Fairooz P. Manjandavida

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.

Original articleIntra-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.

Ciliary Body Medulloepithelioma: Analysis of 41 Cases

PURPOSE To describe the clinical features, histopathology, treatment, and outcomes of ciliary body medulloepithelioma. DESIGN Retrospective study. PARTICIPANTS Forty-one patients with medulloepithelioma. INTERVENTION Cryotherapy, plaque radiotherapy, external beam radiotherapy, tumor removal by partial lamellar sclerouvectomy (PLSU), or enucleation. MAIN OUTCOME MEASURES Metastasis and death. RESULTS Of 41 patients with ciliary body medulloepithelioma, the median age at diagnosis was 5 years. The mean tumor basal diameter was 11 mm, and the mean tumor thickness was 7 mm. Related features included secondary glaucoma (n = 18, 44%), iris neovascularization (n = 21, 51%), cataract (n = 19, 46%), lens subluxation (n = 11, 27%), lens coloboma (n = 8, 20%), retrolental neoplastic cyclitic membrane (n = 21, 51%), intratumoral cysts (n = 25, 61%), and extraocular extension (n = 4, 10%). There was systemic association with pleuropulmonary blastoma in 2 cases (5%). Primary tumor treatment included enucleation (n = 21, 60%), tumor removal by PLSU (n = 8, 23%), plaque radiotherapy (n = 3, 9%), external beam radiotherapy (n = 1, 3%), cryotherapy (n = 1, 3%), or palliative chemotherapy (n = 1, 3%). In 1 case, medulloepithelioma was diagnosed histopathologically after inadvertent evisceration for blind painful eye. Subsequent treatment for residual or recurrent tumor in cases treated conservatively/inappropriately (n = 15) was necessary in 7 cases (47%). Histopathology disclosed benign features in 6 cases (20%), malignant features in 24 cases (80%), teratoid features in 11 cases (37%), and nonteratoid features in 19 cases (63%). In the 26 enucleated eyes, other features included retrolental neoplastic cyclitic membrane (n = 18, 69%), neoplastic epiretinal membrane (n = 6, 23%), and persistent hyaloid artery (n = 6, 23%). Systemic metastasis occurred in 3 cases (8%) over a mean follow-up of 49 months, all of whom presented with extrascleral extension of tumor due to mean delay in diagnosis by 39 months. CONCLUSIONS Medulloepithelioma most commonly occurs in children. Systemic association with pleuropulmonary blastoma rarely is found. Patients with extrascleral medulloepithelioma are at risk for metastasis.

The role of intravitreal chemotherapy for retinoblastoma

Targeted therapy in retinoblastoma (RB) is widely accepted as the current management tool with an aim of increasing drug availability at the tumor location. Inevitably the effect is several times higher compared to systemic delivery of chemotherapeutic drugs and carries less systemic toxicity. Despite tremendous advancement in saving life, eye salvage in advanced RB especially with active vitreous seeds remains a challenge. The hypoxic environment of the vitreous and reduced vitreous concentration of the drugs delivered makes these tumor seeds resistant to chemotherapy. Direct delivery of chemotherapeutic drugs into the vitreous cavity aids to overcome these challenges and is progressively being accepted worldwide. However, intraocular procedure in RB was abandoned due to high risk of extraocular tumor dissemination. Recently, the forbidden therapeutic technique was re-explored and modified for safe use. Although eye salvage rate has tremendously improved after intravitreal chemotherapy (IVitC), retinal toxicity, and vision salvage are yet to be validated. In our preliminary report of intravitreal melphalan in 11 eyes, we reported 100% eye salvage and 0% recurrence with an extended 15 months mean follow-up. In this review, we analyzed published reports on IVitC in RB via PubMed, Medline, and conference proceedings citation index, electronic database search, without language restriction that included case series and reports of humans and experimental animal eyes with RB receiving IVitC.

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.

Tumors of the ocular surface: A review

Tumors of the Ocular Surface clinically manifest with a very wide spectrum and include several forms of epithelial, stromal, caruncular, and secondary tumors. As a group, these tumors are seen commonly in the clinical practice of a comprehensive ophthalmologist, cornea specialist, and an ocular oncologist. This review is aimed to discuss the common tumors of the ocular surface and emphasize on their clinical diagnosis and appropriate management.

Cryotherapy-induced release of epiretinal membrane associated with retinal vasoproliferative tumor: analysis of 16 cases.

Purpose: To evaluate epiretinal membrane (ERM) response after cryotherapy for retinal vasoproliferative tumors (VPTs). Method: Retrospective interventional case series. Results: Of 16 eyes with VPT and ERM, the tumor was classified as primary in 12 (75%) eyes or secondary in 4 (25%) eyes. The median patient age was 44 years (mean, 43 years; range, 9–70 years). The tumor was located in extramacular zone (n = 16, 100%) and inferotemporal quadrant (n = 12, 75%). The mean tumor base was 6 mm, and thickness was 3 mm. The ERM involved the macula in 12 (75%) eyes and extramacular zone in 4 (25%) eyes, with best-corrected visual acuity of 20/40 or better in 6 (38%) eyes. Associated features included cystoid macular edema (n = 8, 50%), subretinal fluid (n = 10, 63%), vitreous cells (n = 9, 56%), and vitreous hemorrhage (n = 7, 44%). Single-session cryotherapy (double freeze–thaw) to the VPT was performed in each case. Over mean follow-up of 68 months (median, 54 months; range, 8–252 months), tumor regression was documented in 16 (100%) cases, with ERM release in 10 (63%) cases. After ERM release, the foveal anatomy was normal in 12 (75%) eyes. Final visual acuity improved (n = 5, 31%), remained stable (n = 9, 56%), or worsened (n = 2, 13%). Posttreatment best-corrected visual acuity was 20/40 or better in 10 (63%) eyes. Conclusion: Cryotherapy is remarkably effective for VPT of 6 mm or less in basal dimension. After cryotherapy, VPT-related ERM spontaneously released in 63% of the cases, without the need for surgical intervention.

Optical coherence tomography characteristics of epi-iridic membrane in a child with recurrent hyphema and presumed juvenile xanthogranuloma

We report a case of spontaneous hyphema in a 6-month-old girl with no history of trauma and no visible iris mass. Subtle green-blue heterochromia was noted in the right eye. The iris crypts in the right eye appeared flattened by a thin, transparent layer on the iris surface. Anterior segment optical coherence tomography (AS-OCT) disclosed a thin homogenous membrane overlying the entire iris surface in the right eye. Fluorescein angiography revealed diffuse hyperfluorescence without neovascularization. These features were suggestive of diffuse iris juvenile xanthogranuloma. Sub-Tenons triamcinolone acetate plus topical corticosteroids eyedrops resolved the condition within 1 month.

Malignant Teratoid Ciliary Body Medulloepithelioma in a Neonate

Ciliary body medulloepithelioma is an intraocular tumor manifesting in early childhood, rarely at birth. A unique case of intraocular malignant teratoid ciliary body medulloepithelioma in a neonate presenting as buphthalmos at birth is reported. There was rapid progression with extraocular extension within 2 months and developed regional lymph node metastasis despite enucleation. The child underwent lymph node dissection and local radiotherapy with complete remission.

Retinoblastoma: Recent Update and Management Frontiers.

Worldwide, retinoblastoma is the most common intraocular cancer in children. This malignancy poses a looming threat of blindness and death to a young child, perhaps even a newborn infant. The ocular oncologist is a critical director of the child’s course, orchestrating a multidisciplinary team to urgently and comprehensively provide care with the singular goal of protection of the patient’s life. The approach of the ocular oncologist in the management of retinoblastoma has undergone tremendous change in the recent years. This success can be attributed to advances in genetic research, standardized grouping and staging of the disease with clinical validation, multidisciplinary team approach, and standardized protocol-based management strategies. Following successful life salvage, secondary goals remain globe salvage and protection of long-term vision. There is delicate balance of treatment alternatives with long-term ocular and systemic morbidity. We have personally witnessed the rollercoaster evolution of retinoblastoma management from enucleation to external radiation to focal plaque radiation to systemic chemotherapy to current targeted local delivery of chemotherapeutic agents. The introduction of systemic intravenous chemotherapy (IVC), known as chemoreduction, in the 1990s was a fulcrum that successfully pivoted retinoblastoma therapy into the arena of chemotherapy with unquestionably improved outcomes. Systemic chemotherapy is cost-effective and is considered the primary therapeutic modality for management of retinoblastoma in most developing countries. Apart from reducing the tumor volume (chemoreduction) and preventing systemic metastasis, IVC has the potential advantage in children with germline mutation for prevention of highly fatal pinealoblastoma and minimizing long-term second cancers. Treatment outcomes depend on patient compliance and chemotherapy drug delivery, but perhaps the most important factors for outcomes include seeding of the tumor into the subretinal space or vitreous cavity. Shields et al showed excellent response to the triple drug protocol including a combination of vincristine (1.5 mg/m), etoposide (150 mg/m), and carboplatin (560 mg/m) delivered every 4 weeks for 6 cycles. In less advanced (groups A, B, and C) cases, globe salvage after IVC and focal consolidation with transpupillary thermotherapy, cryotherapy, and/or plaque radiotherapy ranged from 90% to 100%. Narang et al recently reported remarkably impressive visual outcome following IVC with an ambulatory vision of 20/200 or greater in 71% eyes and 20/40 or greater in 36%. The primacy of this time-tested method has been recently replaced in some cases by superselective and targeted intra-arterial chemotherapy (IAC). It is a rapidly emerging technique that stands as the primary treatment for unilateral retinoblastoma in the Western world. This innovative therapy is slowly gaining acceptance by the rest of the world. The technique was introduced in Japan and was modified and popularized in the West. In contrast to IVC, IAC has minimal systemic absorption and related complications. After an initial hesitation to accept this sophisticated technique of ophthalmic artery catheterization with chemotherapy delivery and tolerating the steep learning curve, several groups have spoken of its safety and efficacy. The protocol involves 3 cycles of IAC including melphalan (3Y7.5 mg) and/or topotecan (0.5Y1 mg) and less commonly carboplatin (15Y30 mg), to a maximum of 6 cycles. A recent update by Shields et al demonstrated overall globe salvage of 72% in primary IAC (group B = 100%, group C = 100%, group D = 94%, and group E = 36%) eyes and 62% after secondary treatment for eyes that failed other treatment modalities. Similarly, Gobin et al reported 82% and 54% in those receiving primary and secondary IAC, respectively. Minimal-exposure IAC involves administration of only 1 to 2 cycles of IAC for tumor control especially in less advanced eyes. The well-known fear for administering IAC and its potential vascular endothelial toxicity with vision-threatening complications are currently less commonly encountered EDITORIAL