Retinoblastoma (RB) is second only to leukemia in childhood, and is the most common primary malignant tumor of the eye in children, with an incidence of about 1/20,000 and an increasing trend in recent years, with about 7202-8102 new RB cases per year worldwide, with familial and hereditary tendencies [1-2]. The tumor mostly occurs before the age of 3 years, 25% of both eyes are involved, and the incidence occupies the first place among ocular tumors, accounting for 33.8% of ocular tumors and 70% of intraocular tumors (Figure 1). It is highly malignant and can cause systemic metastasis and death [1,3]. Currently, the most widely used treatment modalities are ophthalmopexy, systemic combined chemotherapy, and local radiotherapy [2,4]. In particular, children with progressive Rb (Reese-Ellsworth grade V) have to choose total eye removal to preserve life, with an almost 100% eye removal rate, leaving a lifelong disability that brings a significant burden to the family and society [5]. In recent years, clinical reports of intraocular stage retinoblastoma treated by superselective ophthalmic artery intervention with melphalan have emerged abroad, and although the number of cases is relatively small, the results have shown high efficiency and eye-preservation rates [5-7]. The neurovascular surgery department of the Armed Police General Hospital has been carrying out superselective ophthalmic artery interventional perfusion of melphalan for intraocular stage retinoblastoma since 2009, and has achieved certain efficacy, which is summarized in the analysis of its technical points and clinical safety and efficacy. Enrollment conditions and observation index: This study was a retrospective study and was approved by the hospital ethics committee. The tumors were all primary or recurrent Rb Reese-Ellsworth grading grade V, accounting for more than 50% of the retinal area. Eight eyes (12.3%) had stage C, 38 eyes (58.5%) had stage D, and 19 eyes (29.2%) had stage E according to the international intraocular stage RB staging (IIRC). No history of systemic chemotherapy, radiotherapy or local treatment 1 month prior to this treatment. There were no abnormal symptoms or signs other than the primary disease. All children had normal electrocardiogram, cardiac enzymes, liver function, kidney function, coagulation function, and peripheral blood trisomy before surgery. There were no contraindications to interventional treatment. The parents of the children were fully communicated with before the operation and signed the consent form for the interventional procedure. Changes in systemic performance, local changes in the eye and complications related to the interventional technique were the main observation indicators before and after treatment. The systemic performance indicators included temperature, heart rate, cardiac enzymes, liver and kidney function, and blood routine changes, which were recorded three times before, 3 d after, and 10 d after the operation, respectively. Local examination of the affected eye included postoperative eye movement, periocular and eyelid skin swelling, indirect ophthalmoscopy, ocular ultrasound, CT or MRI. In addition to observing the changes of tumor size before and after treatment, we should also observe the presence of vitreous hemorrhage, ocular artery vascular malformation, the relationship between tumor and macula, optic papilla and other important functional areas, and the presence of vitreous implantation, subretinal implantation and retinal detachment. Technical points of superselective ophthalmic artery interventional perfusion melphalan for intraocular stage retinoblastoma (RB): (1) Path selection: The core purpose of superselective interventional intra-arterial perfusion chemotherapy technology is to superselect the affected ophthalmic artery blood vessels through microcatheters, slowly perfuse chemotherapeutic drugs into the ophthalmic artery and enter the tumor tissue through the central retinal artery and other tumor blood supply arteries of the ophthalmic artery, forming high blood concentration in the tumor local, without a large amount of chemotherapeutic drugs entering the systemic. A. Internal carotid artery-ocular artery type: the route used in most cases, where the microcatheter is placed at or into the opening of the ophthalmic artery under the guidance of a microguide. b. External carotid artery-ocular artery: used in cases where the ophthalmic artery is slender or occluded. One of the more commonly used routes is external carotid artery-medial meningeal artery/paramedian meningeal artery-ocular artery. (2) Criteria for microcatheter in place: After the microcatheter is in place, the contrast agent is slowly pushed along the microcatheter with a 1 ml syringe under fluoroscopy. After the chemotherapeutic drug infusion was completed, the above operation was repeated to clarify that the microcatheter was not displaced, and if it was displaced, additional chemotherapeutic drugs could be considered (Figure 2). (3) Chemotherapeutic drug selection, dose, infusion method and duration of treatment: Melphalan (Melphalan), chemically known as levulinic acid nitrogen mustard, is a cell cycle non-specific drug mainly used in the treatment of multiple myeloma, breast and ovarian cancer, with the main side effect of bone marrow suppression, and has been used in recent years for interventional chemotherapy of endoretinal retinoblastoma [5-7]. The drug dose size of melphalan correlates with the type of route used, with route A melphalan doses of 6-8 mg/eye/dose and route B melphalan doses of 8-10 mg/eye/dose. The drug was continuously pumped by an infusion pump for more than 30 min. The effect of chemotherapy was reviewed 1 month after the first chemotherapy session, and the decision to continue the superselected interventional intra-arterial infusion chemotherapy was made based on the results. (4) Interventional safety precautions in children: limit the total contrast dose in children to 4 ml/kg body weight (Nuctech Parker 320); pay attention to radiation protection, use small field of view as much as possible, low X-ray dose, limit the fluoroscopy time, reduce the pulse (3-6 fps), and use a lead suit to cover the gonads. (5) Operation steps: intravenous anesthesia, 1% lidocaine local subcutaneous and infiltration around the femoral artery sheath layer by layer, puncture the right femoral artery by Seldinger technique, after seeing bright red pulsatile bleeding, place the guidewire through the puncture needle, keep the arterial sheath rotated into it when placing it, and fix it with a film after placement. 4F single-curved contrast catheter is used to perform routine internal and external carotid artery imaging on the affected side, and according to the imaging results The treatment route is selected based on the imaging results. The microcatheter was placed in place under the guidance of a microguide according to the microcatheter in place criteria, and the medication was dispensed and pumped. Among the 53 children (65 eyes) in this group, 14 cases had one chemotherapy in 18 eyes, 35 cases had two chemotherapy in 43 eyes, 4 cases had three chemotherapy in 4 eyes, and 116 cases were treated with superselective ophthalmic artery interventional perfusion melphalan, including 98 cases in route A and 18 cases in route B. The success rate of surgical technique was 100%. The tumors in 55 of the 65 eyes were reduced to varying degrees, with an efficiency rate of 84.6% (Figure 3), and 10 eyes were removed due to tumor progression (15.4%). In the 55 eyes without eye removal, no disease progression was detected during the follow-up period. Postoperative complications: (1) Systemic complications: All cases did not show systemic symptoms such as fever, abnormal heart rate, shock and sepsis after treatment, and there was no serious decrease in white blood cells, hemoglobin and platelets in postoperative routine blood and biochemical examination, and no obvious liver and kidney function damage. (2) Ocular complications: The most common complications were eyelid swelling (20/65, 30.8%) and eyelid ptosis (15/65, 23.1%), vitreous hemorrhage in two eyes (2/65, 3.1%), exophthalmos in one eye (1/65, 1.5%) and ocular fixation in one eye (1/65, 1.5%) of two children. No other local complications such as intraocular cellulitis and retinal atrophy were observed in any of the children. (3) Surgical complications: All children did not have anesthesia accidents, the interventional procedures were smooth, the heart rate was stable, and no complications such as cerebrovascular damage and brain damage were seen on postoperative MRI. There was no postoperative femoral artery puncture site hematoma or retroperitoneal hematoma. Discussion Retinoblastoma is a tumor relatively sensitive to chemotherapy, and systemic chemotherapy has achieved more desirable results in the treatment of children with retinoblastoma, improving the rate of eye preservation, and is currently the main means of retinoblastoma treatment [8-9]. However, systemic chemotherapy can cause serious complications such as myelosuppression, sepsis, and secondary tumors, which are difficult for clinicians to overcome, thus limiting the scope of application of systemic chemotherapy in the treatment of retinoblastoma [8-9]. In 1958, Reese [10] and others used direct carotid artery puncture injection of TEM (triethylene melamine) for local chemotherapy of retinoblastoma, and in 1966, Kiribuchi [11] used transfrontal and supraorbital artery injection of 5-fluorouracil to treat retinoblastoma. In 1966, Kiribuchi [11] used local chemotherapy with 5-fluorouracil injection via the frontal artery and supraorbital artery for retinoblastoma; in the late 1980s, the Japanese began to use interventional techniques of balloon occlusion and internal carotid artery infusion (and femoral artery puncture, placing a balloon catheter distal to the affected ophthalmic artery, inflating it, and blocking the flow while infusing chemotherapeutic drugs in its proximal internal carotid artery) to treat retinoblastoma with melphalan injection. retinoblastoma. All of the above attempts have attempted to reduce the complication rate of systemic chemotherapy by increasing the concentration of chemotherapeutic agents in the tumor trophoblastic vessels (mainly the ophthalmic artery) and reducing the amount of systemic chemotherapeutic agents used. These methods have been proven to reduce the complication rate to different degrees and have achieved relatively satisfactory treatment results. Although these methods are an improvement over conventional systemic chemotherapy, they are not strictly speaking superselective intra-arterial infusion chemotherapy techniques, because a large amount of drug still enters the normal blood vessels outside the target vessel during the infusion process, reducing drug utilization and increasing the risk of complications. 2008 Abramson [5] first reported the use of In 2008, Abramson [5] reported the first encouraging results of treating 10 children with Reese-Ellsworth grade V retinoblastoma using a transfemoral artery puncture-microcatheter superselective ophthalmic artery infusion melphalan, a superselective interventional intra-arterial infusion chemotherapy technique. Studies have shown that this approach can increase intraocular arterial chemotherapy drug concentrations by a factor of 10 to 30 compared to systemic chemotherapy, with negligible concentrations in peripheral blood, greatly reducing the incidence of systemic complications. In addition, the chemotherapeutic drugs perfused through the ophthalmic artery can enter the body circulation and then flow into the tumor lesion secondarily through the body circulation, playing a secondary chemotherapeutic role [12]. Only 2 of the 10 children in this study had their eyes removed due to progression of the disease, and none of them had systemic complications from chemotherapy, whereas the rate of eye removal in children with Reese-Ellsworth grade V RB was almost 100% before this treatment modality. The results of the treatment of children in this cohort showed that treatment with superselective interventional intra-arterial instillation chemotherapy was 84.6% effective, and 10 of the eyes were removed due to tumor progression (15.4%). Forty-four eyes that did not undergo removal were followed up to date, and no disease progression was observed. The efficacy was generally consistent with the results reported abroad [5-7]. The age of onset of retinoblastoma is less than 3 years in more than 80% of children, and the youngest child in this group was only 4 months old, which makes it difficult to perform the intervention. The technique of superselective ophthalmic artery intervention with melphalan for intraocular stage retinoblastoma (RB) is invasive and requires the child to be under anesthesia. Whether intraoperative anesthetic drugs, chemotherapeutic drugs, and radiation damage will cause impairment of the child’s organ function, affect the child’s hematopoietic function, cause secondary tumors, and whether the child can tolerate the local toxicity of the treated eye are all issues that must be faced in the implementation of this technique. Carol et al [13-14] suggested that the systemic complications caused by transocular arterial interventional chemotherapy may be related to (1) reaction to contrast agents, (2) longer procedure time, and (3) high perfusion volume, long perfusion time, and high drug concentration of melphalan. And local complications in the eye may be related to necrosis of arterial vascular epithelial cells or toxic effects on nerves in the eye after local hyperperfusion of melphalan [15]. Our data and the results reported from abroad prove that the success rate and safety effectiveness of the technique of intraocular stage retinoblastoma (RB) treatment by superselective ophthalmic arterial interventional perfusion with melphalan can be greatly improved by careful angiographic analysis, gentle operation, ideal microcatheter in place, and reduction of contrast agent use dose and procedure time, resulting in a significant reduction in the incidence of postoperative complications [5-7]. Although this technique is more effective, it is currently performed in only a few large medical interventional centers, even in the world, due to the high technical equipment requirements. The long-term therapeutic efficacy of this treatment requires large case-control studies and long-term patient follow-up. In conclusion, superselective interventional intra-arterial infusion chemotherapy is a safe and effective treatment that greatly reduces the rate of eye removal in children with retinoblastoma, represents an important breakthrough in the treatment of retinoblastoma, and is an important part of the standardized comprehensive treatment of retinoblastoma.