Saudi Journal of Ophthalmology (2014) 28, 152156
Spectral domain optical coherence tomography imagingof punctate outer retinal toxoplasmosis
Peer review under responsibilityof Saudi Ophthalmological Society,King Saud University Production and hosting by Elsevier
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Received 17 February 2014; received in revised form 17 March 2014; accepted 18 March 2014; available online 28 March 2014.
West Coast Retina Medical Group, 1445 Bush Street, San Francisco, CA 94109, United States
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Brandon J. Lujan, MD
Punctate outer retinal toxoplasmosis is a recognized phenotype of this common ocular parasite. We present a case presenting withpoor visual acuity, but with prompt treatment regaining excellent vision by the final time point. Imaging demonstrates progressionof an active lesion adjacent to an inactive retinal scar with color photography, fluorescein angiography, and Spectral Domain Opti-cal Coherence Tomography (SD-OCT). SD-OCT imaging of the chorioretinal scar demonstrated alternating hypertrophy and atro-phy of the retinal pigment epithelium along with a discrete break in Bruchs membrane. At baseline, the active lesiondemonstrated a large collection of inflammatory subretinal fluid adjacent to an area of active retinitis. Over time, the subretinalmaterial was found to resolve, there was restoration of the foveal anatomy, and the area of retinitis progressed into a chorioretinalscar.
Keywords: Subretinal fluid, Inflammation, Retinitis, Chorioretinal scar, Bruchs membrane, Retinal pigment epithelium, Toxo-plasmosis
2014 Production and hosting by Elsevier B.V. on behalf of Saudi Ophthalmological Society, King Saud University.http://dx.doi.org/10.1016/j.sjopt.2014.03.010
Ocular toxoplasmosis has been reported to be the mostcommon worldwide cause of posterior uveitis.1,2 The classicpresentation of ocular toxoplasmosis includes an exuberantvitritis with an area of active fluffy retinal whitening borderingan adjacent pigmented scar, several subtypes have been de-scribed including the one described in this case: PunctateOuter Retinal Toxoplasmosis (PORT).3 This variant is typifiedby a relative paucity of intraocular inflammation, thus permit-ting excellent chorioretinal imaging of pathological changesof the retina. Spectral Domain Optical Coherence Tomogra-phy (SD-OCT) imaging may provide new insights into thepathogenesis of PORT.
A 13-year-old girl presented with a four-day history of aprofound decrease in vision in her right eye unassociatedwith pain or redness. She did not recall any previous occur-rences of decreased vision in either eye. She reported a viralillness approximately three weeks prior to presentation char-acterized by fever and cough, which resolved spontaneously.She was presumed to be immunocompetent, had no addi-tional past medical or ocular history nor was taking anymedication.
The best-corrected visual acuity (BCVA) was 8/200 ODand 20/20 OS. Intraocular pressure was 19 mmHg OD and21 mmHg OS. Visual fields were full to confrontation,
SD-OCT of punctate outer retinal toxoplasmosis 153
and the blood pressure was 119/74. The anterior segmentexamination revealed Grade 0.5 + cell in the patients righteye, but there were no keratic precipitates or hypopyon pres-ent. There was Grade 1 + vitreous cell in the right eye. Exam-ination of the left eye was unremarkable.
The dilated fundus examination of the right eye demon-strated macular elevation with irregular yellowwhite spotscentrally at the level of the deep retina (Fig. 1A). Adjacentto this, at the 10 oclock position was an area of active retini-tis with focal retinal thickening. Inferotemporally, there wasan old hyper-pigmented chorioretinal scar with a surroundinghalo of retinal pigment epithelium (RPE) disturbance. Be-tween the area of active retinitis and the chorioretinal scar,there was an intervening area of apparently uninvolved ret-ina. The disk margin appeared sharp. Dilated examinationof the left eye was unremarkable without chorioretinal scars.
Fluorescein angiography demonstrated early blockage inthe area of the focal retinitis and from the chorioretinal scarin the early frames (Fig. 1B). There was progressive leakageof the active area of retinitis (Fig. 1C), with an adjacentwell-circumscribed area of pooling apparent in the lateframes (Fig. 1D). There was late hyperfluorescence apparentwithin the old scar and mild disk leakage.
Spectral Domain Optical Coherence Tomography (SD-OCT) using Cirrus HD-OCT (Carl Zeiss Meditec, Inc.) revealeda large subfoveal collection of subretinal fluid (SRF) (Fig. 1E).There was an irregularly thickened hyper-reflective interfaceappearing deep into the outer nuclear layer (ONL) liningthe superior aspect of the subretinal fluid space. There wasweakly reflective material at the base of the fluid accumula-
Figure 1. A. Fundus photograph of affected eye at presentation demonstratinarea of active retinitis and inferotemporal chorioretinal scar. Lines indicate thedemonstrating early blocking and increasing hyper-fluorescence of area ofdemonstrating large collection of subretinal fluid with weakly reflective mate(white arrow), with a string of material tethered across. F. Septum within subfluid nasal enclosing fibrin like material. Area of active retinitis adjacent to fdemonstrating alternating areas of irregularly bunched RPE (dark arrow) adshaped structure (white arrow) shown with frank disruption of RPE and Bruch
tion that contained several small hyper-reflective punctatefoci (dark arrow). The images revealed string-like structuretethered between the materials at the base of the fluid cavityto the hyper-reflective band superiorly (white arrow). Therewas no frank RPE detachment, however Bruchs membranecould be seen as a distinct structure, indicating that subtleRPE detachment may be present. There was no apparent fo-cal choroidal thickening, though the chorio-scleral interfacecould not be visualized throughout the scans.
A septum within the SRF accumulation was visible inFig. 1F. Temporally, the abnormal but recognizable inner-segment/outer-segment (IS/OS) junction (also called theEllipsoid Zone) was visible and seen to lead to a split (whitearrow) between the material occupying the base of the fluidcollection and the continuation of the material superiorly.Multiple hyper-reflective foci were seen within the subretinalspace. Adjacent to this space and overlying the SRF was thearea of retinitis visualized on the color photograph and angi-ography (dark arrow). There was increased hyper-reflectivityextending through the full thickness of the retina. The normalhypo-reflective inner nuclear layer (INL) and ONL were notvisualized due to this hyper-reflectivity, which was indicativeof inflammation.
An SD-OCT image was obtained through the old chorio-retinal scar (Fig. 1G) which demonstrated central irregularthickening of the RPE causing marked attenuation of theunderlying choroid (dark arrow) surrounded by a zone ofRPE atrophy and increased choroidal visibility. There wereno normal laminations of the overlying retina present. Therewas a bulb-shaped structure apparent (white arrow) that ap-
g subretinal fluid with fine whiteyellow spots adjacent to superotemporallocations of SD-OCT images in E, F, and G. BD. Fluorescein angiogramactive retinitis as well as pooling of the subretinal space. E. SD-OCT
rial at base (dark arrow) and lined superiorly by hyper-reflective materialretinal fluid visualized with frank sub-retinal fluid temporal, and loculatedluid pocket (dark arrow). G. Cross-section through old chorioretinal scarjacent atrophy with visualization of underlying Bruchs membrane. Bulb-s membrane.
Figure 3. A. Fundus photograph one month after presentation showingresolution of subretinal fluid with persistent pigmentary changes andconsolidation of area of retinitis. Line demonstrates location of SD-OCTimage B. B. Discreet area of full-thickness hyper-reflectivity visualized withunderlying Bruchs membrane visible and early atrophy.
154 B.J. Lujan
pears to pierce through the RPE and Bruchs membrane fromthe choroid to the retina.
The diagnosis of ocular toxoplasmosis was made clinicallyand treatment with 800 mg/160 mg Trimethoprim/Sulfa-methoxazole (Bactrim DS) twice a day for 60 days waspromptly initiated. No steroidal medication was given.
One week after presentation, BCVA had improved to 20/160 OD, anterior segment cell was absent but trace vitreouscell remained. Fundus examination revealed a reduction inthe subretinal fluid collection and an enlargement of the yel-lowwhite spots at the level of the deep retina (Fig. 2A).The areas of active retinitis and old retinitis appeared un-changed. SD-OCT demonstrated persistence of SRF withan increased accumulation of material hanging from theundersurface of the retina like stalactites in a cave(Fig. 2B). The external limiting membrane can clearly beseen moving over the fluid accumulation. At the base ofthe SRF, there was still weakly hyper-reflective materialpresent. There was a focal RPE detachment with a punctatearea of increased choroidal reflectivity. The septum of thismaterial, which had been apparent at presentation, wasdiminished (Fig. 2C) but the area of full-thickness hyper-reflectivity associated with the focal retinitis was stillapparent.
One month after initial presentation, BCVA had improvedto 20/40. The fluid centrally had cleared and no white dotsremained at the level of the deep retina (Fig. 3A). There werespiculated pigmentary changes present in the RPE. Ondilated examination, the area of active retinitis hadcontracted and the edges of the lesion were more distinct.SD-OCT revealed a more discreet area of full thicknesshyper-reflectivity, with improved visualization of adjacentretinal layers (Fig. 3B). A limited pigment epithelial detach-ment immediately underneath the retinitis was visible, as wellas circumferential RPE loss and increased Bruchs membranevisualization.
Figure 2. A. Fundus photograph of affected eye one week after presentation demonstrating larger yellowwhite subretinal spots and early consolidationof retinitis. Lines indicate locations of SD-OCT images in B and C. B. SD-OCT through subretinal fluid pocket showing subretinal material accumulations(white arrow) and clearly visualized external limiting membrane moving above the subretinal fluid (asterisk). C. SD-OCT demonstrating decreasedsubretinal fluid under persistent retinitis.
Figure 4. A. Fundus photograph three months after presentation showing persistent pigmentary changes adjacent to fovea and area of previous retinitiswith hard edges and early hyper-pigmentation. Lines demonstrate location of SD-OCT images B and C. B. Region of previously active retinitis showssmall mound of deep hyper-reflective material within zone of RPE atrophy. C. Normal foveal architecture with slightly irregular thickening of the IS/OSjunction in the temporal perifovea and more temporal area of RPE atrophy and photoreceptor disruption.
SD-OCT of punctate outer retinal toxoplasmosis 155
Three months after initial presentation, BCVA was 20/20.Clinically, there was no remaining active retinitis, but therewas increasing chorioretinal scarring at this location with in-creased pigmentation centrally and circumferential RPE atro-phy (Fig. 4A). SD-OCT demonstrated that the area of PEDtwo months earlier now demonstrated diffuse RPE lossaccompanied by visualization of Bruchs membrane and in-creased choroidal visualization (Fig. 4B). Centrally, the fovealcontour and retinal layers normalized. The IS/OS junction waspresent throughout, with only slight thickening irregularity oftemporal IS/OS and the photoreceptor outer segment tipshyper-reflective band remaining perifoveally. Temporal tothe perifovea there was a region of RPE and outer retinalatrophy, which comprised the inferior aspect of the resolvedarea of active retinitis.
Several authors have demonstrated some of the classicOCT features of ocular toxoplasmosis,4,5 or focused on punc-tate outer retinal toxoplasmosis (PORT).6 There are severalfindings in this case that have not been visualized by SD-OCT in PORT previously. Most prominently, the visualizationof the changes to the SRF space and the finding of the necro-tic chorioretinal lesion penetrating through Bruchs mem-brane were visualized within the inactive scar.
The features of SRF, photoreceptor accumulations, and aseptum of presumed fibrinous material have been previouslyattributed to cases of the VogtKoyanagiHarada Disease7,8
and Acute Posterior Multifocal Placoid Pigment Epitheliopa-thy.9 These diseases likely all have a common final pathwayresulting in the marked inflammatory process that results inthe creation of the vigorous fibrin response that has beenhypothesized.
Recently, this finding has also been reported in Toxo-plasmosis, being called a huge outer retinal cystoid space(HORC).10 The assertion that this finding represents
intraretinal fluid has several weaknesses. First, there is noanatomical potential space where this fluid could accumu-late as the ONL, ELM, and IS/OS junction represent opticalboundaries within the photoreceptor and Muller cell com-plex. Consequently, fluid would either have to be in theouter plexiform layer or in the subretinal space, and theONL is visualized clearly above the fluid in its subfoveallocation. The authors further maintain that because the fi-brin at the base of the fluid is roughly the same thicknessas the ELM to RPE that this likely represents retinal tissue.While this similarity in thickness is interesting, the possibilityof this representing inflammatory debris within the extracel-lular matrix where the photoreceptor tips had recently re-sided is equally plausible. Evidence for the HORC actuallybeing subretinal fluid is convincingly supported by thepresent case, which clearly shows the ELM above the lesionat follow-up (Fig 2B).
The hyper-reflective band beneath the ONL may correlateto a structure within the photoreceptors. However, thesource of that reflectivity cannot be the normal photorecep-tor wave-guided IS/OS junction, as it does not display the ex-pected directional reflectivity properties. Specifically, theintensity of the layer would be expected to diminish withincreasing angle of incidence from the OCT light source.11
Consequently, the source of this reflection may be secondaryto a new hyper-reflective surface within the photoreceptor asa result of the pathological changes observed. Whatever thesource of this reflection, the photoreceptors must not havebeen permanently damaged as they normalize at the finaltime point.
Doft and Gass concluded that the failure of the observeddeep retinal spots to be associated with angiographicchanges suggested that that they represented focal outerretinal gliotic scars.3 The use of SD-OCT in this case, raisesthe possibility that these changes are due to the accumula-tion of photoreceptor fragments dangling down from theelevated retina. These are numerous and small at the initial
156 B.J. Lujan
presentation, and became larger as they appear to aggre-gate by one week, perhaps due to a mix of regenerating pho-toreceptors and circulating fibrin.
The striking appearance of the complete loss of Bruchsmembrane and the RPE is visualized within the inferotempo-ral atrophic scar in Fig. 1G. Fluorescein angiography demon-strates early hyperfluorescence and late staining within thisarea, though no intraretinal or subretinal fluid is present. Thislesion may represent the initial site of chorioretinal invasioninto the retina, and there may be a fibrotic response givingthe appearance of the bulb on OCT. Furthermore, this couldrepresent a location of chorioretinal anastomosis at the loca-tion of a defect in Bruchs membrane.12 Ultimately, patholog-ical correlation will be required to fully validate eachcomponent of the chorioretinal anatomy that is exquisitelyvisualized by SD-OCT.
Conflict of interest
The authors declare that there is no conflict of interest
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Spectral domain optical coherence tomography imaging of punctate outer retinal toxoplasmosisIntroductionCase reportDiscussionConflict of interestReferences