Intrauterine growth restriction (IUGR) is a critical challenge in perinatal medicine and is associated with significant morbidity and mortality. This review explores the intricate involvement of early developmental senescence in IUGR. We highlight the dual role of cellular senescence in both normal development and pathological conditions, emphasizing the need for further research to elucidate these mechanisms and develop targeted interventions. We discuss how oxidative stress and mitochondrial dysfunction affect senescence determinants. We present emerging therapeutic strategies aimed at targeting senescence and inflammation in the placenta. We also introduce Rytvela, an interleukin-1 (IL-1) receptor modulator developed in our laboratory, which selectively attenuates pro-inflammatory signaling while preserving essential immune responses, which in turn mitigate senescence. By addressing senescence-related dysfunctions, such interventions may improve placental performance and fetal outcomes, opening up new directions for the clinical management of IUGR.

Purpose: To analyze the anatomic and functional outcomes of lamellar macular hole (LMH) and epiretinal membrane foveoschisis (ERMF) surgery. Patients and Methods: This is a retrospective interventional cohort study of ninety patients with unilateral idiopathic LMH or ERMF who underwent pars plana vitrectomy (PPV) with membrane peeling between 2014 and 2021. We evaluated the anatomic and functional success of PPV with membrane peeling for treating LMH and ERMF, compared surgical outcomes between the two entities, and identified predictive factors for anatomical and functional success. Primary outcomes included final postoperative best-corrected visual acuity (BCVA) and LMH or ERMF closure. Variables associated with final BCVA were assessed using a multiple linear regression model. Results: 51 subjects presented with ERMF, while 39 presented with LMH. LMH or ERMF closure occurred in 80 cases. LMH cases had a lower rate of closure (LMH closure rate: 76.9%, vs ERMF closure rate: 98.0%, p=0.002) and were more at risk of developing a postoperative macular hole (p=0.008). A significant difference was observed between median [Q1, Q3] preoperative BCVA (0.42 [0.26, 0.61] logMAR) and final BCVA (0.31 [0.14, 0.48] logMAR, p=0.024). BCVA varied from 0.52 [0.40, 0.74] logMAR preoperatively to 0.36 [0.30, 0.66] logMAR postoperatively in the LMH subgroup (p=0.060), and from 0.32 [0.20, 0.54] logMAR preoperatively to 0.22 [0.10, 0.40] logMAR postoperatively in the ERMF subgroup (p=0.146). LMH without epiretinal proliferation (β=0.194, p=0.040) was associated with worse final BCVA in multivariate analysis. Conclusion: Results support the effectiveness of PPV as a treatment for LMH. LMHs had worse anatomic outcomes than ERMFs.

Background: Choroidal involution is a common feature of age-related ischemic retinopathies such as age-related macular degeneration (AMD). It is now well recognized that endothelial progenitor cells (EPCs) are essential to endothelial repair processes and in maintaining vascular integrity. However, the contribution of EPCs and the role of senescence in age-related choroidal vascular degeneration remain to be investigated. In this study, we compared the senescent phenotype of EPCs in the choroid and performed whole-genome profiling of EPCs derived from young versus old rats. Methods and Results: We isolated and compared the retinas of young (6-weeks-old) and old (16–18-month-old) rats. The thickness of the choroid and outer nuclear layer (ONL), along with local quantification of CD34+ EPCs, was performed. Compared to young rats, older rats displayed a significant reduction in choroidal and ONL thickness associated with markedly fewer choroid-localized EPCs; this was attested by lower expression of several EPC markers (CXCR4, CD34, CD117, CD133, and KLF-2). Choroid and choroid-localized EPCs displayed abundant senescence as revealed by increased β-gal and P53 expression and decreased Lamin-B1 (immunostaining and RT-qPCR). Concordantly, choroidal cells and EPCs isolated from older rats were unable to form vascular networks ex vivo. To better understand the potential mechanisms associated with the dysfunctional EPCs linked to age-related choroidal involution, we performed whole-genome profiling (mRNA and miRNA) of EPCs derived from old and young rats using next-generation sequencing (NGS); 802 genes were significantly modulated in old vs. young EPCs, corresponding to ~2% of total genes expressed. Using a bioinformatic algorithm, the KEGG pathways suggested that these genes participate in the modulation of several key signaling processes including inflammation, G protein-coupled receptors, and hematopoietic cell lineages. Moreover, we identified 13 miRNAs involved in the regulation of immune system processes, cell cycle arrest and senescence, which are significantly modulated in EPCs from old rats compared to young ones. Conclusions: Our results suggest that age-related choroidal involution is associated with fewer EPCs, albeit displaying a senescence-like phenotype. One would be tempted to propose that biological modification of native EPCs (such as with senolytic agents) could potentially provide a new strategy to preserve the vascular integrity of the aged choroid, and evade progression to degenerative maculopathies.

Purpose: To analyze the anatomic and functional outcomes of lamellar macular hole (LMH) surgery. Patients and methods: This is a retrospective interventional cohort study of ninety patients with unilateral idiopathic LMH who underwent pars plana vitrectomy (PPV) with membrane peeling for LMH between 2014 and 2021. We evaluated the anatomic and functional success of PPV with membrane peeling for treating LMH, compared surgical outcomes between the two LMH subtypes (“true” LMH and epiretinal foveoschisis (ERMF)), and identified predictive factors for anatomical and functional success. Primary outcomes included final postoperative best-corrected visual acuity (BCVA) and LMH closure. Variables associated with final BCVA were assessed using a multiple linear regression model. Results: 51 subjects presented with ERMF, while 39 presented with “true” LMH. LMH closure occurred in 80 cases. “True” LMH cases had a lower rate of closure (“true” LMH closure rate: 76.9%, vs. ERMF closure rate: 94.2%, p=0.005) and were more at risk of developing a postoperative macular hole (p=0.008). A significant difference was observed between median [Q1, Q3] preoperative BCVA (0.42 [0.26, 0.61]) and final BCVA (0.31 [0.14, 0.48], p=0.024). “True” LMH without epiretinal proliferation (β=0.194, p=0.040) was associated with worse final BCVA in multivariate analysis. Conclusion: Results support the effectiveness of PPV as a treatment for LMH. “True” LMHs had worse anatomic outcomes than ERMFs.

Purpose: To assess the anatomic and functional outcomes in primary uncomplicated rhegmatogenous retinal detachment (RRD) compared to RRD associated with macular hole (MH). Methods: This retrospective cohort study included 1303 eyes with RRD and 30 eyes with MH-RRD operated on between 2014 and 2018 at a single tertiary center. Main outcomes were single-surgery anatomic success (SSAS), MH closure and final pinhole visual acuity (PHVA). Results: Of the 1333 patients, 867 (65%) were male, and median [Q1, Q3] age was 63 [57, 70]. Most of these were macula-off detachments (n=764, 57%) with a higher proportion in MH-RRD (n=26, 87%) than primary RRD (n=738, 57%) (p=0.004). Baseline VA was lower in MH-RRD (p<0.001). Postoperative PHVA at three months was 0.30 [0.18, 0.54] in primary RRD vs. 0.85 [0.60, 1.30] in MH-RRD (p<0.001); final PHVA was 0.18 [0.10, 0.40] vs. 0.68 [0.40, 0.90] (p<0.001) respectively. Primary MH closure was achieved in 27 (90%) MH-RRD cases; at final follow-up, all 30 MH-RRDs had attached retinas with one persistent MH. MH presence was not significantly associated with SSAS (p=0.391), while increasing age was a negative predictor of SSAS (p=0.008). Male sex (p<0.001), SF ₆ tamponade (p<0.001), SSAS (p<0.001), and longer follow-up (p<0.001) were positive predictors of final PHVA. Conclusion: SSAS did not significantly differ between the two groups though the small MH-RRD sample may have contributed to this. Functional outcomes were poorer in MH-RRD, likely due to more macula-off RRD, more retinal breaks, occasional MH closure failure and residual sequelae related to the MH.