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Key Points: Question: Is the long-term efficacy of adjuvant 3-cycle carboplatin, etoposide, and vincristine (CEV) regimen considered noninferior to the standard 6-cycle CEV regimen in patients with pathologically high-risk retinoblastoma? Findings: In this noninferiority randomized clinical trial of 187 patients with a median follow-up of 79.0 months, 5-year disease-free survival for patients receiving 3-cycle and 6-cycle CEV was 90.4% and 89.2%, respectively. The difference met the noninferiority margin criterion of 12%. Meaning: A 3-cycle CEV regimen demonstrated noninferiority compared with a 6-cycle approach and was and proved to be an efficacious adjuvant chemotherapy regimen for individuals diagnosed with pathologically high-risk retinoblastoma. Importance: Adjuvant therapy is an important and effective treatment for retinoblastoma. However, there is a lack of head-to-head clinical trials comparing 3 vs 6 cycles of CEV chemotherapy (carboplatin, etoposide, and vincristine) for enucleated unilateral retinoblastoma with high-risk pathological features. Objective: To assess whether 3 cycles of CEV chemotherapy is noninferior to 6 cycles for enucleated unilateral retinoblastoma with high-risk pathological features. Design, Setting, and Participants: This double-center, randomized, open-label, noninferiority trial was conducted at 2 premier eye centers in China and included 187 patients who had undergone enucleation for unilateral retinoblastoma with high-risk pathological features (massive choroidal infiltration, retrolaminar optic nerve invasion, or scleral infiltration) between August 2013 and March 2024. The final date of follow-up was March 21, 2024. Interventions: Patients were randomly assigned to receive either 3 (n = 94) or 6 (n = 93) cycles of CEV chemotherapy regimen after enucleation. Main Outcomes and Measures: The primary end point was disease-free survival, with a noninferiority margin of 12%. Secondary end points encompassed overall survival, safety, economic burden, and the quality of life of children. Results: All 187 patients (median [IQR] age, 25.0 [20.0-37.0] months; 83 [44.4%] female) completed the trial. Median (IQR) follow-up was 79.0 (65.5-102.5) months. Five-year disease-free survival was 90.4% for the 3-cycle group vs 89.2% for the 6-cycle group (difference, 1.2% [95% CI, −7.5% to 9.8%]), which met the noninferiority criterion (P =.003 for noninferiority). The 6-cycle group experienced a higher frequency of adverse events, greater reduction in quality of life scores, and increased costs compared with the 3-cycle group. Conclusions and Relevance: Among patients with unilateral pathologic high-risk retinoblastoma, 3 cycles of CEV chemotherapy resulted in 5-year disease-free survival that was noninferior to 6 cycles of CEV chemotherapy. Trial Registration: ClinicalTrials.gov Identifier: NCT01906814 This randomized clinical trial examines whether 3 cycles of carboplatin, etoposide, and vincristine chemotherapy is noninferior to 6 cycles for enucleated unilateral retinoblastoma with high-risk pathological features. [ABSTRACT FROM AUTHOR]

Cell cycle deregulation is involved in the pathogenesis of many cancers and is often associated with protein kinase aberrations, including the polo-like kinase 1 (PLK1). We used retinoblastoma, an intraocular malignancy that lacks targeted therapy, as a disease model and set out to reveal targetability of PLK1 with a small molecular inhibitor ON-01910.Na. First, transcriptomic analysis on patient retinoblastoma tissues suggested that cell cycle progression was deregulated and confirmed that PLK1 pathway was upregulated. Next, antitumor activity of ON-01910.Na was investigated in both cellular and animal levels. Cytotoxicity induced by ON-01910.Na was tumor specific and dose dependent in retinoblastoma cells, while nontumor cells were minimally affected. In three-dimensional culture, ON-01910.Na demonstrated efficient drug penetrability with multilayer cell death. Posttreatment transcriptomic findings revealed that cell cycle arrest and MAPK cascade activation were induced following PLK1 inhibition and eventually resulted in apoptotic cell death. In Balb/c nude mice, a safe threshold of 0.8 nmol intravitreal dosage of ON-01910.Na was established for intraocular safety, which was demonstrated by structural integrity and functional preservation. Furthermore, intraocular and subcutaneous xenograft were significantly reduced with ON-01910.Na treatments. For the first time, we demonstrated targetability of PLK1 in retinoblastoma by efficiently causing cell cycle arrest and apoptosis. Our study is supportive that local treatment of ON-01910.Na may be a novel, effective modality benefiting patients with PLK1-aberrant tumors. [ABSTRACT FROM AUTHOR]

Purpose: The purposed of this study was to investigate the fibroblast growth factor receptor 2 (FGFR2) gene in one Chinese family with Crouzon syndrome and to characterize the related clinical features., Methods: One family underwent complete ophthalmic examinations, and two patients were diagnosed with Crouzon syndrome. Genomic DNA was extracted from leukocytes of peripheral blood collected from the family and 100 unrelated control subjects from the same population. Exons 8 and 10 of FGFR2 were amplified by polymerase chain reaction (PCR) and directly sequenced. We performed ophthalmic examinations, including best-corrected visual acuity, slit-lamp examination, fundus examination, Pentacam, Goldmann perimetry, and computed tomography (CT) of the skull., Results: The two patients were affected with shallow orbits and ocular proptosis, accompanied by midface hypoplasia, craniosynostosis, and clinically normal hands and feet. A heterozygous FGFR2 missense mutation c.866A>C (Gln289Pro) in exon 8 was identified in the affected individuals, but not in any of the unaffected family members and the normal controls., Conclusions: Although FGFR2 mutations and polymorphisms have been reported in various ethnic groups, especially in the area of osteology, we report, for the first time, the identification of one new FGFR2 mutation in Chinese patients with Crouzon syndrome.

Purpose: To explore factors which lead to recurrence of idiopathic orbital inflammatory pseudotumor (IOIP)., Methods: Idiopathic orbital inflammatory pseudotumor in 209 cases between Jan 1, 1978 and Dec 31, 1999 in our hospital was evaluated retrospectively. The comparison of clinical and pathological parameters between patients with at least one episode of recurrence and those with no recurrence at all was performed and analyzed using logistic regression method., Results: Follow-up results (with a mean follow-up time of 3.4 years, ranging from 0.5 year to 21.0 years) showed that the recurrence rate of IOIP was 41%. Sex and proptosis were associated with the recurrence of IOIP. Male gender was more likely to relapse than female counterparts, with the male being 52% and female being 25%. The severer the proptosis is, the higher the rate of recurrence. Among the clinical subtypes of IOIP, the rate of recurrence (17%) in cases with dacryoadenitis was the lowest, followed by anterior local orbital mass (44%), posterior orbital mass (54%), myositis (75%) and diffuse subtype (100%). However, the clinical subtypes did not show significant relationship with the recurrence of IOIP., Conclusions: Male gender and severe proptosis are associated with a higher recurrent rate in patients with IOIP.

Purpose: To summarize the clinical manifestation of thyroid-associated ophthalmopathy (TAO) with elevated intraocular pressure (IOP), and to analyze the contributing factors., Methods: One hundred and six cases (188 eyes) of ocular hypertension in 339 cases (597 eyes) with TAO were collected from 1994 to 2001 and their clinic manifestations were summarized and analyzed., Results: It was demonstrated that the incidence of ocular hypertension in TAO was 31.3%, and was more frequently found in the male than in the female. The elevated IOP in TAO was found to be partially related to compression of the eyeball by enlarged extraocular muscles, the elevated intraorbital pressure as result of the proliferation of intraorbital connective tissue and the enlargement as well as swelling of extraocular muscles. It was also related to the severity of TAO other than the course of TAO. The ocular hypertension in most cases can be controlled with reduction of IOP by methylprednisolone or orbital decompression., Conclusion: Specific clinical features were found in TAO patients with ocular hypertension. It should be differentiated with primary glaucoma. The IOP in most cases can be controlled by prompt and effective treatment of TAO.

Objective: To study the pathological features of uveal melanoma and to evaluate their influence on patients' prognosis., Methods: Paraffin embedded uveal melanoma tissues of 115 cases were examined using routine pathologic methods. Three histological types were classified according to the modified Callender system and patients were followed clinically. The data were done regression and survival analysis by SPSS statistic soft., Results: The patient with epithelial cell type, mixed type, and spindle cell type uveal melanoma have different life times, the average life time is 35.6 +/- 21.5 months, 63.7 +/- 37.0 months, 69.5 +/- 36.5 months in turn, patients with epithelial uveal melanoma had shorter survival time than other two types. The survival time was negatively related to the largest diameter of contact area with the sclera, the largest height and the depth of tumor invasion to the sclera., Conclusions: Epithelial uveal melanoma is more malignant than the other two types. Histological classification of this tumor combined with other pathologic features can indicate the patient's prognosis.