Progressive, subretinal fibrosis mimicking retinal necrosis with poor visual prognosis in sympathetic ophthalmia: A rare finding.

We report a rare finding of progressive subretinal fibrosis mimicking retinal necrosis in 2 cases of sympathetic ophthalmia. Histopathology of the inciting eye and vitreous biopsy of the sympathizing eye ruled out infections and masquerades. Progression of inflammation and rapid deterioration of vision inspite of maximum immunosuppression are key findings in this variant of sympathetic ophthalmia.

Sympathetic ophthalmia is a rare, bilateral, diffuse granulomatous intraocular inflammation that occurs after a surgery or penetrating trauma to one eye.[1] Most commonly described ocular manifestations include granulomatous panuveitis, exudative retinal detachment, papillitis, presence of Dalen Fuchs nodules and depigmentary alterations in the fundus. High-dose corticosteroids and immunosuppressants initiated at an early stage is necessary for a good visual prognosis.[1] Very rarely, they present with severe subretinal fibrosis resulting in poor visual prognosis. We report a rare finding of progressive subretinal fibrosis mimicking retinal necrosis with poor visual prognosis in two cases of sympathetic ophthalmia.

Case Reports

Case 1

A 50-year-old diabetic male with a history of trauma followed by multiple retinal surgeries in the right eye (OD) presented to us with diminution of vision in the left eye (OS) of 2-month duration. Previous records indicate on and off treatment with oral steroids with partial response started elsewhere. Ocular examination showed a phthisical OD. His best corrected visual acuity (BCVA) in OS was 6/12. Slit lamp and fundus examinations (OS) showed medium sized keratic precipitates, 2 + anterior chamber reaction, vitritis, peripapillary retinal elevation, disc hyperemia and multiple subretinal coin-shaped lesions in midperiphery [Fig. 1a and b]. Intraocular pressures by applanation tonometry (OS) were 26 mm of Hg. Gonioscopy showed open angles with hyperpigmentation. Ultrasonography (OS) showed a choroidal thickness of 1.6 mm. Laboratory investigations including complete haemogram, serum angiotensin converting enzyme, venereal disease research laboratory test (VDRL), treponemal pallidum Haemagglutination test (TPHA), antinuclear antibodies, enzyme-linked immunosorbent assays (ELISA) for human immunodeficiency virus (HIV) and toxoplasmosis were negative. Mantoux test, chest radiology and ultrasonography of abdomen were negative. Multiplex polymerase chain reaction on the aqueous for eubacterial, panfungal, herpes viruses, toxoplasma and mycobacterium tuberculosis (MTb) were negative. Treatment included oral steroids (1 mg/kg body weight), azathioprine (2 mg/kg body wt), hourly instillation of topical prednisolone acetate1% eye drops, timolol eye drops 0.5% bd and brinzolamide eye drops 1% tid. Subsequent follow-up 2 weeks later showed decrease in vitritis. However, he developed herpes zoster (left thoracic dermatome) a month later. The steroids and immunosuppressives were discontinued for 2 weeks till the resolution of active zoster skin lesions. He came back a month later with worsening of inflammation and deterioration of vision to counting fingers close to face [Fig. 1c and d]. A core vitrectomy (OS) was done and the vitreous was sent for a detailed histopathology and microbiology examination. Cytology showed few lymphocytes and macrophages suggestive of chronic inflammation. Microbiology including staining, culture and multiplex PCR were negative for bacteria, herpes viruses and toxoplasma. Enucleation of the right pthisical eye showed chronic granulomatous inflammation in the choroid. Immunohistochemistry showed CD20, CD3, CD45 positivity suggestive of both B- and T-cell response. The peripapillary elevation with multiple subretinal deposits [Fig. 2a] and large confluent subretinal lesions with indistinct borders [Fig. 2b] were visible more clearly after vitrectomy. These lesions subsequently showed fibrosis with demarcation of borders following treatment with oral steroids and azathioprine [Fig. 2c and d]. His BCVA (OS) was counting fingers 3 m.

Figure 1

Fundus photograph of the left eye showing vitritis, multiple sub retinal deposits, peripapillary elevation (a), large, subretinal confluent deposits at presentation (b), increase in vitritis with time (c) and coalescing of subretinal lesions mimicking retinal necrosis (d)

Figure 2

Fundus photograph of the left eye showing peripapillary elevation with multiple subretinal deposits visible clearly after vitrectomy (a), large areas of confluent subretinal lesions with indistinct borders (b), which show fibrosis after treatment with oral steroids, and immunesuppression (c and d)

Multimodal imaging showed larger and more hypointense areas on indocyanine green angiography in comparison to fluorescein angiography [Fig. 3a] and staining of confluent lesions on fluorescein angiography. OCT showed multiple intraretinal, subretinal hyperreflective lesions and retinal pigment epithelium (RPE) undulations [Fig. 3b]. Magnetic resonance imaging (MRI) orbit and cranium were not significant. Audiometry evaluations showed bilateral moderate to severe sensorineural hearing loss in right and left ears, respectively.

Figure 3

Multiple modal imaging showing larger and more hypointense areas on indocyanine green angiography than fluorescein angiography (a). Spectral optical coherence tomography showing retinal pigment epithelium undulations and multiple hyperreflective intraretinal deposits and alterations in the outer and inner retinal layers (b)

As his inflammation continued to worsen with deterioration of vision, pulse doses of intravenous methyl prednisolone (1 mg/kg/day for 3 days) and intravenous cyclophosphamide (six cycles) were given. He eventually developed no perception of light (OS) over 3 months.

Case 2

A 54-year-old male with a history of trauma followed by multiple retinal surgeries in the left eye presented to us with pain and diminution of vision in OD of 3 months duration. He had a history of receiving antituberculosis therapy for pulmonary tuberculosis 20 years ago.

On examination, his BCVA (OD) was counting fingers close to face. Left eye was a pthisical eye. Slit lamp examination (OD) showed medium sized keratic precipitates and an anterior chamber reaction (2+). Fundus examination showed vitritis, disc hyperemia, peripapillary retinal elevation, a choroidal scar in the posterior pole and plenty of subretinal lesions, coalescing in some areas mimicking retinal necrosis [Fig. 4a] Ultrasonography showed no significant choroidal thickening (1.6 mm). Fluorescein angiography showed disc leakage, multiple hyperfluorescent lesions in the mid and late phases and vascular wall staining. The large coalescent lesions showed staining in late phases. ICG showed multiple, hypointense choroidal lesions. Spectral OCT showed intraretinal and outer retinal hyper reflective lesions. RPE undulations were seen [Fig. 4b]. Laboratory investigations including complete haemogram, peripheral blood smear, ELISA for HIV, antinuclear antibodies, serum angiotensin converting enzyme, toxoplasmosis, VDRL, TPHA, Quantiferon TB gold test, liver function tests, serum creatinine, random blood sugars and urine routine were negative. Chest radiology showed collapse of the left lung due to the past pulmonary tuberculosis [Fig. 4c]. Three consecutive sputum samples for acid fast bacilli (AFB) were negative. Right eye underwent a vitreous biopsy [Fig. 4d]. Cytology showed few lymphocytes and macrophages suggestive of chronic inflammation. Microbiology including staining, culture and multiplex PCR were negative for bacteria, fungi, herpes viruses, toxoplasma and MTB. MRI orbits and cranium was normal. Under an infectious disease specialist's supervision, he was started on oral steroids (1 mg/kg body wt) and azathioprine (2 mg/kg body wt). As the steroids were tapered to 30 mg/day, he developed a worsening of inflammation and decrease in vision to perception of light. Under a pulmonologist and infectious disease specialist's supervision, intravenous methyl prednisolone (1 mg/kg body wt for 3 days) with posterior subtenon injection of triamcinolone acetonide and intravenous cyclophosphamide (four cycles) were given. However, his vision deteriorated to no perception of light. He refused further treatment and was lost to follow-up.

Figure 4

Fundus photograph of right eye of case 2 showing peripapillary retinal elevation, choroidal scar in the posterior pole and multiple creamish yellow subretinal deposits with vitritis (a). Spectral optical coherence tomography shows retinal pigment epithelium undulations (b). Chest X-ray showing collapse of the left lung (c). Fundus photograph of right eye of case 2 showing peripapillary retinal elevation and multiple subretinal lesions (d) clearly visible following vitrectomy

Discussion

A variant of sympathetic ophthalmia presenting as progressive subretinal fibrosis with poor prognosis has been described in a few reports from western literature.[234] However, such a variant has not been described from the developing world (Medline search). We present this variant in two cases of sympathetic ophthalmia from south India. What is interesting in these two cases is that the subretinal fibrosis initially mimicked retinal necrosis. The large confluent yellowish creamy areas with ill-defined borders and nonvisualization of the retinal blood vessels over these areas amidst intense vitritis mimicked retinal necrosis. Second, in both cases of sympathetic ophthalmia, there was a diagnostic dilemma of an infection. Case 1 had a history of herpes zoster while case 2 had a history of pulmonary tuberculosis. Due to the atypical clinical presentation, infections needed to be ruled out in both cases. Only after vitrectomy, the dense, white, subretinal fibrosis could be visualized, whose margins had now become more clearly demarcated with treatment. Third, the rapid progression of subretinal fibrosis and very poor visual prognosis, in both the cases, inspite of maximum immunosuppressive therapy was puzzling. The diagnostic challenge to rule out infections in such presentations from the developing world and very poor visual prognosis despite maximum treatment is highlighted in these two cases.

Conclusion

A rare presentation of progressive subretinal fibrosis in sympathetic ophthalmia mimicking retinal necrosis is highlighted in this report. It also draws attention to the very poor visual prognosis associated with this variant of sympathetic ophthalmia.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

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Conflicts of interest

There are no conflicts of interest.