Chorioretinal folds (CRF), or infoldings of the inner choroid, retinal pigment epithelium, and retina were originally described by Nettleship [1], and have been further characterized by Norton [2] and Newell [3] using ophthalmoscopy and fluorescein angiography in various posterior segment diseases. Reported associations include high hyperopia [4-7], age-related macular degeneration [2,4,8], hypotony [9], disc edema, idiopathic uveal effusion syndrome (IUES) [10], and external globe compression [11]. The term choroidal folds and chorioretinal folds have often been used interchangeably, however the former has occasionally been used to denote folds of the choroid and retinal pigment epithelium occurring without evidence of distortion of the overlying inner retinal tissue. Nevertheless, the two terms likely represent the same entity, and are recognized to have significant overlap by most authors [11,12].

Previous imaging reports have included angiography, fundus autofluorescence [13], and time-domain optical coherence tomography [12], but have lacked the resolution possible with current spectraldomain (SD-OCT) technology. Additionally, the pathogenesis of chorioretinal fold formation is incompletely understood. The authors hypothesized that enhanced depth imaging SD-OCT may reveal specific aspects of the choroid that may be helpful in understanding CRF pathogenesis. The purpose of the present report was to investigate the morphology of chorioretinal folds as imaged by high resolution SDOCT, and to investigate aspects of choroidal thickness and morphology using enhanced depth imaging (EDI).

Consecutive patients were prospectively evaluated over a twomonth period with EDI SD-OCT (Spectralis, Heidelberg Engineering, Heidelberg, Germany). All patients were seen and evaluated at a single vitreoretinal specialist office (Charles Retina Institute, Memphis, TN). Patients were evaluated with complete ophthalmic examination, EDI SD-OCT 12-line radial raster scan centered on the foveola with 20 scans averaged/raster. The treatment of all patients and data conformed with the tenets set forth in the Declaration of Helsinki, and was performed in accordance with the Health Insurance Portability and Accountability Act of 1996. The study was performed as part of an ongoing IRB approved study examining choroidal thickness and morphology.

628 patient SD-OCT examinations were initially reviewed for the presence of CRF. CRF were present in 11 patients (2%). Lesions simulating CRF, but were not considered true CRF after OCT analysis were present in 22 patients. Overall mean age ± standard deviation in patients with CRF was 66 ± 10 years. Patients consisted of 5 males and 6 females, 9 Caucasians, and 2 African Americans. Chorioretinal folds were bilateral in 5 patients and unilateral in 6. Mean spherical equivalent refraction (phakic or prior to cataract extraction) was 0.82 ± 4.5. Chorioretinal folds consisted of distinct infoldings of the inner choroid, RPE, and outer retina and did not appear to correspond to specific choroidal vessels in all cases. Overall mean subfoveal choroidal thickness was 421 ± 216. Mean best-corrected Snellen visual acuity (converted to log of minimum angle of resolution) was 0.32 ± 0.49, and overall mean intraocular pressure on the day of the examination (Goldmann applanation) was 13 ± 3 mm Hg.

Hyperopia

Cases 1-3 (5 eyes) presented with CRF and high hyperopia. Representative images are demonstrated in Figure 1. CRF were horizontal, asymptomatic, and unassociated with additional chorioretinal pathology in all cases. All patients were phakic and mean overall spherical equivalent was 7.25 ± 1.5 diopters. Mean subfoveal choroidal thickness was 493 ± 189 μm. Cases 1 and 2 were bilateral and associated with good vision (20/20-20/25). Case 3 was unilateral and associated with anisometropic amblyopia with BCVA of 20/70 and without any metamorphopsia or additional chorioretinal pathology.

Figure 1: Imaging characteristics of chorioretinal folds in high hyperopia. (A) Fundus autofluorescence demonstrating horizontal chorioretinal folds (arrow) in this 54 year-old patient with a spherical equivalent of +7.50 diopters; (B) Scanning laser ophthalmoscopic image demonstrating scan position for SD-OCT in (C) Enhanced depth imaging of chorioretinal folds consist of distinct infoldings of the choriocapillaris, RPE, and outer retina; the subfoveal choroidal thickness is 463 μm.

Idiopathic uveal effusion

Cases 3 and 4 (4 eyes) presented with nanophthalmos and idiopathic uveal effusion syndrome (IUES). Both cases demonstrated marked nanophthalmos on high resolution computed tomography and magnetic resonance imaging of the orbits, with axial globe diameter between 14 and 16 mm, with posterior scleral thickness greater than 3 mm in both cases. Representative images are presented in Figure 2. Mean spherical equivalent was 10.5 ± 0.7 diopters. Mean subfoveal choroidal thickness was 647 ± 161 μm. Case 3 (Figure 2) presented with multiple serous pigment epithelial detachments (PED) in both eyes and subretinal fluid in her left eye with BCVA of 20/100 and 20/25 with metamorphopsia in her right eye. Case 4 lacked subretinal fluid but SD-OCT revealed serous PED and diffusely thick choroid.

Figure 2: Imaging characteristics of chorioretinal folds in idiopathic uveal effusion syndrome. (A) Fundus photography of the right eye of this 61 yearold female with a spherical equivalent of +9.75 diopters demonstrating horizontal chorioretinal folds (arrow) and a large serous pigment epithelial detachment (asterisk); (B) Left eye demonstrating horizontal chorioretinal folds and central macular subretinal fluid (arrowheads); (C and D) Scanning laser ophthalmoscopic images, green line denotes scan position for SDOCT images in (E) demonstrating infolding of the choriocapillaris, RPE, and outer retina; subfoveal choroidal thickness is 731 μm and (F) Chorioretinal folds similar to (E), with central macular subretinal fluid, subfoveal choroidal thickness is 760 μm.

Secondary

Cases 5-8 (4 eyes) presented with unilateral CRF following ocular surgery, two following encircling scleral buckle (Figure 3) and two with chronic hypotony following pars plana vitrectomy or trabeculectomy. Cases 5 and 6 had previous scleral buckle without vitrectomy, and reported metamorphopsia, each with vision of 20/40 in the affected eye. Case 5 had spherical equivalent of -2.00 diopters and subfoveal choroidal thickness of 275 μm which was identical to the fellow eye. Case 6 was a high myope with spherical equivalent of -8.25 and subfoveal choroidal thickness of 82 μm, which was similar to the fellow eye. CRF in cases 5 and 6 appeared as distinct infoldings of the inner choroid, RPE and outer retina (Figure 3) without a diffusely thick choroid. Cases 7 had chronic hypotony with intraocular pressure of 3 mmHg following trabeculectomy. EDI SD-OCT revealed typical CRF with a diffusely thick choroid of 428 μm and BCVA of 20/200. The fellow eye had choroidal thickness of 228 μm with BCVA of 20/20. Case 8 had a chronic retinal detachment and intraocular pressure of 4 mm Hg. Subfoveal choroidal thickness was 340 μm and 212 μm in the unaffected fellow eye. Cases 9 and 10 (4 eyes) had bilateral CRF with mean spherical equivalent of -1.25 and -0.75, respectively. Both patients had a diffusely thick choroid (mean 686 ± 74 μm) with normal anterior chamber angle. Both patients had BCVA of 20/20 in both eyes but reported metamorphopsia. CRF appeared identical to those seen in other patients with a diffusely thick choroid in the present series. Case 11 presented with unilateral CRF 2 years following blunt ocular trauma and choroidal rupture. Subfoveal choroidal thickness was 241 μm which was similar to the fellow eye.

Figure 3: Chorioretinal folds following scleral buckle. (A) Scanning laser ophthalmoscopic image demonstrating subretinal proliferative vitreoretinopathy (arrow) and scan position for SD-OCT image in (B) demonstrating chorioretinal folds involving the choriocapillaris, RPE, and outer retina; this 43 year-old patient with a spherical equivalent of -1.25 diopters has a normal subfoveal choroidal thickness of 223 μm.

Lesions simulating chorioretinal folds

22 patients (36 eyes) presented with an ophthalmoscopic appearance that was consistent with CRF, but SD-OCT revealed similar or simulating lesions that were not true chorioretinal folds. Mean age in this subgroup was 71 ± 12 years. In 17 patients, all with a diagnosis of atrophic age-related macular degeneration, EDI SDOCT revealed a diffusely thin choroid, drusen, subretinal drusenoid deposits, and focal chorioretinal contour changes that corresponded to specific choroidal vessels (Figure 4). 5 additional patients had a similar SD-OCT appearance but lacked features of age-related macular degeneration, and thus represented age-related choroidal atrophy. The overall mean subfoveal choroidal thickness in this group was 88 ± 24 μm. One patient presented with metamorphopsia and a submacular choroidal varix (Figure 4) without additional chorioretinal pathology and demonstrated focal elevations of the choroid corresponding to a specific dilated choroidal vessel.

Figure 4: Differentiating features of chorioretinal folds and elevations corresponding to specific choroidal vessels. (A) This 46 year-old patient with chorioretinal folds and oral topiramate use has a thick subfoveal choroid (461 μm) and infoldings in the choriocapillaris, RPE, and outer retina which do not correspond to specific choroidal vessels; (B) In contrast, this 84 year-old patient with age-related choroidal atrophy has multiple focal elevations of the RPE and outer retina (arrows) that correspond to specific choroidal vessels in an overall thin choroid (96 μm); (C) This 57 year-old male with a symptomatic submacular choroidal varix has focal chorioretinal contour changes which, similar to B., corresponds to the underlying choroidal vessel; the vessel lumen diameter measures 245 μm and the choroid measures less than 100 μm in adjacent locations.

The imaging results of the present series indicate that CRF consist of distinct infoldings of the inner choroid and outer retina, which are consistent with previous reports. With EDI SD-OCT, we have demonstrated a significantly thicker than average choroid in patients with CRF in the context of high hyperopia, uveal effusion, and hypotony. Patients with secondary CRF due to scleral buckle or trauma demonstrated choroidal thickness in the normal range, but with similar morphology of the inner choroid, RPE, and outer retina. Giuffre et al., in the only prior report of OCT analysis of chorioretinal folds, used time-domain OCT to evaluate 8 patients. In that series, Giuffre et al. demonstrated similar features to the present analysis, but lacked choroidal thickness data due to the low resolution and lack of enhanced depth imaging. They identified two variants of CRF, differentiated by the presence of retinal undulations in some patients (chorioretinal folds) and the lack of retinal involvement in others (choroidal folds). That report did stress, however, the significant overlap among the two entities. In the present series, all patients with true chorioretinal folds demonstrated infoldings of the inner choroid (choriocapillaris), RPE, and outer retina. We did not observe significant inner retinal contour changes in cases of true CRF. Interestingly, several patients in the present series presented with chorioretinal contour changes which appeared similar to CRF on ophthalmoscopy, but SD-OCT revealed a focal elevation involving the outer retina and retinal pigment epithelium (RPE) corresponding to a specific choroidal vessel (Figure 4). We have termed this entity focal choroidal elevation, which appears as a relatively common feature of patients with age-related choroidal atrophy and age-related macular degeneration, and is the subject of a forthcoming investigation. We do not feel this entity represents true CRF, but is rather the consequence of a relatively thin choroid resulting in the RPE being draped over the more rigid underlying choroidal vessels. This may represent a subset of previously reported CRF in agerelated macular degeneration, and in fact has some features in common with the OCT appearance of Giuffre et al. [12] (Figures 1d and 2a). Gass [8] reported radial CRF in association with contracted choroidal neovascularization, which likely represents a subset of true CRF due to mechanical fibrovascular contraction of the RPE in exudative agerelated macular degeneration.

The largest single group of patients with CRF in the present series represented bilateral high hyperopia and revealed horizontal chorioretinal folds in the absence of additional chorioretinal pathology that appeared asymptomatic. In contrast to patients with high hyperopia alone, patients with CRF due to uveal effusion or secondary causes reported metamorphopsia, and often had reduced vision either from CRF or subretinal fluid. Serous PED was a common feature in patients with uveal effusion, which was absent from patients with high hyperopia or hypotony. In patients with hypotony, the choroid appeared thickened secondarily, as evident by the asymmetric and normal choroidal thickness in the fellow eye. This is similar to previous reports indicating that chronic sub-clinical CRF are often asymptomatic, but may lead to significant visual consequence when develop acutely or are secondary to additional underlying pathology [9,11].

The results of the present series may offer insight into the underlying pathogenesis of chorioretinal folds. As previously theorized [8,10,14], the diffusely thickened choroid in cases of high hyperopia, idiopathic uveal effusion, hypotony, and topiramate use is consistent with a spectrum of choroidal effusion. This may be secondary to anatomic variants, as in hyperopia or medication use, as in topiramate. We hypothesize that the development of CRF results from a diffusely thickened choroid which effectively decreases the internal circumference of the vitreous cavity, thereby leading to the RPE/inner choroid complex being thrown into redundant folds. We also observed cases in which the choroid demonstrated a normal thickness, such as in encircling scleral buckle and trauma. In the case of scleral buckle, the internal circumference of the vitreous cavity is reduced due to external compression, which likely represents a similar mechanical mechanism as in high hyperopia but without a primary choroidal process.

The present series is limited by small sample size, single-center study location, and lack of longitudinal analysis. We observed CRF in 2% of patients seen over a two-month study period that likely overestimates the true prevalence of the finding due to the sub-specialist referral center location. We conclude that CRF due to high hyperopia, IUES, topiramate, and hypotony involve an overall thick choroid and involve infoldings of the choriocapillaris, RPE, and outer retina. This is in contrast to CRF secondary to trauma or scleral buckle, which have an identical inner choroidal morphology but a normal choroidal thickness. EDI SD-OCT is helpful in differentiating true chorioretinal folds from additional simulating lesions, such as focal choroidal elevations, which may be more common than true chorioretinal folds.

We describe the morphologic characteristics of chorioretinal folds using spectral domain optical coherence tomography and identify a diffusely thickened choroid in cases associated with hyperopia and hypotony but a normal choroidal thickness in cases associated with previous surgery or trauma.

The authors have no financial interest or conflict of interest regarding the material presented in this report.