Sandor Ferenczy

CORRELATION OF FOVEAL AVASCULAR ZONE SIZE WITH FOVEAL MORPHOLOGY IN NORMAL EYES USING OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

Purpose: To analyze the foveal avascular zone (FAZ) in normal eyes using optical coherence tomography angiography. Methods: Prospective noncomparative case series. The parafoveal region of 70 eyes from 67 healthy subjects was imaged using optical coherence tomography angiography to visualize the superficial and deep capillary plexuses and correlated with standard macular volume scans using spectral domain optical coherence tomography to determine foveal morphology. Results: In all 70 eyes imaged, 2 vascular plexuses could be detected within the retina: a superficial plexus within the ganglion cell layer and a deep plexus within the inner nuclear layer. A measurable FAZ was visualized in both plexuses in all imaged eyes. The FAZ area was variable in the study population with a mean of 0.266 mm2 ± 0.097 mm2 in the superficial plexus (range: 0.071 mm2–0.527 mm2) and a mean of 0.495 mm2 ± 0.227 mm2 in the deep plexus (range: 0.160 mm2–0.795 mm2). The FAZ area was significantly larger in the deep plexus (P < 0.0001) compared with superficial plexus. The FAZ area in both plexuses correlated inversely with central macular thickness and central macular volume (P < 0.0001). No significant correlation was found between superficial plexus FAZ area and age (P = 0.55) or sex (P = 0.34). In the same manner, no significant correlation was found between deep plexus FAZ area and age (P = 0.13) or sex (P = 0.13). Conclusion: Optical coherence tomography angiography provides a noninvasive method to visualize and measure the superficial and deep plexus FAZ in a normal population. The FAZ can vary in size and shape, with the FAZ area significantly larger in the deep compared with the superficial plexus. Both superficial and deep FAZ area correlate inversely with foveal thickness and volume.

Enhanced Depth Imaging Optical Coherence Tomography of Small Choroidal Melanoma: Comparison With Choroidal Nevus

OBJECTIVE To evaluate characteristics of small choroidal melanoma using enhanced depth imaging spectral-domain optical coherence tomography (EDI-OCT). DESIGN Retrospective comparative analysis. RESULTS Of 37 eyes with small choroidal melanoma imaged using EDI-OCT, the mean tumor thickness was 1025 μm by EDI-OCT compared with 2300 μm by ultrasonography. By EDI-OCT, choroidal features included optical shadowing in 36 (100%) and overlying choriocapillaris thinning in 37 (100%). Outer retinal features included shaggy photoreceptors in 18 (49%), as well as absence (structural loss) of photoreceptors in 9 (24%), inner segment-outer segment junction in 24 (65%), external limiting membrane in 16 (43%), outer nuclear layer in 6 (16%), and outer plexiform layer in 4 (11%). Inner retinal features included irregularity of inner nuclear layer in 3 (8%), inner plexiform layer in 3 (8%), ganglion cell layer in 3 (8%), and nerve fiber layer in 2 (5%). Also identified were subretinal fluid in 34 (92%), subretinal lipofuscin deposition in 35 (95%), and intraretinal edema in 6 (16%). Using EDI-OCT, a comparison with similar-sized choroidal nevus revealed that small choroidal melanoma showed increased tumor thickness, subretinal fluid, subretinal lipofuscin deposition, and retinal pigment epithelium atrophy. Statistically significant EDI-OCT features for small choroidal melanoma included intraretinal edema (P=.003), shaggy photoreceptors or loss of photoreceptors (P=.005), loss of external limiting membrane (P=.008), loss of inner segment-outer segment junction (P=.02), irregularity of inner plexiform layer (P=.04), and irregularity of ganglion cell layer (P=.04) (t test and χ2 test). Shaggy photoreceptors were found overlying small choroidal melanoma in 18 (49%) but were not observed overlying choroidal nevus (P<.001). CONCLUSIONS Small choroidal melanoma tumor thickness was overestimated by 55% on ultrasonography compared with EDI-OCT. The EDI-OCT features of small choroidal melanoma compared with choroidal nevus include increased tumor thickness, subretinal fluid, subretinal lipofuscin deposition, and retinal irregularities, including shaggy photoreceptors.

Enhanced Depth Imaging Optical Coherence Tomography of Choroidal Nevus in 104 Cases

PURPOSE To describe the characteristics of choroidal nevus using the enhanced depth imaging (EDI) feature of spectral-domain optical coherence tomography (OCT). DESIGN Retrospective, observational case series. PARTICIPANTS One hundred four eyes with choroidal nevus. METHODS Spectral-domain EDI OCT was performed with a Heidelberg Spectralis HRA+OCT (Heidelberg Engineering, Heidelberg, Germany) using a custom scan acquisition protocol of up to 13 raster lines of 9-mm scan length with automatic real-time image averaging set at 100 images. The thickness of choroidal nevus was measured by combining Heidelbergs autosegmentation with manual segmentation. MAIN OUTCOME MEASURES Imaging features and thickness correlation of choroidal nevus by EDI OCT versus standard ultrasonography. RESULTS Of 104 eyes with choroidal nevus imaged with EDI OCT, 51 (49%) displayed image detail suitable for study. The remaining 53 cases were suboptimal because of statistically identified factors of age older than 60 years (P = 0.027), female gender (P = 0.008), extramacular location of nevus (P<0.001), mean distance from foveola more than 3 mm (P = 0.002), mean distance from optic disc more than 4 mm (P<0.001), and mean maximal basal diameter more than 5 mm (P = 0.006). Of the 51 suitable cases, mean nevus thickness was 685 μm (median, 628 μm; range, 184-1643 μm) by EDI OCT compared with 1500 μm (median, 1500 μm; range, 1000-2700 μm) by ultrasonography. The most common EDI OCT imaging features included partial (59%) or complete (35%) choroidal shadowing deep to the nevus, choriocapillaris thinning overlying the nevus (94%), retinal pigment epithelial (RPE) atrophy (43%), RPE loss (14%), RPE nodularity (8%), photoreceptor loss (43%), inner segment-outer segment junction (IS-OS) irregularity (37%), IS-OS loss (6%), external limiting membrane irregularity (18%), outer nuclear and outer plexiform layer irregularity (8%), and inner nuclear layer irregularity (6%). Overlying subretinal fluid was identified by EDI OCT (16%), ophthalmoscopic examination (8%), and ultrasonographic evaluation (0%). A comparison of pigmented versus nonpigmented nevus showed only 1 significant difference of more intense choroidal shadowing with pigmented nevus (P = 0.046). CONCLUSIONS Imaging of choroidal nevus with EDI OCT enables precise measurement of tumor thickness with comparatively reduced thickness relative to ultrasonography. Using EDI OCT, 94% of choroidal nevi were found to have overlying choriocapillaris thinning.

Enhanced depth imaging optical coherence tomography of intraocular tumors: from placid to seasick to rock and rolling topography--the 2013 Francesco Orzalesi Lecture.

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.

Optical coherence tomography of retinal and choroidal tumors.

Optical coherence tomography (OCT) has revolutionized the field of ophthalmology since its introduction 20 years ago. Originally intended primarily for retina specialists to image the macula, it has found its role in other subspecialties that include glaucoma, cornea, and ocular oncology. In ocular oncology, OCT provides axial resolution to approximately 7 microns with cross-sectional images of the retina, delivering valuable information on the effects of intraocular tumors on the retinal architecture. Some effects include retinal edema, subretinal fluid, retinal atrophy, photoreceptor loss, outer retinal thinning, and retinal pigment epithelial detachment. With more advanced technology, OCT now provides imaging deeper into the choroid using a technique called enhanced depth imaging. This allows characterization of the thickness and reflective quality of small (<3 mm thick) choroidal lesions including choroidal nevus and melanoma. Future improvements in image resolution and depth will allow better understanding of the mechanisms of visual loss, tumor growth, and tumor management.

Hand-held spectral-domain optical coherence tomography of small macular retinoblastoma in infants before and after chemotherapy.

PURPOSE To demonstrate the utility of hand-held spectral-domain optical coherence tomography (SD-OCT) in assessing retinal structure in cases of macular retinoblastoma. METHODS In this retrospective, observational case series, three young children with macular retinoblastoma were treated at a tertiary care hospital. At examination under anesthesia, each patient was evaluated with SD-OCT for analysis of retinal tumor and macula. The main outcomes were retinal morphology before and after chemotherapy. RESULTS The mean patient age was 16 months (median: 9 months; range: 7 to 33 months). All patients had small exophytic macular retinoblastoma with subretinal fluid in the foveola. At presentation, the mean tumor thickness was 4.8 mm (range: 4.0 to 6.0 mm) and mean tumor base was 10.3 mm (range: 8.0 to 12.0 mm). SD-OCT documented tumor surface as smooth (n = 2) or irregular (n = 1), involvement of full-thickness retina (n = 3), and optical density as low (n = 3). The surrounding retina showed abrupt transition to tumor (n = 3), without intraretinal edema (n = 3), and with underlying subretinal fluid (n = 3). Following chemotherapy, all tumors showed regression with mean thickness of 2.6 mm (range: 2.2 to 3.0 mm). SD-OCT documented tumor surface as smooth (n = 1) or irregular (n = 2), and optical density as medium (n = 1) or high (n = 2). At the tumor site, the retina showed full-thickness disorganization but with abrupt transition to normal retina (n = 3). The foveola was anatomically intact (n = 1) or with outer retinal thinning (n = 2). Subretinal fluid was resolved in each case (n = 3). CONCLUSIONS SD-OCT can provide precise anatomic monitoring of the macular region in infants and young children with small macular retinoblastoma. This may serve as a guide for visual potential in the preverbal child.

IMAGE QUALITY AND ARTIFACTS ON OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY: Comparison of Pathologic and Paired Fellow Eyes in 65 Patients With Unilateral Choroidal Melanoma Treated With Plaque Radiotherapy.

Purpose: To study image quality and artifacts seen on optical coherence tomography angiography (OCTA). Methods: Sixty-five consecutive patients with unilateral posterior uveal melanoma treated with plaque radiotherapy had OCTA during follow-up. Optical coherence tomography angiography was performed on both the affected and fellow eye. Signal strength and frequency of image artifacts on en face images were compared between affected and fellow eyes. Results: A total of 130 eyes in 65 patients were analyzed, the mean age at time of OCTA was 55 years (median: 56, range: 12–81 years), and 39 (39/65, 60%) were female. Majority of tumors were located in the choroid (62/65, 95%) and extramacular (55/65, 85%). The mean distance to the foveola was 4 mm (median: 3, range: 0–18 mm) and optic nerve was 4 mm (median: 4, range: 0–16 mm). Optical coherence tomography angiography was performed at a mean 46 months after plaque radiotherapy. Most patients had a history of radiation maculopathy or papillopathy in the treated eye at the time of OCTA (46/65, 71%). Overall, 95 eyes (95/130, 73%) had at least one significant artifact on OCTA. The most common major artifacts were loss of focus (71/130, 55%), broad (>5 pixels width and >4 lines) blink lines (48/130, 37%), motion artifact (34/130, 26%), specular dot (33/130, 25%), and edge duplication (10/130, 8%). Statistically, eyes treated with plaque radiotherapy (affected vs. fellow eye) were more likely to have at least one major OCTA artifact (92 vs. 54%, P < 0.001) and, specifically, loss of focus was more frequent (78 vs. 31%, P < 0.001). Multivariate analysis found decreased visual acuity significantly associated with higher incidence of broad blink lines (P = 0.0166) and loss of signal (P < 0.0001), whereas male sex was associated with increased loss of signal (P = 0.0015), and distance to the foveola was related to edge duplication (P = 0.0119). Conclusion: Image artifacts on OCTA are commonly encountered and appear to be more frequent in eyes with pathology and poor visual acuity. Recognition of these artifacts might help improve image interpretation and decision making.

Combined hamartoma of the retina and retinal pigment epithelium: findings on enhanced depth imaging optical coherence tomography in eight eyes.

Purpose: To assess combined hamartoma of the retina and retinal pigment epithelium with enhanced depth imaging optical coherence tomography. Methods: Retrospective, observational cases series in eight eyes of eight patients, with comparison between affected and unaffected eyes regarding enhanced depth imaging optical coherence tomography features of tumor, fovea, and choroid. Results: The mean age at presentation was 7 years. The tumor was macular (n = 5) or extramacular (n = 3). Enhanced depth imaging optical coherence tomography revealed irregularities in inner retina (n = 8) and/or all retinal layers (n = 3), with epiretinal membrane (n = 8), causing an inner retinal sawtooth (mini-peak) pattern (n = 2), full thickness retinal folds (maxi-peak) (n = 3), or both (n = 3). In the 5 macular tumors, foveal retinal thickness measured mean 608 &mgr;m compared with 244 &mgr;m in the unaffected eye (P = 0.0004). Mean tumor epicenter retinal thickness in 8 tumors measured 650 &mgr;m compared with 327 &mgr;m in a corresponding area in the unaffected eye (P = 0.01). In all cases, choroidal thickness beneath the tumor epicenter was decreased at mean 210 &mgr;m compared with 328 &mgr;m in the corresponding area of unaffected eye (P = 0.009). Conclusion: Enhanced depth imaging optical coherence tomography of combined hamartoma revealed epiretinal membrane with vitreoretinal traction in a sawtooth (mini-peak) or folded (maxi-peak) pattern. Combined hamartoma seems to be a thickened retinal mass secondary to focal vitreoretinal traction.

VARIABILITY IN FOVEAL AVASCULAR ZONE AND CAPILLARY DENSITY USING OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY MACHINES IN HEALTHY EYES.

Purpose: To evaluate the variability in foveal avascular zone (FAZ) and capillary density measurements on optical coherence tomography angiography using Optovue RTVue XR Avanti (OA) (Optovue) and Zeiss Cirrus HD-OCT 5000 (ZC) (Carl Zeiss Meditec). Methods: In this prospective, comparative case series, parafoveal (3 × 3 mm) optical coherence tomography angiography scans were obtained on healthy volunteers using both the Avanti and Cirrus. The FAZ area and capillary density at the level of both the superficial and deep capillary plexus were measured automatically using the built-in ReVue software (Optovue) with the Avanti as well as manually using ImageJ (National Institutes of Health) with both machines. Results: There were 50 eyes in 25 healthy volunteers included in the analysis. Mean subject age was 33 years and there were 14 women (56%). On optical coherence tomography, mean central macular thickness was significantly greater on OA (259.1 &mgr;m) than ZC (257.6 &mgr;m, P = 0.0228). On optical coherence tomography angiography, mean superficial and deep plexus FAZ measured 0.2855 mm2 and 0.3465 mm2 on Avanti automated (A-A), 0.2739 mm2 and 0.3637 mm2 on Avanti manual (A-M), and 0.2657 mm2 and 0.3993 mm2 on Cirrus manual (C-M), respectively. There were no statistically significant differences in superficial plexus FAZ measurements between the A-A and A-M (P = 0.4019) or A-A and C-M (P = 0.1336). The A-M measured significantly larger than C-M (P = 0.0396). Deep plexus FAZ measurements were similar on A-A and A-M (P = 0.6299), but both were significantly less compared with C-M (P < 0.0001 for A-A vs. C-M, P = 0.0184 for A-M vs. C-M). Mean superficial and deep plexus capillary densities were 53.6% and 59.3% on A-A, 48.1% and 47.7% on A-M, and 52.5% and 48.1% on C-M, respectively. Superficial plexus capillary density measurements were statistically similar on A-A and C-M (P = 0.0623), but both were significantly higher than A-M (P < 0.0001 for A-A vs. A-M, P < 0.0001 for A-M vs. C-M). However, deep plexus capillary density measurements on A-A were significantly higher than A-M (P < 0.0001) and C-M (P < 0.0001), but A-M and C-M measurements were similar (P = 0.5986). There was no significant difference in all parameters measured in both eyes of one subject using any of the three measuring techniques. Conclusion: While measurements taken with the same machine and technique are consistent and reliable between fellow eyes, significant variability exists in FAZ and capillary density measurements among different machines and techniques. Comparison of measurements across machines and techniques should be considered with caution.

PARAFOVEAL CAPILLARY DENSITY AFTER PLAQUE RADIOTHERAPY FOR CHOROIDAL MELANOMA: Analysis of Eyes Without Radiation Maculopathy.

Purpose: To study the parafoveal capillary density using optical coherence tomography angiography (OCTA) in eyes treated with plaque radiotherapy. Research Design: Retrospective comparative case series. Participants: Ten patients treated with plaque radiotherapy for choroidal melanoma without evident radiation maculopathy on ophthalmoscopy or optical coherence tomography were imaged with OCTA. Main Outcome Measure: Comparison of the parafoveal capillary density in the superficial and deep capillary plexuses in the irradiated versus fellow nonirradiated eye. Results: Overall, mean patient age was 55 years (median: 57, range: 45–65 years), and majority were white (9/10, 90%) and female (9/10, 90%). No patient had diabetes mellitus, and 2 (2/10, 20%) had controlled systemic hypertension. The melanoma was located in the choroid in all patients (10/10, 100%), with 2 (2/10, 20%) in the macular region. The mean largest basal diameter was 11 mm (12, 6–16 mm), and mean thickness was 5 mm (5, 2–10 mm). Mean radiation dose to the tumor apex was 72 Gy (median: 70 Gy, range: 70–85 Gy). Mean foveolar radiation dose was 53 Gy (median: 35 Gy, range: 14–110 Gy). Mean follow-up duration after plaque radiotherapy was 17 months (median: 16 months, range: 5–39 months). There was no ophthalmoscopic evidence of radiation maculopathy throughout the follow-up in every case. Optical coherence tomography demonstrated normal foveal contour without edema or subretinal fluid in every case. On OCTA, there was no significant difference in signal strength (P = 0.1151), central macular thickness (P = 0.9316), and foveal avascular zone area in the superficial (P = 0.1595), and deep (P = 0.1534) capillary plexuses between the irradiated versus fellow eyes. However, there was a statistically significant decrease in capillary density in the parafoveal superficial (P = 0.0005) and deep (P = 0.0067) plexuses in the irradiated eye. In addition, mean logMAR visual acuity was 0.2 (0.1, 0.0–0.5) (Snellen equivalent 20/32) in the irradiated eye and 0.0 (0.0, range: 0.0–0.1) (Snellen equivalent 20/20) in the fellow eye (P = 0.0252). Conclusion: Optical coherence tomography angiography allows qualitative and quantitative analysis of parafoveal capillary density. After plaque radiotherapy for choroidal melanoma, in eyes with normal macular features on ophthalmoscopy and optical coherence tomography, there is a statistically significant decrease in parafoveal capillary density and logMAR visual acuity in irradiated eyes compared with fellow eyes. These subclinical ischemic findings represent the commencement of radiation maculopathy.