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The long-term survival of uveal melanoma patients in the US is not known. We compared long-term survival estimates using relative survival, excess absolute risk (EAR), Kaplan-Meier (KM), and competing risk analyses. Population based cohort study. Pooled databases from Surveillance, Epidemiology, and End Results data (SEER, SEER-9+SEER-13+SEER-18). Overall Survival (OS), Metastasis Free Survival (MFS) and relative survival, computed directly or estimated via a model fitted to excess mortality. There were 10678 cases of uveal melanoma spanning a period of 42 years (1975-2016). The median age at diagnosis was 63 years (range 3-99). Over half the patients were still alive at the end of 2016 (53%, 5625). The KM estimates of MFS were 0.729 (0.719, 0.74), 0.648 (0.633, 0.663), and 0.616 (0.596, 0.636) at 10, 20, and 30 years, respectively. The cumulative probabilities of melanoma metastatic death at 10, 20 and 30 years were 0.241 (0.236, 0.245), 0.289 (0.283, 0.294), and 0.301 (0.295, 0.307). In the first 5 years since diagnosis of uveal melanoma, the proportion of deaths attributable to uveal melanoma were 1.3 with rapid fall after 10 years. Death due to melanoma were rare beyond 20 years. Relative survival (RS) plateaued to ~60% across 20 to 30 years. EAR parametric modeling yielded a survival probability of 57%. Relative survival methods can be used to estimate long term survival of uveal melanoma patients without knowing the exact cause of death. RS and EAR provide more realistic estimates as they compare the survival to that of a normal matched population. Death due to melanoma were rare beyond 20 years with normal life expectancy reached at 25 years after primary therapy.

To determine if a greater than expected number of cases (clustering) of uveal melanoma occurred within Ohio for any specific region or time period as compared to others. Analysis of population database. Ohio Cancer Incidence Surveillance System (OCISS) database (2000-2019) was accessed for the diagnosis of uveal melanoma using the International Classification of Disease for Oncology codes: C69.3 (choroid), C69.4 (ciliary body and iris). Counties within Ohio were grouped by geographic regions (7) and socioeconomic variables. Age- and race-standardized incidence ratios (SIR) were calculated to determine temporal or geographic clustering. Over the twenty-year period, the total number of uveal melanoma cases reported within Ohio were 1,617 with the overall age-adjusted annual incidence of 6.72 cases per million population (95% CI 6.30-7.16). There was an increase in the incidence of uveal melanoma over 20 years (p<0.001) across seven geographic regions, but no significant difference in incidence rates between the regions. There was no difference in incidence based on county classification by age composition (p = 0.14) or education level (p = 0.11). Counties with a low median household income (p<0.001), those classified as urban (p = 0.004), and those with a greater minority population (p = 0.004) had lower incidence. Less populated counties had a higher incidence of uveal melanoma (p<0.001). There is no evidence of geographic or temporal clustering of uveal melanoma within Ohio from 2000 to 2019.

Purpose: The objective of this study was to identify the diagnostic features of optic nerve head melanocytoma (ONH-MCT) on spectral domain optical coherence tomography (SD OCT) and OCT angiography (OCT-A). Methods: Retrospective study of 11 patients for their demographic, clinical features and imaging including SD OCT (tumour location, extent and interface) and OCT-A (surface and intrinsic vascularity) were reviewed. Flow rate percentage (FR %) was calculated over the lesion and compared to fellow eye and similar pigmented lesions. Results: The average age was 52.8 ± 10.9 years. ONH-MCT tumors occupied 3-tissue spaces- optic disc (n = 2), retinal layer (n = 5) and retina-choroidal layers (n = 4). SD OCT (11 eyes) showed elevated hyper reflective disorganized retinal layers with posterior shadowing (9 eyes) and hyper reflective dots within the tumor (all eyes). Microvascular features on OCT-A (8 eyes) in radial peripapillary capillary slab showed surface vascularization (7 eyes) and intrinsic vascularity in choroidal slab (8 eyes) with surrounding hypo reflective boundary. The mean FR % was higher at 65.1 ± 3.77% (CI: 61.9-68.2) compared to mean FR at 60.4 ± 1.06% (CI: 59.5-61.2) in the fellow eye (p = 0.01). Comparison with nevus and melanoma SD OCT showed a high reflective choroidal layer with normal or irregular outer retinal layers respectively; OCT-A showed hypo reflective area at the center with hyper reflective boundary and iso reflective area at center with hyper reflective boundary respectively. Conclusion: SD OCT and OCT-A features may help to differentiate ONH-MCT from clinically similar looking pigmented lesions like nevus and melanoma.

International Ocean Discovery Program Expedition 355 drilled Sites U1456 and U1457 in Laxmi Basin (eastern Arabian Sea) to document the impact of the South Asian monsoon on weathering and erosion of the Himalaya. We revised the chronostratigraphic framework for these sites using a combination of biostratigraphy, magnetostratigraphy and strontium isotope stratigraphy. The sedimentary section at the two sites is similar and we divided it into six units bounded by unconformities or emplaced as a mass-transport deposit (MTD). Unit 1 underlies the MTD, and is of early-middle Miocene age at Site U1456 and early Paleocene age at Site U1457. An unconformity (U1) created by emplacement of the MTD (unit 2) during the late Miocene Epoch (at c. 9.83-9.69 Ma) separates units 1 and 2 and is identified by a marked change in lithology. Unit 3 consists of hemipelagic sediment with thin interbeds of graded sandstone of late Miocene age, separated from unit 4 by a second unconformity (U2) of 0.5-0.9 Myr duration. Unit 4 consists of upper Miocene interbedded mudstone and sandstone and hemipelagic chalk deposited between c. 8 and 6 Ma. A c. 1.4-1.6 Myr hiatus (U3) encompasses the Miocene-Pliocene boundary and separates unit 4 from unit 5. Unit 5 includes upper Pliocene - lower Pleistocene siliciclastic sediment that is separated from unit 6 by a c. 0.45 Myr hiatus (U4) in the lower Pleistocene sediments. Unit 6 includes a thick package of rapidly deposited Pleistocene sand and mud overlain by predominantly hemipelagic sediment deposited since c. 1.2 Ma.

Uveal melanoma is the most common malignancy of the adult eye. The overall mortality rate is high because this aggressive cancer often metastasizes before ophthalmic diagnosis. Quantitative proteomic analysis of primary metastasizing and non-metastasizing tumors was pursued for insights into mechanisms and biomarkers of uveal melanoma metastasis. Eight metastatic and 7 non-metastatic human primary uveal melanoma tumors were analyzed by LC MS/MS iTRAQ technology with Bruch's membrane/choroid complex from normal postmortem eyes as control tissue. Tryptic peptides from tumor and control proteins were labeled with iTRAQ tags, fractionated by cation exchange chromatography, and analyzed by LC MS/MS. Protein identification utilized the Mascot search engine and the human Uni-Prot/Swiss-Protein database with false discovery ≤ 1%; protein quantitation utilized the Mascot weighted average method. Proteins designated differentially expressed exhibited quantitative differences (p ≤ 0.05, t-test) in a training set of five metastatic and five non-metastatic tumors. Logistic regression models developed from the training set were used to classify the metastatic status of five independent tumors. Of 1644 proteins identified and quantified in 5 metastatic and 5 non-metastatic tumors, 12 proteins were found uniquely in ≥ 3 metastatic tumors, 28 were found significantly elevated and 30 significantly decreased only in metastatic tumors, and 31 were designated differentially expressed between metastatic and non-metastatic tumors. Logistic regression modeling of differentially expressed collagen alpha-3(VI) and heat shock protein beta-1 allowed correct prediction of metastasis status for each of five independent tumor specimens. The present data provide new clues to molecular differences in metastatic and non-metastatic uveal melanoma tumors. While sample size is limited and validation required, the results support collagen alpha-3(VI) and heat shock protein beta-1 as candidate biomarkers of uveal melanoma metastasis and establish a quantitative proteomic database for uveal melanoma primary tumors.

Graft versus H\\host disease (GVHD) can be a devastating complication following bone marrow transplantation. Acute or chronic systemic GVHD can be lethal, and severe damage of different organs and tissues can occur with both types of GVHD. Ocular involvement, either in an acute or chronic presentation, may range from mild to severe with accompanying vision loss present in 60–90 % of patients. Chronic ocular GVHD, the most common form of GVHD, affects mainly the lacrimal gland, meibomian glands, cornea and conjunctiva, mimicking other immunologically mediated inflammatory diseases of the ocular surface without specific symptoms or signs. However, dry eye disease is the main manifestation of GVHD. The long-term treatment of ocular GVHD continues to be challenging and involves a multidisciplinary approach wherein the ophthalmologist plays a major role. Besides systemic immunosuppression and ocular lubricants, topical steroids and topical cyclosporine are commonly prescribed. Newer therapeutic interventions for moderate and severe ocular GVHD include the use of serum eye drops and scleral contact lenses. In this manuscript, we review the mechanisms, clinical findings, and treatment of ocular GVHD.

AimTo conduct a performance analysis of intra-arterial chemotherapy (IAC).Material and methodsComprehensive 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).Results416 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).DiscussionImproved selection criteria are needed to identify eyes suitable for IAC.

AimTo describe the technique and results of a minimally invasive surgical technique for resection of small iris lesions.MethodsConsecutive case series of 22 patients with localised, small iris lesions that were resected using the described surgical technique that composed of multiple, small corneal incisions created to allow for internal iris resection with 23-gauge horizontal vitrectomy scissors, followed by guarded tumour aspiration through a clear plastic tubing (diameter 3.5 mm) primed with viscoelastic agent.ResultsThe mean largest basal diameter was 3.0 mm (range 1.5–5.0 mm; median 3.0 mm) and mean thickness was 1.3 mm (range 0.5–2.5 mm; median 1.0 mm). Use of multiple (2–4) small corneal incisions (range 2.0–3.0 mm; mean 2.8 mm) allowed reduced postoperative morbidity (significant hyphema (0%), hypotony (0%), wound leak (0%), >2 line change in best corrected visual acuity at postoperative 1 week (4.5%) and mean corneal astigmatism of 1.0 D (range 0.14–2.99 D; median 0.8 D) at postoperative 4–12 weeks. The tumour could be resected with clear surgical margins in all neoplastic cases (benign (2), borderline (1) and malignant (16)). Local recurrence or metastases were not observed in any melanoma case over a mean follow-up of 33.0 months (range 1.0–90.0 months; median 33.5 months).ConclusionsSmall incision guarded hydroaspiration is a minimally invasive surgical technique for resection of select small iris lesions. Use of multiple small corneal incisions avoids morbidity associated with a single large corneoscleral incision, and use of guarded aspiration may eliminate the risk of wound contamination by the malignant tumour.

AimsTo characterise the clinical and topographical features of circumscribed choroidal haemangioma (CCH) and to visualise the patterns of tumour extent in the ocular fundus.MethodsData on the size, shape and location of 113 CCH were converted into a database of two-dimensional retinal charts by means of computer drawing software. The extent of the tumours was visualised by merging the charts and displaying the number of overlapping tumours on colour-coded maps.ResultsThe mean largest tumour diameter was 7.2 mm (range, 2.5–11.0 mm), mean tumour height was 2.4 mm (range, 0.7–4.6 mm) and mean diameter/height ratio was 3.2 (range, 2.1–6.0). The mean distance from the posterior tumour margin to the foveola and optic disc margin was 1.7 mm (range, 0–15 mm) and 2.4 mm (range, 0–11 mm), respectively. The hemispheric location of the tumour centroid was temporal in 75 eyes (66%) and nasal in 38 (34%) (p=0.0005) and the distribution between the superior and inferior hemispheres was 68 (60%) and 45 (40%), respectively (p=0.03). The presence of subretinal fluid (SRF) was significantly associated with young age at diagnosis (p=0.0002), low tumour diameter/height ratio (p=0.0004), nasal hemisphere location (p=0.006) and close proximity to the optic disc (p=0.004).ConclusionsThe superotemporal quadrant close to the macula is the most frequent location of CCH. The tumours are generally characterised by a diameter/height ratio of >2. Tumours in young patients, with marked elevation, in nasal hemisphere and in proximity to the optic disc are associated with SRF exudation.

PurposeTo report outcomes and complications of fine-needle aspiration biopsy (FNAB) of uveal melanoma performed for diagnostic and prognostic purposes.MethodsProspective interventional case series of 150 consecutive patients with a clinical diagnosis of uveal melanoma. The FNAB approach (transcorneal (TCO), transscleral (TSC) and transvitreal (TVT) was primarily determined by the location of the tumour. The FNAB was performed using a 25-gauge needle using a previously published technique. Prognostication was done using fluorescent in situ hybridisation detection of monosomy of chromosome 3.ResultsFNAB was obtained via TCO (8), TSC (71) and TVT (64) approach and impression smear in seven cases. Diagnostic yield was 92%. False-negative results were observed in 8%. Diagnostic yield was significantly correlated to biopsy approach (TCO 100%, TSC 96%, TSV 86%; p=0.029) and tumour size (basal diameter >5.0 mm; height >2.5 mm). Persistent haemorrhage (subretinal haemorrhage or vitreous) requiring surgical intervention (1%) and rhegmatogenous retinal detachment (1%) were rare. Endophthalmitis, hypotony, tumour recurrence, episcleral seeding were not observed over the average follow-up of 37 months. Prognostication could be performed in 85% of cases. Overall, only 47% of eligible patients enrolled into the adjuvant therapy trial.ConclusionsFNAB for uveal melanoma with 25-gauge needle is a safe procedure that can yield diagnostic and prognostic information in vast majority of cases (92% and 85%, respectively). Even so, only about half of the eligible cases eventually enrolled into the adjuvant therapy trial. Possibility of negative FNAB yield should be considered when counselling patients with small tumours. Alternative means of diagnostic biopsy and methods of prognostication need to be assessed for small tumours.