Case of the Month

Edited by Robert N. Johnson, MD

Figures 1A and B: Slit lamp photos of the right and left eye. Fibrin membranes behind the pupil of the right eye are present. The left eye is unremarkable with no inflammation.

Figure 2: Wide-field photograph of the left eye. Disc hyperemia is present. Subtle serous fluid can be seen iin the nasal macula. RPE thinning is noted inferiorly, related to his myopic fundus changes.

Case History

A 61-year-old Caucasian male presented with a 2-week history of worsening vision in his left eye.  He described the vision as gradually dimming, with a pulsating quality, associated with moderate, daily left eye pain.  In the fellow eye over the prior year, he had undergone five pars plana vitrectomy procedures for recurrent retinal detachments, complicated by proliferative vitreoretinopathy and hypotony.  His most recent procedure was performed two months prior to presentation.  His past medical history was notable for rosacea and obstructive sleep apnea, for which he takes doxycycline and metronidazole and uses a continuous positive airway pressure (CPAP) machine.  His past ocular history, family history and review of systems were otherwise noncontributory.

On examination, his best-corrected visual acuity was hand motions in the right eye and 20/100 in the left eye.  Of note, his vision was 20/20 in his left eye two months prior to presentation.  There was no relative afferent pupillary defect and ocular motility was normal in both eyes.  Intraocular pressures were 5 and 14 in the right and left eyes, respectively.  Anterior segment examination in both eyes (Figures 1A and B) was unremarkable with the exception of a fibrin membrane behind the pupil and aphakia in the right eye.  There was no conjunctival injection, corneal edema or anterior segment inflammation in the left eye.  The posterior segment examination of the right eye revealed persistent retinal detachment including the fovea extending from approximately 6:00 to 9:00 posterior to the scleral buckle with subretinal fibrosis, an encircling scleral buckle, 360 degree endolaser, and a 30% gas bubble.  Fundus examination of the left eye (Figure 2) was significant for optic disc edema with hyperemia, a posterior vitreous detachment, and a serous macular detachment. Fundus autofluorescence of the left eye (Figure 3) was significant for irregular increased autofluorescence nasal to the optic nerve.  Fluorescein angiography revealed multiple ~500um areas of hypofluorescence throughout the posterior pole and hyperfluorescent staining of the optic nerve in the left eye (Figure 4).  Indocyanine green angiography similarly depicted hypocyanescent spots scattered throughout the left fundus (Figure 5), particularly in late phases.

Optical coherence tomography (OCT) scans of the left eye (Figures 6A and B) showed a shallow serous macular detachment extending nasal to the optic nerve and a significantly increased choroidal thickness. B-scan ultrasonography imaging of the left eye (Figure 7) showed a diffusely thickened choroid.

Figure 3: Fundus autofluorescence of the left eye. Note the irregular areas of increased peripapillary autofluorescence.

Figure 4: Wide-field fluorescein angiogram of the left eye. Note the multiple, small (~500um) sized areas of hypofluorescence.

Figure 5: Wide-field indocyanine green angiogram of the left eye. Note the multiple small areas of hypocyanescence.

Figure 6A: Vertical OCT scan through the macula. Note the serous macula detachment, and the irregularly thickened choroid producing folds.

Figure 6B: Horizontal OCT scan through macula. Note the serous detachment in the macula and nasally. The choroid is significantly thickened.

Figure 7: B-scan ultrasound of the left eye showing a diffusely thickened choroid.

Differential Diagnosis

Vogt-Koyanagi-Harada (VKH) syndrome, syphilis, tuberculosis, sarcoidosis, multifocal choroiditis, birdshot chorioretinopathy, chronic endophthalmitis (P. acnes), phacoanaphylactic endophthalmitis, sympathetic ophthalmia

Additional Case History

The patient was started on prednisone 80 mg by mouth daily for a presumptive diagnosis of sympathetic ophthalmia.  Nine days later, OCT imaging showed a significantly decreased choroidal thickness and reduction of the serous detachment in the left eye (Figure 8).  The patient began a slow taper of the systemic prednisone.  After a month of treatment, the subretinal fluid had completely resolved, the choroidal thickness had nearly returned to normal (Figure 9), and the patient’s vision had improved to 20/25.  However, when the patient was tapered to prednisone 5mg daily 11 weeks after treatment began, his vision worsened to 20/40 and there was noted to be an increase in choroidal thickness on OCT (Figure 10).  Therefore, his prednisone was increased to 40mg daily and he was started on mycophenolate mofetil 1 gram daily.  At last follow-up 10 months after presentation, he was stable on mycophenolate mofetil 1 gram daily and prednisone 15mg daily, his vision had improved to 20/13 and his choroidal thickness remained within normal limits (Figure 11). His dose of mycophenolate mofetil was increased to 2 grams daily.

Figure 8: OCT scan through the macula 8 days after Prednisone 80mg qday was started. The choroidal thickening has improved substantially. Some serous fluid in the macula and nasally remain.

Figure 9: OCT through macula one month following beginning Prednisone 80mg qday. The serous detachment has resolved, and the choroidal thickening has improved substantially.

Figure 10: OCT scan through the macula after the Prednisone had been tapered. The choroid has become more thickened.

Figure 11: OCT scan through the nerve and macula. The choroidal thickness is reduced from time of diagnosis, and while appearing a bit thicker than many eyes, is likely near normal for this individual.

Discussion

Sympathetic ophthalmia (SO) is a rare, diffuse, bilateral, granulomatous uveitis that can occur anytime after a penetrating accidental or surgical trauma.  While SO rarely develops sooner than 2 weeks after injury and 90% of cases will present within one year, although there have been reports of SO occurring from a few days to several decades after the inciting event.¹ The incidence can vary depending on the underlying injury, and has been reported as high as 0.2 to 0.5% after penetrating ocular injury.² Additionally, although SO can occur after any intraocular procedure, pars plana vitrectomy has been shown to be the leading surgical cause of sympathetic ophthalmia, with an estimated risk of approximately 0.01%.³

The diagnosis is made from the constellation of clinical and imaging findings, rather than from a specific serologic or pathologic test.  Patients often present with mild pain, photophobia, epiphora and blurring of vision in the sympathizing eye.² Anterior segment examination is variable, but classically exhibits conjunctival injection, granulomatous inflammation with mutton-fat keratic precipitates on the corneal endothelium, and flare.1 Iris synechiae or nodules may or may not be present.  Posterior segment findings include vitritis, retinal vasculitis, choroiditis, or papillitis.² Retinal edema or exudative detachment of the retina may also be present.  Small yellow-white deposits, known as Dalen-Fuchs nodules, may be detected particularly in the midperiphery.  Cases, such as ours can present with no anterior segment findings and only posterior findings.

Chronic SO can cause depigmentation of the choroid, leading to a “sunset-glow” fundus appearance similar to VKH.  As in our case, the findings can be quite variable so a history of trauma or previous surgery is extremely helpful.

Although no specific finding is pathognomonic for the disease, multimodal imaging can be particularly helpful in the diagnosis of SO.  In the acute phase, fluorescein angiography can either show early pinpoint hyperfluorescent leaks, believed to represent disruption of retinal pigment epithelial (RPE) cell junctions, or numerous hypofluorescent spots with pooling in the later phases, thought to be consistent with choroidal granulomas.⁴ In the chronic phase, fluorescein angiography may exhibit window defects consistent with chorioretinal damage and atrophy, subretinal fibrosis, and/or choroidal neovascularization.  Indocyanine green angiography most commonly shows multiple hypocyanescent spots or patches, which can attenuate or regress with treatment and are therefore good markers of disease activity.  Ultrasound imaging may be notable for choroidal thickening or exudative retinal detachment.  On OCT imaging, serous detachments of the retina and thickening of the choroid can be seen in acute phases.  Dalen-Fuchs nodules can also be seen as round hyperreflective lesions at the level of the outer retina disrupting the RPE.⁴ OCT imaging is an excellent method to monitor disease activity as in our case, where choroidal thickening has been quite helpful.

The mainstay of treatment for sympathetic ophthalmia is initial high dose systemic corticosteroids, with a transition to or addition of immunosuppressive steroid-sparing therapy as the steroid is slowly tapered.¹ It is likely that most patients will need long term low-dose steroid treatment. Local supplementation of sub-tenon’s triamcinolone acetonide or intravitreal steroid can also be considered.  A recent paper by Payal and Foster of 19 patients treated for sympathetic ophthalmia over 8 years found encouraging results: 3 patients (15.78%) maintained remission without any treatment for more than 5 years with 20/25 or better vision, 13 (68.42%) were inactive on treatment, and 11 (57.9%) maintained 20/40 or better vision.⁵ Therefore, with appropriate and timely diagnosis and treatment, a good visual outcome is possible.

References

1. Ryan S. Retina, 5th ed. 2013:1318-1325.
2. Arevalo JF, Garcia RA, Al-Dhibi HA, Sanchez JG, Suarez-Tata L. Update on sympathetic ophthalmia. Middle East AFr J Ophthalmol 2012; 19(1):13-21.
3. Gass JD. Sympathetic ophthalmia following vitrectomy. Am J Ophthalmol 1982; 93:552–8.
4. Mahajan S, Invernizzi A, Agrawal R, Biswas J, Rao NA, Gupta V. Multimodal imaging in sympathetic ophthalmia. Ocul Immunol Inflamm. 2017; 25(2): 152-159.
5. Payal AR, Foster CS. Long-term drug-free remission and visual outcomes in sympathetic ophthalmia. Ocul Immunol Inflamm. 2017; 25(2): 190-195.