Aparna Ramasubramanian

Intra-arterial Chemotherapy for Retinoblastoma: Report No. 1, Control of Retinal Tumors, Subretinal Seeds, and Vitreous Seeds

OBJECTIVE To describe tumor control following intra-arterial chemotherapy (IAC) for retinoblastoma. METHODS A retrospective interventional series in which 17 patients were treated with ophthalmic artery injection of melphalan, 5 mg, was undertaken to determine retinoblastoma control. RESULTS Of 190 children with retinoblastoma, 17 (9%) were treated with IAC. Catheterization was successful in 37 of 38 attempts. The treatment was primary in 13 cases (1 failed catheterization) and secondary in 4. The median retinoblastoma base was 20 mm and the median retinoblastoma thickness was 9.0 mm. Iris neovascularization was present in 5 cases. Following IAC, complete response of the main tumor was found in 14 cases (88%) and partial response was found in 2 (12%). Eyes with complete response and followed up for a minimum of 1 year (n = 10) showed no solid tumor recurrence. Of 11 eyes with subretinal seeds, 9 (82%) had complete response, 1 (9%) had partial response, and 1 (9%) had recurrence. Of 9 eyes with vitreous seeds, 6 (67%) had complete response, 2 (22%) had partial response, and 1 (11%) had recurrence. Globe salvage was achieved in 8 of 12 eyes (67%) treated with primary IAC, including 2 of 2 group C eyes, 4 of 4 group D eyes, and 2 of 6 group E eyes according to the International Classification of Retinoblastoma. Globe salvage was achieved in 2 of 4 eyes (50%) treated secondarily after failure of other methods. CONCLUSIONS Of 12 eyes managed with IAC as primary treatment, globe salvage was achieved in 67%. Eyes classified as group C or D showed 100% globe salvage, whereas group E had 33% salvage. Of 4 eyes managed with IAC as secondary treatment, globe salvage was achieved in 50%.

Intra-arterial Chemotherapy for Retinoblastoma: Report No. 2, Treatment Complications

OBJECTIVE To describe treatment complications following intra-arterial chemotherapy (IAC) for retinoblastoma. METHODS A retrospective interventional series of ophthalmic artery cannulation for IAC injection (3 planned sessions at 1-month intervals) was undertaken. Thirty-eight catheterizations of 17 eyes of 17 patients were performed from September 2008 to September 2010. Fluoroscopy of the ophthalmic artery was performed before and immediately after treatment. Heparin was given during the procedure and aspirin (40 mg) was given orally for 1 week. The treatment complications were determined. RESULTS Only 17 of 190 children were selected for treatment with IAC during this period. Following successful ophthalmic artery cannulation in 16 cases, there was no evidence of metastasis, stroke, brain injury, or persistent systemic toxic effects. Fluoroscopy demonstrated patent ophthalmic artery immediately before and after IAC injection in each case. Following therapy, orbital and adnexal findings at 1 month included eyelid edema (n = 13), blepharoptosis (n = 10), cilia loss (n = 1), and orbital congestion with temporary dysmotility (n = 12). These findings resolved within 6 months in all cases. Following therapy, vascular findings included ophthalmic artery stenosis (permanent in 3 cases, temporary in 1 case), confirmed on fluoroscopy in 3 cases. Concomitant central or branch retinal artery occlusion was noted (permanent in 2 cases, temporary in 1 case). Subtle retinal pigment epithelial mottling in 9 cases that slowly evolved to later-onset underlying choroidal atrophy in 5 cases was noted. CONCLUSIONS Treatment with IAC for retinoblastoma can lead to mild and severe short-term ocular complications, including eyelid edema as well as potentially blinding vascular obstruction. This procedure should be used with caution.

Conjunctival Squamous Cell Carcinoma Arising in Immunosuppressed Patients (Organ Transplant, Human Immunodeficiency Virus Infection)

PURPOSE To describe the relationship between chronic systemic immune suppression and conjunctival squamous cell carcinoma (SCC). DESIGN Retrospective interventional case series. PARTICIPANTS Thirteen immunosuppressed patients with conjunctival SCC. METHODS Surgical excision in all cases plus additional topical interferon alpha-2B or mitomycin. MAIN OUTCOME MEASURES Tumor control. RESULTS There were 3 groups of patients with chronic immunosuppression and conjunctival SCC, including 8 patients who received an organ transplant, 4 patients with human immunodeficiency virus (HIV), and 1 patient with systemic lupus erythematosus (SLE) receiving long-term corticosteroids. The transplanted organ was kidney (n=4) (1 with additional pancreas transplant), lung (n=2), liver (n=1), and heart (n=1). The mean patient age at presentation for the organ transplant group was 60 years, and the mean interval from transplant to conjunctival SCC was 8.2 years. Management included surgical excision (n=8) plus additional topical interferon alpha-2B (n=3) and mitomycin C (n=1). Three patients showed aggressive recurrence or new tumor, and 1 patient died of brain invasion of SCC. In the HIV group, the mean patient age at presentation was 54 years and the mean interval from HIV diagnosis to conjunctival SCC was 5 years. Management included surgical excision (n=5) plus additional topical interferon alpha-2B (n=3) and mitomycin C (n=1). One patient showed aggressive extensive recurrence requiring enucleation and radiotherapy, and there were no related deaths. The patient with SLE was 49 years old, had been taking systemic corticosteroids for 18 years, and showed control with surgical resection and topical interferon alpha-2B. Of the 5 patients treated with excision and prompt topical interferon alpha-2B, none showed recurrence or new tumor. CONCLUSIONS Conjunctival SCC can occur in immunosuppressed patients and can be more aggressive and invasive, requiring enucleation or exenteration. Surgical resection plus topical interferon alpha-2B might reduce the risk for recurrence or new tumor. FINANCIAL DISCLOSURE(S) The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Chemoreduction for Group E Retinoblastoma: Comparison of Chemoreduction Alone Versus Chemoreduction Plus Low-Dose External Radiotherapy in 76 Eyes

PURPOSE To evaluate chemoreduction (CRD) for group E retinoblastoma. DESIGN Retrospective, comparative case series. PARTICIPANTS Seventy-six eyes of 56 patients with group E retinoblastoma were treated with CRD alone or CRD plus low-dose prophylactic external beam radiotherapy (CRD+P-EBR). The CRD included vincristine, etoposide, and carboplatin (6 cycles). The P-EBR was given routinely 2 months after completion of CRD at a suggested dose of 2600 cGy. Therapeutic EBR (T-EBR) was only given at the time of extensive tumor recurrence at a suggested dose of 3800 cGy. METHODS Retrospective chart review. MAIN OUTCOME MEASURES Globe salvage. RESULTS Of the 76 eyes, 64 received CRD alone and 12 received CRD+P-EBR. At the 2-year follow-up, globe salvage was achieved in 29 (53%) of 55 eyes in the CRD group and in 10 (91%) of 11 eyes in the CRD+P-EBR group. At 5 years, globe salvage was achieved in 20 (48%) of 42 eyes in the CRD group and in 4 (80%) of 5 eyes in the CRD+P-EBR group (P=0.347). Of the 64 eyes in the CRD group, 16 (25%) were salvaged with CRD alone and 13 (20%) with CRD+T-EBR, whereas 22 (34%) were enucleated after CRD alone and 13 (20%) were enucleated after CRD+T-EBR. Of the 12 eyes in the CRD+P-EBR group, 10 (83%) were salvaged with CRD+P-EBR, whereas 2 (17%) were enucleated and none required T-EBR. The median dose for T-EBR was 3800 cGy, and that for P-EBR was 2600 cGy. Eyes treated with CRD+P-EBR showed significantly less recurrence, leading to less chance of enucleation or therapeutic radiotherapy than that for CRD alone (P<0.001). Visual acuity was 20/100 or better or fix and follow in 9 (32%) of 28 salvaged eyes in the CRD group and in 4 (40%) of 10 in the CRD+P-EBR group. At 5 years, there were no patients in either group with metastasis of pinealoblastoma or who had died. In one patient in the CRD group, a second cancer developed. CONCLUSIONS Group E retinoblastoma managed with CRD+P-EBR showed significantly less need for enucleation or therapeutic radiotherapy than eyes treated with CRD alone. These findings merit further study and consideration.

Superselective Catheterization of the Ophthalmic Artery for Intraarterial Chemotherapy for Retinoblastoma

A 14-month-old boy with bilateral familial retinoblastoma was referred with recurrent retinoblastoma in the left eye after failure of seven cycles of chemoreduction (vincristine, etoposide, carboplatin), thermotherapy, and cryotherapy. The recurrent, highly vascular macular retinoblastoma measured 1Manual Small Incision 20-Gauge Pars Plana Vitrectomy The 25-gauge transconjunctival sutureless vitrectomy system was introduced by Fujii et al1 in 2002, followed by the introduction of the 23gauge system by Eckardt2 in 2005. Although the sutureless vitrectomy system may reduce surgical time and trauma and hasten postoperative recovery, problems such as flexibility, increased resistance, low infusion and aspiration rates, hypotony, endophthalmitis, and higher costs of special instruments have limited its use.3 Some authors have reported several types of sutureless transconjunctival 20-gauge pars plana vitrectomy.4–7 However, all of them needed new instruments that increased the cost. Furthermore, sutureless7 or a single suture of the scleral incision4,5 may increase the risk of wound leaking and endophthalmitis. Given the disadvantages of the previous sutureless vitrectomy systems, we present a manual small incision 20-gauge pars plana vitrectomy (MSIV) technique using the regular 20-gauge vitrectomy instruments.

Irradiation Toxic Effects During Intra-arterial Chemotherapy for Retinoblastoma: Should We Be Concerned?

OBJECTIVE To evaluate irradiation toxic effects from fluoroscopy during intra-arterial chemotherapy for retinoblastoma. DESIGN Prospective trial. PARTICIPANTS Eight patients treated with intra-arterial chemotherapy. MAIN OUTCOME MEASURES Irradiation toxic effects in vital organs. RESULTS The mean patient age was 29 months (range, 10-74 months) and 63% were male. The mean irradiation dose to the skin of the affected eye was 0.19173 Gy, to the contralateral eye was 0.03533 Gy, to the chest wall was 0.00296 Gy, and to the abdominal wall was 0.00104 Gy. The estimated irradiation dose to the lens in the treatment eye was 0.16 Gy, which, in accumulated doses, could be cataractogenic. The estimated irradiation dose from a single fluoroscopy session to other organs, including the brain (0.05560 Gy), thyroid (0.00192 Gy), bone marrow (0.00059 Gy), and gonads (0.00015 Gy), was far lower than the minimal toxic level. CONCLUSIONS Careful use of fluoroscopy during intra-arterial chemotherapy with limited irradiation exposure is advised. Accumulated irradiation toxic effects following multiple sessions of intra-arterial chemotherapy could be cataractogenic and possibly carcinogenic, especially in irradiation-sensitive patients with retinoblastoma.

Retinoblastoma Regression Patterns Following Chemoreduction and Adjuvant Therapy in 557 Tumors

OBJECTIVE To evaluate retinoblastoma regression patterns following chemoreduction and adjuvant therapy. PARTICIPANTS A total of 557 retinoblastomas. METHODS A retrospective medical record review following 6 cycles of chemoreduction and tumor consolidation (thermotherapy or cryotherapy). Regression patterns included type 0 (no remnant), type 1 (calcified remnant), type 2 (noncalcified remnant), type 3 (partially calcified remnant), and type 4 (flat scar). MAIN OUTCOME MEASURES Regression pattern. RESULTS Retinoblastoma regressions were type 0 (n = 10), type 1 (n = 75), type 2 (n = 28), type 3 (n = 127), and type 4 (n = 317). Tumors with an initial thickness of 3 mm or less regressed most often to type 4 (92%), those 3 to 8 mm regressed to type 3 (34%) or type 4 (40%), and those thicker than 8 mm regressed to type 1 (40%) or type 3 (49%). Factors predictive of type 1 regression included larger tumor base and closer foveolar proximity. Factors predictive of type 3 included older age, larger tumor base, macular location, closer foveolar proximity, and lack of consolidation. Factors predictive of type 4 included familial hereditary pattern, smaller tumor base, greater foveolar distance, and tumor consolidation. CONCLUSIONS Following chemoreduction, most small retinoblastomas result in a flat scar, intermediate tumors in a flat or partially calcified remnant, and large tumors in a more completely calcified remnant.

Incidence of Pineal Gland Cyst and Pineoblastoma in Children With Retinoblastoma During the Chemoreduction Era

PURPOSE To report on the frequency of cysts and tumors of the pineal gland in patients with retinoblastoma. DESIGN Observational retrospective case control study. METHODS SETTING Institutional. study population: Four hundred eight patients treated for retinoblastoma from January 2000 to January 2012 at Wills Eye Institute, Philadelphia, Pennsylvania, USA. OBSERVATION PROCEDURE Magnetic resonance imaging (MRI) features of the pineal gland were evaluated in all patients with retinoblastoma. Characteristics of patients with pineal cysts and pineoblastoma were reviewed. MAIN OUTCOME MEASURES Comparison of frequency of pineal gland cyst and pineoblastoma in children managed with systemic chemoreduction vs other methods. RESULTS Of 408 patients, treatment included systemic chemoreduction in 252 (62%) and nonchemoreduction methods in 156 (38%). Overall, 34 patients (8%) manifested pineal gland cyst and 4 (1%) showed pineoblastoma. Of all 408 patients, comparison (chemoreduction vs nonchemoreduction) revealed pineal cyst (20/252 vs 14/156, P = .7) and pineoblastoma (1/252 vs 3/156, P = .1). The pineal cyst (n = 34) (mean diameter 4 mm) was asymptomatic (n = 34), followed conservatively (n = 34), and with minimal enlargement (n = 2, 9%) but without progression to pineoblastoma. The cyst was found in 22 germline and 12 nongermline patients (P = .15). Among the 4 patients with pineoblastoma, all had germline mutation and 2 had family history of retinoblastoma. Among all patients with family history of retinoblastoma (n = 45), 2 (4%) developed pineoblastoma. The pineoblastoma was asymptomatic in 2 patients and symptomatic with vomiting and headache in 2 patients. The mean interval from date of retinoblastoma detection to pineal cyst was 2 months (median 2, range 0-8 months) and to pineoblastoma was 27 months (median 28, range 7-46 months). Management included aggressive chemotherapy and radiotherapy, with 2 survivors. CONCLUSIONS Pineal gland cyst was incidentally detected in 8% of retinoblastoma patients, causing no symptoms, and without progression to pineoblastoma. Pineoblastoma was detected in 1% of patients and fewer patients who received systemic chemotherapy developed pineoblastoma, possibly indicating a systemic protective effect.

Autofluorescence Of Choroidal Hemangioma In 34 Consecutive Eyes

Purpose: The purpose of this study was to describe the autofluorescence (AF) features of choroidal hemangioma in 34 consecutive patients. Methods: Standard fundus photography and AF photography (580-nm excitation, 695-nm barrier filter) were performed on all patients. The clinical features were correlated with AF features. The main outcome measures were autofluorescence features of choroidal hemangioma (intrinsic AF) and overlying retinal pigment epithelium (extrinsic AF). Results: There were 27 eyes with circumscribed choroidal hemangioma (CCH) and 7 eyes with diffuse choroidal hemangioma (DCH). The mean patient age was 53 years for CCH and 15 years for DCH. Intrinsic AF of untreated CCH was generally iso-AF (n = 7, 58%) and for treated CCH was hypo-AF (n = 15, 100%). Extrinsic AF of CCH disclosed hyper-AF (orange pigment and fresh subretinal fluid) and hypo-AF (retinal pigment epithelium hyperplasia, fibrous metaplasia, and atrophy). Intrinsic AF of untreated DCH was generally hypo-AF (n = 2, 67%) and for treated DCH was hypo-AF (n = 3, 75%). Extrinsic AF of DCH was similar to CCH. Conclusion: Choroidal hemangioma shows little intrinsic AF. Overlying orange pigment and fresh subretinal fluid show hyper-AF and retinal pigment epithelium hyperplasia and atrophy show hypo-AF.

Ranibizumab for coloboma-related choroidal neovascular membrane in a child

Optic nerve and retinochoroidal coloboma are caused by incomplete closure of the embryonic fissure during fetal development.(1) Affected patients carry a risk for retinal detachment and less so for choroidal neovascular membranes (CNVM) secondary to the altered anatomy. Because of the rarity of this condition and the even more unusual occurrence of such complications, there are only a few case reports on the treatment of coloboma-related CNVM. Herein we report the results of ranibizumab and laser photocoagulation for coloboma-related CNVM in a child.