Multifocal Choroiditis with Retinal Vasculitis, Optic Neuropathy, and Keratoconus in a Young Saudi Male.

The purpose of this study is to describe an association of unilateral multifocal choroiditis (MFC), retinal vasculitis, optic neuropathy, and bilateral keratoconus in a young Saudi male. A 27-year-old male patient with stable bilateral keratoconus presented with a painless vision loss in his left eye. Ophthalmic examinations revealed multiple foci of idiopathic chorioretinitis, retinal vasculitis, and mild optic disc leakage on fluorescein angiography, all of which resolved on systemic therapy with mycophenolate mofetil and prednisone after 3 months. Systemic medication was stopped after 8 months. One year after presentation, patient's visual acuity has improved and remained stable. Systemic immunomodulatory therapy can be effective in managing and leading to resolution of MFC, retinal vasculitis, and optic disc leak in young patients.

Introduction

Idiopathic multifocal choroiditis (MFC) typically affects young patients, often women, with no associated systemic disease. The characteristic inflammatory changes of the choroid, choriocapillaris, and retinal pigment epithelium (RPE) are yellow-white foci beneath the retina.[12] Other ocular complications, including choroidal neovascular membrane[23] and optic neuropathy,[4] can further decrease vision. Herein, we describe an unusual association and treatment of idiopathic MFC with optic neuropathy, retinal vasculitis, and keratoconus in a young male from Saudi Arabia.

Case Report

A 27-year-old patient presented to Emergency Room at the King Khaled Eye Specialist Hospital complaining of 1 week history of decreased vision in the left eye (OS) without pain. The patient had no history of systemic diseases and was known to have bilateral keratoconus corrected with glasses and contact lenses. Results of systemic examination were unremarkable; he had not been exposed to any common infections. The right eye had best-corrected visual acuity at initial examination 20/25 with normal intraocular pressure and normal clinical examination. The OS corrected to 2/200 and had normal intraocular pressure. There was a 1+ relative afferent pupillary defect; ocular movements were normal. The anterior segment examination revealed no acute inflammatory reaction. There were no vitreous cells present. Fundus examination of the OS showed multiple small yellow-white lesions in the posterior pole and around the optic nerve head [Figure 1]. The optic disc showed normal margins, cupping and was not swollen. No subretinal fluid or hemorrhage was observed.

Figure 1

(a) Color fundus photo of left eye of a 27-year-old male with decreased visual acuity demonstrates multiple yellowish focal and placoid subretinal lesions (white arrow). (b) Slit lamp photography of the same eye shows inferior steeper curving of the slit beam suggestive of keratoconus. (c) Fundus autofluorescence image of the same eye shows hypoautofluorescent spots corresponding to lesions on fundus photo. (d) Indocyanine green angiography of the same eye demonstrates deep choroidal hypofluorescent lesions (white arrowhead)

Fundus autofluorescence of the OS showed multiple areas of hypoautoflurescence corresponding to the areas of lesions on ophthalmoscopy. Fundus fluorescein angiography (FFA) of the OS showed the focal lesions to be hypofluorescent in the early and hyperfluorescent in the late stages of the angiogram in addition to retinal vasculitis [Figure 2]. The optic nerve head demonstrated late hyperfluorescence. Spectral-domain optical coherence tomography (OCT) images of the right eye were normal whereas OS showed small hyperreflective lesions at the level of RPE and outer retina without subretinal fluid.

Figure 2

(a) Ultra-wide-field fluorescein angiography of asymptomatic right eye shows normal angiogram. (b) Ultra-wide-field fluorescein angiography of the left eye shows posterior pole lesions with retinal vasculitis. (c) Magnified image of B shows hyperfluorescent lesions, engorged veins (superior to the optic disk) and retinal vasculitis (white arrowhead)

The following investigations were performed for the patient: computer tomography of the chest, complete blood cell count, erythrocyte sedimentation rate, liver function tests, blood nitrogen urea, electrolyte panel, serum angiotensin-converting enzyme, antinuclear antibody, anti-DNA antibody, Bartonella serology, Venereal Disease Research Laboratory test, fluorescent treponemal antibody absorption test, tuberculin skin test, QuantiFERON tuberculosis test, and magnetic resonance imaging of the brain to rule out cerebral vasculitis. All of the above investigations were normal.

After infectious etiology has been excluded to the best of our knowledge, the treatment was started with oral mycophenolate mofetil 500 mg twice a day and prednisone 60 mg a day tapered within 2 months to maintenance dose of 5 mg with regular follow-up visits. At examination, 2 months later, the juxtafoveal subretinal lesions became confluent. His visual acuity improved after 2 months of therapy and was 20/80 in OS at the last follow-up 1 year after the disease onset. Due to worsening of obesity, prednisone was discontinued. Subsequently, the patient wished to stop all immunomodulatory therapy. On the last examination, retinal findings were stable and follow-up FFA showed resolved vasculitis and no leakage from optic disc [Figure 3].

Figure 3

(a) Color fundus photo of the same eye 1 year after immunomodulatory therapy demonstrates stable placoid subretinal lesions. (b and c) Optical coherence tomography horizontal (b) and vertical (c) sections through the fovea show hyperreflective subretinal lesions. Fluorescein angiogram shows the same lesions as hypofluorescent in the early phase (d) and hyperfluorescent (e) in late phases. Posterior pole lesions show staining but no active leak and vasculitis is resolved. Blurring of the inferior half of images is due to keratoconus

Comment

To the best of our knowledge, this is the first description of a constellation of posterior MFC, optic neuropathy, retinal vasculitis with keratoconus in a young adult. MFC is an inflammatory disease that frequently results in ocular complications (such as choroidal neovascularization [CNV]) and loss of visual acuity. When no infectious or noninfectious etiology is found, the disease is categorized as idiopathic such as in our patient.

Primary lesions, in this case, were confined to the posterior pole and around the optic disc in one eye. The lesions were demonstrated on fundus autofluorescence and indocyanine green angiography even better than on color fundus photography as reported previously.[5] They were similar to lesions described in punctate inner choroidopathy (PIC) with no associated CNV. Recent reports have identified MFC/PIC variant as a separate nosologic entity.[36] Imaging studies have shown that MFC/PIC can have adjacent photoreceptor attenuation of variable severity including chorioretinal atrophic lesions, central photoreceptor loss, and outer (zonal) retinal atrophy.[7] Our case shares OCT features that would certainly fall into that entity.

Optic neuropathy is an infrequent and underreported complication of MFC. Thorne et al. published the first case series of 8 patients with optic disc edema/pallor associated with MFC/panuveitis. They suggested that optic neuropathy was steroid-responsive but steroid-dependent, and recurrences of optic nerve inflammation might occur resulting in vision loss. Our patient presented with mild afferent pupillary defect and mild leakage on fluorescein angiogram in late phases, both of which completely disappeared on systemic immunomodulatory therapy. Optic disc edema was clinically not evident and the fluorescein leakage may thus be a sign of papillitis. Visual field function was not tested due to poor fixation at presentation.

Retinal vasculitis not associated with systemic infection or inflammation can rarely be an accompanying sign of some white dot syndromes. Entities where retinal vasculitis has been reported include birdshot chorioretinopathy, acute posterior multifocal placoid pigment epitheliopathy, and MFC.[8] The former two, however, are phenotypically excluded in our case.

A typically described patient with MFC/PIC is usually a young, mildly myopic female. Our patient was a male with high myopic astigmatism in both eyes due to inferior keratoconus [Figure 4]. Keratoconus is very common in Saudi Arabia;[9] thus, association with neurochoroiditis and vasculitis in this patient may be incidental. Of interest is an observation of dramatic visual acuity improvement after immunomodulatory therapy. The combination of agents and initial dose was selected based on prior reports.[10] Best-corrected visual acuity was tested repeatedly before and after treatment, including hard contact lens fitting. While choroidal and RPE lesions at presentation were perifoveal, after treatment they have not disappeared but stabilized and therefore, are not believed to contribute significantly to vision improvement. One of the possible reasons for vision gain is a reduction in keratoconus steepening. There is recent evidence of overexpression of inflammatory mediators including cytokines, matrix metalloproteinases (MMPs), tumor necrosis factor-alpha (TNF-α), and interleukin 6 (IL-6) in tears of patients with keratoconus, thus suggesting an inflammatory component to the disease.[11] Mycophenolate mofetil has been shown to downregulate numerous inflammatory cytokines including IL-6. Most recently, immunomodulatory therapy achieved downregulation of IL-6, TNF-α, and MMP-9 levels that were overexpressed in eyes with keratoconus.[12] Therefore, this mechanism is plausible in our patient. The limitation of this report is that corneal topography before and after treatment was taken with different instruments which make direct comparison difficult.

Figure 4

Pentacam-4 map refractive images of the right (1) and left (2) corneas showing the characteristic features of keratoconus; sagittal curvature map of the anterior corneal surface (A) shows significant inferior paracentral steeping. The anterior elevation map (B) and the posterior elevation map (D) all show inferior paracentral islands with significant elevations corresponding with an area of significant paracentral thinning (C)

Conclusion

In summary, we describe a unique and previously unreported presentation and course of posterior uveitis in a young Saudi male. Systemic immunomodulatory therapy may be effective in the resolution of MFC, retinal vasculitis, and optic disc leakage, along with a reduction in corneal steepening secondary to keratoconus, in young patients.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.