Jonathan W. Kim

A Phase I/II Study of Direct Intraarterial (Ophthalmic Artery) Chemotherapy with Melphalan for Intraocular Retinoblastoma: Initial Results

OBJECTIVE To develop a technique that would allow us to cannulate repeatedly the ophthalmic artery of young children with advanced retinoblastoma, to find a dose of melphalan that would be tolerable and tumoricidal for retinoblastoma when given intraarterially, and to study the local ocular and systemic side effects of intraarterial melphalan in these children. DESIGN Phase I/II clinical trial. PARTICIPANTS Ten children with advanced retinoblastoma (Reese-Ellsworth V) eyes who were indicated for enucleation were entered into an institutional review board-approved protocol of ophthalmic artery infusion of melphalan to avoid enucleation. METHODS Cannulation of the ophthalmic artery was performed by a femoral artery approach using microcatheters while the children were under anesthesia and anticoagulated. Chemotherapy (melphalan) was infused into the artery over a 30-minute period. MAIN OUTCOME MEASURES Ophthalmic examinations, retinal photography, and electroretinograms were used to document local toxicity, whereas physical examinations and complete blood counts were used to measure systemic toxicity. RESULTS The ophthalmic arteries were successfully cannulated in 9 cases (total, 27 times), as many as 6 times in 1 patient. Dramatic regression of tumors, vitreous seeds, and subretinal seeds were seen in each case. No severe systemic side effects (sepsis, anemia, neutropenia, fever, or death) occurred. No transfusions were required (red cells or platelets). Three patients developed conjunctival and lid edema that resolved without treatment. There was no toxicity to the cornea, anterior segment, pupil, or motility. One (previously irradiated) eye developed retinal ischemia; another eye had no toxicity after intraarterial chemotherapy but did develop a radiationlike retinopathy after brachytherapy. Vision stabilized or improved in all but 1 patient after treatment. Electroretinograms were generally poor (advanced eyes were treated), but in 2 cases, the electroretinogram improved after treatment (and resolution of a retinal detachment). Seven eyes avoided enucleation. Two intraarterially treated eyes were enucleated, with no viable tumors identified pathologically. CONCLUSIONS We developed a technique of direct ophthalmic artery infusion of melphalan for children with retinoblastoma. The technique had minimal systemic side effects (one patient had grade 3 neutropenia) and minimal local toxicity. Among the first 9 cases treated with this technique, 7 eyes destined to be enucleated were salvaged.

Long-term outcomes of Group D eyes in bilateral retinoblastoma patients treated with chemoreduction and low-dose IMRT salvage.

To evaluate outcomes of Group D eyes of bilateral retinoblastoma patients treated with primary chemoreduction and external beam radiation as salvage.

Donor site complications of hard palate mucosal grafting.

Summary The use of hard palate mucosal grafts (HPG) in eyelid surgery is becoming increasingly popular. We present two palatal donor site complications that have not been previously reported. The first is an oro-nasal fistula discovered 1 week following surgery. The second is oral candidiasis, which compromised healing of the palatal donor site. With appropriate treatment, both complications resolved shortly after surgery. Careful preoperative evaluation and postoperative follow-up is recommended to recognize and manage these complications.

Current management strategies for intraocular retinoblastoma.

Survival rates for retinoblastoma patients have increased dramatically over the last century, with documented 5-year survival figures reaching 87–99% in developed countries. During the last decade, there has been a dramatic paradigm shift in the treatment approach for intraocular retinoblastoma, emphasising chemoreduction protocols and minimising the use of external beam radiation. The recognition of the increased risk for second non-ocular cancers with external beam radiation contributed to the growing emergence of chemotherapy. Although chemoreduction protocols vary slightly between institutions, many centres are currently treating intraocular retinoblastoma with carboplatin, vincristine and etoposide as a three-drug regimen given in two to six cycles. Clinical studies have demonstrated that systemic chemotherapy must be combined with other modalities, such as laser treatment and cryotherapy, for adequate tumour control and many eyes with advanced intraocular disease require salvage therapy with radiation or enucleation. Therefore, modern centres treating retinoblastoma continue to manage patients with a variety of modalities, individualising the therapy according to the patient’s presentation and clinical course.

Topical treatment options for conjunctival neoplasms.

Topical therapies offer a nonsurgical method for treating conjunctival tumors by delivering high drug concentrations to the ocular surface. Over the past ten years, topical agents have been used by investigators to treat various premalignant and malignant lesions of the conjunctiva, such as primary acquired melanosis with atypia, conjunctival melanoma, squamous intraepithelial neoplasia and squamous cell carcinoma of the conjunctiva, and pagetoid spread of the conjunctiva arising from sebaceous cell carcinoma. Despite the enthusiasm generated by the success of these agents, there are unanswered questions regarding the clinical efficacy of this new nonsurgical approach, and whether a single topical agent can achieve cure rates comparable with traditional therapies. Furthermore, the long-term consequences of prolonged courses of topical chemotherapeutic drugs on the ocular surface are unknown, and the ideal regimen for each of these agents is still being refined. In this review, we present specific guidelines for treating both melanocytic and squamous neoplasms of the conjunctiva, utilizing the available data in the literature as well as our own clinical experience at the Memorial Sloan-Kettering Cancer Center.

Controversies in the management of optic nerve sheath meningiomas

Optic nerve sheath meningiomas (ONSM) comprise 2% of orbital tumors and 1% of all intracranial meningiomas. Meningiomas arising from the sheath of the optic nerve are benign tumors originating from the outer ‘‘cap cells’’ of the arachnoid layer in the intraorbital, intracanicular, or intracranial segments of the optic nerve. The most common histologic subtypes of ONSM are benign meningothelial and transitional forms; malignant optic sheath meningiomas have never been reported. ONSM typically enlarge slowly within the subarachnoid space, compressing the optic nerve or its blood supply and causing visual deterioration. Despite the rarity of ONSM and their relatively benign behavior, meningiomas arising from the optic nerve sheath are important because they represent the archetype of a compressive optic neuropathy.

Lower-eyelid blepharoplasty

In summary, the concept of one operation for all patients who present for lower-eyelid blepharoplasty should be abandoned. Surgical procedures should be tailored for each individual, depending on the sources of concern and the anatomical defects present. The vast majority of patients are served best by combining transconjunctival blepharoplasty with adjunctive procedures. Transcutaneous lower-lid blepharoplasty has few indications. By combining and choosing the proper techniques, the aesthetics surgeon can achieve lower-eyelid rejuvenation while preserving function and minimizing complications.

Published international classification of retinoblastoma (ICRB) definitions contain inconsistencies--an analysis of impact.

Purpose: To determine the impact of subtle differences (most notably in their classification of group E eyes) in two published versions of the ICRB (Philadelphia and the Childrens Hospital Los Angeles). Methods: Analysis of a series of 96 eyes with intra-ocular retinoblastoma. Results: The disparate criteria of the 2 published ICRB schemas affected group assignment of 5.2% of the eyes (25% of the group E eyes). Conclusion: Discrepancies need to be reconciled to ensure accurate and uniform application of the ICRB.

Orbital recurrence of retinoblastoma following enucleation

Background/aims: To determine the incidence, clinical presentation and histopathological profile of patients developing orbital recurrence following enucleation for retinoblastoma. Methods: A cohort of 1674 consecutive patients undergoing enucleations between 1914 and 2006 was retrospectively reviewed to identify cases of orbital recurrence. A detailed chart review of all identified patients with orbital recurrence following enucleation was performed. The main outcome measures were histopathological features of the enucleated globe, clinical presentation, status of metastatic disease and clinical outcomes of treatment at last follow-up. Results: There were 71 cases of orbital recurrence identified in the study, for an incidence of 4.2% (71 of 1674 cases). The diagnosis of orbital recurrence was made between 1 and 24 months after enucleation (mean 6 months), with 69 of the 71 patients (97%) being diagnosed within the first 12 months. Over a follow-up period of 3–208 months (mean 34.8 months), 60 of 71 patients developed metastatic disease (85%), and 53 of 71 patients died from metastatic retinoblastoma (75%). For the subgroup of cases diagnosed as having orbital recurrences after 1984, 10 of 11 patients (91%) are alive and well. Conclusions: All patients undergoing enucleation for retinoblastoma need to be followed carefully for the first 2 years after surgery for the possibility of orbital relapse. The majority of retinoblastoma patients with orbital tumour recurrence develop systemic metastatic disease, although mortalities appear to be improving in the modern era.

Correction of lower eyelid retraction by transconjunctival retractor excision and lateral eyelid suspension.

PURPOSE To investigate the effectiveness of a procedure that addresses both the lower eyelid retractors and the lateral canthus in the treatment of patients with lower eyelid retraction. METHODS Through a combined lateral canthotomy and full-length transconjunctival incision, the lower eyelid retractors were disinserted across the horizontal length of the eyelid, recessed to the inferior fornix, and excised. A lateral canthopexy elevated the mobilized eyelid, and horizontal length disparity was corrected. RESULTS Forty lower eyelid operations in 23 patients yielded good results; all patients attained significant improvement in both eyelid position and function. No reoperations were required during a mean follow-up period of 28 months. CONCLUSION Although not ideal for severe cases requiring posterior lamellar spacers or anterior lamellar (skin) grafts, this union of techniques successfully treats many types of lower eyelid retraction.