Emil Anthony T. Say

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.

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.

INTRAVITREOUS CHEMOTHERAPY FOR ACTIVE VITREOUS SEEDING FROM RETINOBLASTOMA: Outcomes After 192 Consecutive Injections. The 2015 Howard Naquin Lecture.

Purpose: To investigate on the safety and efficacy of intravitreous chemotherapy for retinoblastoma seeding in a relatively large cohort and provide information on the necessary number of injections and long-term control. Methods: Retrospective interventional case series of 40 consecutive eyes with viable vitreous seeding after standard treatment of retinoblastoma. All eyes received intravitreal melphalan injection (20–30 &mgr;g) and additional topotecan (20 &mgr;g) as needed using the trans pars plana route with triple freeze–thaw cryotherapy at needle withdrawal for prevention of extraocular seeding for planned six cycles. Results: The mean patient age at presentation was 36 months, and interval to need for vitreous injection was 14 months. Viable vitreous (n = 40 eyes) and additional subretinal (n = 2 eyes) seeds were documented. There was a total of 192 injections using melphalan (n = 148) and/or topotecan (n = 44) with mean number of injections per eye of melphalan at 4 (median, 4; range, 1–6) and topotecan at 3 (median, 3; range, 1–5). Fewer than six planned melphalan injections (n = 31 cases, 78%) were necessary because of rapid and complete vitreous seed control (n = 30 eyes) or melphalan allergy (n = 1 eye). Fewer than six planned topotecan injections (n = 14 cases, 100%) were necessary because of rapid and complete vitreous seed control in all cases. At median 3-year follow-up, therapeutic success with continued seed regression was observed in all 40 eyes (100%). Globe salvage was attained in 35 cases (88%), and enucleation (n = 5) was necessary for extensive recurrent subretinal seeds (n = 2), neovascular glaucoma with vitreous hemorrhage (n = 2), and hemorrhagic retinal necrosis (n = 1). Side effects included focal retinal pigment epithelial mottling at the site of injection (n = 12), minor focal paraxial lens opacity (not requiring cataract surgery) (n = 11), transient focal vitreous hemorrhage (n = 5), transient hypotony (n = 3), transient retinal hemorrhage (n = 2), optic disc edema (n = 1), and hemorrhagic retinal necrosis (n = 1). There was no case of endophthalmitis, extraocular tumor extension, metastasis, or death. Conclusion: Intravitreal melphalan and/or topotecan injection for retinoblastoma vitreous seeding provides lasting tumor control at 3 years with approximately 4 injections.

Phacomatosis Pigmentovascularis of Cesioflammea Type in 7 Patients: Combination of Ocular Pigmentation (Melanocytosis or Melanosis) and Nevus Flammeus With Risk for Melanoma

OBJECTIVE To describe the features of phacomatosis pigmentovascularis (cesioflammea type). DESIGN Noninterventional retrospective case series composed of 7 patients. RESULTS Nevus flammeus combined with ipsilateral ocular melanocytosis or melanosis was seen in all 7 patients. Additional contralateral nevus flammeus was observed in 3 patients. Nevus flammeus (unilateral in 4 patients and bilateral in 3 patients) was distributed in trigeminal nerves V1 (n = 3), V2 (n = 7), and V3 (n = 5). Related findings included diffuse choroidal hemangioma (n = 1) and glaucoma (n = 1), with no patients having brain hemangioma or seizures. Ocular pigmentary abnormalities (unilateral in all 7 patients) included congenital ocular melanocytosis (n = 6) and conjunctival acquired melanosis (n = 1). Pigmentation was sectorial (partial) in 5 patients and complete in 2 patients. Melanocytosis involved the periocular skin in 1 patient, sclera in 2 patients, iris in 2 patients, and choroid in 4 patients. In 3 of 6 patients, melanocytosis was visible in the choroid only on dilated fundus evaluation. Related tumors included choroidal melanoma (n = 3), optic disc melanocytoma (n = 1), and conjunctival melanoma in situ (primary acquired melanosis) (n = 1). Melanoma metastasis developed in 1 patient. CONCLUSIONS Phacomatosis pigmentovascularis shows features of nevus flammeus and more serious ocular pigmentary abnormalities (uveoscleral melanocytosis and conjunctival melanosis). Melanocytosis may be detected only by dilated ocular fundus examination, as found in 3 of 6 patients. Furthermore, choroidal melanoma can develop from melanocytosis, as noted in 3 of our 6 patients (50%). All patients with nevus flammeus should be examined for phacomatosis pigmentovascularis by an ophthalmologist because ocular melanocytosis and uveal melanoma may remain hidden within the eye.

OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY OF THE MACULA AFTER PLAQUE RADIOTHERAPY OF CHOROIDAL MELANOMA: Comparison of Irradiated Versus Nonirradiated Eyes in 65 Patients.

Purpose: To study radiation retinopathy after plaque radiotherapy of choroidal melanoma using optical coherence tomography angiography. Methods: Retrospective comparative analysis of 65 consecutive patients with choroidal melanoma, treated with standard dose I-125 plaque radiotherapy and imaged with optical coherence tomography angiography. A comparison of irradiated versus contralateral, nonirradiated (control) eyes was performed. Results: The mean patient age was 55 years. Underlying medical diseases included diabetes mellitus (4/65, 4%) or hypertension (25/65, 38%), but no patient demonstrated disease-related retinopathy. The mean pretreatment melanoma diameter was 11 mm and mean thickness was 5 mm. The mean radiation dose to the foveola was 5663 centiGray. At mean follow-up of 46 months after plaque radiotherapy, the most frequent qualitative finding on optical coherence tomography angiography (irradiated eye) was nonperfusion in the superficial capillary plexus (19/65, 29%) and deep capillary plexus (20/65, 31%), followed by loss of choriocapillaris within tumor margins (11/65, 17%). The quantitative findings revealed foveal avascular zone with significantly larger mean area (irradiated vs. nonirradiated eye) in the superficial plexus (0.961 vs. 0.280 mm2, P < 0.0001) and deep plexus (1.396 vs. 0.458 mm2, P < 0.0001), even in eyes without clinical evidence of radiation maculopathy (superficial 0.278 mm2, P = 0.03; deep 0.454 mm2, P = 0.02). Parafoveal capillary density (superficial and deep) was decreased in all irradiated eyes (P < 0.001). This difference was maintained after subgroup analysis of eyes with (P < 0.001) or without (P < 0.001) clinical evidence of radiation maculopathy. Mean logMAR visual acuity was significantly reduced in irradiated eyes (0.7 vs. 0.1 [Snellen equivalent 20/100 vs. 20/25], P < 0.001) and the reduced vision was significant even in eyes without clinical evidence of radiation maculopathy (0.4 vs. 0.1 [Snellen equivalent 20/50 vs. 20/25], P < 0.001). Conclusion: Optical coherence tomography angiography demonstrated significant enlargement of the foveal avascular zone and decreased parafoveal capillary density of both superficial and deep capillary plexuses in eyes after plaque radiotherapy of choroidal melanoma, even in eyes with no clinical evidence of radiation maculopathy.

Oncocytic lesions (oncocytoma) of the ocular adnexa: report of 15 cases and review of literature.

Purpose: To describe the clinical, imaging, and pathology features of oncocytic lesions in the ocular adnexa. Methods: Retrospective, noncomparative, interventional case series. Results: Fifteen oncocytic neoplasms (n = 15 patients) were classified as oncocytoma in 14 (93%) and oncocytic hyperplasia in 1 (7%). The mean patient age was 66 years (median = 66, range = 44–82), and 9 (60%) were male. The tumor involved the caruncle (n = 13, 86%), bulbar conjunctiva (n = 1, 7%), and plica semilunaris (n = 1, 7%). All cases were unifocal and most often presented as a painless mass (n = 12, 80%), evolving over a median 6 months (mean = 12, range = 1–48 months). The mean tumor base was 4.1 mm (median = 4.0, range = 1–10), and the tumor was well-circumscribed (n = 14), dark blue (n = 7), and cystic (n = 10). Ultrasound biomicroscopy and anterior segment optical coherence tomography disclosed mixed solid and cystic components. Complete surgical excision was curative without recurrence after a mean follow up of 39 months. Histopathology disclosed columnar cells with copious quantities of intensely eosinophilic cytoplasm in the lining epithelium (oncocytic hyperplasia) and in some cases with cystadenomatous proliferation (oncocytoma). Conclusion: Oncocytic lesions of the ocular adnexae are typically well-circumscribed, cystic lesions that most often involve the caruncle. Surgical excision can be curative. Epithelial cells with copious quantities of intensely eosinophilic cytoplasm characterize oncocytic transformation histopathologically.

Unilateral Retinoblastoma Managed With Intravenous Chemotherapy Versus Intra-Arterial Chemotherapy. Outcomes Based on the International Classification of Retinoblastoma.

PurposeThe objective of this study was to compare outcomes after intravenous chemotherapy (IVC) versus intra-arterial chemotherapy (IAC) for unilateral retinoblastoma. DesignA retrospective comparative interventional case series. MethodsPatients with unilateral retinoblastoma managed with either IVC using vincristine, etoposide, and carboplatin or IAC using melphalan with or without topotecan with a minimum of 1-year follow-up were compared. The primary outcome measure was globe salvage. ResultsOf 91 patients with unilateral retinoblastoma, IVC was employed in 42 (46%) cases and IAC in 49 (54%). By comparison (IVC vs IAC), patients in the IAC group had greater mean tumor diameter (14 vs 18 mm, P < 0.001) and thickness (7 vs 10 mm, P = 0.001), greater percentage with active vitreous seeds (29% vs 55%, P = 0.01), and greater total retinal detachment (10% vs 43%, P < 0.001). There were no cases of group A in either treatment arm. Globe salvage was not significantly different in groups B, C, or E, but there was significantly improved globe salvage with IAC for group D (48% vs 91%, P = 0.004). Control was significantly better with IAC for solid tumor (62% vs 92%, P = 0.002), subretinal seeds (31% vs 86%, P = 0.006), and vitreous seeds (25% vs 74%, P = 0.006). There were no patients with pinealoblastoma, second cancer, metastasis, or death in either group. ConclusionsFor unilateral retinoblastoma, IAC provided significantly superior globe salvage compared with IVC for group D eyes. In addition, IAC provided significantly superior control for solid tumor, subretinal seeds, and vitreous seeds.

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.

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.

Juvenile Xanthogranuloma Involving the Eye and Ocular Adnexa: Tumor Control, Visual Outcomes, and Globe Salvage in 30 Patients

PURPOSE To report clinical features and treatment outcomes of ocular juvenile xanthogranuloma (JXG). DESIGN Retrospective case series. PARTICIPANTS There were 32 tumors in 31 eyes of 30 patients with ocular JXG. METHODS Review of medical records. MAIN OUTCOME MEASURES Tumor control, intraocular pressure (IOP), and visual acuity. RESULTS The mean patient age at presentation was 51 months (median, 15 months; range, 1-443 months). Eye redness (12/30, 40%) and hyphema (4/30, 13%) were the most common presenting symptoms. Cutaneous JXG was concurrently present in 3 patients (3/30, 10%), and spinal JXG was present in 1 patient (1/30, 3%). The ocular tissue affected by JXG included the iris (21/31, 68%), conjunctiva (6/31, 19%), eyelid (2/31, 6%), choroid (2/31, 6%), and orbit (1/31, 3%). Those with iris JXG presented at a median age of 13 months compared with 30 months for those with conjunctival JXG. In the iris JXG group, mean IOP was 19 mmHg (median, 18 mmHg; range, 11-30 mmHg) and hyphema was noted in 8 eyes (8/21, 38%). The iris tumor was nodular (16/21, 76%) or diffuse (5/21, 24%). Fine-needle aspiration biopsy was used in 10 cases and confirmed JXG cytologically in all cases. The iris lesion was treated with topical (18/21, 86%) and/or periocular (4/21, 19%) corticosteroids. The eyelid, conjunctiva, and orbital JXG were treated with excisional biopsy in 5 patients (5/9, 56%), topical corticosteroids in 2 patients (2/9, 22%), and observation in 2 patients (2/9, 22%). Of 28 patients with a mean follow-up of 15 months (median, 6 months; range, 1-68 months), tumor regression was achieved in all cases, without recurrence. Two patients were lost to follow-up. Upon follow-up of the iris JXG group, visual acuity was stable or improved (18/19 patients, 95%) and IOP was controlled long-term without medication (14/21 patients, 74%). No eyes were managed with enucleation. CONCLUSIONS Ocular JXG preferentially affects the iris and is often isolated without cutaneous involvement. Iris JXG responds to topical or periocular corticosteroids, often with stabilization or improvement of vision and IOP.