and its propensity to undulating course of remissions and exacerbations render repetitive dye-based FFA and ICG angiography impractical and even hazardous in routine clinical practice due to their invasive nature [3, 4, 10].
1.2 Swept-source optical coherence tomography (SS-OCT) and optical coherence tomography angiography (SS-OCTA) technology: novel imaging modality in uveitides
The introduction of swept-source optical coherence tomography (SS-OCT) technology revolutionized imaging of ocular posterior segment in uveitides and circumvented several classical obstacles that long represented significant hindrance to correct diagnosis. Firstly, SS-OCT employed a long wavelength laser source (1050 nm) operating at an ultra-high scanning speed (100.000 A-scan/second). The tandem of ultra-high-speed image acquisition, laser beam collimation and reduced sensitivity roll-off feature helped defraying scattering of the scanning light as it traveled through the retina, with subsequent rendition of ultra-high-definition images of retinal layers quasi-in-vivo histological tissue dissection [11, 12]
Moreover, these features enhanced beam penetration in media opacities and poorly dilatable pupils, which are common features associated with uveitis and that pose significant impediment to interpretable images. New morphological changes in the vitreo-retinal interface, the retina, the choroidal layers, and changes in choroidal thickness secondary to uveitides were unveiled and employed as biomarkers for diagnosis of uveitis, detection of ensuing complications and monitoring disease progression and response to therapy. Secondly, superior axial resolution and greater depth of penetration of the incident beam in enhanced depth (EDI)- and SS-OCT imaging allowed simultaneous documentation of pathological changes in the vitreous, vitreo-retinal interface, retina, and choroid in a single frame amenable to scrutiny and exploration of the true magnitude of tissue involvement by the disease process [13, 14, 15, 16, 17, 18].
Thirdly, SS-OCT incorporated a blood flow detection algorithm; OCTARA (Optical Coherence Tomography Angiography Ratio Analysis). This novel feature allowed evaluation of the retinal vascular plexuses and of the choriocapillaris that are frequently targeted in uveitides. The algorithm relies on decorrelation motion contrast between rapidly repeated SS-OCT B-scans to visualize blood flow in vivo without the need for contrast injection. This OCTA implement benefits from being merged with SS-OCT technology to generate separate en-face images of the retinal SCP, DCP, and the choriocapillaris. It is worthy of note that OCTARA algorithm generates OCTA images by registering B-scan repetition at each scan location then computing a ratio-based result between corresponding image pixels. This method preserves the integrity of the OCT spectrum and does not result in compromised axial resolution, an inherent disadvantage of other OCTA technologies [19, 20, 21, 22].
OCTA excelled in delineating inflammatory CNV that could complicate posterior uveitis and determining its state whether active, quiescent, or recurrent based on the neovascular network morphological criteria [10, 23, 24]. Inflammatory CNV has long posed a diagnostic predicament in the past due to overlapping leakage and/or fluorescence patterns with non-neovascular inflammatory tissue on FFA and ICG, respectively. Likewise, CNV and non-neovascular inflammatory lesions frequently exhibit similar light backscattering properties that render them indistinguishable from each other on structural OCT [3, 4, 25, 26].
It is worthy of note that OCTA does not provide information on vascular leakage, which is a crucial index of the integrity of the inner BRB in cases of vasculitis associated with uveitides. In cases of active vasculitis, OCTA could be even misleading as the leakage of plasma from a disrupted inner BRB into the extra-cellular compartment might slow-down the blood stream velocity well below the detection threshold of OCTA, which might be falsely interpreted by OCTA as reduced vessel density and capillary non-perfusion .
2. Authors’ case presentations
In the following case presentations, we present our experience with SS-OCT and SS-OCTA using the swept-source DRI OCT Triton machine version 10.11 (Topcon Corporation, Tokyo, Japan) and the OCTARA algorithm (Topcon Corporation, Tokyo, Japan), respectively, in imaging common non-infectious and infectious uveitides, with emphasis on the importance of multi-modal imaging approach in which different imaging modalities complement one another to reveal the true extent of the ongoing pathology.
2.1 Non-infectious uveitides
2.1.1 Vogt-Koyanagi-Harada (VKH)
VKH is a multi-system disorder featuring ocular, auditory, integumentary, and neurological manifestations. Ocular involvement in VKH is in the form of bilateral granulomatous panuveitis that is notorious of profound drop of vision, hence the need for early aggressive treatment. Posterior segment involvement in the acute stage comprises diffuse choroiditis, optic disc hyperemia, multifocal serous retinal detachment or bullous exudative retinal detachment. As the chronic stage of the disease ensues, the patient develops ocular depigmentation in the form of chorioretinal depigmented scars and retinal pigmentary disturbances [27, 28].
The primary target tissue in VKH is the choroidal stroma which endures dense infiltration with inflammatory cells and subsequent thickening due to engorgement of choroidal vessels and serous exudation. Eventually, the RPE dehisces giving way to the inflammatory infiltrates and serous fluid into the sub-retinal space. RPE folds develop due to displacement by the thickened choroid. The choriocapillaris undergoes ischemic changes especially in recurrent cases in the form of localized vascular loss. This could be explained by severe hypoperfusion secondary to inflammation or by pressure atrophy from inflammatory granulomas [29, 30]. These areas of choriocapillaris loss appear on OCTA examination as sharply demarcated flow-voids that might recover after resolution of inflammation [31, 32]. Recurrent attacks of inflammation with subsequent breaching of the RPE-Bruch’s complex could trigger CNV formation. In that context OCTA helps differentiating CNV from inflammatory tissue by demonstrating the hyperintense signal characteristic of CNV formation in the outer retina slab [3, 4].
126.96.36.199 Case presentation
A 58-year-old male presenting with bilateral diminution of vision of approximately 3 months duration. The patient reported more severe drop of vision in the left eye. He had history of previous similar attacks of visual disturbances in both eyes. His best-corrected visual acuity (BCVA) was 6/60 and 1/60 in the right and left eyes, respectively. Fundus examination of the right eye revealed multifocal serous retinal detachment in the posterior pole along with extensive sub-retinal exudate formation and optic nerve head (ONH) hyperemia. FFA revealed multiple leaking points at the level of the RPE with pooling of dye into the sub-retinal space and hyperfluorescence of the ONH due to leakage from dilated optic disc vessels. Fundus examination of the left eye showed similar findings in the posterior pole in addition to a sub-macular greenish-yellow lesion that demonstrated early hyperfluorescence with minimal leakage and late staining suggestive of predominantly scarred CNV.
188.8.131.52.1 SS-OCT and SS-OCTA features
The corresponding SS-OCT scan of the right eye showed marked thickening of the choroid with secondary undulations of the overlying RPE layer. The sub-retinal space showed multiple loculi of serous fluid and complete disruption of the ellipsoid zone. SS-OCTA revealed loss of the normal hyperintense homogenous texture of the choriocapillaris and the development of moth-eaten like hypointense areas. SS-OCT examination of the left eye revealed large sub-foveal hyperreflective lesion with complete disorganization of the outer retinal layers and minimal overlying subretinal fluid, reminiscent of inactive type 2 CNV. SS-OCTA examination of the left eye confirmed inactive CNV formation. After receiving systemic steroid treatment the patient had complete resolution of the acute attack, with restoration of the normal retinal architecture and normal choroidal thickness in the right eye. BCVA in the right eye improved to 6/6 (Figure 1(A)–(D)).
184.108.40.206 Case presentation
A 16-year-old female presenting with bilateral diminution of vision of approximately 2 weeks duration. Her BCVA was 6/60 bilaterally. Fundus examination of both eyes revealed multifocal serous retinal detachment in the posterior pole along with yellowish sub-retinal exudate formation and ONH hyperemia. FFA revealed numerous leaking points at the level of the RPE with pooling of dye into the sub-retinal space and hyperfluorescence of the ONH due to leakage from dilated optic disc vessels. Five months after the patient received high-dose steroid therapy, the fundus of both eyes showed resolution of the previously noted neurosensory detachments and development of diffuse RPE and choroidal pigmentary disturbances. The macular area of the left eye showed a sub-retinal greenish lesion suggestive of CNV formation.
220.127.116.11.1 SS-OCT and SS-OCTA features
The corresponding SS-OCT scan of the right eye in the chronic stage showed residual neurosensory detachment with persistent thickening of the choroid. SS-OCT of the left eye showed sub-retinal hyperreflective amorphous lesion corresponding to the macular lesion seen in the color photo. SS-OCT was inconclusive in differentiating the sub-retinal inflammatory material from CNV due to similar optical reflectance properties of both lesions. On the other hand, SS-OCTA of the left eye decisively excluded CNV formation (Figure 2(A) and (B)).
2.1.2 Serpiginous choroiditis
Serpiginous choroiditis is an autoimmune disorder characterized by primary choriocapillaropathy in the form of progressive vascular occlusion of the choriocapillaris and possibly larger choroidal vessels with secondary ischemic damage of the RPE and neurosensory retina. The classic presentation of the acute form is single or multiple sub-retinal creamy-white lesions developing at the edge of the optic disc and wind in the posterior pole in a centripetal serpentine or helical pattern. Less typical variants of the disease that do not have a peripapillary component include macular serpiginous, and ampiginous choroiditis. The latter form has an initial benign clinical presentation reminiscent of acute posterior multifocal placoid pigment epitheliopathy, and later follows a relentless progressive course. Serpiginous choroiditis is bilateral with propensity to recurrence. Disease re-activation is characterized by development of newer lesions at the edges of old healed scars. Chronic stage is characterized by diffuse atrophy and disappearance of the choriocapillaris with subsequent secondary atrophy of the RPE and outer retina, scarring and RPE pigmentary disturbances [33, 34]. The resultant choroidal thinning and loss of choriocapillaris will cause alteration of the normal structural OCT features in the form of forward bowing of the choroid with loss of the normal bowl-shaped configuration and anterior displacement of the Sattler’s vessel layer, hence development of diffuse irregular flow-voids and enhanced visualization of the medium and large-sized choroidal vessels on OCTA slab of the choriocapillaris [35, 36, 37]. The disease is notorious of aggressive course with propensity to involve the macular area and subsequent profound vision loss, which prompts briskly intervention with high-dose steroid therapy or other immunosuppressive agents for vision salvage .
18.104.22.168 Case presentation
A 28-year-old female patient who was a known case of bilateral serpiginous choroiditis. The patient presented with recent complaint of drop of vision approximately 1 month ago. Fundus examination in both eyes revealed large sharply circumscribed areas of sub-retinal fibrosis, with dense RPE clumps formation and variable degree of RPE pigmentary disturbances. Some of the lesions have coalesced together forming a continuum of sub-retinal scarring that involved almost the entire posterior pole. The distribution of the lesions was suggestive of previous episodes of classic form of serpiginous choroiditis. BCVA was counting fingers (CF) at 50 cm and 3/60 in the right and left eyes, respectively.
22.214.171.124.1 SS-OCT and SS-OCTA features
SS-OCT in both eyes showed marked thinning of the choroid with loss of the normal bowl-shaped configuration due to severe erosion of the choriocapillaris. The outer retina showed marked disorganization and atrophy. The RPE-Bruch’s complex, external limiting membrane layer (ELM) and inner segment-outer segment photoreceptors junction (IS/OS) were replaced by amorphous hyperreflective material. SS-OCTA showed irregular hypointense areas of flow-void amidst areas of preserved choriocapillaris denoting patchy loss of choriocapillaris (Figure 3(A) and (B)).
126.96.36.199 Case presentation
A 37-year-old female patient who was a known case of bilateral serpiginous choroiditis presenting for routine follow-up. BCVA was 6/60 and 6/36 in the right and left eyes, respectively. The posterior pole in both eyes showed large well-circumscribed areas of extensive chorioretinal atrophy involving the peripapillary area and extending into the macular region. The retinal layers and even underlying choroidal vasculature have virtually disappeared from wide areas of the lesion with unveiling of the underlying sclera.
188.8.131.52.1 SS-OCT and SS-OCTA features
SS-OCT in both eyes showed marked thinning of the fovea, and marked disorganization and atrophy of the outer retinal layers. The choroid showed diffuse loss of the choriocapillaris and of the larger choroidal vessels with subsequent loss of the normal bowl-shaped configuration. SS-OCTA showed diffuse loss of the choriocapillaris with unveiling of the larger choroidal vessels (Figure 4(A) and (B)).
2.1.3 Multifocal choroiditis (MFC) and punctate inner choroidopathy (PIC)
MFC and PIC are idiopathic chorioretinal inflammatory disorders that are grouped under the spectrum of white dot syndromes. The phenotypic features of both entities overlap in many aspects to the extent that they are considered variants of the same disorder rather than separate clinical entities. MFC/PIC have predilection for young myopic females. Their hallmark is the development of yellowish-white chorioretinal lesions scattered throughout the posterior pole and the periphery of the fundus. Histologically, these lesions are composed of aggregates of inflammatory cells beneath the RPE that cause multifocal conical elevation of the RPE cell layer in the form of inflammatory PED. These lesions eventually breakthrough the RPE into the sub-retinal space with subsequent release of the inflammatory infiltrates into the outer retina. Recurrent episodes of inflammation cause structural retinal damage. The chorioretinal pathologic cascade is associated with vitritis that is most marked in cases of MFC compared to PIC. As chronicity ensues these lesions develop into punched-out chorioretinal scars [38, 39, 40, 41]. Secondary CNV formation is a frequent complication, mounting up to one-third of cases, though some studies report much higher incidence [42, 43, 44]. CNV superimposed on MFC/PIC is usually a type 2 variant and is notoriously difficult to detect or to follow-up its response to anti-vascular endothelial growth factor (anti-VEGF) agents using conventional angiography techniques or structural OCT because it is characterized by minimal leakage on angiography and fluid accumulation on OCT, in addition to overlapping angiographic and OCT features with MFC/PIC-induced inflammation .
184.108.40.206 Case presentation
A 37-year-old female who is a known case of PIC presenting with drop of vision in the right eye of approximately 2-month duration. BCVA was 5/60 and 6/12 in the right and left eyes, respectively. Fundus examination of the right eye revealed features of myopic fundus with multiple discrete punched-out sub-retinal lesions scattered in the posterior pole and extending towards the equator. Most lesions were yellowish-white in color, whereas few lesions demonstrated variable degree of pigmentation. The foveal area showed a grayish sub-retinal lesion that exhibited typical features of classic CNV on FFA. SS-OCT confirmed the presence of type 2 CNV. SS-OCTA demonstrated hyperintense signal and characteristic features of active CNV. The patient received anti-VEGF injections for the right eye. At this stage her left fundus showed tessellated appearance with peripapillary atrophy due to myopia without signs of PIC. The patient returned 9 months later with complaints of metamorphopsia in the left eye. BCVA in the left eye has dropped to 6/18. Fundus examination revealed multiple scattered sub-retinal creamy white lesions. She was started on oral steroid therapy and the fundus lesions went onto remission though metamorphopsia persisted. Three months later she presented with worsening metamorphopsia and more drop of vision. BCVA in the left eye was 6/36. FFA, SS-OCT, and SS-OCTA revealed presence of CNV.
220.127.116.11.1 SS-OCT and SS-OCTA features
SS-OCT showed sub-RPE hyperreflective knob-like projections either confined to the sub-RPE space or breaking through into the sub-retinal space. SS-OCTA of the choriocapillaris revealed scattered foci of flow-voids corresponding to the location of the scarred punched-out lesions in the fundus. The foveal lesion suggestive of neovascular growth on color fundus photo and on FFA appeared as a sub-foveal amorphous hyperreflective material above the RPE suggestive of type 2 CNV with minimal overlying fluid. SS-OCTA at the level of the outer retina confirmed the hyperintense signal of flow within neovascular complex (Figures 5(A) and (B) and 6(A) and (B)).
18.104.22.168 Case presentation
A 31-year-old female who is a known case of MFC presented with drop of vision in the left eye of approximately 3 weeks duration. BCVA was 6/6 and 3/60 in the right and left eyes, respectively. Fundus examination in the left eye revealed a sub-foveal yellowish-white lesion approximately 1 disc diameter (DD) in size. The posterior pole temporal to the lesion showed sub-retinal punched-out healed lesions of old episode of MFC. FFA demonstrated sub-foveal classic CNV formation. SS-OCT and SS-OCTA confirmed presence of neovascular growth. The patient started anti-VEGF injection that caused regression of the CNV. Her BCVA in the left eye after 3 ranibizumab injections and 7-month follow-up was 6/24.
22.214.171.124.1 SS-OCT and SS-OCTA features
SS-OCT examination revealed the presence of type 2 CNV with minimal overlying sub-retinal fluid. SS-OCTA revealed the hyperintense signal characteristic of flow within active neovascular network. On follow-up visits after the patient received anti-VEGF intravitreal injections, the morphology of the CNV on SS-OCT showed minimal variation. On the other hand, SS-OCTA was conclusive in documenting the regression of the CNV in response to anti-VEGF treatment (Figure 7(A) and (B)).
2.2 Infectious uveitides
Ocular toxoplasmosis is an infectious granulomatous posterior uveitis. The disease is considered the most common cause of posterior uveitis worldwide. Ocular involvement occurs as part of systemic toxoplasmosis. Infection is either congenital via transplacental transmission of the protozoan Toxoplasma gondii form an infected mother, or acquired due to ingestion of contaminated water or food or ingestion of undercooked meat containing toxoplasma cysts . The clinical presentation is in the form of focal necrotizing retinochoroiditis in the posterior pole. The lesion can develop de novo or can present in the form of a satellite lesion, which is an acute focus of retinochoroiditis developing adjacent to an old chorioretinal scar. The lesion is associated with overlying vitritis which could be severe enough to obscure visualization of the fundus apart from the yellowish-white necrotizing focal lesion giving rise to the characteristic spotlight-in-the-fog appearance. As the acute episode subsides, a quiescent hyperpigmented scar develops which could lead to profound visual loss should it affect the macula or the papillomacular bundle . On structural OCT, an active lesion features thickening and disorganization of the neurosensory retina, thickening of the choroid underlying the lesion and evidence of vitritis in the form of hyperreflective dots and thickening of the posterior hyaloid. As the lesion heals, the patient develops a chorioretinal scar with marked thinning and disorganization of the neurosensory retina and thinning of the underlying choroid. Choroidal neovascularization and vitreoretinal interface disturbances in the form of vitreoretinal tractional bands can develop [17, 18, 46].
126.96.36.199 Case presentation
A 13-year-old male presented to our clinic complaining of diminution of vision in his right eye of 3 days duration. Fundus examination revealed whitish retinal lesion inferonasal to the ONH with feathery indistinct edges and overlying vitritis. The ONH was inflamed with blurred edges. BCVA was 6/60 and 6/6 in the right and left eyes, respectively. Due to proximity of the lesion to the optic disc and the macula, we started the patient on oral sulfadiazine, pyrimethamine, and folinic acid. Oral steroids were started 24 h after initiation of antimicrobial regimen. At 2-month follow-up visit, the fundus showed resolution of previously noted vitritis and disc hyperemia, and regression of the retinal lesion, which appeared smaller in size and had well-defined boundaries. BCVA in the right eye improved to 6/6.
188.8.131.52.1 SS-OCT and SS-OCTA features
SS-OCT showed focal thickening with complete disorganization of the neurosensory retina, disruption of the ELM, IS/OS, and RPE cell layer with focal thickening of the choroid beneath the lesion. The overlying vitreous showed dense infiltration with hyperreflective foci indicating vitritis. SS-OCTA showed localized hypointense signal in the SCP, DCP, and choriocapillaris corresponding due to the masking by the focal lesion. During follow-up the previously noted hypointense signal regressed in size in proportion to regression of the lesion (Figure 8(A) and (B)).
184.108.40.206 Case presentation
A 26-year-old female presented to our clinic complaining of diminution of vision in her right eye of 1 week duration. Fundus examination revealed yellowish-white retinal lesion composed of a larger focus and smaller adjacent lesions overlying the papillomacular bundle. BCVA was 6/24 and 6/6 in the right and left eyes, respectively. As the lesion involved the papillomacular bundle, the patient was started on oral sulfadiazine, pyrimethamine, and folinic acid. Oral steroids were started 24 h after initiation of antimicrobial regimen.
220.127.116.11.1 SS-OCT and SS-OCTA features
SS-OCT showed focal thickening with complete disorganization of the neurosensory retina, disruption of the ELM, IS/OS, and RPE cell layer with focal thickening of the choroid beneath the lesion. The posterior hyaloid was thickened and partially attached to the focal retinal lesion. SS-OCTA showed localized hypointense signal in the SCP, DCP, and choriocapillaris corresponding to the masking effect of the focal lesion (Figure 9(A) and (B)).
18.104.22.168 Case presentation
A female child, 8 years old presented to our office. Her mother reported noticing deviation of the right eye of her child and poor vision upon covering the left eye. BCVA was HM and 6/6 in the right and left eyes, respectively. Fundus examination of the right eye revealed a large saucer-shaped deeply excavated pigmented chorioretinal scar occupying the macular area.
22.214.171.124.1 SS-OCT and SS-OCTA features
SS-OCT showed marked thinning and disorganization of the retina, irregular elevation and thickening of the RPE and altered choroidal contour. SS-OCTA showed complete loss of the choriocapillaris at the site of the scar with unveiling of the large choroidal vessels underneath (Figure 10).
The introduction of SS-OCT and SS-OCTA technology greatly propelled the management course of uveitis by unveiling previously unexplored areas of retinal and choroidal pathological morphology in uveitides, and by introducing new inflammatory biomarkers that helped monitoring the disease response to various therapeutic agents. The non-invasive nature of the new technology added to its versatility in particular clinical situations in which conventional angiography could be impractical or hazardous especially in lengthy follow-up protocols, pediatric patients, pregnant females, and patients with severely compromised renal function. However, this nascent technology should be considered an important complimentary tool to conventional angiographic tests without substituting them. Conventional FFA and ICG still maintain the lead role in diagnosis of uveitides by providing yet unmatched information on leakage which is by far the most important biomarker in monitoring the state of inner blood-retina-barrier in inflammatory entities as uveitides.