Publications by authors named "Antonio Longo"

110 Publications

Primary vitrectomy for degenerative and tractional lamellar macular holes: A systematic review and meta-analysis.

PLoS One 2021 5;16(3):e0246667. Epub 2021 Mar 5.

Department of Surgical Sciences, Eye Clinic Section, University of Turin, Turin, Italy.

Purpose: To assess the efficacy of vitrectomy in degenerative and tractional lamellar macular holes (LMHs) by meta-analysis of published studies.

Methods: PubMed, Medline and Embase databases were searched up to May 2020. Included cohorts were divided into three groups: degenerative LMH group, lamellar hole associated epiretinal proliferation (LHEP) group and tractional LMH group. LHEP is likely to be associated with degenerative LMHs, but less commonly could be associated with mixed LMHs. To reduce risk of possible misclassification bias, eyes with LHEP which could not have been precisely classified by the authors, were included into the LHEP group. The primary outcome was to investigate the visual change following primary vitrectomy in the degenerative LMH and LHEP group versus the tractional LMH group. A sensitivity analysis excluding the LHEP group was also performed on the primary outcome. Mean difference (MD) in best corrected visual acuity between baseline and post-treatment was calculated, along with 95% confidence interval (CI). Rate of incidence of post-operative full-thickness macular hole (FTMH) was assessed as secondary outcome.

Results: Thirteen studies were included. Pooled analyses including all groups showed a significant visual improvement following vitrectomy (pre-post MD = -0.17;95%CI = -0.22,-0.12;p<0.001), with no difference in visual improvement between the degenerative LMH and LHEP group and the tractional LMH group. The sensitivity analysis excluding LHEP group confirmed no difference in visual change between the degenerative LMH group (pre-post MD = -0.18;95%CI = -0.24,-0.12;p<0.001) and the tractional LMH group (MD = -0.16;95%CI = -0.26,-0.07;p<0.001). The incidence rate of post-operative FTMH was higher in the degenerative LMH and LHEP group than in the tractional LMH group (p = 0.002).

Conclusion: Primary vitrectomy for LMH ensured a favorable visual outcome, with no difference in visual gain between degenerative and tractional LMHs. However, a higher incidence of post-operative FTMHs was found in eyes with the degenerative LMH subtype.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0246667PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7935291PMC
March 2021

Current molecular and clinical insights into uveal melanoma (Review).

Int J Oncol 2021 Apr 2;58(4):1-0. Epub 2021 Mar 2.

Department of Ophthalmology, University of Catania, I‑95123 Catania, Italy.

Uveal melanoma (UM) represents the most prominent primary eye cancer in adults. With an incidence of approximately 5 cases per million individuals annually in the United States, UM could be considered a relatively rare cancer. The 90‑95% of UM cases arise from the choroid. Diagnosis is based mainly on a clinical examination and ancillary tests, with ocular ultrasonography being of greatest value. Differential diagnosis can prove challenging in the case of indeterminate choroidal lesions and, sometimes, monitoring for documented growth may be the proper approach. Fine needle aspiration biopsy tends to be performed with a prognostic purpose, often in combination with radiotherapy. Gene expression profiling has allowed for the grading of UMs into two classes, which feature different metastatic risks. Patients with UM require a specialized multidisciplinary management. Primary tumor treatment can be either enucleation or globe preserving. Usually, enucleation is reserved for larger tumors, while radiotherapy is preferred for small/medium melanomas. The prognosis is unfavorable due to the high mortality rate and high tendency to metastasize. Following the development of metastatic disease, the mortality rate increases to 80% within one year, due to both the absence of an effective treatment and the aggressiveness of the condition. Novel molecular studies have allowed for a better understanding of the genetic and epigenetic mechanisms involved in UM biological activity, which differs compared to skin melanomas. The most commonly mutated genes are GNAQ, GNA11 and BAP1. Research in this field could help to identify effective diagnostic and prognostic biomarkers, as well as novel therapeutic targets.
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http://dx.doi.org/10.3892/ijo.2021.5190DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7910016PMC
April 2021

Fluocinolone acetonide vitreous insert for chronic diabetic macular oedema: a systematic review with meta-analysis of real-world experience.

Sci Rep 2021 Feb 26;11(1):4800. Epub 2021 Feb 26.

Department of Surgical Sciences, Eye Clinic Section, University of Turin, 10122, Turin, Italy.

We conducted a meta-analysis of real-world studies on the 0.19 mg Fluocinolone Acetonide (FAc) intravitreal implant for chronic diabetic macular oedema (DMO), comparing these findings with the Fluocinolone Acetonide for Diabetic Macular Edema (FAME) study. The primary outcome was mean change of best corrected visual acuity (BCVA) at 24 months. Secondary outcomes were 36-month mean BCVA, mean central macular thickness (CMT) change, rates of eyes receiving supplementary intravitreal therapy, cataract surgery, intraocular pressure (IOP)-lowering drops and glaucoma surgery. Mean differences (MDs) with 95% confidence intervals (CIs) were calculated. Nine real-world studies were included. The FAc implant yielded a significantly improved BCVA at 24 and 36 months (24-month MD = 4.52; 95% CI 2.56-6.48; 36-month MD = 8.10; 95% CI 6.34-9.86). These findings were comparable with the FAME study. The FAc implant yielded significantly reduced 24- and 36-month CMT. Pooled proportions of cataract surgery, IOP-lowering drops and glaucoma surgery were 39%, 27% and 3%, respectively, all lower than the FAME study. Pooled estimate of supplementary intravitreal therapy was 39%, higher than the 15.2% of the FAME study. This meta-analysis of real-world studies confirms favorable visual and anatomical outcomes following FAc insert for chronic DMO. In real-life studies more than one third of patients received supplementary intravitreal therapy, an issue that needs to be further explored.
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http://dx.doi.org/10.1038/s41598-021-84362-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7910468PMC
February 2021

Retinal Vascular Assessment in Psoriasis: A Multicenter Study.

Front Neurosci 2021 25;15:629401. Epub 2021 Jan 25.

Department of Surgical Science, Eye Clinic, University of Turin, Turin, Italy.

Purpose: To investigate the vascular status of the macula in psoriasis patients without history of ocular inflammation by Optical Coherence Tomography Angiography (OCTA).

Methods: This prospective cross-sectional multicenter study included 55 psoriasis patients and 55 control healthy subjects. A complete eye examination and 6 mm × 6 mm OCTA imaging were performed. Retinal vascular status was evaluated by analyzing vascular density (VD) of superficial vascular plexus (superficial wVD) and deep vascular plexuses (deep wVD) in a 6 mm × 6 mm area and in foveal (superficial fVD and deep fVD) and parafoveal sectors (superficial pVD and deep pVD). In addition, foveal thickness (FT) and foveal avascular zone (FAZ) and clinical variables, including best corrected visual acuity (BCVA), intraocular pressure and refractive condition, were collected.

Results: BCVA, intraocular pressure and refractive condition were comparable between cases and controls. OCTA imaging showed that superficial wVD and superficial pVD were lower in the psoriasis group in comparison with controls ( = 0.009 and = 0.01, respectively). Similarly, deep wVD and pVD were lower in the psoriasis group in comparison with control subjects ( = 0.03 and = 0.01, respectively). In a sub-analysis of 47 patients affected by psoriasis without psoriatic arthritis, lower values of wVD and pVD in both superficial and deep capillary plexuses were registered.

Conclusion: OCTA is a useful tool which provides data on vascular status of the retina in psoriasis with no ocular involvement. VD data may suggest that vascular changes may occur earlier than clinical onset of posterior inflammation.
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http://dx.doi.org/10.3389/fnins.2021.629401DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7868328PMC
January 2021

Solitary fibrous tumor of the orbital region: report of a case with emphasis on the diagnostic utility of STAT-6.

Pathologica 2020 Dec;112(4):195-199

Department of Medical and Surgical Sciences and Advanced Technologies, G.F. Ingrassia, Azienda Ospedaliero-Universitaria "Policlinico Vittorio Emanuele", Anatomic Pathology, School of Medicine, University of Catania, Italy.

Solitary fibrous tumor (SFT) is a relatively rare soft tissue neoplasm originally described in the pleura. Since its first description, several cases arising in extra-pleural superficial and deep soft tissues have been reported in the literature. SFT arising in the head and neck region is quite rare, representing about the 6% of all SFTs, and the sinonasal tract is the most common involved region, followed by the orbit, the oral cavity and the salivary glands. Herein, we report the clinico-pathologic features of a rare case of SFT of the orbital region, emphasizing the diagnostic role of the immunomarker STAT-6. A 52-year-old female presented to our hospital with a nodular mass in the left orbital region. Histological examination revealed a uniformly hypercellular tumor composed of pale to slightly eosinophilic bland-looking spindle cells arranged in intersecting short fascicles with interspersed stellate-shaped, keloid-type collagen fibers. Notable hypocellular areas, perivascular hyalinization and hemangiopericytoma-like branching vascular pattern were absent. Immunohistochemically, neoplastic cells were diffusely positive for vimentin, CD34 and STAT-6. The introduction of STAT-6 in daily diagnostic practice is helpful to confidentially render a diagnosis of SFT even in the presence of unusual morphology and site.
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http://dx.doi.org/10.32074/1591-951X-9-20DOI Listing
December 2020

LncRNA Acts as an Oncogene in Uveal Melanoma by Regulating an RNA-Based Network.

Cancers (Basel) 2020 Dec 21;12(12). Epub 2020 Dec 21.

Department of Biomedical and Biotechnological Sciences-Section of Biology and Genetics, University of Catania, 95123 Catania, Italy.

Uveal melanoma (UM) is the most common primary intraocular malignant tumor in adults; little is known about the contribution of non-coding RNAs (ncRNAs) to UM pathogenesis. Competitive endogenous RNA (ceRNA) networks based on RNA-RNA interactions regulate physiological and pathological processes. Through a combined approach of in silico and experimental biology, we investigated the expression of a set of long non-coding RNAs (lncRNAs) in patient biopsies, identifying as a potential oncogene in UM. The detection of dysregulation associated with several in vitro functional assays allowed us to investigate its ceRNA regulatory network and shed light on its potential involvement in cancer-related processes, such as epithelial to mesenchymal transition (EMT) and CoCl-induced hypoxia-like response. In vitro transient silencing of impaired cell proliferation and migration, and affected mRNA expression of , , , , and . A "miRNA sponge" and "miRNA protector" model have been hypothesized for -induced regulation of mRNAs. In vitro inhibition of suggested its role as a potential activator of expression. Comprehensively, may be considered a new oncogene in UM and a potential target for RNA-based therapeutic approaches.
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http://dx.doi.org/10.3390/cancers12123867DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7767460PMC
December 2020

TGF-β Serum Levels in Diabetic Retinopathy Patients and the Role of Anti-VEGF Therapy.

Int J Mol Sci 2020 Dec 15;21(24). Epub 2020 Dec 15.

Department of Biomedical and Biotechnological Sciences, School of Medicine, University of Catania, 95123 Catania, Italy.

Transforming growth factor β1 (TGFβ1) is a proinflammatory cytokine that has been implicated in the pathogenesis of diabetic retinopathy (DR), particularly in the late phase of disease. The aim of the present study was to validate serum TGFβ1 as a diagnostic and prognostic biomarker of DR stages. Thirty-eight subjects were enrolled and, after diagnosis and evaluation of inclusion and exclusion criteria, were assigned to six groups: (1) healthy age-matched control, (2) diabetic without DR, (3) non-proliferative diabetic retinopathy (NPDR) naïve to treatment, (4) NPDR treated with intravitreal (IVT) aflibercept, (5) proliferative diabetic retinopathy (PDR) naïve to treatment and (6) PDR treated with IVT aflibercept. Serum levels of vascular endothelial growth factor A (VEGF-A), placental growth factor (PlGF) and TGFβ1 were measured by means of enzyme-linked immunosorbent assay (ELISA). Foveal macular thickness (FMT) in enrolled subjects was evaluated by means of structural-optical coherence tomography (S-OCT). VEGF-A serum levels decreased in NPDR and PDR patients treated with aflibercept, compared to naïve DR patients. PlGF serum levels were modulated only in aflibercept-treated NPDR patients. Particularly, TGFβ1 serum levels were predictive of disease progression from NPDR to PDR. A Multivariate ANOVA analysis (M-ANOVA) was also carried out to assess the effects of fixed factors on glycated hemoglobin (HbA1c) levels, TGFβ1, and diabetes duration. In conclusion, our data have strengthened the hypothesis that TGFβ1 would be a biomarker and pharmacological target of diabetic retinopathy.
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http://dx.doi.org/10.3390/ijms21249558DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7765505PMC
December 2020

The "Reverse Air-Leak Test" : A New Technique for the Assessment of Low Colorectal Anastomosis.

Ann Coloproctol 2020 Dec 4. Epub 2020 Dec 4.

Department of Coloproctology and Pelvic Disease, St Elisabeth Hospital, Vienna, Austria.

Background: Anastomotic leakage is a fearsome complication in rectal surgery. Surgeons perform the classic air-leak test, although its real effectiveness is still debated. The aim of this study was to describe a personal technique of reverse air leak test in which low colorectal anastomosis were assessed transanally through the intra-rectal irrigation of a few mL of saline solution.

Methods: From October 2014 to November 2019 eleven patients with low rectal cancer (Type 1 in Roullier classification) were included in this study. At the beginning of the procedure, a circular anal dilator (CAD) was inserted into the anus. A side-to-end colorectal anastomosis was performed. A few mL of saline solution were injected into the rectum and the entire anastomotic line was directly explored. The appearance of bubbles was considered as an anastomotic defect and repaired with an interrupted suture. A fluorescence angiography after intravenous injection of Indocyanine green was performed in order to evaluate the perfusion of the anastomosis.

Results: In 4 cases (36.3%) the reverse air-leak test was positive. The defect was repaired and a confirmation test was performed. In all patients, near-infrared evaluation showed not perfusion defect (grade 0) in low colorectal anastomosis. No post-operative fistula was detected in cohort study. A protective stoma was performed in 10 patients. At 90-days there were no complications and stoma closure was performed as planned.

Conclusion: The reverse air-leak test is a simple, feasible and effective procedure to identify anastomotic leak in low colorectal anastomoses.
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http://dx.doi.org/10.3393/ac.2020.09.21.1DOI Listing
December 2020

The Macro-Autophagy-Related Protein Beclin-1 Immunohistochemical Expression Correlates With Tumor Cell Type and Clinical Behavior of Uveal Melanoma.

Front Oncol 2020 20;10:589849. Epub 2020 Nov 20.

Section of Anatomic Pathology, Department Gian Filippo Ingrassia, University of Catania, Catania, Italy.

Uveal melanoma, in spite of its rarity, represents the most common primitive intraocular malignant neoplasm of the adults; it affects choroid, ciliary bodied and iris and remains clinically silent for a long time, being accidentally discovered by routine ophthalmic exams. Prognosis of uveal melanoma is poor and frequently characterized by liver metastases, within 10-15 years from diagnosis. Autophagy is a multi-step catabolic process by which cells remove damaged organelles and proteins and recycle nutrients. It has been hypothesized that in early stages of tumorigenesis autophagy has a tumor suppressor role while, in more advanced stages, it may represent a survival mechanism of neoplastic cells in response to stress. Several proteins related to autophagy cascade have been investigated in numerous subtypes of human cancer, with overall controversal results. In this paper we studied the immunohistochemical expression of 3 autophagy related proteins (Beclin-1, p62 and ATG7) in a cohort of 85 primary uveal melanoma treated by primary enucleation (39 with metastasis and 46 non metastatic) and correlated their expression with clinico-pathological parameters and blood vascular microvessel density, in order to investigate the potential prognostic role of autophagy in this rare neoplasm. We found that high immunohistochemical levels of Beclin-1 correlated with a lower risk of metastasis and higher disease-free survival times, indicating a positive prognostic role for Beclin-1 in uveal melanoma. No statistically significative differences regarding the expression of ATG7 and p62 between metastatic and non metastatic patients was detected.
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http://dx.doi.org/10.3389/fonc.2020.589849DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7714947PMC
November 2020

Intravitreal anti-vascular endothelial growth factors, panretinal photocoagulation and combined treatment for proliferative diabetic retinopathy: a systematic review and network meta-analysis.

Acta Ophthalmol 2020 Dec 16. Epub 2020 Dec 16.

Department of Surgical Sciences, Eye Clinic Section, University of Turin, Turin, Italy.

Purpose: To conduct a systematic review with network meta-analysis (NMA) of randomized clinical trials (RCTs) comparing panretinal photocoagulation (PRP) versus anti-vascular endothelial growth factor (VEGF) treatment alone or in combination with PRP, for proliferative diabetic retinopathy (PDR).

Methods: PubMed, Medline and Embase databases were searched for RCTs comparing PRP versus intravitreal anti-VEGF therapy and/or combined PRP and intravitreal anti-VEGF for PDR. The primary outcome measures were the mean best corrected visual acuity (BCVA) change and the regression of neovascularization. Mean change of central macular thickness (CMT), the subgroup analyses of patients without diabetic macular oedema (DME) and the rate of vitreous haemorrhage and vitrectomy were secondary outcomes. Frequentist NMAs were performed.

Results: Twelve RCTs were included. For the 12-month mean BCVA change, NMA showed a better visual outcome in both the anti-VEGF group and combined group compared to PRP [anti-VEGF vs PRP, mean difference (MD) = 3.42; standard error (SE) = 1.5; combined vs PRP, MD = 3.92; SE = 1.65], with no difference between combined group and anti-VEGF (MD = -0.50; SE = 1.87). No difference in neovascularization regression was found between PRP and anti-VEGF alone or in combination with PRP, but there was significant inconsistency (p = 0.016). Subgroup analyses in patients without DME yielded no difference for the 12-month visual outcome between the three interventions, but with significant inconsistency (p = 0.005).

Conclusion: This NMA showed limited evidence of comparable efficacy in terms of neovascularization regression between PRP and anti-VEGF therapy alone or in combination with PRP, but better visual outcomes were associated with anti-VEGF use. Intravitreal anti-VEGF therapy could be a valid therapeutic option in association with PRP.
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http://dx.doi.org/10.1111/aos.14681DOI Listing
December 2020

Treat and extend versus fixed regimen in neovascular age related macular degeneration: A systematic review and meta-analysis.

Eur J Ophthalmol 2020 Oct 29:1120672120964699. Epub 2020 Oct 29.

Department of Surgical Science, Eye Clinic, University of Torino, Torino, Piemonte, Italy.

Purpose: To compare efficacy of treat and extend (T&E) versus fixed regimen treatment protocols in neovascular age-related macular degeneration (nAMD).

Methods: Randomized clinical trials (RCTs) comparing T&E versus fixed regimen protocols for nAMD were systematically searched. Primary outcome was to compare the mean best corrected visual acuity (BCVA) change in T&E regimen versus fixed regimen. Secondary outcomes were change in the mean optical coherence tomography (OCT) central retinal thickness (CRT) and mean number of injections. Standardized mean difference (SMD) along with 95% confidence intervals (CIs) were calculated. Random-effect models were used for meta-analyses.

Results: Four RCTs were included, with a total of 649 and 621 eyes in the T&E and fixed regimen cohort at 12 months, and 267 and 249 eyes at 24 months. Pooled analysis of mean BCVA change included all four RCTs at 12 months and two RCTs at 24 months, showing no difference between the two groups (12-month: SMD = 0.08, 95% CI: -0.20 to 0.35,  = 0.55; 24-month: SMD = 0.04, 95% CI: -0.13 to 0.21,  = 0.64). Pooled analysis of OCT CRT change at 12 months included three studies, showing no difference between the two groups (SMD = 0.03, 95% CI: -0.46 to 0.51,  = 0.91). Pooled analysis of mean injection number included all four RCTs at 12 months and two RCTs at 24 months, showing significant difference between the two groups (12-month: SMD = -1.11, 95% CI: -1.67 to -0.56,  < 0.001; 24-month: SMD = -1.34, 95% CI: -1.54 to -1.15,  < 0.001).

Conclusion: A T&E regimen proved as effective as a fixed dosage regimen throughout a 24-month follow-up and with a lower number of injections.
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http://dx.doi.org/10.1177/1120672120964699DOI Listing
October 2020

Retinal Thickness and Microvascular Pattern in Early Parkinson's Disease.

Front Neurol 2020 7;11:533375. Epub 2020 Oct 7.

Section of Neurosciences, Department of Medical, Surgical Sciences and Advanced Technologies GF Ingrassia, University of Catania, Catania, Italy.

A thinning of intraretinal layers has been previously described in Parkinson's disease (PD) patients compared to healthy controls (HCs). Few studies evaluated the possible correlation between retinal thickness and retinal microvascularization. Thus, here we assessed the thickness of retinal layers and microvascular pattern in early PD patients and HCs, using, respectively, spectral-domain optical coherence tomography (SD-OCT) and SD-OCT-angiography (SD-OCT-A), and more interestingly, we evaluated a possible correlation between retinal thickness and microvascular pattern. Patients fulfilling criteria for clinically established/clinically probable PD and HCs were enrolled. Exclusion criteria were any ocular, retinal, and systemic disease impairing the visual system. Retinal vascularization was analyzed using SD-OCT-A, and retinal layer thickness was assessed using SD-OCT. Forty-one eyes from 21 PD patients and 33 eyes from 17 HCs were evaluated. Peripapillary retinal nerve fiber layer (RNFL) and macular RNFL, ganglionic cell layer (GCL), inner plexiform layer (IPL), and inner nuclear layer (INL), resulted to be thinner in PD compared to HCs. Among PD patients, a positive correlation between RNFL, GCL, and IPL thickness and microvascular density was found in the foveal region, also adjusting by age, sex, and, especially, hypertension. Such findings were already present in the early stage of disease and were irrespective of dopaminergic treatment. Thus, the retina might be considered a biomarker of PD and could be a useful instrument for onset and disease progression.
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http://dx.doi.org/10.3389/fneur.2020.533375DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7575742PMC
October 2020

Factors predicting normal visual acuity following anatomically successful macular hole surgery.

Acta Ophthalmol 2020 Aug 24. Epub 2020 Aug 24.

Department of Surgical Sciences, Eye Clinic Section, University of Turin, Turin, Italy.

Purpose: To assess the incidence of normal vision following anatomically successful macular hole surgery and associated clinical variables.

Methods: Multicentre, retrospective chart review. Preoperative, intraoperative and postoperative clinical data were extracted from electronic medical records from seven European vitreoretinal units. Inclusion criteria were as follows: eyes undergoing primary vitrectomy for idiopathic full-thickness macular hole from January 2015 to January 2018; postoperative macular hole closure confirmed by spectral domain optical coherence tomography (OCT); preoperative pseudophakia or phakic eyes receiving combined cataract surgery; one-year follow-up. The primary outcome was 'normal vision' defined as a final best-corrected visual acuity (BCVA) ≥ 20/25. Univariate, multivariate and decision-tree analyses were conducted to evaluate the clinical variables associated with 'normal vision'. Odds ratios (OR) and confidence intervals (CIs) were calculated.

Results: Of 327 eligible cases, 91 (27.8%) achieved 'normal vision' at 1 year. Multivariate analysis identified variables significantly associated with 'normal vision': shorter symptom duration (odds ratio [OR]=1.05; 95% confidence interval [CI]:1.02-1.09; p = 0.002), smaller preoperative OCT minimum linear diameter (OR per 100-micron increase = 1.65; 95%CI:1.31-2.08; p < 0.001) and better mean preoperative BCVA (OR = 15.13; 95%CI: 3.59-63.65; p < 0.001). The decision-tree analysis found that the most significant variable associated with 'normal vision' was symptom duration. 'Normal vision' was achieved in 70.6% of eyes operated within one week from symptom onset and in 45% of eyes with symptom duration between 1 and 3 weeks.

Conclusions: These findings suggested urgent surgery is justified for small macular holes of short duration.
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http://dx.doi.org/10.1111/aos.14575DOI Listing
August 2020

Safety and Efficacy of Second Ahmed Valve Implant in Refractory Glaucoma.

J Clin Med 2020 Jun 29;9(7). Epub 2020 Jun 29.

Department of Surgical, Medical and Molecular Pathology and of the Critical Area, University of Pisa, 56126 Pisa, Italy.

Background: Refractory glaucoma still represents a challenge for ophthalmologists to manage intraocular pressure. The present study aimed to evaluate long term efficacy and safety of a second Ahmed valve implantation after the failure of a first implant in patients with refractory glaucoma and elevated intraocular pressure (IOP).

Methods: Retrospective, multicenter non-comparative case series. Twenty-eight patients were retrospectively recruited between January 2011 and December 2017. Demographic data, glaucoma type, visual acuity, intraocular pressure, medical therapy, and complications were registered. Three criteria of success were established: Type 1 surgical success: IOP ≤ 15 mmHg and a reduction of IOP ≥ 40% from baseline; Type 2 surgical success: IOP ≤ 18 mmHg and a reduction of IOP ≥ 30% from baseline; and Type 3 surgical success: IOP ≤ 21 mmHg and a reduction of IOP ≥ 20% from baseline. Surgical failure has been established as IOP less than 5 mmHg or over 21 mmHg and less than a 20% reduction of IOP from baseline despite medications in two consecutive visits, light perception loss referable to glaucoma, and the necessity for further glaucoma surgery. Failure was observed in six (21%) patients. (3) Results: Mean IOP and mean glaucoma medication number significantly reduced from baseline after the second implantation, and the surgical success rate at 72 months ranged from 10% to 78% based on the different criteria of success. Failure was observed in six (21%) patients.

Conclusions: This study confirmed the safety and efficacy of a second Ahmed valve implantation in patients with refractory glaucoma and elevated IOP at baseline.
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http://dx.doi.org/10.3390/jcm9072039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7408983PMC
June 2020

Intravitreal dexamethasone implant one month before versus concomitant with cataract surgery in patients with diabetic macular oedema: the dexcat study.

Acta Ophthalmol 2021 Feb 26;99(1):e74-e80. Epub 2020 Jun 26.

Department of Ophthalmology, University of Catania, Catania, Italy.

Purpose: To report clinical outcomes of two different timings of intravitreal dexamethasone (DEX) implant administration for prevention of diabetic macular oedema (DME) worsening following cataract surgery.

Methods: This multicentre, retrospective study included patients with DME who received an intravitreal DEX implant 1 month before cataract surgery, 'precataract DEX' group, or at the time of cataract surgery, 'concomitant treatments' group. Inclusion criteria were a follow-up ≥3 months and ophthalmological examination with optical coherence tomography (OCT) imaging at baseline (cataract surgery) and throughout follow-up. Anatomical improvement was considered to be a decrease in OCT central subfield (CSF) thickness ≥20% compared to baseline. The primary outcomes were anatomical and functional results at 3 months.

Results: Two hundred twenty-one patients were included: 136 in the 'precataract DEX' group and 85 in the 'concomitant treatments' group. At 3 months, a reduction of CSF thickness ≥ 20% was found in 7.3% of eyes in the 'precataract DEX group' and in 83.7% of eyes in the 'concomitant treatments' group (p < 0.001), with mean CSF thickness lower in the latter group (371 ± 52 µm versus 325 ± 57 µm, p < 0.001). At 3 months, mean best-corrected visual acuity had improved from baseline in both groups (p < 0.001), with no difference between groups (p = 0. 20). No serious systemic adverse events were reported.

Conclusion: Both approaches prevented a worsening of DME, showing a comparable visual outcome. Dexamethasone (DEX) implant given at the same time as cataract surgery provided a better anatomical outcome.
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http://dx.doi.org/10.1111/aos.14516DOI Listing
February 2021

Preoperative, Intraoperative and Postoperative Corticosteroid Use as an Adjunctive Treatment for Rhegmatogenous Retinal Detachment.

J Clin Med 2020 May 21;9(5). Epub 2020 May 21.

Department of Ophthalmology, University of Catania, 95100 Catania, Italy.

The treatment for rhegmatogenous retinal detachment (RRD) is surgery, including pars plana vitrectomy (PPV) and scleral buckling (SB). Despite surgical advances, degeneration of the photoreceptors and post-operative complications, such as proliferative vitreoretinopathy (PVR), often occurs as the result of inflammation, preventing complete visual recovery or causing RRD recurrence. There is increasing evidence that in the presence of RRD, the activation of inflammatory processes occurs and the surgery itself induces an inflammatory response. This comprehensive review focuses on the use of different formulations of corticosteroids (CCS), as an adjunctive treatment to surgery, either PPV or SB, for RRD repair. The purpose was to review the efficacy and safety of CCS in improving functional and anatomical outcomes and in preventing postoperative complications. This review is organized according to the timing of CCS administration: preoperative, intraoperative, and postoperative. The evidence reviewed supported the role of the pre-operative use of CCS in the treatment of combined RRD and choroidal detachment (CD), reducing CD height. No solid consensus exists on intraoperative and postoperative use of CCS to treat and prevent postoperative complications. However, a large randomized clinical trial including more than 200 eyes suggested that oral prednisone after surgery decreases the rate of postoperative grade B PVR.
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http://dx.doi.org/10.3390/jcm9051556DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7290919PMC
May 2020

Loss of macroH2A1 decreases mitochondrial metabolism and reduces the aggressiveness of uveal melanoma cells.

Aging (Albany NY) 2020 05 12;12(10):9745-9760. Epub 2020 May 12.

Center for Translational Medicine (CTM), International Clinical Research Center (FNUSA-ICRC), St Anne's University Hospital, Brno, Czech Republic.

Uveal melanoma (UM) is the most common primary intraocular tumour in adults. The most accurate prognostic factor of UM is classification by gene expression profiling. Currently, the role of epigenetics is much less defined compared to genetic mechanisms. We recently showed a strong prognostic role of the expression levels of histone variant macroH2A1 in UM patients. Here, we assessed the mechanistic effects of macroH2A1 on UM progression.UM cell lines were stably knocked down (KD) for macroH2A1, and proliferation and colony formation capacity were evaluated. Mitochondrial function was assayed through qPCR and HPLC analyses. Correlation between mitochondrial gene expression and cancer aggressiveness was studied using a bioinformatics approach.MacroH2A1 loss significantly attenuated UM cells proliferation and aggressiveness. Furthermore, genes involved in oxidative phosphorylation displayed a decreased expression in KD cells. Consistently, macroH2A1 loss resulted also in a significant decrease of mitochondrial transcription factor A (TFAM) expression, suggesting impaired mitochondrial replication. Bioinformatics analyses uncovered that the expression of genes involved in mitochondrial metabolism correlates with macroH2A1 and with cancer aggressiveness in UM patients. Altogether, our results suggest that macroH2A1 controls UM cells progression and it may represent a molecular target to develop new pharmacological strategies for UM treatment.
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http://dx.doi.org/10.18632/aging.103241DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7288915PMC
May 2020

The Glaucoma Italian Pediatric Study (GIPSy): The Long-term Effect of Topical Latanoprost on Central Corneal Thickness.

J Glaucoma 2020 06;29(6):441-447

Section of Ophthalmology, Department of Surgical and Clinical, Diagnostic and Pediatric Sciences, IRCCS Fondazione Policlinico San Matteo, University of Pavia, Pavia, Italy.

Precis: Central corneal thickness (CCT) may increase over time in children affected by primary congenital glaucoma and treated with latanoprost for at least 30 months.

Purpose: The purpose of this study was to investigate CCT modification over time in a population of primary pediatric glaucoma (PPG) patients prescribed a monotherapy of latanoprost.

Materials And Methods: The present paper reports the results of a post hoc analysis on patients enrolled in the Glaucoma Italian Pediatric Study (GIPSy). Children affected by PPG, with a postsurgical intraocular pressure between 22 and 26 mm Hg and treated with latanoprost monotherapy for at least 30 months were eligible for the analysis. CCT variation from baseline was investigated over the follow-up using univariable and multivariable longitudinal linear mixed models. The impact of age, sex, and intraocular pressure on CCT variation were evaluated taking into account the interaction of each variable with time.

Results: Twenty-seven eyes (20 patients) were included in the analysis. Mean duration of latanoprost treatment was 36.6 months (SD 2.5) and mean CCT at baseline was 551 μm (SD 37.7). A significant increase of CCT over time was revealed by multivariable analysis, taking into account the impact of age at baseline and its interaction with time (P=0.03). The interaction between age and time was significant (P=0.04), indicating that older age at baseline was associated with lower increase of CCT over time. No variation of CCT was found in univariable analysis (P=0.28).

Conclusion: In this population of PPG patients treated with latanoprost for at least 30 months, CCT significantly increased over time, when the impact of age and its interaction with time were considered.
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http://dx.doi.org/10.1097/IJG.0000000000001495DOI Listing
June 2020

International consensus on natural orifice specimen extraction surgery (NOSES) for gastric cancer (2019).

Gastroenterol Rep (Oxf) 2020 Feb 24;8(1):5-10. Epub 2020 Jan 24.

Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P. R. China.

At present, natural orifice specimen extraction surgery (NOSES) has attracted more and more attention worldwide, because of its great advantages including minimal cutaneous trauma and post-operative pain, fast post-operative recovery, short hospital stay, and positive psychological impact. However, NOSES for the treatment of gastric cancer (GC) is still in its infancy, and there is great potential to improve its theoretical system and clinical practice. Especially, several key points including oncological outcomes, bacteriological concerns, indication selection, and standardized surgical procedures are raised with this innovative technique. Therefore, it is necessary to achieve an international consensus to regulate the implementation of GC-NOSES, which is of great significance for healthy and orderly development of NOSES worldwide.
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http://dx.doi.org/10.1093/gastro/goz067DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7034234PMC
February 2020

How Have Intravitreal Anti-VEGF and Dexamethasone Implant Been Used in Italy? A Multiregional, Population-Based Study in the Years 2010-2016.

Biomed Res Int 2020 11;2020:7582763. Epub 2020 Jan 11.

Unit of Clinical Pharmacology, A.O.U. "G. Martino", Messina, Italy.

Purpose: To describe intravitreal anti-VEGF drug and dexamethasone use in four Italian regions.

Methods: Four regional claims databases were used to measure drug prevalence, compare dosing intervals to those recommended in the summary of product characteristics (SPC), and identify switchers. Bilateral treatment and diabetic macular edema (DME) coding algorithms were validated, linking claims with a sample of prospectively collected ophthalmological data.

Results: Overall, 41,836 patients received ≥1 study drug in 2010-2016 (4.8 per 10,000 persons). In 2016, anti-VEGF drug use ranged from 0.8 (Basilicata) to 5.7 (Lombardy) per 10,000 persons while intravitreal dexamethasone use ranged from 0.2 (Basilicata) to 1.4 (Lombardy) per 10,000 persons. Overall, 40,815 persons were incident users of study drugs. Among incident users with ≥1 year of follow-up ( = 30,745), 16.0% ( = 30,745), 16.0% ( = 30,745), 16.0% (.

Conclusion: Study drug use increased over time in Lombardy, Basilicata, Calabria, and Sicily, despite a large heterogeneity in prevalence of use across regions. Drug treatment appeared to be partly in line with SPC, suggesting that improvement in clinical practice may be needed to maximize drug benefits.
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http://dx.doi.org/10.1155/2020/7582763DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6977336PMC
September 2020

Protective effect of PACAP against ultraviolet B radiation-induced human corneal endothelial cell injury.

Neuropeptides 2020 Feb 20;79:101978. Epub 2019 Nov 20.

Department of Biomedical and Biotechnological Sciences, Section of Human Anatomy and Histology, University of Catania, Catania, Italy. Electronic address:

The human cornea, a sophisticated example of natural engineering, is composed in the innermost layer by endothelial cells maintaining stromal hydration and clarity. Different types of insults, including ultraviolet (UV) radiations, can lead to corneal opacity due to their degenerative and limited proliferative capability. In our previous studies, we have shown the protective effects of pituitary adenylate cyclase activating polypeptide (PACAP) in human corneal endothelial cells (HCECs), after growth factors deprivation. The aim of the present work has been to investigate the effect of this peptide on UV-B-induced HCECs injury. The results have shown that UV-B irradiations induced apoptotic cells death and consequently alteration in human corneal endothelial barrier. We found that PACAP treatment significantly increased viability, trans-endothelial electrical resistance and tight junctions expression of HCECs exposed to UV-B insult. In conclusion, data have suggested that this peptide could have protective effect to preserve the physiological state of human corneal endothelium exposed to UV-B damage.
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http://dx.doi.org/10.1016/j.npep.2019.101978DOI Listing
February 2020

Vascular changes after vitrectomy for rhegmatogenous retinal detachment: optical coherence tomography angiography study.

Acta Ophthalmol 2019 Nov 26. Epub 2019 Nov 26.

Department of Ophthalmology, University of Catania, Catania, Italy.

Purpose: To analyse the postoperative foveal avascular zone (FAZ) area, superficial vessel density (SVD) and deep vessel density (DVD) and their correlation with functional (best-corrected visual acuity, BCVA) and anatomical outcomes (foveal macular thickness, FMT) after surgery for rhegmatogenous retinal detachment (RRD) repair.

Method: Patients with RRD eyes, successfully treated with a single pars plana vitrectomy (PPV) with gas tamponade and a minimum 12 months follow-up, were re-examined. Foveal avascular zone (FAZ) area, SVD, DVD and FMT were evaluated by using optical coherence tomography angiography (OCTA) and compared to fellow eye.

Results: Fifty-six patients with macula-on and 37 with macula-off RRD were included in the study. In both groups, no difference in FMT and FAZ area was found compared to fellow eyes. In macula-on RRD eyes, a lower parafoveal DVD (p = 0.001) was detected; FAZ area was related to FMT (p = 0.025), and the postoperative BCVA was correlated with parafoveal DVD (p = 0.010) and FAZ area (p = 0.003). In macula-off RRD eyes, lower parafoveal SDV (p = 0.012), and foveal and parafoveal DVD (p = 0.012 and p < 0.001, respectively) were observed. BCVA was related to FAZ area (p = 0.012), foveal SVD (p = 0.005) and parafoveal DVD (p = 0.010).

Conclusion: Rhegmatogenous retinal detachment eyes successfully treated with PPV had lower vessel density in the superficial and deep retinal plexus compared to fellow healthy eyes; BCVA was related to FAZ area and vessel density.
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http://dx.doi.org/10.1111/aos.14315DOI Listing
November 2019

Incidence and Risk Factors for Tractional Macular Detachment after Anti-Vascular Endothelial Growth Factor Agent Pretreatment before Vitrectomy for Complicated Proliferative Diabetic Retinopathy.

J Clin Med 2019 Nov 13;8(11). Epub 2019 Nov 13.

Department of Ophthalmology, University of Catania, 95100 Catania, Italy.

The study's purpose was to determine the incidence, risk factors, and outcomes of tractional macular detachment after anti-vascular endothelial growth factor (VEGF) pretreatment before vitrectomy for complicated proliferative diabetic retinopathy. Patients who underwent primary vitrectomy for complicated proliferative diabetic retinopathy, from January 2012 to 31 December 2018, were enrolled. Ophthalmic and pre-operative data were extracted from electronic record systems. All eyes with a valuable Optical Coherence Tomography (OCT)performed within 5 days before injection of anti-VEGF and on the day of vitrectomy were included. Multivariable logistic regression showed that significant risk factors for developing tractional macular detachment included days between anti-VEGF and vitrectomy (OR, 0.71 [95% CI 0.65-0.76]; < 0.001), vitreous hemorrhage (OR, 0.23 [95% CI 0.11-0.49]; < 0.001), and age (OR, 1.05 [95% CI 1.02-1.08]; < 0.001). Decision-tree analysis showed that the stronger predictors of tractional macular detachment were the time between anti-VEGF injection and vitrectomy ( < 0.001). Secondary predictors were the presence of vitreous hemorrhage ( = 0.012) in eyes that underwent vitrectomy between 6 and 10 days after anti-VEGF injection and younger age ( = 0.031) in eyes that underwent vitrectomy 10 days after anti-VEGF injection. Tractional macular detachment occurs in 10% of eyes after anti-VEGF injection, the main risk factors being days between anti-VEGF injection and vitrectomy, vitreous hemorrhage, and age.
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http://dx.doi.org/10.3390/jcm8111960DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6912392PMC
November 2019

Risk of Death Associated With Intravitreal Anti-Vascular Endothelial Growth Factor Therapy: A Systematic Review and Meta-analysis.

JAMA Ophthalmol 2019 Nov 21. Epub 2019 Nov 21.

Department of Neurosciences, Psychology, Drug Research and Child Health, University of Firenze and Azienda Ospedaliero Universitaria Careggi, Florence, Italy.

Importance: Although intravitreal anti-vascular endothelial growth factor (VEGF) treatment represents the first-line therapy for many retinal diseases, the issue of their systemic safety is debatable.

Objectives: To assess whether intravitreal anti-VEGF therapy might be associated with increased risk of mortality and which variables are associated with the increase.

Data Sources: PubMed, MEDLINE, and Embase databases, the Cochrane Library, and ClinicalTrials.gov were systematically searched from inception to May 6, 2019.

Study Selection: Randomized clinical trials comparing intravitreal anti-VEGF treatment with control groups and with follow-up of at least 6 months were selected.

Data Extraction And Synthesis: Data were independently collected by 2 investigators. Meta-analyses were conducted using the frequentist and Bayesian methods. For the frequentist approach, random- and fixed-effects models were used, with random-effects models considered the primary technique. Odds ratios (ORs) with 95% CIs were computed. For the bayesian approach, uninformative and informative priors were used. Odds ratios with 95% credible intervals (CrIs) were computed. Meta-regression analyses were based on random-effects models.

Main Outcomes And Measures: The primary outcome measure was the all-cause death rate. Secondary outcomes included meta-regression analyses on the following variables: type of drug, number of injections, follow-up time, diagnosis, and cardiovascular risk.

Results: Of 2336 studies identified, 34 unique studies with 8887 unique participants were included in the present meta-analysis. For the frequentist analysis, fixed- and random-effects models yielded similar estimates (ORs, 1.34 [95% CI, 0.95-2.07; P = .09] and 1.34 [95% CI, 0.89-2.01; P = .17], respectively). For the Bayesian approach, noninformative and informative priors yielded similar results (ORs, 1.34 [95% CrI, 0.79-2.34; 0.13 probability of OR≤1.00] and 1.40 [95% CrI, 0.82-2.32; 0.11 probability of OR≤1.00], respectively). Meta-regression analyses showed the following risk for 1 injection more: frequentist OR of 1.12 (95% CI, 1.04-1.22; P = .005) and Bayesian OR of 1.06 (95% CrI, 0.98-1.15; 0.06 probability of OR≤1.00).

Conclusions And Relevance: In this study, no difference was found in the mortality rate between intravitreal anti-VEGF treatment and control groups. Additional data seem warranted to determine whether the mortality rate is increased in patients receiving a greater number of injections.
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http://dx.doi.org/10.1001/jamaophthalmol.2019.4636DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6902107PMC
November 2019

Immunobiology of Uveal Melanoma: State of the Art and Therapeutic Targets.

Front Oncol 2019 5;9:1145. Epub 2019 Nov 5.

Department of Ophthalmology, University of Catania, Catania, Italy.

Uveal Melanoma (UM) represents the most common primary intraocular malignant tumor in adults. Although it originates from melanocytes as cutaneous melanoma, it shows significant clinical and biological differences with the latter, including high resistance to immune therapy. Indeed, UM can evade immune surveillance via multiple mechanisms, such as the expression of inhibitory checkpoints (e.g., ) and the production of and soluble , among others. More in-depth understanding of these mechanisms will suggest potential targets for the design of novel and more effective management strategies for UM patients.
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http://dx.doi.org/10.3389/fonc.2019.01145DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6848265PMC
November 2019

Risk of acute stroke in patients with retinal artery occlusion: a systematic review and meta-analysis.

Eye (Lond) 2020 04 16;34(4):683-689. Epub 2019 Sep 16.

Department of Ophthalmology, University of Catania, Catania, Italy.

Objective: To estimate the incidence of acute cerebral ischaemia detected by magnetic resonance imaging (MRI) in acute central retinal artery occlusion (CRAO), branch retinal artery occlusion (BRAO) and transient monocular vision loss (TMVL).

Methods: Studies reporting the incidence of acute cerebral ischaemia, detected by MRI, within 7 days from diagnosis of acute CRAO, BRAO and TMVL up to January 2019 were systematically searched for on Pubmed, Medline and Cochrane Library. Meta-analysis was performed using random effects model. The primary outcome was the pooled estimate of incidence of acute cerebral ischaemia in CRAO, BRAO and TMVL cohorts including both neurologically symptomatic and asymptomatic patients, expressed as a proportion along with 95% confidence intervals (CIs). The pooled estimate of incidence of asymptomatic acute cerebral ischaemia represented a secondary outcome measure.

Results: For the primary outcome, the pooled proportion of acute cerebral ischaemia was 0.30 (CI 0.24-0.36) in the CRAO cohort, and 0.25 (CI 0.16-0.37) in the BRAO cohort, without statistical heterogeneity. The rate of acute cerebral ischaemia was 11.8% in the TMVL cohort. For the secondary outcome, the pooled proportion of asymptomatic acute cerebral ischaemia was 0.22 (CI 0.16-0.28) in the CRAO cohort, 0.29 (CI 0.20-0.41) in the BRAO cohort and 0.08 (CI 0.05-0.15) in the TMVL cohort, with no statistical heterogeneity.

Conclusions: 30% of patients with acute CRAO and 25% of patients with acute BRAO presented an acute cerebral ischaemia on MRI. Such high rates support a care pathway of prompt referral of such patients for neurological evaluation and brain imaging.
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http://dx.doi.org/10.1038/s41433-019-0576-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7093449PMC
April 2020

The Effectiveness of 0.6% Povidone Iodine Eye Drops in Reducing the Conjunctival Bacterial Load and Needle Contamination in Patients Undergoing Anti-VEGF Intravitreal Injection: A Prospective, Randomized Study.

J Clin Med 2019 Jul 13;8(7). Epub 2019 Jul 13.

Department of Ophthalmology, University of Catania, 95123 Catania, Italy.

The study purpose was to assess the efficacy of a preservative-free 0.6% povidone iodine eye drops as perioperative prophylactic treatment for reducing conjunctival bacterial load and the rate of needle contamination in patients undergoing intravitreal anti-vascular endothelial growth factor injection. Enrolled patients were randomized to either the study group (0.6% povidone iodine, three day-prophylactic treatment before the injection) or to the control group (placebo, three day-prophylactic treatment). Conjunctival swabs were obtained before and after the prophylactic treatment in both groups. Intravitreal injections were performed in a sterile fashion. The injection needle and a control needle were collected for microbiological culture. Data from 254 and 253 eyes in the study group and control group, respectively, were analyzed. Bacterial growth from conjunctival swab cultures was significantly lower after 0.6% povidone iodine prophylaxis compared to baseline and to placebo prophylaxis ( < 0.001), showing an 82% eradication rate in the study group. No injection needle showed bacterial contamination in the study group, whereas six needles were culture-positive in the control group ( = 0.015). No serious ocular and non-ocular adverse events were recorded. The 0.6% povidone iodine solution proved an effective treatment in reducing conjunctival bacterial load and risk of needle contamination.
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http://dx.doi.org/10.3390/jcm8071031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6678890PMC
July 2019

Characterization of the Pathophysiological Role of CD47 in Uveal Melanoma.

Molecules 2019 Jul 4;24(13). Epub 2019 Jul 4.

Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy.

Uveal melanoma (UM) represents the most frequent primary intraocular tumor, however, limited therapeutic options are still available. We have previously shown that cluster of differentiation 47 (CD47) is significantly upregulated in UM cells following inflammatory stimuli and that it represents a predictor of disease progression. Here, we aimed to better characterize the pathophysiological role of CD47 in UM. We show that CD47 is not modulated at different cancer stages, although patients with the lowest expression of CD47 show significant better progression-free survival, after correcting for the presence of BAP1, GNAQ, and GNA11 mutations. By stratifying patients based on the expression of CD47 in the tumor, we observed that patients with high levels of CD47 have a significant increase in immune score as compared to patients with low levels of CD47. In particular, deconvolution analysis of infiltrating immune cell populations revealed that a significantly higher number of CD4+ and CD8+ T cells can be found in patients with high CD47 levels, with the most enriched populations being the Th2, Treg, and CD8+ Tcm cells. We also show that a large number of transcripts are significantly modulated between the groups of patients with high and low levels of CD47, with a significant enrichment of interferon IFN-alpha regulated genes. The results from this study may propel the development of anti-CD47 therapies for UM patients.
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http://dx.doi.org/10.3390/molecules24132450DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6651482PMC
July 2019

Intravitreal aflibercept for the treatment of radiation-induced macular edema after ruthenium 106 plaque radiotherapy for choroidal melanoma.

Graefes Arch Clin Exp Ophthalmol 2019 Jul 12;257(7):1547-1554. Epub 2019 May 12.

Department of Ophthalmology, University of Catania, Catania, Italy.

Purpose: To assess the efficacy of intravitreal aflibercept in patients suffering from post-radiation macular edema following plaque radiotherapy for choroidal melanoma.

Methods: This prospective, interventional case series included patients affected by radiation maculopathy (RM) with macular edema secondary to ruthenium-106 plaque brachytherapy for choroidal melanoma. The effect of intravitreal aflibercept on best-corrected visual acuity (BCVA), central foveal thickness (CFT) detected by spectral domain optical coherence tomography (sd-OCT), and Horgan's grading scale of RM was evaluated throughout the 24-month follow-up. Intraocular pressure (IOP) and possible complications were also recorded.

Results: Nine eyes of 9 patients were included. A mean of 4.4 ± 1.2 injections were given over the 24 months. At the end of follow-up, mean BCVA was significantly improved, from 0.9 ± 0.19 logMAR at baseline to 0.56 ± 0.3 logMAR (P = 0.028), and mean CFT was significantly decreased, from 546 ± 123 μm at baseline to 223 ± 34 μm (P < 0.001). Intravitreal aflibercept lowered baseline maculopathy stage as well. No significant change in IOP values and no complications, such as endophthalmitis, was recorded.

Conclusion: Intravitreal aflibercept is an effective treatment for patients with radiation-induced macular edema, allowing functional and anatomical improvements to be achieved with a relatively low number of injections.
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http://dx.doi.org/10.1007/s00417-019-04347-6DOI Listing
July 2019

Immunoexpression of SPANX-C in metastatic uveal melanoma.

Pathol Res Pract 2019 Jul 29;215(7):152431. Epub 2019 Apr 29.

Oasi Institute for Research on Mental Retardation and Brain Aging (IRCCS), Troina, Italy.

Uveal melanoma is a rare disease but it is the most common primary intraocular malignant tumor in adults with poor late prognosis. About 50% of patients will develop liver metastasis far from the enucleation within 10-15 years. Our study examined SPANX-C expression levels in primary uveal melanoma both with and without metastasis to assess if they can be used to predict metastasis. This study included a total of 55 patients, 28 males and 27 females, with uveal melanoma. A significantly high expression of SPANX-C was seen in 19/23 (82.6%) patients with metastasis, and only in 11/32 (38.5%) patients without metastasis. In conclusion, we found that SPANX-C expression could play a role in tumor progression of uveal melanoma.
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http://dx.doi.org/10.1016/j.prp.2019.04.023DOI Listing
July 2019