Intravitreal Melphalan Injections Research Articles

Efficacy of intravitreal injections of melphalan in the treatment of retinoblastoma vitreous seeding.

The introduction of intravitreal injections of melphalan (IVIM) has significantly improved the efficacy of retinoblastoma treatment and the prognosis for eye preservation. To evaluate the results of using IVIM to treat retinoblastoma vitreous seeding. This was a clinical, retrospective, single-center study. Twenty-six children (27 eyes) who met all of the following inclusion criteria qualified for the study: 1) active vitreous seeding at the time of retinoblastoma diagnosis; 2) IVIM performed between 1 January 2017 and 30 September 2020; and 3) a minimum follow-up period of 12 months since the last IVIM. Doses of 20-40 μg melphalan per injection were used. The eye observation period from the last IVIM to the last ophthalmic examination averaged 32.41 months (median 30.00; range 13.00-56.00). Success (no active tumors in the vitreous body) was achieved in 24 eyes (88.9%), and a doubtful result (recurrence in the retina with a difficult-to-determine etiology) in 2 eyes (7.4%). In 1 eye (3.7%), despite treatment, active tumors were still present in the vitreous body. Out of all 27 eyes, 4 eyeballs were removed, but the direct cause of enucleation was not vitreous seeding. There were no complications in the form of intraocular inflammation, extraocular retinoblastoma or distant metastases. There was 1 case of anterior uveitis and 1 case of cataract. The IVIM is a highly effective and safe form of treatment for retinoblastoma vitreous seeding.

Vitreous metastasis from cutaneous melanoma: diagnosis and management

Purpose: To report the clinical findings, treatments, and outcomes in a series of patients with vitreous metastasis from cutaneous melanoma. Methods: This single-center, retrospective, interventional case series included patients with biopsy-confirmed vitreous metastasis from cutaneous melanoma diagnosed between 1997 and 2020. Standard 23- or 25-gauge pars plana vitrectomy was performed for diagnostic sampling. Sclerotomies were treated with double or triple freeze-thaw cryotherapy. Perioperative intravitreal injections of melphalan (32 µg/0.075 mL) were administered, when indicated. Visual acuity, intraocular pressure, and systemic and ocular treatment responses were reported. Results: Five eyes of five patients with unilateral vitreous metastasis from cutaneous melanoma were identified. The median age at diagnosis was 84 (range, 37-88) years. The median follow-up after ophthalmic diagnosis was 28 (8.5-36) months; one patient did not have a follow-up. The initial visual acuity ranged from 20/30 to hand motions. Baseline clinical findings included pigmented or non-pigmented cellular infiltration of the vitreous (5/5), anterior segment (4/5), and retina (3/5). Four patients had secondary glaucoma. Systemic therapy included checkpoint inhibitor immunotherapy (n=3, all with partial/complete response), systemic chemotherapy (n=2), surgical resection (n=3), and radiation (n=2). The median time from primary diagnosis to vitreous metastasis was 2 (2-15) years. One patient had an active systemic disease at the time of vitreous metastasis. The final visual acuity ranged from 20/40 to no light perception. Ophthalmic treatment included vitrectomy in all five patients, intravitreal administration of melphalan in three, and intravitreal administration of methotrexate in one. One patient required enucleation, and histopathology revealed extensive invasion by melanoma cells. Conclusions: Vitreous metastasis from cutaneous melanoma can present as a diffuse infiltration of pigmented or non-pigmented cells into the vitreous and may be misdiagnosed as uveitis. Diagnostic pars plana vitrectomy and periodic intravitreal chemotherapy may be indicated.

Ocular and systemic toxicity of high-dose intravitreal topotecan in rabbits: Implications for retinoblastoma treatment

Although many more eyes of children with retinoblastoma are salvaged now compared to just 10 years ago, the control of vitreous seeding remains a challenge. The introduction of intravitreal injection of melphalan has enabled more eyes to be salvaged safely but with definite retinal toxicity. Intensive treatment with high-dose intravitreal topotecan may be a strategy to control tumor burden because of its cell cycle-dependent cytotoxicity and the proven safety in humans. Therefore, we evaluated the ocular and systemic safety of repeated high-dose intravitreal injections of topotecan in rabbits.Systemic and ocular toxicity was assessed in non-tumor-bearing rabbits after four weekly injections of three doses of topotecan (10 μg, 25 μg, and 50 μg) or vehicle alone. Animals were evaluated weekly for general and ophthalmic clinical status. One week after the last injection, vitreous and plasma samples were collected for drug quantification and the enucleated eyes were subjected to histological assessment.Weight, hair loss, or changes in hematologic values were absent during the study period across all animal groups. Eyes injected with all topotecan doses or vehicle showed no signs of anterior segment inflammation, clinical or histologic evidence of damage to the retina, and ERG parameters remained unaltered throughout the study. Vitreous and plasma topotecan lactone concentrations were undetectable.Four weekly intravitreal injections of topotecan up to 50 μg in the animal model or a 100 μg human equivalent dose were not toxic for the rabbit eye. High doses of topotecan may show promising translation to the clinic for the management of difficult-to-treat retinoblastoma vitreous seeds.

Combination of Brachytherapy and Intravitreal Chemotherapy in the Treatment of Retinoblastoma with Vitreous Seeding

Purpose: The aim of this study was to report the efficacy of combined intravitreal chemotherapy (IVC) and ruthenium-106 brachytherapy in retinoblastoma, either as first-line or second-line treatment, following systemic chemoreduction or intra-arterial chemotherapy. Methods: Retrospective data of 18 eyes from 18 patients treated with IVC and brachytherapy from August 2014 to December 2019 were collected. Results: The method described was our first-line therapy in 6 patients, whereas it was used as second-line treatment after chemoreduction in the remaining 12 patients. The eyes showed the following classification at initial presentation: 2 group B eyes, 3 group C eyes, and 13 group D eyes. The mean follow-up was 19.5 months (range 2–53 months). The mean patient age at brachytherapy was 34.0 months (range 15–83 months). The median prescribed dose at the tumour base and apex was 574.5 ± 306.7 Gy and 88.5 ± 12.2 Gy, respectively. The ocular retention rate was 66.7%. Six eyes had to be enucleated due to uncontrollable subretinal and recurrent vitreous seeding, tumour relapse, recurrence of a solid tumour elsewhere in the eye, and persistent vitreous bleeding with loss of tumour control. The mean number of intravitreal injections of melphalan was 5.0. Two patients received a simultaneous injection of topotecan for insufficient therapeutic response. With regard to radiogenic complications, we could observe temporary retinal and vitreous bleeding (27.8%), serous retinal detachment (44.4%), and radiogenic maculopathy and retinopathy (11.1%). None of the children showed metastatic disease during follow-up. Conclusion: Ruthenium-106 plaque therapy in combination with IVC is an effective local therapy with good tumour control rates even in advanced eyes. Overall, the analysed therapeutic approach shows an acceptable side-effect profile, especially when considering that external-beam radiation therapy and systemic polychemotherapy or at least the number of cycles needed, with their increased incidence of adverse events, can thus be avoided.

Outcomes of intravitreal melphalan for vitreous seedings in retinoblastoma resistant to systemic chemotherapy

PurposeTo determine the efficacy of intravitreal injection of melphalan for vitreous seedings resistant to systemic chemotherapy. Methods and materialProspective non comparative study investigates 105 consecutive eyes of 105 retinoblastoma patients in a tertiary care hospital. Patients with persistent or recurrent vitreous seeds were included in the study. Injection melphalan was prepared under aseptic conditions. Injection was given at 2–4 mm away from the limbus using 27gauge needle. Cryotherapy was applied at injection site before and during removal of needle. Eye was copiously irrigated soon after the injection to minimize the chances of surface toxicity. After injection intravitreal melphalan, eye pad was applied for 2 h and patients were instructed to instill topical antibiotic and steroid drops for one week. Patients were examined the next day and then weekly till 3rd week. At each follow up, examination under microscope (EUA) and indirect ophthalmoscopy was done. Retinal images were taken using retcam MII for comparison with the previous ones. ResultsTwenty-five (23.8%) out of 105 eyes showed complete regression of vitreous seeds with one injection of intravitreal melphalan after one month. Thirty-one (29.5%) eyes required further 3 intravitreal injections for complete regression, while thirty-four (32.4%) eyes required further 6 intravitreal injections for complete regression. Fifteen (14.3%) eyes did not show regression of vitreous seeds even after 6 intravitreal injections and were planned for second line chemotherapy. ConclusionIntravitreal injection melphalan shows promising results in the treatment of vitreous seeds in retinoblastoma, resistant to systemic chemotherapy.

Vitreous Seed Classification and Regression Patterns in Eyes With Retinoblastoma.

This work subclassifies retinoblastoma vitreous seeds and evaluates the efficacy, regression patterns, and adverse effects of combination intravitreal melphalan and topotecan chemotherapy for resistant and recurrent vitreous seeds. A retrospective review of medical records was conducted of patients with retinoblastoma and resistant or recurrent vitreous seeds who were treated with intravitreal melphalan and topotecan injections from August 2014 to July 2018. Main outcome measures included regression pattern, time for regression, time for recurrence of seeds, treatment outcomes, and ocular toxicity. Nineteen eyes received 138 intravitreal injections over 74 treatment sessions (mean, 7.26 injections per eye); vitreous seeds regressed in 18 eyes. Of cloud vitreous seeds, curvilinear (n = 2) and sphero-linear (n = 2) subtypes were observed. During regression, some sphere seeds showed an intermediary streak-like pattern and took longer to regress (mean, 11.13 ± 14.05 months and 11.67 ± 8.62 injections) than those without the intermediary streak-like pattern (mean, 3.55 ± 2.57 months and 4.2 ± 1.87 injections). Mean follow-up was 34.87 ± 21.09 months (median, 35 months; range, 11-96 months). Anterior segment toxicity was seen in 10 (53%) eyes and posterior segment toxicity in 5 (26%) eyes. Kaplan-Meier survival estimates for globe salvage at 2 years was 94% and 73% at 5 years. Kaplan-Meier survival for vitreous seed-free status was 94% at 2 years and 65% at 5 years. An expanded vitreous seed classification system that further subcategorizes hitherto unrecognized vitreous seed morphology is needed. An intermediate streaking process results in a prolonged regression time for sphere vitreous seeds.

Successful treatment of ciliary body medulloepithelioma with intraocular melphalan chemotherapy: a case report

BackgroundIntraocular medulloepithelioma is commonly treated with primary enucleation. Conservative treatment options include brachytherapy, local resection and/or cryotherapy in selected cases. We report for the first time the use of targeted chemotherapy to treat a ciliary body medulloepithelioma with aqueous and vitreous seeding.Case presentationA 17-month-old boy with a diagnosis of ciliary body medulloepithelioma with concomitant seeding and neovascular glaucoma in the right eye was seen for a second opinion after parental refusal of enucleation. Examination under anesthesia showed multiple free-floating cysts in the pupillary area associated with iris neovascularization and a subluxated and notched lens. Ultrasound biomicroscopy revealed a partially cystic mass adjacent to the ciliary body between the 5 and 9 o’clock meridians as well as multiple nodules in the posterior chamber invading the anterior vitreous inferiorly. Fluorescein angiography demonstrated peripheral retinal ischemia. Left eye was unremarkable. Diagnosis of intraocular medulloepithelioma with no extraocular invasion was confirmed and conservative treatment initiated with combined intracameral and intravitreal melphalan injections given according to the previously described safety-enhanced technique. Ciliary tumor and seeding totally regressed after a total of 3 combined intracameral (total dose 8.1 μg) and intravitreal (total dose 70 μg) melphalan injections given every 7–10 days. Ischemic retina was treated with cryoablation as necessary. Three years later, ab interno trabeculotomy followed by 360° gonioscopy-assisted transluminal trabeculotomy 6 months later was performed for uncontrolled intraocular pressure despite antihypertensive drugs combined to cyclophotocoagulation and 7 intravitreal anti-VEGF injections for recurrent iris neovascularization. Cataract was removed at the same operative time. The child has remained disease- and metastasis-free at a 5-year follow-up since the last melphalan injection (25-month follow-up after the combined lensectomy-trabeculotomy) with a controlled intraocular pressure under topical quadritherapy and a best corrected Snellen visual acuity of 0.08.ConclusionsWe report for the first time complete regression of a non-infiltrating ciliary body medulloepithelioma with seeding achieved with only a small number of intracameral and intravitreal melphalan injections. Concomitant secondary neovascular glaucoma and cataract needed appropriate management to allow long-term eye and vision preservation.

Intravitreal melphalan therapy for vitreous seeds in retinoblastoma: Implementation and outcomes of a new chemotherapy protocol.

Retinoblastoma is the most common paediatric ocular tumour, which appears in the retina. Without treatment, retinoblastoma grows and destroys the internal ocular globe architecture, even leading to metastasis. When treated, overall survival is close to 97%, the alkylating drug melphalan being the most extensively used chemotherapeutic agent in localised treatment. The aim of this study is to describe the implementation of a new intravitreal chemotherapy retinoblastoma treatment protocol for children implanting vitreous seeds through intravitreal melphalan injections and to evaluate the patients' health outcomes treated with it. Between December 2014 and July 2018, seven patients were treated with this protocol. They received a mean of 3.3 cycles of intravitreal melphalan with standard doses of 30 mcg per cycle. In the seven eyes treated in our hospital, the response was as expected; three eyes with vitreous seedings (43%) were successfully treated. The main adverse effects presented by all patients were scars at cryogenisation points. In two patients, the appearance of 'salt and pepper' retinopathy was reported. Oncology pharmacists, as part of the treatment team, can provide information about recommended doses, expected adverse effects, stability of preparations, most appropriate method of processing, packaging, and methods of drug administration, to ensure efficacy and especially safety in the administration of these drugs.

An audit of retinal lymphoma treatment at the University of California San Francisco.

To evaluate retinal lymphoma treatment at the University of California San Francisco. Prospective observational audit. Patients were treated systemically, usually with: methotrexate, temozolomide, and rituximab induction; etoposide consolidation; and maintenance with lenalidomide or another immunomodulatory agent. Persistent disease was treated initially by ocular radiotherapy or intravitreal melphalan and latterly by vitrectomy. The cohort comprised eight females and two males. The median age was 58 years (range, 38-73). Ocular manifestations were initially unilateral in four patients. Vitreous and subretinal infiltrates were initially present in 16 and 12 eyes, respectively, with three eyes having vision of 20/200 or worse. Four patients had a history of central nervous system (CNS) lymphoma. The median ophthalmic follow-up was 37 months (range, 8-56). Diagnostic and therapeutic vitrectomy were performed in 10 and 2 eyes, respectively. All patients had systemic chemotherapy and eight received maintenance immunotherapy. Four patients underwent ocular radiotherapy, bilaterally in two. One patient received bilateral intravitreal melphalan injections. Two eyes of four patients developed lymphoma during the study and two patients developed CNS disease. At study close, subretinal deposits were subtle in nine eyes and more prominent in two, whereas vitreous infiltrates were minimal in nine eyes, mild in one and moderate in one. The latest visual acuity was significantly worse than at presentation in two eyes and better in two. All patients were alive with no active CNS disease. Subretinal lymphomatous infiltrates respond to systemic chemotherapy with immunomodulatory maintenance, but dense vitreous infiltrates require therapeutic vitrectomy.

Heterochromia following intravitreal chemotherapy in two cases

Intravitreal chemotherapy is recognized as an effective treatment for retinoblastoma with vitreous (and occasionally subretinal) seeding refractory to intravenous or intra-arterial chemotherapy. However, this treatment carries with it the risk of toxicity to both the posterior and anterior segments of the eye, including retinal pigment epithelial mottling, ischemic/hemorrhagic retinopathy, posterior synechia, cataract, scleral necrosis, and focal iris depigmentation. We report 2 cases of iris heterochromia secondary to profound iris stromal depigmentation following intravitreal melphalan and topotecan injections.

Ocular toxicity of intravitreal melphalan for retinoblastoma in Chinese patients

BackgroundTo evaluate the efficacy, complications, and clinical characteristics, including the ocular toxicity, of intravitreal melphalan(IVM) treatment for vitreous seeding in Chinese retinoblastoma patients.MethodsThis was a retrospective, non-comparative analysis including 30 consecutive eyes of 23 patients with viable persistent or recurrent vitreous seeding following retinoblastoma treatment. All of the eyes received IVM injections (20–33 μg). Vitreous seeding control, determination of the ocular toxicity, and the clinical characteristics of intravitreal melphalan treatments were observed.ResultsThe mean patient age at the time of the injection was 28 months (median = 22 months, range = 12–50 months). In total, 80 injections were administered in 30 eyes, the overall enucleation-free survival rate was 83.3% (25/30). The complications included retinal pigment epithelium (RPE) and choroidal atrophy (19/30, 63.3%), pupillary synechiae (13/30, 43.3%), iris atrophy (12/30, 40%), retinal vascular occlusion (12/30, 40.0%), optic atrophy (6/30, 20%), vitreous hemorrhage (3/30, 10%), persistent hypotonia and phthisis bulbi (4/30 13.3%), and cataracts (8/30, 26.6%). Twelve eyes demonstrated grade 3 or greater IVM-associated retinal or anterior segment toxicity post injection. Mean dosage given showed significant difference between the groups. There were no significant differences in the retinal toxicity grades regarding the seed classification or seed regression patterns.ConclusionsIntravitreal melphalan is an effective treatment for refractory vitreous seeding from retinoblastoma, but exhibits both anterior and posterior segment toxicity in Chinese patients.

Posterior Vitreous Detachment and the Associated Risk of Retinal Toxicity with Intravitreal Melphalan Treatment for Retinoblastoma

Background/Aims: The presence of a posterior vitreous detachment (PVD) may play a role in the development of severe retinal toxicity following intravitreal melphalan (IVM) injection for vitreous seeding. We aimed to evaluate the incidence of PVD in retinoblastoma eyes and its association with retinal toxicity after IVM. Methods: We reviewed 112 eyes of 81 retinoblastoma patients with B-scan images available for review from 2010 to 2017. A cohort with vitreous seeding treated with IVM was compared to a cohort that did not undergo injection. The primary outcome measure was the presence of PVD at diagnosis and after treatment. Secondary measures included IVM-associated retinal toxicity and other ocular complications. Results: The incidence of PVD was 20% at diagnosis, and in eyes with B-scans available both at diagnosis and after treatment 18% of eyes developed a PVD over the course of therapy, more frequently after IVM (p = 0.05). Of 34 eyes receiving IVM treatment, the incidences of posterior segment toxicity and globe salvage were similar between eyes with and without PVD (p = 0.4015 and 0.52, respectively). Conclusion: In this cohort of patients, there did not appear to be an association with the presence of PVD during IVM and the development of retinal toxicity.

Changes in Retinal Thickness on OCT from Intravitreal Melphalan

ABSTRACT: PURPOSE To quantify changes in central retinal thickness (CRT) on intraoperative spectral domain optical coherence tomography (SD-OCT) pre- and post- intravitreal melphalan (IVM) injection for retinoblastoma (Rb). METHODS Retrospective review of 5 eyes of 5 patients with Rb without macular tumor involvement treated with IVM injection for vitreous seeding. Automated and manual ETDRS measurements of CRT sub-foveally were derived from SD-OCT images pre- and post- IVM injection. RESULTS Mean age of patients at first IVM was 512 days (range=133-1005). Mean follow-up duration was 266 days (range=21-532). Grade 1, Grade IV, and Grade V chorioretinal toxicity occurred in 2 eyes, 2 eyes, and 1 eye, respectively. Overall, mean automated and manual CRT decreased pre- to post-IVM injection from 316.87 to 248.18 μm and from 314.14 to 243 μm, respectively. CONCLUSION There is clinically evident thinning of central retinal thickness on OCT in patients with intravitreal melphalan related Grade IV and V chorioretinal toxicity.

Safety and efficacy of posterior sub-Tenon's carboplatin injection versus intravitreal melphalan therapy in the management of retinoblastoma with secondary vitreous seeds.

To evaluate the safety and efficacy of posterior sub-Tenon's carboplatin injection compared to intravitreal melphalan injection in the management of retinoblastoma (RB) with secondary vitreous seeds. The outcome measures were vitreous seeds regression, need for other treatment modalities to achieve ocular salvage and treatment side effects. A prospective interventional comparative nonrandomized study included RB eyes developed secondary vitreous seeds during the period of follow up. They subdivided into two groups: study group I where posterior sub-Tenon's carboplatin (20 mg/2 mL) was injected and study group II where intravitreal melphalan (20 µg /0.1 mL) was injected. The injections repeated every 2-4wk. Thirty-three eyes were included in the study. Seventeen eyes (16 patients) in study group I and 16 eyes (16 patients) in study group II. Ten eyes (30.3%) were completely salvaged following local chemotherapies. Ocular salvage was 23.5% following posterior sub-Tenon's carboplatin injection versus 37.5% following intravitreal melphalan raised to 47.1% and 75% with addition of external beam radiotherapy (EBR) with no statistically significant difference between the study groups (P=0.16). A statistically significant correlation was found between ocular salvage rate and type of vitreous seeds either dust, spheres and clouds (r=0.42, P=0.015) and eyes harbor new solid tumor growth (r=0.35, P=0.045). The mean and median follow up periods following local chemotherapy injections were 2.0y in the study group I and 2.37y in the study group II. Few complications were reported: periorbital edema in all eyes and ocular motility disturbances in 13 eyes (76.5%) following posterior sub-Tenon's carboplatin injection. Vitreous hemorrhage developed in 2 eyes (12.5%) and localized retinopathy in 5 eyes (31.25%) following intravitreal melphalan. Local chemotherapy for treatment of RB with secondary vitreous seeds is safe and can salvage 30.3% of eyes without EBR. There is a superiority of intravitreal melphalan in ocular salvage however, no statistically significant difference between both groups.

Retinal Toxicity of Intravitreal Melphalan in Albino Rabbits

Background: Intravitreal melphalan injections have been used for treating retinoblastoma with vitreous seeds. The aim of this study was to evaluate the safety margins for intravitreal melphalan, using clinical observations, electrophysiological testing and morphological observations. Methods: In this experimental study, 18 albino rabbits, were treated with intravitreal injection of 0.1 ml melphalan solution to the right, experimental eye, and were divided into 4 dose groups: 5 μg (N=4); 15 μg (N=4); 30 μg (N=5); 60 μg (N=5). The left, control eye, of each rabbit was injected with 0.1 ml saline. Clinical examination, electroretinography (ERG) and visual evoked potentials (VEP) were conducted at baseline and periodically throughout the 4-week follow-up. The eyes were then enucleated and the retinas were prepared for histology and glial fibrillary acidic protein (GFAP) immunocytochemistry. Results: No clinical, ERG, or histologic damage were found in rabbits treated with 5 μg melphalan. However, expression of glial fibrillary acidic protein was detected in retinal Muller cells of the experimental eyes and not in the control eyes. With all other doses of melphalan, dose-dependent funduscopic changes, ERG amplitude, histological damage and GFAP expression were found. VEP responses were similar between the experimental eyes and control eyes of all rabbits regardless of melphalan dose injected into the eye, indicating no change in retinal output. Conclusions: These findings indicate that intravitreal melphalan dose of 5 μg in rabbits, approximately equivalent to 10 μg in human, appears to be safe, but induce a mild stress to the retina. However, higher doses are toxic, and their utilization should be executed with caution, particularly if visual potential exists.

Assessment of retinoblastoma RNA reflux after intravitreal injection of melphalan

BackgroundIntravitreal injection of chemotherapy in retinoblastoma eyes with vitreous seeds may lead to a risk of extraocular tumour dissemination that has not been assessed so far.AimsTo develop a sensitive and...

Short-term efficacy of intravitreal injection of melphalan for refractory vitreous seeding from retinoblastoma

Objective: To evaluate the efficacy and safety of intravitreal chemotherapy for refractory vitreous seeding from retinoblastoma. Methods: Retrospective series of case studies. Nine patients (13 eyes) with the diagnosis of refractory vitreous seeding were enrolled in Department of Ophthalmology of Eye& ENT Hospital of Fudan University from March 2014 to October 2015.There were 6 males and 3 females. Children aged 8 to 40 months, median age of 18 months. In the 13 eyes, 3 eyes were E period, 9 eyes were D period, and 1 eyes were C period. The fundus was examined by indirect ophthalmoscope and recorded by RetcamIII. Systemic chemotherapy was performed using the VEC protocol, that is vincristine, etoposide, and carboplatin. Local treatment also involves cryotherapy and/or thermotherapy. All patients were treated with intravitreal injection of melphalan. They underwent intravitreal melphalan, once every 4 weeks, with an average of 3 times of injections. The treatment dose of melphalan is 20 to 40 μg per dose. Observe the vitreous seed control and complications of therapy. Results: Vitreous seeds control was attained in all cases. There was no case of orbital extension or remote metastasis. Complications included retinal pigment epithelial and choroidal atrophy in 7 eyes, pupillary synechia and iris atrophy in 2 eyes,retinal vasculitis and vascular occlusion in 2 eyes, optic atrophy in 2 eyes, vitreous hemorrhage in 1 eye, and temporary hypotony in 3 eyes. Conclusions: Intravitreal melphalan is an effective treatment for refractory vitreous seeding from retinoblastoma. High dose may lead to local adverse reactions. (Chin J Ophthalmol, 2017, 53: 570-574).

Long-term outcomes of Group D retinoblastoma eyes during the intravitreal melphalan era.

To evaluate outcomes of Group D retinoblastoma (Rb) eyes during the intravitreal melphalan era. Retrospective chart review of patients diagnosed with Group D Rb from 2011 to 2016 was done. Overall, 76 Group D eyes of 68 patients were included; salvage therapy included systemic chemoreduction with vincristine, etoposide, and carboplatin with local consolidation, followed by intravitreal injection of melphalan for recurrent or persistent seeding. External beam radiation was not used as a treatment modality. Primary outcome measurement was globe salvage. Of 76 Group D eyes, 24 were enucleated primarily and 52 were treated with intent to salvage the globe. Systemic chemoreduction salvaged 25 of 52 eyes (48%). Tumor recurrences were diagnosed in 27 eyes (52%); five with massive retinal recurrences underwent enucleation and 22 were treated with intravitreal melphalan injection. Of the 22 injected eyes, 14 (64%) were salvaged and eight required enucleation primarily for retinal recurrences. Success in eradicating vitreous seeds was 100%. The Kaplan-Meier 3-year survival estimate for treated eyes is 76.5% (95% CI: 61.4-86.3). Median follow-up for the group of 76 Group D eyes was 29.5 months (SD 17.9 months). During a 6-year period that included the initiation of intravitreal melphalan at our institution, the salvage rate of treated Group D eyes was 75% (39/52 eyes). Intravitreal melphalan was utilized for ocular salvage in 42% (22/52 eyes). Systemic chemoreduction combined with intravitreal melphalan for seeding demonstrated a high overall salvage rate for Group D eyes in this cohort.

Not All Seeds Are Created Equal: Seed Classification Is Predictive of Outcomes in Retinoblastoma

Intravitreal chemotherapy has emerged as an important modality for treating vitreous seeding in retinoblastoma. A classification system has been described as predictive of response to intravitreal melphalan (IVM) in patients treated predominantly with primary intra-arterial chemotherapy. The objective of this study is to evaluate the outcomes of retinoblastoma treated with intravenous chemotherapy and IVM as salvage for vitreous seeding, and further to determine whether vitreous seed classification (dust, spheres, cloud) is predictive of the total number and dose of IVM injections required for treatment in this cohort. A nonrandomized retrospective review. Retinoblastoma patients treated at a single center with intravenous chemotherapy and IVM. Retrospective review of patients with vitreous seeding from retinoblastoma treated with intravenous chemotherapy and IVM from 2012 to2016. Primary outcome measure was eradication of seeds and globe salvage. Secondary measures included IVM-associated toxicity and complications. Overall, 28 eyes of 25 patients were included, with a total of 110 IVM injections. By seed classification, eyes with dust (n= 15) required a median of 3 injections, spheres (n= 8) required 4 injections, and clouds (n= 5) required 6 injections. Spherical seeds were only seen in recurrent vitreous seeding. Of the 28 treated eyes, 9 were enucleated, 6 for recurrent retinal disease, resulting in an overall globe salvage rate of 68%. The salvage rate secondary to active retinoblastoma was 79%. Dust classification was the most prevalent seeding type of the 9 enucleated eyes. There was 100% regression of vitreous seeds after intravitreal injection and no eye was treated with radiation or enucleated for seeding. Twelve eyes demonstrated grade 3 or greater IVM-associated retinal or anterior segment toxicity post injection. Mean follow-up was 33 months (range, 9-51 months). IVM is an effective treatment for vitreous seeding after intravenous chemotherapy for retinoblastoma. As with eyes treated with intra-arterial chemotherapy, seed classification is predictive of the total number and dose of IVM injections in eyes treated with intravenous chemotherapy. Eyes with clouds required significantly more injections than eyes with dust or spheres.

Intravitreal chemotherapy in the management of vitreous disease in retinoblastoma.

To evaluate the therapeutic outcome of intravitreal melphalan injection in the management of vitreous disease in patients with retinoblastoma. We particularly aimed to assess whether higher melphalan dose with lower number of injections was more effective and associated with fewer side effects. This retrospective, interventional, noncomparative, and nonrandomized study included 39 eyes of 37 patients. Vitreous seeds were classified as dust, sphere, and cloud types. Intravitreal injections were performed through pars plana free of any visible tumor using 30-G needle. Response of the seeds (disappearance, conversion into inactive debris, or progression) and enucleation rate were determined as outcome measures. All patients previously received systemic or intra-arterial chemotherapy. Vitreous seeding was primary in 54% of eyes and secondary in 46% of eyes. Vitreous seeds were classified as dust in 9 (23.1%) eyes, sphere in 24 (61.5%) eyes, and cloud in 6 (15.4%) eyes. Melphalan dose varied between 20 and 40 µg and 20 (51.3%) eyes received >30 µg. The total number of injections was 70 (range 1-5, mean 1.8 per eye). Various types of regression were obtained in 27 (69.2%) eyes. Sphere-type seeds were the most responsive to melphalan. Nonresponse and disease progression were noted in 12 (30.8%) eyes. After a mean follow-up of 11.8 months, 17 (44%) eyes were enucleated. Vitreous hemorrhage (18%) and retinal pigment epithelial alterations (8%) were the most common side effects. Intravitreal melphalan at 30-40 µg in 1 or 2 injections proved effective in 69.2% of eyes with vitreous disease.