From the Department of Ophthalmology, Doheny Eye Institute, Keck School of Medicine, University of Southern California, Los Angeles, California.
The authors have no financial or proprietary interest in the materials presented herein.
Address correspondence to Amani A. Fawzi, MD, Northwestern University, Department of Ophthalmology, 645 N. Michigan Ave., Chicago, IL 60611. E-mail: email@example.com
Advances in optical coherence tomography (OCT) have enhanced our ability to study retinal diseases and shed light on their pathophysiology.1 Recently, there has been increasing interest in photoreceptor layer abnormalities in patients with central serous chorioretinopathy (CSC). OCT characteristics in patients with classic CSC include loss of the photoreceptor inner segment/outer segment junction or intermediate line in the detached portion of the retina,2 changes in retinal thickness,3 focal hyperreflective deposits in the outer retinal layers,4 and elongated photoreceptor outer segments.5–7 We present a case of bilateral, multifocal CSC in a renal transplant recipient, where OCT demonstrates a well-defined, hyperreflective membrane underlying the detached photoreceptors and correlate OCT findings to fundus autofluorescence.
A 33-year-old woman presented with a history of end-stage renal failure due to suspected IgA nephropathy. She received a deceased donor renal transplant in the Philippines on May 13, 2010, and subsequently developed systemic hypertension and steroid-induced diabetes. She had received immunosuppressive therapy with a variety of agents, most recently prednisone taper and sirolimus 2 mg daily prior to her most recent hospitalization. Despite her immunosuppressive therapy, she was hospitalized twice at the University of Southern California Hospital for episodes of acute transplant rejection diagnosed by renal biopsy 2 and 3 months following the transplant surgery. Both episodes were resolved with Solu-Medrol (Pfizer Inc., New York, NY) and prednisone taper. During her most recent episode of rejection, 4 months following transplantation, her work-up revealed cytomegalovirus infection by polymerase chain reaction of the cerebrospinal fluid and serum. The patient complained of progressively blurry vision and the ophthalmology service was consulted to rule out cytomegalovirus retinitis. The patient denied any previous episodes of blurry vision or ocular history.
The initial examination revealed visual acuity of 20/25 in the right eye and 20/20 in the left eye. Dilated fundus examination demonstrated multiple areas of subretinal fluid in the posterior pole with shallow inferior serous retinal detachments in both eyes. Two days later, she was treated with 10 mg of dexamethasone intravenously. Her visual acuity decreased to 20/400 in the right eye and 20/100 in the left eye. Dilated fundus examination revealed more extensive subretinal fluid and exudation. The patient also had some alteration of her mental status as her renal function was deteriorating. She underwent further systemic work-up for Cyptococccus, Toxoplasma, herpes simplex virus, Epstein–Barr virus, human immunodeficiency virus antibodies, fluorescent treponemal antibody absorption (FTA-ABS), rapid plasma reagin, cerebrospinal fluid FTA-ABS, and cerebral spinal fluid Cryptococcus. All results were negative, including the brain magnetic resonance imaging. With improved renal function, 3 days later the patient underwent further ophthalmologic evaluation including OCT (HD-OCT; Carl Zeiss Meditec, Inc., Dublin, CA), fluorescein angiography, and fundus autofluorescence using the Topcon TRC-50IX camera with the Spaide filter (Topcon Medical Systems Inc., Paramus, NJ). OCT showed multiple, small retinal pigment epithelial disruptions and detachments, and subretinal fluid with a hyper-reflective membrane underneath the detached photo-receptors (Fig.1). Fluorescein angiography showed numerous small areas of punctate leakage throughout the posterior pole in both eyes. Fundus autofluorescence revealed diffuse small hypoautofluorescent dots, scattered in a background of mild hyperautofluorescence. We recommended discontinuing steroid pulse therapy. The patient’s visual acuity gradually improved to 20/40 in both eyes over the following 3 weeks with resolution of subretinal fluid. The examination findings, imaging studies, response to steroid taper, and clinical course were all consistent with bilateral, multifocal CSC in an organ transplant recipient.8
Figure 1. Multimodal imaging in a patient with transplant central serous chorioretinopathy. (A and B) Fundus photographs revealing retinal pigment epithelial mottling and exudative retinal detachment in the posterior pole in both eyes. (C and D) Fluorescein angiography revealing multiple pinpoint areas of leakage. (E and F) Green light fundus autofluorescence images highlighting the numerous hypoautofluorescent dots in a background of slight hyperautofluorescence. (G and H) An optical coherence tomography B-scan through the fovea of each eye revealing multiple small retinal pigment epithelial detachments, subretinal fluid, and a hyperreflective membrane underlying the outer photoreceptor segments as delineated with the red arrows.
We used multimodal imaging to characterize the retinal findings in a case of severe multifocal, bilateral CSC and retinal detachment in a transplant recipient. To our knowledge, there have not been previous reports of a well-defined, hyperreflective membrane underlying the outer segments captured using high-resolution spectral-domain OCT in a patient with CSC. This hyperreflective membrane may be unique to patients with organ transplant CSC. We used fundus autofluorescence in registration with OCT to elucidate the characteristics of the membrane. Blood vessels were used to manually register the OCT infrared image to the fundus autofluorescence to better characterize the funduscopic changes (Fig. 2). As shown in the figure, the small retinal pigment epithelial elevations/disruptions correlate to the hypoautofluorescent spots on the fundus autofluorescence, although the intensity of the hypoautofluorescent spots was variable and more difficult to visualize in the fovea.
Figure 2. Manually registered fundus autofluorescence (FAF) and infrared images (registered to optical coherence tomography [OCT] fundus image). FAF images (upper right) were manually registered to the infrared image of the high-definition OCT (upper left) using blood vessels and the optic nerve as points of reference. The OCT B-scans were then studied to identify the areas of subretinal hyperreflective membrane or retinal pigment epithelial (RPE) detachment and evaluate if they correspond to hyperautofluorescent or hypoautofluorescent areas. Hypoautofluorescent areas were also evaluated for corresponding changes on the OCT. Line A reveals that hypoautofluorescent spots correspond to RPE detachments and disruptions. Line B shows that RPE detachments and disruptions correspond to hypoautofluorescent dots on the FAF of varying intensity. Line C reveals that the hyperreflective membrane under the retina does not correspond to any focal hyperautofluorescence on the FAF, although this determination is difficult because the membrane is rather diffuse.
We cannot determine with certainty the exact etiology of this hyperreflective OCT finding. Given the generalized increased autofluorescence in the posterior pole, one possibility is that it represents degenerated photoreceptor outer segments. This may occur due to prolonged separation from the retinal pigment epithelial and lack of a recycling mechanism leading to the accumulation of autofluorescent degenerating photoreceptor debris. Another possible origin for this membrane may be exudative material arising from the leaking choroidal vessels and accumulating in the subretinal space, as previously described.4
Imaging of more cases using a combined fundus autofluorescence and OCT approach may help elucidate the mechanism. The focal hypoautofluorescence may represent stretching or disruption of the underlying retinal pigment epithelial cells and is the main source of background fluorescence in fundus autofluorescence. In addition, when we examined the areas of OCT with membranous deposits underlying the retina, we did not find corresponding focal hyperautofluorescence on the fundus autofluorescence (Fig. 2). This may favor an exudative origin to this membrane rather than degenerating photoreceptors. However, it is possible that the diffuse membrane is responsible for the generalized increased fundus autofluorescence in the posterior pole and may represent a confluent layer of degenerating photoreceptors debris.9
This patient had classic findings of multifocal CSC including bilateral, punctate areas of leakage on fluorescein angiography with corresponding areas of serous retinal detachment (Fig. 1).6 Additionally, she had several classic OCT findings including subretinal deposits with punctate areas of hyperreflectivity (Fig. 1).2–4 Using Stratus OCT, previous studies have demonstrated the presence of “reflective masses” suggestive of fibrinous exudates.3,4,6 More recently, higher resolution OCT has shown loss of the inner segment/outer segment junction2 or intermediate line in cases of chronic CSC.5 In contrast, our patient had a thick membrane under the detached portion of retina (Figs. 1 and 2). Cyst-like septations (Fig. 2C) close to areas of retinal pigment epithelial elevation and pinpoint hyperfluorescence on fluorescein angiography resemble the OCT septations seen in patients with Vogt-Koyanagi-Harada syndrome (VKH) and seem to similarly erupt from the retinal pigment epithelium.10 Similarities between severe cases of transplant CSC to VKH were previously suggested in a large series showing higher prevalence of severe CSC in Hispanic and Asian transplant recipients (the same racial backgrounds that tend to develop VKH).8 Few studies have explored OCT findings in these patients, perhaps underscoring the underreporting of this entity. Using multimodal imaging in other patients may help elucidate this finding and identify other similarities to VKH.
The importance of distinguishing multifocal CSC from VKH in clinical practice cannot be overemphasized, especially given their tendency to occur in similar ethnic backgrounds and the presence overlapping findings on fluorescein angiography and OCT. Transplant CSC is exacerbated by corticosteroids, in contrast to VKH, which is treated with high-dose corticosteroids.8,10,11 Strong clinical suspicion and clinical history remain the most important tools to differentiate the two entities. Our patient developed vision loss during hospitalization, allowing us to promptly establish the diagnosis and initiate steroid withdrawal. To further support our diagnosis of CSC, the patient improved once the systemic corticosteroids were discontinued.
Renal transplant recipients with multifocal CSC can develop membranous deposits underlying the detached retina as illustrated in our patient. Additional patient series are needed to establish whether this finding is unique to CSC in the setting of transplant recipients. OCT, fluorescein angiography, and fundus autofluorescence in addition to the clinical history and course can be useful in distinguishing this entity from other infectious or inflammatory etiologies. Further studies using registered fundus autofluorescence and OCT are needed to shed light on the nature of the subretinal membranous deposits. Prompt diagnosis and discontinuation of steroids, as shown in this case, may be the key to visual improvement in these patients.
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