High-Dose Intravitreal Topotecan for Recurrent Retinoblastoma, Subretinal Seeds, and Vitreous Seeds in 13 Consecutive Cases.

PURPOSE: To evaluate the efficacy and safety of high-dose intravitreal topotecan (IvitTopo) for recurrent retinoblastoma. METHODS: There were 13 patients with recurrent retinoblastoma treated with high-dose IvitTopo (90 micrograms (µg)/0.18cc-100 µg/0.20cc). The primary outcome measures were tumor control, globe salvage, and treatment complications. RESULTS: At date first seen (DFS), median patient age was 9 months, and the affected eye was classified as International Classification of Retinoblastoma (ICRB) Group B (n=2, 15%), Group C (n=3, 23%), or Group D (n=8, 62%) retinoblastoma with initial therapy of intravenous chemotherapy (n=9, 69%) or intra-arterial chemotherapy (n=4, 31%). Recurrent tumor was detected at median 10 months as solid tumor (n=3), subretinal seeds (n=10), and/or vitreous seeds (n=3) and high-dose IvitTopo (median 3 injections) delivered at monthly intervals. Additional chemotherapy was delivered by intra-arterial (n=8, 62%) or intravenous (n=1, 8%) routes, and 1 eye received additional cryotherapy (n=1, 8%). In 3 cases (23%) there was no additional therapy. At mean follow-up of 9 months, regression of solid tumor, subretinal seeds and vitreous seeds was achieved in 12 cases (92%), and globe salvage was achieved in all cases (n=13, 100%). Of those 3 eyes treated with high-dose IvitTopo alone, tumor control was initially achieved in all cases (100%), but one case that previously demonstrated massive vitreous seeding showed late recurrence of a solitary vitreous seed at 8 months. There were no complications. CONCLUSIONS: High-dose IvitTopo is an effective and safe therapy for recurrent retinoblastoma, in conjunction with other therapy, and possibly as a stand-alone therapy.

Truxima (rituximab-abbs) for Periocular Xanthogranuloma with Adult-Onset Asthma and Systemic IgG4-Related Disease.

A 58-year-old female with a 3-year history of adult-onset asthma, bilateral blepharoptosis, dry eye, and yellow-orange xanthelasma-like plaques extensively involving both upper eyelids presented with a diagnosis of adult-onset asthma with periocular xanthogranuloma (AAPOX) and systemic IgG4-related disease. Over the next 8 years, she received 10 intralesional triamcinolone injections (40-80 mg) in the right upper eyelid, 7 intralesional triamcinolone injections (30-60 mg) in the left upper eyelid, underwent right anterior orbitotomy twice followed by 4 doses of rituximab (1000 mg intravenous infusion) without regression of the AAPOX. The patient was then treated with 2 monthly doses of Truxima (1000 mg intravenous infusion), a biosimilar to rituximab. At the most recent follow-up, 13 months later, the xanthelasma-like plaques and orbital infiltration had markedly improved. To the best of the authors' knowledge, this is the first report of Truxima being used to treat AAPOX with systemic IgG4-related disease and to generate a sustained clinical response.

Conjunctival Melanoma in 430 Cases: Comparative Analysis of the Impact of Orbital Invasion on Tumor Recurrence, Metastasis, and Death.

PURPOSE: To compare the clinical features at presentation and treatment outcomes of conjunctival melanoma by absence/presence of orbital invasion. METHODS: A retrospective review of patients with conjunctival melanoma managed at a single tertiary referral center from April 18, 1974, to September 9, 2019. RESULTS: Of 430 patients with conjunctival melanoma, 21 (5%) had orbital invasion at presentation. A comparison between the 2 groups (orbital invasion absent vs. present) revealed that the orbital invasion group had a higher frequency of prior eyelid incisional biopsy (5% vs. 24%, P = 0.006), greater tumor basal diameter (12.2 vs. 17.3, P = 0.009), greater tumor thickness (2.4 vs. 7.0, P < 0.001), more quadrants involved (1.8 vs. 2.5, P = 0.002), and more clock hours involved (4.4 vs. 5.8, P = 0.037). In addition, those with orbital invasion were more likely to undergo exenteration as primary treatment (1% vs. 24%, P < 0.001). Multivariate relative risk regression analysis revealed that variables predictive of orbital invasion included greater tumor thickness (P < 0.001) and greater involvement of the fornix (P = 0.031) and tarsus (P = 0.033). Outcomes revealed orbital invasion group with greater 5-year/10-year distant metastatic rate (16%/21% vs. 63%/63%, P = 0.005), and greater melanoma-related death rate (7%/13% vs. 38%/53%, P = 0.001). CONCLUSIONS: Conjunctival melanoma with orbital invasion at presentation demonstrate larger, more extensive tumors involving the fornix or tarsus, and with greater rate of melanoma-related metastasis and death.

Bilateral Conjunctival Actinic Granuloma With Necrobiotic Vasculitic Pattern: A Diagnosis of Exclusion.

A 53-year-old Caucasian male presented with an inflamed-appearing limbal nodule in his OD, clinically compatible with nodular episcleritis, that was unresponsive to topical corticosteroid therapy. Excisional biopsy of the lesion was performed and histopathological examination revealed foci of necrotizing vasculitis and granulomatous inflammation in a background of intense actinic elastosis. Infectious stains for organisms were negative. A comprehensive systemic evaluation for vasculitides was negative. Three years later, the patient returned with a clinically and histopathologically identical lesion in his OS. Systemic evaluation was noncontributory again, and a diagnosis of bilateral conjunctival actinic granuloma with necrobiotic vasculitic pattern was made.

Mutational Landscape and Outcomes of Conjunctival Melanoma in 101 Patients.

PURPOSE: To evaluate targetable mutations and molecular genetic pathways in conjunctival melanoma with clinical correlation. DESIGN: Observational case series. PARTICIPANTS: Patients with conjunctival melanoma. MAIN OUTCOME MEASURES: Mutational profile of the tumor by next-generation sequencing (NGS), alternative lengthening of telomeres (ALT) by fluorescence in situ hybridization (FISH), and ATRX immunohistochemistry. Outcomes at 2 years and 5 years of tumor-related metastasis and death were recorded. RESULTS: Of the 101 patients, mean age at presentation was 60 years, 52% were male, and 88% were White. The NGS panels initially targeted BRAF only (n = 6, 6%), BRAF/NRAS (n = 17, 17%), and BRAF/NRAS/NF1 (n = 10, 10%). Sixty-eight tumors were tested with the expanded 592-gene panel. Next-generation sequencing identified high-frequency mutations in NF1 (29/74, 39%), BRAF (31/101, 31%), NRAS (25/95, 26%), and ATRX (17/68, 25%). Of those with an ATRX mutation, 12 (71%) had an additional NF1 mutation. A subset analysis of 21 melanomas showed that the ATRX mutation was associated with loss of ATRX protein expression and ALT. Loss of ATRX expression and ALT were present in both intraepithelial and invasive tumors, suggesting that an ATRX mutation is an early event in conjunctival melanoma progression. The NF1 and ATRX mutations were associated with tarsal (vs. nontarsal) tumors (NF1: 28% vs. 9%, P = 0.035, ATRX: 41% vs. 14%, P = 0.021) and orbital (vs. nonorbital) tumors (ATRX: 24% vs. 2%, P = 0.007). ATRXMUT (vs. ATRXWT) tumors were associated with a lower 2-year rate of metastasis (0% vs. 24%, P = 0.005). NRASMUT (vs. NRASWT) tumors were associated with a greater 2-year rate of metastasis (28% vs. 14%, P = 0.07) and death (16% vs. 4%, P = 0.04), with a 5-fold increased risk of death (relative risk, 5.45 [95% confidence interval, 1.11-26.71], P = 0.039). CONCLUSIONS: This study confirms the high frequency of previously documented BRAF and NRAS mutations and recently reported ATRX and NF1 mutations in conjunctival melanoma. An NRAS mutation implied increased risk for metastasis and death. Loss of ATRX and ALT may be early events in conjunctival melanoma development.

Intramuscular Eyelid Myxoma.

Myxomas are a heterogeneous group of mesenchymal tumors. Soft tissue myxomas are divided into myocardial, intramuscular, juxta-articular, superficial, aggressive, and nerve sheath myxomas. Although benign, myxomas have site-specific biologic behavior and syndromic associations, which can influence prognosis and management. In addition, myxomas need to be distinguished from malignant neoplasms, such as myxofibrosarcomas, low-grade fibromyxoid sarcomas, myxoid liposarcomas, and peripheral nerve sheath tumors. While myxomas can occur throughout the body, these tumors arise more commonly in the thigh, shoulder, buttocks, and upper extremity, and less often in the head and neck. Rarely, myxomas can arise in a periocular location, typically in the conjunctiva and eyelid skin. In this case report, we present a patient with recurrent intramuscular myxoma of the eyelid and discuss the differential diagnosis and syndromic associations of this neoplasm. To our knowledge, there have been no prior reports of intramuscular myxoma of the eyelid and orbit.

Conjunctival 'mucoepidermoid carcinoma' revisited: a revision of terminology, based on morphologic, immunohistochemical and molecular findings of 14 cases, and the 2018 WHO Classification of Tumours of the Eye.

In 2018, the consensus meeting for the WHO Classification of Tumours of the Eye decided that conjunctival mucoepidermoid carcinoma should be reclassified as adenosquamous carcinoma, as this represented a better morphological fit. To examine the applicability of this terminology, we studied the clinical, histopathological, immunohistochemical and molecular pathology of 14 cases that were originally diagnosed as conjunctival mucoepidermoid carcinoma. There were 7 (50%) females and 7 (50%) males. The median age was 64 years. The left eye was affected in 8 and the right eye in 6 patients. In-situ carcinoma was present in 11/14 (79%) cases and comprised in-situ squamous cell carcinoma (SCC) and conjunctival intraepithelial neoplasia with mucinous differentiation (CIN-Muc). Invasive carcinoma was present in 11/14 (79%) cases. Group 1 (1/11 cases, 9%) comprised invasive SCC only. Group 2 (6/11 cases, 55%) comprised SCC with mucinous differentiation, manifesting as scattered intracellular mucin, occasionally together with intercellular mucin, with no evidence of true glandular differentiation. Group 3 (3/11 cases. 27%) comprised true adenosquamous carcinoma. Group 4 (1/11 cases, 9%) comprised pure adenocarcinoma. Thirteen of 14 cases (93%) underwent FISH for MAML2 translocation and none were rearranged. Two cases harboured high-risk HPV (type 16 and 18). The combined findings confirm that all lesions in our study were not mucoepidermoid carcinoma, but represented predominantly SCC with mucinous differentiation and adenosquamous carcinoma. We, therefore, recommend future revision of the WHO classification to include SCC with mucinous differentiation alongside adenosquamous carcinoma.

Conjunctival Melanoma: Features and Outcomes Based on the Fitzpatrick Skin Type in 540 Patients at a Single Ocular Oncology Center.

PURPOSE: To determine the association of Fitzpatrick skin type (FST) with conjunctival melanoma. METHODS: Retrospective case series of 540 patients with conjunctival melanoma to assess clinical features and outcomes per FST. RESULTS: The FST was Type I (n = 126, 23%), II (n = 337, 62%), III (n = 56, 10%), IV (n = 8, 2%), V (n = 12, 2%), and VI (n = 1, <1%). A comparison (FST I vs. II vs. III, IV, V, and VI) revealed Types I and II associated with older mean patient age (63.9 vs. 60.7 vs. 51.1 years, p < 0.001), greater percentage of female patients (68% vs. 44% vs. 42%, p < 0.001), lower frequency of complexion associated melanosis (1% vs. 2% vs. 13%, p < 0.001), smaller tumor thickness (2.1 vs. 2.8 vs. 3.6 mm, p = 0.01), and less eyelid involvement (13% vs. 13% vs. 28%, p = 0.02). Kaplan-Meier estimates for 5-year risk showed no difference by Types for visual acuity loss ≥3 lines, local tumor recurrence, exenteration, metastasis, or death. CONCLUSION AND RELEVANCE: Most patients with conjunctival melanoma show FST I or II, and this demonstrated no association with 5-year rate of vision loss, tumor recurrence, exenteration, metastasis, or death.

Delayed implant infection with Cutibacterium acnes (Propionibacterium acnes) 30 years after silicone sheet orbital floor implant.

Purpose: To report a case of delayed implant infection with Cutibacterium acnes (C. acnes, previously known as Propionibacterium acnes) 30 years after silicone sheet orbital floor implant.Methods: Case report with orbital imaging.Results: A 61-year-old male with a history of traumatic orbital floor fracture right eye (OD) repaired using a silicone sheet orbital floor implant 30 years prior, presented with 6 months of painless blepharoptosis and diplopia OD. On examination, there was 3 mm right upper eyelid blepharoptosis and hyperglobus. There was no globe proptosis, dysmotility, or compression and no cutaneous erythema, hyperthermia, discharge, or tenderness to palpation. Orbital magnetic resonance imaging (MRI) revealed a cystic mass in the inferior orbit in the region of the floor implant, measuring 25 mm in diameter and 10 mm in thickness. By MRI, T1-weighted images revealed a hypointense signal within the mass and T2-weighted images showed hyperintense signal with a flat hypointensity centrally representing the floor implant. Microbiologic cultures grew C. acnes.Conclusions: C. acnes can manifest several decades after placement of an orbital prosthetic implant, leading to delayed infection.

Orbital Atypical Lipomatous Tumor/Well-Differentiated Liposarcoma Masquerading as Pleomorphic Lipoma: A Diagnostic Challenge.

Atypical lipomatous tumor/well-differentiated liposarcoma is a common neoplasm of the superficial and deep soft tissues of the extremities, trunk, and retroperitoneum. Atypical lipomatous tumor/well-differentiated liposarcoma is very rare in the orbit, with only 19 previously reported cases. The authors describe a 22-year-old woman who presented with an 8-month history of diplopia and was found to have an orbital mass on MRI. The excised tumor initially was interpreted as spindle cell/pleomorphic lipoma based on its morphologic and immunohistochemical features. Nine years later, the patient returned with a recurrence that required surgical debulking. Histopathologic and molecular cytogenetic evaluation of both primary and recurrent lesions disclosed Atypical lipomatous tumor/well-differentiated liposarcoma. This case highlights the diagnostic challenges and the importance of molecular genetic studies in evaluation of fatty orbital tumors.

LARGE UVEAL MELANOMA (≥10 MM THICKNESS): Clinical Features and Millimeter-by-Millimeter Risk of Metastasis in 1311 Cases. The 2018 Albert E. Finley Lecture.

PURPOSE: To analyze the clinical features and rate of metastatic disease in eyes with large (≥10 mm thickness) uveal melanoma. DESIGN: Retrospective noncomparative case series. PARTICIPANTS: There were 1,311 consecutive patients. METHODS: Retrospective medical chart review. MAIN OUTCOME MEASURES: Clinical features and rate of metastatic melanoma. RESULTS: Of 1,311 patients with large melanoma, the mean age was 59 years (median 60, range 6-98 years) and 95% were white. Mean tumor basal dimension was 17 mm (median 17, range 7-25 mm), and mean tumor thickness was 12 mm (median 12, range 10-24 mm). Mean distance to the foveola was 6 mm (median 6, range 0-19 mm) and to optic nerve was 6 mm (median 5, range 0-19 mm). Of all eyes, using Kaplan-Meier analysis, metastasis occurred in 11, 30, 45, and 52% at 1, 3, 5, and 7 years, respectively. According to tumor thickness (10.0-11.0, 11.1-12.0, 12.1-13.0, 13.1-14.0, 14.1-15.0, 15.1-16.0, and >16.0 mm), metastasis at 1 year was found in 7, 12, 13, 15, 18, 22, and 20%; metastasis at 3 years was 24, 27, 37, 35, 51, 69, and 57%; metastasis at 5 years was 38%, 42%, 56%, 48%, 61%, not available, and 66%; and metastasis at 7 years was 47%, 47%, 61%, 57%, 61%, not available, and 66%. Clinical features associated with fewer metastatic events included Bruch membrane rupture (7-year metastasis at 48%, P = 0.018) and macular location (7-year metastasis at 32%, P = 0.014), whereas those with worse outcome included extraocular extension (7-year metastasis at 79%, P < 0.001). There was no significant difference in rate of melanoma-related metastasis for patients treated with plaque radiotherapy versus enucleation. CONCLUSION: Large uveal melanoma demonstrates 7-year rate of metastasis at 52%, with generalized increasing risk per 1-mm or 2-mm thickness increments. Extraocular extension was associated with greater metastatic rate, whereas Bruch membrane rupture and macular location demonstrated lower rate.

Orbital Schwannoma: Radiographic and Histopathologic Correlation in 15 Cases.

PURPOSE: To evaluate the relationship between radiographic and histopathologic features of orbital schwannoma. METHODS: Retrospective review of 15 patients with orbital schwannoma managed at an ocular oncology service. RESULTS: The mean patient age at the time of presentation was 42 years old (median 40, range 15-64 years). The orbital schwannoma was found incidentally (n = 2) or with symptoms of proptosis (n = 2), blurred vision (n = 3), pain (n = 3), eyelid swelling (n = 2), diplopia (n = 2), or headache (n = 1). The mean duration of symptoms was 15 months (median, 9; range 1-60 months). The tumor occupied the superior (n = 11) or inferior (n = 4) orbit. Antero-posterior tumor location involved the anterior (n = 2), middle (n = 3), posterior (n = 4), or entire (n = 6) orbit. MRI was performed in 12 patients (80%) and CT was the only form of imaging in 3 patients (20%). The T1-weighted MRI (n = 11) showed the mass as isointense (n = 10) or hyperintense (n = 1) to the extraocular muscles). On T2-weighted MRI (n = 10), the mass demonstrated hyperintensity (n = 9) or hypointensity (n = 1). Histopathologic assessment demonstrated Antoni A (n = 12) and Antoni B (n = 12) patterns. Antoni A pattern correlated with hyperintensity on T1-weighted MRI and hypointensity on T2-weighted MRI. Antoni B pattern correlated with hypointensity on T1-weighted MRI and hyperintensity on T2-weighted MRI. As Antoni B approached >50% of the solid mass (n = 8), both T1- and T2-weighted MRI images were more likely to be heterogeneous (n = 7, 88% and n = 6, 75%, respectively). CONCLUSION: Orbital schwannomas are nearly always benign, well-encapsulated slowly progressive tumors. Due to the biphasic distribution of Antoni A and Antoni B pattern, the appearance on MRI has a variable degree of heterogeneity. Antoni A pattern correlated with hyperintensity and Antoni B pattern correlated with hypointensity on T1-weighted MRI.

Diffuse Anterior Retinoblastoma with Globe Salvage and Visual Preservation in 3 Consecutive Cases.

PURPOSE: Diffuse anterior retinoblastoma is an exquisitely rare variant of retinoblastoma in which the tumor resides in the anterior segment of the eye, without apparent retinal involvement. Previously published cases have been managed with enucleation. We describe globe salvage and visual preservation in 3 consecutive cases using chemotherapy and radiotherapy. DESIGN: Retrospective case series. PARTICIPANTS: Three children with diffuse anterior retinoblastoma. METHODS: Plaque radiotherapy plus intravenous chemotherapy. MAIN OUTCOME MEASURES: Globe and vision preservation. RESULTS: The mean patient age at presentation elsewhere was 5.7 years (median, 7; range, 3-7 years). There were 2 white female patients and 1 African American male patient. The initial observation by parents/caregiver was reduced vision (n = 1), red eye (n = 1), or cloudy eye (n = 1), and the initial finding by physician was iris tumor (n = 2) or hyphema (n = 1). Referring diagnosis was iris melanoma (n = 1), infectious endotheliitis (n = 1), and possible tumor (nonspecified) (n = 1). At our evaluation, visual acuity was 20/50 to 20/60 (n = 2) and fix no follow (n = 1). In all cases, the opposite eye was normal. Mean intraocular pressure was 20 mm Hg (median, 16; range, 15-30 mmHg). Our examination revealed solid iris tumor (n = 3), ciliary body involvement (n = 2), and anterior chamber seeding (n = 3). In no case was there choroidal or retinal tumor, vitreous seed or subretinal seed, or extrascleral extension. Clear corneal fine-needle aspiration biopsy confirmed the diagnosis as retinoblastoma in each case. Treatment included plaque radiotherapy (n = 3) plus additional systemic chemotherapy (n = 2). At mean follow-up of 35 months (median, 34; range, 20-51 months), there has been no recurrence, extrascleral extension, enucleation, metastasis, or death. In all 3 cases, cataract surgery was necessary at a mean interval of 16 months after complete and stable regression of retinoblastoma. CONCLUSIONS: The rare diffuse anterior form of retinoblastoma can be managed with globe-salvaging alternatives and with visual preservation in selected cases.

Update on orbital lymphatic malformations.

PURPOSE OF REVIEW: The purpose of this article is to review the recent published literature in 2015 on lymphatic malformation and provide updated information on the disease. Specifically, this article will describe recent advances in identifying and managing lymphatic malformations. RECENT FINDINGS: All articles discussed in this article emphasize the difficulty in treating lymphatic malformations. Most patients have long complicated histories with multiple recurrences. Studies are trying to identify which lesions will be successful treated by certain therapeutic modality. Treatment includes nonsurgical and surgical therapies. SUMMARY: Lymphatic malformations are difficult lesions to treat because they do not respect tissue planes. The use of sclerosing agents shows great promise for treating macrocysts. More knowledge is needed in the development of the disease process. Hopefully, antilymphangiogenic agent can provide targeted treatment.

Pediatric Idiopathic Orbital Inflammation: Clinical Features of 30 Cases.

PURPOSE: Pediatric idiopathic orbital inflammation (IOI) is a rare entity with little known about the clinical presentation and natural history. The authors report the demographics, clinical presentations, radiographic and histopathologic characteristics, and treatment outcome of 30 children with IOI. METHODS: Retrospective chart review of 30 patients 18 years and younger diagnosed with IOI and statistical analysis using analysis of variance and Fisher's exact test. This study was reviewed and approved by the Institutional Review Board of SUNY Downstate Medical Center. RESULTS: There were 9 males (30%) and 21 females (70%) with pediatric IOI who presented at a median age of 11 years (range 2-18 years). Primary IOI was found in 19 patients (63%) and recurrent IOI in 11 patients (37%). Overall, 26 patients (87%) had unilateral IOI while 4 patients (13%) had bilateral disease at presentation. There were 12 patients (40%) with systemic constitutional signs. The most common ophthalmic findings included periorbital edema (n = 20, 67%) and blepharoptosis (n = 17, 57%). All patients had orbital radiography with common findings of dacryoadenitis (n = 12, 40%), orbital mass (n = 12, 40%), or myositis (n=10, 33%). The presence of a radiographic orbital mass was significantly related to the clinical presence of blepharoptosis (p = 0.03). The most common treatment was oral glucocorticoids in 24 patients (80%). Over mean follow up of 19 months (range 6-64 months), females were more likely to display recurrent disease (p = 0.01). CONCLUSIONS: Idiopathic orbital inflammation is an uncommon but important cause of acute orbital syndrome in children, manifesting as a bilateral condition in 13% and with constitutional symptoms in 40%. Posttreatment recurrence is found in 37% of cases.

Periocular Melanoma In Situ Treated With Imiquimod.

PURPOSE: To evaluate the efficacy of topical 5% imiquimod cream in the treatment of periocular melanoma in situ (lentigo maligna). DESIGN: Retrospective case series. SUBJECTS: There were 12 patients in this series, and the mean patient age was 77 years. The anatomical locations were the lower eyelid (n=5), upper and lower eyelid (n=4), lower eyelid including the eyelid margin (n=1), brow (n=1), and the medial canthus (n=1). Topical 5% imiquimod cream was used as a primary treatment (n=6) or as an adjunctive therapy following local excision (n=2), cryotherapy (n=2), or excisional biopsy with cryotherapy (n=2). METHODS: Twelve patients with periocular melanoma in situ were treated with topical 5% imiquimod cream daily for a mean treatment period of 3.9 months. The clinical features of the patients and the responses to treatment were evaluated in a retrospective case series. MAIN OUTCOME MEASURES: Histologic clearance of atypical melanocytes. RESULTS: Eleven patients achieved complete histologic clearance of atypical melanocytes on post-treatment biopsy. One patient could not tolerate local irritation from imiquimod and stopped in the first month of therapy with residual disease. The median follow-up time was 1.5 years. Side effects included redness (n=12), discomfort (n=6), swelling (n=4), ectropion (n=1), and conjunctival chemosis (n=1). The patients experienced no systemic side effects from the treatment. CONCLUSIONS: Topical 5% imiquimod cream is an effective option as primary or adjunct therapy in the treatment of periocular melanoma in situ.

Hydroxyapatite orbital implant in children following enucleation: analysis of 531 sockets.

PURPOSE: To evaluate the features and long-term outcomes of hydroxyapatite (HA) orbital implant following enucleation in pediatric patients. METHODS: A retrospective review was performed on clinical records of patients ≤18 years of age , managed with enucleation and HA implant placement. Recorded outcomes included implant-related complications, implant and prosthesis motility, and patient cosmetic satisfaction. RESULTS: There were 525 children (531 sockets) with HA implant following enucleation. The mean age at HA implant placement was 3 years (median, 2 years; range, 4 days to 17 years). Indications for enucleation included retinoblastoma (n = 457, 86%), uveal melanoma (n = 17, 3%), medulloepithelioma (n = 8, 2%), and others (n = 49, 9%). The HA implant was uncoated (n = 370, 70%) or polymer coated (n = 161, 30%). For the 370 uncoated implants, wrapping was provided with scleral (n = 346, 94%) or bovine pericardium (n = 1, <1%), and 23 patients (6%) had no wrapping. The extraocular muscles were attached to the implant/polymer coat/wrap (n = 531, 100%), by suturing 4 rectus muscles (n = 349, 66%) or all 6 muscles (n = 182, 34%). Over mean follow up of 60 months, in 477 orbital implants, complications included conjunctival thinning (n = 10, 2%), implant infection (n = 6, 1%), implant exposure (n = 13, 3%), and implant migration/extrusion (n = 0, 0%). Motility for implant was judged as excellent (n = 245, 78%) and small-angle prosthesis motility was excellent (n = 196, 59%). Patient/family satisfaction with cosmetic outcome was rated as excellent in 471 implants (99%). CONCLUSIONS: Following enucleation in children, long-term outcomes of the HA orbital implant are excellent with favorable patient cosmetic satisfaction and rare complication.

Intra-arterial chemotherapy for retinoblastoma in 70 eyes: outcomes based on the international classification of retinoblastoma.

OBJECTIVE: To analyze our 5-year experience of intra-arterial chemotherapy (IAC) for retinoblastoma as primary or secondary therapy. DESIGN: Retrospective interventional case series. PARTICIPANTS: A total of 70 eyes of 67 patients. INTERVENTION: Ophthalmic artery chemotherapy infusion under fluoroscopic guidance was performed using melphalan (3, 5, or 7.5 mg) in every case, with additional topotecan (1 mg) and/or carboplatin (30 or 50 mg) as necessary. MAIN OUTCOME MEASURES: Tumor control and treatment complications. RESULTS: The mean patient age at IAC was 30 months. The treatment was primary in 36 eyes and secondary in 34 eyes. Those primary therapy eyes were classified according to the International Classification of Retinoblastoma (ICRB) as group A (n = 0), B (n = 1), C (n = 4), D (n = 17), or E (n = 14). The secondary therapy eyes had failed previous intravenous chemotherapy (n = 34) in every case. Each eye received a mean of 3 IAC sessions per eye (median, 3; range, 1-7 sessions). After IAC with a mean follow-up of 19 months, globe salvage was achieved in 72% of primary-treated cases and in 62% of secondary-treated cases. Specifically, primary therapy achieved globe salvage for group B (100%), group C (100%), group D (94%), and group E (36%). Of all 70 eyes, complete regression was achieved for solid tumor in 48 of 51 eyes (94%), subretinal seeds in 40 of 42 eyes (95%), and vitreous seeds in 34 of 39 eyes (87%). After each catheterization (n = 198), the main complications included transient eyelid edema (5%), blepharoptosis (5%), and forehead hyperemia (2%). More lasting complications included vitreous hemorrhage (2%), branch retinal artery obstruction (1%), ophthalmic artery spasm with reperfusion (2%), ophthalmic artery obstruction (2%), partial choroidal ischemia (2%), and optic neuropathy (<1%). Over the past 3 years, the combined incidence of ophthalmic, retinal, and choroidal vascular ischemia was reduced to 1%. There was no patient with stroke, seizure, neurologic impairment, limb ischemia, secondary leukemia, metastasis, or death. CONCLUSIONS: Five-year experience with IAC indicates that this technique is remarkably effective for the management of retinoblastoma as both a primary and a secondary treatment.

Targeted retinoblastoma management: when to use intravenous, intra-arterial, periocular, and intravitreal chemotherapy.

PURPOSE OF REVIEW: The management of retinoblastoma is complex and involves strategically chosen methods of enucleation, radiotherapy, chemotherapy, laser photocoagulation, thermotherapy, and cryotherapy. Chemotherapy has become the most common eye-sparing modality. There are four routes of delivery of chemotherapy for retinoblastoma, including intravenous, intra-arterial, periocular, and intravitreal techniques. The purpose of this review is to discuss the current rationale for each method and the anticipated outcomes. RECENT FINDINGS: The diagnosis of retinoblastoma should be clinically established prior to embarking on a chemotherapy protocol. There are over 25 conditions that can closely simulate retinoblastoma in a young child. In addition, enucleation is an acceptable method for management, particularly with advanced retinoblastoma. Intravenous chemotherapy is generally used for germline mutation (bilateral, familial) retinoblastoma with excellent tumor control for groups A, B, and C and intermediate control for group D eyes. Intra-arterial chemotherapy is used as primary therapy in selected cases for nongermline mutation (unilateral) retinoblastoma with excellent control, and also used as secondary therapy for recurrent solid retinoblastoma, subretinal seeds, and vitreous seeds. Periocular chemotherapy is employed to boost local chemotherapy dose in advanced bilateral groups D and E eyes or for localized recurrences. Intravitreal chemotherapy is used for recurrent vitreous seeds from retinoblastoma. Patients at high risk for metastases should receive intravenous chemotherapy. SUMMARY: Chemotherapy is effective for retinoblastoma and the targeted treatment route depends on the clinical features and anticipated outcomes.