Cord blood platelet-rich plasma: proteomics analysis for ophthalmic applications Maria Cristina Savastano, Federico Giannuzzi, Alfonso Savastano, Valentina Cestrone, Francesco Boselli, Matteo Mario Carlà, Nicola Claudio D’Onofrio, Ilaria Biagini, Clara Rizzo, Maria Bianchi, Caterina Giovanna Valentini, Luciana Teofili, Andrea Urbani, Federica Iavarone, Stanislao Rizzo Clinical Proteomics, 2025 Our objective is to determine the protein and complements constituents of Cord blood Platelet-rich plasma (CB-PRP), based on the hypothesis that it contains beneficial components capable of arresting or potentially decelerating the advancement of atrophic age-related macular degeneration (dry-AMD), with the support of radiomics. Two distinct pools of CB-PRP were assessed, each pool obtained from a total of 15 umbilical cord-blood donors. One aliquot of each pool respectively was subjected to proteomic analysis in order to enhance the significance of our findings, by identifying proteins that are shared between the two sample pools and gaining insights into the pathways they are associated with. The bioinformatics analysis was developed using Reactome software. Three-hundred-seven (307) distinct proteins were found. Two hundred fifteen (215) of the elements mentioned above are shared by both pools. Seventy (70) elements are exclusive to pool S1, while pool S2 contains 22. We detected 109 representative and statistically significant pathways out of 549. We found proteins related to the immune system, signal transduction, vesicle-mediated transport, cell-cell communication, hemostasis, cellular responses to stimuli, cell cycle, and developmental biology. The analysis showed the presence of P15692-12, representing VEGF factor A, long form. With over 200 proteins, the CB-PRP can increase the immune response, including BCR, CD-22, FCGR, phospholipids, IL-10, FCGR-3A, and others. Discovering crucial trophic and complement-regulating variables is highly significant for potential applications in dry AMD. Our future research will examine the effects of intravitreal CB-PRP on dry-AMD eyes.
Intravitreal Injections of Cord Blood Platelet-Rich Plasma in Dry Age-Related Macular Degeneration: Regenerative Therapy Maria Cristina Savastano, Claudia Fossataro, Alessandro Berni, Alfonso Savastano, Valentina Cestrone, Federico Giannuzzi, Francesco Boselli, Matteo Mario Carlà, Mattia Cusato, Francesco Mottola, Riccardo Pirolo, Elena D'Agostino, Ilaria Biagini, Sofia Marcelli, Alessandro Gravina, Mengxi Shen, Clara Rizzo, Caterina Giovanna Valentini, Maria Bianchi, Luciana Teofili, Yuxuan Cheng, Ruikang K. Wang, Philip J. Rosenfeld, Stanislao Rizzo Ophthalmology Science, 2025 Purpose: Intravitreal injections (IVIs) of umbilical cord blood platelet-rich plasma (CB-PRP) were investigated to assess their safety and efficacy in slowing the progression of atrophy in eyes with late-stage dry age-related macular degeneration (AMD). Design: Randomized, controlled, prospective study. Subjects: Patients with AMD aged >65 years and diagnosed with bilateral geographic atrophy were enrolled. Methods: One eye of each subject received the treatment of intravitreal CB-PRP 0.05 ml, while the fellow eye received a sham injection. Atrophic areas were identified as large choroidal hypertransmission defects (hyperTDs) on en face subretinal pigment epithelium slabs (64-400 μm beneath Bruch's membrane) obtained 0.321 from swept-source OCT angiography scans. The main outcome was the mean annualized growth rate of the square root transformed area measurements in both treated and nontreated eyes. Main Outcome Measures: The mean ± standard deviation (SD) square root hyperTD area in the treated eyes was 3.30 ± 0.99 mm at baseline and 3.49 ± 0.98 mm after CB-PRP (IVI). In nontreated eyes, the mean square root hyperTD area was 2.96 ± 0.94 mm at baseline and 3.18 ± 0.94 mm after sham injections. Results: = 0.007). No adverse events were recorded. Conclusions: These preliminary data suggest that intravitreal CB-PRP injections might be safe and effective in slowing the progression of atrophy in AMD. Extended follow-up and larger sample sizes are needed to confirm our findings and determine the optimal treatment regimen for this novel treatment option in late-stage dry AMD. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
Radiomic Feature Extraction from OCT Angiography of Idiopathic Epiretinal Membranes and Correlation with Visual Acuity: A Pilot Study Maria Cristina Savastano, Marica Vagni, Matteo Mario Carlà, Huong Elena Tran, Claudia Fossataro, Valentina Cestrone, Francesco Boselli, Federico Giannuzzi, Sofia Marcelli, Ilaria Biagini, Luca Boldrini, Stanislao Rizzo Ophthalmology Science, 2025 Purpose: To explore the correlation between radiomics features extracted from OCT angiography (OCTA) of epiretinal membranes (ERMs) and baseline best-corrected visual acuity (BCVA). Design: Retrospective observational monocentric study. Participants: Eighty-three eyes affected by idiopathic ERMs, categorized into low (≤70 letters) and high (70 letters) BCVA groups. Methods: crop of structural and vascular en-face OCTA scans of superficial and deep retina slab, and choriocapillaris of each eye was selected. PyRadiomics was used to extract 86 features belonging to 2 different families: intensity-based statistical features describing the gray-level distribution, and textural features capturing the spatial arrangement of pixels. By employing a greedy strategy, 4 radiomic features were selected to build the final logistic regression model. The ability of the model to discriminate between low and high baseline BCVA was quantified in terms of area under the receiver operating characteristics curve (AUC). Main Outcome Measures: The 4 selected informative radiomic features were as follows: the difference average (glcm_DifferenceAverage), quantifying the average difference in gray-level between neighboring pixels; the informational measure of correlation (glcm_Imc1), giving information about the spatial correlation of pixel intensities inside the image; the long run low gray-level emphasis (glrlm_LongRunLowGrayLevelEmphasis), highlighting long segments of low gray-level values within the image; and the large area emphasis (glszm_LargeAreaEmphasis), which quantifies the tendency for larger zones of uniform intensity to occur. Results: = 0.047). Overall, these radiomic features predicted BCVA with an AUC (95% confidence interval) of 0.74 (0.63-0.85) and sensitivity/specificity of 0.67/0.75. During the cross-validation, the metrics remained stable. Conclusions: Radiomics features of the choriocapillaris in idiopathic ERMs showed a correlation with BCVA, with lower structural complexity and higher homogeneity, together with the presence of homogeneous areas with low-intensity pixel values, reflecting flow voids due to reduced microvascular perfusion, and were correlated with lower visual acuity. Financial Disclosures: The author(s) have no proprietary or commercial interest in any materials discussed in this article.
Retinal Dystrophies Associated with Mutations in the RP1 Gene: Genotype–Phenotype Correlations Vito Spagnuolo, Marco Piergentili, Ilaria Passerini, Vittoria Murro, Dario Pasquale Mucciolo, Dario Giorgio, Martina Maccari, Elisabetta Pelo, Ilaria Biagini, Fabrizio Giansanti, Gianni Virgili, Andrea Sodi Current Issues in Molecular Biology, 2025 Background: We evaluated the genetic and phenotypic features of a cohort of 10 Italian patients affected by Retinitis Pigmentosa (RP) associated with RP1 sequence variants. Methods: A retrospective, cross-sectional genotype–phenotype correlation study was conducted on a cohort of ten Italian patients (four males and six females) seen at Careggi University Hospital between 2012 and 2024, all affected by RP carrying pathogenic variants in the RP1 gene. A comprehensive ophthalmic assessment and pedigree analysis were performed, focusing on the onset of disease symptoms, the patient’s age at first diagnosis, follow-up duration, and the presence of comorbidities. Results: Our cohort included ten Italian patients with a mean age of 59 (range of 32–79 years). The median age when symptoms first presented was 43 years (range of 2–74), with a mean follow-up period of 9.3 ± 2.6 years. The main symptoms at presentation were hemeralopia and visual field constriction. Fundus examination revealed a classic RP phenotype. Fundus autofluorescence (FAF), optical coherence tomography (OCT), Electroretinogram (ERG), and visual field testing confirmed the typical features of classic retinitis pigmentosa in most cases. Conclusions: This single-center cohort of Italian patients provides insights into the clinical and genetic characteristics of RP1-associated RP. By comprehensively identifying genetic variations and their associated clinical manifestations, therapeutic interventions targeting specific genetic abnormalities can be better tailored. This approach holds promise for improving the prognosis and quality of life for individuals with RP1-associated RP.
OCT Angiography of Type 1 Macular Neovascularization in AMD: A Morphometric Evaluation Maria Cristina Savastano, Claudia Fossataro, Matteo Mario Carlà, Valentina Cestrone, Ilaria Biagini, Clara Rizzo, Raphael Kilian, Sandrine A. Zweifel, Daniel R. Muth, Francesco Faraldi, Stanislao Rizzo, David Sarraf Translational Vision Science and Technology, 2025 Purpose To determine biomarkers of macular neovascularization (MNV) in neovascular age-related macular degeneration through the application of an automatic algorithm based optical coherence tomography angiography (OCTA) analysis. Methods In this retrospective, observational, single-center, cross-sectional study, patients with a diagnosis of age-related macular degeneration complicated by type 1 MNV were included. MNV was detected with OCTA and scans were analyzed with a qualitative and quantitative open-source image processing package. For each analyzed image, we automatically acquired the following data: Total MNV area, vessel area, vessel density (VD), total number of branches, total number of vascular junctions, mean vessel length, mean vessel diameter, fractal dimension (FD), junction density, and vessel tortuosity. Results The following morphological parameters revealed a significant negative correlation with best-corrected visual acuity: MNV area – Spearman ρ = −0.309 (P = 0.002); vessel area – Spearman ρ = −0.315 (P = 0.002); total number of vascular junctions – Spearman ρ = −0.285 (P = 0.005), and VL – Spearman ρ = −0.304 (P = 0.003). Immature MNV lesions were significantly associated with better vessel area than mature and hypermature lesions. Conclusions Several automated MNV-associated morphological parameters can correlate with the best-corrected visual acuity. Further studies are warranted to determine if these OCTA biomarkers can be applied to guide anti-vascular endothelial growth factor therapy and predict response to treatment. Translational Relevance The analysis of MNV biomarkers may have prognostic value in terms of visual function.
OCT analysis of preoperative foveal microstructure in recent-onset macula-off rhegmatogenous retinal detachment: visual acuity prognostic factors Maria Cristina Savastano, Matteo Mario Carlà, Federico Giannuzzi, Claudia Fossataro, Valentina Cestrone, Francesco Boselli, Ilaria Biagini, Flavia Beccia, Quatrale Raffaele, Gianni Gravina, Clara Rizzo, Alfonso Savastano, Stanislao Rizzo British Journal of Ophthalmology, 2024 BackgroundTo evaluate, in patients undergoing macula-off rhegmatogenous retinal detachment surgery (RRD), the correlation between preoperative optical coherence tomography (OCT) morphological features and postoperative visual acuity.MethodsRetrospective interventional non-randomised clinical trial on 89 eyes of 89 patients undergoing pars plana vitrectomy for macula-off primary RRD at Policlinico Universitario Agostino Gemelli from 2020 to 2023. Preoperative 6×6 mm OCT B scans with Nidek Mirante (Nidek, Gamagori, Japan) were performed, collecting the following features: foveal involvement (fovea-on vs fovea-off), subretinal hyper-reflective points (HRPs), outer retinal corrugations (ORCs) and intraretinal cystic spaces (ICS) in the outer nuclear layer. The patients were followed in a 6-month follow-up to evaluate best-corrected visual acuity (BCVA) outcomes.ResultsPreoperative mean BCVA was 0.15±0.22 and improved to 0.29±0.3 decimals at 6 months (p<0.001). The presence of subretinal HRPs showed a significant negative impact on BCVA improvement in the univariate regression analysis (r=−0.264, p=0.024), as well as the presence of foveal detachment (r=−0.355, p=0.012). The other OCT features did not show a significant correlation with BCVA improvement: ORCs (r=0.072, p=0.257) and ICS (r=−0.020, p=0.734). In the multivariate regression analysis, the negative impact of foveal detachment was confirmed (r=−0.199, p=0.05) while the statistical significance of subretinal HRPs was lost (r=−0.135, p=0.105).ConclusionsThe negative impact of foveal involvement in a macula-off RRD was confirmed. Moreover, the presence of subretinal HRPs, as a possible indirect marker of inflammatory response extent, may act as a negative predictor for postoperative visual recover.Trial registration numberNCT05747144.
Optical Coherence Tomography Advanced Parameters in Patients With Multiple Sclerosis: Ophthalmological and Neurological Assessments MARIA CRISTINA SAVASTANO, VIVIANA NOCITI, FEDERICO GIANNUZZI, VALENTINA CESTRONE, MATTEO MARIO CARLÀ, CLAUDIA FOSSATARO, ILARIA BIAGINI, CLARA RIZZO, RAPHAEL KILIAN, MARCO BISURGI, PAOLO CALABRESI, MASSIMILIANO MIRABELLA, STANISLAO RIZZO American Journal of Ophthalmology, 2024 PURPOSE: To evaluate ophthalmological, neurological, radiological, and laboratory data in patients with multiple sclerosis (MS) and to identify new ophthalmological factors that could be helpful as biomarkers of the disease, potentially leading to an earlier prediction of disease course and disability progression. DESIGN: Retrospective, cross-sectional-study. METHODS: Best-corrected visual acuity (BCVA), ophthalmological biomicroscopy of the anterior segment and fundus, structural optical coherence tomography (OCT) with retinal nerve fiber layer (RNFL) and ganglion cell complex (GCC), and OCT angiography (OCTA) with vascular density (VD) were performed. The following clinical and neuro-radiological features were assessed: MS phenotype, disease duration, clinical severity, type of treatment, and T2-weighted lesion and T1-weighted Gd+ enhancing lesion number on the brain and spinal cord MRI. RESULTS: One hundred and six patients (212 eyes) were analyzed. Sixty-six of them (62.2%) had MS and 40 (37.8%) were matched healthy controls (HCs). patients with MS showed lower RNFL, GCC, and VD in the radial peripapillary capillary plexus than controls in both eyes (P < .05). By Performing a logistic regression with a distinct MS outcome for both eyes, we were able to demonstrate that the value that was most predictive of MS was the average GCC thickness (P = .009). Regression analysis demonstrated that patients with a higher T2-weighted lesions showed a lower RNFL thickness value and reduced GCC and VD values than those with a low lesion load (P < .01 and P < .05, respectively). Similarly, relapsing MS patients showed lower RNFL values (P < .05). CONCLUSIONS: Several OCT and OCTA-optic nerve parameters could be useful prognostic biomarkers for the MS disease course in clinical practice. However, it is necessary to do additional research with larger sample sizes in order to validate these findings.
Utility values and electronic device use in low-vision people attending rehabilitation services: Data from a nation-wide registry in Italy Gianni Virgili, Eliana Costanzo, Ilaria Biagini, Mariacristina Parravano, Alessia Di Simone, Filippo Amore, Mauro Tettamanti, Simona Di Pietro, Giovanni L. Ciaffoni, Giovanni Sato, Giovanni Giacomelli, Federico Bartolomei Plos One, 2024 Purpose To estimate utility values associated with visual loss using EuroQol (EQ-5D) questionnaire, the impact of low-vision (LV) device use on utilities and the contribution of Instrumental Activities of Daily Living (IADL) score in patients attending vision rehabilitation (VR) services enrolled in the Italian Device & Aids Register (D.A.Re). Methods This is a multicenter, prospective, cross-sectional study. D.A.Re. collects general and clinical information, vision-specific variables, use of electronic devices and quality of life questionnaires. Results A total of 442 patients (75.0±16.6 years, 275 female) were included, 88 (19.9%) used specialised electronic LV devices, and 116 (26.2%) used smartphones and tablets. Users of smartphones and tablets were younger than non-users (67.5 vs. 77.6 years, p<0.001), but overall, their age ranged between 20 and 93. Stronger associations were found between vision-specific variables and IADL score compared to EQ-5D score. In multivariable age-adjusted models, the utility value of using smartphones and tablets on EQ-5D score was 0.12 (p<0.01), slightly larger than that of 1.0 logMAR difference (-0.09, p<0.01) or visual field damage within 10° of fixation (-0.10, p<0.01). Use of portable low-vision electronic devices and being employed or student (vs. retired) was also associated with better utility values (0.12 and 0.15, respectively, p<0.05). Conclusions Visual loss is associated with loss of utilities in Italian patients attending VR services, whereas special-purpose electronic aids, and smartphone and tablet use are associated with better utility values. We found that IADL may be more sensitive to visual loss than EQ-5D and could be a valid health-related quality of life outcome in trials on VR.
Retinal Pigment Epithelium and Outer Retinal Atrophy (RORA) in Retinitis Pigmentosa: Functional, Structural, and Genetic Evaluation Maria Cristina Savastano, Giorgio Placidi, Claudia Fossataro, Federico Giannuzzi, Nicola Claudio D'Onofrio, Lorenzo Hu, Valentina Cestrone, Elena D'Agostino, Ilaria Biagini, Ludovica Paris, Giorgia Coppa, Clara Rizzo, Raphael Kilian, Pietro Chiurazzi, Matteo Bertelli, Paolo Enrico Maltese, Benedetto Falsini, Stanislao Rizzo Translational Vision Science and Technology, 2024 Purpose To examine whether the extension of retinal pigment epithelium (RPE) and outer retinal atrophy (RORA) and various other morphofunctional parameters correlate with the genetic assessment and severity of retinitis pigmentosa (RP). Methods Thirty-eight patients (76 eyes) with RP were prospectively enrolled and underwent full ophthalmic examination, including visual field testing, full-field electroretinography (ERG), and optical coherence tomography angiography. The severity of the disease was calculated using the RP stage scoring system, and the area of RORA was assessed using the automatically calculated area of sub-RPE illumination. Blood or saliva samples were collected from subjects, and DNA extraction was performed to evaluate genetic mutations and nucleotide and amino acid variations. Results There was a statistically significant correlation between the extent of RORA and patient age, best-corrected visual acuity, ellipsoid zone extension, and disease severity in both eyes (each, P < 0.05). In contrast, RORA did not correlate with either the visual field or the ERG amplitude. Cumulative score and grade severity were both significantly correlated with superficial and deep capillary plexus density (both, P < 0.001) in both eyes. Evaluating RORA, we found genes with an overall less severe phenotype, such as EYS, PCDH15, and PRPF31, and those with a worse phenotype, such as RPGR. Conclusions The correlation of RORA with structural, functional, and genetic assessment in RP disease leads us to consider RORA as a potential biomarker for prediction of disease stage. Multicenter studies are needed to confirm our findings. Translational Relevance The morphofunctional and genetic correlations suggest a role for RORA in RP diagnosis and follow-up.
Chorioretinal biomarkers in hypothalamic amenorrhea Maria Cristina Savastano, Claudia Fossataro, Matteo Mario Carlà, Valentina Cestrone, Ilaria Biagini, Leonardo Sammarco, Federico Giannuzzi, Romina Fasciani, Rosanna Apa, Antonio Lanzone, Alice Diterlizzi, Martina Policriti, Enrico Di Stasio, Raphael Killian, Clara Rizzo, Stanislao Rizzo Graefe S Archive for Clinical and Experimental Ophthalmology, 2024
The Impact of Hyperopia on Academic Performance Among Children: A Systematic Review Sonia Mavi, Ving Fai Chan, Gianni Virgili, Ilaria Biagini, Nathan Congdon, Prabhath Piyasena, Ai Chee Yong, Elise B. Ciner, Marjean Taylor Kulp, T. Rowan Candy, Megan Collins, Andrew Bastawrous, Priya Morjaria, Elanor Watts, Lynett Erita Masiwa, Christopher Kumora, Bruce Moore, Julie-Anne Little Asia Pacific Journal of Ophthalmology, 2022
