OBJECTIVE: Carcinoma of unknown primary (CUP) poses a formidable diagnostic challenge, characterised by high mortality rates and an elusive primary tumour site. While Positron emission tomography (PET) scans are routinely employed in the initial evaluation of CUP patients, identifying the primary tumour remains an ongoing struggle. In light of this, the aim of this case report is to introduce a novel radiological description, termed the \'Starburst\' sign, derived from distinctive PET scan appearances associated with CUP.
METHODS: In this report, we present the case of a 47-year-old female patient who presented with abdominal symptoms. Upon investigation, extensive peritoneal disease was observed, yet the primary tumour source remained unidentified. Despite further diagnostic efforts, including a normal gastroscopy, a PET scan was able to confirm the presence of high-volume metastatic disease, without an identifiable primary tumour. Palliative treatment was initiated, but unfortunately, the patient\'s condition deteriorated rapidly, leading to her demise.
CONCLUSIONS: The \'Starburst\' sign, a unique radiological description of CUP in PET scans, has significant potential in advancing our understanding of the disease. It provides a visual analogy to a dying star, aiding comprehension of complex pathophysiology and implications of metastatic lesions. The introduction of the \'Starburst\' sign benefits patients and healthcare professionals, enhancing education, assessment, and treatment of CUP. This novel description contributes to knowledge in the field and can impact clinical management.

One common complaint with natural opacified lenses is the deleterious effects of higher-order ocular aberrations and intraocular scatter, such as halos and starbursts, which are not always remedied with surgery and intraocular lens (IOL) implantation. Blue-light filtering (BLF) IOL filter scatter-prone short-wave light. Here, we determine whether BLF IOL reduce halo and starburst size.
This study was a case-control design, between- and within-subjects (contralateral implantation). Sixty-nine participants with either the BLF IOL (n = 25; AlconSN60AT), clear IOL (n = 24; AlconSA60AT or WF), or both (n = 20) IOL participated. Participants were exposed to a point source of broadband simulated sunlight, which created the appearance of halos/starbursts. Dysphotopsia was measured as the diameter of broadband light-induced halos and starbursts.
A case-control analysis. Halo size was significantly larger (t[35.05] = 2.98, p = 0.005) in participants with the clear control lens (M = 3°55\' ± 2°48\'), compared to the BLF IOL (M = 1°84\' ± 1°34\'). Starburst size was not significantly different between groups. Contralateral analysis. Halo size was significantly smaller (t = -3.89, p = .001) in test eyes with the BLF (M = 3°16\' ± 2°35\') compared to the fellow control eyes (M = 5°42\' ± 3°17\'). Starburst size was also significantly smaller (t = -2.60, p < 0.018) in BLF test eyes (M = 9°57\' ± 4°25\') than the fellow eye with the clear IOL (M = 12°33\' ± 5°25\').
BLF IOL filter short-wave light and mimic retinal screening by the young, natural crystalline lens. Such filtering can reduce some deleterious effects of bright light by decreasing ocular diffusion/halos and starbursts.

OBJECTIVE: Dim light vision disturbances (DLD) comprise a wide range of symptoms affecting the quality of vision at low illumination including glare, halos, and starbursts. This exploratory study investigated 1.0% phentolamine mesylate ophthalmic solution (PMOS) as a treatment to improve vision and image quality for patients with DLD.
METHODS: In this placebo-controlled, randomized, double-masked clinical trial, 24 adult patients with severe DLD were randomized in a 2:1 ratio to receive either one dose of PMOS or placebo. Subjects were eligible if they reported experiencing severe night vision difficulty that was not eliminated by distance spectacle correction and scored ≥0.3 log units below the normal range of contrast sensitivity assessed under mesopic conditions with glare at ≥2 spatial frequencies. Key efficacy outcomes were change from baseline in pupil diameter, contrast sensitivity, and visual acuity. Safety measures including intraocular pressure, conjunctival hyperemia, and systemic effects were also assessed.
RESULTS: Eight subjects were randomized to placebo (63% female; mean age 47 years) and 16 were randomized to PMOS (75% female; mean age 42 years). Mean (SD) pupil diameter of PMOS-treated subjects decreased significantly - 1.3 mm (0 to - 2.8 mm) with p < 0.0001. Mean contrast sensitivity with glare in PMOS-treated subjects improved significantly post-treatment at spatial frequencies 3, 6, 12, and 18 cycles per degree (p ≤ 0.03). PMOS also demonstrated improvements in the numbers of letters read for mesopic and photopic, high- and low-contrast visual acuity (LCVA). Importantly, a statistically greater proportion of PMOS-treated eyes registered mesopic LCVA 5 letter (69% vs. 31%, p = 0.029) and 10 letter (34% vs. 6%, p = 0.04) improvement, with a trend at 15 letters (19% vs. 0%, p = 0.16). PMOS was well tolerated with the only reported side effect being a mild increase in conjunctival hyperemia.
CONCLUSIONS: PMOS was well tolerated and effectively reduced pupil size with improvements in contrast sensitivity and visual acuity in adults with severe DLD. Future Phase 3 studies should be conducted to further evaluate its potential to treat DLD.
BACKGROUND: The trial registration number is NCT04004507 (02/07/2019). Retrospectively registered.

OBJECTIVE: To analyse in depth the associations between objectively measured corneal higher-order aberrations (HOAs) and subjectively perceived visual quality after small incision lenticule extraction (SMILE) as quantified with the standardized and clinically validated quality of vision (QOV) questionnaire.
METHODS: This cross-sectional study included patients after bilateral simultaneous SMILE for the treatment of myopia and/or myopic astigmatism with plano target refraction. Scheimpflug imaging (Pentacam HR; Oculus Optikgeräte GmbH, Wetzlar, Germany) was used to objectively quantify corneal HOAs. The standardized and validated QOV questionnaire was employed to gauge patients\' subjectively perceived visual quality regarding frequency, severity and bothering effect of visual disturbances.
RESULTS: A total of 394 eyes of 197 patients with a mean age of 32.4 ± 7.7 years and a mean postoperative follow-up of 24.3 ± 14.1 months were included. SMILE induced a statistically significant (p < 0.001) increase in spherical aberration (0.074 ± 0.131 µm), coma (0.142 ± 0.179 µm), trefoil (0.018 ± 0.067 µm) as well as in total HOAs (0.191 ± 0.176 µm). Surgically induced and postoperative levels of HOA showed no correlation with the three QOV scores representative of overall visual symptom frequency, severity and bothering effect (all R2 values ≤ 0.016). In addition, the associations between specific visual symptoms (e.g. starburst) and singular HOA terms (e.g. haloes) were very weak (all Rho values ≤ 0.164).
CONCLUSIONS: Small incision lenticule extraction induced significant amounts of corneal HOAs that, however, showed no clear relationships to patient-reported QOV or specific long-term visual symptoms.

Many neuronal types occur as pairs that are similar in most respects but differ in a key feature. In some pairs of retinal neurons, called paramorphic, one member responds to increases and the other to decreases in luminance (ON and OFF responses). Here, we focused on one such pair, starburst amacrine cells (SACs), to explore how closely related neuronal types diversify. We find that ON and OFF SACs are transcriptionally distinct prior to their segregation, dendritic outgrowth, and synapse formation. The transcriptional repressor Fezf1 is selectively expressed by postmitotic ON SACs and promotes the ON fate and gene expression program while repressing the OFF fate and program. The atypical Rho GTPase Rnd3 is selectively expressed by OFF SACs and regulates their migration but is repressed by Fezf1 in ON SACs, enabling differential positioning of the two types. These results define a transcriptional program that controls diversification of a paramorphic pair.

OBJECTIVE: The aim of this work was to examine the impact of Seidel spherical aberration (SA) on optimum refractive state for detecting and discriminating small bright lights on a dark background.
METHODS: An adaptive-optics system was used to correct ocular aberrations of cyclopleged eyes and then systematically introduce five levels of Seidel SA for a 7-mm diameter pupil: 0,±0.18, and±0.36diopters (D)mm-2. For each level of SA, subjects were required to detect one or resolve two points of light (0.54 arc min diameter) on a dark background. Refractive error was measured by adjusting stimulus vergence to minimize detection and resolution thresholds. Two other novel focusing tasks for single points of light required maximizing the perceived intensity of a bright point\'s core and minimizing its overall perceived size (i.e. minimize starburst artifacts). Except for the detection task, luminance of the point of light was 1000cdm-2 on a black background lower than 0.5cdm-2.
RESULTS: Positive SA introduced myopic shifts relative to the best subjective focus for dark letters on a bright background when there was no SA, whereas negative SA introduced hyperopic shifts in optimal focus. The changes in optimal focus were -1.7, -2.4, -2.0, and -9.2D of focus per Dmm-2 of SA for the detection task, resolution task, and maximization of core\'s intensity and minimization of size, respectively.
CONCLUSIONS: Ocular SA can be a significant contributor to changes in refractive state when viewing high-contrast point sources typically encountered in nighttime environments.

To test the hypothesis that marginal ray deviations determine perceived starburst sizes, and to explore different strategies for decreasing starburst size in highly aberrated eyes.
Perceived size of starburst images and visual acuities were measured psychophysically for eyes with varying levels of spherical aberration, pupil sizes, and defocus. Computationally, we use a polychromatic eye model including the typical levels of higher order aberrations (HOAs) for keratoconic and post-LASIK eyes to quantify the image quality (the visually weighted Strehl ratio derived from the optical transfer function, VSOTF) with different pupil sizes at both photopic and mesopic light levels.
For distance corrected post-LASIK and keratoconic eyes with a night-time pupil (e.g., 7 mm), the starburst diameter is about 1.5 degrees (1 degree for normal presbyopic eyes), which can be reduced to ≤0.25 degrees with pupil sizes ≤3 mm. Starburst size is predicted from the magnitude of the longitudinal spherical aberration. Refracting the eye to focus the pupil margin also removed starbursts, but, unlike small pupils, significantly degraded visual acuity. Reducing pupil diameter to 3 mm improved image quality for these highly aberrated eyes by about 2.7 ×  to 1.7 ×  relative to the natural pupils when light levels were varied from 0.1 to 1000 cd m-2 , respectively.
Subjects with highly aberrated eyes observed larger starbursts around bright lights at night predictable by the deviated marginal rays. These were effectively attenuated by reducing pupil diameters to ≤3 mm, which did not cause a drop in visual acuity or modelled image quality even at mesopic light levels.

Retinal direction-selective ganglion cells (DSGCs) have the remarkable ability to encode motion over a wide range of contrasts, relying on well-coordinated excitation and inhibition (E/I). E/I is orchestrated by a diverse set of glutamatergic bipolar cells that drive DSGCs directly, as well as indirectly through feedforward GABAergic/cholinergic signals mediated by starburst amacrine cells. Determining how direction-selective responses are generated across varied stimulus conditions requires understanding how glutamate, acetylcholine, and GABA signals are precisely coordinated. Here, we use a combination of paired patch-clamp recordings, serial EM, and large-scale multi-electrode array recordings to show that a single high-sensitivity source of glutamate is processed differentially by starbursts via AMPA receptors and DSGCs via NMDA receptors. We further demonstrate how this novel synaptic arrangement enables DSGCs to encode direction robustly near threshold contrasts. Together, these results reveal a space-efficient synaptic circuit model for direction computations, in which \"silent\" NMDA receptors play critical roles.

The retina contains two populations of cholinergic amacrine cells, one positioned in the ganglion cell layer (GCL) and the other in the inner nuclear layer (INL), that together comprise ∼1/2 of a percent of all retinal neurons. The present study examined the genetic control of cholinergic amacrine cell number and distribution between these two layers. The total number of cholinergic amacrine cells was quantified in the C57BL/6J and A/J inbred mouse strains, and in 25 recombinant inbred strains derived from them, and variations in their number and ratio (GCL/INL) across these strains were mapped to genomic loci. The total cholinergic amacrine cell number was found to vary across the strains, from 27,000 to 40,000 cells, despite little variation within individual strains. The number of cells was always lower within the GCL relative to the INL, and the sizes of the two populations were strongly correlated, yet there was variation in their ratio between the strains. Approximately 1/3 of that variation in cell ratio was mapped to a locus on chromosome 3, where Sex determining region Y box 2 (Sox2) was identified as a candidate gene due to the presence of a 6-nucleotide insertion in the protein-coding sequence in C57BL/6J and because of robust and selective expression in cholinergic amacrine cells. Conditionally deleting Sox2 from the population of nascent cholinergic amacrine cells perturbed the normal ratio of cells situated in the GCL versus the INL and induced a bistratifying morphology, with dendrites distributed to both ON and OFF strata within the inner plexiform layer.