Predictive model for iris melanoma.

AimTo develop a predictive model for the diagnosis of iris melanoma. METHODS: Retrospective consecutive case series that included 100 cases of pathologically confirmed iris melanoma and 112 cases of Iris naevus, either pathological confirmation or documented stability of >1 year. Patient demographic data, features of clinical presentation, tumour characteristics and follow-up were collected. Iris melanoma with ciliary body extension was excluded. Lasso logistic regression with 10-fold cross-validation was used to select the tuning parameter. Discrimination was assessed with the area under the curve (AUC) and calibration by a plot. RESULTS: There was a significant asymmetry in the location of both nevi and melanoma with preference for inferior iris quadrants (83, 74%) and (79, 79%), respectively (p=0.50). Tumour seeding, glaucoma and hyphaema were present only in melanoma. The features that favoured the diagnosis of melanoma were size (increased height (OR 3.35); increased the largest basal diameter (OR 1.64)), pupillary distortion (ectropion uvea or corectopia (OR 2.55)), peripheral extension (angle or iris root involvement (OR 2.83)), secondary effects (pigment dispersion (OR 1.12)) and vascularity (OR 6.79). The optimism-corrected AUC was 0.865. The calibration plot indicated good calibration with most of the points falling near the identity line and the confidence band containing the identity line through most of the range of probabilities. CONCLUSIONS: The predictive model provides direct diagnostic prediction of the lesion being iris melanoma expressed as probability (%). Use of a prediction calculator (app) can enhance decision-making and patient counselling. Further refinements can be undertaken with additional datasets, forming the basis for automated diagnosis.

The role of temperature on the development of circadian rhythms in honey bee workers.

Circadian rhythms in honey bees are involved in various processes that impact colony survival. For example, young nurses take care of the brood constantly throughout the day and lack circadian rhythms. At the same time, foragers use the circadian clock to remember and predict food availability in subsequent days. Previous studies exploring the ontogeny of circadian rhythms of workers showed that the onset of rhythms is faster in the colony environment (~2 days) than if workers were immediately isolated after eclosion (7-9 days). However, which specific environmental factors influenced the early development of worker circadian rhythms remained unknown. We hypothesized that brood nest temperature plays a key role in the development of circadian rhythmicity in young workers. Our results show that young workers kept at brood nest-like temperatures (33-35 °C) in the laboratory develop circadian rhythms faster and in greater proportion than bees kept at lower temperatures (24-26 °C). In addition, we examined if the effect of colony temperature during the first 48 h after emergence is sufficient to increase the rate and proportion of development of circadian rhythmicity. We observed that twice as many individuals exposed to 35 °C during the first 48 h developed circadian rhythms compared to individuals kept at 25 °C, suggesting a critical developmental period where brood nest temperatures are important for the development of the circadian system. Together, our findings show that temperature, which is socially regulated inside the hive, is a key factor that influences the ontogeny of circadian rhythmicity of workers.

Angiographic Features of Iris Melanocytic Tumors: Nevus versus Melanoma.

Introduction: Determining the nature of iris melanocytic tumors based on clinical exam alone remains challenging. Tumor-associated vasculature of iris melanocytic lesions may facilitate the ability to discern between iris nevus and melanoma. Methods: In a single-institution, retrospective, observational study of 45 patients with pathologically confirmed iris melanoma and 15 patients with iris nevi that were either clinically stable or pathologically confirmed were included. Tumor characteristics and associated vasculature were identified on clinical exam and slit-lamp photographs. Fluorescein angiographic parameters including feeder vessels, intrinsic vessels, leakage, masking, and angiographic silence were assessed. Results: Feeder vessels were present in 17 (43%) melanomas and were absent in the nevus group (p = 0.002). Thirty-three (83%) iris melanomas and 5 (33%) iris nevi were observed to have intrinsic vessels, and a statistically significant association of intrinsic vessels with malignancy (p = 0.001) was noted. Fluorescein leakage was also observed more frequently in iris melanoma 39 (98%) than in nevi 9 (60) with a significant difference (p = 0.001). Angiographic silence occurred in 3 nevi (20%) and was not observed in any melanoma (p = 0.017). Overall, the presence of intrinsic vessels +/- feeder vessels had high sensitivity (0.85) and high positive predictive value (0.87) for diagnosis of iris melanoma. Conclusions: Anterior segment fluorescein angiography allows for the assessment of tumor-associated vascular patterns and demonstrates utility in differentiating iris nevi from melanoma. Feeder vessels were only observed in iris melanoma and were absent in iris nevi. The intrinsic vessels were present more frequently in melanomas and are thus associated with malignancy. Angiographic silence is indicative of iris nevi.

Iris melanoma: Prognostication for metastasis.

Uveal melanoma prognostication studies have mainly included posterior uveal melanomas located in the ciliary body and choroid, often excluding iris melanoma. In this study, we report prognostic status and survival outcomes in a series of 35 patients with biopsy-proven iris melanoma. Fluorescence in situ hybridization was performed in 10 (29%) cases and 2 (5%) underwent multiplex ligation-dependent probe amplification. In total, 9 cases demonstrated disomy 3, 2 cases with monosomy 3 (fluorescence in situ hybridization), and 1 had a technical failure. On gene expression profile testing, 20 of the 23 cases (90%) were gene expression profile class 1A, and the remaining 3 (10%) were class 1B. No patient had a Class 2 status. The median follow-up period was 49 months (mean 59, range 2-156 months). No metastasis was reported during follow-up, and metastasis-free survival was 100%. A review of the published literature revealed 47 cases with high-risk status on molecular prediction, of which only 6 (13%) developed metastasis. Ciliary body involvement was reported in 5 cases and was unknown in 2 cases. We conclude that molecular prognostication of iris melanoma demonstrates low-risk prognostic status in the majority of cases irrespective of the technique used. Even those with high-risk status do not develop metastasis unless the tumor involves the ciliary body.

Anterior Uveal Melanocytoma: Role of Diagnostic FNAB.

Introduction: Anterior uveal melanocytoma (AUM) pose a diagnostic challenge as they can mimic growing melanomas. Establishing a definitive diagnosis of melanocytoma necessitates cytologic or histopathologic confirmation. We describe the clinical presentation and characteristics of fifteen pathologically proven AUM cases and assess the role of fine needle aspiration biopsy (FNAB) as a safe and effective tool for diagnosis. Methods: Retrospective review of pathologically confirmed AUM cases was performed. Demographic data, presenting symptoms, clinical features, diagnostic approach, cytological and histological features, and clinical outcomes were collected. Results: Fifteen patients with pathologically confirmed AUM were identified. The mean and median age of diagnosis were 50 and 53 years, respectively (range 3-77 years). The melanocytoma was localized to the iris (5, 33%) or ciliary body (7, 47%), and 3 patients had iridociliary involvement (20%). Presentation was due to concern for growth in 4 (29%), visual symptoms in 1 (7%), and was an incidental finding in 10 (64%) patients. Pigmentation of the tumor varied with 9 (60%) appearing brown and 3 (20%) black in color. The color of 3 (20%) ciliary body tumors could not be assessed. The diagnosis was confirmed with FNAB in 6 (40%), excisional biopsy in 7 (47%), and incisional biopsy in 2 (13%). Cytologic and histologic preparations demonstrated predominance of round to polygonal cells with heavily pigmented cytoplasm and small round nuclei. One patient who underwent excisional biopsy had prior FNAB that was interpreted as suspicious for melanoma (false-positive). Instances of false-negative cytology were not observed as demonstrated by the subsequent stable clinical course during the mean follow-up of 21.2 months (range = 1.0-63.0 months). FNAB-related complications were not observed in any case. Conclusion: FNAB offers a minimally invasive and safe diagnostic approach for pathologic confirmation of AUM. However, limitations of FNAB including false-negative and false-positive biopsies must be considered when excluding underlying malignancy. Continued observation to document tumor stability should be considered.

The Role of Colony Temperature in the Entrainment of Circadian Rhythms of Honey Bee Foragers.

Honey bees utilize their circadian rhythms to accurately predict the time of day. This ability allows foragers to remember the specific timing of food availability and its location for several days. Previous studies have provided strong evidence toward light/dark cycles being the primary Zeitgeber for honey bees. Work in our laboratory described large individual variation in the endogenous period length of honey bee foragers from the same colony and differences in the endogenous rhythms under different constant temperatures. In this study, we further this work by examining the temperature inside the honey bee colony. By placing temperature and light data loggers at different locations inside the colony we measured temperature at various locations within the colony. We observed significant oscillations of the temperature inside the hive, that show seasonal patterns. We then simulated the observed temperature oscillations in the laboratory and found that using the temperature cycle as a Zeitgeber, foragers present large individual differences in the phase of locomotor rhythms for temperature. Moreover, foragers successfully synchronize their locomotor rhythms to these simulated temperature cycles. Advancing the cycle by six hours, resulting in changes in the phase of activity in some foragers in the assay. The results are shown in this study highlight the importance of temperature as a potential Zeitgeber in the field. Future studies will examine the possible functional and evolutionary role of the observed phase differences of circadian rhythms.