Middle-aged man reports new onset diplopia
A 40-year-old African-American male patient presented to our clinic for his first eye exam with a complaint of new onset horizontal diplopia for several days. He reported it was worse at distance and when looking to his left. He denied trauma, headache, redness or vision changes in either eye.
His ocular history was otherwise unremarkable. His medical history was positive only for hypertension, which was currently being treated with oral antihypertensive medication. His social and family history was otherwise unremarkable. He denied any known drug allergies.
The patient’s best-corrected visual acuity was 20/20 OD and 20/20 OS with +0.50 D sphere lenses.
Pupil testing and confrontation visual fields were within normal limits in both eyes. However, there was a clear abduction deficit of the left eye in attempted left gaze that was consistent with both his complaints and consistent with a left abducens nerve palsy (CN VI). IOPs were 13 mm Hg OD and 13 mm Hg OS with Goldmann tonometry. Dilated fundus examination (which included 90 D ophthalmoscopy, binocular indirect ophthalmoscopy and widefield fundus photography of both eyes) revealed distinct nerve margins (no evidence of papilledema) as well as an undulating/wrinkling appearance to his posterior poles in both eyes.
Additional testing included: OCT, OCT angiography, fundus autofluorescence imaging and posterior segment ultrasonography. Urgent magnetic resonance imaging (secondary to his new onset CN VI palsy) and neurological consultation resulted in a new diagnosis of multiple sclerosis.
The abducens nerve palsy resolved with intravenous corticosteroid treatment (under the supervision of his neurologist) over the next few weeks. Curiously, his bilateral posterior pole appearances have remain unchanged over a 6-month period since first noted and proved more difficult to explain.
What’s Your Diagnosis?
A number of differential diagnoses of bilateral posterior pole appearances were considered.
Epiretinal membrane is a common finding of retinal surface wrinkling, usually associated with posterior vitreous detachment or inflammation in the posterior pole, and it can be bilateral. However, this does not cause wrinkling of RPE/choroidal tissues because this is a superficial retinal wrinkling. OCT helped rule this out as a cause in this case.
Central serous chorioretinopathy (CSCR) has many associations, is more common in young men than women and usually is unilateral more so than bilateral. It typically has characteristic neurosensory detachments near the fovea or in the posterior poles and is easily seen on OCT imaging. Fundus autofluorescence imaging can reveal retinal pigmented epithelial patterns suggesting previous episodes of subretinal fluid leakage suggestive of CSCR. However, both the autofluorescence and OCT imaging ruled out this potential differential diagnosis in this case.
Cystoid macular edema has many causes, ocular and/or systemic. Characteristic cystic spaces can be noted on OCT images, but they were absent in this case, and, therefore, it was ruled out.
Chronic posterior iritis was a differential diagnosis, but the patient had no prior history of iritis or subclinical iritis signs such as keratic precipitates or posterior synechiae and no known systemic history to suggest posterior iritis. This was ruled out easily with a standard comprehensive eye exam in this case.
Posterior scleritis can cause an undulating posterior pole appearance as in this case and can be both unilateral or bilateral. It is usually associated with a known systemic cause (but not always) and textbook clinical finding of “T-sign” noted on posterior segment ultrasonography. The T-sign was notably absent in this case, and the patient had no associated systemic conditions. Therefore, this was ruled out.
Rhegmatogenous and/or exudated retinal detachments are possible and might present in a similar fashion to this case, however this was ruled out by OCT imaging and dilated retinal exam.
Hypotony retinopathy can be caused by overfiltration of glaucoma surgical procedures resulting in very low IOP. However, this was ruled out by the patient’s ocular history and absence of ocular surgeries. Additionally, his IOP was within normal ranges that would not be low enough to cause hypotony retinopathy.
Orbital tumors can cause choroidal folds due to compression of the posterior wall of the involved eye; however, that would be an exceedingly rare cause of bilateral choroidal/chorioretinal folds, as this would require two orbital tumors. This was as ruled out in this case by the patient’s brain MRI, which failed to show any orbital tumors.
Choroidal/chorioretinal folds are a wavy, undulating appearance of posterior poles. They can be asymptomatic or symptomatic in some patients, and either unilateral or bilateral. Historically, they are associated with hyperopia, orbital tumors and idiopathic causes. They can be confirmed by OCT imaging, fundus autofluorescence and lack of T-sign on posterior segment ultrasonography. This diagnosis fits this case very well in retrospect.
Chorioretinal vs. choroidal folds
Chorioretinal folds are a relatively uncommon clinical finding and were first documented in 1884 by Nettleship. They have since been described as pseudo-sinusoidal undulations of the inner choroid, Bruch’s membrane and retinal pigment epithelium (RPE) that can secondarily include the overlying neurosensory retina. They also have been described as striae, grooves and/or lines in the posterior pole that can have numerous varied patterns in which they can be arranged.
The appearance is typically of linear-like light and dark streaks found during funduscopy, typically confined to the posterior pole. The alternating light and dark bands in the posterior pole correlate with the stretched and thinner RPE peaks (light bands) and compressed troughs (dark bands) characteristic of chorioretinal folds. A known underlying autoimmune disease has been associated with chorioretinal folds in approximately 28% of cases (Olsen et al.). Interestingly, multiple sclerosis, considered to be part of the autoimmune spectrum of diseases, has been associated with chorioretinal folds in approximately 2.5% of cases.
The terms “chorioretinal folds” and “choroidal folds” have been used interchangeably to describe the retinal appearance encountered clinically. Choroidal folds are typically thought of as an undulating/wavy choroid, Bruch’s membrane and RPE with intact/flat overlying retinal tissues. When the retinal tissues also have an undulating/wavy appearance to them, in addition to the choroid/RPE complex, “chorioretinal folds” is the preferred term. However, in some cases differentiation between the two can be very difficult, as both may coexist in the same eye. Therefore, “chorioretinal folds” and “choroidal folds” are often used interchangeably in a clinical context.
Signs, symptoms
Approximately 44% to 58% of chorioretinal folds cases are reported to be unilateral, while 42% to 56% are bilateral (Olsen et al., Bagnis et al.). Visual acuity can be reduced depending on the severity of macula involvement. Patients may or may not have visual symptoms associated with the chorioretinal folds. If visual symptoms are present, reduced visual acuity or metamorphopsia are likely to be the main complaints, which would indicate distortion or disruption of the overlying photoreceptors in the affected retinal areas. In chronic chorioretinal folds, most patients deny metamorphopsia and have normal, or near-normal, visual acuity.
It has been suggested that any condition causing thickening or shortening of the sclera can produce the characteristic undulating wrinkles found in chorioretinal folds (Olsen et al., Corvi et al., Bagnis et al., Giuffrè et al.). Some have also suggested that chorioretinal folds occur when either external or internal compressive forces overcome the natural tension of the choroid and RPE complex that then allows the folds to appear as they do clinically (Del Turco et al.). Some authors have even suggested that prior episodes of resolved posterior scleritis or other inflammation may leave the chorioretinal folds as a residual change (this might be a potential explanation regarding the origin of the chorioretinal folds described in this case report) (Olsen et al.).
In line with this thought, Olsen et al. reported six cases of idiopathic chorioretinal folds, and five of those six cases had previously undiagnosed ocular inflammatory episodes, which they suggest might have led to the formation of the chorioretinal folds in those cases. Despite the above attempts to explain the pathophysiology, many authors still believe the true pathogenesis of chorioretinal fold formation has not yet been completely elucidated.
Etiology
The broad disease categories associated with chorioretinal folds involve ocular and nonocular causes and can include idiopathic, infectious, infiltrative, neoplastic and inflammatory associations. Specific causes and associations that have been reported in the literature are numerous but have included idiopathic, papilledema (ie, pseudotumor cerebri, space occupying lesions), optic neuritis/neuropathies, thyroid eye disease, choroidal neovascularization (ie, age-related macular degeneration), hyperopia (even mild amounts), central serous chorioretinopathy, choroidal nevi, orbital and choroidal tumors, surgical procedures (ie, glaucoma surgery resulting in hypotony, or scleral buckling procedures), choroidal edema/inflammation (ie, posterior scleritis, uveal effusion), systemic autoimmune diseases (ie, rheumatoid arthritis, inflammatory bowel disease, psoriasis, polymyalgia rheumatica, multiple sclerosis, Vogt-Koyanagi-Harada disease) and infectious diseases (ie, sinusitis, Lyme disease).
The most common associations with chorioretinal folds in a fairly recent study (n = 40) were reported to be hypertension (47.5%), hyperopia (45%) and known systemic autoimmune disease (28%) (Olsen et al.). The most common known systemic autoimmune disease associated with chorioretinal folds was rheumatoid arthritis, but multiple sclerosis was also associated with chorioretinal folds in 2.5% of their total cases (one out of 40 patients), showing the rarity of this association. Interestingly, the “idiopathic” category of chorioretinal folds has reduced in size over the years as an increase in associations/causes have been identified. Currently, chorioretinal folds appear to be truly idiopathic in approximately 11% to 17% of cases (Olsen et al., Del Turco et al.).
Diagnostic tools
Clinical tests and tools to evaluate and detect choroidal folds include comprehensive eye examination (with ophthalmoscopy), color retinal photography, fluorescein angiography, indocyanine green angiography, fundus autofluorescence imaging and OCT. Neuroimaging (ie, orbital magnetic resonance imaging or computed tomography) should be considered in select cases. Posterior segment ultrasonography does not necessarily detect chorioretinal folds but can be used to rule out associated diseases in select cases, such as in suspected posterior scleritis cases.
OCT can be of large clinical value when examining patients to visualize the chorioretinal folds themselves and also can help rule out the larger differential diagnoses of chorioretinal folds, specifically epiretinal membranes and central serous chorioretinopathy. Expected findings of chorioretinal folds on OCT include undulating/wavy choroid and retinal tissues of apparently normal thickness. Obtaining OCT cross sectional scans of the retina perpendicular to the direction of the chorioretinal folds may highlight the chorioretinal folds in a more obvious manner for the clinician, making the diagnosis easier.
OCT angiography (OCTA) is a new OCT technology in which erythrocyte movement in retinal blood vessels can be mapped out and then segmented to different structural layers of the retina and choroid for evaluating blood flow to those specific layers. OCTA can also show a reduction of the blood flow signal corresponding to the chorioretinal folds, typically in the choriocapillaris layer of the OCTA scan.
The standard choriocapillaris layer thickness for the Zeiss Angioplex OCTA software used in this case report is 20 µm. Additionally, by using the choriocapillaris layer structural images, it is possible to obtain clearer images of chorioretinal folds in patients such as the one in this case. Therefore, OCTA can strongly be considered as an additional tool (in conjunction with regular structural OCT scans) for structural and blood flow analysis in cases of suspected or confirmed chorioretinal folds.
Chorioretinal folds should be considered a clinical finding rather than a diagnosis, as there are numerous known causes and associations. Once chorioretinal folds are clinically identified, a prompt systemic investigation for a known cause should be sought. Only when local or systemic conditions are ruled out can the chorioretinal folds truly be labeled as idiopathic.
A thorough diagnostic algorithm has recently been published in hopes of streamlining the management of these cases of chorioretinal folds and efficiently finding any potential systemic associations (Bagnis et al.). Treatment of chorioretinal folds should be directed at the underlying cause(s).
Thoughts on this case
It might be possible that this patient’s bilateral presentation could simply be associated with his mild amount of bilateral hyperopia or hypertension, both reported to be known associations. However, multiple sclerosis is a rare systemic association of chorioretinal folds and could be significant in this case. However, it’s important to keep in mind that association does not necessarily imply causation.
For example, hypertension was associated with choroidal folds in almost half of the cases by Olsen and colleagues, but if hypertension is truly a causative condition of chorioretinal folds, then with the massive amounts of people diagnosed with hypertension in the U.S., why aren’t chorioretinal folds seen much more frequently in our clinical settings?
Appropriate clinical protocols/tools should be used to help identify underlying diseases or associations when chorioretinal folds are encountered clinically. According to the author’s knowledge and research for this case report, there have only been three cases described in the literature of using OCTA to specifically examine chorioretinal folds. This adds another case of OCTA technology adjunctively highlighting a case of bilateral chorioretinal folds. It also highlights the importance of searching for underlying systemic associations of chorioretinal folds.
I suspect that the patient’s hyperopia, and perhaps even his multiple sclerosis (a known rare association with chorioretinal folds), are the best explanations for his bilateral chorioretinal folds. It might also be possible that neither are causative, and perhaps he represents a presentation of idiopathic bilateral chorioretinal folds with a confounding associated systemic condition (ie, multiple sclerosis). It will be difficult to say for sure unless his clinical appearance changes in a way to suggest otherwise in the future. Fortunately, his vision and bilateral chorioretinal folds have remained unchanged for approximately 6 months from his baseline exam. He was asked to return in another 6 months from his last exam, but at the time of writing this report, has not yet returned as requested.
References:
- Bagnis A, et al. Chorioretinal folds: a proposed diagnostic algorithm. Int Ophthalmol. 2019;doi:10.1007/s10792-019-01083-y.
- Corvi F, et al. Atypical presentation of chorioretinal folds-related maculopathy. Optom Vis Sci. 2016;93:1304–1314.
- Del Turco C, et al. Optical coherence tomography angiography features of chorioretinal folds: A case series. Eur J Ophthalmol. 2017;27:e35–e38.
- Giuffrè G, et al. Optical coherence tomography of chorioretinal and choroidal folds. Acta Ophthalmol Scand. 2007;85:333–336.
- Jaworski A, et al. Aetiology and management of choroidal folds. Clin Exp Optom. 1999;82:169–176.
- Olsen TW, et al. Chorioretinal folds: Associated disorders and a related maculopathy. Am J Ophthalmol. 2014;157:1038–1047.
- Rosenfeld PJ, et al. Zeiss Angioplex spectral domain optical coherence tomography angiography: technical aspects. Dev Ophthalmol. 2016;56:18–29.
- Sarraf D, et al. Bilateral choroidal folds and optic neuropathy: A variant of the crowded disk syndrome? Ophthalmol. 2003;110:1047–1052.
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