Evaluation of cystoid change phenotypes in ocular toxoplasmosis using optical coherence tomography

Abstract

Purpose: To present unique cystoid changes occurring in patients with ocular toxoplasmosis observed in spectral domain optical coherence tomography (OCT).

Methods: Forty-six patients (80 eyes) with a diagnosis of ocular toxoplasmosis, who underwent volume OCT examination between January 2005 and October 2012, were retrospectively collected. Review of clinical examination findings, fundus photographs, fluorescein angiograms (FA) and OCT image sets obtained at initial visits and follow-up. Qualitative and quantitative analyses of cystoid space phenotypes visualized using OCT.

Results: Of the 80 eyes included, 17 eyes (15 patients) demonstrated cystoid changes in the macula on OCT. Six eyes (7.5%) had cystoid macular edema (CME), 2 eyes (2.5%) had huge outer retinal cystoid space (HORC), 12 eyes (15%) had cystoid degeneration and additional 3 eyes (3.75%) had outer retinal tubulation due to age related macular degeneration. In one eye with HORC, the lesion was seen in the photoreceptor outer segment, accompanied by photoreceptor elongation and splitting. Three eyes presented with paravascular cystoid degeneration in the inner retina without other macular OCT abnormality.

Conclusions: In this study, different phenotypes of cystoid spaces seen in eyes with ocular toxoplasmosis using spectral domain OCT (SD-OCT) were demonstrated. CME presented as an uncommon feature, consistently with previous findings. Identification of rare morphological cystoid features (HORC with/without photoreceptor enlongation or splitting) on clinical examination had provided evidence to previous experimental models, which may also expand the clinical spectrum of the disease. Cystoid degeneration in the inner retina next to the retinal vessels in otherwise "normal" looking macula was observed, which may suggest more often clinical evaluation for those patients. Further studies are needed to verify the relevance of cystoid features seen on SD-OCT in assisting with the diagnosis and management of ocular toxoplasmosis.

Figure 1. Case examples of cystoid space (CS) phenotypes in ocular toxoplasmosis as seen on optical coherence tomography (OCT).

[A–C] Examples of cystoid degeneration next to retinal vessels in the inner retina. Figure B was from the right eye of an 18 year-old woman. She was with a previous diagnosis of ocular toxoplasmosis and presented with decreased vision of one week's duration in the same eye. VA in the right eye was 20/25. Examination of the fundus of the right eye revealed vitreous cells, and an active creamy yellow lesion (about 1/3 disc diameters in size) with retinal hemorrhage on the nasal aspect of the optic disc with temporal optic nerve head swelling. Macular was with no obvious abnormality. OCT imaging of the right macula demonstrated an ERM with a few punctate spots in the vitreous, intraretinal CSs (in one B-scan, adjacent to a retinal vessel), along with absence of other retinal abnormalities. [D, G] Examples of cystoid macular edema (CME). Figure G was from the right eye of a 51 year-old man presenting for a regular follow-up examination of ocular toxoplasmosis. He had previously been diagnosed with ocular toxoplasmosis affecting the right eye at 17 years old. In his right eye, VA was 20/125 and anterior segment examination was unremarkable. Dilated fundus examination revealed a central macular scar with no findings suggestive of disease activity. OCT imaging showed multiple small CSs in the OPL and ONL, with increased retinal thickness, and categorized as CME. [E, H] Examples of outer retina tubulation. Figure E and H were from the right eye of a 70 year-old man, with a previous diagnosis of bilateral ocular toxoplasmosis. On examination, his VA was 20/20 on the right eye. Fundus examination revealed an old macular scar in the right eye without signs of disease activity. The patient had been diagnosed with choroidal neovascularization (CNV) secondary to age related macular degeneration in 2011 and treated with three injections of intravitreal ranibizumab (Lucentis, Genentech, USA) to the right eye. OCT imaging of the right eye demonstrated outer retina tubulation in the degenerated outer retina. [F,I] Examples of cystoid degeneration next to old scars.

Figure 2. Case example of huge outer retinal cystoid space (CS) as seen on optical coherence tomography (OCT) in a patient with ocular toxoplasmosis.

Two days after initial presentation [A–N] and at subsequent follow-ups [P–Q] (note: [d–f] is the magnified view of [D–F]). The OCT scans were taken within a 20°×15° (5.8×4.4 mm) area. Distance between adjacent B-scans (B-scans B, C, D, E, G are adjacent; H, I, J are adjacent) was 243 µm. Two days after initial presentation, a membranous structure is seen on OCT. One part of this structure is seen lying over the retinal pigment epithelium (RPE) and forming the floor of the huge outer retinal CS (HORC) [B–E, G], while another part is separated from the RPE by an accumulation of subretinal fluid (SRF) [H–J]. The line representing the external limiting membrane (ELM) is distinct in the area unaffected by HORC; however, it is continuous with the upper border of the highly reflective membranous structure in the area affected by HORC [D–F, d–f]. The photoreceptor inner segment/outer segment junction (IS/OS junction) is distinct in the area unaffected by HORC, becoming less distinct in the area with overlying HORC. Photoreceptor IS/OS disruption and outer segment (OS) irregularity is also observed [E, G–J, e–f]. The retinal thickness map [L], mean HORC height map [M], and the mean maximum SRF height map [N], are shown for the Early Treatment Diabetic Retinopathy Study (ETDRS) grid. The presumed interpretation of the structural changes are also shown (the outer retina is the area between the black arrows) [K]. OCT images obtained 15 days later demonstrate that the HORC is no longer present [O]. Punctate hyperreflective foci are seen in the posterior vitreous overlying this area. The ELM is almost completely distinct in all B-scans. In contrast, the photoreceptor IS/OS junction is still not fully distinct. Irregularity of the PR and outer nuclear layer (ONL) presenting as local hyperreflective foci is seen at the previous junction of the HORCs with the normal retina. This feature persists at subsequent visits [P–Q]. A hyporeflective space between the ELM or presumed IS/OS and inner boundary of the RPE is observed subfoveally, with possible hyperreflective material above RPE. Subsequent OCT images were obtained approximately one month [P] and two months [Q] following initial presentation. No HORC or SRF is seen at these points. The photoreceptor IS/OS junction is more clearly seen, with a thickness value of 68 µm [Q].

Figure 3. Case example of huge outer retinal cystoid space (CS) as seen on optical coherence tomography (OCT) in a patient with ocular toxoplasmosis.

Part 1 (Part A–K) was present with huge outer retinal CS (HORC) on June 29 2012 (f, h, c were the magnified views of F, H, C). The OCT scans were taken within a 20°×15° (5.9×4.4 mm) area. Distance between adjacent B-scans (B-scans B, C, D, E, F are adjacent; G, H, I are adjacent) was 244 µm. Predominant hyper reflective foci (HRF) were seen within the HORCs. One part of a membranous structure lies on the retinal pigment epithelium (RPE) (C–I) and possibly as a lower border of HORCs (C–D). The line representing the external limiting membrane (ELM) is only distinct in area without HORCs (B–I). Photoreceptor inner segment/outer segment junction (IS/OS) elongation and splitting were seen in F, H. IS/OS disruption and outer segment (OS) irregularity were observed (F, H). The retinal thickness map (J) and the mean maximum height of HORCs (K) were shown in on the Early Treatment Diabetic Retinopathy Study (ETDRS) grid. The presumed interpretations of the structural changes were shown in fa (CS in the outer retina, excluding photoreceptor inner segment) and fb (CS in the outer retina, involving photoreceptor inner segment)(outer retina is the area between the black arrows). Part 2: Part L-L3 were the examples of OCT images 4 days later. HORCs became separated from the above retina, forming a hyporeflective empty space (L1-2). The reflectivity inside the HORCs became more hyperreflective (L1). OPL irregularity with increased thickness and change of reflectance was also seen (L3). Part M-m2 were OCT images on July 19 2012 (m1 and m2 are the magnified views for M1). Inner and outer retina necrosis happened at the location where previous HORCs existed (M1). A new HORCs presenting between IS/OS and RPE was seen. A membranous structure locating under this HORCs but above RPE with unique thickness was labeled as OS (m2). Part N-N2 were the examples on August 30 (n1 was the magnified view of N1). HORCs presented in M became smaller (N1), but clearly between IS/OS and RPE inner boundary. Retina degeneration, especially in the subfoveal area, along with thickened and detached posterior hyaloid was shown in N2. Part O and Part P were the OCT images on October 4 2012 and October 29 2012, respectively. Cystoid degeneration was seen in both visits. A local hypereflective band between IS/OS and RPE inner boundary (p) were present at the location with HORCs seen in M and N, which implied previous disruption of OS.