Presumed atypical peripapillary Vogt-Koyanagi-Harada disease.

PURPOSE: To describe a case of bilateral presumed atypical Harada disease with sequential, not simultaneous, involvement of the peripapillary retina (subretinal fluid) in a healthy patient with no systemic complaints. OBSERVATION: A 35-year-old healthy white man presented with sudden paracentral visual loss in the left eye. His medical history was unremarkable. However, he reported a similar episode 20 months earlier in the right eye that was associated with macular serous retinal detachment. The right eye showed evidence of reactive peripapillary atrophy and pigmentary alteration in the macula. Optical coherence tomography scans of the posterior left eye segment revealed a diffuse thickened choroid, papillomacular subretinal exudate and discontinuity of the ellipsoid layer with suggestion of vitreous cellularity. Autofluorescence imaging of the left eye showed peripapillary hyperautofluorescence. A fluorescein angiogram revealed progressive staining and pooling of the peripapillary retina with corresponding retinal vasculitis. Indocyanine green angiography revealed multiple hypocyanescent lesions with an area of hypercyanescence temporal to the disc. Rheumatologic evaluation and laboratory tests were all negative. Chest tomography was normal. Considering the apparent absence of infectious diseases, the patient was started on 60 mg/day prednisone. After 8 days, visual acuity improved to 20/250, improving to 20/20 vision six months after a slow steroid wean.
CONCLUSION: We believe our case represented a variant of the Vogt-Koyanagi-Harada syndrome in an atypical situation, because the patient fulfilled the presumed criteria. Furthermore, the findings of clinical and complementary examinations led to this nosological entity to the exclusion of others. IMPORTANCE: The point of this case is to alert ophthalmologists to the existence of this atypical presentation of the disease so that it should be included among the differential diagnoses of pathologies that present with these findings.

Introduction

Serous retinal detachment represents a diagnostic challenge because of its etiological diversity. Inflammatory and infectious diseases should be considered in order to direct appropriate clinical management.

We describe a case of bilateral presumed atypical Harada disease with sequential, not simultaneous, involvement of the peripapillary retina with subretinal fluid, in a healthy patient with no systemic complaints.

Case report

A 35-year-old healthy white man presented with sudden paracentral visual loss in the left eye. His medical history was unremarkable. He had reported a similar episode 20 months earlier in the right eye that was associated with macular serous retinal detachment (Fig. 1-a and 1-b). At that time, the exam of the left eye showed no abnormalities (Fig. 1-c), and the results of systemic and laboratory investigations, including a study of the cerebrospinal fluid, were normal. He was diagnosed elsewhere with an optic disc pit maculopathy in the right eye. Laser treatment associated with a pneumatic retinopexy was performed and this was believed to have resulted in complete regression of the retinal detachment (Fig. 1-d). By the time we first examined the patient, visual acuity was 20/25 in both eyes. Extrinsic ocular motility, pupillary reflexes and anterior segment biomicroscopy were normal in both eyes. Right eye retinography revealed evidence of reactive peripapillary atrophy and pigmentary alteration in the macula (Fig. 2-a). In the left eye, retinography revealed peripapillary serous retinal detachment (Fig. 2-b). Autofluorescence imaging in right eye revealed peripapillary hypoautofluorescence and in the left eye there was peripapillary hyperautofluorescence. Fluorescein angiogram (FA) in the left eye revealed progressive staining and pooling of the peripapillary retina with corresponding retinal vasculitis (Fig. 2-c). Indocyanine green angiography (ICGA) revealed multiple hypocyanescent lesions with an area of hypercyanescence temporal to the disc (Fig. 2-c). Spectral-domain optical coherence tomography (OCT-SD) scans through the posterior left eye segment revealed a diffuse thickened choroid, papillomacular subretinal exudate and discontinuity of the ellipsoid layer with suggestion of vitreous cellularity (Fig. 2-d). There was no evidence of pits in either eye. Laboratory tests were required at that time.

Fig. 1

(a–b): Serous retinal detachment shown on OCT (yellow arrows), mainly in the lower macula, and vitreous cellularity (red arrows) seen 20 months earlier.(c): No abnormalities was seen on OCT of the left eye at the same time. (d): Resolution of serous retinal detachment after treatment. Peripapillary atrophy secondary to laser treatment (yellow circle).

Fig. 2

(a): Reactive peripapillary atrophy and pigmentary alteration in the macula of right eye. (b): Changes observed in the left eye at the onset. Peripapillary serous detachment in the left eye (yellow arrow). (c): Overlap of FA (peripapillary image) on ICGA (peripheral image): Peripapillary hyperfluorescence observed on FA in an early stage leakage with perivascular staining (yellow arrow). On ICGA, a more extensive area of leakage was observed. Note “dark dots” (red arrow) and “stromal vessels” (blue arrow). (d): The yellow arrow indicates the degeneration of photoreceptors and presence of septum with accumulation of subretinal fluid. The image also shows a thickened choroid on OCT-EDI. (e): Evolution after a few days, showing an increased area of serous detachment reaching the fovea (retinography, yellow arrows delimitates the area of subretinal fluid). (f): OCT showing an increase in the subretinal fluid, affecting the foveal zone: amorphous substance (yellow arrow) and vitreous cellularity (red arrow). (g): Improved appearance of the macula on retinography after treatment completion. (h): Improvement of serous detachment on OCT-SD. The regeneration stage of the papillomacular bundle photoreceptors (yellow arrow) after treatment with oral steroid.

During this period, the patient presented with worsening vision in the left eye, and an increased area of serous detachment reaching the fovea could be seen on retinography (Fig. 2-e), red-free, autofluorescence and infra-red. The OCT-SD showed an increase in the sub-retinal fluid, affecting the foveal zone, in addition to the increase of the amorphous substance and the vitreous cellularity (Fig. 2-f).

Laboratory tests, including hemogram, erythrocyte sedimentation rate, C-reactive protein, rheumatoid factor and antinuclear antibodies were normal. We excluded the following infectious diseases: HIV, syphilis, toxoplasmosis, cytomegalovirus, herpes simplex, herpes zoster and Bartonella henselae. Chest tomography was normal. Considering the apparent absence of infectious diseases, the patient was started on 60 mg/day prednisone. After 8 days, visual acuity improved to 20/250, improving to 20/20 vision six months after slow steroid wean. This improvement could be demonstrated on retinography (Fig. 2-g), OCT-SD (Fig. 2-h) and infra-red.

Discussion

These fundoscopic findings in a previously-healthy young white man revealing rapidly progressive low visual acuity suggested a heterogeneous group of pathologies that could be responsible.

Infectious causes, including syphilis and tuberculosis, were excluded due to negative serologies. Chest tomography showed no abnormalities, making the possibility of sarcoidosis highly unlikely.

Ocular ultrasonography and neuroimaging showed no signs suggestive of scleritis, tumor or lymphoma that were not consistent with the FA and ICGA.

Some diseases belonging to the group of white dots syndrome should be considered. Acute zonal occult outer retinopathy (AZOOR), acute posterior multifocal placoid pigment epitheliopathy (APMPPE) and serpiginous choroiditis may be accompanied by vitritis and low visual acuity, depending on the extension of involvement of the external retina and fovea. The peripapillary RPE atrophy observed in the patient's right eye can be found in more advanced cases of AZOOR and serpiginous choroiditis. Chao et al. described a case of multiple evanescent white dots syndrome (MEWDS) with similar characteristics to those found in our case, including thickening of the choriocapillaris and serous detachment observed on optical coherence tomography. However, despite the presence of early hypofluorescent lesions in FA, also found in APMPPE, multifocal choroiditis and panuveitis, there were no typical angiographic or fundoscopic patterns of any spectrum of these pathologies, as seen in this case.

Although the diagnosis of Vogt-Koyanagi-Harada syndrome (VKHS) requires bilateral ocular involvement, there have been reports in the literature of unilateral and bilateral non-simultaneous involvement., Typical findings of VKHS that are found in FA (such as pin points) were not detected in our patient. Furthermore, a circumscribed type of peripapillary serous retinal detachment that slowly advanced to the macula in both eyes is an atypical presentation of Harada disease as well. Our patient initially presented with peripapillary serous retinal detachment in the left eye, eighteen months after a similar event in the right eye that had been misdiagnosed as a papilla pit. We believe both eyes suffered from the same syndromic condition, but in distinct periods, because the clinical presentation and findings from the complementary exams were similar. This observation reinforces the probable diagnosis of VKHS, with bilateral ocular involvement occurring non-simultaneously.

The diagnostic criteria for VKHS were published in 2014 (Table 1). In this case report, the patient met the criteria for the probable form, because trauma and previous ocular surgeries were excluded, as were other ocular and systemic pathologies.,

Table 1

Diagnostic criteria for Vogt-Koyanagi-Harada disease.

Complete Vogt-Koyanagi-Harada disease (criteria 1 to 5 must be present)

1. No history of penetrating ocular trauma or surgery preceding the initial onset of uveitis.

2. No clinical or laboratory evidence suggestive of other ocular disease entities.

3. Bilateral ocular involvement (a or b must be met, depending on the stage of disease when the patient is examined).

A. Early manifestations of disease.

(1) There must be evidence of a diffuse choroiditis (with or without anterior uveitis, vitreous inflammatory reaction, or optic disk hyperemia), which may manifest as one of the following:

(a) Focal areas of subretinal fluid, or

(b) Bullous serous retinal detachments.

(2) With equivocal fundus findings; both of the following must be present as well:

(a) Focal areas of delay in choroidal perfusion, multifocal areas of pinpoint leakage, large placoid areas of hyperfluorescence, pooling within subretinal fluid, and optic nerve staining (listed in order of sequential appearance) by fluorescein angiography, and

(b) Diffuse choroidal thickening, without evidence of posterior scleritis by ultrasonography.

B. Late manifestations of disease.

(1) History suggestive of prior presence of findings from 3A, and either both (2) and (3) below, or multiple signs from (3):

(2) Ocular depigmentation (either of the following manifestations is sufficient):

(a) Sunset glow fundus, or

(b) Sugiura sign.

(3) Other ocular signs:

(a) Nummular chorioretinal depigmented scars, or

(b) Retinal pigment epithelium clumping and/or migration, or

(c) Recurrent or chronic anterior uveitis.

4. Neurological/auditory findings (may have resolved by time of examination).

A. Meningismus (malaise, fever, headache, nausea, abdominal pain, stiffness of the neck and back, or a combination of these factors; headache alone is not sufficient to meet definition of meningismus, however), or

B. Tinnitus, or

C. Cerebrospinal fluid pleocytosis.

5. Integumentary finding (not preceding onset of central nervous system or ocular disease).

A. Alopecia, or

B. Poliosis, or

C. Vitiligo.

Incomplete Vogt-Koyanagi-Harada disease (criteria 1 to 3 and either 4 or 5 must be present)

1. No history of penetrating ocular trauma or surgery preceding the initial onset of uveitis, and

2. No clinical or laboratory evidence suggestive of other ocular disease entities, and

3. Bilateral ocular involvement.

4. Neurologic/auditory findings; as defined for complete Vogt-Koyanagi-Harada disease above, or

5. Integumentary findings; as defined for complete Vogt-Koyanagi-Harada disease above.

Probable Vogt-Koyanagi-Harada disease (isolated ocular disease; criteria 1 to 3 must be present)

1. No history of penetrating ocular trauma or surgery preceding the initial onset of uveitis.

2. No clinical or laboratory evidence suggestive of other ocular disease entities.

3. Bilateral ocular involvement as defined for complete Vogt-Koyanagi-Harada disease above.

Conclusion

We believe our case represented a variant of the VKHS in an atypical situation, because the patient fulfilled the presumed criteria. Furthermore, the findings of clinical and complementary examinations led to this nosological entity to the exclusion of the others.

It is important to promptly diagnose atypical VKHS, so that early therapy can be directed in order to improve visual prognosis.

Patient consent: Written consent to publish this case has not been obtained.

This report does not contain any personal identifying information.

Acknowledgements and disclosures

Funding

No funding or grant support.

Conflicts of interest

The following authors have no financial disclosures: Abucham-Neto, J.Z; Ferraz, A.A.B; Masson, A.P; Nascimento, P.A; Souza Cunha, E. Authorship: All authors attest that they meet the current ICMJE criteria for Authorship.