Lifetime dairy product consumption and breast cancer risk: a prospective cohort study by tumor subtypes.

BACKGROUND: Previous literature on dairy products and risk of breast cancer is inconsistent, and the relationship may depend on the life-period of dietary assessment. OBJECTIVE: We examined dairy consumption from adolescence through later adulthood and incidence of breast cancer by menopausal status and tumor molecular subtypes in the Nurses' Health Study (NHS), a prospective cohort study. METHODS: We analyzed data from 63,847 females in the NHS collected from 1980 to 2018. Average intake of dairy products during adulthood was assessed by validated semiquantitative food frequency questionnaires throughout follow-up. Participants recalled adolescent dietary intake in 1986. Multivariable Cox proportional hazards models were used to estimate hazard ratios (HRs) relating dairy product consumption to breast cancer risk overall, by menopausal status, and by subtypes. RESULTS: We documented 5733 incident cases of invasive breast cancer during 32 y of follow-up (n = 5298 postmenopausal). Lifetime, adolescent, adulthood, and postmenopausal total dairy and milk intakes were not associated with overall breast cancer risk (nonsignificant HRs comparing highest with lowest quintile range = 0.97-1.08), although there was a suggestive positive association between adolescent milk intake and breast cancer risk (HR: 1.09; 95% CI: 1.00, 1.18). Higher lifetime and premenopausal cheese intakes were associated with modestly lower risks of breast cancer (comparing highest with lowest quintile, HR for lifetime cheese intake: 0.90; 95% CI: 0.82, 0.98; HR for premenopausal cheese intake: 0.89; 95% CI: 0.79, 1.00). Results varied by tumor subtype and some evidence for heterogeneity was observed for an association between premenopausal milk intake and breast cancer (HR for estrogen receptor [ER]-positive: 0.84; 95% CI: 0.72, 0.99; ER-negative: 1.36; 95% CI: 1.00, 1.84; P heterogeneity = 0.04). CONCLUSIONS: These findings suggest that overall dairy consumption was not associated with risk of breast cancer. However, heterogeneity was observed for type of dairy food, period of life, and tumor subtypes.

Involvement of FSP1-CoQ10-NADH and GSH-GPx-4 pathways in retinal pigment epithelium ferroptosis.

Retinal pigment epithelium (RPE) degeneration plays an important role in a group of retinal disorders such as retinal degeneration (RD) and age-related macular degeneration (AMD). The mechanism of RPE cell death is not yet fully elucidated. Ferroptosis, a novel regulated cell death pathway, participates in cancer and several neurodegenerative diseases. Glutathione peroxidase 4 (GPx-4) and ferroptosis suppressor protein 1 (FSP1) have been proposed to be two main regulators of ferroptosis in these diseases; yet, their roles in RPE degeneration remain elusive. Here, we report that both FSP1-CoQ10-NADH and GSH-GPx-4 pathways inhibit retinal ferroptosis in sodium iodate (SIO)-induced retinal degeneration pathologies in human primary RPE cells (HRPEpiC), ARPE-19 cell line, and mice. GSH-GPx-4 signaling was compromised after a toxic injury caused by SIO, which was aggravated by silencing GPx-4, and ferroptosis inhibitors robustly protected RPE cells from the challenge. Interestingly, while inhibition of FSP1 caused RPE cell death, which was aggravated by SIO exposure, overexpression of FSP1 effectively protected RPE cells from SIO-induced injury, accompanied by a significant down-regulation of CoQ10/NADH and lipid peroxidation. Most importantly, in vivo results showed that Ferrostatin-1 not only remarkably alleviated SIO-induced RPE cell loss, photoreceptor death, and retinal dysfunction but also significantly ameliorated the compromised GSH-GPx-4 and FSP1-CoQ10-NADH signaling in RPE cells isolated from SIO-induced RPE degeneration. These data describe a distinct role for ferroptosis in controlling RPE cell death in vitro and in vivo and may provide a new avenue for identifying treatment targets for RPE degeneration.

The role of anti-vascular endothelial growth factor in treatment of retinopathy of prematurity-a current review.

The review aims to evaluate the uses of conventional laser therapy and intravitreal injection of various anti-VEGF in terms of efficacy and side effects for the treatment of retinopathy of prematurity. A literature search of the publication, concerning conventional laser treatment and intravitreal injection of anti-VEGF for ROP. A total of 40 articles were reviewed after curation by the authors for relevance. Intravitreal anti-VEGF showed better ocular efficacy in zone I ROP while laser therapy had a lower recurrence rate in zone II. Comparing the two mainstay anti-VEGF agents, bevacizumab showed lower ROP recurrence rate than ranibizumab. Anti-VEGF has a higher chance in developing persistent peripheral avascularisation compared to conventional laser therapy, but a lower chance of developing high myopia. Ranibizumab has a lower systemic absorption than bevacizumab, despite having no difference in the incidence of persistent peripheral avascularisation. In conclusion, it is advised that intravitreal anti-VEGF should be used as the first-line treatment for zone I ROP while laser therapy should be the mainstay for zone II ROP owing to the different pathogenetic mechanisms. In patients with recurrence after initial anti-VEGF injection, that given ranibizumab may opt to repeat the injection while that given bevacizumab should consider supplement laser ablative treatment.

A prospective randomized clinical trial comparing nepafenac, intravitreal triamcinolone and no adjuvant therapy for epiretinal membrane.

PURPOSE: To compare the efficacy of topical nepafenac 0.1% versus intravitreal triamcinolone acetonide (IVTA) at the conclusion of vitrectomy surgery versus no adjuvant therapy (NAT) in improving macular morphology post-operatively in patients undergoing vitrectomy for epiretinal membrane (ERM), as measured by optical coherence tomography (OCT) imaging and best-corrected visual acuity (BCVA). METHODS: Design: Prospective randomized clinical trial Setting: Multi-centre 80 patients scheduled to undergo vitrectomy surgery for idiopathic ERM were randomized to receive either IVTA (4 mg/0.1 cc) at the end of surgery, topical nepafenac sodium 0.1% TID for 1 month post-operation or no adjuvant treatment (NAT). Optical coherence tomography (OCT) imaging, best-corrected visual acuity and intraocular pressure (IOP) were measured before surgery, and 1 and 2 months post-operation. RESULTS: Although all three groups showed reduction in macular thickness post-operation, the NAT group showed the most improvement, with a reduction of 136.18 ± 29.84 µm at two months. There was no statistically significant difference in macular thickness between the groups at each time point, p = 0.158. The NAT group also had the best recovery in BCVA with an improvement of 0.207 logMAR (10.35 letters) at two months post-operation. There was no statistically significant difference in BCVA between the groups, p = 0.606. There was statistically significant difference in the IOP between the three groups, p = 0.04 only at 1-month visit. The IVTA group had the highest rise in average IOP at both 1 and 2 months post-operation (2.72 and 1.58 mmHg, respectively). CONCLUSION: Our study data suggest there was no advantage in the use of topical nepafenac or IVTA for post-vitrectomy ERM surgery.

Disorganization of the inner retinal layers in diabetic macular edema: systematic review / Desorganização das camadas internas da retina sem edema macular diabético: uma revisão sistemática

ABSTRACT The objective of this article was to review the disorganization of inner retinal layers as a biomarker in diabetic macular edema. A systematic search was conducted in PubMed®/MEDLINE®, Cochrane and Embase until August 2021. The keywords used were: "disorganization of inner retinal layers (DRIL)", "diabetic macular edema (DME)" and "biomarkers". No restrictions were imposed on the types of study to be included. The studies selected for eligibility were those that included the diagnosis of diabetic macular edema (center involved, resolved), that were well documented with spectral domain optical coherence tomography, that included disorganization of inner retinal layers as one of the reported alterations, with a follow-up of at least 3 months, and those in which the best corrected visual acuity was evaluated pre and post. There were no limitations regarding the type of treatment established. References of identified studies were searched for additional relevant articles. Articles not published in peer review journals were excluded. All studies were evaluated by two investigators independently. When one of them was in doubt, it was assessed by a third evaluator. A total of seven studies were included. Four were retrospective, longitudinal cohort study and three cross-sectional observational. Regarding the population studied, 61.5% were men and 38.4% were women, most of them had diabetes mellitus type 2 (85.8%). Regarding the stage of diabetes, the percentage of patients with mild nonproliferative diabetic retinopathy was 28.2%, with moderate nonproliferative diabetic retinopathy was 28.5%, with severe nonproliferative diabetic retinopathy was 15.9% and with nonproliferative diabetic retinopathy was 27.4%. In 100% of the studies, the diagnosis of diabetic macular edema in the center involved was included by spectral domain optical coherence tomography (Heidelberg). In all the studies, the presence of disorganization of inner retinal layers was recorded and its association with best corrected visual acuity was evaluated. The measurement was carried out using the LogMAR scale. In all the studies, the presence or absence of disorganization of inner retinal layers was associated with the best corrected worse/better final visual acuity using p <0.05 as a statical significance. The disorganization of inner retinal layers as a biomarker and their presence have shown to be important predictors of visual acuity in the future in patients with diabetic macular edema. Histopathological studies are required to understand its mechanism of action.

RESUMO O objetivo deste artigo foi revisar sobre a desorganização das camadas internas da retina como biomarcador no edema macular diabético. Uma busca sistemática foi realizada no PubMed®/MEDLINE®, Cochrane e Embase até agosto de 2021. As palavras-chave utilizadas foram "disorganization of inner retinal layers (DRIL)", "diabetic macular edema (DME)" e "biomarkers". Não foram impostas restrições quanto aos tipos de estudo a serem incluídos. Os estudos selecionados para elegibilidade foram aqueles que incluíram o diagnóstico de edema macular diabético (centro envolvido, resolvido), que foram bem documentados com tomografia de coerência óptica de domínio espectral, que incluíram a desorganização das camadas internas da retina como uma das alterações relatadas, com acompanhamento de pelo menos 3 meses, e aqueles em que a melhor acuidade visual corrigida foi avaliada pré e pós. Não houve limitações quanto ao tipo de tratamento estabelecido. Referências de estudos identificados foram pesquisadas para artigos relevantes adicionais. Foram excluídos os artigos não publicados em revistas de revisão por pares. Todos os estudos foram avaliados por dois investigadores de forma independente. Quando havia dúvida com algum deles, a mesma era avaliada por um terceiro avaliador. Um total de sete estudos foram incluídos. Quatro eram estudos de coorte retrospectivos longitudinais e três eram observacionais transversais. Em relação à população estudada, a proporção de homens foi de 61,5% e de mulheres, 38,4%, a maioria com diabetes mellitus tipo 2 (85,8%). Em relação ao estágio do diabetes, o percentual de pacientes com retinopatia diabética não proliferativa leve foi de 28,2%, retinopatia diabética não proliferativa moderada foi de 28,5%, de retinopatia diabética não proliferativa grave foi de 15,9% e de retinopatia diabética não proliferativa foi de 27,4%. Em 100% dos estudos, o diagnóstico de edema macular diabético no centro envolvido foi incluído pela tomografia de coerência óptica de domínio espectral (Heidelberg). Em todos os estudos, foi registrada a presença de desorganização das camadas internas da retina e avaliada sua associação com a melhor acuidade visual corrigida. A medição foi realizada usando a escala LogMAR. Em todos os estudos, a presença ou ausência de desorganização das camadas internas da retina foi associada a pior/melhor acuidade visual final melhor corrigida usando p<0,05 como significância estática. A desorganização das camadas internas da retina como biomarcador e sua presença têm se mostrado importantes como preditor da acuidade visual no futuro em pacientes com edema macular diabético. Estudos histopatológicos são necessários para entender seu mecanismo de ação.

Green Light-Triggered Intraocular Drug Release for Intravenous Chemotherapy of Retinoblastoma.

Retinoblastoma is one of the most severe ocular diseases, of which current chemotherapy is limited to the repetitive intravitreal injections of chemotherapeutics. Systemic drug administration is a less invasive route; however, it is also less efficient for ocular drug delivery because of the existence of blood-retinal barrier and systemic side effects. Here, a photoresponsive drug release system is reported, which is self-assembled from photocleavable trigonal small molecules, to achieve light-triggered intraocular drug accumulation. After intravenous injection of drug-loaded nanocarriers, green light can trigger the disassembly of the nanocarriers in retinal blood vessels, which leads to intraocular drug release and accumulation to suppress retinoblastoma growth. This proof-of-concept study would advance the development of light-triggered drug release systems for the intravenous treatment of eye diseases.

Silicone oil in vitreoretinal surgery: indications, complications, new developments and alternative long-term tamponade agents.

Silicone oil (SO) has been used as a long-term tamponade agent in the treatment of complicated vitreoretinal diseases for about half a century, during which time many advances in surgical techniques and technologies have been made. This review summarizes the chemical and physical properties of SO, its indications and complications, including particularly emulsification. The mechanisms and risk factors for emulsification are discussed, as well as novel strategies for its effective removal. Finally, the review focuses on new improved formulations of SO, including research into slow-release pharmacological agents within SO and provides an overview of alternatives to SO for the purpose of long-term tamponade that are being developed.

What Is the Cause of Toxicity of Silicone Oil?

PURPOSE: To investigate the toxicity of the low-molecular-weight components (LMWCs) in ophthalmic silicone oils (SilOils) on retinal cell lines. METHODS: The toxicity of six types of LMWCs were studied and compared with conventional SilOil 1000 cSt. In vitro cytotoxic tests of LMWCs, in both liquid and emulsified forms, on three retinal cell lines (Müller cells (rMC-1), photoreceptor cells (661W) and retinal pigment epithelial cells (ARPE-19)) were conducted using a transwell cell culturing system. The morphology and viability of cells were assessed by light microscopy and Cell Counting Kit-8 (CCK-8) assay at different time points (6, 24 and 72 h). The ARPE-19 apoptotic pathway was investigated by Mitochondrial Membrane Potential/Annexin V Apoptosis Kit at different time points (6, 24 and 72 h). RESULTS: Apart from dodecamethylpentasiloxane (L5), all liquid LMWCs showed varying degrees of acute cytotoxicity on retinal cell lines within 72 h. Emulsified LMWCs showed comparable cytotoxicity with liquid LMWCs on retinal cell lines. Cyclic LMWCs, octamethylcyclotetrasiloxane (D4) and decamethylcyclopentasiloxane (D5) had significantly higher cytotoxicity when compared with their linear counterparts decamethyltetrasiloxane (L4) and L5 with similar molecular formula. Using ARPE-19 cells as an example, we showed that LMWCs induce the apoptosis of retinal cells. CONCLUSIONS: Most LMWCs, in both liquid and emulsified forms, can induce acute cytotoxicity. In addition, cyclic LMWCs are suspected to have higher cytotoxicity than their linear counterparts. Therefore, LMWCs are suspected to be the main cause of the long-term toxicity of ophthalmic SilOil, due to their toxicity and propensity to cause ophthalmic SilOil to emulsify. The amount of LMWCs should be considered as the paramount parameter when referring to the quality of SilOil.

Endoscopic vitreoretinal surgery: Review of current applications and future trends.

Endoscopy provides unique optical properties to circumvent anterior segment opacities and visualize difficult-to-access anatomical regions, including retroirideal, retrolental, ciliary body, and anterior retinal structures. We summarize the basic principles and utilization of endoscopic vitreoretinal surgery, along with recent technological advances in the field base on a structured literature search in Pubmed, Embase, and Google Scholar database up to February, 2020. Endoscopy has been used in the management of retinal detachment, ischemic retinopathies with neovascular glaucoma, severe ocular trauma, endophthalmitis, lens-related disorders in the posterior segment, pediatric vitreoretinal diseases, and implantation of retinal prostheses. Ongoing development of endoscopic technology aims to provide higher resolution images with endoscopes of smaller diameter. New surgical techniques supported by the adoption of endoscopy are available to manage challenging surgical scenarios. Endoscopy can be a useful adjunct to microscope wide-angle viewing systems in the management of complex vitreoretinal diseases.

Novel Programmed Cell Death as Therapeutic Targets in Age-Related Macular Degeneration?

Age-related macular degeneration (AMD) is a leading cause of severe visual loss among the elderly. AMD patients are tormented by progressive central blurring/loss of vision and have limited therapeutic options to date. Drusen accumulation causing retinal pigment epithelial (RPE) cell damage is the hallmark of AMD pathogenesis, in which oxidative stress and inflammation are the well-known molecular mechanisms. However, the underlying mechanisms of how RPE responds when exposed to drusen are still poorly understood. Programmed cell death (PCD) plays an important role in cellular responses to stress and the regulation of homeostasis and diseases. Apart from the classical apoptosis, recent studies also discovered novel PCD pathways such as pyroptosis, necroptosis, and ferroptosis, which may contribute to RPE cell death in AMD. This evidence may yield new treatment targets for AMD. In this review, we summarized and analyzed recent advances on the association between novel PCD and AMD, proposing PCD's role as a therapeutic new target for future AMD treatment.

A de novo mutation in PITX2 underlies a unique form of Axenfeld-Rieger syndrome with corneal neovascularization and extensive proliferative vitreoretinopathy.

BACKGROUND: Axenfeld-Rieger syndrome is characterized by a spectrum of anterior segment dysgenesis involving neural-crest-derived tissues, most commonly secondary to mutations in the transcription factor genes PITX2 and FOXC1. MATERIALS AND METHODS: Single retrospective case report. RESULTS: A full-term infant presented at 5 weeks of age with bilateral Peters anomaly and Axenfeld-Rieger syndrome, with development of atypical features of progressive corneal neovascularization and proliferative vitreoretinopathy. Despite surgical interventions, the patient progressed to bilateral phthisis bulbi by 22 months of age. Genetic testing revealed a novel de novo p.Leu212Valfs*39 mutation in PITX2, leading to loss of a C-terminal OAR domain that functions in transcriptional regulation. CONCLUSIONS: It is important to consider mutations in PITX2 in atypical cases of anterior segment dysgenesis that also present with abnormalities in the angiogenesis of the anterior and posterior segments.

Treatment of large, chronic and persistent macular hole with internal limiting membrane transposition and tuck technique.

BACKGROUND: Large, chronic full thickness macular holes which failed previous treatments are difficult to manage and even left untreated due to poor prognosis. A retrospective review of consecutive cases with chronic (at least 1 year) full thickness macular holes and internal limiting membrane (ILM) free flap transposition with tuck technique, after previously failed vitrectomy. METHODS: This was a retrospective and interventional study conducted in a single centre by a single surgeon. Patients with full thickness macular hole for at least 1 year and at least one previously failed vitrectomy with ILM peeling were recruited. A 25G vitrectomy with ILM free flap transposition was done without assistance of PFCL, viscoelastic or autologous blood. The free flap was manually tucked into the macular hole free space and gas fluid exchange was performed with 20% SF6 as tamponade. The patients were postured prone for 2 weeks postoperatively. Best corrected visual acuity, macular hole duration, previous surgeries, optical coherence tomography (OCT) appearance, hole size and closure rate were recorded. RESULTS: 8 consecutive patients were included from May 2016 to Feb 2018. Transposition surgery was performed an average of 1481 days (SD 1096) after diagnosis of macular hole and average of 1226 days (SD 1242) after first vitrectomy. Macular hole mean size was 821 µm (SD 361.3), preoperative VA was logMAR 1.038 (SD 0.19), postoperative VA was logMAR 0.69 (SD 0.19) at 3 months. There were 1.13 lines gained and a significant improvement of logMAR 0.33 (p = 0.0084) at 6 months. Hole closure was seen in 7 out of 8 eyes (87.5%). The OCT with failed closure showed ILM flap within a flat hole, however no overlying neurosensory layers was seen. The duration from diagnosis to surgery was 2349 days in this case. CONCLUSION: Free flap ILM transposition tuck without the use of additional intraoperative tamponade is an effective technique in treating large chronic macular holes with previously failed primary macular hole surgeries.Trial registration (IRB of the Hong Kong University and Hospital Authority Hong Kong West Cluster, ref UW19-440), June 17, 2019.

Polypoidal choroidal vasculopathy in Canada.

Polypoidal choroidal vasculopathy (PCV) is an exudative age-related macular degeneration (AMD) subtype found more frequently among Asians than Caucasians. If untreated, it may lead to severe vision loss. PCV appears to be frequently underdiagnosed in Canada, although misdiagnosis of PCV as AMD carries the risk of inadequate treatment and unsatisfactory clinical outcomes. Diagnosis can be made on the basis of multimodal imaging, including optical coherence tomography (OCT) and OCT angiography combined with colour fundus photography, or by other imaging techniques; the gold-standard indocyanine green angiography (ICGA) is not widely used in Canada. Treatment involves anti-vascular endothelial growth factor (anti-VEGF) agents (bevacizumab, ranibizumab, or aflibercept), alone or in combination with photodynamic therapy (PDT). Recent clinical trials have shown that ranibizumab in combination with PDT is superior to ranibizumab monotherapy (EVEREST II), and aflibercept monotherapy is as effective in patients meeting PDT rescue criteria as aflibercept combined with rescue PDT (PLANET). It appears that most Canadian PCV patients are treated with anti-VEGF monotherapy, with or without PDT.

Visual outcomes after treatment in pediatric patients with Coats' disease.

OBJECTIVE: To report visual outcomes for children with Coats' disease after treatment. DESIGN: Retrospective case series. PARTICIPANTS: Pediatric patients with Coats' disease treated between 2000 and 2018 at a tertiary care pediatric hospital. METHODS: Review of medical records. The primary outcome was visual acuity at final follow-up. Anatomical outcomes, retreatment, and risk factors for a poor outcome were also assessed. RESULTS: There were 30 patients with Coats' disease. All cases were unilateral, and 28 (93%) were male. At presentation, 14 (47%) had stage 2 disease (retinal exudates) and 16 (53%) had stage 3 disease (subtotal or total exudative retinal detachment). All patients underwent laser photocoagulation and (or) cryopexy as primary treatment, combined with antivascular endothelial growth factor injection in 7 patients, posterior sclerotomy in 5 patients, and pars plana vitrectomy in 1 patient. Retreatment was required in 16 (53%) patients. After a median follow-up of 3.8 years, visual acuity was 20/50 or better in 6 patients (20%), 20/60 to 20/150 in 3 (10%), 20/200 to counting fingers in 8 (23%), and hand motion or worse in 14 (47%). Greater severity of disease at presentation was significantly associated with a poor visual outcome (p = 0.0001). In terms of complications, 7 (23%) eyes developed cataracts and 2 (7%) progressed to phthisis bulbi, but no patients required enucleation. CONCLUSIONS: The visual prognosis for children with Coats' disease remains poor, particularly in patients with more severe disease at presentation. The risk of severe complications and enucleation is low after treatment.

Long-term visual and anatomic outcomes following early surgery for persistent fetal vasculature: a single-center, 20-year review.

BACKGROUND: Persistent fetal vasculature (PFV) is a spectrum of congenital anomalies caused by complete or partial failure of the ocular fetal vasculature to regress. We report the visual and anatomic outcomes in a large cohort of patients who underwent early surgery for PFV. METHODS: We retrospectively reviewed the medical records of patients who underwent lensectomy and anterior or core vitrectomy for unilateral PFV without primary intraocular lens implantation through limbal or pars plana/plicata approach. Inclusion criteria were surgery prior to 7 months of age, with at least 12 months of follow-up. Eyes with severe posterior segment involvement and retinal detachment deemed beyond repair were excluded. RESULTS: A total of 58 patients met inclusion criteria. Mean age at surgery was 2.1 ± 1.5 months. Mean follow-up was 6.7 ± 4.2 years. At final follow-up, 19 eyes (33%) had visual acuity better than 1.0 logMAR. Thirty-three eyes (57%) developed 1 or more postoperative adverse events: glaucoma in 21 (36%) and retinal detachment in 11 (19%), 8 of which occurred in eyes that had pars plana or pars plicata incisions (P = 0.002). In patients with limbal incisions, 17 of 40 (43%) achieved a visual acuity better than 1.0 logMAR, compared with 2 of 18 patients (11%) with a pars plana/pars plicata incision (P = 0.03). CONCLUSIONS: In our study cohort, early surgery for PFV achieved functional visual acuity in about one-third of patients. Limbal approach to surgery may result in better visual acuity and anatomic results.

Coriolus Versicolor and Ganoderma Lucidum Related Natural Products as an Adjunct Therapy for Cancers: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background: Cancer incidence and mortality rates keep rising globally. Coriolus versicolor and Ganoderma lucidum related natural products are commonly applied as a complementary therapeutic option for different stages and types of cancers. The aim of this study is to evaluate the efficacy and safety of the products for cancer therapy. Methods: Randomized controlled trials were identified by systematic search over seven databases from inceptions to May 10, 2019. Two independent reviewers extracted data and assessed the study quality. Meta-analyses were performed to pool hazard ratio (HR), risk ratio (RR), mean differences (MD), and 95% CI using random-effects models. The sources of heterogeneity were explored by subgroup analyses and sensitivity analyses. Publication bias was detected by Funnel plots, Begg's test, and Egger's test. Results: Twenty-three trials involving 4,246 cancer patients were included in this work. C. versicolor and G. lucidum related natural products were significantly associated with lower risks of mortality (HR: 0.82; 95% CI: 0.72, 0.94) and higher total efficacy (RR: 1.30; 95% CI: 1.09, 1.55), but not associated with control rate (RR: 1.05; 95% CI: 0.96, 1.14) compared with control treatment. There was no significant difference between C. versicolor related natural products and control treatment in the effect on relapse-free survival (HR: 1.19; 95% CI: 0.91, 1.55). Compared with control treatment, C. versicolor and G. lucidum related natural products had a favorable effect on elevated levels of CD3 (MD: 9.03%; 95% CI: 2.10, 16.50) and CD4 (MD: 9.2%; 95% CI: 1.01, 17.39), but had no effect on the levels of CD8 (MD: -5.52%; 95% CI: -23.17, 12.13), CD4/CD8 (MD: 0.73; 95% CI:-0.45, 1.91), or NK(MD: 5.87%; 95% CI: -1.06, 12.8). Conclusion: In this meta-analysis, we found that C. versicolor and G. lucidum related natural products might have potential benefits on the overall survival and quality of life in cancer patients.

Hong Kong Chinese Medicine Clinical Practice Guideline for Cancer Palliative Care: Pain, Constipation, and Insomnia.

It is common for patients with cancers in Hong Kong seeking Chinese Medicine (CM) therapies as supportive care during cancer treatment and to manage treatment-related side effects. This article provides clinical practice guideline (CPG) on the use of CM for specific clinical indications caused by cancer and during cancer treatment, including pain, constipation, and insomnia, and aims to guide local licensed CM practitioners and provide beneficial reference for social medical decision makers and patients. In this manuscript, we summarize the clinical manifestation, CM pattern classification, and CM intervention including herbal treatment, acupuncture treatment, regulating, and nursing based on pattern differentiation.

Accuracy of scleral transillumination techniques to identify infant ciliary body for sclerostomy and intravitreal injections.

IMPORTANCE: There is variation in the literature for sclerotomy and intravitreal injection placement in young children, ranging from 0.5 to 3.0 mm from the limbus. We assess the accuracy of scleral transillumination to identify the ciliary body in infants for safe sclerotomy and intravitreal injections in young children. BACKGROUND: The study compares the perilimbal "dark band" seen on scleral transillumination (STI) with the ultrasound biomicroscopy (UBM), and compares these measurements with the current guidelines for sclerotomy in infants. DESIGN: Prospective case series in a tertiary paediatric hospital. PARTICIPANTS: Children aged ≤36 months undergoing general anaesthesia for eye procedures. METHODS: Scleral transillumination was performed to measure the perilimbal dark band. UBM of the ciliary body region was then performed, and correlated with transillumination findings. MAIN OUTCOME MEASURES: The midpoints of STI and UBM were compared to current cadaver-based guidelines to assess the safe point for sclerotomy. RESULTS: Twenty children were recruited, 36 STI and 35 UBM measurements were obtained. The posterior edge of the dark band had good correlation with the posterior border of the ciliary body. Transillumination and UBM correlated well for midpoint measurements. The midpoint of the dark band on transillumination was confirmed to be in the ciliary body by UBM in all cases. CONCLUSIONS AND RELEVANCE: The STI technique is a useful and fast technique to demonstrate the ciliary body. The midpoint of the dark band on STI correlates well with the UBM, and has a potential use for confirming safe-entry into the posterior segment if using current guidelines. The current cadaver-based paediatric guidelines safely avoid retinal injury.

Recurrent grade 4 panuveitis with serous retinal detachment related to nivolumab treatment in a patient with metastatic renal cell carcinoma.

Blockade of programmed cell death-1 (PD-1) has become one of the most promising immunotherapies for many human cancers. However, immune-related adverse events can be produced by anti-PD-1 therapy. Uveitis is a rare but potentially devastating side effect of anti-PD-1 therapy. Delay in diagnosis or improper treatment may eventually lead to irreversible blindness. Therefore, it is important for the oncologist and the ophthalmologist to recognize and manage this adverse event properly in patients receiving anti-PD-1 therapy in a timely manner. Here we present a grade 4 panuveitis with bilateral serous retinal detachment following treatment with nivolumab for metastatic renal cell carcinoma. Oral prednisone, topical steroid eye drops, periorbital injection of steroid and finally intravitreal injection of steroid implant were administered in our patient. We observed that intravitreal injection of dexamethasone implant, but not the periorbital injection of steroid or the steroid eye drops, was effective to control the posterior uveitis and serous retinal detachment. Oral prednisone was also effective, but it might affect the efficacy of anti-PD-1 therapy and promote tumor growth. We also summarize 15 cases of uveitis reported to date related to nivolumab or pembrolizumab therapy in the present study. The symptoms, signs, potential underlying mechanisms and treatment options regarding this adverse event are discussed.

A meta-analysis of the effect of a dexamethasone intravitreal implant versus intravitreal anti-vascular endothelial growth factor treatment for diabetic macular edema.

BACKGROUND: This meta-analysis evaluated the effectiveness and safety of dexamethasone (DEX) implant and intravitreal anti-vascular endothelial growth factor (VEGF) treatment for diabetic macular edema (DME). METHODS: The PubMed, Embase, clinicaltrials.gov website and Cochrane Library databases were comprehensively searched for studies comparing DEX implant with anti-VEGF in patients with DME. Best-corrected visual acuity (BCVA), central subfield thickness (CST) and adverse events were extracted from the final eligible studies. Review Manager (RevMan) 5.3 for Mac was used to analyze the data and GRADE profiler were used to access the quality of outcomes. RESULTS: Based on four randomized clinical trials assessing a total of 521 eyes, the DEX implant can achieve visual acuity improvement for DME at rates similar to those achieved via anti-VEGF treatment (mean difference [MD] = - 0.43, P = 0.35), with superior anatomic outcomes at 6 months (MD = - 86.71 µm, P = 0.02), while requiring fewer injections, in comparison to anti-VEGF treatment. Although the mean reduction in CST did not showed significant difference at 12 months (MD = - 33.77 µm, P = 0.21), the significant in BCVA from baseline to 12 months supported the anti-VEGF treatment (MD = - 3.26, P < 0.00001). No statistically significant differences in terms of the serious adverse events. However, use of the DEX implant has higher risk of intraocular pressure elevation and cataract than anti-VEGF treatment. CONCLUSIONS: Compared with anti-VEGF, DEX implant improved anatomical outcomes significantly. However, this did not translate to improved visual acuity, which may be due to the progression of cataract. Therefore, the DEX implant may be recommended as a first chioce for select cases, such as for pseudophakic eyes, anti-VEGF-resistant eyes, or patients reluctant to receive intravitreal injections frequently.