Case Report: Foveolitis as an Indicator of Underlying Undiagnosed Dengue Fever

INTRODUCTION

Individuals living in the tropical and subtropical nations are more vulnerable to dengue virus infections. The affected individuals comprise about two-fifths of the world population. ¹ Dengue infection is now endemic in many countries, particularly in the Southeast Asia, Indian subcontinent, and the Americas. ² The actual incidence of dengue fever may be at a much higher level, as many cases with less severe systemic manifestations may be underreported. ³

Recently, there has been a spike in the number of reported cases of dengue and allied ocular complications from all over the world, including India. ^3,4 This may be attributed to the rapid resurgence of the principal vector, Aedes aegypti, due to overcrowding and urbanization along with the hot and humid climate of the tropical countries. ⁵

We describe a case of a young woman, who initially presented to the ophthalmologists with acute unilateral diminution of vision and fever. She was subsequently diagnosed as dengue foveolitis and was treated successfully with oral steroids and supportive treatments.

CASE REPORT

A 30-year-old Indian woman presented to the ophthalmology department of a tertiary care center in North India with sudden painless diminution of vision in the left eye (LE) for the last 2 days. Systemic history revealed the presence of fever, myalgia, and arthralgia for 5 days before the onset of ocular symptoms. The fever was low-grade and continuous, and was relieved by taking antipyretic medication. At presentation, her vitals were stable with normal systemic examination findings. On ocular examination, her best-corrected visual acuity (BCVA) in the right eye (RE) was 20/20 and in the LE was 20/120. Anterior segment examination and pupillary reaction were normal in both eyes. Fundus was unremarkable in the RE, whereas the LE had few superficial retinal hemorrhages and few ill-defined tiny yellowish subretinal lesions at the center of the macula with a dull foveal reflex (Figure 1). Amsler grid charting revealed a central scotoma in the LE. With a provisional diagnosis of hemorrhagic maculopathy, further investigations were performed to identify the cause. Fundus fluorescein angiography (FFA) of the RE was normal (Figure 2A); the LE showed perifoveal capillary leakage in the late phase and few blocked fluorescences corresponding to the areas of retinal hemorrhages (Figure 2B). The macular spectral-domain optical coherence tomography (SDOCT) scan of RE was normal (Figure 2C). Spectral-domain OCT macular scan of the LE (Figure 2D) showed focal discontinuity in the ellipsoid zone (EZ) and disruption in the external limiting membrane (ELM). Furthermore, a hyperreflective conical lesion was noted arising beneath the ELM and traversing full thickness of the retina, causing disruption of foveal contour. This was also associated with few parafoveal intraretinal cystoid spaces. These findings on LE OCT were consistent with foveolitis. The retinal pigment epithelium appeared to be intact.

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Fundus images of the patient. (A) Normal right eye fundus. (B) Left eye fundus revealing superficial retinal hemorrhages (black arrow) and ill-defined tiny yellowish subretinal lesions at the center of the posterior pole (yellow arrow).

Citation: The American Journal of Tropical Medicine and Hygiene 104, 1; 10.4269/ajtmh.20-0806

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Ancillary ophthalmic imaging on presentation. (A) Normal fundus fluorescein angiography (FFA) of the right eye (RE). (B) Late phase FFA of the left eye (LE) revealing perifoveal capillary leakages (yellow dotted circle) and few blocked fluorescence corresponding to the areas of retinal hemorrhages. (C) Spectral domain optical coherence tomography (SDOCT) showing normal foveal contour in the RE. (D) Spectral domain optical coherence tomography of the LE showed focal discontinuity in the ellipsoid zone and the external limiting membrane just above the intact retinal pigment epithelium (area within red bracket). A subfoveal hyperreflective lesion with conical elevation (white arrow) and few tiny parafoveal intraretinal cystoid spaces (yellow arrow) was also noticed.

Citation: The American Journal of Tropical Medicine and Hygiene 104, 1; 10.4269/ajtmh.20-0806

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By corroborating the patient’s history and clinical picture along with multimodal imaging findings, she was investigated for acute undifferentiated febrile illness, and a physician consultation was sought. Keeping in mind the local endemic diseases, the patient was subjected to further blood investigations. Complete blood count was deranged with reduced total leucocyte count (2,100 cells/µL) and thrombocytopenia (89 × 109/L). The dengue virus Nonstructural protein 1 and IgM antibody against dengue turned out to be positive. Hence, a diagnosis of dengue maculopathy was made in the LE.

The patient was started on 1 mg/kg oral prednisolone per day and was asked to maintain proper fluid intake. She was kept under close follow-up with both ophthalmologist and general physician with regular monitoring of blood counts.

Two weeks following initiation of oral steroids, the BCVA of the LE improved to 20/40, and fundoscopy showed partial resolution of the foveal lesion and hemorrhages (Figure 3A). Repeat SDOCT macular scan of the LE showed a small residual localized linear hyperreflective lesion in the outer nuclear layer with complete restoration of the continuity of the EZ and ELM and disappearance of the conical elevation (Figure 3B). Oral steroid was gradually tapered in the next 6 weeks.

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Repeat imaging of the left eye (LE) 2 weeks after initiation of treatment. (A) Fundus image showed partial resolution of the foveal lesions and hemorrhages. (B) Spectral-domain optical coherence tomography of the LE through the macula showed a residual localized linear hyperreflective lesion in the outer nuclear layer (yellow arrow) with restoration of the continuity of the ellipsoid zone and external limiting membrane.

Citation: The American Journal of Tropical Medicine and Hygiene 104, 1; 10.4269/ajtmh.20-0806

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At 3 months follow-up, near-complete resolution of hemorrhagic maculopathy was noted in the LE (Figure 4B), and BCVA was restored to 20/20 in the LE. Corresponding OCT revealed normal foveal contour and restoration of all retinal layers (Figure 4D). Repeat hemogram revealed normal values of total leucocyte count (5,600 cells/µL) and platelets (165 × 10⁹/L).

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Fundus images after 3 months of initial presentation. (A) Right eye (RE) having normal appearance. (B) Left eye (LE) fundus almost normal, except very few punctate residual retinal hemorrhages. (C and D) Optical coherence tomography of the RE and LE, respectively, at 3 months showing normal foveal contour and retinal layers.

Citation: The American Journal of Tropical Medicine and Hygiene 104, 1; 10.4269/ajtmh.20-0806

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DISCUSSION

Ocular manifestations in dengue can vary from subtle signs such as subconjunctival hemorrhage, uveitis, and retinal hemorrhages to more serious complications such as maculopathy, foveolitis, macular edema, retinal vascular occlusion, optic neuropathy, and choroiditis. Dengue maculopathy has been reported in about 10% of hospitalized dengue fever cases. ^6–9 Transient thrombocytopenia is a commonly encountered hematological derangement in dengue fever. As the infection is brought under control, the normalization of platelet count is also observed in most cases. Malhotra et al. ¹⁰ have also shown that there is a significant positive association between degree of thrombocytopenia and retinal abnormalities.

Many studies have revealed that ocular features usually manifest within 10 days of onset of fever, as was seen in our patient. ^3,11 The pathophysiologic mechanism behind ophthalmic complications of dengue has not been fully elucidated. Many studies point to the likelihood of an immune-mediated process. ^12,13 Chang et al. ¹⁴ attributed the pathophysiology to immune complex deposition on the walls of small caliber retinal vessels, leading to further inflammatory damage. The delay observed in our case between the onset of fever and ocular manifestations could correspond to the time interval for antibody production, immune complex deposition, or production of autoantibodies. This may imply that the ocular manifestations seen in dengue fever are due to an immune-mediated process rather than a direct viral insult. Dengue foveolitis corresponds to a disruption of the outer neurosensory retina in OCT, which is seen clinically as yellow–orange lesions in the foveal region. ¹⁵ Foveolitis can present with a BCVA ranging from 20/20 to counting fingers. ^6,7,9 They usually present on day 7 after the onset of the dengue fever. ¹⁶

Optical coherence tomography is a very useful tool in monitoring the dengue foveolitis as was shown by Teoh et al. ¹⁶ The authors categorized the type of macular edema based on their appearance on OCT and correlated it with the visual acuity and the prognosis. The three patterns seen on OCT included type 1 (diffuse retinal thickening; 44.6%), type 2 (cystoid macular edema; 21.6%), and type 3 (foveolitis; 33.8%). Diffuse retinal thickening in OCT was associated with best prognosis, and foveolitis group was associated with poorest prognosis. All patients in the foveolitis group had persistent central or paracentral scotoma even after structural restoration in OCT. ¹⁶ Although our patient had type 3 (foveolitis) pattern on OCT at presentation, her visual acuity was restored to baseline without any persistent scotoma at the end of 3 months. Agarwal et al. ¹⁷ have demonstrated conical foveal elevation and disruption of outer retinal layers by swept-source OCT in their study and attributed both ischemic and inflammatory component for pathogenesis of dengue maculopathy. Optical coherence tomography findings in our patient were consistent with those described by Agarwal et al. Fundus fluorescein angiography of dengue fever patients may demonstrate features of subtle vasculitis such as vascular occlusion or leakage, which may not be visible by simple fundus examination or in colored fundus photographs. ^18,19

Many patients with dengue-associated ocular disease have a self-limiting course and resolve spontaneously without any treatment. Both systemic and topical steroids have been found to be effective in persistently symptomatic patients with decreased vision because of dengue-associated ocular complications. Bacsal et al. ¹³ had treated patients with ocular complications secondary to dengue with oral prednisolone (1 mg/kg) alone, and tapering according to clinical response yielded good outcomes in those patients. In cases which have macular involvement, a mild persistent visual impairment is usually noted, but in our patient, there was complete recovery. ^3,8,13,20 Agarwal et al. ¹⁷ have treated 32 eyes of dengue foveolitis with 0.5–1 mg/kg/day oral corticosteroid gradually tapered over 4–6 weeks, and demonstrated visual improvement and restoration of integrity of retinal layers in all of the treated eyes. However, the authors noticed persistent ischemia of deep retinal plexuses in all eyes despite corticosteroid-induced improvement of inflammatory vitreoretinal changes.

The number of case reports describing dengue fever presenting initially to an ophthalmologist is limited in the literature. ^3,8,20 Gupta et al. ³ described three cases, which presented with painless diminution of vision and a preexisting history of fever and constitutional symptoms. These cases were later diagnosed to be serologically positive for dengue virus. The authors also added that the frequency of dengue fever may be greater than that which is reported because cases with milder symptoms may remain undiagnosed. ³ Tabbara also reported multifocal retinochoroiditis in two patients of acute onset diminution of vision following a brief period of febrile illness and serologic evidence of dengue fever subsequent to ocular diagnosis. ⁸ Akanda et al. ²⁰ described a case, which presented with fever and diarrhea initially and was empirically treated with antibiotics. However, subsequent development of scotomas and further testing revealed dengue infection in this patient.

To conclude, our case, in concurrence with a few limited reports in the literature, encourages ophthalmologists and physicians to be cognizant of the extended ocular spectrum of dengue fever, for timely diagnosis and referral of these patients.