Medicine › Ophthalmology

Ocular Oncology and Treatments

Works Count: 46440

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Description

This cluster of papers focuses on the research, diagnosis, and treatment of ocular cancers, particularly uveal melanoma and retinoblastoma. It covers topics such as genetic mutations, metastatic disease, various treatment modalities including radiation therapy and intraocular chemotherapy, prognostic factors, and tumor classification.

Keywords

Uveal Melanoma; Retinoblastoma; Ocular Surface Neoplasia; Metastatic Disease; Choroidal Melanoma; Genetic Mutations; Radiation Therapy; Prognostic Factors; Intraocular Chemotherapy; Tumor Classification

Intraocular Retinoblastoma: the Case for a New Group Classification

2005-03-01

A LINNMURPHREE

Prognostic implications of monosomy 3 in uveal melanoma

1996-05-01

N Bornfeld , Gabriele Prescher , R Becher +3 more

The retinoblastoma susceptibility gene encodes a nuclear phosphoprotein associated with DNA binding activity

1987-10-01

W H Lee , Jin‐Yuh Shew , Frank Hong +5 more

Frequent inactivation of the retinoblastoma anti-oncogene is restricted to a subset of human tumor cells.

1990-04-01

Jordan M. Horowitz , S H Park , Emil Bogenmann +6 more

We have used polyclonal anti-synthetic peptide serum to study the role of retinoblastoma gene (RB) inactivation in a variety of human tumor cell lines. Our analysis indicates that inactivation of … We have used polyclonal anti-synthetic peptide serum to study the role of retinoblastoma gene (RB) inactivation in a variety of human tumor cell lines. Our analysis indicates that inactivation of the RB protein, p105-Rb, is universal in retinoblastoma cells, vindicating the predictions of the Knudson "two-hit" hypothesis. In addition, our analysis has shown that inactivations of the RB gene are nearly as frequent in a more common human tumor, small cell lung carcinoma. One-third of bladder carcinomas surveyed also carry altered or absent p105-Rb. Other human tumors by contrast demonstrate only infrequent inactivation of the RB gene. These results suggest that inactivation of the RB gene is a critical step in the pathogenesis of a subset of human tumors.

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The epidemiological challenge of the most frequent eye cancer: retinoblastoma, an issue of birth and death

2009-08-24

Tero Kivelä

Many papers on retinoblastoma open with a statement that it is the most common primary intraocular cancer in children and a rare disease. True enough. After reflecting a little longer … Many papers on retinoblastoma open with a statement that it is the most common primary intraocular cancer in children and a rare disease. True enough. After reflecting a little longer on the epidemiology of eye cancer, however, this statement probably should be revised to read: “retinoblastoma is the most frequent primary intraocular cancer and is gaining importance rapidly.” Let us substantiate this claim and evaluate its consequences in some detail. First, just how frequent is retinoblastoma? Not an easy question to answer because investigators are estimating its incidence in many ways. A recent issue featured two papers on the subject from the Western hemisphere. MacCarthy and coworkers,1 who analysed data from 1601 children with retinoblastoma diagnosed in England, Scotland and Wales between 1963 and 2002, arrive at an annual incidence rate of 3.5 per million children less than 15 years of age. Broaddus and colleagues2 from the USA estimate the rate to be 11.8 per million children below 5 years of age, based on 658 entries in the Surveillance, Epidemiology, and End Results (SEER) programme database from 1975 to 2004. MacCarthy and coworkers also provide a cumulative incidence estimate of 53 per million for the first 14 years of life, which is useful because by that age, essentially all retinoblastomas have been detected, and they report that 95% of tumours were diagnosed before the age of 5 years.1 Presuming that this percentage is constant, one can calculate the corresponding estimate to be 62 per million for the SEER study. Although they are of the same order of magnitude, the estimates, or any estimate based on the number of children of particular age, will be influenced by differences in child and adolescent mortality between countries, the more so the wider is the age cohort considered. Because retinoblastoma is …

Expression of recessive alleles by chromosomal mechanisms in retinoblastoma

1983-10-01

Webster K. Cavenee , Thaddeus P. Dryja , Robert A. Phillips +6 more

Incidence of cancer in children in the United States. Sex-, race-, and 1-year age-specific rates by histologic type

1995-04-15

James G. Gurney , Richard K. Severson , Scott Davis +1 more

Background. Rates of cancer in children usually are presented in 5-year age groups, despite large variations of incidence within these groups. The purpose of this report is to provide histology-specific … Background. Rates of cancer in children usually are presented in 5-year age groups, despite large variations of incidence within these groups. The purpose of this report is to provide histology-specific incidence rates within single-year age groups, stratified by sex and race, among children. Methods. Data from the National Cancer Institute's SEER Program were used to calculate incidence rates among children younger than 15 years of age at diagnosis. The SEER population denominator file was modified to allow calculation of rates within single years of age. Results. Large differences in rates within 5-year age groups were found for many histologic types. Retinobiastoma and Wilms' tumor, for instance, had up to eight-fold differences. Substantial differences also were observed for non-Hodgkin's lymphoma, neuroblastoma, Hodgkin's disease, acute lymphoid leukemia, acute myeloid leukemia, and osteosarcoma. In general, rates were higher among males than females, although female rates were often higher among young children. Rates of white children were generally higher than those of black children, especially during the first 5 years of life. Embryonal tumors comprised the majority of neoplasms during the first 2 years of life. Conclusion. Important demographic patterns of cancer incidence in children are obscured when data are summarized into 5-year age groups. Cancer 1995;75:2186–95.

Suppression of the Neoplastic Phenotype by Replacement of the RB Gene in Human Cancer Cells

1988-12-16

Huei-Jen Su Huang , Jiing‐Kuan Yee , Jin‐Yuh Shew +5 more

Mutational inactivation of the retinoblastoma susceptibility (RB) gene has been proposed as a crucial step in the formation of retinoblastoma and other types of human cancer. This hypothesis was tested … Mutational inactivation of the retinoblastoma susceptibility (RB) gene has been proposed as a crucial step in the formation of retinoblastoma and other types of human cancer. This hypothesis was tested by introducing, via retroviral-mediated gene transfer, a cloned RB gene into retinoblastoma or osteosarcoma cells that had inactivated endogenous RB genes. Expression of the exogenous RB gene affected cell morphology, growth rate, soft agar colony formation, and tumorigenicity in nude mice. This demonstration of suppression of the neoplastic phenotype by a single gene provides direct evidence for an essential role of the RB gene in tumorigenesis.

Requirement for a functional Rb-1 gene in murine development

1992-09-01

Alan R. Clarke , Els Robanus Maandag , M van Roon +5 more

The Cowden syndrome: a clinical and genetic study in 21 patients

1986-03-01

Th. M. Starink , J.P.W. van der Veen , F. Arwert +4 more

An analysis of the findings in 21 patients with the Cowden syndrome or the multiple hamartoma syndrome is presented. The Cowden syndrome is a cancer‐associated genodermatosis with characteristic mucocutaneous findings … An analysis of the findings in 21 patients with the Cowden syndrome or the multiple hamartoma syndrome is presented. The Cowden syndrome is a cancer‐associated genodermatosis with characteristic mucocutaneous findings and a wide array of associated abnormalities including a high incidence of breast cancer in female patients. Genetic studies confirmed autosomal dominant inheritance with a high penetrance in both sexes and moderate interfamilial and intrafamilial differences in the expressivity of a number of symptoms. Familial occurrence was present in 4 of the 7 families. There was a strong predominance of female patients (6:1), which may be fortuitous. Mucocutaneous changes were the most constant (100% incidence) and characteristic findings; they almost invariably became manifest in the second decade. Four of our 18 female patients (22%) were treated for breast cancer, a lower incidence than reported previously. No increased incidence of other types of malignancies was found. Craniomegaly (high head circumference) was found to be the most common extracutaneous manifestation (80% incidence); craniomegaly appears to be an important early marker. We also found high incidences of gastrointestinal polyps (approximately 60%) and cutaneous fibromas (76%), while the incidence of thyroid abnormalities, thus far regarded as the most common extracutaneous finding, was similar to that reported previously (62%). G‐banded karyotype and preliminary DNA‐repair studies revealed no clear abnormalities. No linkage with the loci of HLA, and immunoglobulin haplotypes was found.

Human Retinoblastoma Susceptibility Gene: Cloning, Identification, and Sequence

1987-03-13

Wen‐Hwa Lee , Robert Bookstein , Frank Hong +3 more

Recent evidence indicates the existence of a genetic locus in chromosome region 13q14 that confers susceptibility to retinoblastoma, a cancer of the eye in children. A gene encoding a messenger … Recent evidence indicates the existence of a genetic locus in chromosome region 13q14 that confers susceptibility to retinoblastoma, a cancer of the eye in children. A gene encoding a messenger RNA (mRNA) of 4.6 kilobases (kb), located in the proximity of esterase D, was identified as the retinoblastoma susceptibility (RB) gene on the basis of chromosomal location, homozygous deletion, and tumor-specific alterations in expression. Transcription of this gene was abnormal in six of six retinoblastomas examined: in two tumors, RB mRNA was not detectable, while four others expressed variable quantities of RB mRNA with decreased molecular size of about 4.0 kb. In contrast, full-length RB mRNA was present in human fetal retina and placenta, and in other tumors such as neuroblastoma and medulloblastoma. DNA from retinoblastoma cells had a homozygous gene deletion in one case and hemizygous deletion in another case, while the remainder were not grossly different from normal human control DNA. The gene contains at least 12 exons distributed in a region of over 100 kb. Sequence analysis of complementary DNA clones yielded a single long open reading frame that could encode a hypothetical protein of 816 amino acids. A computer-assisted search of a protein sequence database revealed no closely related proteins. Features of the predicted amino acid sequence include potential metal-binding domains similar to those found in nucleic acid-binding proteins. These results provide a framework for further study of recessive genetic mechanisms in human cancers.

Abnormalities in Structure and Expression of the Human Retinoblastoma Gene in SCLC

1988-07-15

J. William Harbour , Shinn-Liang Lai , Jacqueline Whang‐Peng +3 more

Small cell lung cancer (SCLC) has been associated with loss of heterozygosity at several distinct genetic loci including chromosomes 3p, 13q, and 17p. To determine whether the retinoblastoma gene ( … Small cell lung cancer (SCLC) has been associated with loss of heterozygosity at several distinct genetic loci including chromosomes 3p, 13q, and 17p. To determine whether the retinoblastoma gene ( Rb ) localized at 13q14, might be the target of recessive mutations in lung cancer, eight primary SCLC tumors and 50 cell lines representing all major histologic types of lung cancer were examined with the Rb complementary DNA probe. Structural abnormalities within the Rb gene were observed in 1/8 (13%) primary SCLC tumors, 4/22 (18%) SCLC lines, and 1/4 (25%) pulmonary carcinoid lines (comparable to the 20 to 40% observed in retinoblastoma), but were not detected in other major types of lung cancer. Rb messenger RNA expression was absent in 60% of the SCLC lines and 75% of pulmonary carcinoid lines, including all samples with DNA abnormalities. In contrast, Rb transcripts were found in 90% of non-SCLC lung cancer lines and in normal human lung. The finding of abnormalities of the Rb gene in SCLC and pulmonary carcinoids (both neuroendocrine tumors) suggests that this gene may be involved in the pathogenesis of a common adult malignancy.

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Identification of cellular proteins that can interact specifically with the T/ElA-binding region of the retinoblastoma gene product

1991-02-01

William G. Kaelin , David C. Pallas , James A. DeCaprio +2 more

The Human Papilloma Virus-16 E7 Oncoprotein Is Able to Bind to the Retinoblastoma Gene Product

1989-02-17

Nicholas J. Dyson , Peter M. Howley , Karl Münger +1 more

Deletions or mutations of the retinoblastoma gene, RB1, are common features of many tumors and tumor cell lines. Recently, the RB1 gene product, p105-RB, has been shown to form stable … Deletions or mutations of the retinoblastoma gene, RB1, are common features of many tumors and tumor cell lines. Recently, the RB1 gene product, p105-RB, has been shown to form stable protein/protein complexes with the oncoproteins of two DNA tumor viruses, the adenovirus E1A proteins and the simian virus 40 (SV40) large T antigen. Neither of these viruses is thought to be associated with human cancer, but they can cause tumors in rodents. Binding between the RB anti-oncoprotein and the adenovirus or SV40 oncoprotein can be recapitulated in vitro with coimmunoprecipitation mixing assays. These assays have been used to demonstrate that the E7 oncoprotein of the human papilloma virus type-16 can form similar complexes with p105-RB. Human papilloma virus-16 is found associated with approximately 50 percent of cervical carcinomas. These results suggest that these three DNA viruses may utilize similar mechanisms in transformation and implicate RB binding as a possible step in human papilloma virus-associated carcinogenesis.

Epidemiologic aspects of uveal melanoma

1988-01-01

Kathleen M. Egan , Johanna M. Seddon , Robert J. Glynn +2 more

Structural Evidence for the Authenticity of the Human Retinoblastoma Gene

1987-06-26

Yuen-Kai Fung , A. Linn Murphree , Anne Tang +3 more

The retinoblastoma (Rb) gene is the prototype for a class of recessive human cancer genes in which loss of activity of both normal alleles is thought to be associated with … The retinoblastoma (Rb) gene is the prototype for a class of recessive human cancer genes in which loss of activity of both normal alleles is thought to be associated with tumorigenesis. Sixteen of 40 retinoblastomas examined with a complementary DNA probe shown to be the Rb gene had identifiable structural changes of the Rb gene including in some cases homozygous internal deletions with corresponding truncated transcripts. An osteosarcoma also had a homozygous internal deletion with a truncated transcript. In addition, possible hot spots for deletion were identified within the Rb genomic locus. Among those tumors with no identifiable structural changes there was either absence of an Rb transcript or abnormal expression of the Rb transcript. Comparison of the structural changes in the tumor cells and fibroblasts of certain patients provided support for Knudson's two-hit hypothesis for the development of retinoblastoma at the molecular level. The ability to detect germline structural deletions in fibroblasts from some patients with bilateral retinoblastoma also indicates that the isolated gene is useful for diagnostic purposes.

Frequent somatic mutations of GNAQ in uveal melanoma and blue naevi

2008-12-10

Catherine D. Van Raamsdonk , Vladimir Bezrookove , Gary Green +6 more

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Very Long-Term Prognosis of Patients with Malignant Uveal Melanoma

2003-10-24

Emma Kujala , Teemu Ma ̈kitie , Tero Kivelä

To investigate the very long-term prognosis of patients with uveal melanoma and the clinical characteristics influencing it.Charts, registry data, and histopathologic specimens of 289 consecutive patients with choroidal and ciliary … To investigate the very long-term prognosis of patients with uveal melanoma and the clinical characteristics influencing it.Charts, registry data, and histopathologic specimens of 289 consecutive patients with choroidal and ciliary body melanoma treated in the district of the Helsinki University Central Hospital, Finland, between 1962 and 1981 were audited. Definitions for coding the cause of death were adapted from the Collaborative Ocular Melanoma Study (COMS). Competing risks were taken into account by using cumulative incidence analysis and competing risks regression.Of the 289 patients treated, 239 were deceased at the end of follow-up. The audited cause of death was uveal melanoma in 145 (61%) of them. The median follow-up of the 50 survivors was 28 years. The original histopathologic diagnosis of metastasis and second cancer was correct in 91% of all specimens, but immunohistochemical reassessment changed 10% of biopsy and 7% of autopsy diagnoses. Of 45 positive autopsies, 18% were performed without suspicion of melanoma. Uveal melanoma-related mortality was 31% (95% confidence interval [CI], 26-37) by 5 years, 45% (95% CI, 40-51) by 15 years, 49% (95% CI, 43-55) by 25 years, and 52% (95% CI, 45-58) by 35 years, according to cumulative incidence analysis. Of patients who died of uveal melanoma, 62%, 90%, 98%, and 100% did so within 5, 15, 25, and 35 years, respectively. Between 15 and 35 years, 20% to 33% of deaths were still due to uveal melanoma. By competing risks regression analysis, the hazard ratio was 1.08 (P=0.0012) for each millimeter increase in tumor diameter, 2.27 (P=0.0076) for extraocular growth, and 1.89 (P=0.0011) for ciliary body involvement.Metastatic uveal melanoma was the leading single cause of death throughout the study. Cumulative incidences provide a sound basis for patient counseling and design of trials.

Frequent Mutation of <i>BAP1</i> in Metastasizing Uveal Melanomas

2010-11-05

J. William Harbour , Michael D. Onken , Elisha Roberson +7 more

An Eye on Metastasis Despite the considerable progress being made in elucidating the cell biology of metastasis, little is known about the genetic alterations that promote metastasis of human tumors, … An Eye on Metastasis Despite the considerable progress being made in elucidating the cell biology of metastasis, little is known about the genetic alterations that promote metastasis of human tumors, the cause of most cancer deaths. A potentially important clue now emerges from the work of Harbour et al. (p. 1410 , published online 4 November), who used an exome-sequencing approach to search for genetic mutations in uveal melanomas, an eye cancer associated with a high rate of fatal metastasis. Remarkably, over 80% of tumor samples with a high metastatic risk had inactivating somatic mutations in the gene encoding BAP1 (BRCA1-associated protein 1), a nuclear protein involved in controlling protein degradation. Thus, in this tumor type, mutational inactivation of BAP1 may be a key event in the acquisition of metastatic competence.

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Second primary neoplasms in patients with retinoblastoma

1986-05-01

G J Draper , B M Sanders , J E Kingston

Epigenetic changes may contribute to the formation and spontaneous regression of retinoblastoma

1989-09-01

Valerie Greger , Eberhard Passarge , Wolfgang H�pping +2 more

Effects of an Rb mutation in the mouse

1992-09-01

Tyler Jacks , Amin Fazeli , Earlene M. Schmitt +3 more

The International Classification of Retinoblastoma Predicts Chemoreduction Success

2006-09-26

Carol L. Shields , Arman Mashayekhi , Angela K. Au +4 more

Suppression of Tumorigenicity of Human Prostate Carcinoma Cells by Replacing a Mutated RB Gene

1990-02-09

Robert Bookstein , Jin‐Yuh Shew , Phang‐Lang Chen +2 more

Introduction of a normal retinoblastoma gene ( RB ) into retinoblastoma cells was previously shown to suppress several aspects of their neoplastic phenotype, including tumorigenicity in nude mice, thereby directly … Introduction of a normal retinoblastoma gene ( RB ) into retinoblastoma cells was previously shown to suppress several aspects of their neoplastic phenotype, including tumorigenicity in nude mice, thereby directly demonstrating a cancer suppression function of RB . To explore the possibility of a similar activity in a common adult tumor, RB expression was examined in three human prostate carcinoma cell lines. One of these, DU145, contained an abnormally small protein translated from an RB messenger RNA transcript that lacked 105 nucleotides encoded by exon 21. To assess the functional consequences of this mutation, normal RB expression was restored in DU145 cells by retrovirus-mediated gene transfer. Cells that maintained stable exogenous RB expression lost their ability to form tumors in nude mice, although their growth rate in culture was apparently unaltered. These results suggest that RB inactivation can play a significant role in the genesis of a common adult neoplasm and that restoration of normal RB -encoded protein in tumors could have clinical utility.

Germline mutations in BAP1 predispose to melanocytic tumors

2011-08-28

Thomas Wiesner , Anna C. Obenauf , Rajmohan Murali +7 more

Mutations in<i>GNA11</i>in Uveal Melanoma

2010-11-17

Catherine D. Van Raamsdonk , Klaus Griewank , Michelle B. Crosby +7 more

Uveal melanoma is the most common intraocular cancer. There are no effective therapies for metastatic disease. Mutations in GNAQ, the gene encoding an alpha subunit of heterotrimeric G proteins, are … Uveal melanoma is the most common intraocular cancer. There are no effective therapies for metastatic disease. Mutations in GNAQ, the gene encoding an alpha subunit of heterotrimeric G proteins, are found in 40% of uveal melanomas.

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Mutation and Cancer: Statistical Study of Retinoblastoma

1971-04-01

Alfred G. Knudson

Based upon observations on 48 cases of retinoblastoma and published reports, the hypothesis is developed that retinoblastoma is a cancer caused by two mutational events. In the dominantly inherited form, … Based upon observations on 48 cases of retinoblastoma and published reports, the hypothesis is developed that retinoblastoma is a cancer caused by two mutational events. In the dominantly inherited form, one mutation is inherited via the germinal cells and the second occurs in somatic cells. In the nonhereditary form, both mutations occur in somatic cells. The second mutation produces an average of three retinoblastomas per individual inheriting the first mutation. Using Poisson statistics, one can calculate that this number (three) can explain the occasional gene carrier who gets no tumor, those who develop only unilateral tumors, and those who develop bilateral tumors, as well as explaining instances of multiple tumors in one eye. This value for the mean number of tumors occurring in genetic carriers may be used to estimate the mutation rate for each mutation. The germinal and somatic rates for the first, and the somatic rate for the second, mutation, are approximately equal. The germinal mutation may arise in some instances from a delayed mutation.

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Survey of 520 Eyes with Uveal Metastases

1997-08-01

Carol L. Shields , Jerry A. Shields , Nicole Groß +2 more

Inactivation of the Retinoblastoma Susceptibility Gene in Human Breast Cancers

1988-07-08

Eva Y.-H.P. Lee , Hoang To , Jin-Yuh Shew +3 more

Mutational inactivation of the retinoblastoma susceptibility (RB) gene, a recessive cancer gene, has been implicated in the genesis of retinoblastoma and certain other human neoplasms. This gene is now shown … Mutational inactivation of the retinoblastoma susceptibility (RB) gene, a recessive cancer gene, has been implicated in the genesis of retinoblastoma and certain other human neoplasms. This gene is now shown to be inactivated in two of nine human breast cancer cell lines examined. The RB gene of one cell line had a homozygous internal duplication of a 5-kilobase region containing exons 5 and 6. The RB messenger RNA transcript was correspondingly lengthened, and its translation was probably terminated prematurely due to a shifted reading frame. The other cell line had a homozygous deletion of the RB gene that removed the entire gene beyond exon 2. The RB gene product, pp110 RB , was not detectable in either cell line by immunoprecipitation with specific antibodies. These findings are significant in relation to proposed genetic mechanisms of breast cancer formation.

A human DNA segment with properties of the gene that predisposes to retinoblastoma and osteosarcoma

1986-10-01

Stephen Friend , René Bernards , Snezna Rogelj +4 more

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Survey of 1264 patients with orbital tumors and simulating lesions

2004-05-01

Jerry A. Shields , Carol L. Shields , Richard Scartozzi

Metastasis of Uveal Melanoma Millimeter-by-Millimeter in 8033 Consecutive Eyes

2009-08-01

Carol L. Shields

<h3>Objective</h3> To determine the rate of metastasis of uveal melanoma on the basis of tumor thickness in millimeters. <h3>Methods</h3> Retrospective medical record review. <h3>Results</h3> The mean (median) patient age was … <h3>Objective</h3> To determine the rate of metastasis of uveal melanoma on the basis of tumor thickness in millimeters. <h3>Methods</h3> Retrospective medical record review. <h3>Results</h3> The mean (median) patient age was 58 (59) years. A total of 8033 eyes were examined. Of the 285 eyes with iris melanoma, the mean tumor thickness was 2.7 mm and metastasis occurred in 0.5%, 4%, and 7% at 3, 5, and 10 years, respectively. Of the 492 eyes with ciliary body melanoma, the mean tumor thickness was 6.6 mm and metastasis occurred in 12%, 19%, and 33% at 3, 5, and 10 years, respectively. Of the 7256 eyes with choroidal melanoma, the mean tumor thickness was 5.5 mm and metastasis occurred in 8%, 15%, and 25% at 3, 5, and 10 years, respectively. For all uveal melanoma, metastasis at 5, 10, and 20 years was 6%, 12%, and 20% for small melanoma (0-3.0 mm thickness), 14%, 26%, and 37% for medium melanoma (3.1-8.0 mm), and 35%, 49%, and 67% for large melanoma (>8.0 mm). More specifically, metastasis per millimeter increment at 10 years was 6% (0-1.0 mm thickness), 12% (1.1-2.0 mm), 12% (2.1-3.0 mm), 16% (3.1-4.0 mm), 27% (4.1-5.0 mm), 28% (5.1-6.0 mm), 29% (6.1-7.0 mm), 41% (7.1-8.0 mm), 50% (8.1-9.0 mm), 44% (9.1-10.0 mm), and 51% (>10.0 mm). Clinical factors predictive of metastasis by multivariate analysis included increasing patient age, ciliary body location, increasing tumor diameter, increasing tumor thickness, having a brown tumor, and the presence of subretinal fluid, intraocular hemorrhage, or extraocular extension. <h3>Conclusion</h3> Increasing millimeter thickness of uveal melanoma is associated with increasing risk for metastasis.

Mortality From Second Tumors Among Long-Term Survivors of Retinoblastoma

1993-07-21

Charis Eng , F. P. Li , David H. Abramson +6 more

Journal Article Mortality From Second Tumors Among Long-Term Survivors of Retinoblastoma Get access Charis Eng, Charis Eng Divisions of Medical Oncology and Cancer Epidemiology and Control, Dana-Farber Cancer InstituteBoston, Mass.Harvard … Journal Article Mortality From Second Tumors Among Long-Term Survivors of Retinoblastoma Get access Charis Eng, Charis Eng Divisions of Medical Oncology and Cancer Epidemiology and Control, Dana-Farber Cancer InstituteBoston, Mass.Harvard Medical SchoolBoston, Mass. Correspondence to: John D. Boice, Jr., Sc.D., Radiation Epidemiology Branch, National Cancer Institute, EPN 408, 6130 Executive Blvd, Rockville, MD 20852. Search for other works by this author on: Oxford Academic PubMed Google Scholar Frederick P. Li, Frederick P. Li Division of Cancer Epidemiology and Control, Dana-Farber Cancer Institute, and Harvard School of Public HealthBoston, Mass. Search for other works by this author on: Oxford Academic PubMed Google Scholar David H. Abramson, David H. Abramson Ophthalmic Oncology Center, New York Hospital-Cornell Medical CenterNew York, N.Y. Search for other works by this author on: Oxford Academic PubMed Google Scholar Robert M. Ellsworth, Robert M. Ellsworth Ophthalmic Oncology Center, New York Hospital-Cornell Medical CenterNew York, N.Y. Search for other works by this author on: Oxford Academic PubMed Google Scholar F. Lennie Wong, F. Lennie Wong Radiation Epidemiology Branch, National Cancer InstituteRockville, Md. Search for other works by this author on: Oxford Academic PubMed Google Scholar Marlene B. Goldman, Marlene B. Goldman Harvard School of Public Health Search for other works by this author on: Oxford Academic PubMed Google Scholar Johanna Seddon, Johanna Seddon Massachusetts Eye and Ear InfirmaryBoston, Mass.Harvard Medical School Search for other works by this author on: Oxford Academic PubMed Google Scholar Nancy Tarbell, Nancy Tarbell Joint Center for Radiation Therapy, Boston Children's HospitalBoston, Mass.Harvard Medical School Search for other works by this author on: Oxford Academic PubMed Google Scholar John D. Boice, Jr. John D. Boice, Jr. Radiation Epidemiology Branch, National Cancer InstituteRockville, Md. Correspondence to: John D. Boice, Jr., Sc.D., Radiation Epidemiology Branch, National Cancer Institute, EPN 408, 6130 Executive Blvd, Rockville, MD 20852. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 85, Issue 14, 21 July 1993, Pages 1121–1128, https://doi.org/10.1093/jnci/85.14.1121 Published: 21 July 1993 Article history Received: 22 September 1992 Revision received: 22 March 1993 Accepted: 06 May 1993 Published: 21 July 1993

Gene Expression Profiling in Uveal Melanoma Reveals Two Molecular Classes and Predicts Metastatic Death

2004-10-15

Michael D. Onken , Lori A. Worley , Justis P. Ehlers +1 more

Abstract Melanomas are notoriously difficult to classify because of a lack of discrete clinical and pathological stages. Here, we show that primary uveal melanomas surprisingly cluster into two distinct molecular … Abstract Melanomas are notoriously difficult to classify because of a lack of discrete clinical and pathological stages. Here, we show that primary uveal melanomas surprisingly cluster into two distinct molecular classes based on gene expression profile. Genes that discriminate class 1 (low-grade) from class 2 (high-grade) include highly significant clusters of down-regulated genes on chromosome 3 and up-regulated genes on chromosome 8q, which is consistent with previous cytogenetic studies. A three-gene signature allows biopsy-size tumor samples to be assigned accurately to tumor classes using either array or PCR platforms. Most importantly, this molecular classification strongly predicts metastatic death and outperforms other clinical and pathological prognostic indicators. These studies offer new insights into melanoma pathogenesis, and they provide a practical foundation for effective clinical predictive testing.

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Uveal Melanoma: Trends in Incidence, Treatment, and Survival

2011-06-28

Arun D. Singh , Mary E. Turell , Allan Topham

Analysis of BRAF V600E mutation in 1,320 nervous system tumors reveals high mutation frequencies in pleomorphic xanthoastrocytoma, ganglioglioma and extra-cerebellar pilocytic astrocytoma

2011-01-28

Genevieve Schindler , David Capper , Jochen Meyer +7 more

Phosphorylation of the retinoblastoma gene product is modulated during the cell cycle and cellular differentiation

1989-09-01

Phang‐Lang Chen , Peter Scully , Jin‐Yuh Shew +2 more

Cancer incidence after retinoblastoma. Radiation dose and sarcoma risk

1997-10-15

F. Lennie Wong

There is a substantial risk of a second cancer for persons with hereditary retinoblastoma, which is enhanced by radiotherapy.To examine long-term risk of new primary cancers in survivors of childhood … There is a substantial risk of a second cancer for persons with hereditary retinoblastoma, which is enhanced by radiotherapy.To examine long-term risk of new primary cancers in survivors of childhood retinoblastoma and quantify the role of radiotherapy in sarcoma development.Cohort incidence study of patients with retinoblastoma followed for a median of 20 years, and nested case-control study of a radiation dose-response relationship for bone and soft tissue sarcomas.A total of 1604 patients with retinoblastoma who survived at least 1 year after diagnosis, identified from hospital records in Massachusetts and New York during 1914 to 1984.Incidence of subsequent cancers was statistically significantly elevated only in the 961 patients with hereditary retinoblastoma, in whom 190 cancers were diagnosed, vs 6.3 expected in the general population (relative risk [RR], 30 [95% confidence interval, 26-47]). Cumulative incidence (+/-SE) of a second cancer at 50 years after diagnosis was 51.0% (+/-6.2%) for hereditary retinoblastoma, and 5.0% (+/-3.0%) for nonhereditary retinoblastoma. All 114 sarcomas of diverse histologic types occurred in patients with hereditary retinoblastoma. For soft tissue sarcomas, the RRs showed a stepwise increase at all dose categories, and were statistically significant at 10 to 29.9 Gy and 30 to 59.9 Gy. A radiation risk for all sarcomas combined was evident at doses above 5 Gy, rising to 10.7-fold at doses of 60 Gy or greater (P<.05).Genetic predisposition has a substantial impact on risk of subsequent cancers in retinoblastoma patients, which is further increased by radiation treatment. A radiation dose-response relationship is demonstrated for all sarcomas and, for the first time in humans, for soft tissue sarcomas. Retinoblastoma patients should be examined for new cancers and followed into later life to determine whether their extraordinary cancer risk extends to common cancers of adulthood.

SV40 large tumor antigen forms a specific complex with the product of the retinoblastoma susceptibility gene

1988-07-01

James A. DeCaprio

The Molecular Genetics of Cancer

1987-01-16

J. Michael Bishop

Cancer has myriad causes, but many of these may act by damaging DNA. Both dominant and recessive forms of genetic damage have been found in human cancer cells. The damage … Cancer has myriad causes, but many of these may act by damaging DNA. Both dominant and recessive forms of genetic damage have been found in human cancer cells. The damage is likely to play a role in tumorigenesis, and it can therefore form the basis for new approaches to the diagnosis, prognosis, and therapy of cancer.

Carcinoma Metastatic to the Eye and Orbit

1974-10-01

Andrew P. Ferry

Of 227 cases of carcinoma metastatic to the eye or orbit, the predominant involvement was in the eye in 196 cases, the orbit in 28, and in the optic nerve … Of 227 cases of carcinoma metastatic to the eye or orbit, the predominant involvement was in the eye in 196 cases, the orbit in 28, and in the optic nerve in 3 cases. There was no preponderance of left-sided involvement. The primary sites accounting for the most cases were the breast (40%) and the lung (29%). Of the 217 patients regarding whom follow-up information was obtainable, 192 were known to have died of metastatic tumor. The median survival was 7.4 months from the time of ocular/orbital operation. Data are presented suggesting that, contrary to prevailing opinion, the most common malignant tumor of the eye is metastatic carcinoma, rather than primary uveal malignant melanoma.

Uveal melanoma: relatively rare but deadly cancer

2016-12-02

Swathi Kaliki , Carol L. Shields

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The COMS Randomized Trial of Iodine 125 Brachytherapy for Choroidal Melanoma

2006-12-01

To report refined rates of death and related outcomes by treatment arm through 12 years after primary treatment of choroidal melanoma and to evaluate characteristics of patients and tumors as … To report refined rates of death and related outcomes by treatment arm through 12 years after primary treatment of choroidal melanoma and to evaluate characteristics of patients and tumors as predictors of relative treatment effectiveness and time to death.Randomized multicenter clinical trial of iodine 125 ((125)I) brachytherapy vs enucleation conducted as part of the Collaborative Ocular Melanoma Study. Eligible patients were free of metastasis and other cancers at enrollment. All patients were followed up for 5 to 15 years at scheduled examinations for metastasis or another cancer or until death. Decedents were classified by the independent Mortality Coding Committee as having histopathologically confirmed melanoma metastasis, suspected melanoma metastasis without histopathologic confirmation, another cancer but not melanoma metastasis, or no malignancy.Deaths from all causes and deaths with histopathologically confirmed melanoma metastasis.Within 12 years after enrollment, 471 of 1317 patients died. Of 515 patients eligible for 12 years of follow-up, 231 (45%) were alive and clinically cancer free 12 years after treatment. For patients in both treatment arms, 5- and 10-year all-cause mortality rates were 19% and 35%, respectively; by 12 years, cumulative all-cause mortality was 43% among patients in the (125)I brachytherapy arm and 41% among those in the enucleation arm. Five-, 10-, and 12-year rates of death with histopathologically confirmed melanoma metastasis were 10%, 18%, and 21%, respectively, in the (125)I brachytherapy arm and 11%, 17%, and 17%, respectively, in the enucleation arm. Older age and larger maximum basal tumor diameter were the primary predictors of time to death from all causes and death with melanoma metastasis.Longer follow-up of patients confirmed the earlier report of no survival differences between patients whose tumors were treated with (125)I brachytherapy and those treated with enucleation.Estimated mortality rates by baseline characteristics should facilitate counseling of patients who have choroidal melanoma of a size and in a location suitable for enucleation or (125)I brachytherapy and no evidence of metastasis or another malignancy.

Integrative Analysis Identifies Four Molecular and Clinical Subsets in Uveal Melanoma

2017-08-01

A. Gordon Robertson , Juliann Shih , Christina Yau +7 more

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Overall Survival Benefit with Tebentafusp in Metastatic Uveal Melanoma

2021-09-22

Paul Nathan , Jessica C. Hassel , Piotr Rutkowski +7 more

Uveal melanoma is a disease that is distinct from cutaneous melanoma, with a low tumor mutational burden and a 1-year overall survival of approximately 50% in patients with metastatic uveal … Uveal melanoma is a disease that is distinct from cutaneous melanoma, with a low tumor mutational burden and a 1-year overall survival of approximately 50% in patients with metastatic uveal melanoma. Data showing a proven overall survival benefit with a systemic treatment are lacking. Tebentafusp is a bispecific protein consisting of an affinity-enhanced T-cell receptor fused to an anti-CD3 effector that can redirect T cells to target glycoprotein 100-positive cells.In this open-label, phase 3 trial, we randomly assigned previously untreated HLA-A*02:01-positive patients with metastatic uveal melanoma in a 2:1 ratio to receive tebentafusp (tebentafusp group) or the investigator's choice of therapy with single-agent pembrolizumab, ipilimumab, or dacarbazine (control group), stratified according to the lactate dehydrogenase level. The primary end point was overall survival.A total of 378 patients were randomly assigned to either the tebentafusp group (252 patients) or the control group (126 patients). Overall survival at 1 year was 73% in the tebentafusp group and 59% in the control group (hazard ratio for death, 0.51; 95% confidence interval [CI], 0.37 to 0.71; P<0.001) in the intention-to-treat population. Progression-free survival was also significantly higher in the tebentafusp group than in the control group (31% vs. 19% at 6 months; hazard ratio for disease progression or death, 0.73; 95% CI, 0.58 to 0.94; P = 0.01). The most common treatment-related adverse events in the tebentafusp group were cytokine-mediated events (due to T-cell activation) and skin-related events (due to glycoprotein 100-positive melanocytes), including rash (83%), pyrexia (76%), and pruritus (69%). These adverse events decreased in incidence and severity after the first three or four doses and infrequently led to discontinuation of the trial treatment (2%). No treatment-related deaths were reported.Treatment with tebentafusp resulted in longer overall survival than the control therapy among previously untreated patients with metastatic uveal melanoma. (Funded by Immunocore; ClinicalTrials.gov number, NCT03070392; EudraCT number, 2015-003153-18.).

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The COMS Randomized Trial of Iodine 125 Brachytherapy for Choroidal Melanoma, III: Initial Mortality Findings

2001-07-01

Marie Diener‐West , John D. Earle , Shai Fine +5 more

Objectives: To report initial mortality findings from the Collaborative Ocular Melanoma Study (COMS) randomized clinical trial of iodine 125 brachytherapy vs enucleation for treatment of choroidal melanoma.Methods: Patients were evaluated … Objectives: To report initial mortality findings from the Collaborative Ocular Melanoma Study (COMS) randomized clinical trial of iodine 125 brachytherapy vs enucleation for treatment of choroidal melanoma.Methods: Patients were evaluated for eligibility at 43 participating clinical centers in the United States and Canada.Eligible consenting patients were assigned randomly at the time of enrollment to enucleation or 125 I brachytherapy.Patients were examined at specified intervals after enrollment for data collection purposes.Findings presented herein are based on data received by September 30, 2000.Data for each patient were analyzed with the treatment group to which the patient was assigned randomly at the time of enrollment.Results: During the 11 1 ⁄2-year accrual period, 1317 patients enrolled; 660 were assigned randomly to enucleation and 657 to 125 I brachytherapy.Only 2 patients in the enucleation arm were found to have been misdiagnosed when histopathology was reviewed centrally.All but 17 patients (1.3%) received the assigned treatment.Adherence to the brachytherapy protocol was excellent, with 91% of patients treated per protocol.Based on time since enrollment,

Uveal melanoma

2020-04-09

Martine J. Jager , Carol L. Shields , Colleen M. Cebulla +7 more

Retinoblastoma

2012-03-12

Helen Dimaras , Kahaki Kimani , E Dimba +4 more

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Development of Metastatic Disease After Enrollment in the COMS Trials for Treatment of Choroidal Melanoma

2005-12-01

Marie Diener‐West , Sandra M. Reynolds , Donna J Agugliaro +7 more

<h3>Objective</h3> To describe the time between treatment for choroidal melanoma and first diagnosis of metastatic disease, sites of metastasis, treatments for metastasis, and time between diagnosis of metastasis and death. … <h3>Objective</h3> To describe the time between treatment for choroidal melanoma and first diagnosis of metastatic disease, sites of metastasis, treatments for metastasis, and time between diagnosis of metastasis and death. <h3>Design</h3> Prospective, longitudinal follow-up of patients diagnosed with choroidal melanoma who were enrolled in 2 randomized trials conducted by the Collaborative Ocular Melanoma Study Group. <h3>Methods</h3> Systemic and laboratory evaluations were performed during follow-up according to a standard protocol for 2320 patients enrolled in the Collaborative Ocular Melanoma Study trials without evidence of melanoma metastasis or other primary cancer at baseline. <h3>Results</h3> Seven hundred thirty-nine patients were diagnosed with at least 1 site of metastasis during follow-up after treatment for choroidal melanoma. Five- and 10-year cumulative metastasis rates were 25% (95% confidence interval, 23%-27%) and 34% (95% confidence interval, 32%-37%), respectively. Liver was the most common site (89%). The death rate following the report of melanoma metastasis was 80% at 1 year (95% confidence interval, 77%-83%) and 92% at 2 years (95% confidence interval, 89%-94%). Overall survival after metastasis did not vary by baseline size of primary tumor nor treatment for metastasis (when known). Long-term survival after diagnosis of metastasis was uncommon; only 8 patients survived 5 or more years. <h3>Conclusion</h3> Metastasis rate increased significantly with increasing primary tumor dimensions at time of patient enrollment. Prognosis after metastatic disease remains poor. Effective methods are needed to prevent, diagnose, and treat metastasis from choroidal melanoma.

Retrospective multicenter analysis of real-life toxicity and outcome of ipilimumab and nivolumab in metastatic uveal melanoma

2025-06-24

Amélie Ciernik , Laure Ciernik , Peter Bonczkowitz +7 more | The Oncologist

Abstract Background Uveal melanoma (UM) is the most common primary ocular malignancy with a high rate of metastases. While immune checkpoint inhibitors (ICIs), including ipilimumab and nivolumab (ipi+nivo), have shown … Abstract Background Uveal melanoma (UM) is the most common primary ocular malignancy with a high rate of metastases. While immune checkpoint inhibitors (ICIs), including ipilimumab and nivolumab (ipi+nivo), have shown efficacy in metastatic cutaneous melanoma, their success in metastatic UM (MUM) remains limited. This study evaluates toxicity and outcomes of ipi+nivo in the largest, multicenter MUM cohort. Methods We analyzed 131 MUM patients treated with ipi+nivo from 2016-2024 across five international centers. Rates of toxicity, response, and survival outcomes were assessed. Results Among 131 patients, 37.4% of patients received four cycles of ipi+nivo. The most common reason for ipi+nivo discontinuation (31.3%) was toxicity. Of all treated patients, 80.2% experienced immune-related adverse events (irAEs). The overall response rate (ORR) was 16.4%, and the disease control rate (DCR) was 43.4%. Progression-free survival (PFS) was three months, and the median overall survival (OS) was 18 months. Patients receiving ipi+nivo as second-line therapy had lower ORR compared to patients who received ipi+nivo as first-line therapy (p = 0.04). Patients with exclusively extrahepatic metastases had a better ORR and OS compared to those with hepatic or mixed metastases (p = 0.02, p = 0.02, respectively). 20.6% of patients developed eosinophilia during treatment, which was associated with improved median OS (24 months vs. 15 months, p = 0.02). Conclusions Ipi+nivo shows moderate efficacy and clinically relevant toxicities in patients with MUM. Eosinophilia is a potential prognostic biomarker, that merits further investigation.

Diagnosis and management of orbital tumors

2025-06-24

A. Eckardt , Nils‐Claudius Gellrich | International Journal of Oral and Maxillofacial Surgery

Super-enhancers orchestrate transcriptional dysregulation and metabolic reprogramming in uveal melanoma

2025-06-23

Hui Pan , Weihuan Shao , Huixue Wang +5 more | Communications Biology

Uveal melanoma (UM) is the most common intraocular malignancy in adults and frequently metastasizes. Somatic mutations and chromatin aberrations have been implicated in the pathogenesis of this deadly disease. Despite … Uveal melanoma (UM) is the most common intraocular malignancy in adults and frequently metastasizes. Somatic mutations and chromatin aberrations have been implicated in the pathogenesis of this deadly disease. Despite rapid progress in elucidating the genetic landscape of UM, the epigenetic architecture underlying UM pathogenesis remains incompletely understood. Here, we describe a super-enhancer-mediated epigenetic pipeline through genome-scale histone acetylation and transcriptional profiling. We first characterized the active landscape of super-enhancer profiles in UM via chromatin immunoprecipitation sequencing (ChIP-seq). We identified master transcription factors specifically driven by UM-specific super-enhancers, and our pipeline identified transcription factor AP-2 alpha (TFAP2A), which is highly associated with metabolism and oncogenesis, as the top essential regulator in UM. TFAP2A occupied predicted super-enhancers associated with the oncogene Solute Carrier Family 7 member 8 (SLC7A8) in UM, thereby elucidating a mechanism for regulating oncogene expression. Collectively, our data illustrate the potential for epigenetic targeting of super-enhancer-mediated oncogene dependencies in UM, highlighting an epigenetic vulnerability that can be exploited for precision therapy.

Optic Nerve Invasion in Retinoblastoma: Impact of Eye Salvage and Adjuvant Chemotherapy

2025-06-23

Zhao Feng , Junyang Zhao , Donna D’Souza +3 more | Investigative Ophthalmology & Visual Science

Optic nerve invasion (ONI) is an important risk factor for extraocular metastasis in retinoblastoma. This study evaluates the impact of pre-enucleation chemotherapy, delayed enucleation, and adjuvant chemotherapy on survival in … Optic nerve invasion (ONI) is an important risk factor for extraocular metastasis in retinoblastoma. This study evaluates the impact of pre-enucleation chemotherapy, delayed enucleation, and adjuvant chemotherapy on survival in patients with varying degree of ONI on histopathology. A retrospective review of consecutive enucleated eyes with any degree of ONI from 29 Chinese treatment centers 2012-2017. Children with other high-risk histopathological features, extraocular disease at diagnosis or bilateral enucleation were excluded. Among 2500 enucleated eyes, 386 eyes with isolated ONI (one eye per child) met the inclusion criteria: prelaminar (n = 204), intralaminar (n = 70), retrolaminar without tumor at transected optic nerve (n = 96), or retrolaminar with tumor at transected end (n = 16). Primary enucleation was performed in 59% of cases, whereas 41% underwent secondary enucleation after eye salvage therapies. Delayed enucleation beyond six months from diagnosis significantly increased the likelihood of tumor at optic nerve transection (21% vs. 2%; P < 0.001). The five-year cause-specific survival (CSS) was 96.7% overall: prelaminar (100%), intralaminar (98%), retrolaminar without transected end involvement (94%), or tumor at transected optic nerve (58%). Secondarily enucleated eyes with retrolaminar ONI without transected end involvement had lower CSS than those primarily enucleated (85.6% vs. 100%; P = 0.022). The five-year CSS was higher but not statistically significant, for eyes treated with or without adjuvant chemotherapy: intralaminar ONI (100% vs. 95.7%; P = 0.193), retrolaminar ONI without tumor at transected end (100% vs. 93.5; P = 0.413), and tumor at the transected end (80.0% vs. 45.0%; P = 0.192). Timely enucleation reduces the risk of tumor involvement at optic nerve transection. Delay in enucleation by pre-enucleation chemotherapy may reduce the effectiveness of subsequent adjuvant chemotherapy.

Challenges for Opticians in Evaluating Small Pigmented Choroidal Lesions: Potential Support From the Mel<i>AI</i>noma Deep Learning Algorithm

2025-06-23

Shiva Sabazade , Marco A. Lumia Michalski , Sara Wittskog +3 more | Translational Vision Science & Technology

To evaluate the diagnostic accuracy of Swedish opticians/optometrists when triaging small pigmented choroidal lesions and determine whether the MelAInoma deep learning algorithm improves referral decisions. Twenty-nine opticians/optometrists graded 25 fundus … To evaluate the diagnostic accuracy of Swedish opticians/optometrists when triaging small pigmented choroidal lesions and determine whether the MelAInoma deep learning algorithm improves referral decisions. Twenty-nine opticians/optometrists graded 25 fundus photographs (5 melanomas, 20 nevi) with the Mushroom shape, Orange pigment, Large size, Enlargement, Subretinal fluid (MOLES) system and recorded referrals; 25 then used MelAInoma. Predefined referral thresholds were MOLES ≥1 or ≥3 and MelAInoma >63. Diagnostic test statistics-including sensitivity, specificity, positive (PPV) and negative (NPV) predictive values, accuracy, and standard deviation (SD)-plus odds of correct referral and decision curve net benefit were computed. With MOLES ≥1, mean ± SD sensitivity was 98% ± 6%, specificity was 17% ± 16%, PPV was 23%, NPV was 99%, and accuracy was 33%. Raising the cutoff to MOLES ≥3 lowered sensitivity to 75% ± 29% but increased specificity to 53% ± 28%, PPV to 34%, NPV to 93%, and accuracy to 57%. MelAInoma achieved 80% sensitivity, 90% specificity, PPV 67%, NPV 95%, and 88% accuracy. Algorithm guidance quadrupled the odds of correctly referring a melanoma, reduced false-positive referrals 10-fold, and provided net clinical benefit to unaided triage across all relevant threshold probabilities. Although the findings are based on a small image set, including only five melanomas, which limits generalizability, the results suggest that opticians and optometrists detect small choroidal melanomas with high sensitivity but limited specificity. Incorporating MelAInoma at the predefined threshold reduced sensitivity, substantially improved specificity, and markedly reduced unnecessary referrals. MelAInoma offers practical artificial intelligence support that can streamline community referrals and facilitate earlier treatment of uveal melanoma.

Twelve reasons delays in uveal melanoma treatment might affect prognosis

2025-06-23

Gustav Stålhammar | British Journal of Ophthalmology

Bibliometric analysis of immunotherapy in treatment of uveal melanoma

2025-06-20

Wei Chen , Hui Zhang , Dan Xiao +4 more | Medicine

Bibliometric analysis is a well-established method for evaluating published research and identifying emerging trends in scientific fields. While recent years have witnessed a surge of research on immunotherapy for uveal … Bibliometric analysis is a well-established method for evaluating published research and identifying emerging trends in scientific fields. While recent years have witnessed a surge of research on immunotherapy for uveal melanoma (ITFUM), a comprehensive bibliometric assessment of this domain is lacking. This study aims to conduct a thorough bibliometric analysis to examine the current state, areas of interest, and emerging trends in ITFUM research. A comprehensive collection of 418 publications on ITFUM, sourced from the Web of Science database between January 1, 2000 and May 10, 2024, was analyzed. Employing various bibliometric tools, including HisCite, VOSviewer, CiteSpace, and the bibliometrix package, the study examined data on countries, institutions, authors, journals, references, and keywords. The United States emerged as the leading contributor, accounting for 147 (35.17%) of the published articles. Leiden University was the most productive institution, with 24 (5.74%) publications. The author with the highest publication output was Jager, Martine J. with 15 (3.59%) publications. The journal Cancers demonstrated the highest productivity, with 37 (8.85%) articles. The trend topics between 2023 and 2024 have been identified as "gene," "proton-beam therapy," and "inhibitor." This comprehensive bibliometric analysis provides valuable insights into the current state, collaborative efforts, and future research directions in the field of ITFUM. Further research is needed to identify comprehensive biomarkers and enhance our understanding of the interactions between uveal melanoma cells and infiltrating immune cells. Additionally, efforts should focus on increasing M1-type tumor-associated macrophages, promoting dendritic cells maturation, inhibiting NKT cells, activating NK cells, and refining dendritic cells vaccines and T cell adoptive therapies.

Iris Ganglion Cell

2025-06-20

Thomas J. Cummings | JAMA Ophthalmology

This case report discusses the finding of a ganglion cell in the iris of an adult patient who underwent enucleation for uveal melanoma. This case report discusses the finding of a ganglion cell in the iris of an adult patient who underwent enucleation for uveal melanoma.

Secondary Sinonasal Malignancies After Retinoblastoma

2025-06-20

Amitouj S. Sidhu , J.M. Herrera , Michael W. Jones +5 more | Ophthalmic Plastic and Reconstructive Surgery

Purpose: Retinoblastoma (RB) is the most common intraocular tumor in childhood. Survivors of RB are at risk of developing secondary malignancies. Prior radiotherapy substantially increases the risk of malignancy in … Purpose: Retinoblastoma (RB) is the most common intraocular tumor in childhood. Survivors of RB are at risk of developing secondary malignancies. Prior radiotherapy substantially increases the risk of malignancy in the orbit, brain, and nasal cavities. The authors report 2 new cases of secondary sino-orbital malignancies in RB survivors who underwent radiotherapy during early childhood. A literature review on secondary sinonasal and orbital malignancies in RB is presented. Methods: A case series and literature review of relevant publications on the topic was performed, with appropriate data extracted. Results: Twelve cases of secondary sinonasal and orbital malignancies in RB survivors have been reported, including 5 cases of adenocarcinoma, 2 cases of sinonasal neuroendocrine carcinoma, and 2 cases of olfactory neuroblastoma were also reported. Single cases each of leiomyosarcoma and squamous cell carcinoma were reported. Secondary malignancies are more common in hereditary RB with germline mutations in the RB1 gene. Radiotherapy significantly increases the risk of secondary malignant neoplasms. Secondary sinonasal malignancies are rare in RB survivors. Conclusions: Ophthalmologists should be vigilant of the increased risk of developing secondary orbital and sinonasal malignancies in patients with retinoblastoma, especially in germline mutations and postradiotherapy. Life-long follow-up in RB survivors is recommended to detect and effectively manage these rare but fatal secondary malignant neoplasms.

A Golgi apparatus-related signature for predicting prognosis and evaluating the tumor immune microenvironment of uveal melanoma

2025-06-20

Xian Ge , Fei Ge , Linlin Xiao +1 more | Medicine

Uveal melanoma (UVM), a highly invasive and metastatic primary eye cancer with poor prognosis, contributes significantly to melanoma-related deaths despite being less common. Despite advances in therapy, the mortality rate … Uveal melanoma (UVM), a highly invasive and metastatic primary eye cancer with poor prognosis, contributes significantly to melanoma-related deaths despite being less common. Despite advances in therapy, the mortality rate remains unchanged due to frequent liver metastases and limited effective prognostic biomarkers. This study employed gene expression data from The Cancer Genome Atlas and Gene Expression Omnibus databases to investigate Golgi apparatus-related gene sets (GGRGs) in UVM. Survival analysis, consensus clustering, and principal component analysis were conducted to identify GGRGs associated with patient outcomes. Additionally, tumor microenvironment was assessed using IOBR tools, and a nomogram was constructed based on Cox regression models for predicting survival probabilities. The biological function of carbohydrate sulfotransferase protein family (CHST9) was evaluated by colony formation assay, transwell invasion assay, and wound healing assay. Univariate Cox regression identified 343 GGRGs significantly correlated with UVM prognosis. Consensus clustering revealed 2 distinct subtypes (cluster1 and cluster2) differing significantly in survival, with cluster2 showing more favorable outcomes. Principal component analysis effectively separated these clusters, while Kaplan-Meier curves confirmed their survival disparity. Least Absolute Shrinkage and Selection Operator Cox regression analysis pinpointed a 5-GGRGs-based signature, termed GGRGs-derived index (GGI), composed of lunatic fringe, KDELR3, CHST9, ATP8B3, and ACAN. This GGI stratified UVM cases into High_GGI and Low_GGI groups across multiple datasets, with the Low_GGI group consistently demonstrating significantly improved survival rates compared to the High_GGI group. Notably, the Low_GGI and High_GGI groups exhibited marked differences in clinicopathological characteristics, drug sensitivities, and immune infiltration levels. Ultimately, GGI and age emerged as independent prognostic factors for UVM and were incorporated into a nomogram, which displayed outstanding performance in predicting patient prognosis. Depletion of CHST9 expression dramatically inhibited the proliferative capacity of UVM cells, concurrently suppressing their metastatic activity and invasive properties. GGRGs are promising predictors of UVM prognosis and may inform personalized treatment strategies, contributing to a deeper understanding of the molecular mechanisms driving this aggressive cancer.

Intra-arterial chemotherapy for retinoblastoma: a performance analysis

2025-06-20

Yehonatan Weinberger , Saloni Kapoor , Emily C. Zabor +1 more | British Journal of Ophthalmology

Aim To conduct a performance analysis of intra-arterial chemotherapy (IAC). Material and methods Comprehensive data search in MEDLINE from inception until December 2023. Peer-reviewed, English-language, clinical studies (retrospective, prospective, trials, … Aim To conduct a performance analysis of intra-arterial chemotherapy (IAC). Material and methods Comprehensive data search in MEDLINE from inception until December 2023. Peer-reviewed, English-language, clinical studies (retrospective, prospective, trials, non-randomised) and case series. Two authors abstracted data independently using a standardised form. Study heterogeneity calculation and influence statistics with a leave-one-out analysis were carried out. Globe salvage rates (GSR) (overall, primary and secondary), per international classification of retinoblastoma groups and adjuvant intravitreal chemotherapy were carried out. Performance was assessed using learning curve, experience and study variable effects (site, size and year). Results 416 identified studies met the selection criteria. 43 studies (3174 eyes) were included for random-effects meta-analysis. The statistical test for heterogeneity was significant (p value<0.001). Overall GSR was 73% (95% CI 68 to 77%) and comparable when used as primary (69%, 95% CI 63 to 75%) or as secondary treatment (66%, 95% CI 58 to 74%). GSR was higher (66%, 95% CI 60 to 71%), for group D eyes than for group E eyes (49%, 95% CI 39 to 59%). There was insufficient evidence to conclude the modifying effect of adjuvant intravitreal chemotherapy. Analysis for learning curve effect revealed no improvement in GSR from a unique centre with time. Analysis for the experience effect was precluded due to lack of sufficient data. GSR was not impacted by the national income level of the study site (p value 0.07), study size (<50 eyes vs >=50 eyes, p value 0.449) or year (<=2020 versus >2020, p value <0.0.075). Discussion Improved selection criteria are needed to identify eyes suitable for IAC.

Topical chemotherapy for the treatment of melanocytic conjunctival tumors: An updated review

2025-06-19

Panagiota Tzortzi , Argyrios Tzamalis , Asimina Mataftsi +1 more | European Journal of Ophthalmology

Melanocytic conjunctival tumors including conjunctival melanoma and primary acquired melanosis with atypia, are rare but aggressive, capable of local invasion, systemic spread, and recurrence despite treatment. While surgery remains the … Melanocytic conjunctival tumors including conjunctival melanoma and primary acquired melanosis with atypia, are rare but aggressive, capable of local invasion, systemic spread, and recurrence despite treatment. While surgery remains the standard approach, topical chemotherapy using mitomycin C and interferon alpha-2b has emerged as an alternative. This systematic review, analyzed 22 studies encompassing 116 cases. Among these, 28 cases were treated with mitomycin C as a primary therapy achieving a 60.7% remission rate, and 48 were treated with mitomycin C as adjuvant therapy yielding a 68.8% remission rate. Interferon alpha-2b achieved 87.5% remission across primary and adjuvant applications. Overall, remission was achieved in 74.1% of cases (86 patients). Topical chemotherapy provides a non-surgical approach that treats the entire conjunctival surface eliminating reliance on precise tumor margin identification. Primary mitomycin C demonstrated efficacy in managing diffuse, superficial, and intraepithelial disease whereas adjuvant was more effective for nodular and invasive lesions. Interferon alpha-2b, associated with fewer adverse effects, is a valuable alternative, particularly in cases intolerant to mitomycin C. These findings underscore the potential of topical chemotherapy as both a primary and adjuvant option, highlighting the need for further studies to refine treatment protocols and assess long-term outcomes.

Clinicopathological Features and RB1 Gene Polymorphism in Sudanese Retinoblastoma Patients

2025-06-19

Wifaq Siam , Mona Ellaithi , Hind Mohamed Abushama +6 more | Journal of cancer research updates

Background: Retinoblastoma is a highly aggressive eye cancer affecting infants and young children, with outcomes dependent on early diagnosis. Mortality remains high in low-resource settings. This study aimed to characterize … Background: Retinoblastoma is a highly aggressive eye cancer affecting infants and young children, with outcomes dependent on early diagnosis. Mortality remains high in low-resource settings. This study aimed to characterize retinoblastoma among Sudanese patients, including an analysis of clinicopathological features and the status of RB1 gene polymorphisms. Material and Methods: This is cross-sectional study included 99 Sudanese patients diagnosed with retinoblastoma in Khartoum Teaching Eye Hospital and Mecca Eye Complex. Clinicopathological features and demographic data were retrieved from patient’s medical records and histopathology Laboratory Information System (LIS). Genomic DNA was isolated from formalin fixed paraffin embedded (FFPE) retinoblastoma tissue blocks. Detection of RB 1 gene polymorphism was conducted through Polymerase Chain Reaction (PCR). BLAT search genome used to compare the results of breakpoint sequencing with a reference genomic sequence. Results: Total of 99 retinoblastoma patients were included, (53.5%) were female and (46.5%) were male, with (79.8%) having unilateral lesions and (20.2%) bilateral. Nerve invasion was present in (44.4%) of the cases. Half of patients were diagnosed at advance stage (T4) (58.6%) and at high grade were (Grade 3) (69.7%). (15%) of the cases were from Damazin state, followed by Nyala (13.1%). Conclusion: Detection of retinoblastoma in Sudanese patients often occurs at advanced stages and grades, leading to poorer clinical outcomes. Genetic testing is crucial to identify individuals predisposed to this illness, enabling early intervention and management.

Long-Term Clinical Outcomes for Adolescent and Young-Adult Uveal Melanoma Patients Treated with Dedicated Particle-Beam Radiation

2025-06-19

Carly Zako , Arina Nisanova , Vivian Weinberg +7 more | Cancers

Uveal melanoma (UM) is a rare tumor and a challenging diagnosis for adolescent and young-adult (AYA) patients, as it can threaten vision, quality of life, and life expectancy [...]. Uveal melanoma (UM) is a rare tumor and a challenging diagnosis for adolescent and young-adult (AYA) patients, as it can threaten vision, quality of life, and life expectancy [...].

Prognostic Biopsy of Choroidal Melanoma Before and After Ruthenium-106 Plaque Brachytherapy: Impact on Success of Cytogenetic Analysis

2025-06-19

Keri McLean , Helen Kalirai , Mohamed Amer +4 more | Cancers

Background/Objectives: To determine if the results of cytogenetic analyses of choroidal melanoma biopsies after ruthenium-106 plaque brachytherapy (RPB) are affected by this procedure. Methods: A retrospective study was conducted on … Background/Objectives: To determine if the results of cytogenetic analyses of choroidal melanoma biopsies after ruthenium-106 plaque brachytherapy (RPB) are affected by this procedure. Methods: A retrospective study was conducted on 368 patients with choroidal melanoma treated with RPB who underwent cytogenetic testing at the Liverpool Ocular Oncology Centre (LOOC) between May 2012 and November 2024. Data on demographics, tumor characteristics, treatment date, biopsy timing (pre- or post-RPB), and cytogenetic results were extracted from the LOOC database. Statistical analysis included descriptive statistics, binary, and multinomial logistic regression to assess associations between biopsy timing and biopsy success rates. Results: Biopsies were performed before RPB in 58.7% (216/368) cases, and post-PBR in 41.3%. Cytomorphological identification and molecular genetic testing were successful in 96.4% and 85.1% cases, respectively. Timing of biopsy, patient demographics, and tumor characteristics did not significantly influence cytogenetic test outcomes. Molecular testing could not be performed on 6.8% (25/368) cases as the DNA was insufficient in these samples. Genetic testing success slightly declined beyond three months post-RPB, though a few cases had delayed biopsy (n = 8). Pre-RPB biopsies more frequently demonstrated monosomy 3, whereas post-RPB biopsies had higher rates of disomy 3 (χ2, p < 0.05). Conclusions: Prognostic biopsies post-RPB provide reliable cytomorphological and molecular genetic results using MLPA or MSA. Test failure is not significantly influenced by biopsy timing, patient or tumor characteristics, biopsy modality, or genetic technique. Insufficient DNA yield remains a key limitation, emphasizing the importance of obtaining adequate tissue samples. Biopsies within three months are preferable to optimize success in molecular testing.

Mapping RB1 gene mutations in retinoblastoma: a study of 200 cases from North India

2025-06-19

Ria Ratna , Akhil Varshney , Shailja Tibrewal +3 more | Ophthalmic Genetics

Retinoblastoma is a pediatric ocular malignancy caused by biallelic inactivation of the RB1 gene, with genetic testing crucial for determining heritability. This retrospective observational study analyzed the genotypic and phenotypic … Retinoblastoma is a pediatric ocular malignancy caused by biallelic inactivation of the RB1 gene, with genetic testing crucial for determining heritability. This retrospective observational study analyzed the genotypic and phenotypic profiles of 200 RB patients from North India who underwent genetic testing at a tertiary eye hospital between January 2022 and April 2024. Targeted RB1 gene analysis was performed using next-generation sequencing on blood samples, with methylation specific-multiplex ligation-dependent probe amplification detecting large deletions or duplications. Phenotypic features, including age of onset, laterality, disease severity, metastasis, and recurrence, were assessed. Among 200 patients, 113 had unilateral RB, 85 bilateral, and two trilateral, with mean onset ages of 33 months for unilateral and 14 months for bilateral cases. Intraocular tumors were present in 84%, extraocular extension in 16%, and metastasis in 16% of cases. Pathogenic RB1 variations were identified in 48% of patients, predominantly in bilateral cases (77.08%). A trend toward mutation clustering in exons 14-21 was observed in 57% of patients. While bilateral disease showed a statistically significant correlation with genotype for non-sense variations (p = 0.05); no other clinical features were linked to specific mutations. This study highlights unique regional genotypic patterns and emphasizes the potential for cost-effective testing strategies in resource-limited settings.

Factors associated with lost to follow-up and delayed follow-up in patients with choroidal nevus

2025-06-19

P. Connor Lentz , Muhammad B. Qureshi , Timothy T. Xu +4 more | Eye

Low-Dose Quercetin Dephosphorylates AKT and Suppresses Proteins Related to Migration in Human Metastatic Uveal Melanoma Cells

2025-06-18

Petra Fodor , József Király , Zsuzsanna Szabó +3 more | Life

Background: Uveal melanoma (UM) is the most common intraocular cancer of the eye, with high metastatic potential in adults. In 50% of patients, UM spreads to other tissues, causing a … Background: Uveal melanoma (UM) is the most common intraocular cancer of the eye, with high metastatic potential in adults. In 50% of patients, UM spreads to other tissues, causing a fatal outcome. Flavonoids are bioactive phenolic compounds found in fruits and plants, thus commonly present in the natural diet. Quercetin is the most remarkable agent among flavonols proved to have an anticancer effect. Thus, we aimed to investigate the effect of quercetin on a metastatic UM cell line MM28. Methods: MM28 cells were treated with increasing concentrations of quercetin (0.1-10 µM). The changes of proliferation and migration markers were studied both in gene and protein expression level by qPCR, Western blotting, and Proteome Profiler Human XL Oncology Array. Results: Quercetin had only a slight anti-proliferative effect on MM28 cells. However, 1 µM of quercetin significantly elevated the mRNA expression of the Maspin gene and downregulated MMP2 gene expression. In addition, the protein expression levels of pAKT, NF-κB, and MMP8 were significantly decreased by the treatment. Conclusions: Our findings indicate that low-dose (1 µM) quercetin treatment is able to suppress the expression of certain migration markers, and therefore, it might be a useful adjuvant compound to reduce metastasis formation of UM.

Global trends and emerging insights in ocular tumor-associated metabolites: a bibliometric and visualization analysis

2025-06-18

S. Z. Cai , Weihe Xu , Dongyi Yu +1 more | Frontiers in Molecular Biosciences

Objective This study aims to perform a comprehensive bibliometric analysis of global research on ocular tumor metabolomics, identifying key research trends, influential contributors, and emerging themes from 1995 to 2024. … Objective This study aims to perform a comprehensive bibliometric analysis of global research on ocular tumor metabolomics, identifying key research trends, influential contributors, and emerging themes from 1995 to 2024. Methods A systematic search was conducted in the Web of Science Core Collection (WoSCC) database to retrieve publications related to ocular tumor metabolomics from 1 January 1995, to 12 December 2024. Bibliometric analyses, including publication trends, citation networks, and keyword co-occurrence patterns, were performed using VOSviewer and CiteSpace. Collaborative networks, co-cited references, and keyword burst analyses were mapped to uncover shifts in research focus and global cooperation. Results Both annual publication volume and citation frequency have shown a wave-like increase since 2000. Initially, research activity was limited during the early period (2000-2006), followed by a phase of slow growth between 2007 and 2015. A surge in publications occurred after 2016, peaking in 2022 with 81 articles. Despite the increase in publications, citation frequency declined after 2019, indicating a gap between research output and scholarly impact. The United States, China, and Italy were the top contributing countries, with the U.S. maintaining a leadership role. Keyword analysis revealed key research themes, including biomarkers, uveal melanoma, and immunotherapy, with a shift towards gene expression, tumor metastasis, and liquid biopsy in recent years. Keyword burst analysis identified retinoblastoma protein and gene expression as major research hotspots. Conclusion Ocular tumor metabolomics research has made significant strides in recent years. This analysis provides a comprehensive framework for future research, emphasizing the need for interdisciplinary collaborations and the development of non-invasive diagnostic tools to improve the diagnosis, prognosis, and treatment of ocular tumors.

A Technical Report for Definitive Treatment of Uveal Melanoma With Stereotactic Radiosurgery and Retrobulbar Anesthesia

2025-06-18

Austin D. Williams , Milton Boniuk , Daniel A. Hamstra +2 more | Cureus

Post-radiation choroidal melanoma pathomorphosis assessment in clinical practice

2025-06-18

И. Е. Панова , E.M. Svistunova , E. V. Samkovich +4 more | Russian Journal of Archive of Pathology

Objective. To study the pathomorphological changes in eyes that underwent secondary enucleation following various types of organ-preserving treatments for choroidal melanoma (CM). Material and methods. The study included 22 enucleated … Objective. To study the pathomorphological changes in eyes that underwent secondary enucleation following various types of organ-preserving treatments for choroidal melanoma (CM). Material and methods. The study included 22 enucleated eyes with CM. Secondary enucleation was performed between 2 and 120 months after isolated and combined brachytherapy with Ru-106 and Rh-106 radioisotopes, proton therapy, and Gamma Knife treatment. The reasons for enucleation included progressive tumor growth in 12 patients and complications in 10 patients. Pathomorphological examinations were conducted at the National Center for Clinical Morphological Diagnostics, Saint Petersburg. Results. The majority of the enucleated eyes showed spindle-cell tumors with varying degrees of pigmentation, scleral invasion (95.5%), Bruch’s membrane rupture (90.5%), peri- and intratumoral lymphocytic infiltration (85.7%), signs of perineural invasion (22.7%), and involvement of the optic nerve in the tumor process (28.6%). In the study group, signs of vascular invasion in the tumor parenchyma were observed in only 4.8% of the enucleated eyes. Therapeutic pathomorphosis was evaluated according to Mandard et al. (1994), where TRG4 (60.0%) was frequently diagnosed, and Becker et al. (2003), where TRG3 (65.0%) predominated. The mitotic activity ranged from 1.0 to 5.0 mitoses per 1 mm², with an average of 1.6±1.5. Conclusions. The presence of viable tumor cells and their mitotic activity, regardless of the organ-preserving treatment, reflects the absence of the so-called “devitalization” of the tumor and determines the high risk of continued tumor growth and its possible metastasis.

Uveal Melanoma and the Lynch Syndrome Tumor Spectrum

2025-06-18

Anaïs Le Ven , Marie-Charlotte Villy , André B. Silveira +7 more | JAMA Ophthalmology

Importance To date, no environmental factors and few therapeutic options are known for uveal melanoma (UM), the most common malignant intraocular primary tumor in adults. Identification of new predisposition factors … Importance To date, no environmental factors and few therapeutic options are known for uveal melanoma (UM), the most common malignant intraocular primary tumor in adults. Identification of new predisposition factors could lead to better monitoring and possibly improved treatments of patients with UM. Objective To identify new genetic alterations predisposing for UM. Design, Setting, and Participants This was a prospective cohort study conducted at Institut Curie in Paris, France, among 381 consecutive patients diagnosed with UM between July 2021 and February 2023. UM was diagnosed clinically by ophthalmologists, and a senior pathologist confirmed the diagnosis when tumor or biopsy was available. All participants received genetic counseling and consented to extended genetic testing. A panel of 122 genes predisposing to cancer were analyzed by targeted sequencing on germline DNA from these patients. Main Outcomes and Measures Frequency of pathogenic variants (PVs) in genes from a targeted panel, with classification of germline PVs done according to the American College of Medical Genetics and Genomics guidelines and the French Unicancer Genetics Group. Results A total of 79 PVs were identified in 70 participants (41 female and 29 male; mean [SD] age, 60.6 [15.3] years). Among them, 21 were found in clinically relevant genes, with an enrichment in the mismatch repair (MMR) genes, involved in Lynch syndrome, a frequent predisposition to colon and endometrial cancers. This finding suggested MMR germline PVs could also predispose to UM. One tumor was available from a participant carrying a MLH1 germline PV. The tumor exhibited a monosomy 3 with loss of the wild-type allele of MLH1 , located on chromosome 3. Loss of expression of MLH1 was observed by immunohistochemistry, and MMR variant signatures SBS6, ID1, and ID2 were identified from the whole-genome sequencing of this tumor, supporting the possibility that MLH1 contributes to the oncogenesis of this UM. Conclusions and Relevance This prospective germline study on patients with UM provided evidence supporting the notion that MMR germline alterations are enriched among patients with UM and may contribute to oncogenesis of UM, and that UM may therefore be a rare tumor manifestation of Lynch syndrome.

The refractive parameters of treated retinoblastoma eyes

2025-06-18

Hany Anwar Abdallah , Momen Mahmoud Hamdi , Md. Saifur Rahman +2 more | Ocular Oncology and Pathology

Introduction: The study aimed to investigate the effect of treated retinoblastoma on refractive parameters. Methods: A case control study was conducted in the Ophthalmology department at Ain Shams University from … Introduction: The study aimed to investigate the effect of treated retinoblastoma on refractive parameters. Methods: A case control study was conducted in the Ophthalmology department at Ain Shams University from September 2023 to April 2024. Refractive parameters of treated retinoblastoma eyes were compared to those of age matched: a) fellow eyes of unilateral retinoblastoma children, b) normal eyes of healthy controls. Cycloplegic refraction, ocular biometry and anterior segment optical coherence tomography were performed. Image J software was used to calibrate the radii of curvature of lens surfaces. Results: The study included 35 diseased eyes and 25 fellow eyes of 49 retinoblastoma subjects as well as 26 normal eyes of 26 healthy controls. A statistically significant difference existed between retinoblastoma eyes and eyes of healthy controls regarding refractive astigmatism (P=0.02), corneal astigmatism (P=0.047), anterior chamber depth (P<0.001) and posterior lens curvature (P=0.041). A statistically significant difference existed between RB eyes and fellow eyes regarding refractive astigmatism (P<0.001) and corneal astigmatism (P=0.001). There was no statistically significant difference between fellow eyes and eyes of healthy controls regarding any of refractive parameters. Conclusion: Treated retinoblastoma eyes had shallower anterior chamber, more rounded lens, more astigmatic corneas and more refractive astigmatism than healthy eyes.

Management of Vasoproliferative Tumor in a Patient With Coats' Disease: Multiple Therapeutic Approach in Current Era

2025-06-17

Leonardo Bottazzi , Gaia L'Abbate , Claudia Fossataro +5 more | Ophthalmic surgery, lasers & imaging retina

This case report describes a vasoproliferative tumor in a 16-year-old male patient with Coats' disease, treated with laser photocoagulation, cryoablation, and anti-vascular endothelial growth factor injections therapies, that developed an … This case report describes a vasoproliferative tumor in a 16-year-old male patient with Coats' disease, treated with laser photocoagulation, cryoablation, and anti-vascular endothelial growth factor injections therapies, that developed an epiretinal membrane as a complication. The surgical treatment in association with the retinal laser treatment greatly improved visual acuity. At 8 months follow-up from surgery, visual acuity had significantly improved, and macular anatomy recovered. Vasoproliferative tumors may occur in patients with Coats' disease, and in such a clinical scenario, a multiple therapeutical approach should be considered, in order to reach the best anatomical and functional outcome for the patient. [ Ophthalmic Surg Lasers Imaging Retina 2025;56:XX–XX.]

BAP1 Loss on Immunocytochemistry and Its Association With Monosomy 3 in Uveal Melanoma Fine‐Needle Aspirations

2025-06-17

Precious Ann Fortes , Michelle Nguyen , Po Chu Fung +4 more | Diagnostic Cytopathology

ABSTRACT Background Loss of nuclear BRCA1‐associated protein 1 (nBAP1) expression is strongly linked to monosomy 3 in uveal melanoma. While fine‐needle aspiration (FNA) aids diagnosis, the prognostic value of nBAP1 … ABSTRACT Background Loss of nuclear BRCA1‐associated protein 1 (nBAP1) expression is strongly linked to monosomy 3 in uveal melanoma. While fine‐needle aspiration (FNA) aids diagnosis, the prognostic value of nBAP1 immunocytochemistry (ICC) is still being investigated. This study examines the correlation between nBAP1 loss on ICC and fluorescence in situ hybridization (FISH) findings, as well as its clinical impact. Methods Intraocular FNA cytology specimens with clinical concern for uveal melanoma from April 2015 to March 2023 with available nBAP1 ICC, FISH results, and clinical follow‐up were examined. Two independent reviewers, blinded to the cytogenetic results, interpreted the nBAP1 ICC as either loss or retained. Statistical analysis using Fisher's exact test was utilized to evaluate the relationship between nBAP1 loss on ICC and FISH findings. Kaplan–Meier survival plots were constructed to examine the metastasis‐free survival. Results Among the 79 cases included in the study, 86.1% (68/79) showed nBAP1 loss. Approximately 63.2% of patients with nBAP1 loss had monosomy 3, whereas none with nBAP1 retained had monosomy 3 ( p < 0.001). Of the nBAP1 loss cases, 41.2% (28/68) had monosomy 3 alone, while 22.1% (15/68) had both monosomy 3 and 6p gain. Patients with nBAP1 loss had a significantly higher risk of metastasis ( p ≤ 0.04), with a 5‐year metastasis‐free survival of 57.1% versus 100% in nBAP1 retained cases. Conclusion BAP1 ICC is a cost‐effective prognostic tool in uveal melanoma FNAs, strongly correlating with monosomy 3 and poor outcomes. Integrating BAP1 ICC with FISH enhances risk stratification, enabling earlier identification of high‐risk patients and guiding treatment decisions.

A case of rapidly growing conjunctival squamous cell carcinoma in a 3-year-old child with xeroderma pigmentosum: a case report

2025-06-17

Birhanu Reta , Micheale Hailu Weldegebriel , Hindeya Hailu Hagos +3 more | Journal of Medical Case Reports

Xeroderma pigmentosum is a rare autosomal recessive disorder characterized by hypersensitivity to ultraviolet light owing to mutation of nucleotide excision repair genes. Cutaneous and ocular malignancies commonly occur in the … Xeroderma pigmentosum is a rare autosomal recessive disorder characterized by hypersensitivity to ultraviolet light owing to mutation of nucleotide excision repair genes. Cutaneous and ocular malignancies commonly occur in the first decade of life in patients with xeroderma pigmentosum. Squamous cell carcinoma is the most common ocular malignancy in xeroderma pigmentosum. This case report aims to highlight that ocular malignancy can occur as early as the first few years of age in xeroderma pigmentosum, and the malignancies can progress rapidly unless early intervention is made. We present a case of a 3-year-old male child from Tigray, Ethiopia, who is born to consanguineous parents and presented with right eye swelling and photophobia of 1-month duration. On physical examination, there was a fungating, ulcerated mass over the right palpebral conjunctiva and dry lentigos, scaly skin with poikiloderma over his face, neck, hands, and leg. A clinical diagnosis of xeroderma pigmentosum was made on the basis of history and cutaneous manifestations, and histopathologic examination of the conjunctival mass confirmed squamous cell carcinoma with orbital soft tissue extension. Ocular malignancies are disabling manifestations of xeroderma pigmentosum that usually occur in the first decade of life. Patients with xeroderma pigmentosum should be strongly advised on lifetime protection against ultraviolet light exposure, vitamin D supplementation, and frequent dermatologic and ophthalmologic examination to detect and treat early-stage malignancies. Delayed diagnosis of ocular malignancies may result in more aggressive management such as enucleation and exenteration.

Chemotherapy Approaches in the Treatment of Childhood Retinoblastoma: Comparison of Intravenous, Intra-arterial and Intravitreal Therapies

2025-06-16

Gabriel Queiroz Sabbag , Marcus Baia Fonseca , Isabella P. Lerio +7 more | European Journal of Cancer

Outcomes and adverse events following intra-arterial chemotherapy for retinoblastoma: A single center study in South India

2025-06-16

Abhishek Das , Kothapally Saiteja , Parag K. Shah +2 more | World Journal of Clinical Pediatrics

BACKGROUND Intra-arterial chemotherapy (IAC) has become a first-line standard treatment for retinoblastoma (RB). However, studies describing its adverse events are sparse, especially from the developing world. Our study described the … BACKGROUND Intra-arterial chemotherapy (IAC) has become a first-line standard treatment for retinoblastoma (RB). However, studies describing its adverse events are sparse, especially from the developing world. Our study described the outcomes and adverse events from a single center in South India. AIM To describe the challenges, treatment outcomes, and complications of selective IAC for RB in Indian eyes. METHODS This study was a single center, retrospective study that included 17 patients with RB who underwent IAC using melphalan (5/7.5 mg) and topotecan (1/2 mg) (n = 12) or melphalan (5 mg) alone (n = 3) or triple therapy that included carboplatin (30 mg) along with these drugs (n = 2) between January 2018 and December 2023. In all, 17 IAC procedures were performed using selective ophthalmic artery cannulation. Treatment outcomes were evaluated in terms of tumor control, vitreous and subretinal seed control, complications, and globe salvage rates. RESULTS Out of the 17 patients, 11 were diagnosed with unilateral RB and 6 were diagnosed with bilateral RB. The mean age at the time of diagnosis was 19.8 months. The mean interval between the first symptom and presentation was 6.5 months. IAC was employed as the primary (n = 9) or secondary (n = 8) modality of treatment. Each eye received a mean of 1.5 IAC sessions (median: 1 session; range: 1-3 sessions). Eyes were classified according to the international classification of RB as group B (n = 5), group C (n = 1), group D (n = 4), and group E (n = 7). Following IAC, complete regression of the main tumor was seen in 15 eyes (88%) and partial regression in 2 eyes (12%). Globe salvage was achieved in 15 eyes (88%). Adverse effects included vitreous hemorrhage (n = 3), rhegmatogenous retinal detachment (n = 2), choroidal ischemia (n = 1), isolated subretinal hemorrhage (n = 2), retinal pigment epithelium degeneration (n = 2), forehead pigmentation (n = 1), third nerve palsy with complete ptosis (n = 1), and 30-degree exotropia (n = 1). The mean follow-up period was 28.6 months (median: 24 months, range: 1–72 months). CONCLUSION IAC is an effective way to control RB and globe preservation. In the Indian context we encountered many challenges highlighting the importance of case selection. Further studies in India are required to thoroughly understand IAC as a treatment for RB.

Liquid biopsy as a potential tool for diagnosis and clinical monitoring of cutaneous and uveal melanoma

2025-06-14

Letícia S. Ferraz , Arthur Soares Souza , Tiago Rodrigues +1 more | The Journal of Liquid Biopsy

Ophthalmic Tumors

2025-06-14

| TNM Online

Abstract Tumours of the eye and its adnexa are a disparate group including carcinoma, melanoma, sarcomas and retinoblastoma. For histological nomenclature and diagnostic criteria, reference to the World Health Organization … Abstract Tumours of the eye and its adnexa are a disparate group including carcinoma, melanoma, sarcomas and retinoblastoma. For histological nomenclature and diagnostic criteria, reference to the World Health Organization histological classification is recommended. There should be histological confirmation of the disease and division of cases by histological type, for example, mucoepidermoid and squamous cell carcinoma. The regional lymph nodes are the preauricular, submandibular and cervical lymph nodes. The International Classification of Diseases for Oncology (ICD‐O‐4C69.0) applies only to conjunctival melanoma. There should be histological confirmation of the disease. In bilateral cases, the eyes should be classified separately. The classification does not apply to complete spontaneous regression of the tumour. There should be histological confirmation of the disease in an enucleated eye. The chapter presents prognostic factors for survival for uveal melanoma and retinoblastoma.

Emerging Techniques in the Treatment of Conjunctival Melanoma

2025-06-13

Wenzhao Li , Nandini Venkateswaran , Michael Antonietti +3 more | Current Ophthalmology Reports

Abstract Purpose of review In this article, we summarize the pathogenesis, diagnostic challenges, current management, and emerging therapeutic strategies for conjunctival melanoma (CM). Recent findings CM is a deadly disease … Abstract Purpose of review In this article, we summarize the pathogenesis, diagnostic challenges, current management, and emerging therapeutic strategies for conjunctival melanoma (CM). Recent findings CM is a deadly disease with rising global incidence. Key mutations, including BRAF, NF1, and TERT, play crucial roles in CM pathogenesis and may serve as targets for therapy. Advanced imaging and histopathological analysis have improved early detection and prognostic assessment. Treatment depends on tumor stage and includes surgical excision with adjuvant chemotherapy, radiotherapy, or orbital exenteration in advanced cases. Systemic workup is always indicated. Immune checkpoint inhibitors, successful in cutaneous melanoma, show promise in CM based off early studies, although more research is needed to confirm their benefit. Summary CM remains a significant clinical challenge and requires a multidisciplinary approach to diagnosis and treatment. Incorporating genetic profiling and targeted therapies is crucial to improving patient outcomes.

Intra-Arterial Melphalan Chemotherapy for Retinoblastoma in a Developing Nation: Real-World Outcomes and Prognostic Factors

2025-06-12

Yacoub A. Yousef , Mona Mohammad , Odai Al-Jabari +7 more | Cancers

Background: Intra-arterial chemotherapy (IAC) is increasingly useful for treating intraocular retinoblastoma (Rb). It offers targeted delivery of chemotherapy with reduced systemic exposure. In this study, we evaluate management outcomes and … Background: Intra-arterial chemotherapy (IAC) is increasingly useful for treating intraocular retinoblastoma (Rb). It offers targeted delivery of chemotherapy with reduced systemic exposure. In this study, we evaluate management outcomes and identify predictive factors for globe salvage following IAC in children with Rb. Methods: This retrospective study included 20 eyes of 20 melphalan-based IAC-treated patients (67 sessions) between 2015 and 2023 in a tertiary cancer center (King Hussein Cancer Center) in Jordan. Data collection included patients’ demographics, tumor staging, eye salvage, complications, and survival, followed by statistical comparisons between eye salvage rates and clinical factors. Results: The median age of IAC initiation was 38 months (range: 6–78 months). IAC was used as a primary treatment in 35% (7/20) of eyes and as a secondary treatment following systemic chemotherapy in 65% (13/20) of eyes. Nineteen (95%) eyes showed initial tumor regression, 15 (75%) eyes showed short term tumor control, and long-term eye salvage was achieved in 11 (55%) eyes. Poor prognostic factors for eye salvage included advanced tumor stage (Group D/E: 43% salvage rate vs. Group C: 83%; p = 0.047), vitreous seeding at the time of IAC (38% with seeding vs. 75% without; p = 0.046), use of IAC as a secondary rather than a primary treatment (46% vs. 71%; p = 0.047), and the need for >3 IAC cycles (20% success with >3 cycles vs. 67% with ≤3 cycles; p = 0.034). Complications were notable: systemic adverse effects were seen in five (25%) patients, including neutropenia (20%) and bronchospasm (6%). Procedure-related complications were seen with 22% of injections, including failure of the procedure (7%), ophthalmic artery spasm (6%), and intra-procedural stroke (3%). Five (25%) eyes developed ocular complications, including vitreous hemorrhage (15%), retinal detachment (10%), optic atrophy (10%), and retinal or choroidal ischemia (10%). Notably, all infants under 12 months of age (4/4) developed complications, including the two events of stroke. At a median follow-up of 60 months, eye salvage was achieved in 11 (55%) eyes, and none of the 9 (45%) enucleated eyes showed high-risk pathological features. There was no orbital recurrence, and one (5%) child developed CNS metastasis and passed away. Conclusion: IAC achieves long-term globe salvage in 55% of Rb cases; however, outcomes are poorer with Group D/E tumors, vitreous seeds, prior IVC failure, or requiring >3 IAC cycles. While reducing systemic chemotherapy toxicity, IAC carries significant risks of vision- and life-threatening complications. Infants and single-eyed patients require particularly cautious consideration. Though IAC remains crucial for globe preservation, optimal implementation demands improved patient selection criteria, multicenter collaboration, and long-term outcome studies to maximize safety and efficacy.

ASO Author Reflections: Percutaneous Hepatic Perfusion with Melphalan/Hepatic Delivery System Versus Best Alternative Care for Patients with Metastatic Uveal Melanoma

2025-06-12

Jonathan S. Zager , Johnny John | Annals of Surgical Oncology

Early Genetic Evolution of Driver Mutations in Uveal Melanoma

2025-06-12

James J. Dollar , Christina L. Decatur , Ezekiel Weis +7 more | medRxiv (Cold Spring Harbor Laboratory)

ABSTRACT Uveal melanoma (UM) is an aggressive cancer of the eye that frequently results in metastatic death. UMs are most likely to metastasize when they are small, at a time … ABSTRACT Uveal melanoma (UM) is an aggressive cancer of the eye that frequently results in metastatic death. UMs are most likely to metastasize when they are small, at a time when they are difficult to distinguish from benign nevi and often observed without treatment. Unfortunately, little is known about the early genetic evolution of UM or potential biomarkers to indicate small tumors undergoing malignant transformation. Here, we performed targeted next generation sequencing for the 7 canonical UM driver mutations in 1140 primary UMs, including 131 small early-stage tumors. We found that the evolutionary burst of genetic aberrations that determines the archetypal UM subtypes and metastatic propensity has already occurred by the time most small tumors are biopsied, although a significantly larger proportion of small tumors are still evolving compared to larger tumors. We found that the 15-gene expression profile (15-GEP) support vector machine discriminant score was the best indicator of tumors in transition from low-risk Class 1 to high-risk Class 2 signature. While BAP1 , SF3B1 and EIF1AX mutations were associated with poor, intermediate and good prognosis, respectively, mutation analysis was inferior to the prospectively validated 15-GEP + PRAME expression classifier for predicting metastasis-free and overall survival. These results provide a more complete picture of genetic evolution in UM, and they move us closer to a molecular definition of malignant transformation in this cancer type.

A nomogram to predict cancer-specific survival of ocular melanoma

2025-06-12

Ruisheng Huang , Jian Chen , Limin Lin +2 more | Discover Oncology

To develop a nomogram that accurately predicts cancer-specific survival (CSS) in patients with ocular melanoma (OM). Patient data for individuals diagnosed with OM between 2004 and 2015 were obtained from … To develop a nomogram that accurately predicts cancer-specific survival (CSS) in patients with ocular melanoma (OM). Patient data for individuals diagnosed with OM between 2004 and 2015 were obtained from the Surveillance, Epidemiology, and End Results (SEER) database. The patients were then randomly divided into a training group and a validation group. Multivariate Cox proportional hazards regression analysis was utilized to identify significant variables. Subsequently, an independent variable-based nomogram was developed. Finally, multiple methods were used to verify and evaluate the performance of the nomogram. A total of 5,053 eligible patients diagnosed with OM were randomly divided into a training group (n = 3,537, 70%) and a validation group (n = 1,516, 30%). Age, race, primary site, histological type, American Joint Committee on Cancer (AJCC) stage, SEER stage, surgery, radiotherapy and chemotherapy were identified as independent prognostic factors for predicting the CSS of OM. These factors were incorporated into the development of a nomogram. Compared with AJCC, the nomogram is better than AJCC in concordance index (C-index), receiver operating characteristic (ROC) curve, net reclassification index (NRI), integrated discrimination improvement index (IDI), calibration curve and decision curve analysis (DCA). We developed a nomogram that can be used to predict the 3, 5 and 8 years cancer-specific survival (CSS) rates for patients diagnosed with OM. The nomogram offers a more precise and personalized approach for predicting patient survival outcomes while assisting ophthalmologists in devising improved clinical management strategies and treatment plans.

Multimodal Imaging in Bilateral Isolated Choroidal Melanocytosis

2025-06-10

Rouzbeh Abbasgholizadeh , Giovanni Bellisario , Ye He +3 more | Retinal Cases & Brief Reports

Purpose: To report a rare case of bilateral isolated choroidal melanocytosis and highlight the need for thorough imaging evaluation. Methods: Multimodal imaging, including ultra-widefield fundus photography, fundus autofluorescence, optical coherence … Purpose: To report a rare case of bilateral isolated choroidal melanocytosis and highlight the need for thorough imaging evaluation. Methods: Multimodal imaging, including ultra-widefield fundus photography, fundus autofluorescence, optical coherence tomography (OCT), and OCT angiography, was utilized to assess the findings. Results: A 58-year-old hispanic female was referred for evaluation of unusual pigmentation in both eyes. She reported occasional floaters but had no other ocular symptoms. Dilated fundus examination and ultra-widefield color fundus imaging revealed extensive choroidal hyperpigmentation involving 360 degrees of the peripheral retina in both eyes. Fundus autofluorescence imaging demonstrated that the hyperpigmented regions were mildly hypofluorescent relative to the less pigmented central regions. Widefield OCT angiography demonstrated absence of any vascular abnormalities in the retina or inner choroid. Widefield structural OCT revealed normal retinal thickness and structure overlying the hyperpigmented areas. There was no choroidal elevation, but the choroidal stroma in the more peripheral regions of the fundus appeared more hyperreflective compared to the presumed normally pigmented central regions. While no choroidal elevation was noted, there was a mild increase in sub-foveal choroidal thickness. No evidence of scleral or periocular cutaneous pigmentation was observed. The overall findings, considering the patient’s ethnicity and skin pigmentation, favored a diagnosis of bilateral idiopathic choroidal melanocytosis. Conclusion: Bilateral isolated choroidal melanocytosis, can be diagnosed accurately through comprehensive imaging. Vigilant monitoring is essential due to the potential risk of malignant transformation.

UVEAL METASTASIS FROM PROSTATE CANCER

2025-06-10

Vladimir Vorobev , А. В. Щербатых , K. B. Lelyavin +4 more | Baikal Medical Journal

Background. Ocular metastases from prostate cancer are extremely rare, accounting for less than 1 % of all orbital tumors. Despite their rarity, these lesions are clinically significant due to the … Background. Ocular metastases from prostate cancer are extremely rare, accounting for less than 1 % of all orbital tumors. Despite their rarity, these lesions are clinically significant due to the risk of vision loss and pain, and they often indicate advanced systemic disease. Objective. To review the current literature on the clinical features, diagnostic methods, treatment strategies, and prognosis of ocular metastases from prostate cancer. Results. Common manifestations include proptosis, visual acuity decline, diplopia, and orbital pain. Metastases typically involve the orbit or choroid. Diagnosis requires a high degree of clinical suspicion and includes orbital magnetic resonance imaging, PSMA positron emission tomography/computed tomography, ophthalmoscopy, and histopathological confirmation via biopsy. Elevated prostate-specific antigen levels with ocular symptoms strongly suggest metastatic prostate cancer. Treatment is mainly palliative and involves systemic androgen deprivation therapy, chemotherapy, and local radiotherapy. In some cases, regression of ocular lesions and symptom relief can be achieved, particularly if therapy is initiated early. Nevertheless, the median survival after diagnosis of ocular metastases is generally limited to 7–24 months. Conclusion. Ocular involvement in prostate cancer represents a rare but serious metastatic manifestation. Early detection and a multidisciplinary therapeutic approach are essential to reduce symptom burden and improve quality of life. Further research and accumulation of clinical data are necessary to develop optimal management strategies for this uncommon complication.

Stallard’s Contribution to Uveal Melanoma Management

2025-06-09

Bertil Damato | Ocular Oncology and Pathology

Hyla (‘Henry’) Bristow Stallard (1901 – 1973) was an English ophthalmologist who made a significant contribution to ophthalmology and to ocular oncology. He achieved international fame as an athlete during … Hyla (‘Henry’) Bristow Stallard (1901 – 1973) was an English ophthalmologist who made a significant contribution to ophthalmology and to ocular oncology. He achieved international fame as an athlete during his early years, breaking several records and winning a medal in the 1924 Paris Olympic Games. He served as Consultant Surgeon and Pathologist at Moorfields and St. Bartholomew’s Hospitals. During is training, he wrote a thesis entitled ‘Radiant Energy as (a) a pathogenic and (b) a therapeutic agent in ophthalmic disorders’, for which he was awarded the Gifford Edmonds Prize Essay in 1932. In 1946, he published his influential textbook on eye surgery, which ran to six editions. In the introduction to this book, he highlighted the requirements of a good surgeon, which are as valid today as they were in his time. He published numerous scientific articles and delivered many eponymous lectures in several countries, receiving a large number of prestigious awards. In 1972, he was elected President of the Ophthalmological Society of the United Kingdom. One of Stallard’s great achievements was the development of plaque brachytherapy for choroidal melanomas, which involved designing the applicator, determining the required radiation dosimetry, and publishing long-term outcome studies. This was at a time when these tumors were widely considered to be untreatable with radiotherapy because they are so radioresistant. He also pioneered iris melanoma brachytherapy, trans-retinal and trans-scleral tumor biopsy, partial choroidectomy, iridocyclectomy and iridectomy, orbital surgery, retinoblastoma treatment and he invented or designed several instruments. His legacy extends beyond specific therapeutic techniques by inspiring ophthalmologists to teach, perform research, and publish their findings and innovations for the benefit of future patients around the world. This review focuses on Stallard’s contribution to the treatment of uveal melanoma.

Managing retinoblastoma in 2025

2025-06-05

Eugenia M. Ramos‐Dávila , Basil K. Williams , Maura Di Nicola | Current Opinion in Ophthalmology

Purpose of review The management of retinoblastoma is an evolving field, with ongoing research focused on novel diagnostic techniques and therapeutic interventions. This review aims to summarize the current treatment … Purpose of review The management of retinoblastoma is an evolving field, with ongoing research focused on novel diagnostic techniques and therapeutic interventions. This review aims to summarize the current treatment options for retinoblastoma and explore future directions in the field. Recent findings Early diagnosis remains crucial for improving prognosis in retinoblastoma, as prompt identification significantly enhances treatment success. New diagnostic imaging strategies as well as prenatal testing are being developed to detect subclinical disease in high-risk patients, allowing for earlier intervention. Recurrent or refractory disease remains a challenge, but encouraging results have been observed with intravenous chemotherapy, intra-arterial chemotherapy, and intravitreal chemotherapy as salvage therapies. Other strategies, including anterior chamber chemotherapy, novel drug formulations, and advanced delivery methods like sustained release chemotherapy in the form of a chemoplaque, are being explored to address these persistent challenges. Summary Significant progress in retinoblastoma treatment has led to a dramatic improvement in globe salvage rates. Nevertheless, challenges remain. Delayed diagnosis, particularly in low-income and middle-income regions, continues to contribute to reduced survival rates. Additionally, the management of advanced disease, as well as recurrent or refractory tumors, remain critical issues. The development of new drugs and delivery methods as well as modified treatment strategies offer promise in overcoming these obstacles.