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.

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.

Background: To explore the agreement between clinical judgment and Guided Progression Analysis II (GPAII) in the evaluation of visual fields (VF) progression in patients with glaucoma. Methods: Three glaucoma experts and three general ophthalmologists were asked to rate the VF series by classifying them as progressive through the observation of the overview report. The agreement between clinical judgment and GPAII event analysis (EA) and trend analysis (TA) was assessed by Cohen statistic. The sensitivity and specificity of clinical judgment in detecting the presence of progression was evaluated considering the results of GPAII as the reference standard. Results: 66 VF series were included in the study. Glaucoma experts, general ophthalmologists, GPAII EA, and GPAII TA found progression in 39%, 38%, 15%, and 21% of the VF series (p < 0.05). The clinical judgment of glaucoma experts and general ophthalmologists was discordant with GPAII EA in 27.2% and 28.7% (k = 0.35, 95% CI 0.15–0.56 and k = 0.30, 95% CI 0.09–0.52) and with GPAII TA in 21.2% and 25.7% of the VF series examined (k = 0.51, 95% CI 0.31–0.72 and k = 0.41, 95% CI 0.18–0.62). Considering the GPAII EA and TA as reference standard, glaucoma experts showed a sensitivity of 90% and 92.8% and a specificity of 69.6% and 75%, while general ophthalmologists showed a sensitivity of 80% and 78.5% and a specificity of 69.6% and 73%. Conclusions: The agreement between clinical judgment and GPAII ranges from fair to moderate. Glaucoma experts showed better ability than general ophthalmologists in detecting VF progression.

Background: Radiation maculopathy (RM) is a delayed, sight-threatening complication of ocular radiotherapy. Traditionally regarded as a pure microvascular disease, emerging evidence points to the central role played by retinal neuroinflammation, driven by microglial activation and cytokine dysregulation affecting both the retina and the choroid. Hyperreflective retinal foci, neuroinflammatory in origin (I-HRF), visualized through advanced imaging modalities such as spectral domain optical coherence tomography (OCT), have been identified as early and critical biomarkers of both preclinical and clinical retinal neuroinflammation. Materials and Methods: This review synthesizes findings from experimental and clinical studies to explore the pathophysiology of neuroinflammation and the associated imaging parameters in RM. Results: The integration of experimental and clinical evidence specifically underscores the significance of I-HRF as an early indicator of neuroinflammation in RM. OCT enables the identification and quantification of these biomarkers, which are linked to microglial activation and cytokine dysregulation. Conclusions: The pathophysiology of RM has evolved from a predominantly vascular condition to one strongly secondary to neuroinflammatory mechanisms involving the retina and choroid. In particular, I-HRF, as early biomarkers, offers the potential for preclinical diagnosis and therapeutic intervention, paving the way for improved management of this sight-threatening complication.

Several soluble mediators are activated during myogenesis and progression, and severe neurodegeneration, with related biomarkers, characterizes high myopia-related retinal atrophy. Targets of oxidative stress, epigenetics and neurogenic inflammation have been reported in the prospecting of some bioindicators to mirror retinal insults occurring in high myopia. The aim of the present study was to assess the expression of a few selected biomarkers belonging to the neurotrophin (NGF and BDNF), oxidative (NO, KEAP1/NRF2), and epigenetic (DNMT3 and HD1) pathways. Sixty-five (65; 76.25 ± 9.40 years) specimens—aqueous, anterior capsule (AC), and lens epithelial cells (LEC)—were collected at the time of cataract surgery and used for ELISA (aqueous) and transcripts analysis (AC/LEC). Biosamples were grouped as emmetrope (23; 81.00 ± 6.70 years); myopia (24; 75.96 ± 7.30); and high (pathological) myopia (18; 70.56 ± 11.68 years), depending on axial length (AL) and refractive error (RE). Comparisons and correlations were carried out between myopic and high-myopic subgroups. NGF and BDNF were lowered in myopic samples; NGF and BDNF transcripts were differentially expressed in LEC, and their expression correlated positively with NGF and negatively with BDNF, with the expression of the αSMA phenotype. NGF and BDNF correlated negatively with NO and nitrites. Oxidative stress (iNOS/NOX1/NOX4 and KEAP1/NRF2) and epigenetic (DNMTα3/HD1) transcripts were upregulated in myopic LEC, compared with emmetropic ones. Herein, we prospect the contribution of NGF and BDNF in both neuroinflammation and neuroprotection occurring in this chronic disease.

This pilot study explored whether the ceruloplasmin (CP) and ferritin (FT) levels in ocular fluids could serve as biomarkers for early neurodegenerative diseases (Alzheimer’s, Parkinson’s, and other dementias). CP and FT are known to modulate neurodegenerative tissue responses. We analysed aqueous and vitreous samples from 26 patients (8M/18F, aged 60–85) who were undergoing elective vitreoretinal (VR) surgery. Of these, 14 had idiopathic epiretinal membranes (ERMs), 6 had idiopathic macular holes (MH), and 6 were patients with Alzheimer’s disease (AD) who presented with VR disorders (VRDs). CP, FT, and selected neuroinflammatory mediators such as interferon γ (IFN-γ), interleukin (IL-6), vascular endothelial growth factor (VEGF), nerve growth factor (NGF), and brain-derived neurotrophic factor (BDNF) were quantified. Odds ratio analysis was applied to assess the CP/FT ratio’s association with subretinal drusen. We found distinct CP and FT profiles in VRD samples. In aqueous fluid, the CP increased and the FT decreased in early-stage ERM, which reduced the CP/FT ratio. Similar patterns were observed in vitreous fluid. The CP levels correlated with the VEGF (aqueous), IL-4 (vitreous), NGF, and BDNF levels; FT correlated with IL-6 and NGF. A higher CP/FT ratio was associated with increased risk for neurodegenerative conditions. Our findings support the quantification of CP and FT in ocular fluids as a promising approach for identifying early neurodegenerative changes and suggest that the CP/FT ratio may be linked to drusen imaging and clinical neurodegenerative history.