Imaging and histopathological studies have demonstrated that structural changes of the retina affect subjects with Alzheimer’s disease (AD) or mild cognitive impairment (MCI). The aim of this study was to quantitatively investigate the retinal vessels in these disorders, using dynamic vessel analyzer (DVA) and optical coherence tomography angiography (OCTA) analysis. Twelve subjects with AD, 12 subjects with MCI, and 32 gender- and age-matched controls were prospectively enrolled. Mean ± SD age was 72.9 ± 7.2 years in the AD group, 76.3 ± 6.9 years in the MCI group, and 71.6 ± 5.9 years in the control group (p = 0.104). In the DVA dynamic analysis, the arterial dilation was decreased in the AD group (0.77 ± 2.06%), in the comparison with the control group (3.53 ± 1.25%, p = 0.002). The reaction amplitude was decreased both in AD (0.21 ± 1.80%, <0.0001) and MCI (2.29 ± 1.81%, p = 0.048) subjects, compared with controls (3.86 ± 1.94%). OCTA variables did not differ among groups. In the Pearson correlation analysis, amyloid β level in the cerebrospinal fluid was directly correlated with the arterial dilation (R = 0.441, p = 0.040) and reaction amplitude (R = 0.580, p = 0.005). This study demonstrate that Alzheimer’s and MCI subjects are characterized by a significant impairment of the retinal neurovascular coupling. This impairment is inversely correlated with the level of amyloid β in the cerebrospinal fluid.

Aims To describe the vascular changes in patients affected by non-neovascular age-related macular degeneration (AMD), featuring reticular pseudodrusen (RPD), drusen, or both RPD and drusen by means of optical coherence tomography angiography (OCT-A). Methods Cross-sectional observational case series. Patients with non-neovascular AMD presenting at the Medical Retina Service of the Department of Ophthalmology, University Vita-Salute San Raffaele in Milan were recruited. Patients underwent best-corrected visual acuity, biomicroscopy, infrared reflectance, short-wavelength fundus autofluorescence and OCT-A (AngioPlex, CIRRUS HD-OCT 5000, Carl Zeiss Meditech, Dublin, USA). Main outcome was quantification of vessel density, stromal tissue, and vascular/stromal (V/S) ratio at the choriocapillaris (CC), the Sattler and Haller's and the whole choroid layers among different groups of patients with non-neovascular AMD by means of binarised OCT-A scans. Results 45 eyes of 34 patients were enrolled (15 eyes of 11 patients with RPD, group 1; 15 eyes of 11 patients with drusen, group 2; 15 eyes of 12 patients with mixed phenotype, group 3). The CC, the Sattler and Haller's and the whole choroid vessel density were reduced in all groups of patients (p=0.023, p=0.007 and p=0.011 in group 1, group 2 and group 3 for the CC; p=0.021, p=0.037 and p=0.043 in group 1, group 2 and group 3 for the Sattler and Haller's density; p=0.016, p=0.002 and p<0.001 in group 1, group 2 and group 3 for the choroidal density), with significantly lower V/S ratios compared with healthy controls. Conclusions Patients with non-neovascular AMD show significant choroidal vascular depletion and fibrotic replacement, suggesting a possible role in the pathogenesis and progression of the disease.

Background/aims To describe the morphological features of choroidal neovascularisation (CNV) and to report the ability of optical coherence tomography angiography (OCT-A) to detect the presence of myopic CNV by means of this new technique. Methods Myopic CNV cases were individuated from a pool of patients with pathological myopia consecutively presenting between October 2015 and March 2016. OCT-A images were assessed for classification of morphological features, and to estimate sensitivity and specificity. Results Thirty-six eyes of 28 consecutive patients with myopic CNV were included. In 4 out of 36 eyes it was not possible to classify the CNV ‘shape’, ‘core’, ‘margin’ and ‘appearance’ because the vascular network was not clearly visualised due to the poor quality of the examination. CNV shape on OCT-A was rated as circular in 9 eyes and irregular in 23 eyes. CNV core was visible in 11 eyes. CNV margin was considered as well defined in 16 eyes and poorly defined in 16 eyes. CNV appearance showed an ‘interlacing’ aspect in 16 eyes and a ‘tangled’ aspect in the other 16 eyes. A total of 11 CNVs were defined as active, 9 of which (81.8%) were interlacing, while a total of 21 were inactive, 14 of which (66.7%) were tangled. OCT-A sensitivity turned out to be 90.48% and specificity was 93.75%. Conclusions We describe the OCT-A features of myopic CNV secondary to pathological myopia and demonstrate its high sensitivity and specificity for neovascular detection. Qualitative evaluation of OCT-A characteristics may allow one to recognise different patterns, possibly corresponding to different degrees of neovascular activity.

Background Endometrial cancers with more than one molecular feature—POLE mutations (POLEmut), mismatch repair protein deficiency (MMRd), p53 abnormality (p53abn)—are called ‘multiple classifiers’. Objective To describe our cohort of multiple classifiers and to report the results of a review on their incidence and the techniques used to identify them. Methods Multiple classifiers identified at the European Institute of Oncology, Milan, between April 2019 and Decmber 2022, were included. Clinicopathological, molecular characteristics, and oncologic outcomes were summarized and compared between single and multiple classifiers sharing common features. Studies on molecular classification of endometrial cancer were searched in the PubMed Database to collect data on the incidence of multiple classifiers and the techniques used for classification. Results Among 422 patients, 48 (11.4%) were multiple classifiers: 15 (3.6%) POLEmut-p53abn, 2 (0.5%) POLEmut-MMRd, 28 (6.6%) MMRd-p53abn, and 3 (0.7%) POLEmut-MMRd-p53abn. MMRd-p53abn and MMRd differed in histotype (non-endometrioid: 14.8% vs 2.0%, p=0.006), grade (high-grade: 55.6% vs 22.2%, p=0.001), and MMR proteins expression, whereas they differed from p53abn in histotype (non-endometrioid: 14.8% vs 50.0%, p=0.006). POLEmut-p53abn and POLEmut differed only in grade (high-grade: 66.7% vs 22.7%, p=0.008), while they differed from p53abn in age (56.1 vs 66.7 years, p=0.003), stage (advanced: 6.7% vs 53.4%, p=0.001), and histotype (non-endometrioid: 6.7% vs 50.0%, p=0.002). Two (7.1%) patients with MMRd-p53abn, 4 (4.0%) with MMRd, and 25 (34.3%) with p53abn had a recurrence. No recurrences were observed in POLEmut-p53abn and POLEmut. TP53 sequencing allowed the detection of additional 7 (18.9%) multiple classifiers with normal p53 immunostaining. The incidence of multiple classifiers ranged from 1.8% to 9.8% in 10 published studies including >100 patients. When only p53 immunohistochemistry was performed, the highest incidence was 3.9%. Conclusions The characteristics of POLEmut-p53abn resembled those of POLEmut, whereas MMRd-p53abn appeared to be intermediate between MMRd and p53abn. The high proportion of multiple classifiers may be related to the methods used for molecular classification, which included both p53 immunohistochemistry and TP53 sequencing.