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Maria Vadalà,1,2 Valentina Sunseri Trapani,1 Giulia Guarrasi,1 Nicasio Ventura,1 Massimo Castellucci,1 Salvatore Cillino1 1Biomedicine, Neuroscience and Advanced Diagnostic Department, University of Palermo, Palermo, Italy; 2IEMEST, Euro-Mediterranean Institute of Science and Technology, Palermo, ItalyCorrespondence: Maria VadalàBiomedicine, Neuroscience and Advanced Diagnostic (BIND) Department, Ophthalmology Institute, University of Palermo, Palermo 90127, ItalyTel +39 091 6553909Email maria.vadala@unipa.itPurpose: There has been an increasing clinical interest in specific retinal parameters as non-invasive biomarkers of retinal inflammation in diabetic macular edema (DME) that have been shown to have prognostic value, such as hyperreflective retinal fields (HRFs) and subfoveal neuroretinal detachment (SND).Methods: We conducted a prospective, non-comparative study of treatment-naïve patients with DME to evaluate the efficacy of a Pro Re Nata (PRN) regimen of intravitreal dexamethasone implant 0.7 mg (DexI, Ozurdex™). After administration, patients underwent subsequent injections according to PRN criteria in case of edema relapse, but not earlier than 4 months after the previous treatment. Patients were evaluated at baseline, within 15 days of injection, and every month thereafter. During all visits, best-corrected visual acuity (BCVA) was recorded; central retinal thickness (CRT), type of edema, presence of SND, and presence and number of HRFs were evaluated using swept-source optical coherence tomography (SS-OCT) 3D. Treatment outcome was defined as changes in BCVA, CRT, SND and HRFs at 12 (T12) and 24 (T24) months compared with baseline (T0).Results: The study enrolled 24 eyes of 18 patients. The mean duration of follow-up was 18± 6.6 months; for all eyes, T12 data were available, while follow-up reached T24 for 12 eyes. BCVA improved significantly and CRT decreased significantly during treatment; the edema was no longer detectable in 13/24 eyes at T12 and 8/12 eyes at T24. No patient presented SND at T12 and T24, and the mean number of HRFs decreased significantly during treatment. Results with CRT and HRFs correlated with BCVA at 12 and 24 months. No significant adverse events were observed.Conclusion: In patients with DME, the intravitreal dexamethasone implant was effective and safe in improving both functional and tomographic parameters. This result is consistent with improvement in biomarkers of inflammation.Keywords: dexamethasone implant, diabetic macular edema, intravitreal implants, Ozurdex, real-world, inflammation

OBJECTIVE: In Europe, a great number of investigations and studies followed up to develop safer techniques performed by physicians only. Successful dedicated medical protocols included the implant of single fibers with ex- tractable root. The aim of our study was to evaluate the efficacy of biocompatible artificial hair implants in patients with androgenetic alopecia. PATIENTS AND METHODS: 682 patients (488 males and 184 females) aged between 25 and 70 years old, with diagnosed AGA, requiring no invasive nor surgical hair restoration, with problems of baldness and refusing surgical options appealed to the Second Opinion Medical Consulting (Modena, Italy), and were included in the present protocol. Before the treatment, all patients underwent a test implant to rule out hypersensitivity by implanting 100 fibers on a selected skin spot. If no reaction was detected, five weeks later 5001,200 fibers were further implanted per session at a minimum interval of 5 weeks until the required aesthetic result was achieved. RESULTS: The average number of sessions for each patient was 5. The average number of implanted fibers was 2,100 (ranging from 800 to 12,000). The treated scalp area returned to normal appearance and tenderness in 3 days. CONCLUSIONS: The socio-phycological benefit and the life quality improvement of our patients have been the focus of the study. On our side, the accurate selection, small hair units for each implant session, customized dermatological consultation and the use of highly biocompatible fibers have been the proper strategy to achieve the goal. [ABSTRACT FROM AUTHOR]

Objective. Several studies support the active role of Carcinine, an L-carnosine metabolite, in insulin resistance and dyslipidaemia, to modulate the insulinemic/glycaemic profile and fat metabolism. Materials and methods. 100 (50 women and 50 men) volunteers, aged between 40 and 85 years with a body mass index (BMI) between 25 and 34,9 kg/m2, spontaneously addressed to our "Second Opinion Medical Consulting Network" (Modena, Italy) between 2019 and 2020, were included in this anecdotal, observational, retrospective trial. The aim of the study was to find an adequate possibly natural treatment for unbalanced insulin resistance pattern notwithstanding ongoing administration of statins, and hypoglycaemic chemical agents in healthy overweight/obese subjected. All the patients were divided in two groups: 1) the first group included 50 patients that were administered with a specific galenic nutraceutical product containing 20 mg of carcinine, and 2) the second group included 50 patients, which were administered with lithothamnion calcareum alga (190 mg) and three-time day for two months. The waist circumference, glycaemia, homeostasis model assessment (HOMA-IR), glycated haemoglobin, total cholesterol values were detected at time 0, and time 1 (after treatment). At the same time, the pre versus post treatment, Advanced Glycation End products (AGEs), that play an important role in the development of diabetic vascular complications, were instrumentally measured at time 1 and 2. Results. After 60 mg/day of Carcinina treatment, glycaemia (p=0,001), glycated haemoglobin (p<0,001), total cholesterol (p<0,003), serum insulin (p<0.05) were significantly reduced, respect to placebo period. Abdominal circumference (p<0.2), HOMA index (p<0.03) progressively were reduced as well. No cardiovascular risk and untoward effects were observed at the prescribed dosages. The AGE reader test showed a statistically meaningful reduced risk due to reduced amount. Conclusions. Carcinine, at the daily dose of 60 mg/day, was able to modify, safely, the AGEs that induced cardiovascular risk, the waist circumference, and some glycolipid-metabolic parameters in overweight/obese patients with altered blood glucose pattern, improving significantly the impending metabolic syndrome. [ABSTRACT FROM AUTHOR]

Objectives. Ten million new cases of dementia are recorded annually worldwide, with agitation and idiopathic weight loss being the most common symptoms. Several pharmacological therapies have emerged in recent years, but the clinical use of cannabis extracts in older patients with AD is constantly growing. This retrospective, analytical, observational, spontaneous trial aimed to enhance the clinical action of THC: CBD cannabis extract administration in AD patients with severe symptoms such as agitation, weight loss, cognitive impairment, and sleep disturbance. Methods. Thirty patients (9 men and 21 women) diagnosed with mild, moderate, or severe AD, aged 65-90 years, appealing to our Second Opinion Medical Consultation (Modena, Italy), were enrolled and required to use oil-diluted cannabis extract, Bedrocan® (22% THC, 0.5% CBD, Olive Oil 50 ml), twice a day for 12 weeks. The efficacy of cannabinoid therapy was evaluated at baseline and 12 weeks after therapy, employing three self-administered questionnaires completed by the parents of the enrolled patients: NPI-Q, CMAI, and MMSE. Key findings. The NPI-Q demonstrated a reduction (p<0.0001) in agitation, apathy, irritability, sleep disturbances, and eating disturbances, consequently improving caregiver distress. Levels of physically and verbally aggressive behaviours, measured using the CMAI questionnaire, were lower (p<0.0001) in all patients. The MMSSE questionnaire confirmed a significant decrease (p<0.0001) in cognitive impairment in 45% of the patients. Conclusion. Our anecdotical, spontaneous, and observational study demonstrated the efficacy and safety of oil-diluted cannabis extract in patients with AD. The limitations of our study are: 1) small patient cohort, 2) absence of control group, 3) self-administered questionnaires that are the most practical but not objective instruments to assess the neurologic functions of AD patients. [ABSTRACT FROM AUTHOR]

Objectives. Our main aim was to investigate the short-term therapeutic effects, safety/tolerability of natural compound, composed of melatonin (1,5 mg) and cannabis extracts (2.5 mg CBD) in patients with sleep disorders Methods. In this spontaneous, anecdotal, retrospective, "compassionate-use," observational, open-label study, 20 patients (age 43-96 years) were appealed to our "Second Opinion Medical Consulting Network" (Modena, Italy), because of a variable pattern of sleep disorders and anxiety and were instructed to take sublingually the compound (20 drops) overnight for 3 months of treatment. Tolerability and adverse effects were assessed monthly during the treatment period through direct contact (email or telephone) or visit if required. Results. PSQUI and HAM-A scores evidenced reduction in mood alterations, including anxiety, panic, paranoia, depression (P < 0.03), in pain (P < 0.02) and good general health perceptions. Conclusions. These data suggest that the formula CBD-melatonin could be competitive with the classic hypnotic synthetic drugs, the antioxidant activity of melatonin offers a further benefit to the brain network, restoring the biological clock functions, while CBD, reducing chronic pain perception, helps to complete the neuromuscular relaxation and to relieve anxiety fulfilling a very balanced sensation of wellbeing during the sleep. [ABSTRACT FROM AUTHOR]

Multiple chemical sensitivity (MCS) is increasingly widespread disease, characterized by non-specific and recurring symptoms from various organs associated with exposure to common chemicals, even if inhaled at low concentrations, usually harmless for normal people. MCS is not yet well recognized from common point of view and for this reason affected patients risk marginalization and their symptoms are often trivialized. It is actually a devastating chronic disease that affects not only the patients in the daily routine but partly conditions their survival. Despite more than 50 years of research, the action mechanisms of MCS is still undefined. In this study we examine the theories about the etiopathogenesis of multiple chemical sensitivity that include genetic susceptibility factors, immunological factors, neurological factors and psychiatric factors. Since no specific diagnostic markers are currently available for the MCS, the diagnosis can only be supposed on the basis symptomatic criteria and patient's medical history. However new biochemical markers and diagnostic imaging techniques have emerged, useful to postulate at least the clinical-diagnostic hypothesis of MCS and in this paper we discuss a list of biomarkers studied for the diagnosis of MCS, based on the available scientific literature. At last but not least, we propose four-levels MCS tests that could help the clinician in the diagnosis of the pathology both through the use of quantifiable serological parameters, both through diagnostic tools, genetic testing and through clinical observation of symptoms. [ABSTRACT FROM AUTHOR]

Objective. To investigate the therapeutic effect of CBD-ointment administered on severe skin chronic diseases and/or on their outcome scars. Methods. A spontaneous, anecdotal, retrospective study of 20 patients with two most frequent skin disorders: psoriasis (n: 5 patients), atopic dermatitis (n: 5) and resulting outcome scars (n: 10). The subjects were instructed to administer topical CBD-enriched ointment to lesioned skin areas twice daily for three months treatment. Results. Based on skin evaluations (hydration, TEWL, elasticity), clinical questionnaires (SCORAD, ADI, PASI), and supported by photographic data and investigators' clinical assessment, the results showed that topical treatment with CBD-enriched ointment significantly improved the skin parameters, the symptoms and also the PASI index score. No irritant or allergic reactions were documented during the period treatment. Conclusions. The topical administration of CBD ointment, without any THC, is a safe and effective non-invasive alternative for improve the quality of life in patients with some skin disorders, especially on inflammatory background. [ABSTRACT FROM AUTHOR]

Chronic kidney disease (CKD) is a progressive condition that affects more than 10% of the population worldwide, accounting for more than 843 million (M) individuals. The prevalence of CKD (844 M patients) is higher than that of diabetes mellitus (422 M patients), cancer (42 M patients), and HIV (37 M patients), but people are often less aware of it. Global expert groups predict reductions in the nephrology workforce in the next decade, with a declining interest in nephrology careers. Over time, KDIGO guidelines have also focused on topics related to the prevention or management of CKD patients in real-life settings. On these premises, a new educational program with international experts in the field of nephrology took place from November 2022 until March 2023 in Milan, Italy. This multinational masterclass provided an educational platform providing unbiased education on diagnosis and treatment by sharing the most recent research data on CKD and comorbidities, therefore creating a snowball effect to increase the implementation of best practices worldwide, using examples from 'real-life' patient outcomes. This paper provides an overview of the International Nephrology Masterclass (INM) concept, summarizing the key lectures and discussions, and giving an outline of future key developments.

Background/Objectives: The complications of hypertension depend not only on the mean blood pressure (BP) but also on its variability (BPV). Recent studies suggest that the choroid may serve as an indicator of systemic vascular damage. These studies have been made possible by the increased availability of optical coherence tomography (OCT). The aim of our study was to analyze the relationship between short-term BP variability (STBPV) and choroid-retinal thickness in hypertensive patients. Methods: A total of 98 patients with a mean age of 49 ± 12 years were enrolled in the study. All participants underwent 24 h blood pressure (BP) monitoring to measure 24 h mean systolic (SBP) and diastolic blood pressure (DBP), along with their respective standard deviations (SD), the weighted SD of 24 h SBP and DBP, and the average real variability (ARV) of 24 h SBP and DBP. The choroid-retinal region was assessed using Swept-Source OCT, with choroidal thickness (ChT) and retinal thickness divided into three concentric rings, and their mean choroidal thickness (ChT-or) was calculated. Results: The choroidal thickness of the concentric rings was found to be inversely correlated with all ARV values of the monitored blood pressure means. In particular, a correlation was observed between the ARV of daytime DBP and ChT-or. This correlation remained statistically significant (β = -0.34; p = 0.02) even after adjustment for various confounding factors. The ARV of daytime DBP was the only STBPV index to maintain a significant association, in the multivariate analysis, with the central ring mean thickness (β = -0.314; p = 0.001) and the inner choroidal ring mean thickness (β = -0.262; p = 0.003). Conclusions: Our study demonstrated an independent negative association between short-term BP variability (STBPV), when expressed as ARV of daytime DBP, and choroidal thickness. This finding confirms the value of choroidal thickness as a marker of cardiovascular risk.

Aims: Maternally inherited diabetes and deafness (MIDD) is a complex disorder characterized by multiorgan clinical manifestations, including diabetes, hearing loss, and ophthalmic complications. This pilot study aimed to elucidate the intricate interplay between nuclear and mitochondrial genetics, epigenetic modifications, and their potential implications in the pathogenesis of MIDD., Main Methods: A comprehensive genomic approach was employed to analyze a Sicilian family affected by clinically characterized MIDD, negative to the only known causative m.3243 A > G variant, integrating whole-exome sequencing and whole-genome bisulfite sequencing of both nuclear and mitochondrial analyses., Key Findings: Rare and deleterious variants were identified across multiple nuclear genes involved in retinal homeostasis, mitochondrial function, and epigenetic regulation, while complementary mitochondrial DNA analysis revealed a rich tapestry of genetic diversity across genes encoding components of the electron transport chain and ATP synthesis machinery. Epigenetic analyses uncovered significant differentially methylated regions across the genome and within the mitochondrial genome, suggesting a nuanced landscape of epigenetic modulation., Significance: The integration of genetic and epigenetic data highlighted the potential crosstalk between nuclear and mitochondrial regulation, with specific mtDNA variants influencing methylation patterns and potentially impacting the expression and regulation of mitochondrial genes. This pilot study provides valuable insights into the complex molecular mechanisms underlying MIDD, emphasizing the interplay between nucleus and mitochondrion, tracing the way for future research into targeted therapeutic interventions and personalized approaches for disease management., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Palliative radiotherapy (RT) effectively relieves pain in patients with bone metastases (BMs). Furthermore, several clinical trials, in most cases conducted in high-income countries (HICs), proved that single-fraction RT is equally effective compared to multi-fractionated RT. However, the evidence is scarce regarding low/middle-income countries (LMICs), where the diagnosis of BMs could be later and RT techniques less advanced. Therefore, we conducted a systematic literature review to evaluate the efficacy of palliative RT of BMs in the LMIC setting. A literature search was performed independently by two authors on the PubMed, Cochrane and Scopus databases. Overall, 333 records were screened and after the selection process, 11 papers were included in the analysis. Complete pain response rates ranged from 11.5% to 37.1% (median: 22%) for single-fraction RT and from 0% to 35.1% (median: 19%) for multi-fractionated RT. Partial pain response rates ranged from 23.1% to 76.9% (median: 53.8%) for single fraction RT and from 23.8% to 84.6% (median: 65%) for multi-fractionated RT. Four randomized trials compared single-fraction RT with multiple-fraction RT and none of them showed significant differences in terms of pain relief. Our analysis showed that pain response rates after palliative RT recorded in LMIC are like those reported in studies performed in HIC. Even in this setting, RT in single fraction shows comparable pain response rates to multifractional RT., (© 2024 The Authors. Journal of Medical Imaging and Radiation Oncology published by John Wiley & Sons Australia, Ltd on behalf of Royal Australian and New Zealand College of Radiologists.)

Introduction: This study assessed the European School of Advanced Studies in Ophthalmology (ESASO) classification's prognostic value for diabetic macular edema (DME) in predicting intravitreal therapy outcomes., Methods: In this retrospective, multicenter study, patients aged > 50 years with type 1 or 2 diabetes and DME received intravitreal antivascular endothelial growth factor (anti-VEGF) agents (ranibizumab, bevacizumab, and aflibercept) or steroids (dexamethasone). The primary outcome was visual acuity (VA) change post-treatment, termed as functional response, measured 4-6 weeks post-third anti-VEGF or 12-16 weeks post-steroid injection, stratified by initial DME stage., Results: Of the 560 eyes studied (62% male, mean age 66.7 years), 31% were classified as stage 1 (early), 50% stage 2 (advanced), 17% stage 3 (severe), and 2% stage 4 (atrophic). Visual acuity (VA; decimal) improved by 0.12-0.15 decimals in stages 1-2 but only 0.03 decimal in stage 3 (all p < 0.0001) and 0.01 in stage 4 (p = 0.38). Even in eyes with low baseline VA ≤ 0.3, improvements were significant only in stages 1 and 2 (0.12 and 0.17 decimals, respectively). Central subfield thickness (CST) improvement was greatest in stage 3 (-229 µm, 37.6%, p < 0.0001), but uncorrelated with VA gains, unlike stages 1 and 2 (respectively: -142 µm, 27.4%; - 5 µm, 12%; both p < 0.0001). Stage 4 showed no significant CST change. Baseline disorganization of retinal inner layers and focal damage of the ellipsoid zone/external limiting membrane did not influence VA improvement in stages 1 and 2. Treatment patterns varied, with 61% receiving anti-VEGF and 39% dexamethasone, influenced by DME stage, with no significant differences between therapeutic agents., Conclusion: The ESASO classification, which views the retina as a neurovascular unit and integrates multiple biomarkers, surpasses single biomarkers in predicting visual outcomes. Significant functional improvement occurred only in stages 1 and 2, suggesting reversible damage, whereas stages 3 and 4 likely reflect irreversible damage., (© 2024. The Author(s).)

Locally advanced cervical cancer represents a significant treatment challenge. Body composition parameters such as body mass index, sarcopenia, and sarcopenic obesity, defined by sarcopenia and BMI ≥ 30 kg/m 2 , have been identified as potential prognostic factors, yet their overall impact remains underexplored. This study assessed the relationship between these anthropometric parameters alongside clinical prognostic factors on the prognosis of 173 cervical cancer patients. Survival outcomes in terms of local control (LC), distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS) were analyzed using Kaplan regression methods-Meier and Cox. Older age, lower hemoglobin levels, higher FIGO (International Federation of Gynecology and Obstetrics) stages, and lower total radiation doses were significantly associated with worse outcomes. Univariate analysis showed a significant correlation between BMI and the outcomes examined, revealing that normal-weight patients show higher survival rates, which was not confirmed by the multivariate analysis. Sarcopenia was not correlated with any of the outcomes considered, while sarcopenic obesity was identified as an independent negative predictor of DFS (HR: 5.289, 95% CI: 1.298-21.546, p = 0.020) and OS (HR: 2.645, 95% CI: 1.275-5.488, p = 0.009). This study highlights the potential of sarcopenic obesity as an independent predictor of clinical outcomes. These results support their inclusion in prognostic assessments and treatment planning for patients with advanced cervical cancer.

Background: The implantation of artificial hair is a successful standardized procedure to restore bald areas or scarred alopecic surfaces of the scalp in both sexes., Materials and Methods: Sebometric measurements were taken, pre, 1, 3, and 6 months postimplant in two symmetric frontotemporal areas of the scalp of seven volunteers to be implanted with 50 units of artificial hair. The artificial hair used in this study are Biofibre 4.0 produced by Medicap srl, Italy., Results: The dermaroller assisted procedure was performed only on one side, and the plain random implant contralaterally for comparison. A marked downregulation of the sebum concentration was observed in the dermaroller treated area 1, 3, and 6 months later in respect to the control side., Conclusion: The dermaroller assisted procedure is safe and effective in reducing the foreign body reaction by the sebaceous glands and the vascular axis injured by the implanting needle; a longer standing success of the implanted hair can thus be achieved reducing the burden of inflammatory reaction., (© 2023 The Authors. Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

In the management of symptomatic inoperable retroperitoneal sarcomas (RPS), palliative radiotherapy (RT) is a potential treatment option. However, the efficacy of low doses used in palliative RT is limited in these radioresistant tumors. Therefore, exploring dose escalation strategies targeting specific regions of the tumor may enhance the therapeutic effect of RT in relieving or preventing symptoms. In this case report, we present the case of an 87-year-old patient with rapidly growing undifferentiated liposarcoma in the retroperitoneum, where surgical and systemic therapies were ruled out due to age and comorbidities. RT was administered using volumetric modulated arc therapy, delivering 20 Gy in 4 fractions twice daily to the macroscopic tumor and 40 Gy in 4 fractions twice daily (simultaneous integrated boost) to the central part of the tumor (Gross Tumor Volume minus 2 cm). An 18F- FDG-PET-CT scan performed after RT demonstrated a complete metabolic response throughout the entire tumor mass. Although the patient eventually succumbed to metastatic spread to the bone, liver, and lung after 9 months, no local disease progression or pain/obstructive symptoms were observed. This case highlights the technical and clinical feasibility of delivering ablative doses of RT to the central region of the tumor and suggests the potential for achieving a complete metabolic response and durable tumor control., (© 2023 The Authors. Published by Elsevier Inc. on behalf of University of Washington.)

Locally advanced cervical cancer (LACC) is treated with concurrent chemoradiation (CRT). Predictive models could improve the outcome through treatment personalization. Several factors influence prognosis in LACC, but the role of systemic inflammation indices (IIs) is unclear. This study aims to assess the correlation between IIs and prognosis in a large patient cohort considering several clinical data. We retrospectively analyzed pretreatment IIs (NLR, PLR, MLR, SII, LLR, COP-NLR, APRI, ALRI, SIRI, and ANRI) in 173 LACC patients. Patient, tumor, and treatment characteristics were also considered. Univariate and multivariate Cox's regressions were conducted to assess associations between IIs and clinical factors with local control (LC), distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS). Univariate analysis showed significant correlations between age, HB levels, tumor stage, FIGO stage, and CRT dose with survival outcomes. Specific pretreatment IIs (NLR, PLR, APRI, ANRI, and COP-NLR) demonstrated associations only with LC. The multivariate analysis confirmed Hb levels, CRT dose, and age as significant predictors of OS, while no II was correlated with any clinical outcome. The study findings contradict some prior research on IIs in LACC, emphasizing the need for comprehensive assessments of potential confounding variables.

Purpose: To assess functional and anatomical outcomes of intravitreal anti-Vascular Endothelial Growth Factor (anti-VEGF) monotherapy versus combined with verteporfin Photodynamic Therapy (PDT) for Retinal Angiomatous Proliferation (RAP). Methods: Studies reporting outcomes of intravitreal anti-VEGF monotherapy and/or in combination with verteporfin PDT in RAP eyes with a follow-up ≥ 12 months were searched. The primary outcome was the mean change in best corrected visual acuity (BCVA) at 12 months. Mean change in central macular thickness (CMT) and mean number of injections were considered as secondary outcomes. The mean difference (MD) between pre- and post-treatment values was calculated along with 95% Confidence Interval (95% CI). Meta-regressions were performed to assess the influence of anti-VEGF number of injections on BCVA and CMT outcomes. Results: Thirty-four studies were included. A mean gain of 5.16 letters (95% CI = 3.30-7.01) and 10.38 letters (95% CI = 8.02-12.75) was shown in the anti-VEGF group and combined group, respectively (anti-VEGF group vs. combined group, p < 0.01). A mean CMT reduction of 132.45 µm (95% CI = from -154.99 to -109.90) and 213.93 µm (95% CI = from -280.04 to -147.83) was shown in the anti-VEGF group and combined group, respectively (anti-VEGF group vs. combined group, p < 0.02). A mean of 4.9 injections (95% CI = 4.2-5.6) and 2.8 injections (95% CI = 1.3-4.4) were administered over a 12-month period in the anti-VEGF group and combined group, respectively. Meta-regression analyses showed no influence of injection number on visual and CMT outcomes. High heterogeneity was found across studies for both functional and anatomical outcomes. Conclusion: A combined approach with anti-VEGF and PDT could provide better functional and anatomical outcomes in RAP eyes compared with anti-VEGF monotherapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer GR declared a shared affiliation with the authors MF, AM, GF, MB, RM, AA, AR, AL, TA, and NC to the handling editor at the time of review., (Copyright © 2023 Fallico, Macchi, Maugeri, Favara, Barchitta, Magnano San Lio, Agodi, Russo, Longo, Avitabile, Castellino, Reibaldi, Pignatelli, Vadalà, Patanè, Nebbioso and Bonfiglio.)