Martina Cocuzza

Background/Objectives: Nicotinamide (NAM), a form of vitamin B3 and precursor of nicotinamide adenine dinucleotide (NAD), has emerged as a potential metabolic and neuroprotective strategy in glaucoma. This systematic review aimed to evaluate the available human evidence on NAM-containing and NAD-targeted strategies in glaucoma, integrating interventional, observational, and mechanistic evidence with particular attention to clinical outcomes, methodological quality, and safety. Methods: A systematic literature search was conducted in PubMed, Scopus, and the Cochrane Central Register of Controlled Trials (CENTRAL), with the search updated through 22 August 2026. Eligible studies included randomized and non-randomized interventional studies evaluating NAM-containing or NAD-targeted supplementation strategies, as well as observational human studies investigating NAM/NAD-related biomarkers or mitochondrial metabolic alterations in relation to glaucoma. Risk of bias was assessed according to study design using RoB 2 for randomized trials, ROBINS-I for non-randomized interventional studies, and a domain-based assessment for observational exposure and biomarker studies. Owing to substantial clinical and methodological heterogeneity, findings were synthesized narratively without quantitative pooling. Results: Thirteen eligible reports representing eight unique human studies were included. Randomized trials provided preliminary evidence that NAM-containing interventions may produce short-term functional and electrophysiological effects. NAM supplementation was associated with improvement in inner retinal electrophysiological function in randomized crossover studies, whereas effects on visual field outcomes were inconsistent. A trial combining NAM with pyruvate reported favorable short-term visual field changes, although the specific contribution of NAM could not be isolated. Non-randomized studies provided complementary evidence on vascular, metabolic, structural, electrophysiological, and patient-reported outcomes but were limited by potential confounding and uncontrolled study designs. Observational studies reported associations between glaucoma and altered circulating NAM concentrations and systemic mitochondrial dysfunction. Available studies were generally small and of limited duration, and the evidence was insufficient to establish sustained neuroprotection or modification of glaucoma progression. Conclusions: Human evidence supports the biological plausibility of targeting NAM/NAD metabolism in glaucoma and provides preliminary signals of short-term biological and functional effects. However, current evidence remains insufficient to support routine high-dose NAM supplementation in clinical practice. Larger, adequately powered, long-term randomized controlled trials are required to establish sustained efficacy, optimal dosing, patient selection, and long-term safety.

The aim of this narrative review was to provide a disease-oriented diagnostic framework for selecting and integrating multimodal imaging techniques according to the suspected optic disc disorder. A non-systematic PubMed search was performed to identify relevant literature on optic disc diseases and related imaging appearances. Searches included a combination of terms related to disease features and imaging modalities. The recent introduction of non-invasive imaging devices, such as optical coherence tomography (OCT) and OCT angiography (OCTA), has allowed a remarkable step forward in the knowledge of the optic disc. OCT has revolutionized the diagnosis and monitoring of glaucomatous eyes, providing useful quantitative biomarkers. Fundus examination and color fundus photography are the first step for evaluation of optic disc edema, which requires further exams, including fundus autofluorescence, to exclude the presence of optic disc drusen, ocular ultrasound and in certain cases, fluorescein angiography. Although still limited, OCTA could give a support in the evaluation of vascular diseases that involve the optic disc, such as anterior ischemic optic neuropathy, retinal vein occlusion and proliferative diabetic retinopathy. Analyzing the radial peripapillary capillary plexus, OCTA can also highlight early vascular changes in degenerative diseases (i.e., glaucoma, Alzheimer’s disease or multiple sclerosis). Multimodal imaging is a cornerstone in the neuro-ophthalmology field, offering unparalleled insight into optic nerve head architecture and vascular integrity in both normal and diseased states.

Background: Mirvetuximab soravtansine (MIRV) improves outcomes in FRα-positive, platinum-resistant ovarian cancer; however ocular adverse events (OAEs), particularly corneal epithelial toxicity, are frequent and warrant structured ophthalmologic monitoring. Methods: In this retrospective observational study, 31 consecutive patients receiving MIRV for FRα-positive gynecologic malignancies underwent standardized ophthalmic assessments at baseline and prior to each treatment cycle (every 21 days). The protocol included best corrected visual acuity (BCVA), slit-lamp biomicroscopy, anterior-segment optical coherence tomography (AS-OCT), corneal topography, and tear film analysis. OAEs were graded according to the Common Terminology Criteria for Adverse Events (CTCAE) v5.0, based on symptom severity and functional impairment. Results: OAEs occurred in all patients (31/31, 100%), predominantly grade 1–2. Corneal epithelial toxicity was documented in 28/31 patients (90.3%), while no grade ≥ 3 events were observed. Symptoms typically developed 7–14 days after the second infusion. AS-OCT and corneal topography consistently revealed epithelial microcysts and surface irregularities, which were usually detected during scheduled pre-cycle ophthalmologic evaluations. Tear-film instability (break-up time ≤ 5 s) developed in 19/31 patients (61.3%), generally within 10 days after the second infusion, and improved in all but 2 patients (6.5%) following prophylactic lubrication. Transient refractive changes occurred in 28/31 patients (90.3%) and were associated with a temporary BCVA reduction (mean nadir ~20/32 Snellen), followed by recovery during follow-up. Conclusions: MIRV-related ocular alterations are frequent but reversible and clinically manageable. Multimodal imaging combined with functional and refractive assessment provides sensitive markers of corneal epithelial toxicity and supports integrated ophthalmologic monitoring to preserve visual function and maintain oncologic treatment continuity.

Background/Objectives: This study investigates adaptive changes in long-lasting pattern electroretinogram (PERG) responses in ocular hypertension (OHT) and open-angle glaucoma (OAG) patients, and in healthy subjects. Methods: Sixty consecutive individuals were recruited, including 20 OHT, 20 OAG, and 20 normal subjects. All participants underwent comprehensive ophthalmologic examination, 30–2 perimetry, and retinal nerve fiber layer imaging. Steady-state (7.5 Hz) PERGs were recorded over approximately 2 min, in response to 90% contrast alternating gratings within a large field size. The recordings were acquired into a sequence of 10 averages (packets), lasting 10 s each, following a standardized adaptation paradigm (Next Generation PERG, PERGx). Key outcome measures included PERGx parameters reflecting response amplitude and phase changes over time. Results: The PERGx grand average scalar amplitude, a surrogate of ordinary PERG, was significantly reduced in both OHT and OAG groups compared to normal subjects (p < 0.01). In contrast, minimal adaptation changes were noted in PERGx amplitude among all groups. The PERGx phase exhibited a progressive decline over time, with consistent delays of approximately 20 degrees across all groups. Angular dispersion of the PERGx phase increased significantly in OHT patients compared to normal subjects (p < 0.05). An inverse relationship was observed between PERGx angular dispersion and treated intraocular pressure, specifically in OHT patients. Conclusions: The findings suggest that both OHT and OAG eyes may exhibit temporal abnormalities in PERG adaptation, potentially indicating early dysfunction in retinal ganglion cell activity. Translational Relevance: PERGx phase changes may have significant implications for glaucoma early detection and management.