Fig. 3.1
(a) Venous phase fluorescein angiogram of a choroidal tubercle showing a hypofluorescent tubercle with mild hyperfluorescence at its margins. (b) Late-phase fluorescein angiogram showing diffuse hyperfluorescence of the tubercle due to slow centripetal increase in fluorescence
Another common manifestation is a choroidal granuloma or a “tuberculoma”, which is usually solitary. Tuberculoma is a large granulomatous mass-like lesion in the choroid that appears as a raised nodule at the posterior pole and may mimic a choroidal tumour. It usually does not have its own separate vascular supply. Thus, again in the early phases it would block choroidal fluorescence. However, in the late phases, it may become intensely hyperfluorescent due to large amount of dye accumulating in the lesion. Being an inflammatory choroidal pathology, a tuberculoma may also be associated with an exudative detachment. In late phases dye would pool in this space and further enhance the fluorescence seen around the choroidal mass (Fig. 3.2) [1, 2].
Fig. 3.2
Composite image of the fundus and fluorescein angiography of a choroidal tuberculoma. Note the hyperfluorescence seen in the tuberculoma due to leakage of dye into the lesion. There is associated surrounding hyperfluorescence due to pooling of dye in the surrounding neurosensory detachment
Some large granulomas may start to fluoresce earlier than usual with increasing intensity of the fluorescence in later phases along with a dilated capillary bed [1]. We have also seen subretinal fibrotic changes developing during the healing of large tubercular granulomas (Fig. 3.3) [3].
Fig. 3.3
A healing choroidal tuberculoma with evidence of evolving subretinal scarring at the margins of the lesion
Few common differential diagnoses of tubercular granulomatous mass lesions are haemangioma, melanoma and metastasis. A haemangioma has its own intrinsic large blood-filled spaces separated by septae. This gives it a very characteristic appearance of patchy adjacent areas of hyperfluorescence and hypofluorescence from very early phases of the angiogram. The entire mass never becomes intensely hyperfluorescent (Fig. 3.4a–c) [4].
Fig. 3.4
(a) Fundus image of a peripapillary orange mass suggestive of a circumscribed choroidal haemangioma (black arrows) (b) Arteriovenous phase fluorescein angiogram of the mass shows patchy hyperfluorescence (c) Late-phase fluorescein angiogram of the mass shows persisting patchy hyperfluorescence. Marked increase in the fluorescence is not seen
A melanoma can have its own blood supply and show a characteristic “double circulation” sign from the early phases. Apart from this, a melanoma also does not have very characteristic features on fluorescein angiography [5].
Metastasis also appears as slowly filling hyperfluorescent lesions on FFA . We have found multiple punctate hyperfluorescent dots surrounding such lesions in many of our cases. These could be due to local infiltration of the tumour cells (Fig. 3.5a–c).
Fig. 3.5
(a) Fundus image of a peripapillary yellowish-orange mass (black arrows). (b) Venous phase fluorescein angiogram of the mass shows slowly increasing fluorescence in the mass with a peripheral rim of punctuate hyperfluorescent dots (white arrows). (c) Late-phase fluorescein angiogram of the mass shows a further increase in fluorescence of the mass with persistence of the rim of hyperfluorescent dots
As stated before though some of these features may suggest a particular aetiology, there are no definite diagnostic features of a tubercular granuloma on fluorescein angiography. In fact a sarcoid granuloma could entirely simulate a tubercular granuloma on fluorescein angiography.
Tuberculomas may sometimes be associated with deep retinal and subretinal haemorrhages. In such cases fluorescein angiography may be important to rule out development of a secondary choroidal neovascularisation or a retinal angiomatous proliferation-like lesion. An early inflammatory neovascularisation of the disc may also be picked up in cases of tubercular aetiology [1, 2].
Fluorescein angiography is also helpful in the evaluation of the associated vasculitis seen in some cases. Presence of vitritis, significant exudation and perivenular infiltration into adjacent choroid forming pigmented perivenular scars in cases of vasculitis have been associated with tubercular aetiology [6–9]. We have seen occlusive vasculitis in tubercular cases, especially if there is associated retinitis (Fig. 3.6a–c) [6]. During the healing stage of tubercular retinitis, periarterial plaques (Kyrieleis arteriolitis) have also been seen (Fig. 3.7). In fact, Kyrieleis arteriolitis was first described in a case of suspected tubercular retinitis [10]. However, it is again not pathognomonic of tubercular aetiology and may be seen in a variety of cases of retinitis during the phase of resolution.
Fig. 3.6
(a) Fundus image of a case of diffuse tubercular chorioretinitis. (b) Arterial phase angiogram showing partial filling of the arteries, suggestive of occlusive arteriolitis and an early neovascularisation of the disc. (c) Temporal fluorescein angiogram showing incomplete filling of the vessels with a pigmented paravenous patch of chorioretinitis
Fig. 3.7
Periarterial plaques (Kyrieleis arteriolitis) (white arrows) seen during the healing stage of a case of tubercular chorioretinitis
Ultrawide field imaging that captures around 200 degrees or nearly 80% of retinal surface area (SLO, Optomap P200Tx, Optos PLC, Dunfermline UK) has further enhanced our ability to image even the most peripheral fundus lesions. It provides valuable information in cases with choroidal lesions and associated vasculitis [11]. The exact extent and location of the granulomas and their response to therapy can be assessed more easily. Moreover, the ability to detect peripheral areas of neovascularisation, leakage and capillary nonperfusion enables us to assess associated peripheral vasculitis and helps in better planning of laser photocoagulation for such lesions [11–15].
Few authors have described tubercular choroiditis manifesting as serpiginous-like choroiditis [16–18]. In such cases the active edge of the lesion is initially hypofluorescent with increasing fluorescence in late phases with diffuse staining of the advancing edge. The lesions usually have an amoeboid pattern of extension which is well delineated on FFA. An inactive healed lesion may either present as a window defect or blocked fluorescence due to reactive hyperplasia of pigment epithelium that shows delayed staining [19].
Macular oedema may complicate choroiditis, retinal vasculitis and intermediate uveitis associated with tubercular involvement. It may present in a cystoid pattern with hyperfluorescence in the late phases of the angiogram or a diffuse oedema [1]. These changes are also seen on fluorescein angiography. In fact we have found Ultra wide field angiography (UWFA) a good tool to simultaneously pick up both the peripheral and central changes on fluorescein angiography in cases of uveitis. This is all the more helpful in cases where the pupil in small due to synechia [12].
Indocyanine Green (ICG) Angiography
Indocyanine green (ICG) angiography involves the use of ICG dye along with longer wavelength of light to capture fundus images. ICG is different from sodium fluorescein as it is much more protein bound (98% compared to 80%) and fluoresces in the infrared spectrum. Moreover, ICG leaks only from the choriocapillaris and stays in the choroidal stroma for long, unlike fluorescein dye that leaks from choroidal as well as retinal vessels. Blockage of fluorescence in FFA from RPE further compounds evaluation of choroid that is overcome in ICG angiography [20].
In cases of choroiditis, especially Vogt-Koyanagi-Harada syndrome, it may help to detect subtle subclinical lesions. It has been proposed as the investigation of choice to monitor response to therapy in such cases of choroiditis. Experience with ICG in cases of tubercular aetiology is limited. Herbort et al. [20] described two different ICG presentations with hypofluorescent lesions in all phases of angiography being ascribed to full-thickness choroidal involvement or atrophy and early hypofluorescent lesions becoming hyperfluorescent in mid and later phases due to partial choroidal thickness involvement. Tayanc et al. [21] reported two cases of ocular tuberculosis with choroidal granuloma wherein ICG was performed. The first case showed two hypofluorescent lesions in the choroid although only one lesion was seen clinically. The second case had a hypofluorescent lesion much bigger in size than the clinically visualised lesion. In both cases, hypofluorescence persisted throughout the angiogram. With treatment both cases showed decrease in hypofluorescence of the lesions. The role of ICG was further evaluated in tubercular chorioretinitis by Wolfensberger et al. [22] who described four different clinical signs in such cases. Gupta et al. reported cases with large granulomas wherein early hypofluorescence in the entire lesion was followed by late hyperfluorescence in the periphery and persisting hypofluorescence in the central dense core [23]. ICG angiography has also been utilised in delineating the hypofluorescent active edges in serpiginous-like choroiditis [17].
Fundus Autofluorescence
Fundus autofluorescence (FAF) is a noninvasive imaging technique that details the health of the RPE. As RPE and choriocapillaris are the proposed major sites of involvement in tubercular serpiginous-like choroiditis (SLC), FAF can play an important role in assessing disease activity and resolution of such lesions.
FAF has several advantages over both FFA and ICGA. Besides being noninvasive, it is easier to interpret than FFA in cases where there are active lesions interspersed between healed regions. Similarly, it overcomes the shortcomings of ICGA which cannot differentiate between active and healed lesions as both appear hypofluorescent on it.
Gupta et al. [24] have described different stages in the resolution of SLC lesions using FAF imaging. The acute stage (stage 1) shows an ill-defined amorphous lesion with halo-like hyper-autofluorescence and ill-defined margins. With resolution, the lesion progresses through different stages with increasing hypo-autofluorescence in an outward-in fashion. The central stippled hyper-autofluorescence has been shown to persist until the entire lesion becomes hypo-autofluorescent (stage 4). This marks the end of activity and RPE atrophy.
Optical Coherence Tomography (OCT)
OCT technology, since its inception, has evolved immensely. Beginning with time domain technology, we have now moved on to commercially available spectral domain and now swept-source OCT that provide much better resolution and deeper penetration. With advancement in technology, our ability to characterise pathological changes at a microscopic level in vivo has greatly improved. We can now obtain images from the level of the posterior hyaloid to the choroidal-scleral interface with swept-source OCT. These have further enhanced our understanding of choroidal pathologies and their response to therapy. Introduction of OCT angiography (OCTA), a dyeless angiography, has improved pickup rates of choroidal neovascularisation. Spectral domain OCTA can also image choroidal vasculature. This will further enhance our understanding of how these choroidal lesions affect the choroidal vasculature.
Macular oedema may complicate various forms of uveitis associated with ocular tuberculosis. OCT plays an important role in assessing macular involvement and its response to treatment. Three different forms of macular oedema have been associated with tubercular infection, namely, cystoid macular oedema, diffuse macular oedema and serous retinal detachment (Fig. 3.8) [25]. Increased thickness of macula corresponds with poor visual acuity. As the oedema responds to treatment, there is a decrease in thickness and improvement in visual acuity. We have found en face imaging using swept-source OCT to best highlight the presence and extent of cystoid macular oedema.
