Woman presents with monocular decrease in vision

A 30-year-old Indian woman was referred to the uveitis service with a chief complaint of decreased vision in the right eye for several months. She started having pain in the right eye with black flashes and headaches 4 months earlier.

She was seen initially by another ophthalmologist, who referred her with a presumptive diagnosis of central retinal vein occlusion in the right eye. She had no ocular or medical history and denied a history of trauma, recent travel or medications. Review of systems was significant for an occasional productive cough that had been present for 4 months. She denied any night sweats, chills, fevers, chest pain or weight loss.

On exam, best corrected visual acuity was 20/50 in the right eye and 20/20 in the left eye. Pupils were equal, round and briskly reactive to light bilaterally with no relative afferent pupillary defect. Extraocular motility was full bilaterally. IOPs were normal. Confrontation visual fields showed partial superior temporal deficiency in the right eye and full in the left eye.

Slit lamp exam was remarkable for 1+ anterior vitreous cell in the right eye. There was no anterior chamber cell or flare. Dilated fundus exam of the right eye revealed lesions in a serpentine pattern in the superonasal, nasal and inferonasal periphery and active superonasal choroiditis inferior to the inferior arcade (Figure 1). The remainder of the fundus exam in the right eye was unremarkable. Posterior segment exam of the left eye was normal.

Fluorescein angiography of the right eye showed hyperfluorescence of the active lesions, diffuse microvascular leakage, macular leakage and disc leakage. The inactive scars demonstrated transmission hyperfluorescence (Figure 2). Enhanced depth imaging OCT (EDI-OCT) of the border of an inferior active lesion revealed elevated choroidal infiltrate with disruption of the outer layers of the retina (Figure 3). OCT of the macula demonstrated cystoid macular edema with subretinal and intraretinal fluid in the right eye (Figure 4a). In comparison, OCT of the macula in the left eye was unremarkable (Figure 4b).

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Vitritis with these characteristic fundus lesions appears to be serpiginous choroiditis (SC). It is characterized by a geographic pattern of choroiditis that extends from the juxtapapillary choroid and spreads centrifugally, affecting the overlying retinal pigment epithelium (RPE) and the outer retina. The serpentine lesions extending from the optic disc are typically bilateral. It usually affects middle-aged healthy individuals. Serpiginous choroiditis typically has a quiet anterior chamber, as in this case.

The aforementioned disease entity is thought to be largely due to an abnormal immune response. This patient was noted to have a positive Mycobacterium tuberculosis test on referral. In the setting of this positive test, her symptoms and the findings of unilateral multifocal chorioretinitis in a characteristic serpiginous pattern, there was high suspicion for tuberculous serpiginous-like choroidopathy (SLC), otherwise known as infectious multifocal serpiginoid choroiditis (MSC). SLC presents commonly with fundus findings reminiscent of SC and evidence of active tuberculosis in patients from an endemic area. Other infectious etiologies that can cause a similar presentation and should be considered are herpes and syphilis.

It is difficult to differentiate between SC and SLC clinically. Apart from laboratory workup, EDI-OCT may be a useful tool as SLC appears to manifest as elevated choroidal lesions causing elevation of the RPE-Bruch’s membrane due to infiltration of the choroid, which is not usually present in SC lesions.

Before referral, this patient was diagnosed with posterior uveitis and cystoid macular edema (CME). She was treated with prednisolone twice daily and ketorolac. Bloodwork, including complete blood count with differential, interferon-gamma release assay (IGRA), angiotensin-converting enzyme and lysozyme, was remarkable for slightly elevated neutrophiles and a positive IGRA test. Chest X-ray showed no pulmonary involvement.

On initial referral to the uveitis service and based on clinical presentation, imaging and positive IGRA test, the patient was diagnosed with SLC. Ketorolac was discontinued, and prednisolone eye drops were increased to three times daily. In the setting of positive IGRA test and symptoms of ocular tuberculosis (OTB), she was seen by an infectious disease specialist and started on antitubercular therapy (ATT) with rifampin, isoniazid, pyrazinamide, ethambutol and vitamin B6. She could not tolerate pyrazinamide and was switched to rifampin, isoniazid, ethambutol and levofloxacin with a plan to continue for 6 months. Three weeks after initiation of ATT, prednisolone was discontinued, and she was started on oral prednisone 40 mg daily. She was seen 2 weeks later with dramatic improvement in vision to 20/25 in the right eye and complete resolution of CME. Prednisone was decreased to 30 mg daily, which she is taking currently.

Tuberculosis (TB) is a chronic infection caused by Mycobacterium tuberculosis (Mtb) that poses a serious global health issue. It can affect multiple organs in the body, including the eye. Diagnosis of OTB is challenging due to a wide range of ocular manifestations. It is usually based on evidence of past or present infection and exclusion of other etiologies. Diagnosis can be made based on a positive tuberculin skin test (TST) or IGRA, chest radiography or, in select cases, intraocular fluid examination to detect Mtb DNA.

The most common ocular symptom is tubercular posterior uveitis, in particular tubercular choroiditis. Choroidal involvement can manifest with different phenotypes, including tubercular SLC, multifocal choroiditis (MC) or acute posterior multifocal placoid pigment epitheliopathy. The patient’s presentation with multifocal discrete and confluent yellowish lesions with central healing and active edges without involvement of the optic disc is common for SLC. It can be either bilateral or unilateral with mild vitritis.

In posterior uveitis, there are different lesion types that can present similarly. As stated earlier, the diagnosis of SC vs. SLC can be difficult. It is important to differentiate between these two disease entities because management and hence patient outcomes differ based on diagnosis. Therefore, retinal imaging is often employed, and multiple imaging modalities are recommended. Fundus photography is useful for monitoring the course of the disease. Fluorescein angiography and indocyanine green angiography are helpful in detecting inflammatory lesions and identifying vasculitis. Additional information on the involvement of the choroid can be provided by novel OCT imaging modalities, including EDI-OCT and OCT angiography. EDI-OCT allows visualization of deep ocular tissues such as the choroid and sclera. In the case of SLC, the acute lesions show disruption of ellipsoid and myoid zones and retinal hyperreflectivity with increased choroidal thickness, which aids greatly in distinguishing it from SC.

The exact etiopathogenesis of SLC is not entirely elucidated. Nevertheless, it is grossly divided into direct and indirect mechanisms. The direct mechanism generally involves an immune response to active infection and is supported by resolution and prevention of recurrence in response to ATT, whereas the indirect mechanism is caused by an abnormal immune response and is implied when immunosuppressive therapy is sufficient. Commonly, both mechanisms are at play.

The Collaborative Ocular Tuberculosis Study group recently proposed consensus guidelines on treatment of different OTB phenotypes. Ophthalmologists can initiate ATT based on positive TST and IGRA. However, treatment decisions are limited by specificity and sensitivity of these tests. Furthermore, radiologic results might not always demonstrate active pulmonary disease or previous exposure. Therefore, it is important to gather a thorough history. In general, when patients from TB-endemic regions present with signs and symptoms suspicious for OTB, it is important to rule out non-TB entities. Conversely, in patients from non-endemic areas, it is important to rule out TB.

In terms of management, current evidence suggests that ATT is beneficial in recurrent tubercular anterior uveitis, tubercular intermediate and posterior uveitis, and tubercular retinal vasculitis. The first episode of tubercular anterior uveitis can benefit from ATT only with concomitant positive immunologic or radiologic tests. Systemic steroids can be administered at the beginning of or soon after the administration of ATT in cases of tubercular SLC, tuberculoma and tubercular MC. Systemic corticosteroid-sparing immunosuppressants can also be used when inflammation recurs during steroid taper.