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Acta Ophthalmologica Feb 2022Approximately twenty per cent of Von Hippel-Lindau patients with retinal haemangioblastomas (RH) suffer from visual impairment. Various treatment options are available...
IMPORTANCE
Approximately twenty per cent of Von Hippel-Lindau patients with retinal haemangioblastomas (RH) suffer from visual impairment. Various treatment options are available for peripheral RH. However, management of peripheral RH is complex due to multifocality and bilaterality.
OBJECTIVE
To summarize published evidence on efficacy and safety of different interventions for peripheral RH and to provide treatment recommendations for specialists.
EVIDENCE REVIEW
Comprehensive searches were performed using Medline, Embase, Web of Science and Google Scholar database on 4 March 2020. English publications that described outcomes related to efficacy or complications in at least two patients with peripheral RH were included. Efficacy and safety were estimated by complete tumour eradication rate, pretherapeutic and treatment-related complication rate. Odds ratios (OR) with 95% confidence intervals (CI) were calculated to calculate the risk estimate of complications between treatment options.
FINDINGS
Twenty-seven articles were included in this review describing nine different treatment options for peripheral RH: laser photocoagulation (n = 230), cryotherapy (n = 50), plaque radiotherapy (n = 27), vitreoretinal surgery (n = 88), photodynamic therapy (PDT; n = 14), transpupillary thermotherapy (TTT; n = 10), external beam radiotherapy (n = 3), systemic treatment (n = 7) and intravitreal anti-VEGF (n = 2). Complete tumour eradication was achieved in 86.7% (95% CI: 83.5-89.9%) of all eyes. For the different treatments, this was after laser photocoagulation 89.9% (86.1-93.7%), cryotherapy 70.2% (57.0-83.4%), plaque radiotherapy 96.3% (89.1-100.0%), vitreoretinal surgery (100.0%), PDT 64.3% (38.3-90.3%) and TTT 80.0% (53.8-100.0%). No complete tumour eradication was achieved after systemic therapy, external beam radiotherapy or intravitreal anti-VEGF. Photodynamic therapy and vitreoretinal surgery showed the highest complication rate after treatment compared to the other treatments (OR 10.5 [95% CI: 2.9-38.4]) and (OR 5.9 [95% CI: 3.4-9.9]), respectively. Cases that had pretherapeutic complications showed a higher treatment-related complication rate (OR 14.8 [95% CI: 7.3-30.0]) than cases without complications before treatment.
CONCLUSIONS AND RELEVANCE
These findings suggest that laser photocoagulation is the safest and most effective treatment method for peripheral RH up to 1.5 mm in diameter. Vitreoretinal surgery has the highest success rate for complete tumour eradication and may be the most suitable treatment option in the presence of pretherapeutic complications and for larger tumours.
Topics: Hemangioblastoma; Humans; Laser Coagulation; Photochemotherapy; Retinal Neoplasms; Treatment Outcome; Visual Acuity
PubMed: 33834636
DOI: 10.1111/aos.14865 -
Eye (London, England) Jul 2022Paraneoplastic syndromes affecting the visual system are a group of conditions that arise in the systemic malignancy framework. In this review, we have provided a... (Review)
Review
Paraneoplastic syndromes affecting the visual system are a group of conditions that arise in the systemic malignancy framework. In this review, we have provided a detailed and comprehensive overview of the published literature on the various ophthalmic paraneoplastic manifestations. A systematic review of many databases has been performed to identify ample literature on the paraneoplastic syndromes related to ophthalmology. We have discussed here the clinical features, pathogenesis, and treatment strategies of various ophthalmic paraneoplastic syndromes. It can be challenging to distinguish these disorders from their non-paraneoplastic counterparts and to determine the appropriate systemic assessment for the tumour responsible, to have a proper approach towards the management of the syndrome. METHOD: We searched PubMed, Science Direct and Journal of Ophthalmology for studies published in English between 1995 and April 2020, incorporating the general search term "paraneoplastic ocular syndrome" with connecting terms relevant to subheadings-e.g. Key search terms were cancer-associated retinopathy, (CAR), melanoma-associated retinopathy, (MAR), paraneoplastic retinopathy, autoimmune retinopathy, autoimmune-related retinopathy, and optic neuropathy, (ARRON), acute zonal occult outer retinopathy, (AZOOR), paraneoplastic vitelliform maculopathy, paraneoplastic vitelliform retinopathy, bilateral diffuse uveal melanocytic proliferation, (BDUMP), paraneoplastic optic neuropathy, (PON), polyneuropathy, organomegaly, endocrinopathy, monoclona gammopathy, and skin changes syndrome (POEMS) and various other terms. References from identified studies have been reviewed and included if deemed appropriate, valid, and scientifically important. If referenced in a selected English paper, we contemplated papers in other languages too. We preferentially selected papers that have been published in the last 10 years, but we have included relevant older references.
Topics: Autoantibodies; Autoimmune Diseases; Humans; Optic Nerve Diseases; Paraneoplastic Syndromes, Ocular; Retinal Diseases; Retinal Neoplasms
PubMed: 34345027
DOI: 10.1038/s41433-021-01676-x -
American Journal of Ophthalmology Dec 2015To estimate the incidence of trilateral retinoblastoma in patients with retinoblastoma. (Meta-Analysis)
Meta-Analysis Review
PURPOSE
To estimate the incidence of trilateral retinoblastoma in patients with retinoblastoma.
DESIGN
Systematic review and meta-analysis.
METHODS
We searched Medline and Embase for scientific literature published between January 1966 and July 2015 that assessed trilateral retinoblastoma incidence. We used a random-effects model for the statistical analyses.
RESULTS
We included 23 retinoblastoma cohorts from 26 studies. For patients with bilateral retinoblastoma the unadjusted chance of developing trilateral retinoblastoma across all cohorts was 5.3% (95% confidence interval [CI]: 3.3%-7.7%); the chance of pineal trilateral retinoblastoma was 4.2% (95% CI: 2.6%-6.2%) and the chance of nonpineal trilateral retinoblastoma was 0.8% (95% CI: 0.4%-1.3%). In patients with hereditary retinoblastoma (all bilateral cases, and the unilateral cases with a family history or germline RB1 mutation) we found a trilateral retinoblastoma incidence of 4.1% (95% CI: 1.9%-7.1%) and a pineal trilateral retinoblastoma incidence of 3.7% (95% CI: 1.8%-6.2%). To reduce the risk of overestimation bias we restricted analysis to retinoblastoma cohorts with a minimum size of 100 patients, resulting in adjusted incidences of 3.8% (95% CI: 2.4%-5.4%), 2.9% (95% CI: 1.9%-4.2%), and 0.7% (95% CI: 0.3%-1.2%) for any, pineal, and nonpineal trilateral retinoblastoma, respectively, among patients with bilateral retinoblastoma. Among hereditary retinoblastoma we found an adjusted trilateral retinoblastoma incidence of 3.5% (95% CI: 1.2%-6.7%) and a pineal trilateral retinoblastoma incidence of 3.2% (95% CI: 1.4%-5.6%).
CONCLUSION
The estimated incidence of trilateral retinoblastoma is lower than what is reported in previous literature, especially after exclusion of small cohorts that were subject to overestimation bias in this context.
Topics: Global Health; Humans; Incidence; Retinal Neoplasms; Retinoblastoma
PubMed: 26374932
DOI: 10.1016/j.ajo.2015.09.009 -
The Lancet. Global Health Mar 2022Despite advancements in globe-preserving treatments, improvements in retinoblastoma outcomes are inconsistent across income levels and geographical locations. We aimed... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Despite advancements in globe-preserving treatments, improvements in retinoblastoma outcomes are inconsistent across income levels and geographical locations. We aimed to investigate trends in global retinoblastoma survival and globe preservation during the past 40 years. We also examined associated socioeconomic and health-care factors and global survival disparity.
METHODS
We did a systematic review and meta-analysis by screening articles in any language in nine databases (PubMed, Embase, ScienceDirect, Web of Science, OpenGrey, Global Burden of Disease, Global Health Data Exchange, Global Index Medicus, and International Agency for the Prevention of Blindness) published between Jan 1, 1981, and Oct 8, 2021. We screened for articles that described retinoblastoma overall survival or globe salvage, or both. All reported studies were subsequently stratified into four periods: 1980-89, 1990-99, 2000-09, and 2010-20. Indicators on socioeconomic and health-care factors were extracted from the World Bank and WHO. Ophthalmology-related indicators were further parsed from the International Agency for the Prevention of Blindness. Between-study heterogeneities by income level were assessed by mixed-effect meta-analysis. Associations of retinoblastoma outcome with socioeconomic and health-care factors and factors for survival prediction were investigated by multivariable linear regressions. This study is registered with PROSPERO, number CRD42020221556.
FINDINGS
Our search identified 14 621 articles, of which 314 studies were included for analysis after screening, including 38 130 patients from 80 regions globally presenting during 1980-2020. 255 articles were entered for time-trend meta-analysis, covering 29 106 patients from 73 countries. Both overall survival (from 79% [95% CI 74-84] to 88% [83-93]; p=0·017) and globe salvage rate (from 22% [14-32] to 44% [36-52]; p=0·0003) improved significantly over the four decades. Wide disparities were observed between higher-income and lower-income countries. Overall survival, globe salvage, and globe salvage for advanced intraocular disease correlated positively with income level. Higher overall survival was associated with lower Gini index (p=0·0001) and with populations that had smaller percentages living in rural areas (p=0·0005). Higher globe salvage was associated with better health-care financing and accessibility (p=0·030). Overall survival (p=0·0024) and globe salvage (p=0·022) were both associated positively with education level. Survival gaps were observed in sub-Saharan Africa and southeast and southwest Asia.
INTERPRETATION
Retinoblastoma treatment outcomes have improved globally over the past four decades but large disparities persist between higher-income and lower-income countries, with some areas having major survival gaps. Targeted health-care policy making with increased health-care financing and accessibility are needed in low-income and lower-middle-income countries to improve retinoblastoma outcomes worldwide.
FUNDING
Health and Medical Research Fund (Hong Kong) and Children Cancer's Foundation (Hong Kong).
Topics: Global Health; Health Care Surveys; Humans; Organ Sparing Treatments; Retinoblastoma; Socioeconomic Factors
PubMed: 35093202
DOI: 10.1016/S2214-109X(21)00555-6 -
International Journal of Public Health 2023To study the prevalence and the association of HPV infection in retinoblastoma and to determine the most common genotype presented in RB. Following the PRIMSA... (Meta-Analysis)
Meta-Analysis Review
To study the prevalence and the association of HPV infection in retinoblastoma and to determine the most common genotype presented in RB. Following the PRIMSA guideline, 14 studies reporting HPV infection in RB acquired from six databases were included. The prevalence of HPV from 941 RB samples was 15.6% [95% confidence interval (CI): 7.3-30]. Mexico followed by India and Brazil had the highest HPV prevalence in RB samples, 61.7% (95% CI: 17-93), 22.5% (95% CI: 9-47), and 12.1% (95% CI: 2-52), in order. HPV 16 was the most common genotype presented in RB samples 23% (95% CI: 9-47), followed by HPV 18 10% (95% CI: 3-30) and the combined HPV 16-18 6% (95% CI: 0-50). We did not find a significant association between HPV and RB [odds ratio (OR): 12.2; 95% CI: 0.65-232; = 0.09]. However, after removing the largest-weighted study, a significant association between HPV and RB was observed (OR: 45.9; 95% CI; 8.6-245; < 0.001). HPV prevalence in RB samples was 15% and HPV 16 was the most presented genotype in RB samples. There may be an association between HPV and RB that is needed to be confirmed by high quality future studies. Preventive and treatment measures against HPV infection are essential for the prevention of any possible consequences, in particular, RB.
Topics: Humans; Retinoblastoma; Papillomavirus Infections; Human Papillomavirus Viruses; Cross-Sectional Studies; Human papillomavirus 16; Prevalence; Retinal Neoplasms
PubMed: 37497122
DOI: 10.3389/ijph.2023.1605284 -
BMJ Open Ophthalmology 2022To demonstrate the spectrum of autoimmune retinopathy (AIR) associated with immunotherapy for advanced cutaneous melanoma.
Autoimmune retinopathy with associated anti-retinal antibodies as a potential immune-related adverse event associated with immunotherapy in patients with advanced cutaneous melanoma: case series and systematic review.
OBJECTIVE
To demonstrate the spectrum of autoimmune retinopathy (AIR) associated with immunotherapy for advanced cutaneous melanoma.
METHODS AND ANALYSIS
Retrospective chart review on patients with advanced cutaneous melanoma who developed AIR after initiating immunotherapy. Complete ophthalmic examination and relevant ancillary testing were performed on each patient. The presence of AIR-associated anti-retinal antibodies was confirmed by western blot and/or immunohistochemical staining. Ophthalmic and systemic outcomes after treatment for AIR were followed over time. A systematic review of AIR associated with immunotherapy for cutaneous or non-ocular mucosal melanoma was carried out in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.
RESULTS
Case 1 developed photopsia and nyctalopia with electroretinographic findings characteristic for melanoma-associated retinopathy 1 week after initiating ipilimumab/nivolumab immunotherapy. Case 2 experienced new severe bilateral visual field loss associated with anti-retinal and anti-optic nerve antibodies while on maintenance nivolumab immunotherapy. Case 3 developed decreased visual acuity due to acute exudative polymorphous vitelliform maculopathy within 2 weeks of initiating ipilimumab/nivolumab immunotherapy. All patients had concurrent extraocular immune-related adverse events in addition to the presence of anti-retinal antibodies on serological testing. 14 published cases of AIR associated with immunotherapy for cutaneous or non-ocular mucosal melanoma were identified and reviewed.
CONCLUSIONS
Immune checkpoint inhibition can trigger the development of AIR with varied clinical manifestations in patients with advanced cutaneous melanoma. This study highlights the need for close monitoring in cutaneous melanoma patients receiving immunotherapy who develop new visual symptoms with or without funduscopic changes, as well as the potential role for screening of patients prior to initiating immunotherapy.
Topics: Antibodies, Monoclonal, Humanized; Autoimmune Diseases; Humans; Immunologic Factors; Immunotherapy; Ipilimumab; Melanoma; Nivolumab; Retinal Diseases; Retrospective Studies; Skin Neoplasms; Melanoma, Cutaneous Malignant
PubMed: 35047671
DOI: 10.1136/bmjophth-2021-000889 -
BMC Ophthalmology Nov 2023Vitreoretinal lymphoma (VRL) is usually treated with a combination of intraocular methotrexate (ioMTX), high-dose intravenous methotrexate (HD-MTX), or local... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Vitreoretinal lymphoma (VRL) is usually treated with a combination of intraocular methotrexate (ioMTX), high-dose intravenous methotrexate (HD-MTX), or local radiotherapy (RT) as the first options. The effectiveness and safety of monotherapy like bruton's tyrosine kinase inhibitors (BTKi) for PVRL remain uncertain.
METHODS
A systematic review and meta-analysis of clinical trial data and conference abstracts in VRL patients treated with first-line combination therapy or monotherapy were conducted through a search of PubMed, Embase, and Scopus databases until December 2022. A total of 24 studies comprising 517 patients were included, and survival data were extracted from 279 patients due to inconsistent units across studies.
RESULTS
The combined treatment group used ioMTX + chemotherapy (in 4 studies), RT + chemotherapy (in 2 studies), ioMTX/HD-MTX based regimen (in 2 studies), ioMTX + RT + chemotherapy (in 2 studies), ioMTX + lenalidomide/BTKi (in 2 studies) and combination of multiple therapies (in 7 studies). The monotherapy group was mainly treated with oral monotherapies such as BTKi. The combination therapy had a higher overall response rate (ORR) and complete response rate (CRR) than monotherapy (ORR: 96% vs. 72%, CRR: 92% vs. 63%). Combination therapy also resulted in a longer median progression-free survival (28.8 months vs. 13 months, p = 0.012). However, the combination therapy group had more severe side effects (grade 3/4 toxicity) than the monotherapy group (45% vs. 8%).
CONCLUSION
The study showed combination therapy had better OR and CR rates, longer survival, and more toxicity than monotherapy. While BTK inhibitors were well-tolerated, long-term effectiveness needs confirmation from prospective studies. In addition, given the small number of studies of monotherapy for VRL, more studies are needed to validate its effects.
TRIAL REGISTRATION
CRD42023400305.
Topics: Humans; Methotrexate; Retinal Neoplasms; Prospective Studies; Vitreous Body; Central Nervous System Neoplasms; Lymphoma
PubMed: 37993841
DOI: 10.1186/s12886-023-03226-3 -
Cancer Medicine Aug 2016Carotenoids and retinol are considered biomarkers of fruits and vegetables intake, and are of much interest because of their anti-inflammatory and antioxidant... (Meta-Analysis)
Meta-Analysis Review
Carotenoids and retinol are considered biomarkers of fruits and vegetables intake, and are of much interest because of their anti-inflammatory and antioxidant properties; however, there is inconsistent evidence regarding their protective effects against lung cancer. We conducted a meta-analysis of prospective studies of blood concentrations of carotenoids and retinol, and lung cancer risk. We identified relevant prospective studies published up to December 2014 by searching the PubMed and several other databases. We calculated summary estimates of lung cancer risk for the highest compared with lowest carotenoid and retinol concentrations and dose-response meta-analyses using random effects models. We used fractional polynomial models to assess potential nonlinear relationships. Seventeen prospective studies (18 publications) including 3603 cases and 458,434 participants were included in the meta-analysis. Blood concentrations of α-carotene, β-carotene, total carotenoids, and retinol were significantly inversely associated with lung cancer risk or mortality. The summary relative risk were 0.66 (95% confidence interval [CI]: 0.55-0.80) per 5 μg/100 mL of α-carotene (studies [n] = 5), 0.84 (95% CI: 0.76-0.94) per 20 μg/100 mL of β-carotene (n = 9), 0.66 (95% CI: 0.54-0.81) per 100 μg/100 mL of total carotenoids (n = 4), and 0.81 (95% CI: 0.73-0.90) per 70 μg/100 mL of retinol (n = 8). In stratified analysis by sex, the significant inverse associations for β-carotene and retinol were observed only in men and not in women. Nonlinear associations were observed for β-carotene, β-cryptoxanthin, and lycopene, with stronger associations observed at lower concentrations. There were not enough data to conduct stratified analyses by smoking. In conclusion, higher blood concentrations of several carotenoids and retinol are associated with reduced lung cancer risk. Further studies in never and former smokers are needed to rule out confounding by smoking.
Topics: Biomarkers; Carotenoids; Female; Humans; Lung Neoplasms; Male; Retinal Neoplasms; Risk
PubMed: 27384231
DOI: 10.1002/cam4.676 -
The Cochrane Database of Systematic... Jun 2017Retinoblastoma is the most common primary intraocular malignancy of childhood. Systemic chemotherapy is a common treatment for intraocular retinoblastoma, and laser... (Review)
Review
BACKGROUND
Retinoblastoma is the most common primary intraocular malignancy of childhood. Systemic chemotherapy is a common treatment for intraocular retinoblastoma, and laser treatment is used as adjuvant therapy during or immediately after chemotherapy courses in selected cases.
OBJECTIVES
To compare the effectiveness and safety of adding focal laser therapy to systemically-delivered chemotherapy in treating intraocular retinoblastoma.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2016, Issue 9), MEDLINE Ovid (1946 to 20 October 2016), Embase Ovid (1980 to 20 October 2016), LILACS (Latin American and Caribbean Health Sciences Literature Database) (1982 to 20 October 2016), the ISRCTN registry (www.isrctn.com/editAdvancedSearch); searched 20 October 2016, ClinicalTrials.gov (www.clinicaltrials.gov); searched 20 October 2016, and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en); searched 20 October 2016. We did not use any date or language restrictions in the electronic searches for trials.
SELECTION CRITERIA
We searched for randomised controlled trials (RCTs) of systemic chemotherapy with versus without adjuvant laser therapy for postequatorial retinoblastoma.
DATA COLLECTION AND ANALYSIS
We planned to use standard methodological procedures expected by Cochrane. We planned to meta-analyse the primary outcome, that is the proportion of eyes with recurrence of tumours within three years from treatment MAIN RESULTS: No studies met the inclusion criteria for this review.
AUTHORS' CONCLUSIONS
No evidence from randomised controlled trials was found to support or refute laser therapy in addition to systemic chemotherapy for postequatorial retinoblastoma.
Topics: Combined Modality Therapy; Humans; Laser Therapy; Retinal Neoplasms; Retinoblastoma
PubMed: 28589646
DOI: 10.1002/14651858.CD012366.pub2 -
Journal of Clinical Laboratory Analysis Oct 2021Retinoblastoma is the most common primary intraocular malignancy in children less than 4 years. Retinoblastoma (RB) contains about 3%-5% of all childhood cancers....
BACKGROUND
Retinoblastoma is the most common primary intraocular malignancy in children less than 4 years. Retinoblastoma (RB) contains about 3%-5% of all childhood cancers. Recent studies demonstrated that interacting between RB tumor suppressor and oncoproteins of DNA tumor viruses such as human papillomavirus (HPV). The objective of the current systematic review study was to present conducted studies in the field of HPV infection and its possible role in retinoblastoma.
METHODS
For this systematic review, all relevant original research studies were assessed by searching in electronic databases include PubMed, Embase, Scopus, Google Scholar, and Web of Science by using relevant keywords. The study was designed based on the PRISMA criteria. All publications with English literature and original researches are considered for screening.
RESULTS
Conducted search results lead to 4070 studies. The title and abstract screening lead to 11 studies. Data extraction was performed on 8 included studies. The prevalence of the HPV was ranged from 0 to 69%, and HPV genotype 16 and 18 were the most detected types. The most used method for the detection of the viruses was PCR, and the most assessed sample was formalin-fixed, paraffin-embedded tissue blocks.
CONCLUSION
The association between HPV and retinoblastoma is still inconsistent. The prevalence of the HPV in RB was ranged from 0 to 69%, which indicates a wide range and highlights the importance of further investigation for more accurate statistical of HPV prevalence in RB. Thus, further worldwide studies of larger sample sizes of cohorts should be investigated to clarify this uncertainty.
Topics: Human papillomavirus 16; Human papillomavirus 18; Humans; Papillomavirus Infections; Prevalence; Retinal Neoplasms; Retinoblastoma
PubMed: 34462972
DOI: 10.1002/jcla.23981