In the research process of uveal melanoma (UM), the Collaborative Ocular Melanoma Study (COMS) is a landmark and outstanding clinical study. Its research conclusions are the foundation for today's UM clinical work and guidelines. COMS is the first and largest randomized clinical trials conducted to date, comparing the survival outcomes of two or more treatment regimens for primary malignant intraocular tumors with high reliability. Its research design, methods, and conclusions are still widely cited in this day. Learning from the research experience of COMS, summarizing research data based on Asian populations, and studying treatment methods suitable for Asian UM patients is a powerful supplement to COMS data, but also an expansion of this global research, further improving the level of UM diagnosis and treatment in China.
Objective To observe the different clinical response patterns of uveal melanoma (UM) patients after external scleral plaque radiotherapy (PRT), and to investigate the risk factors of secondary enucleation after treatment failure. MethodsA single-centre retrospective study. Demographic baseline characteristics and clinical data were collected from 465 UM patients treated with 125I external scleral PRT at Beijing Tongren Hospital from March 2011 to September 2017. Among them, 217 were male and 248 were female, tumor all occurred monocularly. The mean age of subjects was 46.7±12.1 years. Reasons for secondary enucleation included local tumor treatment failure, glaucoma, scleral necrosis and patient request. Tumor grading was based on the grading standards established by the American Joint Committee on Cancer (AJCC). The pattern of tumor response after PRT was classified as degenerated type, growth type, stable type or other types according to literature criteria. The median follow-up time after PRT was 59 months to observe tumor changes. Complete follow-up records of 3 or more color doppler ultrasound imaging (CDI) was available in 245 cases. A t-test was performed to compare the patient's age, intraocular pressure, best corrected visual acuity, tumor thickness and maximum basal diameter before treatment; a chi-square test was performed to compare the patient's gender, AJCC T classification of the tumor, whether the ciliary body was involved, presence of subretinal fluid, optic disc invasion and vitreous hemorrhage, tumor shape and location. Kaplan-Meier survival analysis was used to estimate the cumulative probability of secondary enucleation after extra-scleral PRT. Univariate and multivariate Cox proportional hazards regression analyses were used to evaluate the relationship between tumor characteristics and secondary enucleation after extra-scleral PRT. ResultsAmong 465 patients, eecondary enucleation was performed on 78 (16.8%, 78/465) patients during the follow-up period. The 1, 3 and 5 year secondary enucleation rates were 5.4%, 9.3% and 17.1%, respectively. Eye preservation was successful in 387 cases (83.2%, 387/465). Patients treated by secondary enucleation had a larger maximum basal diameter of tumor, a higher proportion of irregular and diffuse morphology, a cumulative macular involved and a higher AJCC T classification, the difference was statistically significant (P＜0.05). There were 115, 76, 27, and 27 cases of degenerated type, stable type, growth type, and other type, respectively. The tumor thickness of the growth type and other types was significantly smaller than that of the degenerated type and the stable type, and the difference was statistically significant (P＜0.05). Univariate Cox analysis showed that the maximum basal diameter of the tumor (HR=1.19), tumor thickness (HR=1.08), AJCC T classification (HR=1.90), growth type response pattern (relative to degenerated type response pattern) (HR=4.20) was associated with failure of eye preservation (P＜0.05). In the multivariate Cox analysis, the largest tumor basal diameter (HR=1.24) and the growth type response pattern (relative to the degenerated type response pattern) (HR=4.59) were still associated with failure of eye preservation (P＜0.05). ConclusionsThe tumor thickness of UM patients with growing and other response patterns after PRT is smaller before treatment; the maximum basal diameter of the tumor and the growing response pattern are independent risk factors for secondary enucleation.
Objective To investigate the histopathological characteristics of choroidal melanoma. Methods The histopathological data from 64 patients with choroidal melanoma were analyzed retrospectively. The tumor size and the cytological types were observed and detected. The locations of the tumor were classified according to the involved part invaded by the anterior margine of the tumor, and the degrees of the development of the tumor were graded according to the extent of the outward infiltration of the tumor cells. Results In 64 patients with choroidal melanoma, There were large, medium, and small tumors in 25(39.1%), 31(48.4%), and 8(12.5%) respectively. The spindle cell type was found in 42 patients (65.6%) including spindle cell A and B type in 15(23.4%) and 27(42.3%) respectively; epithelioid and mixed cell type was found in 7(10.9%) and 10(15.6%) respectively; the other types were found in 5(7.8%). Twenty-five cases（39.1％）had no invasion with sclera, 22（34.4％）had but limited to sclera, 12（18.8％）penetrated through sclera and 5（7.8％）had intra-orbit infiltration. Conclusion The histopathological characteristics of choroidal melanoma are multiple, and spindle cell type is the most common one. The choroidal melanoma can easily invade the sclera. (Chin J Ocul Fundus Dis, 2006, 22: 161-165)
Intraocular tumors is a serious blinding eye disease, which has a serious impact on patients' vision and even life. At present, the main treatments include surgical treatment, radiation therapy, chemotherapy, laser therapy and combination therapy. In recent years, with the wide application of anti-vascular endothelial growth factor (VEGF) in the treatment of ocular diseases, many studies have confirmed that anti-VEGF drugs play an important auxiliary role in the treatment of intraocular tumors and its complications. In terms of the therapeutic effect, intravitreal anti-VEGF combined with other methods have a good prognosis in the treatment of choroidal metastatic carcinoma and retinoblastoma, while the therapeutic effect of uveal melanoma is still controversial. In the treatment of intraocular tumor complications, intravitreal anti-VEGF also has a good effect on the secondary lesions of choroidal osteoma and radiation retinopathy. As for drug safety, intravitreal anti-VEGF can significantly reduce the toxic and side effects of systemic chemotherapeutic therapy. However, the dosage and medication regimen of anti-VEGF drugs in the treatment of intraocular tumors and their complications have not been unified in current studies, and further basic and clinical trials are still needed to explore in the future.
Objective To evaluate the effect of transpupillary thermo therapy (TTT) on the treatment of intraocular tumors. Methods A total of 50 patients with intraocular tumors, including 37 choroidal hemangioma, 2 retinal capillary hemangioma, 5 choroidal osteoma, 4 choroidal melanoma, and 2 retinoblastoma (RB) underwent TTT and were followed up for 1～20 months. Results In 30 patients with choroidal hemangioma (average follow-up was 5.1 months), 29 (96.7%) had pigment scarring in different levels and the retinal detachemnts were partly or completely recovered; 1 had no obvious improvement. The visual acuity was unchanged in 24 (80.0%) patients, improved in 41 (13.3%) and declined in 2 (6.7%). In 2 patients with retinal capillary hemangioma, no effect was found. In 5 eyes (4 patients) with choroidal osteoma (average follow-up was 6 months), no change of the tumor was found in 1 and the atrophic spots were seen in 4; the visual acuity was unchanged in 3, improved in 1 and declined in 1. In 4 patients with choroidal melanoma (average follow-up was 8 months), the tumor was shrunken in 1, unchanged in 2, and enlarged in 1; the visual acuity was unchanged in 2 and declined in 2. In 2 patients with RB, RB was totally shrunken in 1 and partly shrunken in 1. Visual acuity of one child patient who was followed up for 20 months could not be examined, and was unchanged in another one who was followed up for 3 months. No severe complications were found in the patients during the treatment and the follow-up. Conclusions TTT is effective for the treatment of some intraocular tumors except retinal capillary hemangioma. It is a kind of potential treatment for intraocular tumors with few side-effect. (Chin J Ocul Fundus Dis，2003，19：144-148)
Objective To evaluate the role of the cell cycle related genes cyclinD1 and Bcl-2 protein expression in the pathogenesis and infilt ration of the uveal melanoma． Methods Using immunohis tochemistry to detect the cyclinD1 and bcl-2 protein expression in 96 cases of uveal melanoma． Results The expression content of bcl-2 was high in uveal melanoma, and there wasn't any relationship between bcl-2 cell positivity and tumor cell type and extrascleral extension． In contrast, cyclinD1 expression was higher in epithelial cell uveal melanoma than mix cell and spindle cell varieties． There was a positive correlation between cyclinD1 cell positivity and extrascleral extension． Conclusion The expression of bcl-2 protein is important for the survival of the uveal melanoma． CyclinD1 may serve as a sensitive index of its malignancy． (Chin J Ocul Fundus Dis, 2001,17:44-46)
Objective To evaluate the effectivness of photodynamic therapy (PDT) with chloroaluminum sulfonated phthalocyanine (CASPc) in B16F10 melanomas in a rabbit model. Methods B16F10 murine melanoma tumor fragments were implanted transclerally into the subchoroidal space of 38 immunosuppressed New Zealand albino rabbits and examined with indirect ophthalmoscopy and ultrasonography. When the tumors ranged from 2.0~3.8 mm in height, 30 rabbits were treated by PDT, with intravenous injection of CASPc 5 mg/kg, and irradiation at the wavelength of 675 nm of an argon-pumped dye laser after 24 hours. Light dose ranged from 20 J/cm2 to 70 J/cm2. The other 8 animals were treated with light only or photosensitizer only. The animals were followed up for 6~8 weeks. Results The 30 tumor-bearing rabbits were by PDT (laser and CASPc) regressed in 21 animals after treatment. At light doses under 40 J/cm2, tumor regrowth was observed in 9 animals after two weeks of treatment. In all of the 8 control animals, the tumor-bearing eyes were filled with tumor at the third week after implantation with laser doses of 70 J/cm2. Conclusion The study suggest that CASPc PDT may be effective in the treatment of B16F10 choroidal melanomas.(Chin J Ocul Fundus Dis，2004，20：67-132)
Objective To investigate the effects of matrine on proliferation, apoptosis and radiotherapy sensitivity of uveal melanoma cells. MethodsAn animal experiment study. In vitro experiment: MuM2B cells of human choroidal melanoma were randomly divided into control group and matrine 0.25, 0.50, 1.00, 2.00 g/L groups. The cell morphology was observed by transmission electron microscope. Cell proliferation was detected by thiazole blue colorimetry. The mRNA and relative expression levels of CyclinD D (CyclinD), B lymphoblastoma-2 (Bcl-2) and Bcl2-associated X protein (Bax) were detected by real-time polymerase chain reaction and Western blot. In vivo experiment: BALB/C mice were injected with MuM2B cell suspension subcutaneously on the back of forelimb to prepare transplanted tumor model. After successful modeling, they were randomly divided into blank group and matrine treatment group with different concentrations. Mice in blank group were injected with phosphate buffer subcutaneously. Mice in different matrine treatment groups were injected with 15, 25, 50, 100 mg/kg matrine subcutaneously, respectively, for 7 consecutive days. The tumor was weighed and its volume was measured after the last administration. Single factor analysis of variance was used to compare different groups. The t test was used for pairwise comparison between groups. ResultsIn the control group, the cell structure was normal, the distribution was uniform, and no or rare nuclear pyknosis was seen. With the increase of matrine dosage, the nuclear pyretosis increased gradually and cell morphology changed obviously. Compared with the control group, the cell survival rate in 0.50, 1.00 and 2.00 g/L groups gradually decreased with matrine concentration increasing and treatment time prolongating, the relative expression levels of CyclinD and Bcl-2 mRNA and protein gradually decreased, and the relative expression levels of Bax mRNA and protein gradually increased. Under the same radiation dose X-ray irradiation, the cell survival rate of 0.50, 1.00 and 2.00 g/L groups gradually decreased, and the differences were statistically significant (P＜0.05). Compared with blank group, the tumor weight and volume of mice in different doses of matrine group were significantly decreased, and the differences were statistically significant (P＜0.05). ConclusionMatrine can down-regulate the expression of CyclinD and Bcl-2, up-regulate the expression of Bax, promote the apoptosis of MuM2B human melanoma cells, inhibit cell proliferation, and enhance cell radiosensitivity.
Uveal melanoma (UM) is one of the most common primary intraocular malignancy in adults. The incidence of UM is lower in Asia than in Europe and the United States, however, the age of onset of UM patients in Asia is earlier than in the European and American populations. With the improvement of economic living standards in recent years, UM as a rare intraocular tumor has been gradually recognized by the public. In the past 10 years, the research of UM in China has been characterized by a large number and rapid development. Among them, the direction of molecular genetics represented by non-coding RNA, the frontier development of potential anticancer drugs for UM and Chinese traditional medicines are the research hotspots for scholars in China. In the past 10 years, China has made a relatively complete understanding and research progress on the pathogenesis, diagnosis and treatment of UM. On the other hand, compared with European and American countries, China still lacks in frontier research such as immunotherapy. With the further efforts of Chinese ophthalmology researchers and research teams, and with the further development of scientific research in my country, it is believed that the mechanism affecting tumors can be further elucidated, providing more possibilities for treatment and improving the prognosis of UM patients in China.
Objective To observe the macular morphological changes of choroidal melanoma with coherence tomography (OCT) after plaque radiotherapy (PRT). Methods A total of 48 patients (48 eyes) with choroidal melanoma who underwent125I PRT were enrolled in this study. All the patients were examined documenting OCT to get the image of macula. The macula of all the patients was not involved. The median visual acuity was 0.4plusmn;0.2, which ranged from 0.02 to 1.0. There were 18 eyes (37.5%) with retinal detachment, 12 eyes (25.0%) with retinal pigment epithelium (RPE) changes, seven eyes (14.6%) with macular edema, epimacular membrane, detachment combined with edema, exudation and RPE changes, 11 eyes (22.9%) with normal macular structure. The median follow-up time was (10.4plusmn;5.9) months, which ranged from one to 24 months. The tumor control situation and visual acuity were observed in follow-up period. The same equipment and methods of OCT were used to return visit in follow-up period. The macular morphological changes at the final visit and its relationship with PRT and visual acuity were contrastively analyzed. Results All the patients had good control of tumor. The vision acuity improved in two eyes (4.2%), unchanged in 10 eyes (20.8%), and decreased in 36 eyes (75.0%). The differences of the visual acuity was statistically significant between before and after treatment (Z=-3.778,P＜0.05). There were 13 eyes (27.1%) with retinal detachment; nine eyes (18.8%) with RPE changes; 17 eyes (35.4%) with macular edema, detachment combined with edema, exudation and RPE changes; six eyes (12.5%) with proliferation, atrophy, detachment combined with edema, exudation and epimacular membrane;three eyes (6.3%) with normal macular structure. There were 15 patients (31.3%) with two or more abnormal macular morphology after PRT. Conclusions Retinal detachment, RPE changes, macular edema and exudation are common abnormal macular morphology after PRT. The incidence rate of abnormal macular morphology is increased. There are 31.3% patients with two or more abnormal macular morphology.