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.
Objective To observe the therapeutic efficacy and complications of plaque radiotherapy (PRT) combined with transpupillary thermotherapy (TTT) on choroidal melanoma (CM). Methods Thirty unilateral CM patients (30 eyes, including 15 males and 15 females) were treated by PRT and TTT. The visual acuity ranged from 0.1 to 0.8 with an average of 0.3plusmn;0.2. The largest base diameter of tumor ranged from 6.8 mm to 17.9 mm with an average of (11.3plusmn;2.8) mm；The tumor height ranged from 3.9 mm to 10.6 mm with an average of (7.2plusmn;2.4) mm. The criteria of controlled local tumor: based on B-scan ultrasound measurement, the tumor was considered as ldquo;growingrdquo; if tumor height increased 2 mm or tumor largest base diameter increased 250 mu;m, otherwise the tumor was considered ldquo;controlledrdquo;. The followup ranged from 15 to 57 months with an average (33.01plusmn;9.81) months. The local tumor control rate, enucleation rate and visual acuity, complications after treatment were observed.Results The tumor largest base diameter after treatment ranged from 4.6 mm to 17.0 mm with an average (9.79plusmn;3.35) mm, which had statistically significant difference（t=2.195，F=0.49；P=0.032) with that before treatment. The tumor height after treatment ranged from 2.7 mm to 11.9 mm with an average (5.19plusmn;2.57) mm, which had statistically significant difference（t=2.069，F=0.018；P=0.0435) with that before treatment. At the end of follow up, the tumor largest diameter and height increased in two eyes respectively compared with those before treatment. Local tumor control rate was 86.7%. Three eyeballs were enucleated after treatment，the enucleation rate was 10.0%. The visual acuity remained unchanged in 12 eyes，improved in one eye and decreased in 17 eyes. Treatment complications included radiation retinopathy in 12 eyes (40.0%), secondary retinal detachment in three eyes (10.0%), secondary glaucoma in one eye (3.3%), cataract in four eyes (13.3%) and dry eye syndrome in five eyes (16.7%). Conclusion PRT combined with TTT is an effective therapy for choroidal melanoma with less complications.
Objective To investigate the influence of vascular endothelial growth factor (VEGF) antagonist bevacizumab on the growth of human choroidal melanoma (CM) OCM-1 cell xenografts in nude mice, and to explore the probable mechanism.Methods OCM-1 cells were subcutaneously implanted on 18 nude mice to establish ectopic model of human CM. The nude mice with the tumor of 5 mm in diameter were randomly divided into three groups: untreated group (group A), normal saline （NS） group (group B), drug treated group (group C). Bevacizumab was intraperitoneally injected for 14 consecutive days in group C, and the same volume of NS was used at a same way in group B. The volume and weight of implanted tumor as well as inhibitory rates of drug on tumor were calculated, ki67 and survivin proteins were measured with immunohistochemistry, and the mRNA expression of VEGF and survivin were assessed by RT-PCR.Results The volume and weight of tumor was (598.86plusmn;321.81) mm3, (0.66plusmn;0.15) g; (1 715.15plusmn;278.16) mm3, (1.54plusmn;0.39) g and (1 750.23plusmn;206.36) mm3, (1.54plusmn;0.31) g in groups C, A and B, respectively. There were significant differences between group C and A (F=34.53, P=0.00) and group C and group B (F=8.69, P=0.01). The inhibitory rate of these three groups were 57.14%, 5.31%, 6.25%, respectively, and the proliferation index (PI) of ki67 in these three groups were (51.85plusmn;1.32)%, (46.30plusmn;1.39)%, (27.90plusmn;0.90)%, respectively, there were significant differences in ki67 PI between C group and A or B group (H=15.17, P=0.00). The expression of survivin mRNA was (0.49plusmn;0.02), (0.82plusmn;0.05) and (0.61plusmn;0.05) in groupss C, A and B, respectively, there were significant differences between C group and A or B group (F=15.17, P＜0.05) . The expression of VEGF mRNA was (0.32plusmn;0.08), (0.73plusmn;0.07), (0.80plusmn;0.04) in groups C, A and B, significant difference was found between group C and A or B group (F=12.05，P＜0.05). Conclusion Bevacizumab can inhibit the growth of human CM in nude mice probably by inhibiting the activity of VEGF and downregulating survivin expression of the tumor as well as inhibiting the growth of the tumor.
Objective To investigate the expression of pigment epitheliumderived factor (PEDF) and vascular endothelial growth factor (VEGF) in choroidal melanoma. Methods The expression of VEGF and PEDF protein in fifty-eight cases of paraffinembeded choroidal melanoma samples was measured by immunohistochemistry, the expression of PEDF mRNA in thirtynine choroidal melanoma samples was assayed by in situ hybridization. Results PEDF protein was detected in 13/58 cases (22.4%) of choroidal melanoma, the positive rate in nonsclerainvasion group (12/38, 31.6%) was higher (Plt;0.05) than that in sclerainvasion group (1/20, 5%). VEGF protein was detected in 43/58 cases (64%) of choroidal melanoma, the positive rate in nonsclerainvasion group (25/38, 65.8%) was lower (Plt;0.05) than that in sclerainvasion group (18/20, 90%). The expression of PEDF mRNA was detected in 18/39(46.2) cases, the positive rate in nonsclerainvasion group was higher (Plt;0.05) than that in sclerainvasion group. Conclusions Imbalanced expression of VEGF and PEDF in choroidal melanoma may play a key role in the angiogenesis, tumor progression and metastasis.
Objective To evaluate the clinical and histopathological features of diffuse choroidal melanoma. Methods The clinical and histopathological data of 11 patients with diffuse choroidal melanoma were reviewed retrospectively. Those patients were referred to Tianjin Eye Hospital because of visual loss or ophthalmalgia (10 cases), or Coats disease with secondary glaucoma and atrophy bulbi (1 case). The clinical disgnosis included choroidal tumor or melanoma (8 cases), absolutestage glaucoma (2 cases) and atrop hy bulbi with Coats disease (1 case). Nine patients received enucleation, and 2 patients received enucleation combined with orbital exenteration. The cellular proliferation was assessed by Ki-67staining. Results All 11 tumors had grown flatly with a wide base ranged from 12 to 20 mm, and tumor thickness ranged from 2 to 4 mm. There were 9 cases of mixed cell type, 1 case of epithelioid cell type and 1 case of necrotic cell type. The tumors invaded into the sclera in 7 cases and orbital cavity in 3 cases. Secondary glaucoma was found in 7 cases. On average, 9% (7%13%) of tumor cells were Ki67 positive and most of them located at the tumor base. There were more Ki67 positive epithelioid tumor cells than Ki67 positive spindle-shaped cells. Conclusions Diffuse choroidal melanoma had a special growth pattern and is difficult to be recognized, sometimes could be misdiagnosed as glaucoma or other choroidal tumors. With its wide base, this tumor could easily invade the orbit and metastate, and its prognosis is very poor.
Objective To evaluate safty and effects of a single photodynamic therapy(PDT) for circumscribed choroid hemangiomas. Methods We performed a retrospective analysis of 11 eyes of 10 patients who were reated with single standard PDT. Of 10 patients, 6 males, 4 females；mean 40 .2 years old；of 11 eyes, 6 left eyes, 5 right eyes; 1 patient who both eyes wer e involved. Follow-up time varied from 1month to 14months, mean 6.2 month. Results After treatment, all tumors show various degrees of regression and subretinal fluid were absorbed completely or partly. The visual acuity of 8 eyes improved; that of 3 eyes unchanged. Conclusions PDT is effective modality for circumscribed choroid hemangiomas. (Chin J Ocul Fundus Dis,2008,24:111-113)
Objective To isolate and purify the melanoma stem cells (MSC) in choroidal melanoma OCM-1 cells. Methods OCM-1 cells were resuscitated, and after cultured in standard Dubecco's modifided Eagle's medium (DMEM)/F12, they were cultured in serum-free medium (SFM). The cultured MSC were isolated and purified, and the positive rate of CD133, the specific markers of neurostem cells, was observed by flow cytometry (FCM). The 6th generation of the cells were stained by musashi-1 immunocytochemistry, and the rate of the positive cells was observed under the microscope. Results After the Adherent OCM-1 cells cultured in SFM, the number of the adherent number decreased obviously. The cells at the 6th generation grew as the suspended gobbets, which represented the typical grow manner of the stem cells. Positive CD133 could be found in the cells of different generations, which was 2.5％, 21.7％, and 57.8％ in the non-isolated OCM-1 cells, the 1st generation of isolated cells, and the 2nd generation cells, respectively. The positive rate of CD133 in the cells at the sixth generation was 79.8% with b positive expression of musashi-1. Conclusion MSC is in the human choroidal melanoma OCM-1 cells. The suspended stem cells may be purified by limited differentiation and serial passage in SFM. (Chin J Ocul Fundus Dis, 2007, 23: 87-90)
Objective To evaluate the efficacy of transpupillary thermotherapy（TTT）on three kinds of intraocular benign tumors. Methods Seventeen patients with 3 kinds of intraocular tumors，3 eyes of 3 patients with papillary hemangioma，9 eyes of 9 patients with choroidal hemangioma and 8 eyes of 5 patients with choroidal osteoma were treated with transpupillary thermotherapy.All patients underwent pretreatment ocular examination，including visual acuity，biomicroscopy for anterior segment and fundus examination，fundus fluorescein and indocyanine green angiography，optic coherence tomography，perimetry test，ultrasonography，and CT.TTT was conducted with infrared diode laser at810nm.with power of 360-1200 mW;beam diameter of 3 mm or combined 2-5 spots according to the tumor size;the exposure time was 60-80 seconds.The treatment was completed in one session，and another treatment was given 1-3 month later if active leakage demonstrated.The follow-up period was 6-36 months（mean 14.5 month）. Results The best corrected visual acuity with Snellen chart on average for papillary hemangioma was 0.17 before TTT and 0.27 after;for choroidal hemangioma was 0.39 before TTT and 0.46 after;for choroidal osteoma was 0.20 before TTT and 0.31 after.Three eyes with papillary hemangioma had operation to release subretinal fluid and intraocular laser coagulation;the tumor remained reddish color with dilated vessels and patches of hemorrhages on the surface.After TTT the color appeared pale yellowish，hemorrhages absorbed，subretinal fluid subsided，and choroidal retinal atrophy disclosed along the lower border of the tumor.In 9 eyes with choroidal hemangioma, the red-light area disappeared, subretinal fluid subsided, and the pigment proliferation in the treatment area was found.Eight eyes with choroidal osteoma had choroidal neovessels and macular hemorrhages;after TTT blood disappeared，subretinal fluid absorbed，and the color of tumor showed pale yellow with dark pigment and thin scar tissue.There was no significant complication associated with TTT. Conclusions Transpupillary thermotherapy is effective on papillary hemangioma，circumscribed choroidal hemangioma and choroidal osteoma either as preliminary or supplementary treatment. (Chin J Ocul Fundus Dis, 2006, 22:181-184)
Objective To investigate the development and metastasis of malignant choroidal melanoma cell strain OCM-1-gfp modified with green fluorescent protein(GFP) and the factors which affected the tumor biological behaviors. Methods GFP was transfected into malignant melanoma cell strain OCM-1.Melanoma cells with high and stable expression of GFP were injected into subretinal space and the subcutaneous space of hind leg of Balb/c nude mouse respectively in order to establish orthotopic and heterotopic transplanted tumor models.The development and metastasis process of orthotopic tumor models was observed directly by fluorescence microscope，and the size of the hypodermal tumor was measured by vernier.The expressions of 13 genes in melanoma were detected by means of immunohistochemistry staining. Results Malignant choroidal melanoma cell strain OCM-1 stably expressed GFP and preserved the characteristics of parental generation，OCM-1-gfp may develop melanoma and continue to metastasize in nude mouse.Positive expression of most of the antibodies，including Rb，p53，p21，E2F，NFkappa;B，cyclin D1，proliferation cellular nuclear antigen（PCNA），bcl2、bclXL/S，bax，and epithelial growth factor（EGF）and its receptor（EGFR），was found.While the staining of inhibition gene p16 was negative. Conclusions GFP is the marker for observing the development and metastasis of malignant choroidal melanoma in vivo.The rate of tumor formation and development process in orthotopic models does not differs much from which in heterotopic models of malignant choroidal melanoma.The expressions of lots of genes in malignant choroidal melanoma developed from OCM-1-gfp including p16、p53、NFkappa;B，cyclin D，PCNA，EGF，and EGFR are abnormal. (Chin J Ocul Fundus Dis, 2006, 22: 170-173)