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Geographic atrophy (GA), the atrophic late stage of age-related macular degeneration (AMD), is one of the leading causes of vision loss in developed countries. Based on genetic, histological and preclinical studies, the role of the innate immune system in the development and progression of GA is well established. Microglia, the principal resident immune cells, are recognized as key players in innate immunity and contributors to AMD development. Optical coherence tomography (OCT) allows to identify small hyperreflective retinal foci (HRF) with specific features known as aggregates of activated microglial cells as possible in vivo imaging feature of local neuroretinal inflammation. The purpose of this study was to evaluate the presence and amount of small HRF in the eyes of patients with different macular atrophic phenotypes. Patients with GA in both eyes (bilateral GA: B-GA group), patients with GA in one eye and macular new vessels (MNV) in the fellow-eye (unilateral GA: U-GA group) and patients with extensive macular atrophy with pseudodrusen (EMAP), a rare and aggressive variant of atrophic AMD, were retrospectively analyzed. HRF, defined as isolated punctiform elements of small dimensions (≤30 μm) with intermediate reflectivity (similar to that of the nerve fiber layer) and without a shadow cone, were manually identified and quantified. The amount of HRF was correlated to best corrected visual acuity (BCVA), GA lesion size, measured both at near infrared reflectance (NIR), and blue wavelength fundus autofluorescence (FAF) images, to some GA features (multifocal versus unifocal GA; presence versus absence of foveal sparing) and to central retinal thickness (CRT). Forty-six patients (26 in the B-GA group, 16 in the U-GA group and 4 in the EMAP group) were studied. Patients with EMAP were younger compared to patients with B-GA and to patients with U-GA (63.5 ± 6.8 years vs 80.4 ± 8.4 years B-GA, and vs 83.3 ± 6.1 years U-GA; p = 0.0004 and p= <0.0001, respectively). Mean BCVA, mean GA area at NIR and at FAF images, foveal sparing and multifocal versus unifocal GA distribution and mean CRT were not significantly different among groups. GA area was wider on NIR versus FAF in all groups, significantly in B-GA and U-GA groups (11.7 ± 7.6 mm 2 vs 10.6 ± 7.1 mm 2 , p = 0.0087 in B-GA; 7.8 ± 9.2 mm 2 vs 7.7 ± 9.4 mm 2 , p = 0.004 in U-GA). The number of HRF was significantly higher in U-GA compared to B-GA and to EMAP (47.4 ± 7.1 vs 31.6 ± 7.3 B-GA and 28.0 ± 4.9 EMAP, p < 0.0001 for both), while mean HRF number did not significantly differ between B-GA and EMAP (p = 0.1960). HRF count correlated only to CRT, positively in B-GA and negatively in U-GA group. The increase of small HRF, which mirrors retinal microglial activation, characterizes eyes with unilateral GA (and MNV in the fellow eye) but not eyes with bilateral GA or EMAP. The role of activated microglia in the retina of GA eyes needs to be better investigated, mainly considering the actual and new therapeutic strategies with which to reduce either the development or progression of the atrophic macular changes., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The eye, and the cornea in particular, is a common site of chemotherapy induced toxicity, and ocular side effects of both traditional and novel agents have been reported. Corneal confocal microscopy (CCM) is an in vivo technique that allows for the study of all the corneal layers in an easy, non-invasive and reproducible way via the direct visualization of corneal cell morphologies as well as of sub-basal nerve plexus. Thus, it represents a useful way to identify and monitor chemotherapy induced corneal alterations. This work aims to review the use of CCM in identifying corneal toxicity secondary to chemotherapy treatment, as regards both corneal nerves alterations in the setting of chemotherapy induced peripheral neuropathy (CIPN) and other corneal structure changes, particularly involving the corneal epithelium.

Objectives: Achromatopsia (ACHM) is a rare autosomal, recessively inherited disease that is characterized by cone dysfunction, for which several gene therapies are currently on trial. The aim of this study was to find correlations between the morphological macular changes identified using optical coherence tomography (OCT) and some visual functional parameters. Visual acuity (VA), contrast sensitivity (CS), and macular sensitivity obtained by means of microperimetry were assessed. Methods: Adolescents with ACHM underwent macular microperimetry (S-MAIA device) in mesopic condition, macular OCT, best corrected visual acuity (BCVA), low luminance visual acuity (LLVA), near vision acuity (NVA), and CS measurement. Results: Eight patients (15 eyes) with ACHM were analyzed. The mean age was 17 ± 2.7 years, and genetic variants involved the CNGA3 gene (37.5%) and CNGB3 gene (62.5%). OCT staging significantly correlated with microperimetry sensitivity parameters, namely the sensitivity of the central foveal point ( p = 0.0286) and of the first and second perifoveal rings ( p = 0.0008 and p = 0.0014, respectively). No correlations were found between OCT staging and VA measurements, nor with CS value. Conclusions: Among the extensive evaluated visual function tests, only microperimetry sensitivity showed a correlation with morphological macular changes identified at OCT. Microperimetry sensitivity may thus represent a useful visual function tool in natural ACHM history studies considering the upcoming research on gene therapies for the treatment of ACHM.

Background: This study aimed to assess the neuronal and microvascular retinal and choroidal involvement in COVID-19 recovered patients using optical coherence tomography (OCT) and OCT angiography (OCTA)., Methods: This observational cross-sectional study recruited patients recovered from COVID-19 and a group of healthy controls for comparisons. OCT (peripapillary scan and macular map) and OCTA (macular map) were performed to obtain: the central subfield thickness (CST), the macular volume (MV), the peripapillary retinal nerve fibre layer (pRNFL) thickness, the vessel area density (VAD), vessel length fraction (VLF), vessel diameter index (VDI) and fractal dimension (FD) of the superficial vascular plexus (SVP), intermediate capillary plexus (ICP) and deep capillary plexus (DCP), and the vessel density (VD), stromal density (SD) and vascular/stromal (V/S) ratio of the choriocapillaris (CC) and choroid (Ch). Data regarding disease severity, administered therapy and prior comorbidities were collected., Results: We recruited 676 eyes from 338 patients and 98 eyes from 49 healthy controls. VAD of all the three retinal plexuses, VLF and VDI of ICP and DCP and VD of CC were significantly reduced in patients versus controls. No differences were found in CST, MV and pRNFL. A multivariate analysis showed that oxygen therapy, previous cardio/cerebrovascular events and hypertension negatively influenced vascular parameters., Conclusion: A microvascular retinal and choriocapillaris damage may be identified secondary to SARS-CoV-2 infection, even after recovery. OCTA may represent a reproducible and non-invasive tool to assess microangiopathy in these patients, with particular regard to those with previous cardio/cerebrovascular events, hypertension and those who received oxygen therapy., (© 2024. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

This study aimed to assess outer retinal layer (ORL), retinal pigment epithelium (RPE), choroid (Ch) and choriocapillaris (CC) modifications in adolescents with long-lasting (>10 years) type 1 diabetes (T1D) without (noDR) or with diabetic retinopathy (DR). ORL and RPE thickness were measured at optical coherence tomography (OCT) macular scans. Vascular parameters of Ch and CC were quantified after elaboration of macular OCT-angiography (OCTA) images. Insulin dose and auxological and metabolic parameters were correlated with OCT and OCTA findings in patients. ORL thickness was higher in DR eyes than in noDR and healthy controls (HC), and RPE thickness was higher in noDR and DR eyes than in HC, with statistical significance for some sectors in noDR versus HC. No OCTA parameters of CC and Ch differed among groups, and no significant correlation was observed with auxological and metabolic parameters. In conclusion, ORL and RPE were both increased in adolescents with long-lasting T1D. Such changes were not associated with insulin dose and glycemia control, nor to any choroid or choriocapillaris flow change clinically detectable at OCTA, and they could be potential imaging biomarkers of disease progression.

Distal symmetric polyneuropathy (DPN), particularly chronic sensorimotor DPN, represents one of the most frequent complications of diabetes, affecting 50% of diabetic patients and causing an enormous financial burden. Whilst diagnostic methods exist to detect and monitor this condition, they have significant limitations, mainly due to their high subjectivity, invasiveness, and non-repeatability. Corneal confocal microscopy (CCM) is an in vivo, non-invasive, and reproducible diagnostic technique for the study of all corneal layers including the sub-basal nerve plexus, which represents part of the peripheral nervous system. We reviewed the current literature on the use of CCM as an instrument in the assessment of diabetic patients, particularly focusing on its role in the study of sub-basal nerve plexus alterations as a marker of DPN. CCM has been demonstrated to be a valid in vivo tool to detect early sub-basal nerve plexus damage in adult and pediatric diabetic patients, correlating with the severity of DPN. Despite its great potential, CCM has still limited application in daily clinical practice, and more efforts still need to be made to allow the dissemination of this technique among doctors taking care of diabetic patients.

A large spectrum of neurological manifestations has been associated with coronavirus disease 2019 (COVID-19), and recently, the involvement of small fibers has been suggested. This study aims to investigate the involvement of small peripheral nervous fibers in recovered COVID-19 patients using in-vivo corneal confocal microscopy (CCM). Patients recovered from COVID-19 and a control group of healthy subjects underwent in-vivo CCM. Corneal nerve fiber density (CNFD), corneal nerve branch density (CNBD), corneal nerve fiber length (CNFL), corneal nerve fiber total branch density (CTBD), corneal nerve fiber area (CNFA), corneal nerve fiber width (CNFW), fiber tortuosity (FT), number of beadings (NBe), and dendritic cells (DC) density were quantified. We enrolled 302 eyes of 151 patients. CNBD and FT were significantly higher (p = 0.0131, p < 0.0001), whereas CNFW and NBe were significantly lower (p = 0.0056, p = 0.0045) in the COVID-19 group compared to controls. Only CNBD and FT resulted significantly correlated to antiviral drugs (increased) and corticosteroids (decreased). No significant relationship with disease severity parameters was found. COVID-19 may induce peripheral neuropathy in small fibers even months after recovery, regardless of systemic conditions and therapy, and CCM may be a useful tool to identify and monitor these morphological changes.

The purpose of this study was to assess the long-term natural history of choroidal abnormalities (CAs) in a large pediatric neurofibromatosis type 1 (NF1) population, quantifying their progression in number and dimensions. Pediatric patients (<16 years old) affected by NF1 with a minimum follow-up of 3 years with at least one CA in one eye were consecutively recruited. Near-infrared (NIR) imaging was performed to identify CAs, which were quantified in number and size. The CAs area and perimeter were normalized for the optic disc dimensions to avoid possible bias related to the growing process of the eye. Ninety-nine eyes of 53 patients were evaluated. The CAs number, area and perimeter significantly increased during follow-up (p < 0.0001 for each parameter). The patient age at baseline was inversely correlated with the CAs number over time (coefficient = −0.1313, p = 0.0068), while no correlation was found between the patient age and CAs progression in size. In conclusion, we provide evidence that, in NF1 pediatric patients, CAs change over time, increasing both in number and dimensions, independently from the physiological growth of the eye. While the increase of the CAs number occurs particularly at an earlier age, the increase in the CAs dimensions is a slow process that remains constant during childhood.

Inflammatory, angiogenic, and immune processes have been associated with uveal melanoma (UM). The aim of the present study was to evaluate the presence of some specific aqueous humor (AH) soluble biomarkers in eyes affected by UM. Thirty-five eyes affected by primary UM and 35 control eyes, scheduled for cataract surgery, underwent full ophthalmic examination and AH sampling at time of surgery (brachytherapy or cataract surgery, respectively). AH samples were analyzed by means of ELISA, to detect the concentration of selected cytokines, chemokines, and growth factors. Compared with the control group, higher levels of IL-6 (P = .049), IL-8 (P = .006), RANTES (P = .008), EGF (P = .032), bFGF (P = .016), MIF (P = .007), and MCP (P = .020) were detected in eyes with UM. VEGF concentration between the two groups was statistically borderline (P = .058). Comparison between clinical characteristics and cytokine concentrations showed a positive correlation between tumor thickness and IL-8 (P = .032), and degree of serous retinal detachment and IL-6 (P = .021). UM is characterized by the presence of retinal neuroinflammatory, angiogenic, and immune biomarkers in AH. The proteomic analysis of AH could characterize UM microenvironment, allowing to better understand its pathophysiology.

An ectopic pregnancy occurs when a blastocyst implants outside the uterus cavity. It is a condition with increased morbidity and mortality for women in reproductive age. Most of the ectopic pregnancies (95.5%) are located in the fallopian tube. We report a case of an ectopic pregnancy that progressed unruptured and with fetus in situ up to 17 gestational weeks. This case is rare, especially in developed countries where patients have access to healthcare. With this case report we would like to emphasize that ectopic pregnancy should be among the differential diagnoses of abdominal pain even in the second trimester of pregnancy but also the importance of an early vaginal ultrasound examination in its diagnosis.

Twenty-four hirsute women were treated with an inversal sequential scheme of cyproterone acetate, 50 mg/d by oral route from the 1st to the 15th day of the menstrual cycle, along with 100 micrograms/24 h of 17 beta-estradiol transdermally administered from days 1 to 21, for nine cycles at weekly intervals. The acne and seborrhea as well as hirsutism showed a significant improvement in all subjects studied. The plasma testosterone and dehydroepiandrosterone sulfate decrease from 1.5 +/- 1.3 ng/mL and 6.9 +/- 1.3 micrograms/mL to 0.5 +/- 0.03 ng/mL and 2.7 +/- 1.7 micrograms/mL, respectively. Similar values were observed in subjects with idiopathic hirsutism during the treatment. The metabolic parameters, as well as the plasma levels of sex hormone-binding globulin, appeared unaffected by the therapy. Furthermore, the luteinizing hormone and follicle-stimulating hormone secretion was strongly inhibited from the first cycle of treatment. In conclusion, considering the good clinical results and the avoidance of any hepatic effect, this association should be taken into account in the treatment of hirsutism, especially in case of oral estrogen intolerance.