Foveal structure strongly correlates with its neurovascular organization. The findings support a developmental model in which the size of the FAZ determines the extent of centrifugal migration of inner retinal layers, which counteracts in some way the centripetal packing of cone photoreceptors.

Metastatic uveal melanoma is a deadly disease with no proven standard of care. Here we present a metastatic uveal melanoma patient with an exceptional high sensitivity to a PD-1 inhibitor associated with outlier CpG>TpG mutation burden, MBD4 germline deleterious mutation, and somatic MBD4 inactivation in the tumor. We identify additional tumors in The Cancer Genome Atlas (TCGA) cohorts with similar hypermutator profiles in patients carrying germline deleterious MBD4 mutations and somatic loss of heterozygosity. This MBD4-related hypermutator phenotype may explain unexpected responses to immune checkpoint inhibitors.

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Purpose: Uveal melanomas (UM) are genetically simple tumors carrying few copy number alterations (CNA) and a low mutation burden, except in rare MBD4-deficient, hypermutated cases. The genomics of uveal melanoma metastatic progression has not been described. We assessed the genetic heterogeneity of primary and metastatic MBD4-proficient and-deficient uveal melanomas. Experimental Design: We prospectively collected 75 metastatic and 16 primary samples from 25 consecutive uveal melanoma patients, and performed whole-exome sequencing. Results: MBD4-proficient uveal melanomas contained stable genomes at the nucleotide level, acquiring few new single nucleotide variants (SNVs; 16 vs. 13 in metastases and primary tumors, respectively), and no new driver mutation. Five CNAs were recurrently acquired in metastases (losses of 1p, 6q, gains of 1q, 8q, and isodisomy 3). In contrast, MBD4-deficient uveal melanomas carried more than 266 SNVs per sample, with high genetic heterogeneity and TP53, SMARCA4, and GNAS new driver mutations. SNVs in MBD4-deficient contexts were exploited to unveil the timeline of oncogenic events, revealing that metastatic clones arose early after tumor onset. Surprisingly, metastases were not enriched in monosomy 3, a previously defined metastatic risk genomic feature. Monosomy 3 was associated with shorter metastatic-free interval compared with disomy 3 rather than higher rate of relapse. Conclusions: MBD4-proficient uveal melanomas are stable at the nucleotide level, without new actionable alterations when metastatic. In contrast, MBD4 deficiency is associated with high genetic heterogeneity and acquisition of new driver mutations. Monosomy 3 is associated with time to relapse rather than rate of relapse, thus opening avenues for a new genetic prognostic classification of uveal melanomas.

Optical coherence tomography (OCT) allows high-resolution and noninvasive imaging of the structure of the retina in humans. This technique revolutionized the diagnosis of retinal diseases in routine clinical practice. Nevertheless, quantitative analysis of OCT scans is yet limited to retinal thickness measurements. We propose a novel automated method for the segmentation of eight retinal layers in these images. Our approach is based on global segmentation algorithms, such as active contours and Markov random fields. Moreover, a Kalman filter is designed in order to model the approximate parallelism between the photoreceptor segments and detect them. The performance of the algorithm was tested on a set of retinal images acquired in-vivo from healthy subjects. Results have been compared with manual segmentations performed by five different experts, and intra and interphysician variability has been evaluated as well. These comparisons have been carried out directly via the computation of the root mean squared error between the segmented interfaces, region-oriented analysis, and retrospectively on the thickness measures derived from the segmentations. This study was performed on a large database including more than seven hundred images acquired from more than one hundred healthy subjects. OCT image enhancement, by performing image equalization [9], applying directional filters [9] or coherence-enhanced diffusion filtering [10]; A-scans (columns) alignment with regard to a reference retina layer, determined by cross correlation of adjacent columns [6] or with regard to an already detected interface [9,11]. The filtered OCT images are then passed to the interface detection process. This second step is generally based on the search for peak Contents lists available at ScienceDirect

We hypothesise that early changes involve the layer between RPE and the IS/OS interface, first with vitelliform material accumulation beneath the sensory retina, and then with IS/OS alterations, pigments migration towards inner layers and fluid accumulation. These changes come with RPE alterations such as hypertrophy or sub-RPE deposits.

This paper proposes an automated method for the segmentation of eight retinal layers in high resolution OCT images. It has been evaluated based on comparison with manual segmentation performed by five different experts. The method has been successfully applied on a database of 72 images. Quantitative measures are then derived as an aid to ophthalmic diagnosis. A good agreement with measures derived from manual segmentation is obtained which allows us to use the proposed method for retinal variability studies.

Analysis of infrared pictures in classic CNV constantly revealed a whitish ring that is correlated to the limits of the lesion. IR picture is a non invasive imaging of the macula, but the specificity of the features needs to be investigated in further studies.