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doi: 10.1097/IAE.0000000000000288
Review

ENHANCED DEPTH IMAGING OPTICAL COHERENCE TOMOGRAPHY OF INTRAOCULAR TUMORS: From Placid to Seasick to Rock and Rolling Topography—The 2013 Francesco Orzalesi Lecture

Shields, Carol L. MD*; Pellegrini, Marco MD; Ferenczy, Sandor R. CRA*; Shields, Jerry A. MD*

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Author Information

*Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, Pennsylvania; and

Eye Clinic, Department of Biomedical and Clinical Science “Luigi Sacco,” University of Milan, Luigi Sacco Hospital, Milan, Italy.

Reprint requests: Carol L. Shields, MD, Ocular Oncology Service, Suite 1440, Wills Eye Institute, 840 Walnut Street, Philadelphia, PA 19107; e-mail: carol.shields@shieldsoncology.com

Supported by Eye Tumor Research Foundation, Philadelphia, PA (C.L.S. and J.A.S.), Lift for a Cure, Morrisdale, PA (C.L.S. and J.A.S.), and the Lucille Wiedman fund for Pediatric Eye Cancer, Philadelphia, PA (J.A.S., C.L.S.). The funders had no role in the design and conduct of the study, in the collection, analysis, and interpretation of the data, and in the preparation, review, or approval of the manuscript.

None of the authors have any conflicting interests to disclose.

Presented in part as the 2013 Francesco Orzalesi Lecture, Milan, Italy, December 12, 2013 (C.L.S.).

C. L. Shields, has had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

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Abstract

Purpose:

To review enhanced depth imaging optical coherence tomography of intraocular tumors.

Methods:

Review of tumor surface topography and internal characteristics based on published reports and personal experience.

Results:

Using enhanced depth imaging optical coherence tomography, choroidal nevus showed smooth moderate dome-shape and with overlying retinal pigment epithelial alterations, subretinal cleft, and photoreceptor loss. Choroidal melanoma was smooth, moderately dome-shaped, and with overlying “shaggy” photoreceptors. Choroidal metastasis showed “lumpy, bumpy” irregular surface topography, subretinal fluid, and shaggy photoreceptors. Choroidal hemangioma was smooth, acutely dome-shaped and with subretinal fluid and/or cystoid retinal edema. Choroidal lymphoma showed “placid, rippled, or seasick” surface, correlating with increasing tumor thickness. Choroidal osteoma displayed smooth undulating surface with intralesional lamellar lines and tubules, representing bone lamellae or vessels. Choroidal melanocytosis produced flat but uniformly thickened choroid with increased stromal density. Choroidal hemorrhage displayed slightly “scalloped” surface in the outer choroid. All choroidal tumors showed inward compression of the choroidal vasculature, except for hemangioma in which the vessels were expanded. Sclerochoroidal calcification arose within the sclera as a “rocky” or “rolling” topography and solitary idiopathic choroiditis appeared as a domed or “volcanic” focal scleral thickening, each causing intense choroidal compression. Retinal tumors such as small retinoblastoma, astrocytic hamartoma, and hemangioblastoma arose abruptly adjacent to normal retina. Exophytic retinoblastoma and retinal hemangioblastoma depicted a full-thickness disorganized retinal mass with normal retina draped over the margins. Flat astrocytic hamartoma arose within the nerve fiber layer, and thicker tumors involved full-thickness retina with “moth-eaten” or cavitary appearance. Retinal pigment epithelial lesions such as congenital hypertrophy of retinal pigment epithelial showed flat topography with transmission of light through lacunae, occasional subretinal cleft and uniform photoreceptor loss, whereas combined hamartoma of retina/retinal pigment epithelial showed “sawtooth” pattern of vitreoretinal traction leading to mini-peak or maxi-peak retinal folds.

Conclusions:

Enhanced depth imaging optical coherence tomography shows characteristic topographical and intralesional patterns that appear to be suggestive for selected intraocular tumors.

The introduction of optical coherence tomography (OCT) into the field of medicine has provided tremendous improvement in the understanding of the anatomical changes that accompany human diseases.1 Optical coherence tomography is widely used in various fields including gastroenterology, dermatology, cardiology, and ophthalmology.1–5 The early version of OCT using time-domain technology was commercially available in 1995. Time-domain OCT depicted cross-sectional anatomy of the retina with little or no information regarding deeper layers including the choroid and sclera. Early reports on OCT of intraocular tumors focused mostly on the related retinal findings and provided little data on the features of deeper tissues.6–9 Later developments with spectral domain OCT has allowed faster scanning speed of up to 40,000 scans per second, and, most importantly, higher resolution images of 4 μm to 7 μm. Modifications of spectral domain OCT technology with enhanced depth imaging optical coherence tomography (EDI-OCT) has remarkably improved in vivo visualization of the posterior globe to the depths of the choroid and sclera.10 Current axial resolution with EDI-OCT is approximately 3.9 μm. Enhanced depth imaging optical coherence tomography provides new observations on the normal variations in the retina, choroid, and sclera and allows in vivo exploration into the pathology of these tissues during disease states. Herein, we review our current knowledge on EDI-OCT of intraocular tumors.

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Choroid

Choroid Nevus

The choroidal nevus is a relatively common intraocular tumor, benign in nature and with little potential for visual loss or growth into melanoma.6,11–17 In a multiethnic study, choroidal nevus prevalence in the posterior pole of the eye was 4.1% in whites, 0.7% in blacks, 1.2% in Hispanics, and 0.04% in Chinese.13 The clinical features were similar among different races. In a clinic-based study on 3,422 eyes with choroidal nevus, 3 features changed with age: mean nevus thickness (thicker with age), multiplicity of nevi (more likely multifocal with age), and presence of drusen (increase with age).11 The annual transformation rate of choroidal nevus into melanoma has been mathematically estimated at 1 in 8,845.17 Risk factors can assist in identifying nevus with predisposition for transformation.14,16

Time-domain OCT of choroidal nevus has identified overlying retinal alterations of intraretinal edema, subretinal fluid, photoreceptor atrophy, and retinal pigment epithelial (RPE) detachment, with little information on the choroidal features of the nevus.18 Enhanced depth imaging optical coherence tomography of choroidal nevus has provided information on both the retinal and choroidal components.19–22 On EDI-OCT, choroidal nevus appears as a gently domed smooth-surfaced choroidal mass with deep choroidal shadowing depending on the degree of pigmentation19 (Table 1) (Figure 1). A comparison of pigmented versus nonpigmented nevus showed that choroidal shadowing was significantly greater with pigmented nevus (P = 0.046).19 In an analysis of 51 eyes with choroidal nevus, other EDI-OCT features included choriocapillaris thinning overlying the nevus (94%), RPE atrophy (43%), RPE loss (14%), RPE nodularity (8%), photoreceptor loss (43%), inner segment–outer segment junction (IS–OS, ellipsoid) irregularity (37%) or loss (6%), external limiting membrane irregularity (18%), outer nuclear and outer plexiform layer irregularity (8%), and inner nuclear layer irregularity (6%).19 Overlying subretinal fluid was identified by EDI-OCT (16%), most often with retracted or absent photoreceptors.

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In summary, EDI-OCT generally demonstrates choroidal nevus with gentle sloping, smooth-surface topography, chronic overlying RPE, and retinal degenerative finding and, most prominently, photoreceptor retraction or atrophy.

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Choroid Melanoma

The recognition of small choroidal melanoma using characteristic clinical features is critical to early detection and can provide improved patient prognosis.16,23 The prognostic importance of tumor size has been emphasized, noting that an increase of 1 mm in the melanoma thickness leads to approximately 5% increased risk for metastatic disease at 10 years.23 Based on these findings, early detection of choroidal melanoma, when the tumor is small (thickness ≤ 3 mm), is important.

The challenge in early detection of choroidal melanoma relates to its clinical similarity to benign choroidal nevus. Differentiation of melanoma from nevus rests on identification of ophthalmoscopically visible factors suggestive of melanoma such as greater tumor thickness, presence of subretinal fluid and overlying orange pigment (lipofuscin), tumor margin near the optic disc, and absence of drusen and halo.16 Diagnostic testing can confirm these features using OCT for the detection of subretinal fluid and fundus autofluorescence for depiction of RPE hyperautofluorescence of lipofuscin accumulation. Time-domain OCT has been used to evaluate retinal features over choroidal melanoma, with little detail on choroidal component.24,25

More recent experience with spectral domain EDI-OCT of small choroidal melanoma has revealed improved resolution of the choroidal findings as well as the retinal features.26–28 In 37 eyes with small choroidal melanoma (thickness ≤ 3 mm), the mean tumor thickness was 1,025 μm by EDI-OCT compared with 2,300 μm by ultrasonography. The overestimation of tumor thickness on ultrasonography compared with EDI-OCT has been found with most choroidal tumors, probably related to ultrasonographic difficulty in pinpointing the posterior choroidal margin, poorer resolution of the overlying retina on ultrasonography leading to inadvertent inclusion of retinal thickness within choroidal measurement, and relatively gross estimation using ultrasonographic calipers. Mrejen et al have explored the disparate measurements of choroidal lesions using EDI-OCT versus ultrasonography. They suggested factors that could lead to pitfalls for choroidal thickness measurement including patient age, globe myopia, diurnal variation of choroidal thickness, variability of scleral thickness, and the difficulty in identification of the posterior choroidal–scleral interface on ultrasonography and OCT.29

By EDI-OCT, choroidal features of melanoma can be similar to nevus with deep optical shadowing (97%) and overlying choriocapillaris compression (100%)27 (Table 1). Outer retinal features included shaggy photoreceptors (49%) and structural loss of photoreceptors (24%), ellipsoid segment (65%), external limiting membrane (43%), outer nuclear layer (16%), and outer plexiform layer (11%)27 (Figure 2). Inner retinal features included irregularity of inner nuclear layer (8%), inner plexiform layer (8%), ganglion cell layer (8%), and nerve fiber layer (5%). Subretinal fluid (92%), subretinal material compatible with lipofuscin or other bisretinoids (95%), and intraretinal edema (16%) were identified.

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A comparison of EDI-OCT of small choroidal melanoma versus similar-size choroidal nevus revealed statistically significant differences with melanoma (compared with nevus) showing increased tumor thickness (P = 0.0001), subretinal fluid (P = 0.0001), subretinal lipofuscin deposition (P = 0.0001), RPE atrophy (P = 0.0002), intraretinal edema (P = 0.0029), photoreceptor shagginess (P = 0.0054), loss of external limiting membrane (P = 0.0082), loss of ellipsoid layer (P = 0.0233), irregularity of inner plexiform layer (P = 0.0385), and irregularity of ganglion cell layer (P = 0.0385).27 In that analysis, shaggy photoreceptors were found overlying choroidal melanoma (49%) but not observed overlying nevus (0%) (P = 0.0001).

In summary, EDI-OCT of choroidal melanoma generally shows gentle domed-shaped, smooth-surface topography with relatively fresh subretinal fluid demonstrating shaggy photoreceptors. Shaggy photoreceptors could represent swollen photoreceptor tips or could represent macrophages with lipofuscin on the detached posterior retinal surface.

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Choroid Metastasis

Choroidal metastases originate most commonly from breast or lung carcinoma, appearing as a soft yellow mass deep into the retina, often with overlying subretinal fluid.30 Most choroidal metastases are of small-to-medium size with a mean thickness of 3 mm and with tumor epicenter in the macular region or paramacular region.30 The small size and posterior location of most choroidal metastases render these tumors ideal for study with OCT. A previous time-domain OCT study on choroidal metastasis by Arevalo et al31 demonstrated the prominent overlying subretinal fluid but with little detail on the tumor surface topography or intralesional features.

Enhanced depth imaging optical coherence tomography of choroidal metastasis show tumor surface topography as slightly irregular, often with a “lumpy bumpy” appearance32–34 (Table 1). This is in contrast to nevus and melanoma that usually show smooth, dome-shaped topography. Witkin et al demonstrated that EDI-OCT can help identify clinically inapparent choroidal metastasis in a symptomatic patient.32 Al-Dahmash et al34 imaged 31 eyes with choroidal metastasis using EDI-OCT and found 14 (45%) with image detail suitable for study. The metastasis originated from carcinoma of the breast (50%), lung (36%), pancreas (7%), and thyroid gland (7%). The mean tumor basal diameter was 6.4 mm, and the mean thickness was 2.3 mm by B-scan ultrasonography. The tumor location was submacular in 6 eyes (43%) and extramacular in 8 eyes (57%). By EDI-OCT, the mean tumor thickness was 987 μm. The most salient EDI-OCT features of metastasis included an irregular (“lumpy bumpy”) anterior contour (64%), anterior compression of the overlying choriocapillaris (93%), and posterior shadowing (86%)34 (Figure 3). Other features included overlying RPE abnormalities (78%), and structural loss of the interdigitation of the cone outer segment tips (64%), the ellipsoid portion of photoreceptors (57%), external limiting membrane (29%), outer nuclear layer (7%), and outer plexiform layer (7%). The inner retinal layers (inner nuclear layer to nerve fiber layer) were normal. Subretinal fluid (79%), subretinal lipofuscin (7%), and intraretinal edema (14%) were identified. Demerci et al35 observed EDI-OCT features of choroidal metastasis to include choriocapillaris thinning (100%), shaggy photoreceptors (75%), and subretinal fluid with speckles (67%).

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In summary, choroidal metastasis characteristically shows a “lumpy bumpy” topography that can be clinically and ultrasonographically too subtle to be realized. Relatively fresh overlying subretinal fluid might appear with shaggy photoreceptors.

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Choroid Hemangioma

Circumscribed choroidal hemangioma is a benign vascular tumor, classically orange and typically located in the paramacular region of the eye.6,36 This tumor can lead to visual acuity loss from hyperopic shift with subsequent amblyopia, or by producing macular abnormalities such as subretinal fluid, cystoid retinal edema, retinoschisis, RPE alterations, or simple tilting of the foveola. The diagnosis of choroidal hemangioma is established with fundus examination and was confirmed by diagnostic testing with ultrasonography demonstrating acoustic density; fluorescein angiography showed early and persistent hyperfluorescence; and indocyanine green angiography revealed early hyperfluorescence with late “washout” hyperfluorescence and perilesional hyperfluorescent ring.6 These features help differentiate this tumor from simulating lesions including choroidal nevus, melanoma, metastasis, and lymphoma.

Optical coherence tomography has been found to be useful in differentiating choroidal hemangioma from central serous chorioretinopathy and to follow therapeutic response after treatment.37–40 Rojanaporn et al41 studied 10 eyes with newly diagnosed circumscribed choroidal hemangioma, imaged with EDI-OCT and noted a mean tumor diameter of 5.4 mm and a mean tumor thickness of 1,187 μm by EDI-OCT compared with 2,400 μm by ultrasonography. By EDI-OCT, the tumor characteristically showed smooth, gently sloping anterior contour (100%) and gradual choroidal expansion without choriocapillaris compression (100%) (Table 1) (Figure 4). There was visibility of expanded vascular interfaces within the choroidal vascular layers including choriocapillaris, Haller's layer, and Sattler's layer; however, optical shadowing often lead to reduction of deeper choroidal detail. The height of medium (mean, 197 μm) and large (mean, 507 μm) choroidal vessels within the tumor compared with normal medium (mean, 54 μm) and large (mean, 75 μm) vessels was comparatively increased by a mean of 265% (medium vessels) and 576% (large vessels).41

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Other features included partial optical shadowing deep to the hemangioma (90%), intact Bruch's membrane (100%), and outer retinal abnormalities including subretinal fluid (70%), lipofuscin deposition (10%), irregularity and thinning of retinal pigment epithelium (40%), absence or irregularity of the ellipsoid layer (40%), absent external limiting membrane (20%), and disruption of the outer nuclear layer (30%) and outer plexiform layer (30%). The inner retinal abnormalities included irregularity of the inner nuclear layer (30%) and structural loss or edema of the inner plexiform layer (30%). The ganglion cell layer and nerve fiber layer were normal (100%).

In summary, EDI-OCT of circumscribed choroidal hemangioma depicted a smooth, gently sloping choroidal mass with expansion of small, medium, and large size choroidal vessels without compression of choriocapillaris.

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Choroid Lymphoma

Choroidal lymphoma is the infiltration of the posterior uveal tissue with malignant, but often low-grade, B-cell lymphoma.6,42,43 In an analysis of 73 eyes with choroidal lymphoma in 59 patients, this condition manifested as a solitary primary infiltration of the uvea (69%) or as a secondary infiltration in patients with systemic lymphoma (31%).43 The diagnosis is typically established with ophthalmoscopy, as well as with ultrasonography, fluorescein angiography, indocyanine green angiography, magnetic resonance imaging, and, importantly, EDI-OCT.43–45 Choroidal lymphoma can be clinically subtle with thin tumor infiltration that might not be detectable by fundus examination or ultrasonography. In these cases, EDI-OCT is particularly valuable.

Enhanced depth imaging optical coherence tomography of choroidal lymphoma reveals choroidal thickening with inward compression of choroidal vascular tissue.46–48 Shields et al48 described the surface topography of choroidal lymphoma in 14 eyes, comparing the features to the oceanic surface as placid, rippled, or stormy (seasick) (Figure 5). With thin lymphoma infiltration (mean, 1.7 mm), the choroidal surface appeared placid, medium infiltration (mean, 2.8 mm) appeared rippled, and thick infiltration (mean, 4.1 mm) as seasick.48 Markedly thickened infiltrates were not measurable on EDI-OCT. In 8 eyes, in which the tumor thickness was measurable on EDI-OCT, the mean maximal choroidal tumor thickness was 117% greater, at 602 μm compared with the corresponding unaffected contralateral choroid at 278 μm (P = 0.009).48 In summary, EDI-OCT depicts choroidal lymphoma as the ocean surface with placid flat infiltration of the choroid if thin, rippled if thicker, and undulating “seasick” appearance if thick.

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Choroid Osteoma

Choroidal osteoma is a unique tumor that comprises mature bone in the circumpapillary or macular region.49–51 Choroidal osteoma usually presents in young women as a yellow-orange calcified plaque with sharp margins and benign cytology. Choroidal osteoma can lead to poor visual acuity, most often related to choroidal neovascularization, subretinal fluid, or photoreceptor atrophy.50,51 In a retrospective review of 74 cases of choroidal osteoma followed for 10 years, tumor growth was found in 51% of cases, poor visual acuity in 56%, and visual acuity loss (>3 lines) in 45% of eyes.51

In 2007, Shields et al52 evaluated 22 cases of choroidal osteoma with time-domain OCT and observed photoreceptor layer atrophy in all cases with tumor decalcification compared with intact photoreceptors in those with calcified osteoma. Freton and Finger53 evaluated choroidal osteoma using EDI-OCT and commonly noted choroidal compression and retinal degenerative changes. They illustrated one case with tubular horizontal channels similar to those found on histopathology. Pellegrini et al54 described seven eyes with choroidal osteoma and noted that the inner retina was generally intact but the outer retina showed anatomic abnormalities in external limiting membrane, myoid zone, ellipsoid junction, and photoreceptors. Importantly, they recognized intralesional features of tumor layers and sponge-like appearance.

Shields et al55 evaluated 15 consecutive eyes with choroidal osteoma using EDI-OCT. In this analysis, features included hyperreflective horizontal lamellar lines in every case (100%) (Table 1) (Figure 4). These lines can be subtle, but they are not seen with other choroidal tumors and suggest bone lamella or horizontal vessels. The mean number of lamellar sections per scan was 1.2. There were horizontal tubules (presumed vessels) in nine cases and vertical tubules (presumed Haversion canals) in two cases. Of five cases with partial or complete decalcification, overlying photoreceptor thinning or loss was noted in every case.55

In summary, EDI-OCT of choroidal osteoma reveals subtle horizontal hyperreflective lamellar lines in all cases with occasional tumor sponge-like appearance, and horizontal or vertical tubular channels. With tumor decalcification, overlying photoreceptor loss is apparent.

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Choroid Melanocytosis

Ocular melanocytosis is a congenital disorder characterized by increased pigmentation of the uveal tract and episclera and with slight risk for uveal melanoma.6 Patients with choroidal melanoma arising from choroidal melanocytosis have double the risk for metastasis compared with melanoma arising without melanocytosis.56 Therefore, regular ophthalmic assessment in affected patients is advised. Efforts to detect even the smallest uveal melanoma by recognizing minute alterations in retinal and choroidal structure are important; however, the dark fundus pigmentation of melanocytosis can mask subtle melanoma.

Pellegrini et al57 studied unilateral subfoveal choroidal melanocytosis in 15 consecutive cases using EDI-OCT and compared the findings with the opposite normal eye. They noted smooth anterior contour (100%) and thinned or compressed choriocapillaris (100%) (Figure 6). The inner (100%) and outer (93%) retina was normal. The subfoveal choroid was mean 23% thicker in the eye with melanocytosis, measuring mean thickness of 326 μm compared with 264 μm in the uninvolved eye (P = 0.15). A subtle but important finding was increased choroidal perivascular interstitial tissue (presumed melanocytosis) that was 51% thicker in the study eye compared with the opposite normal eye (P = 0.01). This perivascular tissue enwrapped and silhouetted the medium and large vessels. The ratio between the perivascular stromal tissue and subfoveal choroidal thickness was 66% in the involved eye and 54% in the normal eye (P = 0.0001).57 Deep partial (n = 5) or complete (n = 2) tissue shadowing was noted.

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In summary, EDI-OCT of choroidal melanocytosis shows slight increased choroidal thickness with apparent increase in the choroidal perivascular stromal tissue and minimal effect on the overlying retina.

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Choroid Hemorrhage

Choroidal hemorrhage can closely simulate melanoma in color and configuration and can be a source of diagnostic confusion. In an analysis of 1,739 posterior uveal pseudomelanomas, choroidal hemorrhage represented 2%.58 In an analysis of 2 patients with choroidal hemorrhage simulating melanoma, Fung et al59 found on EDI-OCT a hyporeflective area of blood in the outer choroid measuring 439 μm to 1,265 μm in thickness, with a smooth, slightly scalloped anterior surface with inner displacement of choroidal stroma with folds. We have witnessed this finding in subsequent cases (Table 1) (Figure 6).

In summary, EDI-OCT of choroidal hemorrhage reveals a hyporeflective lesion in the outer choroid or supra choroidal space with smooth, slightly scalloped, anterior surface and overlying choroidal folds upon resolution.

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Choroid Granuloma

Choroidal granuloma is an acute or chronic inflammatory condition that is most often related to sarcoidosis, tuberculosis, cryptococcosis, or other infectious agents. Granuloma can be unifocal or multifocal, of various dimensions, and often resolves with corticosteroid or antibacterial/antifungal medications. On EDI-OCT, active granuloma appears as a smooth, dome-shaped elevation with compression or obliteration of choroidal details, mild deeper shadowing, and often with overlying subretinal fluid and shaggy photoreceptors (Figure 7). Inactive granuloma can display choroidal thinning with optical shadowing if overlying RPE hyperplasia and optical transmission if overlying RPE atrophy.

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Choroid Hypopigmentation of Waardenburg Syndrome

Waardenburg syndrome is a congenital anomaly characterized by abnormalities of the eyelids, eyebrows, nasal root, uvea, and scalp hair associated with congenital deafness. A recent study has identified that both the iris and choroid show pigmentary abnormalities.60 In an analysis of 7 patients, iris hypopigmentation was noted in 71% and choroidal hypopigmentation in 71%. On EDI-OCT, there was thinner choroid in affected eyes (mean, 197 μm) compared with the opposite normal choroid (243 μm). The overlying retina was normal.

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Sclera

Choroid Granuloma (Solitary Idiopathic Choroiditis, Helioid Choroiditis)

Solitary idiopathic choroiditis is a presumed inflammatory lesion of the choroid or sclera that appears as a unifocal yellow-white mass, often near the optic disk and measuring approximately 1 mm to 2 mm in diameter. In a clinical analysis of 60 cases, Shields et al61 characterized this condition as occurring mostly in whites (93%), post-equatorial location (93%), and yellow (97%).

Fung et al62 described the EDI-OCT features of classic solitary idiopathic choroiditis in 10 consecutive eyes and noted dome-shaped elevation with smooth surface in all cases (100%) (Table 1) (Figure 8). Importantly, the mass appeared to arise from the sclera in every case and with remarkable choroidal compression down to a mean choroidal thickness of 32 μm. In two cases, the abrupt elevation appeared with “volcanic” configuration. Outer retinal abnormalities were noted.

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In summary, EDI-OCT of solitary idiopathic choroiditis reveals focal scleral thickening with dramatic overlying choroidal compression.

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Sclerochoroidal Calcification

Sclerochoroidal calcification is a condition found in elderly patients with calcium pyrophosphate deposition in the sclera and/or choroid, appearing as a yellow choroidal calcified mass.6,63 These geographic lesions are often bilateral and classically located along the superotemporal or inferotemporal vascular arcades. Sclerochoroidal calcification is an age-related process, with dystrophic calcification at the site of oblique muscle insertions onto the sclera but can occur secondary to systemic disease such as hyperparathyroidism, pseudohypoparathyroidism, hypervitaminosis D, calcium pyrophosphate dehydrate deposition disease, Bartter syndrome, Gitelman syndrome, or chronic renal disease.63

Enhanced depth imaging optical coherence tomography findings of sclerochoroidal calcification are typical.64–66 Fung et al66 studied 13 eyes at a mean age of 74 years and found that the mass was within the sclera in all cases, causing thinning or complete absence of overlying choroid (mean choroidal thickness 28 μm) (Table 1) (Figure 8). The lesion showed anterior tumor surface topography elevated with undulating rocky (38%) or rolling (62%) anterior scleral surface. The lesion showed moderate reflectivity (77%) and an optically bright anterior band (23%). The posterior margin could not be identified in any case.

In summary, EDI-OCT shows sclerochoroidal calcification arising within the sclera and displaying a rocky or rolling undulating anterior surface with extreme thinning of the overlying choroid.

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Retina

Retinoblastoma

Retinoblastoma is a serious intraocular malignancy of childhood that can lead to blindness and death of a child.6,67 In some cases of familial retinoblastoma, the tumor is detected early when small and not affecting central vision.

Time-domain, office-based, OCT can be performed in children at youngest age of 3 years to 4 years, illustrating the retinal mass.68 To image younger patients, portable hand-held spectral domain OCT units have been developed.69 Cao et al69 analyzed 3 infants with small retinoblastomas (mean thickness, 4.8 mm) using hand-held portable OCT in the operating room and noted smooth tumor surface (67%), full-thickness retinal involvement (100%), and low optical density (100%). The foveola was incorporated into the tumor in each case. There was abrupt transition of normal to diseased retina and subretinal fluid was noted in each case (Table 1) (Figure 9). After therapy, tumor surface was smooth (33%), optical density high (67%), and foveola intact (33%). The subretinal fluid resolved in every case.

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In summary, EDI-OCT of small retinoblastoma shows abrupt transition from normal retina to the tumor. Although the foveola appears involved before treatment, the foveola might be intact after treatment.

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Retina Astrocytic Hamartoma

Retinal astrocytic hamartoma appears as a yellow-white retinal mass with minimally dilated feeder vessels and occasional retinal traction. Time-domain OCT has characterized this tumor with retinal elevation and “moth-eaten” lucent areas.70 Serafino et al71 described the EDI-OCT features in 86 eyes of 47 patients with retinal astrocytic hamartoma and classified the tumors into Type I (42%), Type II (26%), Type III (20%), and Type IV (12%). They characterized Type I as flat, generally in the nerve fiber layer, Type II with slight elevation of the nerve fiber layer and retinal traction, Type III with “moth-eaten” lucent areas suggestive of calcification involving inner and outer retina, and Type IV with optically empty intralesional cavities (Table 1) (Figure 9). They found that Type II correlated with cutaneous forehead plaques (P < 0.001) and Type III correlated with brain astrocytoma (P < 0.001). Veronese et al72 further illustrated two cases with OCT-evidence of cavitary retinal astrocytic hamartoma.

In summary, retinal astrocytic hamartoma typically begins in the nerve fiber layer as a relatively flat mass and enlarges to nodular full-thickness mass with “moth-eaten” calcified lucent areas with optical showing or degenerative cavitary appearance.

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Retina Hemangioblastoma

Retinal hemangioblastoma is a benign retinal vascular tumor, often associate with von Hippel–Lindau disease.6,73 This tumor commonly manifests with subretinal fluid, exudation, and vitreoretinal traction. Of note, EDI-OCT shows full-thickness retinal mass with optical shadowing, normal retina draped over the often-exophytic mass, abrupt transition from normal to involved retina, subretinal fluid, intraretinal and subretinal exudation, and retinal edema, often depending on the duration of subretinal fluid (Table 1) (Figure 9). Also, EDI-OCT is useful for following resolution of subretinal fluid and retinal edema.40

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Retinal Pigment Epithelium

Congenital Hypertrophy of the Retinal Pigment Epithelium

Congenital hypertrophy of the retinal pigment epithelium (CHRPE) is a benign, pigmented lesion located at the level of the RPE.6,74 Time-domain OCT of CHRPE has revealed photoreceptor loss immediately overlying the lesion in all cases.75

Fung et al76 used EDI-OCT to analyze 18 eyes with CHRPE and found that all lesions were flat. The RPE was absent (11%), thickened (89%), or irregular (83%). Of 9 lesions in which lacunae were imaged, 8 showed absence of RPE with transmission of OCT through the CHRPE (Table 1) (Figure 10). The overlying retinal findings included marked photoreceptor loss (100%), immediately at the site of the CHRPE. In some cases, subretinal cleft (33%), representing thinned excavated posterior retina, was noted. Other findings included thinning of the retina beginning at the ganglion cell layer (n = 1), outer plexiform layer (n = 4), outer nuclear layer (n = 12), or inner segment/outer segment junction (n = 1). Additional retinal findings included hyperreflective spots (n = 11) and cystoid edema (n = 5). The choroid was normal in affected and normal regions.

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In summary, EDI-OCT of CHRPE classically showed flat irregular RPE with outer retinal thinning or absence and subretinal cleft with normal underlying choroid.

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Congenital Simple Hamartoma of the Retinal Pigment Epithelium

Congenital simple hamartoma of the RPE is a rare pigmented retinal hamartoma, located in the foveal region, and generally remaining stable with minimal effect on visual acuity.77 Time-domain OCT shows dome-shaped elevation of the retinal surface with abrupt, absolute shadowing of the deeper retina. Enhanced depth imaging optical coherence tomography has not yet been published regarding this unique tumor.78,79

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Combined Hamartoma of the Retina and Retinal Pigment Epithelium

Combined hamartoma of the retina and retinal pigment epithelium is a presumed congenital intraocular mass characterized by a mound of disorganized glial, vascular, and melanocytic tissue within the retina and RPE.80,81 Overlying vitreoretinal interface disturbance with retinal traction in a vertical and horizontal direction leads to retinal dragging and ultimate vision loss.82,83 Persistent traction can cause clinically visible retinal folds or tractional retinal detachment. In an analysis of 77 eyes with combined hamartoma, retinal traction was found in 81%, and poor visual acuity of 20/200 or worse in 47%.81

In an analysis of 8 patients with combined hamartoma of the retina and retinal pigment epithelium using EDI-OCT, Arepalli et al84 found obvious irregularities in the inner retina (100%) and/or all retinal layers (38%), with epiretinal membrane (100%), causing a sawtooth (mini-peak) pattern along the inner retina (25%), full-thickness retinal folds (maxi-peak) (38%), or both (38%) (Table 1) (Figure 10). The mean number of mini-peaks per tumor epicenter scan was 5 and were classified as acute (<45°) (n = 3), or hyperacute (45–90°) (n = 2). The mean number of maxi-peaks per tumor epicenter scan was 3 and all were hyperacute (n = 6). In the 5 eyes with macular tumors, the foveal retinal thickness in the affected eye was 150% greater, measuring mean 608 μm compared with 244 μm in the unaffected eye (P = 0.0004). The underlying choroidal thickness was decreased to mean 210 μm compared with 328 μm in the corresponding area of unaffected eye (P = 0.009).

In summary, EDI-OCT of combined hamartoma of the retina and retinal pigment epithelium shows retinal disorganization and epiretinal membrane causing inner retinal traction with characteristic sawtooth pattern (mini-peak) and/or full-thickness retinal folds (maxi-peak).

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Summary

Enhanced depth imaging optical coherence tomography is an important tool in the imaging of intraocular tumors. This technology allows localization of tumor into retinal, choroidal, or scleral layers, provides anatomic information that is useful for diagnosis as well as estimation of visual acuity, and allows submillimeter monitoring of tumors. Further developments with OCT could assist with enhanced detection of intraocular tumors, particularly those that could be vision-threatening or life-threatening, allowing for earlier detection and improved outcomes.

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Keywords:

eye; tumor; enhanced depth imaging optical coherence tomography; nevus; melanoma; metastasis; hemangioma; osteoma; lymphoma; retinoblastoma; astrocytic hamartoma; hemangioblastoma

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